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de Wit TMG, Doherty T, Hendricks M. Community-based follow-up of very low birth weight neonates discharged from a regional hospital in Cape Town: a descriptive study. Glob Health Action 2025; 18:2466277. [PMID: 39981560 PMCID: PMC11849016 DOI: 10.1080/16549716.2025.2466277] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2024] [Accepted: 02/06/2025] [Indexed: 02/22/2025] Open
Abstract
BACKGROUND Neonatal mortality remains a global health concern. In South Africa, 32% of under-five mortality consists of neonates, with 48% of neonatal deaths attributed to prematurity. The Home and Community-Based Services (HCBS) aim to reduce deaths of very low birth weight (VLBW) neonates through community health worker (CHW) home visits. OBJECTIVES This study aimed to describe a cohort of VLBW neonates discharged from a regional hospital including their community follow-up, clinical outcomes and caregivers' perceptions of the HCBS. METHODS This was a descriptive mixed methods study. Routine hospital health information from 1 January to 31 December 2018 was analysed to describe the cohort. The referral pathway and follow-up were assessed through stakeholder meetings and analysing referral forms. Caregivers were interviewed for HCBS data. RESULTS There were 169 VLBW neonates. The mean (SD) gestational age was 30 (±2.21) weeks, and the median (IQR) birthweight was 1210 g (1045-1390 g). At delivery, 85% had respiratory distress and 64% had presumed sepsis. Maternal characteristics included primigravida deliveries (15%), smoking (11%), alcohol use (9%) and teenage pregnancy (5%); 14% required social worker referral. Folder reviews showed referral plans for 49 (43.4%); however, 20 (17.7%) forms were received by HCBS. All five of the interviewed caregivers had positive perceptions of the HCBS. CONCLUSION This study demonstrated a high burden of medically and socially vulnerable VLBW neonates discharged from a regional hospital. Even with established HCBS systems, few VLBW neonates were followed up at home. For the HCBS to be fully effective, promotion, strengthening and monitoring of the referral system are required.
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Affiliation(s)
| | - Tanya Doherty
- Department of Paediatrics and Child Health, University of Cape Town, Cape Town, South Africa
- Health Systems Research Unit, South African Medical Research Council, Parow, Cape Town, South Africa
| | - Michael Hendricks
- Department of Paediatrics and Child Health, University of Cape Town, Cape Town, South Africa
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Hoskins PR, Reynolds RM, Hunt K, Townsend R. Umbilical Artery Wall Shear Stress and Control of the Feto-placental Circulation. ULTRASOUND IN MEDICINE & BIOLOGY 2025:S0301-5629(25)00162-0. [PMID: 40514265 DOI: 10.1016/j.ultrasmedbio.2025.05.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/28/2025] [Revised: 04/23/2025] [Accepted: 05/08/2025] [Indexed: 06/16/2025]
Abstract
The aim of this paper is to review the area of wall shear stress (WSS) in umbilical arteries and to present a new theory for the short-term (seconds) control of placental resistance, which could be mediated by WSS. The endothelium senses changes in WSS, and a series of biological changes ensues with timescales of seconds to weeks. Wall shear stress mediates a control mechanism in which the arterial diameter changes in order to maintain WSS within a narrow range. Umbilical artery WSS has been estimated using a combination of ultrasound measurement of diameter and blood velocity (from maximum Doppler frequency shift), and computational fluid dynamics. The measurement of maximum blood velocity using commercial ultrasound systems is overestimated by typically 20%-40% in clinical ultrasound and 40%-60% in pre-clinical ultrasound. Measurements of WSS that use an estimate of maximum velocity from maximum Doppler frequency will also be overestimated by similar amounts. The overestimation of maximum velocity is due to geometric spectral broadening, which can be corrected at the time of data collection using measurements made from a string or similar phantom. A new hypothesis is described, which is that placental resistance is controlled on a timescale of a few seconds in order to maintain the umbilical artery flow rate constant. This hypothesis originates from observations made in a 1989 paper that investigated the relationship between the umbilical artery heart rate and resistance index. The key observation was that changes in heart rate were followed a few seconds later by changes in resistance index. It is proposed that the basis for the control could be endothelial detection of changes in WSS. Modern ultrasound systems have the technical capability to further investigate this hypothesis.
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Affiliation(s)
- Peter R Hoskins
- Centre for Reproductive Health, Institute for Regeneration and Repair, University of Edinburgh, Edinburgh, UK.
| | - Rebecca M Reynolds
- Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK
| | - Kathryn Hunt
- Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK
| | - Rosemary Townsend
- Centre for Reproductive Health, Institute for Regeneration and Repair, University of Edinburgh, Edinburgh, UK; Centre for Medical Informatics, Usher Institute, University of Edinburgh, Edinburgh, UK
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3
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Chin PY, Moldenhauer LM, Lubell WD, Olson DM, Chemtob S, Keelan JA, Robertson SA. Inhibition of interleukin-1 signaling protects against Group B streptococcus-induced preterm birth and fetal loss in mice. J Reprod Immunol 2025; 169:104520. [PMID: 40139077 DOI: 10.1016/j.jri.2025.104520] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2024] [Revised: 01/20/2025] [Accepted: 03/13/2025] [Indexed: 03/29/2025]
Abstract
Group B streptococcus is a common microbial agent associated with spontaneous preterm birth and fetal inflammatory response syndrome. In this study, we evaluated the utility of rytvela, a novel peptide antagonist of the interleukin-1 receptor, to suppress inflammatory activation, prolong gestation and improve neonatal outcomes induced in mice by Group B streptococcus. Pregnant mice were administered rytvela or PBS on gestation day 16.5, immediately prior and following surgical administration of heat-killed Group B streptococcus (hkGBS) or PBS into the uterine cavity. Treatment with rytvela prevented preterm delivery and alleviated fetal demise in utero and in the perinatal phase elicited by hkGBS. Compared to pups exposed to hkGBS alone, pups of dams co-administered rytvela exhibited substantially improved survival and growth through to weaning. Analysis by qPCR showed expression of inflammatory cytokine genes Il1b, Il6, Tnf, and Ifng in uterine tissues, and Il1b, Il6, and Tnf in fetal membranes, were stimulated by hkGBS and this increase was suppressed by co-administration of rytvela. Premature induction of uterine activation gene Ptgs2 in the myometrium was also attenuated by rytvela treatment. These data show that activation of IL1-mediated signaling in response to Group B streptococcus triggers an inflammatory cascade that causes preterm parturition and fetal inflammatory injury, and that rytvela can suppress inflammatory mediators to substantially improve pregnancy and fetal outcomes. Our findings add to accumulating evidence supporting clinical investigation of rytvela for fetal protection and delaying preterm birth.
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Affiliation(s)
- Peck Y Chin
- Robinson Research Institute and Adelaide Medical School, University of Adelaide, Adelaide, SA 5005, Australia; School of Biomedicine, University of Adelaide, Adelaide, SA 5005, Australia
| | - Lachlan M Moldenhauer
- Robinson Research Institute and Adelaide Medical School, University of Adelaide, Adelaide, SA 5005, Australia; School of Biomedicine, University of Adelaide, Adelaide, SA 5005, Australia
| | - William D Lubell
- Department of Chemistry, Université de Montréal, Montreal, Quebec H3T1J4, Canada
| | - David M Olson
- Departments of Obstetrics & Gynecology, Pediatrics and Physiology, University of Alberta, Edmonton, Alberta T6G2S2, Canada
| | - Sylvain Chemtob
- Department of Pharmacology, Université de Montréal, Montreal, Quebec H3T1J4, Canada
| | - Jeffrey A Keelan
- School of Biomedical Sciences, University of Western Australia, Perth, WA 6008, Australia
| | - Sarah A Robertson
- Robinson Research Institute and Adelaide Medical School, University of Adelaide, Adelaide, SA 5005, Australia; School of Biomedicine, University of Adelaide, Adelaide, SA 5005, Australia.
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4
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Craig A, DeLaGarza-Pineda O. Neonatal Neurocritical Care in Low-Resource Settings: Challenges and Innovations in Hypoxic-Ischemic Encephalopathy. Clin Perinatol 2025; 52:361-374. [PMID: 40350216 DOI: 10.1016/j.clp.2025.02.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/14/2025]
Abstract
Many neonatal neuroprotective strategies have been developed to reduce the impact of hypoxic-ischemic encephalopathy on mortality and long-term neurodevelopmental outcomes. The most effective strategy to date is therapeutic hypothermia, which has been shown to improve survival rates and neurologic outcomes. However, a recent International Liaison Committee on Resuscitation statement recommends using therapeutic hypothermia only in specialized neonatal neurocritical care facilities, which are not universally accessible. Low-resource settings are particularly disadvantaged due to a lack of trained professionals, financial constraints, equipment scarcity, and inadequate infrastructure. While adjunctive neuroprotective therapies and telehealth tools may help to bridge this gap, more evidence is needed to establish effectiveness of these therapies.
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Affiliation(s)
- Alexa Craig
- Department of Pediatrics, Barbara Bush Children's Hospital at MaineHealth, MaineHealth Neurology Scarborough, 92 Campus Drive, Scarborough, ME 04074, USA; Pediatrics, Tufts University School of Medicine, Boston, MA, USA.
| | - Oscar DeLaGarza-Pineda
- Department of Neurology, University Hospital of the Autonomous University of Nuevo Leon, Monterrey, Mexico; Hospital Universitario, Servicio de Neurología, Av Francisco Madero y Av Gonzalitos, s/n, Colonia Mitras Centro, Monterrey, Nuevo León CP 64460, Mexico
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Gaston-Breton R, Disdier C, Hagberg H, Mabondzo A. Hypoxia-ischemia and sexual dimorphism: modeling mitochondrial dysfunction using brain organoids. Cell Biosci 2025; 15:67. [PMID: 40413513 PMCID: PMC12103005 DOI: 10.1186/s13578-025-01402-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2024] [Accepted: 04/27/2025] [Indexed: 05/27/2025] Open
Abstract
Hypoxic-ischemic encephalopathy (HIE) is a leading cause of neurodevelopmental morbidities in full-term infants. There is strong evidence of sexual differences in hypoxic-ischemic (HI) injury where male neonates are at higher risk as they are subject to more pronounced neurological deficits and death than females. The cellular and molecular mechanisms underlying these sexual discrepancies in HI injury are poorly understood. Mitochondrial dysregulation has been increasingly explored in brain diseases and represents a major target during HI events. In this review, we discuss (1) different mitochondrial functions in the central nervous system (2), mitochondrial dysregulation in the context of HI injury (3), sex-dependent mitochondrial pathways in HIE and (4) modeling of mitochondrial dysfunction using human brain organoids. Gaining insight into these novel aspects of mitochondrial function will offer valuable understanding of brain development and neurological disorders such as HI injury, paving the way for the discovery and creation of new treatment approaches.
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Affiliation(s)
- Romane Gaston-Breton
- Université Paris-Saclay, CEA, INRAE, Département Médicaments et Technologies pour la Santé (DMTS), SPI, Laboratoire d'Etude de l'Unité Neurovasculaire & Innovation Thérapeutique (LENIT), Gif-sur-Yvette cedex, 91191, France
| | - Clémence Disdier
- Université Paris-Saclay, CEA, INRAE, Département Médicaments et Technologies pour la Santé (DMTS), SPI, Laboratoire d'Etude de l'Unité Neurovasculaire & Innovation Thérapeutique (LENIT), Gif-sur-Yvette cedex, 91191, France
| | | | - Aloïse Mabondzo
- Université Paris-Saclay, CEA, INRAE, Département Médicaments et Technologies pour la Santé (DMTS), SPI, Laboratoire d'Etude de l'Unité Neurovasculaire & Innovation Thérapeutique (LENIT), Gif-sur-Yvette cedex, 91191, France.
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Dahash B, Lulic-Botica M, Amoah J, Sanabria-Garcia D, Bajaj M. Bacteriological Profile and Antibiotic Susceptibility Patterns of Late-Onset Neonatal Sepsis in Levels III and IV Neonatal Intensive Care Units. Am J Perinatol 2025. [PMID: 40324466 DOI: 10.1055/a-2599-4696] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 05/07/2025]
Abstract
Late-onset sepsis (LOS), which occurs 72 hours after birth, remains an important cause of mortality and morbidity in the neonatal intensive care unit (NICU). Differences in infant populations and the complexity of care at various NICU levels may result in varying bacteriological profiles and antibiotic susceptibility patterns. The objective of the current study was to determine and compare the bacteriological profiles, antibiotic susceptibility, and risk factors for LOS in levels III and IV NICU within a single hospital system. This was a retrospective study of infants with LOS and positive blood cultures, admitted to levels III and IV NICUs between 2012 and 2021. Of the 173 infants included in our study, 105 were admitted to the level IV NICU and 68 to the level III NICU. Infants in the level III NICU had a lower gestational age and birth weight at the time of LOS. Seventy percent of the infants had a central line. Gram-positive organisms were responsible for the vast majority of infections (75%), with coagulase-negative Staphylococcus (CoNS) being the most common bacteria in both units. Gram-negative bacteria were more frequently isolated from the level IV NICU (36.2%) compared to the level III NICU (8.8%). Escherichia coli (E. coli) and Enterobacter sp. were the most frequently isolated gram-negative bacteria. All gram-positive bacteria were susceptible to vancomycin, and all gram-negative bacteria were susceptible to meropenem. The prevalent bacteriological profile and antibiotic susceptibility patterns in the NICU should guide the choice of empiric antibiotics for LOS. It is important to monitor sepsis and antimicrobial resistance patterns in the NICU and implement risk-specific strategies to reduce the burden of LOS. · LOS in NICUs is predominantly caused by gram-positive bacteria, mainly CoNS.. · Higher frequency of gram-negative bacteria, including E. coli and Enterobacter, in level IV NICU.. · All gram-negative isolates were meropenem-sensitive; vancomycin effective for gram-positives..
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Affiliation(s)
- Basma Dahash
- Department of Pediatrics, Children's Hospital of Michigan, Detroit, Michigan
| | | | - Joe Amoah
- Department of Pediatrics, Children's Hospital of Michigan, Detroit, Michigan
| | | | - Monika Bajaj
- Department of Pediatrics, Central Michigan University, Detroit, Michigan
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7
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Groteklaes A, Dresbach T, Mueller A, Sabir H. Application and Acceptance of Bedside MRI in the NICU Setting. J Perinat Neonatal Nurs 2025:00005237-990000000-00104. [PMID: 40434065 DOI: 10.1097/jpn.0000000000000931] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 05/29/2025]
Abstract
PURPOSE This study aims to assess the applicability of ultralow-field (ULF) magnetic resonance imaging (MRI) in the neonatal intensive care unit (NICU), its impact on both the neonate being scanned and neighboring patients, and its effects on medical procedures and early parent-child interaction. BACKGROUND Neonatal MRI is crucial for diagnosis and treatment in the NICU, but access is limited, both in high-income countries and low- and middle-income countries. Portable ULF MRI presents an opportunity to expand access, but its applicability and potential impacts on neonates and nearby patients have not been studied, including its effects on medical care and early parent-child interaction. METHODS We assessed applicability, safety and stress levels of neonates during ULF MRI at a NICU by measuring heart rate, oxygen saturation and blood pressure of the neonate scanned and neighboring patients and by measuring subjective stress levels assessed by attending physicians, nurses and parents. Using questionnaires, we assessed whether medical care and early parent-child interaction was affected. RESULTS No significant differences were found in the physiological measures of the scanned and neighboring neonates. Medical care and parent-child interaction were not affected by ULF MRI. CONCLUSIONS ULF MRI can be safely performed in the NICU without causing stress to neonates or affecting medical care or parent-child interaction. It can be performed at the bedside during natural sleep, requiring fewer resources compared to high-field MRI, making it a viable point-of-care option in both the NICU and low-resource settings. This could significantly increase MRI accessibility.
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Affiliation(s)
- Anne Groteklaes
- Author Affiliation: Department of Neonatology and Pediatric Intensive Care, Children's Hospital, University Hospital Bonn, Bonn, Germany (Drs Groteklaes, Dresbach, Mueller, and Sabir)
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Enyew EF, Getnet M, Gebiru AM, Dessie G. Individual and community level determinants of neonatal mortality in sub saharan Africa: findings from recent demographic and health survey data. Ital J Pediatr 2025; 51:144. [PMID: 40390123 PMCID: PMC12090633 DOI: 10.1186/s13052-025-01997-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2025] [Accepted: 05/11/2025] [Indexed: 05/21/2025] Open
Abstract
BACKGROUND A major cause of deaths among children under five is neonatal mortality, a worldwide problem. However, the problem in sub-Saharan Africa is not well documented. Understanding the prevalence of neonatal death and its related causes is crucial for creating efforts and policies that could help address the problem. This study set out to determine the prevalence of neonatal death and its determinants in sub-Saharan Africa. METHODS Using secondary data analysis of demographic and health surveys conducted between 2014 and 2024 in sub-Saharan Africa. Total weighted samples of 133,448 live births in all during the period in 31 Sub- Saharan Africa. The determinants of neonatal mortality were identified using a multilevel mixed-effects logistic regression model. A multilevel binary logistic regression was fitted to identify the significant determinants of neonatal mortality. The Intra-class Correlation Coefficient, Median Odds Ratio, Proportional Change in Variance was used for assessing the clustering effect, and deviance for model comparison. Variables with a p-value < 0.2 in the Bivariable analysis were considered in the multivariable analysis. In the multivariable multilevel binary logistic regression analysis, Adjusted Odds Ratio with 95% CI was reported to declare statistically significant determinants of neonatal mortality. RESULTS The neonatal mortality in sub-Saharan Africa was 32 per 1000 live births (95% CI: 30, 34). maternal occupation (AOR = 1.26, 95% CI: 1.16, 1.37), home delivery (AOR = 1.29; 95% CI: 1.21, 1.39), caesarean section (AOR = 1.58; 95%CI: 1.36, 1.83), twin births(AOR = 2.48, 95% CI: 2.05, 2.54), birth order of 2-4 (AOR = 1.30, 95% CI: 1.18, 1.44), birth order of ≥ 5 (AOR = 1.43, 95% CI: 1.31, 1.59) and smaller size than average (AOR = 1.49, 95% CI: 1.36, 1.63)were significantly associated with higher odds of neonatal mortality. CONCLUSION According to this study, in sub-Saharan Africa neonatal mortality rate was high. The following factors should be taken into account while developing policies and measures to reduce newborn mortality in sub-Saharan Africa: the mother's education, wealth index, occupation, place of delivery, mode of delivery, twin birth, neonatal sex, birth order, and size at birth.
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Affiliation(s)
- Engidaw Fentahun Enyew
- Department of Anatomy, School of Medicine, College of Medicine and Health Science, University of Gondar, Gondar, Ethiopia.
- Department of Reproductive Health, Institute of Public Health, College of Medicine and Health Science, University of Gondar, Gondar, Ethiopia.
| | - Mihret Getnet
- Department of Human Physiology, School of Medicine, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia
- Department of Epidemiology and biostatistics, Institute of public Health, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia
| | - Ashebir Mamay Gebiru
- Department of Epidemiology and biostatistics, Institute of public Health, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia
- Departments of Health informatics Gondar, Teda Health Science College, Gondar, Ethiopia
| | - Gashaw Dessie
- Department of Biochemistry, School of Medicine, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia
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Tarvonen M, Jernman R, Stefanovic V, Tuppurainen V, Karikoski R, Haataja L, Andersson S. Hypoxic-ischemic encephalopathy following intrapartum asphyxia: is it avoidable? Am J Obstet Gynecol 2025:S0002-9378(25)00305-9. [PMID: 40348116 DOI: 10.1016/j.ajog.2025.04.073] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2025] [Revised: 04/30/2025] [Accepted: 04/30/2025] [Indexed: 05/14/2025]
Abstract
BACKGROUND The proportion of term hypoxic-ischemic encephalopathy arising during intrapartum fetal surveillance remains unclear. Moreover, recent Cochrane review and other studies emphasized the need for research on the impact of admission cardiotocography and highlighted the necessity for a definition of "avoidable perinatal brain injury". OBJECTIVE To assess the impact of intrapartum asphyxia on neonatal hypoxic-ischemic encephalopathy occurrence and identify the proportion of cases that benefit from preventive measures. STUDY DESIGN This retrospective 20-year birth cohort study included admission and intrapartum cardiotocography recordings from spontaneous term (≥37 weeks of gestation) singleton deliveries at 7 maternity hospitals within the Helsinki University Hospital area, Finland, between 2005 and 2024. In newborns diagnosed with hypoxic-ischemic encephalopathy, cases following intrapartum asphyxia were identified by a normal cardiotocogram at admission, whereas antepartum exposure was indicated by an abnormal admission cardiotocogram. Cord blood gases, erythropoietin, and serum S100β concentrations were analyzed, and placentas underwent histopathological examination. Primary outcome was hypoxic-ischemic encephalopathy. Secondary outcome was fetal asphyxia, defined as the presence of severe or moderate acidemia. RESULTS Among 317,126 term newborns, 314 cases of hypoxic-ischemic encephalopathy were identified. Admission cardiotocogram was normal in 141 (44.9%) and abnormal in 173 (55.1%). Of those with a normal admission cardiotocogram, severe acidemia (umbilical artery pH <7.00 and/or base excess ≤-12.0 mmol/L) evolved in 127/141 (90.1%) and moderate acidemia (umbilical artery pH 7.09-7.00 and base excess -10.0 to -11.9 mmol/L) in 11/141 (7.8%). Excluding cases with a perinatal sentinel event and timely deliveries, 70 cases (49.6%) remained in which hypoxic-ischemic encephalopathy presumably developed during labor and was considered potentially avoidable. These findings suggest that in 22.3% (70/314), preventive measures should have been implemented. Newborns with abnormal cardiotocograms had higher median umbilical blood erythropoietin concentrations than those with normal admission cardiotocograms (112 U/L, interquartile range 22-1130 vs 29 U/L, interquartile range 7-680, P<.001), indicating more chronic hypoxia. CONCLUSION Of term newborns with hypoxic-ischemic encephalopathy and normal admission cardiotocogram, 98% were attributable to intrapartum asphyxia. Our findings indicate that half of the cases of intrapartum hypoxic-ischemic encephalopathy with a normal admission cardiotocogram were potentially avoidable, suggesting that one-fifth of all cases could have benefited from preventive measures. The findings underscore the role of optimal intrapartum care in preventing hypoxic-ischemic encephalopathy.
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Affiliation(s)
- Mikko Tarvonen
- Department of Obstetrics and Gynecology, University of Helsinki, and Helsinki University Hospital, Helsinki, Finland.
| | - Riina Jernman
- Department of Obstetrics and Gynecology, University of Helsinki, and Helsinki University Hospital, Helsinki, Finland
| | - Vedran Stefanovic
- Department of Obstetrics and Gynecology, University of Helsinki, and Helsinki University Hospital, Helsinki, Finland
| | - Ville Tuppurainen
- Department of Industrial Engineering and Management, LUT University of Technology, Lappeenranta, Finland, and Helsinki University Hospital Area Administration, Helsinki, Finland
| | - Riitta Karikoski
- Division of Pathology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Leena Haataja
- Children's Hospital, Pediatric Research Center, University of Helsinki, and Helsinki University Hospital, Helsinki, Finland
| | - Sture Andersson
- Children's Hospital, Pediatric Research Center, University of Helsinki, and Helsinki University Hospital, Helsinki, Finland
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10
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Rahman A, Ray M, Madewell ZJ, Igunza KA, Akelo V, Onyango D, Murila F, Mwebia W, Ogbuanu IU, Ojulong J, Kowuor D, Kaluma E, Samura S, El Arifeen S, Gurley ES, Hossain MZ, Islam KM, Biswas R, Assefa N, Teferi T, Eshetu K, Madrid L, Kotloff KL, Tapia MD, Keita AM, Xerinda E, de Assis CM, Kincardett M, Mandomado I, Varo R, Madhi SA, Dangor Z, Baba V, Velaphi S, Adam Y, Blau DM, Mutevedzi PC, Bassat Q, Whitney CG, Rees CA. Adherence to Perinatal Asphyxia or Sepsis Management Guidelines in Low- and Middle-Income Countries. JAMA Netw Open 2025; 8:e2510790. [PMID: 40377940 DOI: 10.1001/jamanetworkopen.2025.10790] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 05/18/2025] Open
Abstract
Importance Most of the 2.3 million annual neonatal deaths occur in sub-Saharan Africa and South Asia, with perinatal asphyxia and neonatal sepsis being the leading causes of neonatal mortality. Most neonatal deaths are considered preventable through high-quality clinical care, which includes adherence to clinical care guidelines. Objective To assess adherence to World Health Organization clinical care guidelines for management of perinatal asphyxia and neonatal sepsis and to identify patient-level factors in adherence among neonates who died from these conditions. Design, Setting, and Participants This cross-sectional study obtained data from December 2015 through October 2023 from the Child Health and Mortality Prevention Surveillance (CHAMPS) catchment areas in 7 low- and middle-income countries in sub-Saharan Africa (Ethiopia, Kenya, Mali, Mozambique, Sierra Leone, and South Africa) and South Asia (Bangladesh). Participants were neonates who were born alive and were aged 0 to 28 days at the time of death and had either perinatal asphyxia or neonatal sepsis. Exposure Medical records of neonates who died from perinatal asphyxia or neonatal sepsis determined by postmortem diagnostics. Main Outcomes and Measures The main outcome was the proportion of deceased neonates who received guideline-adherent treatments before they died. Mixed-effect multivariable logistic regression analyses were performed to identify factors associated with administration of at least bag-valve-mask (BVM) ventilation for perinatal asphyxia. Results Of the 1194 neonates (median [IQR] age at the time of death, 2 [1-6] days; 692 males [58.0%]) who died and were enrolled in CHAMPS with available clinical data, 476 (39.9%) died from perinatal asphyxia, 562 (47.0%) died from neonatal sepsis, and 156 (13.1%) from both conditions. These neonates had a median (IQR) birth weight of 2130 (1266-2988) g. For cases with perinatal asphyxia, guideline adherence ranged from 12.2% (n = 77) for adrenaline administration to 85.4% (540) for supplemental oxygen administration. Only 4.4% of neonates (28) with perinatal asphyxia received all recommended treatments. Among cases with neonatal sepsis, antibiotics were administered to 86.8% (623), although the recommended treatment was administered to only 61.0% (438). In multivariable analyses, neonates in whom clinicians accurately identified perinatal asphyxia were more likely to receive BVM ventilation than those who had received discordant antemortem and postmortem diagnoses (adjusted odds ratio, 2.00; 95% CI, 1.29-3.12). Conclusions and Relevance In this cross-sectional study, clinical care guideline adherence was suboptimal among neonates who died from perinatal asphyxia or neonatal sepsis. This finding underscores the critical need to increase adherence in regions with high rates of neonatal mortality and may inform strategies for strengthening health systems to support compliance with clinical care guidelines.
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Affiliation(s)
- Afruna Rahman
- International Centre for Diarrhoeal Disease Research Bangladesh (ICDDRB), Dhaka, Bangladesh
| | - Meghna Ray
- Hubert Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, Georgia
| | - Zachary J Madewell
- Global Health Center, US Centers for Disease Control and Prevention, Atlanta, Georgia
| | | | - Victor Akelo
- Liverpool School of Tropical Medicine, Liverpool, United Kingdom
- Global Health Institute, Emory University, Atlanta, Georgia
| | | | | | - Winnie Mwebia
- Kenya Medical Research Institute, Center for Global Health Research, Kisumu, Kenya
| | - Ikechukwu Udo Ogbuanu
- Hubert Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, Georgia
- CHAMPS Project, Freetown, Sierra Leone
| | | | | | | | | | - Shams El Arifeen
- International Centre for Diarrhoeal Disease Research Bangladesh (ICDDRB), Dhaka, Bangladesh
| | - Emily S Gurley
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
| | - Mohammad Zahid Hossain
- International Centre for Diarrhoeal Disease Research Bangladesh (ICDDRB), Dhaka, Bangladesh
| | - Kazi Munisul Islam
- International Centre for Diarrhoeal Disease Research Bangladesh (ICDDRB), Dhaka, Bangladesh
| | - Rajib Biswas
- International Centre for Diarrhoeal Disease Research Bangladesh (ICDDRB), Dhaka, Bangladesh
| | - Nega Assefa
- London School of Hygiene and Tropical Medicine, London, United Kingdom
- College of Health and Medical Sciences, Haramaya University, Harar, Ethiopia
| | - Temesgen Teferi
- College of Health and Medical Sciences, Haramaya University, Harar, Ethiopia
| | - Konjit Eshetu
- College of Health and Medical Sciences, Haramaya University, Harar, Ethiopia
| | - Lola Madrid
- London School of Hygiene and Tropical Medicine, London, United Kingdom
| | - Karen L Kotloff
- Department of Pediatrics, Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore
| | - Milagritos D Tapia
- Department of Pediatrics, Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore
| | | | - Elisio Xerinda
- Centro de Investigação em Saúde de Manhiça (CISM), Maputo, Mozambique
| | | | - Milton Kincardett
- Centro de Investigação em Saúde de Manhiça (CISM), Maputo, Mozambique
| | - Inacio Mandomado
- Centro de Investigação em Saúde de Manhiça (CISM), Maputo, Mozambique
| | - Rosauro Varo
- ISGlobal - Hospital Clínic, Universitat de Barcelona, Barcelona, Spain
| | - Shabir A Madhi
- South African Medical Research Council Vaccines and Infectious Diseases Analytics Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
- Wits Infectious Diseases and Oncology Research Institute, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Ziyaad Dangor
- South African Medical Research Council Vaccines and Infectious Diseases Analytics Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Vuyelwa Baba
- Department of Obstetrics and Gynaecology, University of the Witwatersrand, Johannesburg, South Africa
| | - Sithembiso Velaphi
- Department of Pediatrics, Chris Hani Baragwanath Academic Hospital, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Yasmin Adam
- Department of Obstetrics and Gynaecology, University of the Witwatersrand, Johannesburg, South Africa
| | - Dianna M Blau
- Global Health Center, US Centers for Disease Control and Prevention, Atlanta, Georgia
| | | | - Quique Bassat
- Hospital Central de Quelimane, Quelimane, Mozambique
- ISGlobal - Hospital Clínic, Universitat de Barcelona, Barcelona, Spain
- Institución Catalana de Investigación y Estudios Avanzados (ICREA), Pg. Lluís Companys 23, Barcelona, Spain
- Department of Pediatrics, Hospital Sant Joan de Déu, Universitat de Barcelona, Esplugues, Barcelona, Spain
| | | | - Chris A Rees
- Division of Pediatric Emergency Medicine, Emory University School of Medicine, Atlanta, Georgia
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11
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Zakerihamidi M, Boskabadi H. An investigation into the history of maternal risk factors in the incidence of perinatal mortality. J Neonatal Perinatal Med 2025; 18:203-210. [PMID: 40270471 DOI: 10.1177/19345798251324441] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/25/2025]
Abstract
ObjectivesThe rate of perinatal mortality is an important indicator of maternal and neonatal health. Identification of risk factors for perinatal mortality may be effective in its prevention. Accordingly, this study aimed to identify maternal risk factors of perinatal mortality.MethodsA cross-sectional study was conducted on 547 stillbirths and 709 neonatal deaths at Ghaem Hospital of Mashhad, Iran, during 2008-2019. The data were collected using a researcher-made questionnaire in two parts of stillbirth (maternal diseases, main complication, and final diagnosis) and specifications of neonatal death (e.g., gender, length of hospitalization, age, first and fifth minute Apgar scores, gestational age, weight, resuscitation, mode of delivery, preterm rupture of membranes, main cause of death, and maternal diseases). Data analysis was performed by T-test and Chi-square tests using SPSS version 21 (V.21).ResultsOverall, 222 mothers (41%) had stillborn fetus and 325 (77%) with neonatal death had maternal risk factors. The 41% of neonatal deaths and 26% of stillbirths were along with maternal hypertension, 33% of neonatal deaths and 25% of stillbirths were along with maternal preeclampsia, and 9% of neonatal deaths and 12% of stillbirths were along with maternal diabetes. The cases of cesarean and neonatal resuscitation were higher in neonates with maternal risk factors (69% and 58%, respectively) than those with mothers who had no problem (43% and 32%, respectively).ConclusionHypertension, preeclampsia, and diabetes were three important diseases during pregnancy, associated with high stillbirths and neonatal deaths. Neonates of mothers with problem were pretermer or less birth weight and had more problems during delivery and died earlier.
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Affiliation(s)
- Maryam Zakerihamidi
- Department of Midwifery, School of Medical Sciences, Tonekabon Branch, Islamic Azad University, Tonekabon, Iran
| | - Hassan Boskabadi
- Department of Pediatrics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
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12
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McClure EM, Saleem S. Every baby counts: eliminating all preventable child deaths. Lancet Glob Health 2025; 13:e779-e780. [PMID: 40288381 DOI: 10.1016/s2214-109x(25)00140-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2025] [Accepted: 03/19/2025] [Indexed: 04/29/2025]
Affiliation(s)
- Elizabeth M McClure
- Social, Statistical and Environmental Health Sciences, RTI International, Durham, NC, USA.
| | - Sarah Saleem
- Community Health Sciences, The Aga Khan University, Karachi, Pakistan
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13
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Park J, Ke W, Kaage A, Feigin CY, Griffing AH, Pritykin Y, Donia MS, Mallarino R. Cathelicidin antimicrobial peptides mediate immune protection in marsupial neonates. SCIENCE ADVANCES 2025; 11:eads6359. [PMID: 40238884 PMCID: PMC12002115 DOI: 10.1126/sciadv.ads6359] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/21/2024] [Accepted: 03/12/2025] [Indexed: 04/18/2025]
Abstract
Marsupial neonates are born with immature immune systems, making them vulnerable to pathogens. While neonates receive maternal protection, they can also independently combat pathogens, although the mechanisms remain unknown. Using the sugar glider (Petaurus breviceps) as a model, we investigated immunological defense strategies of marsupial neonates. Cathelicidins-a family of antimicrobial peptides expanded in the genomes of marsupials-are highly expressed in developing neutrophils. Sugar glider cathelicidins reside in two genomic clusters, and their coordinated expression is achieved by enhancer sharing within clusters and long-range physical interactions between clusters. Functionally, cathelicidins modulate immune responses and have potent antibacterial effects, sufficient to provide protection in a mouse model of sepsis. Evolutionarily, cathelicidins have a complex history, with marsupials and monotremes uniquely retaining both clusters among tetrapods. Thus, cathelicidins are critical mediators of marsupial immunity, and their evolution may reflect the life history-specific immunological needs of these animals.
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Affiliation(s)
- Jongbeom Park
- Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA
| | - Wenfan Ke
- Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA
- Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08540, USA
| | - Aellah Kaage
- Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA
| | - Charles Y. Feigin
- Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA
| | - Aaron H. Griffing
- Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA
- Department of Chemical and Biological Engineering, Princeton University, Princeton, NJ 08544, USA
| | - Yuri Pritykin
- Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08540, USA
- Department of Computer Science, Princeton University, Princeton, NJ 08544, USA
| | - Mohamed S. Donia
- Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA
| | - Ricardo Mallarino
- Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA
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14
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Murray AL, O'Boyle DS, Walsh BH, Murray DM. Validation of a machine learning algorithm for identifying infants at risk of hypoxic ischaemic encephalopathy in a large unseen data set. Arch Dis Child Fetal Neonatal Ed 2025; 110:279-284. [PMID: 39251344 PMCID: PMC12013575 DOI: 10.1136/archdischild-2024-327366] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2024] [Accepted: 08/21/2024] [Indexed: 09/11/2024]
Abstract
OBJECTIVE To validate a hypoxic ischaemic encephalopathy (HIE) prediction algorithm to identify infants at risk of HIE immediately after birth using readily available clinical data. DESIGN Secondary review of electronic health record data of term deliveries from January 2017 to December 2021. SETTING A tertiary maternity hospital. PATIENTS Infants >36 weeks' gestation with the following clinical variables available: Apgar Score at 1 min and 5 min, postnatal pH, base deficit, and lactate values taken within 1 hour of birth INTERVENTIONS: Previously trained open-source logistic regression and random forest (RF) prediction algorithms were used to calculate a probability index (PI) for each infant for the occurrence of HIE. MAIN OUTCOME Validation of a machine learning algorithm to identify infants at risk of HIE in the immediate postnatal period. RESULTS 1081 had a complete data set available within 1 hour of birth: 76 (6.95%) with HIE and 1005 non-HIE. Of the 76 infants with HIE, 37 were classified as mild, 29 moderate and 10 severe. The best overall accuracy was seen with the RF model. Median (IQR) PI in the HIE group was 0.70 (0.53-0.86) vs 0.05 (0.02-0.15), (p<0.001) in the non-HIE group. The area under the receiver operating characteristics curve for prediction of HIE=0.926 (0.893-0.959, p<0.001). Using a PI cut-off to optimise sensitivity of 0.30, 936 of the 1081 (86.5%) infants were correctly classified. CONCLUSION In a large unseen data set an open-source algorithm could identify infants at risk of HIE in the immediate postnatal period. This may aid focused clinical examination, transfer to tertiary care (if necessary) and timely intervention.
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Affiliation(s)
- Anne L Murray
- Cork University Maternity Hospital, Wilton, Cork, Ireland
- INFANT Centre, Paediatric Academic Unit, Cork University Hospital, Wilton, Cork, Ireland
| | - Daragh S O'Boyle
- INFANT Centre, Paediatric Academic Unit, Cork University Hospital, Wilton, Cork, Ireland
| | - Brian H Walsh
- Cork University Maternity Hospital, Wilton, Cork, Ireland
- INFANT Centre, Paediatric Academic Unit, Cork University Hospital, Wilton, Cork, Ireland
- Department of Paediatrics and Child Health, University College Cork, Cork, Ireland
| | - Deirdre M Murray
- INFANT Centre, Paediatric Academic Unit, Cork University Hospital, Wilton, Cork, Ireland
- Department of Paediatrics and Child Health, University College Cork, Cork, Ireland
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15
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Matcha S, Dilli Batcha JS, Raju AP, Chaudhari BB, Moorkoth S, Mallayasamy S, Lewis LE. Precision dosing of amikacin in term neonates using pharmacometric approach. Pediatr Res 2025:10.1038/s41390-025-04044-7. [PMID: 40210955 DOI: 10.1038/s41390-025-04044-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2024] [Revised: 01/16/2025] [Accepted: 02/02/2025] [Indexed: 04/12/2025]
Abstract
BACKGROUND Maintaining amikacin concentrations within a specific therapeutic window is crucial to avoid sub-therapeutic or toxic levels. This study aimed to design a dosing nomogram for amikacin in neonates using a Population Pharmacokinetic (PopPK) modeling approach. METHODS PopPK model was developed using 101 amikacin concentrations from 80 neonates and validated using model diagnostics, and empirical Bayesian forecasting was performed. Pharmacokinetic profiles were simulated for virtual subjects with a range of covariates to identify suitable dosage regimens. Dosage regimens with the highest probability for the target group were selected to design the dosing nomogram. RESULTS A two-compartment PK model best described the study data. Body weight (WT), serum creatinine (SCR), and post-natal age (PNA) affected the clearance of amikacin. The model predictions are with less than 15% absolute prediction error. WT and SCR were divided into five groups each, with each group repeated for every week of PNA for four weeks for dosing nomogram development. CONCLUSION A PopPK model was developed and successfully-predicted concentrations in the study population. This model was used to develop a nomogram considering significant covariates like WT, SCR, and PNA. The proposed dosing nomogram can assist clinicians in developing individualized dosage regimens. IMPACT Population pharmacokinetic (PopPK) models for amikacin in term neonates were developed using clinical data from an Indian clinical setting and successfully-predicted the amikacin concentrations for the study population. Pharmacokinetic simulations with virtual subjects were used to calculate the probability of target attainment for different dosing regimens. The proposed dosing nomogram can potentially assist clinicians in designing optimal amikacin dosage regimens for neonates.
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Affiliation(s)
- Saikumar Matcha
- Research Scholar, Department of Pharmacy Practice, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, India
- Titus Family Department of Clinical Pharmacy, Alfred E. Mann School of Pharmacy and Pharmaceutical Sciences, Los Angeles, CA, USA
| | - Jaya Shree Dilli Batcha
- Research Scholar, Department of Pharmacy Practice, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, India
- Center for Pharmacometrics, Manipal Academy of Higher Education, Manipal, India
| | - Arun Prasath Raju
- Research Scholar, Department of Pharmacy Practice, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, India
- Center for Pharmacometrics, Manipal Academy of Higher Education, Manipal, India
| | - Bhim Bahadur Chaudhari
- Research Scholar, Department of Pharmaceutical Quality Assurance, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, India
| | - Sudheer Moorkoth
- Professor & Head, Department of Pharmaceutical Quality Assurance, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, India
| | - Surulivelrajan Mallayasamy
- Center for Pharmacometrics, Manipal Academy of Higher Education, Manipal, India.
- Professor & Head, Department of Pharmacy Practice, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, India.
| | - Leslie E Lewis
- Professor & Head, Department of Pediatrics, Kasturba Medical College, Manipal Academy of Higher Education, Manipal, India
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Mathias K, Machado RS, Cardoso T, Naspolini B, Prophiro J, Petronilho F. Exploring NLRP3 Inhibition as a Key Modulator in Neonatal Hypoxic-Ischemic Brain Injury. Neuromolecular Med 2025; 27:25. [PMID: 40198503 DOI: 10.1007/s12017-025-08851-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2025] [Accepted: 03/29/2025] [Indexed: 04/10/2025]
Abstract
Neonatal hypoxic-ischemic (HI) injury is a critical condition associated with significant acute brain damage and long-term neurological impairments. Growing evidence highlights the role of the NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome, a key multiprotein complex driving neuroinflammation, in the progression of neonatal HI brain injury. Activation of the NLRP3 inflammasome triggers the release of pro-inflammatory cytokines, including interleukin-1 beta (IL-1β), which plays a pivotal role in exacerbating brain damage. This article examines current research to better understand the relationship between neonatal HI, NLRP3 inflammasome activation, and neuroinflammatory process. Furthermore, it emphasizes the therapeutic potential of targeting this pathway, proposing its modulation as a promising neuroprotective strategy to reduce neuroinflammation and improve outcomes in affected neonates.
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Affiliation(s)
- Khiany Mathias
- Laboratory of Experimental Neurology, Health Sciences Unit, Graduate Program in Health Sciences, University of Southern Santa Catarina, Criciuma, SC, Brazil
- Health Sciences Unit, Program in Health Sciences, University of South Santa Catarina, Tubarao, SC, Brazil
| | - Richard Simon Machado
- Laboratory of Experimental Neurology, Health Sciences Unit, Graduate Program in Health Sciences, University of Southern Santa Catarina, Criciuma, SC, Brazil
| | - Taise Cardoso
- Laboratory of Experimental Neurology, Health Sciences Unit, Graduate Program in Health Sciences, University of Southern Santa Catarina, Criciuma, SC, Brazil
| | - Beatriz Naspolini
- Laboratory of Experimental Neurology, Health Sciences Unit, Graduate Program in Health Sciences, University of Southern Santa Catarina, Criciuma, SC, Brazil
| | - Josiane Prophiro
- Health Sciences Unit, Program in Health Sciences, University of South Santa Catarina, Tubarao, SC, Brazil
| | - Fabricia Petronilho
- Laboratory of Experimental Neurology, Health Sciences Unit, Graduate Program in Health Sciences, University of Southern Santa Catarina, Criciuma, SC, Brazil.
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Al-Haddad BJS, Olson E, Reardon E, Bonney E. Neurodevelopmental screening for neonates less than 44 weeks gestation in low-income and middle-income countries: a systematic review. BMJ Glob Health 2025; 10:e017683. [PMID: 40180429 PMCID: PMC11966953 DOI: 10.1136/bmjgh-2024-017683] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2024] [Accepted: 03/16/2025] [Indexed: 04/05/2025] Open
Abstract
INTRODUCTION With global improvements in neonatal survival, more small and sick newborns in low-income and middle-income countries (LMICs) are at increased risk of neurodevelopmental disability and delay. While there is increased recognition of the importance of early identification of neurodevelopmental differences and timely initiation of therapy, little is known about standardised neonatal neurodevelopmental screening tools in these settings. METHODS We performed a systematic review to determine what standardised neurodevelopmental assessments had been used in LMICs for neonates before 44 weeks corrected gestational age and published in the literature. We excluded short-term clinical assessments designed for specific pathologies. We performed the search across seven databases, screened studies for eligibility and inclusion and extracted bibliographic data, country, patient characteristics, assessments and study aims. Results were summarised in tabular and graphical presentation. RESULTS There were 2477 records screened, yielding 67 studies for inclusion. Studies in Asian countries made up 65.7%, while Latin America and Africa made up 19.4% and 16.4%, respectively. Physicians and paramedical staff performed the screening assessments in only 16.4% of studies, and 92.5% of studies used inpatient recruitment. The Neonatal Behavioural Neurological Assessment (25.4%) was the most frequently used screening tool followed by the General Movements Assessment (22.4%), the Hammersmith Neonatal Neurological Examination/Dubowitz (16.4%) and the Neonatal Behavioural Assessment Scale (10.4%). CONCLUSIONS We did not identify any one neonatal neurodevelopmental screening assessment that is rapid, globally validated, identifies targets for intervention, has high predictive prognostic value and does not require neonatal or kinesiologic expertise or uncommon equipment. Such an assessment, in concert with evidence-based intervention, therapeutic delivery platforms, established referral pathways and trained personnel would improve functional outcomes for high-risk small and sick neonates in LMICs.
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Affiliation(s)
- Benjamin J S Al-Haddad
- Department of Pediatrics, University of Minnesota Twin Cities, Minneapolis, Minnesota, USA
- University of Minnesota Masonic Institute for the Developing Brain, Minneapolis, Minnesota, USA
| | - Elisabeth Olson
- University of Minnesota Masonic Institute for the Developing Brain, Minneapolis, Minnesota, USA
| | - Erin Reardon
- Libraries, Emory University, Atlanta, Georgia, USA
| | - Emmanuel Bonney
- University of Minnesota Masonic Institute for the Developing Brain, Minneapolis, Minnesota, USA
- University of Minnesota Twin Cities School of Kinesiology, Minneapolis, Minnesota, USA
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18
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Nguyen TQN, Do THG, Nguyen TV, Pham TN, Hoang TBN. Neonatal sepsis in Vietnam: Bacterial profiles and antibiotic susceptibility in a tertiary care setting. Am J Infect Control 2025; 53:453-457. [PMID: 39742918 DOI: 10.1016/j.ajic.2024.12.016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2024] [Revised: 12/24/2024] [Accepted: 12/26/2024] [Indexed: 01/04/2025]
Abstract
BACKGROUND Neonatal sepsis is a leading cause of newborn mortality, particularly in low- and middle-income countries. This study examines the bacterial etiologies and antibiotic resistance patterns of neonatal sepsis in a tertiary hospital in Vietnam. METHODS A prospective cross-sectional study was conducted at National Children's Hospital, Hanoi, Vietnam from January 2021 to December 2022. All neonates with a clinical suspicion of sepsis and a confirmed positive blood culture were identified. Isolated pathogens were identified, and antibiotic susceptibility was assessed using standard protocols. RESULTS In total, 202 neonates were diagnosed with proven sepsis. Among these, 75.2% of cases referred from other hospitals. Early-onset sepsis accounted for 15.8% of these infections. Gram-negative bacteria were responsible for 75.7% of the cases, with Klebsiella pneumoniae being the most prevalent pathogen (32.2%), followed by Staphylococcus aureus (14.9%), and both Serratia marcescens and Escherichia coli (10.9% each). Gram-negative bacteria showed significant resistance to third-generation cephalosporins, carbapenems, while gram-positive bacteria demonstrated considerable resistance to clindamycin and oxacillin. However, most gram-positive isolates were susceptible to vancomycin, and gram-negative bacteria had lower resistance to colistin and fosfomycin. CONCLUSIONS These findings highlight the critical importance of continuous surveillance and tailored antibiotic policies to combat neonatal sepsis effectively.
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Affiliation(s)
- Thi Quynh Nga Nguyen
- Department of Pediatrics, Hanoi Medical University, Ha Noi, Vietnam; Neonatal Center, Vietnam National Children's Hospital, Hanoi, Vietnam.
| | | | - Thi Van Nguyen
- Department of Pediatrics, Hanoi Medical University, Ha Noi, Vietnam
| | - Thao Nguyen Pham
- Department of Pediatrics, Hanoi Medical University, Ha Noi, Vietnam; Neonatal Center, Vietnam National Children's Hospital, Hanoi, Vietnam
| | - Thi Bich Ngoc Hoang
- Department of Microbiology, Vietnam National Children's Hospital, Hanoi, Vietnam
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Tuura RO, Kottke R, Brotschi B, Sabandal C, Hagmann C, Latal B. Elevated cerebral perfusion in neonatal encephalopathy is associated with neurodevelopmental impairments. Pediatr Res 2025; 97:1597-1604. [PMID: 39289590 PMCID: PMC12119360 DOI: 10.1038/s41390-024-03553-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/12/2024] [Revised: 07/19/2024] [Accepted: 08/27/2024] [Indexed: 09/19/2024]
Abstract
BACKGROUND Neonatal encephalopathy (NE) represents a primary cause of neonatal death and neurodevelopmental impairments. In newborns with NE, cerebral hyperperfusion is related to an increased risk of severe adverse outcomes, but less is known about the link between perfusion and mild to moderate developmental impairments or developmental delay. METHODS Using arterial spin labelling perfusion MRI, we investigated the link between perfusion in 36 newborns with NE and developmental outcome at 2 years. RESULTS 53% of the infants demonstrated a normal outcome at 24 months, while two had cerebral palsy with impairments in cognitive, motor, and language domains, and three infants died. The remaining infants showed mild or moderate delays in development in one or two domains. Hyperperfusion across the whole brain was associated with more adverse outcome, including an increased risk of death or severe disability such as cerebral palsy. Among the surviving infants, higher perfusion in the bilateral basal ganglia, thalamus, hippocampus and cerebellum during the neonatal period was related to a poorer cognitive outcome at 2 years. CONCLUSION Hyperperfusion in infants with NE was associated with a more adverse outcome and lower cognitive outcome scores. In addition to severe adverse outcomes, altered perfusion is also related to mild to moderate impairment following HIE. IMPACT STATEMENT Neonates with neonatal encephalopathy (NE) show increased cerebral perfusion globally, which is linked to a more adverse outcome. Higher perfusion in the bilateral basal ganglia, thalamus, hippocampus and cerebellum during the neonatal period was related to a poorer cognitive outcome at 2 years. In addition to severe adverse outcomes altered perfusion is related to mild to moderate impairment following NE. To improve neurodevelopmental outcomes, it is important to improve our understanding of the factors influencing cerebral perfusion in infants with NE.
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Affiliation(s)
- Ruth O'Gorman Tuura
- Center for MR Research, University Children's Hospital Zürich, University of Zürich (UZH), Zürich, Switzerland.
- Children's Research Center, University Children's Hospital Zürich, University of Zürich (UZH), Zürich, Switzerland.
| | - Raimund Kottke
- Children's Research Center, University Children's Hospital Zürich, University of Zürich (UZH), Zürich, Switzerland
- Department of Diagnostic Imaging, University Children's Hospital Zürich, University of Zürich (UZH), Zürich, Switzerland
| | - Barbara Brotschi
- Children's Research Center, University Children's Hospital Zürich, University of Zürich (UZH), Zürich, Switzerland
- Department of Neonatology and Paediatric Intensive Care, University Children's Hospital Zürich, University of Zurich (UZH), Zürich, Switzerland
| | - Carola Sabandal
- Children's Research Center, University Children's Hospital Zürich, University of Zürich (UZH), Zürich, Switzerland
- Department of Anaesthesia, University Children's Hospital Zürich, University of Zurich (UZH), Zürich, Switzerland
| | - Cornelia Hagmann
- Children's Research Center, University Children's Hospital Zürich, University of Zürich (UZH), Zürich, Switzerland
- Department of Neonatology and Paediatric Intensive Care, University Children's Hospital Zürich, University of Zurich (UZH), Zürich, Switzerland
| | - Beatrice Latal
- Children's Research Center, University Children's Hospital Zürich, University of Zürich (UZH), Zürich, Switzerland
- Child Development Center, University Children's Hospital Zurich, University of Zürich (UZH), Zürich, Switzerland
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20
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Menzhulina E, Vitrou J, Merrer J, Holmstrom E, Amara IA, Le Pennec E, Stirnemann J, Ben M' Barek I. Integration of clinical features in a computerized cardiotocography system to predict severe newborn acidemia. Eur J Obstet Gynecol Reprod Biol 2025; 307:78-83. [PMID: 39893788 DOI: 10.1016/j.ejogrb.2025.01.030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2024] [Revised: 01/12/2025] [Accepted: 01/19/2025] [Indexed: 02/04/2025]
Abstract
BACKGROUND Cardiotocography (CTG), used during labor to assess fetal wellbeing, is subject to interobserver variability. Computerized CTG is a promising tool to improve fetal hypoxia detection. OBJECTIVE To assess if adding clinical features improves the performance of a computerized CTG system to predict severe newborn acidemia (blood cord pH below 7.05). METHODS A retrospective multicentric database was built using the data from two sources (the open-source CTU-UHB database and the data from Beaujon university hospital). Four CTG features were extracted from the fetal heart rate (FHR) signal (minimum and maximum value of the baseline, area covered by the accelerations and decelerations). Clinical features were also collected. Severe fetal acidemia was defined by arterial pH < 7.05 on umbilical cord sample. Risk factors for severe acidemia were sought by comparing cases with severe newborn acidemia to the rest of the cohort. We evaluated the accuracy of the model using both CTG and clinical features using area under the curve (AUC) in a cross-center, cross-validation approach. RESULTS The datasets contained 1264 cases including 100 cases with severe acidemia. In univariate analysis, hypertensive disorders and other clinical features showed no significant difference, except for meconium-stained amniotic fluid (p = 0.03). Multivariate analysis revealed that a high deceleration area (OR = 1.09 [1.04--1.11]) and apparition of meconium amniotic fluid increased the risk of newborn acidemia (OR = 2.10[1.24-3.49]). In a k-fold cross-validation approach, DeepCTG®1.5 reached an AUC of 0.77, compared to 0.74 when using CTG features only. CONCLUSION The CTG features have a good accuracy to predict severe newborn acidemia, confirming existing literature. Integrating clinical features tends to enhance the accuracy. Further research will aim at using more advanced machine learning models to combine the features more efficiently.
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Affiliation(s)
- Elena Menzhulina
- Department of gynecology and obstetrics - Hopital Beaujon Assistante Publique des Hôpitaux de Paris, 100 boulevard du Général Leclerc 92100 Clichy, France; Université Paris Cité, 6 rue de l'Ecole de Médecine 75006 Paris, France
| | - Juliette Vitrou
- Department of gynecology and obstetrics - Hopital Beaujon Assistante Publique des Hôpitaux de Paris, 100 boulevard du Général Leclerc 92100 Clichy, France; Université Paris Cité, 6 rue de l'Ecole de Médecine 75006 Paris, France
| | - Jade Merrer
- Unité d'Épidémiologie Clinique, INSERM CIC1426, Hôpital Robert Debré, APHP Paris, France
| | - Emilia Holmstrom
- Department of gynecology and obstetrics - Hopital Beaujon Assistante Publique des Hôpitaux de Paris, 100 boulevard du Général Leclerc 92100 Clichy, France
| | - Inesse Ait Amara
- Department of gynecology and obstetrics - Hopital Beaujon Assistante Publique des Hôpitaux de Paris, 100 boulevard du Général Leclerc 92100 Clichy, France; Université Paris Cité, 6 rue de l'Ecole de Médecine 75006 Paris, France
| | - Erwan Le Pennec
- CMAP, IP Paris, École polytechnique, CNRS 91128 Palaiseau Cédex, France
| | - Julien Stirnemann
- Université Paris Cité, 6 rue de l'Ecole de Médecine 75006 Paris, France; Department of Gynecology and Obstetrics - Hopital Necker Assistante Publique des Hôpitaux de Paris, France
| | - Imane Ben M' Barek
- Department of gynecology and obstetrics - Hopital Beaujon Assistante Publique des Hôpitaux de Paris, 100 boulevard du Général Leclerc 92100 Clichy, France; Université Paris Cité, 6 rue de l'Ecole de Médecine 75006 Paris, France.
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21
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El Ghazouani H, Lahlou L, Yakini S, Bou-iselmane M, Elkhalladi J, Bouaiti EA, Barkat A. Prognostic factors for neonatal mortality at the Agadir regional hospital centre, Morocco: A cohort study. J Taibah Univ Med Sci 2025; 20:151-158. [PMID: 40125535 PMCID: PMC11928835 DOI: 10.1016/j.jtumed.2025.02.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2024] [Revised: 12/26/2024] [Accepted: 02/17/2025] [Indexed: 03/25/2025] Open
Abstract
Introduction Although neonatal mortality is declining globally, progress is slow, particularly in Africa. The goal of this study was to determine the predictive factors associated with survival in newborns at the Agadir Regional Hospital Centre, Morocco. Methods This retrospective cohort study performed at the neonatology department of the Agadir Regional Hospital Centre included neonates, from birth to 28 days old, who were hospitalized between January 1 and May 9, 2022. Prognostic factors were determined through univariate analysis with the Kaplan-Meier survival analysis method, and survival rates were compared with the log-rank test. The Cox model was used to determine factors associated with neonatal survival. Results Of 639 enrolled newborns, 95.9 % were hospitalized during the first week of life. A total of 115 newborns died, resulting in an in-hospital neonatal mortality rate of 18 % (95 % CI [15.2-21.2]), and 98.3 % were early neonatal deaths. The factors associated with elevated death risk were perinatal asphyxia (aHR = 2.61, 95 % CI [1.57-4.43], p < 0.001); prematurity (aHR = 2.15, 95 % CI [1.17-3.94], p = 0.013); neonatal age ≤7 days (aHR = 4.89, 95 % CI [1.14-20.94], p = 0.032); low birth weight (aHR = 2.25, 95 % CI [1.28-3.94], p = 0.005); and hypothermia (aHR = 7.60, 95 % CI [1.71-33.73], p = 0.008). Conclusion The neonatal mortality rate remains high. Developing the skills of healthcare providers, strengthening risk screening for pregnancies, and enhancing resuscitation and early care for newborns are essential to decrease neonatal mortality.
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Affiliation(s)
- Hanane El Ghazouani
- Laboratory of Clinical Epidemiology and Medical-surgical Sciences, Research Team on Health and Nutrition of Mother and Child, Faculty of Medicine and Pharmacy, Mohammed V University, Rabat, Morocco
| | - Laila Lahlou
- Laboratory of Health and Science, Therapeutic Innovation, Translational Research and Epidemiology, Faculty of Medicine and Pharmacy Ibn Zohr University, Agadir, Morocco
| | - Souad Yakini
- Laboratory of Clinical Epidemiology and Medical-surgical Sciences, Research Team on Health and Nutrition of Mother and Child, Faculty of Medicine and Pharmacy, Mohammed V University, Rabat, Morocco
| | - Maryama Bou-iselmane
- Laboratory of Clinical Epidemiology and Medical-surgical Sciences, Research Team on Health and Nutrition of Mother and Child, Faculty of Medicine and Pharmacy, Mohammed V University, Rabat, Morocco
| | - Jaouad Elkhalladi
- Oral Biology and Biotechnology Laboratory, Faculty of Medicine and Pharmacy, Mohammed V University, Rabat, Morocco
| | - El Arbi Bouaiti
- Laboratory of Biostatistics, Clinical Research and Epidemiology, Faculty of Medicine and Pharmacy, Mohammed V University, Rabat, Morocco
| | - Amina Barkat
- Laboratory of Clinical Epidemiology and Medical-surgical Sciences, Research Team on Health and Nutrition of Mother and Child, Faculty of Medicine and Pharmacy, Mohammed V University, Rabat, Morocco
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22
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Hewish A, Dibley MJ, Raihana S, Rahman MM, Islam S, el Arifeen S, Huda T. The neonatal mortality risk of vulnerable newborns in rural Bangladesh: A prospective cohort study within the Shonjibon trial. Trop Med Int Health 2025; 30:283-291. [PMID: 39894679 PMCID: PMC11965014 DOI: 10.1111/tmi.14092] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2025]
Abstract
OBJECTIVES Preterm birth (<37 weeks), low birth weight (2500 g), small-for-gestational-age (birth weight <10th percentile of a given reference), and large-for-gestational-age (birth weight >90th percentile of a given reference) are indicators of vulnerable infants and risk factors for neonatal mortality. We estimated the prevalence and risk of neonatal mortality associated with these phenotypes and their mutually exclusive phenotypes in rural Bangladesh. METHODS We conducted a prospective cohort study in five rural districts of Bangladesh using data collected from births in the Shonjibon Trial from 2013 to 2015. We estimated the prevalence of preterm birth, low birth weight, small-for-gestational-age, and large-for-gestational-age infants, individually and for mutually exclusive phenotypes, using a combination of these phenotypes. Neonatal mortality associated with preterm birth, low birth weight, small-for-gestational-age, large-for-gestational-age, and mutually exclusive phenotypes were calculated using Kaplan-Meier survival analysis and Poisson regression for adjusted relative risks (aRR) with 95% confidence intervals (CI). RESULTS We included 24,314 live births in this study. The prevalence of preterm birth, low birth weight, small-for-gestational-age, and large-for-gestational-age was 26.2%, 22.9%, 41.7%, and 8.2%, respectively. The prevalence of babies born appropriate for gestational age, with term gestation (≥37 weeks) and normal birth weight (≥2500 g) was 33.3%. For individual phenotypes, the neonatal mortality risk was approximately 3-fold for preterm, low birth weight, and large-for-gestational-age newborns and 1.5-fold for small-for-gestational-age newborns compared with appropriate-for-gestational-age, term, and normal birth weight newborns. The risk of neonatal mortality for mutually exclusive phenotypes was highest in small-for-gestational-age, preterm, and low birth weight newborns (aRR = 6.3, 95% CI 4.1-9.6) relative to appropriate for gestational age, term, and normal birth weight newborns. CONCLUSIONS In rural Bangladesh, most infants are born with one or more vulnerable phenotypes associated with an increased risk of neonatal mortality. Our findings highlight the value of categorising newborns using mutually exclusive vulnerable phenotypes and their neonatal mortality risks, which can be used to tailor interventions to improve survival.
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Affiliation(s)
- Alexandra Hewish
- Sydney School of Public Health, Sydney Medical SchoolThe University of SydneyCamperdownNew South WalesAustralia
| | - Michael J. Dibley
- Sydney School of Public Health, Sydney Medical SchoolThe University of SydneyCamperdownNew South WalesAustralia
| | - Shahreen Raihana
- Sydney School of Public Health, Sydney Medical SchoolThe University of SydneyCamperdownNew South WalesAustralia
| | | | - Sajia Islam
- Maternal and Child Health DivisionInternational Centre for Diarrhoeal Disease ResearchDhakaBangladesh
| | - Shams el Arifeen
- Maternal and Child Health DivisionInternational Centre for Diarrhoeal Disease ResearchDhakaBangladesh
| | - Tanvir Huda
- Sydney School of Public Health, Sydney Medical SchoolThe University of SydneyCamperdownNew South WalesAustralia
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23
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Reyes-Corral M, Gil-González L, González-Díaz Á, Tovar-Luzón J, Ayuso MI, Lao-Pérez M, Montaner J, de la Puerta R, Fernández-Torres R, Ybot-González P. Pretreatment with oleuropein protects the neonatal brain from hypoxia-ischemia by inhibiting apoptosis and neuroinflammation. J Cereb Blood Flow Metab 2025; 45:717-734. [PMID: 39157939 DOI: 10.1177/0271678x241270237] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 08/20/2024]
Abstract
Hypoxic-ischemic (HI) encephalopathy is a cerebrovascular injury caused by oxygen deprivation to the brain and remains a major cause of neonatal mortality and morbidity worldwide. Therapeutic hypothermia is the current standard of care but it does not provide complete neuroprotection. Our aim was to investigate the neuroprotective effect of oleuropein (Ole) in a neonatal (seven-day-old) mouse model of HI. Ole, a secoiridoid found in olive leaves, has previously shown to reduce damage against cerebral and other ischemia/reperfusion injuries. Here, we administered Ole as a pretreatment prior to HI induction at 20 or 100 mg/kg. A week after HI, Ole significantly reduced the infarct area and the histological damage as well as white matter injury, by preserving myelination, microglial activation and the astroglial reactive response. Twenty-four hours after HI, Ole reduced the overexpression of caspase-3 and the proinflammatory cytokines IL-6 and TNF-α. Moreover, using UPLC-MS/MS we found that maternal supplementation with Ole during pregnancy and/or lactation led to the accumulation of its metabolite hydroxytyrosol in the brains of the offspring. Overall, our results indicate that pretreatment with Ole confers neuroprotection and can prevent HI-induced brain damage by modulating apoptosis and neuroinflammation.
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Affiliation(s)
- Marta Reyes-Corral
- Institute of Biomedicine of Seville (IBiS), CSIC-US-Junta de Andalucía (SAS), Seville, Spain
| | - Laura Gil-González
- Institute of Biomedicine of Seville (IBiS), CSIC-US-Junta de Andalucía (SAS), Seville, Spain
| | - Ángela González-Díaz
- Institute of Biomedicine of Seville (IBiS), CSIC-US-Junta de Andalucía (SAS), Seville, Spain
| | - Javier Tovar-Luzón
- Institute of Biomedicine of Seville (IBiS), CSIC-US-Junta de Andalucía (SAS), Seville, Spain
| | - María Irene Ayuso
- Institute of Biomedicine of Seville (IBiS), CSIC-US-Junta de Andalucía (SAS), Seville, Spain
- CIBERSAM, ISCIII (Spanish Network for Research in Mental Health), Seville, Spain
| | - Miguel Lao-Pérez
- Institute of Biomedicine of Seville (IBiS), CSIC-US-Junta de Andalucía (SAS), Seville, Spain
| | - Joan Montaner
- Institute of Biomedicine of Seville (IBiS), CSIC-US-Junta de Andalucía (SAS), Seville, Spain
- Department of Neurology, Virgen Macarena University Hospital, Seville, Spain
| | - Rocío de la Puerta
- Department of Pharmacology, Faculty of Pharmacy, University of Seville, Seville, Spain
| | - Rut Fernández-Torres
- Departamento de Química Analítica, Facultad de Química, Universidad de Sevilla, Seville, Spain
| | - Patricia Ybot-González
- Institute of Biomedicine of Seville (IBiS), CSIC-US-Junta de Andalucía (SAS), Seville, Spain
- Spanish National Research Council (CSIC), Spain
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24
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Ziabska K, Gewartowska M, Frontczak-Baniewicz M, Sypecka J, Ziemka-Nalecz M. The Impact of the Histone Deacetylase Inhibitor-Sodium Butyrate on Complement-Mediated Synapse Loss in a Rat Model of Neonatal Hypoxia-Ischemia. Mol Neurobiol 2025; 62:5216-5233. [PMID: 39531190 PMCID: PMC11880148 DOI: 10.1007/s12035-024-04591-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2024] [Accepted: 10/24/2024] [Indexed: 11/16/2024]
Abstract
Perinatal asphyxia is one of the most important causes of morbidity and mortality in newborns. One of the key pathogenic factors in hypoxic-ischemic (HI) brain injury is the inflammatory reaction including complement system activation. Over-activated complement stimulates cells to release inflammatory molecules and is involved in the post-ischemic degradation of synaptic connections. On the other hand, complement is also involved in regenerative processes. The histone deacetylase inhibitor (HDACi)-sodium butyrate (SB)-provides reduction of inflammation by decreasing the expression of the proinflammatory factors. The main purpose of this study was to examine the effect of SB treatment on complement activation and synapse elimination after HI. Neonatal HI was induced in Wistar rats pups by unilateral ligation of the common carotid artery followed by 60-min hypoxia (7.6% O2). SB (300 mg/kg) was administered on a 5-day regimen. Our study has shown decreased levels of synapsin I, synaptophysin, and PSD-95 in the hypoxic-ischemic hemisphere, indicating synaptic loss after neonatal HI. Transmission electron microscopy revealed injury of the synaptic structures in the brain after HI. SB treatment increased the level of the synaptic proteins, improved tissue ultrastructure, and reduced degradation of the synapses. Neonatal HI induced mRNA expression of the complement C1q, C3, C5, and C9, and their receptors C3aR and C5aR. The effect of SB was different depending on the time after induction of hypoxic-ischemic damage. Our study demonstrated that neuroprotective effect of SB may be related to the modulation of complement activity after HI brain injury.
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Affiliation(s)
- Karolina Ziabska
- NeuroRepair Department, Mossakowski Medical Research Institute, Polish Academy of Sciences, 5 A. Pawinskiego Street, 02-106, Warsaw, Poland
| | - Magdalena Gewartowska
- Electron Microscopy Research Unit, Mossakowski Medical Research Institute, Polish Academy of Sciences, 5 A. Pawinskiego Street, 02-106, Warsaw, Poland
| | - Malgorzata Frontczak-Baniewicz
- Electron Microscopy Research Unit, Mossakowski Medical Research Institute, Polish Academy of Sciences, 5 A. Pawinskiego Street, 02-106, Warsaw, Poland
- Higher School of Engineering and Health in Warsaw, 18 Bitwy Warszawskiej 1920r. Street, 02-366, Warsaw, Poland
| | - Joanna Sypecka
- NeuroRepair Department, Mossakowski Medical Research Institute, Polish Academy of Sciences, 5 A. Pawinskiego Street, 02-106, Warsaw, Poland
| | - Malgorzata Ziemka-Nalecz
- NeuroRepair Department, Mossakowski Medical Research Institute, Polish Academy of Sciences, 5 A. Pawinskiego Street, 02-106, Warsaw, Poland.
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25
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Li X, Li T, Fu H, Lin F, Li C, Bai Q, Jin Z. C-reactive protein to platelet ratio as an early biomarker in differentiating neonatal late-onset sepsis in neonates with pneumonia. Sci Rep 2025; 15:10760. [PMID: 40155410 PMCID: PMC11953421 DOI: 10.1038/s41598-025-94845-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2024] [Accepted: 03/17/2025] [Indexed: 04/01/2025] Open
Abstract
Neonates with pneumonia (NWP) may experience unidentified life-threatening sepsis, yet distinguishing NWP from neonates with sepsis (NWS) based solely on clinical presentation remains challenging. This study aimed to evaluate the diagnostic utility of the C-reactive protein to platelet ratio (CPR) in distinguishing neonatal late-onset sepsis (LOS) among NWPs. From February 2016 to March 2022, a total of 1385 NWPs aged over 3 days were included. Of these, 174 neonates with confirmed positive blood cultures were categorized into the sepsis cohort, while the remainder formed the pneumonia cohort. All clinical data were retrospectively extracted from electronic medical records. CPR was calculated as the ratio of C-reactive protein levels to platelet count. Independent risk factors (IRFs) for neonatal LOS were identified through multivariate logistic regression. The diagnostic performance of CPR in identifying LOS among NWPs was analyzed using receiver operating characteristic (ROC) curve metrics. Statistical analyses were conducted using SPSS version 24.0 and MedCalc version 15.2.2. Neonates with NWS demonstrated significantly higher CPR compared to those with NWP alone. Further analysis revealed a notably increased incidence of sepsis among neonates exhibiting elevated CPR levels relative to those with lower values. Correlation analysis identified a direct association between CPR and elevated procalcitonin, creatinine, and urea nitrogen levels, as well as prolonged hospitalization. Multiple logistic regression analysis identified CPR as an IRF for late-onset NWS. ROC curve analysis demonstrated that CPR outperformed CRP and platelet count individually in diagnosing NWS, with a diagnostic sensitivity of 54% and specificity of 85%. CPR serves as an effective initial diagnostic marker with superior accuracy in distinguishing delayed NWS from NWP compared to CRP and platelet count alone.
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Affiliation(s)
- Xiaojuan Li
- Department of Clinical Laboratory, Zhengzhou Key Laboratory of Children's Infection and Immunity, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou, China
| | - Tiewei Li
- Department of Clinical Laboratory, Zhengzhou Key Laboratory of Children's Infection and Immunity, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou, China.
| | - Hui Fu
- Department of Neonatal Medicine, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou, China.
| | - Fatao Lin
- Department of Neonatal Medicine, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou, China
| | - Ci Li
- Department of Clinical Laboratory, Zhengzhou Key Laboratory of Children's Infection and Immunity, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou, China
| | - Qiongdan Bai
- Department of Neonatal Medicine, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou, China
| | - Zhipeng Jin
- Pediatric Intensive Care Unit, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou, China.
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26
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Hitachi M, Miyamichi K, Honda S, Wanjihia V, Nzou SM, Kaneko S. The association between 2017 American College of Cardiology/American Heart Association guideline for hypertension and neonatal outcomes in Kenya: a retrospective study. Trop Med Health 2025; 53:41. [PMID: 40140906 PMCID: PMC11948941 DOI: 10.1186/s41182-025-00724-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2024] [Accepted: 03/07/2025] [Indexed: 03/28/2025] Open
Abstract
BACKGROUND Hypertension in pregnancy serves to screen for adverse perinatal outcomes. In 2017, the American College of Cardiology and American Heart Association recommended a new blood pressure category with lower hypertension thresholds, excluding pregnancy. This study aimed to explore the association between the 2017 redefined blood pressure categories in pregnancy and neonatal outcomes such as preterm birth and low birth weight. METHODS This retrospective study used electronic records of the Maternal and Child Health Handbook registered by the Women and Infant Registration System. All women who had at least one antenatal care visit and delivery between January 2017 and April 2020 and between May and December 2022 were included in the study. A birth of less than 37 weeks was defined as preterm delivery. LBW was identified based on a newborn's birthweight of less than 2500 g. The maximum blood pressure across all antenatal care visits was classified based on the newly recommended criteria. A generalized linear model with binomial distribution and logit link function was used to evaluate the association between new blood pressure categories and neonatal outcomes at different levels of health facilities. RESULTS We analyzed data from 825 women. Of these, the prevalence was 13.7% for elevated blood pressure, 15.2% for stage 1 hypertension, 4.5% for non-severe stage 2 hypertension and 1.2% for severe stage 2 hypertension. For lower-level facilities, no significant associations were identified between the redefined blood pressure category and preterm birth or low birthweight. At higher-level facilities, preterm birth was only significantly associated with severe stage 2 hypertension (adjusted odds ratio:10.94; 95% confidence interval:1.08-110.93; P = 0.04) and low birthweight showed no association with the redefined category. CONCLUSION This study revealed no association between redefined lower blood pressure threshold and preterm birth and low birthweight in under-resourced settings. However, previous studies in well-resourced countries with larger sample sizes also reported a significant association. Therefore, further investigations are required.
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Affiliation(s)
- Mami Hitachi
- Department of Ecoepidemiology, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan.
| | - Kazuchiyo Miyamichi
- Kenya Research Station, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan
| | - Sumihisa Honda
- Department of Nursing, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Violet Wanjihia
- Centre for Public Health Research, Kenya Medical Research Institute, Nairobi, Kenya
| | - Samson Muuo Nzou
- Centre for Microbiology Research, Kenya Medical Research Institute, Nairobi, Kenya
| | - Satoshi Kaneko
- Department of Ecoepidemiology, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan
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27
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Tang MH, Ligthart I, Varga S, Lebeer S, van Overveld FJ, Rijkers GT. Mutual Interactions Between Microbiota and the Human Immune System During the First 1000 Days of Life. BIOLOGY 2025; 14:299. [PMID: 40136555 PMCID: PMC11940030 DOI: 10.3390/biology14030299] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/03/2025] [Revised: 02/25/2025] [Accepted: 03/14/2025] [Indexed: 03/27/2025]
Abstract
The development of the human immune system starts during the fetal period in a largely, but probably not completely, sterile environment. During and after birth, the immune system is exposed to an increasingly complex microbiota. The first microbiota encountered during passage through the birth canal colonize the infant gut and induce the tolerance of the immune system. Transplacentally derived maternal IgG as well as IgA from breast milk protect the infant from infections during the first 100 days, during which the immune system further develops and immunological memory is formed. The Weaning and introduction of solid food expose the immune system to novel (food) antigens and allow for other microbiota to colonize. The cells and molecules involved in the mutual and intricate interactions between microbiota and the developing immune system are now beginning to be recognized. These include bacterial components such as polysaccharide A from Bacteroides fragilis, as well as bacterial metabolites such as the short-chain fatty acid butyrate, indole-3-aldehyde, and indole-3-propionic acid. All these, and probably more, bacterial metabolites have specific immunoregulatory functions which shape the development of the human immune system during the first 1000 days of life.
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Affiliation(s)
- Muy Heang Tang
- Department of Science and Engineering, University College Roosevelt, 4331 CB Middelburg, The Netherlands; (M.H.T.); (I.L.); (S.V.); (F.J.v.O.)
| | - Ishbel Ligthart
- Department of Science and Engineering, University College Roosevelt, 4331 CB Middelburg, The Netherlands; (M.H.T.); (I.L.); (S.V.); (F.J.v.O.)
| | - Samuel Varga
- Department of Science and Engineering, University College Roosevelt, 4331 CB Middelburg, The Netherlands; (M.H.T.); (I.L.); (S.V.); (F.J.v.O.)
| | - Sarah Lebeer
- Lab of Applied Microbiology and Biotechnology, Department of Bioscience Engineering, University of Antwerp, 2020 Antwerpen, Belgium;
| | - Frans J. van Overveld
- Department of Science and Engineering, University College Roosevelt, 4331 CB Middelburg, The Netherlands; (M.H.T.); (I.L.); (S.V.); (F.J.v.O.)
| | - Ger T. Rijkers
- Department of Science and Engineering, University College Roosevelt, 4331 CB Middelburg, The Netherlands; (M.H.T.); (I.L.); (S.V.); (F.J.v.O.)
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Shayo FS, Kessy AT, Amour M. Fidelity of health care providers on adhering to guidelines for managing neonates with respiratory distress using Silverman Anderson Severity (SAS) score tool in limited resource settings: a case study at Amana Regional Referral Hospital. BMC Health Serv Res 2025; 25:381. [PMID: 40087682 PMCID: PMC11907878 DOI: 10.1186/s12913-025-12517-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2024] [Accepted: 03/05/2025] [Indexed: 03/17/2025] Open
Abstract
BACKGROUND This case study was conducted at Amana Regional Referral Hospital, a referral hospital of Ilala District in Dar es Salaam Region, Tanzania. The aim is to assess the adherence of healthcare providers to guidelines when providing health services to neonates with respiratory distress and how supportive the health system is in limited resource settings. METHODS This is a case study that used a qualitative approach to data collection and analysis. A total of 16 participants participated in this study, of which the sample size was reached by the principle of information saturation in the field. The study population was healthcare providers (pediatricians, general medical doctors, and nurses) working in the neonatal ward who were selected purposively depending on their experience in the neonatal ward. In-depth interviews (IDI) and an observation checklist were used for data collection from key informants, and content analysis was used to analyze the data. RESULTS The findings revealed that healthcare providers had partially adhered to guidelines in managing neonates with respiratory distress. The Silverman-Anderson Severity (SAS) score tool is recommended for decision-making in prioritizing neonates with respiratory distress to Continuous Positive Airway Pressure (CPAP) treatment in limited-resource health settings with low laboratory technology. Healthcare providers know the importance of using the SAS score tool, but this study shows partial adherence to the use of it. Understaffing, inadequate training, heavy workloads, and lack of motivation emerged as significant deterrents to adherence which are within the health system, and they negatively impact healthcare provider's adherence. These challenges hindered proper monitoring, documentation, and decision-making processes for CPAP initiation and monitoring. CONCLUSION Partial adherence to guidelines for managing neonates with respiratory distress in the context of consistent use of the SAS score tool by healthcare providers was impacted by challenges like understaffing, heavy workloads, and low motivation. Improving staffing, providing comprehensive training, and ensuring adequate equipment are recommended to enhance guideline adherence and improve neonatal care in resource-limited settings.
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Affiliation(s)
- Fredrick Salvatory Shayo
- Department of Developmental Studies, Muhimbili University of Health and Allied Science, Dar Es Salaam, Tanzania.
| | - Anna Tengia Kessy
- Department of Community Health, Muhimbili University of Health and Allied Science, Dar Es Salaam, Tanzania
| | - Maryam Amour
- Department of Community Health, Muhimbili University of Health and Allied Science, Dar Es Salaam, Tanzania
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29
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Sufriyana H, Amani FZ, Al Hajiri AZZ, Wu YW, Su ECY. Widely accessible prognostication using medical history for fetal growth restriction and small for gestational age in nationwide insured women. Sci Rep 2025; 15:8340. [PMID: 40065124 PMCID: PMC11894118 DOI: 10.1038/s41598-025-92986-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2024] [Accepted: 03/04/2025] [Indexed: 03/14/2025] Open
Abstract
Prevention of fetal growth restriction/small for gestational age (FGR/SGA) is adequate if screening is accurate. Ultrasound and biomarkers can achieve this goal; however, both are often inaccessible. This study aimed to develop, validate, and deploy a prognostic prediction model for screening FGR/SGA using only medical history. From a nationwide health insurance database (n = 1,697,452), we retrospectively selected visits to 22,024 healthcare providers of primary, secondary, and tertiary care. This study used machine learning (including deep learning) to develop prediction models using 54 medical-history predictors. After evaluating model calibration, clinical utility, and explainability, we selected the best by discrimination ability. We also externally validated the models using geographical and temporal splits of ~ 20% of the selected visits. The models were also compared with those from previous studies, which were rigorously selected by a systematic review of Pubmed, Scopus, and Web of Science. We selected 169,746 subjects with 507,319 visits for predictive modeling from the database, which were 12-to-55-year-old female insurance holders who used the healthcare services. The best prediction model was a deep-insight visible neural network. It had an area under the receiver operating characteristics curve of 0.742 (95% confidence interval 0.734 to 0.750) and a sensitivity of 49.09% (95% confidence interval 47.60-50.58% using a threshold with 95% specificity). The model was competitive against the previous models of 30 eligible studies of 381 records, including those using either ultrasound or biomarker measurements. We deployed a web application to apply the model. Our model used only medical history to improve accessibility for FGR/SGA screening. However, future studies are warranted to evaluate if this model's usage impacts patient outcomes.
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Affiliation(s)
- Herdiantri Sufriyana
- Institute of Biomedical Informatics, College of Medicine, National Yang Ming Chiao Tung University, 155 Section 2 Linong Street, Taipei, 112304, Taiwan
- Graduate Institute of Biomedical Informatics, College of Medical Science and Technology, Taipei Medical University, 250 Wu-Xing Street, Taipei, 11031, Taiwan
- Department of Medical Physiology, Faculty of Medicine, Universitas Nahdlatul Ulama Surabaya, 57 Raya Jemursari Road, Surabaya, 60237, Indonesia
| | - Fariska Zata Amani
- Department of Obstetrics and Gynecology, Faculty of Medicine, Universitas Nahdlatul Ulama Surabaya, 57 Raya Jemursari Road, Surabaya, 60237, Indonesia
| | | | - Yu-Wei Wu
- Graduate Institute of Biomedical Informatics, College of Medical Science and Technology, Taipei Medical University, 250 Wu-Xing Street, Taipei, 11031, Taiwan
- Clinical Big Data Research Center, Taipei Medical University Hospital, 250 Wu-Xing Street, Taipei, 11031, Taiwan
| | - Emily Chia-Yu Su
- Institute of Biomedical Informatics, College of Medicine, National Yang Ming Chiao Tung University, 155 Section 2 Linong Street, Taipei, 112304, Taiwan.
- Graduate Institute of Biomedical Informatics, College of Medical Science and Technology, Taipei Medical University, 250 Wu-Xing Street, Taipei, 11031, Taiwan.
- Clinical Big Data Research Center, Taipei Medical University Hospital, 250 Wu-Xing Street, Taipei, 11031, Taiwan.
- Research Center for Artificial Intelligence in Medicine, Taipei Medical University, 250 Wu- Xing Street, Taipei, 11031, Taiwan.
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Wondifraw EB, Wudu MA, Tefera BD, Wondie KY. The burden of neonatal sepsis and its risk factors in Africa. a systematic review and meta-analysis. BMC Public Health 2025; 25:847. [PMID: 40033243 PMCID: PMC11877888 DOI: 10.1186/s12889-025-22076-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2024] [Accepted: 02/24/2025] [Indexed: 03/05/2025] Open
Abstract
BACKGROUND Neonatal sepsis is a significant cause of newborn mortality in low- and middle-income countries (LMICs). Together, infections, complications of preterm birth, and intrapartum-related conditions contribute to nearly 90% of all neonatal deaths. Africa experiences high rates of neonatal deaths due to sepsis, with insufficient prevention efforts. Understanding the burden of neonatal sepsis is essential to reducing these deaths in the region. This study aims to estimate the pooled magnitude of neonatal sepsis and identify its associated risk factors in Africa. METHOD For this study, we gathered data by searching various databases until August 20, 2024, including PubMed/MEDLINE, PubMed Central, Hinari, Google, Cochrane Library, African Journals Online, Web of Science, and Google Scholar. Full-text articles in English, both published and unpublished, from 2000 to 2024 were included. However, sources like citations without abstracts or full texts, unidentified reports, editorials, summaries of research, meta-analyses, and qualitative studies were not included in the study. We evaluated the quality of the selected papers using the Joanna Briggs Institute (JBI) critical appraisal checklist for observational studies. Data extraction was completed in Microsoft Excel, and analysis was conducted using STATA V.17 Statistical Software. We assessed study heterogeneity with the I2 statistic and the Cochrane Q test. Publication bias was evaluated both visually through a funnel plot and statistically through Egger's regression and Begg's tests. Subgroup analyses were performed to identify sources of heterogeneity, and a sensitivity analysis was conducted to find any outlier studies. RESULT This review includes 49 studies with 87,548 neonates. The overall magnitude of neonatal sepsis in Africa was found to be 40.98% (95% confidence interval (CI): 30.50% to 51.46%) P: 0.00. The study found that factors such as prolonged rupture of membranes (Odds ratio (OR) 4.11, 95% CI: 2.81-5.41) P: 0.00, a history of the urinary tract or sexually transmitted infections (OR 3.28, 95% CI: 1.97-4.58) P: 0.00, low birth weight (< 2500 g) (OR 6.95, 95% CI: 3-10.89) P: 0.00, an Appearance, Pulse, Grimace, Activity, Respiration (APGAR) score below 7 at the first minute (OR 7.56, 95% CI: 3.39-11.73) P: 0.00, preterm birth (OR 5.38, 95% CI: 3.23-7.5) P: 0.00, and neonates who were resuscitated at birth (OR 3.26, 95% CI: 1.96-4.56) P: 0.00. CONCLUSION The magnitude of neonatal sepsis in Africa remains high. This study identified several contributing factors, including prolonged rupture of membranes, a history of urinary tract or sexually transmitted infections, low birth weight (< 2500 g), an APGAR score below 7 at one minute, preterm birth, and resuscitation at birth. These findings underscore the importance of routinely screening for risk factors such as prolonged membrane rupture and maternal infections. Enhancing antenatal care, training providers in early neonatal sepsis management, and enforcing infection control measures.
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Affiliation(s)
- Endalk Birrie Wondifraw
- Department of Pediatric and Child Health Nursing, College of Medicine and Health Science, Wollo University, Dessie, Ethiopia.
| | - Muluken Amare Wudu
- Department of Pediatric and Child Health Nursing, College of Medicine and Health Science, Wollo University, Dessie, Ethiopia
| | - Birhanu Desu Tefera
- Department of Emergency and Critical Care Nursing, College of Medicine and Health Science, Wollo University, Dessie, Ethiopia
| | - Kindu Yinges Wondie
- Department of Clinical Midwifery College of Medicine and Health Science, University, Gondar, Gondar, Ethiopia
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Steinberg S, Wong M, Zimlichman E, Tsur A. Novel machine learning applications in peripartum care: a scoping review. Am J Obstet Gynecol MFM 2025; 7:101612. [PMID: 39855597 DOI: 10.1016/j.ajogmf.2025.101612] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2024] [Revised: 01/08/2025] [Accepted: 01/13/2025] [Indexed: 01/27/2025]
Abstract
OBJECTIVE Machine learning (ML), a subtype of artificial intelligence (AI), presents predictive modeling and dynamic diagnostic tools to facilitate early interventions and improve decision-making. Considering the global challenges of maternal, fetal, and neonatal morbidity and mortality, ML holds the potential to enable significant improvements in maternal and neonatal health outcomes. We aimed to conduct a comprehensive review of ML applications in peripartum care, summarizing the potential of these tools to enhance clinical decision-making and identifying emerging trends and research gaps. DATA SOURCES We conducted a scoping review on MEDLINE, Cochrane Library, and EMBASE databases from inception to April 2024. We gathered additional relevant studies through snowball sampling. We meticulously screened titles and abstracts and chose full-text articles for further analysis. STUDY ELIGIBILITY CRITERIA We included primary research articles and abstracts focusing on pregnant individuals, employing ML methods for peripartum care. STUDY APPRAISAL AND SYNTHESIS METHODS No formal quality assessment was performed. Data were extracted using a custom template to capture study characteristics and ML models. Findings were synthesized using summary tables and figures to highlight key trends and results. RESULTS Among 406 studies, 78% were published within the last five years. Most studies originated from high-income or well-resourced countries, with 27% from North America (including 24% from the United States) and 34% from Asia, predominantly China (18%). Studies from low- and middle-income regions were notably scarce, reflecting significant regional disparities. Predictive modeling tasks were the most prevalent (59%), followed by classification tasks (29%). Supervised learning dominated (90%), with algorithms such as Support Vector Machines, Random Forests, and Logistic Regression most commonly used. Key topics included fetal distress and acidemia (32%), preterm birth (22%), mode of delivery (13%), and birth weight (13%). Notably, Explainable AI methods were utilized in only 19% of studies, and external validation was performed in just 5%. Despite these advancements, only 1% of models resulted in accessible clinical tools, and none were fully integrated into healthcare systems. CONCLUSIONS ML holds significant potential to enhance peripartum care by improving diagnostic accuracy and predictive capabilities. However, realizing this potential requires responsible AI practices, including robust validation with external datasets, prospective investigations across diverse populations, and the development of digital and data infrastructure for seamless integration into electronic health records. Additionally, transparent AI that provides insights into risk stratification logic is essential for clinician trust in ML tools. Future research should address understudied areas, prioritize neglected low-income settings, and explore advanced ML approaches to improve maternal and neonatal outcomes.
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Affiliation(s)
- Shani Steinberg
- The Josef Buchmann Gynecology and Maternity Center, Sheba Medical Center (Steinberg, Tsur), Tel Hashomer, Israel; Faculty of Medicine, Tel-Aviv University (Steinberg, Zimlichman, Tsur), Tel-Aviv, Israel.
| | - Melissa Wong
- Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center (Wong), Los Angeles, CA; Division of Informatics, Department of Biomedical Sciences, Cedars-Sinai Medical Center (Wong), Los Angeles, CA
| | - Eyal Zimlichman
- ARC Innovation Center, Sheba Medical Center (Zimlichman, Tsur), Ramat Gan, Israel; Faculty of Medicine, Tel-Aviv University (Steinberg, Zimlichman, Tsur), Tel-Aviv, Israel; The Dina Recanati School of Medicine, Reichmann University (Zimlichman, Tsur), Herzliya, Israel
| | - Abraham Tsur
- The Josef Buchmann Gynecology and Maternity Center, Sheba Medical Center (Steinberg, Tsur), Tel Hashomer, Israel; ARC Innovation Center, Sheba Medical Center (Zimlichman, Tsur), Ramat Gan, Israel; Faculty of Medicine, Tel-Aviv University (Steinberg, Zimlichman, Tsur), Tel-Aviv, Israel; The Dina Recanati School of Medicine, Reichmann University (Zimlichman, Tsur), Herzliya, Israel
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Curtis SN, Mayer CA, Bonfield TL, Raffay TM, DiFiore JM, Martin RJ, Hoffman AC, Folz MA, Bavis RW, Dutschmann M, MacFarlane PM. Unique infrared thermographic profiles and altered hypothalamic neurochemistry associated with mortality in endotoxic shock. Exp Neurol 2025; 385:115130. [PMID: 39732274 DOI: 10.1016/j.expneurol.2024.115130] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2024] [Revised: 12/13/2024] [Accepted: 12/24/2024] [Indexed: 12/30/2024]
Abstract
Neonatal sepsis results in significant morbidity and mortality, but early detection is clinically challenging. In a neonatal rat model of endotoxic shock, we characterised unique infrared thermographic (IRT) profiles in skin temperature that could identify risk of later mortality. Ten-day old rats were placed in a thermally stable isolette and IRT images of cranial (TCR), scapula (TSC) and rump (TRU) skin temperature were obtained continuously for 8 h following an intraperitoneal injection of lipopolysaccharide (LPS) or saline. LPS resulted in ∼74 % mortality (designated as non-survivors, LPSNS) between 4.5 and 7.5 h post-injection. LPSNS and survivors of LPS (LPSS) rats displayed hypothermic tendencies with TCR, TSC and TRU decreasing at ∼80-100 min (T80-100) post-injection. Compared to LPSS rats, however, the hypothermia of LPSNS rats occurred slightly earlier (T80), was more severe, and failed to recover. The TCR, TSC and TRU of LPSS rats fully recovered by 4 h (T240) post-injection. In separate rats, hypothalamic microglia and extracellular matrix (ECM) expression at T240 post-injection were increased in putatively identified LPSNS rats (but not LPSS rats) and negatively correlated with IR temperatures. IRT could be a useful early identifier of infants at risk of death from endotoxic shock, which may be related to early failure of central nervous system (CNS) thermogenic mechanisms mediated by unique hypothalamic changes in inflammatory (microglia) and ECM neurochemistry.
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Affiliation(s)
- Sean N Curtis
- Department of Pediatrics, UH Rainbow Babies & Children's Hospital, Case Western Reserve University School of Medicine, Cleveland, OH, United States of America
| | - Catherine A Mayer
- Department of Pediatrics, UH Rainbow Babies & Children's Hospital, Case Western Reserve University School of Medicine, Cleveland, OH, United States of America
| | - Tracey L Bonfield
- Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, OH, United States of America
| | - Thomas M Raffay
- Department of Pediatrics, UH Rainbow Babies & Children's Hospital, Case Western Reserve University School of Medicine, Cleveland, OH, United States of America
| | - Juliann M DiFiore
- Department of Pediatrics, UH Rainbow Babies & Children's Hospital, Case Western Reserve University School of Medicine, Cleveland, OH, United States of America
| | - Richard J Martin
- Department of Pediatrics, UH Rainbow Babies & Children's Hospital, Case Western Reserve University School of Medicine, Cleveland, OH, United States of America
| | - Adriana C Hoffman
- Department of Pediatrics, UH Rainbow Babies & Children's Hospital, Case Western Reserve University School of Medicine, Cleveland, OH, United States of America
| | - Michael A Folz
- School of Engineering, Case Western Reserve University, Cleveland, OH, United States of America
| | - Ryan W Bavis
- Department of Biology, Bates College, Lewiston, ME, United States of America
| | - Mathias Dutschmann
- Pulmonary, Critical, and Sleep Medicine, Case Western Reserve University School of Medicine, Cleveland, OH, United States of America
| | - Peter M MacFarlane
- Department of Pediatrics, UH Rainbow Babies & Children's Hospital, Case Western Reserve University School of Medicine, Cleveland, OH, United States of America.
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Lassen ML, Larsen LV, Mzee S, Ali SM, Nygaard U, Poulsen A, Lund S. Health-care providers' knowledge and quality of neonatal care in the first 2 h of life in a district hospital on Pemba Island, Tanzania: a prospective cohort study. J Trop Pediatr 2025; 71:fmaf018. [PMID: 40159427 DOI: 10.1093/tropej/fmaf018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/02/2025]
Abstract
To assess the knowledge of health workers on neonatal management, describe neonatal care in the first 2 h of life, and health outcomes of neonates in Tanzania. A prospective cohort study was performed from January to April 2022 at a district hospital on Pemba Island, Tanzania. Women admitted in active labor, and their neonates were eligible for inclusion. Standardized observations in the first 2 h after birth, followed by a clinical examination, and interviews on days 7 and 28 were performed. Health workers were given multiple-choice questions on neonatal management. Immediate skin-to-skin care was performed in 23% of neonates and breastfeeding was initiated during the first hour of life in 46%. At 2 h of life, 10% had blood glucose <2.5 mmol/L (mean: 3.71, SD 1.1), 44.6% had hypothermia with temperature <36.5°C (mean: 36.5, SD 0.5), and 2% low saturation <90%. Health workers had on average 42% correct answers on "neonatal management". The neonatal mortality rate (NMR) corresponds to 23 per 1000 livebirths. Considerable challenges in neonatal care were identified, including low-cost, high-impact interventions such as skin-to-skin care and immediate breastfeeding. The NMR was above the Sustainable Development Goal target. Further research is needed to assess the impact of training on neonatal care and outcomes in this and similar settings.
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Affiliation(s)
- Mathilde Languille Lassen
- Global Health Unit, Department of Paediatrics and Adolescent Medication, The Juliane Marie Centre, Copenhagen University Hospital, Rigshospitalet, Copenhagen 2100, Denmark
| | - Lærke Vinge Larsen
- Global Health Unit, Department of Paediatrics and Adolescent Medication, The Juliane Marie Centre, Copenhagen University Hospital, Rigshospitalet, Copenhagen 2100, Denmark
| | - Said Mzee
- Public Health Laboratory-Ivo de Carneri, Chake Chake, Tanzania
| | | | - Ulrikka Nygaard
- Department of Paediatrics and Adolescent Medicine, The Juliane Marie Centre, Copenhagen University Hospital, Rigshospitalet, Copenhagen 2100, Denmark
| | - Anja Poulsen
- Global Health Unit, Department of Paediatrics and Adolescent Medication, The Juliane Marie Centre, Copenhagen University Hospital, Rigshospitalet, Copenhagen 2100, Denmark
- Department of Paediatrics and Adolescent Medicine, The Juliane Marie Centre, Copenhagen University Hospital, Rigshospitalet, Copenhagen 2100, Denmark
| | - Stine Lund
- Global Health Unit, Department of Paediatrics and Adolescent Medication, The Juliane Marie Centre, Copenhagen University Hospital, Rigshospitalet, Copenhagen 2100, Denmark
- Department of Neonatology, The Juliane Marie Centre, Copenhagen University Hospital, Rigshospitalet, Copenhagen 2100, Denmark
- Department of Pediatrics, Copenhagen University Hospital North Zealand, Hilleroed 3400, Denmark
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Speer EM, Adedeji AA, Lin J, Khorasanchi A, Rasheed A, Bhat M, Mackenzie K, Hennigar R, Reidy KJ, Woroniecki RP. Attenuation of acute kidney injury in a murine model of neonatal Escherichia coli sepsis. Front Cell Infect Microbiol 2025; 14:1507914. [PMID: 39963236 PMCID: PMC11830670 DOI: 10.3389/fcimb.2024.1507914] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2024] [Accepted: 12/23/2024] [Indexed: 02/20/2025] Open
Abstract
Introduction Sepsis is a risk factor for acute kidney injury (AKI) in neonates, for which no effective treatment exists. The phosphodiesterase inhibitor pentoxifylline (PTX) has demonstrated renal protection from ischemia and inflammation in adult rodents. We hypothesized that addition of PTX to antibiotics may attenuate immune and histological AKI in a murine neonatal sepsis model. Methods Postnatal (PN) day 1 C57BL/6J mice were injected with E. coli K1 strain at 105 colony forming units per gram weight or saline control. After 1.5 hours, septic pups randomly received saline, gentamicin or cefotaxime, with/without PTX. 5.5h after sepsis initiation, kidneys and blood were harvested for measurements of biomarkers of inflammation and kidney injury. Renal sections from PN7 mice were used for histology and immunofluorescence. Linear mixed effect models were employed to fit the outcomes including interaction between treatment group and sex. Results Septic mice demonstrated robust expression of pro-inflammatory cytokines, chemokines and biomarkers of tubular injury in renal tissue, which were attenuated in response to combined PTX and antibiotics (gentamicin or cefotaxime): chemokines (p<0.001), plasma (p<0.01) and tissue IL-6 (p<0.05), plasma TNF (p<0.001), NGAL (p<0.01), CXCL10 (p<0.01), osteopontin (p<0.05), and VEGF (p<0.05), with a trend for KIM-1 (tissue concentration: p=0.21, fluorescence area: p=0.12). Interactions between treatment and sex were present for several cytokines and kidney injury biomarkers. Immunofluorescence findings for the tubular injury markers (NGAL and KIM-1) were consistent with biomarker expression in tissue lysates. Conclusion Neonatal E. coli sepsis leads to increased expression of renal tissue inflammation and injury biomarkers consistent with AKI, which may be attenuated with PTX combined with antibiotic treatment.
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Affiliation(s)
- Esther M. Speer
- Department of Pediatrics, Renaissance School of Medicine at Stony Brook University, Stony Brook, NY, United States
| | - Atilade A. Adedeji
- Department of Pediatrics, Renaissance School of Medicine at Stony Brook University, Stony Brook, NY, United States
| | - Joyce Lin
- Department of Pediatrics, Renaissance School of Medicine at Stony Brook University, Stony Brook, NY, United States
| | - Alexandra Khorasanchi
- Department of Pediatrics, Renaissance School of Medicine at Stony Brook University, Stony Brook, NY, United States
| | - Asma Rasheed
- Department of Pediatrics, Renaissance School of Medicine at Stony Brook University, Stony Brook, NY, United States
| | - Maya Bhat
- Department of Pediatrics, Renaissance School of Medicine at Stony Brook University, Stony Brook, NY, United States
| | - Kelly Mackenzie
- Department of Chemistry, Stony Brook University, Stony Brook, NY, United States
| | - Randolph Hennigar
- Department of Pathology, Renaissance School of Medicine at Stony Brook University, Stony Brook, NY, United States
| | - Kimberly J. Reidy
- Division of Pediatric Nephrology, Department of Pediatrics, Children’s Hospital at Montefiore, Bronx, NY, United States
| | - Robert P. Woroniecki
- Department of Pediatrics, Renaissance School of Medicine at Stony Brook University, Stony Brook, NY, United States
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Zhong J, Pankratova S, Doughty R, Flyger CK, Sangild PT, Skovgaard K, Jensen HE, Nguyen DN, Thymann T. Postnatal enteral plasma supplementation following birth asphyxia increases fluid retention and kidney health in newborn pigs. Physiol Rep 2025; 13:e70238. [PMID: 39910739 PMCID: PMC11798866 DOI: 10.14814/phy2.70238] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2024] [Revised: 01/14/2025] [Accepted: 01/27/2025] [Indexed: 02/07/2025] Open
Abstract
Birth asphyxia can result in kidney dysfunction, disturbances in systemic electrolytes and fluid balance in newborns. Currently, there is no proven dietary approach to support asphyxiated newborns. This study investigates whether oral plasma supplementation improves kidney function and overall health in asphyxiated newborns. Cesarean-delivered near-term pigs with or without an 8 min intrauterine clamping of the umbilical cord were fed a milk replacer dissolved in water for 24 h in Experiment 1. Pigs were fed 72 h with milk replacers dissolved in either maternal plasma or water in Experiment 2. Blood, urine, and kidney tissue were collected for further analyses. Asphyxia disrupted blood electrolyte balance. And plasma feeding led to higher fluid retention for both asphyxiated and control pigs. Additionally, plasma feeding may also affect kidney development and protect kidneys from asphyxia induced impairments. Birth asphyxia in pigs led to immediate disturbance of electrolyte balance, impaired fluid retention, and kidney impairments. Plasma feeding may improve postnatal newborn hydration and may also improve the condition of kidneys following asphyxia.
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Affiliation(s)
- Jingren Zhong
- Section for Comparative Pediatrics and Nutrition, Department of Veterinary and Animal SciencesUniversity of CopenhagenFrederiksbergDenmark
| | - Stanislava Pankratova
- Section for Comparative Pediatrics and Nutrition, Department of Veterinary and Animal SciencesUniversity of CopenhagenFrederiksbergDenmark
| | - Richard Doughty
- Department of PathologyAkershus University HospitalLørenskogNorway
| | - Christoffer Kirkelund Flyger
- Section for Pathobiological Sciences, Department of Veterinary and Animal SciencesUniversity of CopenhagenFrederiksbergDenmark
| | - Per Torp Sangild
- Section for Comparative Pediatrics and Nutrition, Department of Veterinary and Animal SciencesUniversity of CopenhagenFrederiksbergDenmark
- Department of PediatricsOdense University HospitalOdenseDenmark
- Department of NeonatologyRigshospitaletCopenhagenDenmark
| | - Kerstin Skovgaard
- Department of Biotechnology and BiomedicineTechnical University of DenmarkLyngbyDenmark
| | - Henrik Elvang Jensen
- Section for Pathobiological Sciences, Department of Veterinary and Animal SciencesUniversity of CopenhagenFrederiksbergDenmark
| | - Duc Ninh Nguyen
- Section for Comparative Pediatrics and Nutrition, Department of Veterinary and Animal SciencesUniversity of CopenhagenFrederiksbergDenmark
| | - Thomas Thymann
- Section for Comparative Pediatrics and Nutrition, Department of Veterinary and Animal SciencesUniversity of CopenhagenFrederiksbergDenmark
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Jafaei S, Kassaeian SS, Danaei N, Gharibi F. Household Catastrophic Health Expenditures in Maternal Care: A Cross-Sectional Study From Semnan, Iran. Health Sci Rep 2025; 8:e70426. [PMID: 39931256 PMCID: PMC11808319 DOI: 10.1002/hsr2.70426] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2024] [Revised: 11/25/2024] [Accepted: 01/21/2025] [Indexed: 02/13/2025] Open
Abstract
Background Due to its indisputable influence on maternal and child health, maternal care is among the most crucial requisites in all health systems. Objective This study aimed to investigate the catastrophic health expenditures (CHE) in maternal care. Methods This cross-sectional survey included 400 pregnant women using systematic random sampling in Semnan, Iran, from July 1, 2022, to September 30, 2022. The study tool was a researcher-made questionnaire, the content validity of which was approved by experts, and CVR and CVI values of 0.89 and 0.91, respectively. The CHE occurs when out-of-pocket medical expenditures account for 40% of household affordability and more, so all pregnancy-related healthcare costs were recorded, and their ratio to the household's nonfood costs was calculated. Due to the qualitative nature of the data, a chi-square test was performed to evaluate the statistical association between demographic and background variables with CHE. Results The mean direct costs for maternal care was $1697, of which 48% was related to diagnostic services, 11% to various therapies, and 41% to medical treatment. The ratio of direct costs to nonfood costs was 48.67%, and 50% of pregnant women and their households suffered from CHE. Furthermore, the factors of educational status, employment status, basic health insurance, supplementary health insurance, mode of delivery, place of delivery, place of receiving care, and the woman's weight during pregnancy had statistically significant relationships with CHE (p < 0.05). Conclusions The status of financial support provided to Iranian pregnant women is not desirable. The Iranian health system should reduce the incidence of CHE in maternal care by taking the following steps: (1) fully covering the costs of maternal care services by strengthening insurance facilities, (2) investing enough money in domestic procurement of diagnostic technology and medical supplements, and (3) providing high-quality maternal care in the public sector facilities.
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Affiliation(s)
- Sana Jafaei
- School of Medicine, Semnan University of Medical SciencesSemnanIran
| | - Sayed Saeed Kassaeian
- Department of Community MedicineSchool of Medicine, Semnan University of Medical SciencesSemnanIran
| | - Navid Danaei
- Department of PediatricsSchool of Medicine, Semnan University of Medical SciencesSemnanIran
| | - Farid Gharibi
- Social Determinants of Health Research CenterSemnan University of Medical SciencesSemnanIran
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Kühne F, de Chamorro NW, Glasmeyer L, Grigoryev M, Shing YL, Buss C, Bührer C, Kaindl AM. Predictors for Development of Asphyxiated Neonates Treated With Therapeutic Hypothermia. Acta Paediatr 2025. [PMID: 39878089 DOI: 10.1111/apa.17598] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2024] [Revised: 01/13/2025] [Accepted: 01/15/2025] [Indexed: 01/31/2025]
Abstract
AIM To describe the long-term neurodevelopmental outcomes of asphyxiated neonates treated with hypothermia in association with neonatal magnetic resonance imaging (MRI) findings. METHODS We evaluated, retrospectively, clinical and radiological single-centre data at 0, 2, and 5 years of age of 53 asphyxiated neonates born between 2005 and 2015. Neonatal cranial MRI was re-evaluated using the Weeke score ranging from 0 (normal finding) to 55 (cerebral devastation) by a single neuroradiologist blinded to patient outcomes. Neurodevelopmental outcomes were evaluated using the Bayley Scales of Infant Development (BSID) at 2 years, and tests assessing intellectual performance at 5 years of age. RESULTS Of the 191 asphyxiated neonates treated with hypothermia, 53 returned for their 5-year follow-up. There were 10 children with MRI scores ≥ 10, all of whom had epilepsy, 9 had severe cognitive impairment, and 9 had cerebral palsy. In contrast, MRI scores < 10 were poorly predictive of later development. BSID at 2 years of age showed good correlation with IQ scores at 5 years of age (Rs = 0.58, p < 0.001). CONCLUSION The Weeke score can be used to identify severely impaired children in the neonatal period. In contrast, the neurocognitive test results at 2 years of age were indicative of mild or moderate impairment at 5 years of age.
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Affiliation(s)
- Fabienne Kühne
- Center for Chronically Sick Children, Charité - Universitätsmedizin Berlin, Berlin, Germany
- Department of Neonatology, Charité - Universitätsmedizin Berlin, Berlin, Germany
- Department of Pediatric Neurology, Charité - Universitätsmedizin Berlin, Berlin, Germany
- German Center for Child and Adolescent Health (DZKJ), partner site Berlin, Berlin, Germany
| | - Nina Wald de Chamorro
- Center for Chronically Sick Children, Charité - Universitätsmedizin Berlin, Berlin, Germany
- Department of Neonatology, Charité - Universitätsmedizin Berlin, Berlin, Germany
- Department of Pediatric Neurology, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Laura Glasmeyer
- Department of Neonatology, Charité - Universitätsmedizin Berlin, Berlin, Germany
- German Heart Center, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Maria Grigoryev
- Institute of Neuroradiology, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Yee Lee Shing
- Department of Psychology, Goethe Universität Frankfurt am Main, Frankfurt, Germany
| | - Claudia Buss
- German Center for Child and Adolescent Health (DZKJ), partner site Berlin, Berlin, Germany
- Institute for Medical Psychology, Charité - Universitätsmedizin Berlin, Berlin, Germany
- Department of Pediatrics, Development, Health and Disease Research Program, University of California, Irvine, California, USA
| | - Christoph Bührer
- Department of Neonatology, Charité - Universitätsmedizin Berlin, Berlin, Germany
- German Center for Child and Adolescent Health (DZKJ), partner site Berlin, Berlin, Germany
| | - Angela M Kaindl
- Center for Chronically Sick Children, Charité - Universitätsmedizin Berlin, Berlin, Germany
- Department of Pediatric Neurology, Charité - Universitätsmedizin Berlin, Berlin, Germany
- German Center for Child and Adolescent Health (DZKJ), partner site Berlin, Berlin, Germany
- Institute for Cell Biology and Neurobiology, Charité - Universitätsmedizin Berlin, Berlin, Germany
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Staffler A, Bellutti M, Zaboli A, Bacher J, Chiodin E. Effects of Resuscitation and Simulation Team Training on the Outcome of Neonates with Hypoxic-Ischemic Encephalopathy in South Tyrol. J Clin Med 2025; 14:854. [PMID: 39941525 PMCID: PMC11818763 DOI: 10.3390/jcm14030854] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2024] [Revised: 01/21/2025] [Accepted: 01/25/2025] [Indexed: 02/16/2025] Open
Abstract
Background/Objectives: Neonatal hypoxic-ischemic encephalopathy (HIE) due to perinatal complications remains an important pathology with a significant burden for neonates, families, and the healthcare system. Resuscitation and simulation team training are key elements in increasing patient safety. In this retrospective cohort study, we evaluated whether regular constant training of all personnel working in delivery rooms in South Tyrol improved the outcome of neonates with HIE. Methods: We retrospectively analyzed three groups of neonates with moderate to severe HIE who required therapeutic hypothermia. The first group included infants born before the systematic introduction of training and was compared to the second group, which included infants born after three years of regular training. A third group, which included infants born after the SARS-CoV-2 pandemic, was compared with the previous two to evaluate retention of skills and the long-term effect of our training program. Results: Over the three study periods, mortality decreased from 41.2% to 0% and 14.3%, respectively. There was also a significant reduction of patients with subclincal seizures detected only through EEG, from 47.1% in the first period to 43.7% and 14.3% in the second and third study periods, respectively. Clinical manifestations of seizures decreased significantly from 47.1% to 37.5% and 10.7%, respectively, as well as severe brain lesions in ultrasound (US) and MRI. Conclusions: In this study, constant and regular simulation training for all birth attendants significantly decreases mortality and improves the outcome in neonates with moderate to severe HIE. This positive effect seems to last even after a one-year period during which training sessions could not be performed due to the COVID-19 pandemic.
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Affiliation(s)
- Alex Staffler
- Division of Neonatology/NICU, Hospital of Bolzano (SABES-ASDAA), Teaching Hospital of Paracelsus Medical University (PMU), 39100 Bolzano, Italy; (M.B.); (E.C.)
| | - Marion Bellutti
- Division of Neonatology/NICU, Hospital of Bolzano (SABES-ASDAA), Teaching Hospital of Paracelsus Medical University (PMU), 39100 Bolzano, Italy; (M.B.); (E.C.)
| | - Arian Zaboli
- Innovation, Research and Teaching Service (SABES-ASDAA), Teaching Hospital of Paracelsus Medical University (PMU), 39100 Bolzano, Italy;
| | - Julia Bacher
- Dornbirn City Hospital, Training Program for General Medicine, 6850 Dornbirn, Austria;
| | - Elisabetta Chiodin
- Division of Neonatology/NICU, Hospital of Bolzano (SABES-ASDAA), Teaching Hospital of Paracelsus Medical University (PMU), 39100 Bolzano, Italy; (M.B.); (E.C.)
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Naha SK, Arpon MEI, Siddique RT, Ripa FR, Hasan MN, Uddin MJ. A study of association between maternal tetanus toxoid immunization and neonatal mortality in the context of Bangladesh. PLoS One 2025; 20:e0316939. [PMID: 39823396 PMCID: PMC11741588 DOI: 10.1371/journal.pone.0316939] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2024] [Accepted: 12/18/2024] [Indexed: 01/19/2025] Open
Abstract
BACKGROUND Maternal tetanus toxoid (MTT) vaccination during pregnancy remains an important factor for reducing infant mortality globally, especially in developing nations, including Bangladesh. Despite commendable progress in reducing child mortality through widespread MTT vaccination during pregnancy, the issue still exists. This analysis explores the impact of MTT vaccination on neonatal mortality in Bangladesh and identifies associated factors. METHODS This research utilizes data from the 2019 Bangladesh Multiple Indicator Cluster Survey (MICS). The dataset consists of 23,402 cases; among them, 587 cases resulted in infant death. The outcome variable was infant mortality, which was binary. The independent variables identified as potential contributors to the cause of death included tetanus toxoid vaccination status, mode of delivery (cesarean section or not), and mother's education level, among others. The Poisson model was employed to analyze the data. RESULTS The analyses showed that the neonatal mortality rate was 2.51%. Notably, 45.90% of mothers received the MTT vaccination during pregnancy. Among them, 23.07% received a single dose, and 22.82% took adequate doses (receiving more than two doses) and adhered to WHO guidelines. The adjusted incidence rate ratio (IRR) was 1.36, which indicates that there was a 36% higher risk of neonatal mortality for those children whose mothers did not take TT (IRR = 1.36, p = 0.081). We also found that women from middle-class households (IRR = 1.58, 95% CI = 0.98, 2.54) and women with higher parity (IRR = 1.96, 95% CI = 0.95, 4.03) also had a higher risk of newborn fatalities. A comparable trend has been observed regarding the correlation between the number of tetanus doses administered and neonatal mortality, where it also emphasizes the importance of receiving adequate doses (a minimum of 2 doses of tetanus vaccine) to mitigate neonatal mortality (adjusted IRR = 0.54, 95% CI = 0.29, 1.01) in comparison to no doses received. CONCLUSION Administering a minimum of one maternal tetanus dose significantly lowers the risk of neonatal mortality. Other than Maternal Tetanus Toxoid vaccination, the analyses underscore various contributors to neonatal mortality, encompassing maternal healthcare, delivery procedures, socio-economic status, and education. Targeted interventions addressing these factors have the potential to efficiently decrease neonatal mortality rates and improve overall maternal and child health.
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Affiliation(s)
- Sujan Kumar Naha
- Department of Statistics, Shahjalal University of Science & Technology, Sylhet, Bangladesh
| | - Md. Efty Islam Arpon
- Department of Statistics, Shahjalal University of Science & Technology, Sylhet, Bangladesh
| | - Rifa Tasfia Siddique
- Department of Statistics, Shahjalal University of Science & Technology, Sylhet, Bangladesh
| | - Farjana Rahman Ripa
- Department of Statistics, Shahjalal University of Science & Technology, Sylhet, Bangladesh
| | - Mohammad Nayeem Hasan
- Department of Statistics, Shahjalal University of Science & Technology, Sylhet, Bangladesh
| | - Md. Jamal Uddin
- Department of Statistics, Shahjalal University of Science & Technology, Sylhet, Bangladesh
- Department of Graduate Studies, Daffodil International University, Dhaka, Bangladesh
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Sompolinsky Y, Lipschuetz M, Cohen-Cymberknoh M, Cohen SM, Kabiri D, Walfisch A, Yagel S, Gordon S, Haklai Z, Applbaum Y. Early childhood respiratory morbidity according to gestational age at birth: A nationwide cohort study. Respir Med 2025; 236:107913. [PMID: 39689734 DOI: 10.1016/j.rmed.2024.107913] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/24/2024] [Revised: 12/13/2024] [Accepted: 12/14/2024] [Indexed: 12/19/2024]
Abstract
BACKGROUND Preterm birth survivors are at risk for short- and long-term respiratory morbidity. This includes increased rates of chronic obstructive pulmonary disease and infectious morbidity. Previous studies showed increased utilization of healthcare services throughout early childhood. However, only a few large-scale studies showed the effect on respiratory morbidity throughout the full spectrum of gestational age at birth. The aim of this study was to show the healthcare burden associated with prematurity, in a large nationwide cohort. STUDY DESIGN Data regarding gestational age at birth, month and year of birth, and infant sex were gathered for all 1,762,149 infants born in Israel between January 1, 2010, and December 31, 2019. Rates of hospitalization, length of hospitalization, and emergency department visits were calculated per 1000 live births and stratified by gestational age. Poisson regression was constructed to adjust for infant sex, year and month of birth. RESULTS Preterm birth occurred in 6.43 % of deliveries (n = 109,405). A negative association was found between gestational age at birth and respiratory morbidity. As gestational age at birth advances, rates of respiratory hospitalization decrease, and length of hospitalization shortens. This association continues even after full term is reached. CONCLUSION The short- and long-term effect of preterm birth poses a significant burden on healthcare systems globally, not only at birth or in infancy, but well into early childhood. These results are a call for action to stakeholders and professional organizations to increase efforts in preventing and treating preterm and early term labor.
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Affiliation(s)
- Yishai Sompolinsky
- Department of Obstetrics & Gynecology, Hadassah Medical Center and Faculty of Medicine, Hebrew University of Jerusalem, Israel
| | - Michal Lipschuetz
- Department of Obstetrics & Gynecology, Hadassah Medical Center and Faculty of Medicine, Hebrew University of Jerusalem, Israel; Henrietta Szold Hadassah Hebrew University School of Nursing in the Faculty of Medicine, Jerusalem, Israel
| | - Malena Cohen-Cymberknoh
- Pediatric Pulmonary Unit and Cystic Fibrosis Center, Hadassah Medical Center and Faculty of Medicine, Hebrew University of Jerusalem, Israel
| | - Sarah M Cohen
- Department of Obstetrics & Gynecology, Hadassah Medical Center and Faculty of Medicine, Hebrew University of Jerusalem, Israel
| | - Doron Kabiri
- Department of Obstetrics & Gynecology, Hadassah Medical Center and Faculty of Medicine, Hebrew University of Jerusalem, Israel
| | - Asnat Walfisch
- Department of Obstetrics and Gynecology, Rabin Medical Center, Petah-Tikva, Israel; Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Simcha Yagel
- Department of Obstetrics & Gynecology, Hadassah Medical Center and Faculty of Medicine, Hebrew University of Jerusalem, Israel.
| | - Shulamit Gordon
- Division of Health Information, Ministry of Health, Jerusalem, Israel
| | - Ziona Haklai
- Division of Health Information, Ministry of Health, Jerusalem, Israel
| | - Yael Applbaum
- Division of Health Information, Ministry of Health, Jerusalem, Israel
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Lawrence SM, Wynn JL, Gordon SM. Neonatal bacteremia and sepsis. REMINGTON AND KLEIN'S INFECTIOUS DISEASES OF THE FETUS AND NEWBORN INFANT 2025:183-232.e25. [DOI: 10.1016/b978-0-323-79525-8.00015-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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Jena BH, Biks GA, Gete YK, Gelaye KA. Determinants of birth asphyxia in urban south Ethiopia. Sci Rep 2024; 14:30725. [PMID: 39730490 DOI: 10.1038/s41598-024-79759-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2024] [Accepted: 11/12/2024] [Indexed: 12/29/2024] Open
Abstract
Birth asphyxia is a well-known cause of neonatal mortality, and the survivors suffer from long-lasting sequels such as seizures, intellectual disabilities, and motor disorders that are great challenges for newborns. Elucidating the determinants of birth asphyxia helps implement evidence-based practice in the local context. Thus, this study aimed at elucidating the determinants of birth asphyxia in urban south Ethiopia. A community-based unmatched nested case-control study was conducted on a cohort of 2548 pregnant women who were followed up until delivery in urban areas of Hadiya Zone, south Ethiopia. All newborns who experienced birth asphyxia (n = 118) were taken as cases. Newborns who were randomly selected from the risk-set (n = 472) were taken as controls (those without birth asphyxia). A binary logistic regression was done using R software. Induction of labor [AOR = 2.98, 95% CI: 1.20, 7.42], prolonged labor [AOR = 2.12, 95% CI: 1.02, 4.37], delivery through cesarean section [AOR = 3.81, 95% CI: 1.67, 8.72], instrumental delivery [AOR = 3.91, 95% CI: 1.72, 8.89], and low birth weight [AOR = 6.52, 95% CI: 3.40, 12.51] were determinants of birth asphyxia. Asphyxia during birth was mainly related to obstetric care and maternal nutrition, highlighting the need to pay attention during the course of labor and maternal nutrition during pregnancy. This study might have selection bias and loss of power so careful interpretation of the results is needed.
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Affiliation(s)
- Belayneh Hamdela Jena
- Department of Epidemiology, School of Public Health, College of Medicine and Health Sciences, Wachemo University, Hossana, Ethiopia.
| | - Gashaw Andargie Biks
- Department of Health System and Policy, Institute of Public Health, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia
| | - Yigzaw Kebede Gete
- Department of Epidemiology and biostatistics, Institute of Public Health, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia
| | - Kassahun Alemu Gelaye
- Department of Epidemiology and biostatistics, Institute of Public Health, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia
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O’Hearn O, Srinivasan L, Devine M, Harris MC. Bacterial meningitis in a quaternary NICU: A multiyear retrospective study. Medicine (Baltimore) 2024; 103:e40978. [PMID: 39705482 PMCID: PMC11666133 DOI: 10.1097/md.0000000000040978] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/19/2024] [Revised: 11/21/2024] [Accepted: 11/27/2024] [Indexed: 12/22/2024] Open
Abstract
Bacterial meningitis causes significant morbidity and mortality in infants. Lumbar punctures are often deferred until the results of blood cultures are known and sometimes not considered, making this population susceptible to a missed diagnosis. There are few studies describing the epidemiology of neonatal meningitis in quaternary neonatal intensive care unit settings. We describe the epidemiology of meningitis in a level IV neonatal intensive care unit; compare pathogens and rates of concordant bacteremia between infants with and without neurosurgical (NS) devices. Retrospective review of infants < 1 year of age in the Children's Hospital of Philadelphia neonatal intensive care unit with bacterial meningitis (June 2007-October 2021). Analysis included summary statistics, Wilcoxon rank sum, Chi square, and Fisher exact tests. We identified 101 episodes of bacterial meningitis (95 infants). 9 infants died. At diagnosis, 26 infants (27%) had NS devices. Group B streptococcus (GBS) and Escherichia coli (E coli) were most common pathogens, however, coagulase-negative staphylococci and Staphylococcus aureus (S aureus) predominated among infants with NS devices. While 86% had positive blood cultures in the absence of a NS device, only 14% of episodes with NS devices had concomitant bacteremia (P < .0001). Although Group B streptococcus and E coli remain most prevalent overall, coagulase-negative staphylococci and S aureus were common pathogens in NS patients. Infants with NS devices rarely had concomitant bacteremia. Meningitis was diagnosed in the absence of a positive blood culture in 36% of episodes, underscoring the importance of developing guidance for lumbar punctures in infants evaluated for sepsis.
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Affiliation(s)
| | - Lakshmi Srinivasan
- University of Pennsylvania, Philadelphia, PA
- Children’s Hospital of Philadelphia, Philadelphia, PA
| | | | - Mary Catherine Harris
- University of Pennsylvania, Philadelphia, PA
- Children’s Hospital of Philadelphia, Philadelphia, PA
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Rahman MM, Amin MT, Ferdous Z, Patwary H, Haider MM. Education of household head and maternal healthcare utilization: the case of Bangladesh. BMC Public Health 2024; 24:3439. [PMID: 39695497 DOI: 10.1186/s12889-024-20819-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2024] [Accepted: 11/21/2024] [Indexed: 12/20/2024] Open
Abstract
BACKGROUND The high maternal mortality ratio in South Asian countries could be attributed to poor maternal healthcare (MHC) utilization. Here household heads (HHs) are the main decision-makers of the households and thus can be key stakeholders in women's MHC uptake. We aim to investigate the role of HHs' education in MHC utilization and explore the educational status of male adolescents who will eventually replace today's HHs in the future. METHOD We investigated antenatal care (ANC), and institutional delivery as two MHC during pregnancy and childbirth using the Bangladesh Multiple Indicator Cluster Survey 2019. Due to the stratified cluster sampling nature of the BMICS 2019, we estimated odds ratios from mixed-effect multiple logistic regression considering women nested within clusters and estimated marginal effects to conclude. Using the Bangladesh Adolescent Health and Wellbeing Survey 2019-20, we estimated region-specific school dropout rates and identified the reasons for and timing of dropout among male adolescents. RESULTS The odds of ANC uptake and institutional delivery decreased by lower levels of HHs' education. Marginal effects of HHs' education on institutional delivery across comparable levels of ANC uptake show that less educated HHs diminish the full potential of ANC uptake in facilitating institutional delivery. The heaviest burden (~ 70%) of less educated (up to primary level) HHs was in the northeastern region. The highest rate of school dropout (40%) was also in the northeastern region. Around 60% of dropouts left school before or just after completing primary level. The primary reasons for dropout were lack of interest and financial constraints. CONCLUSION Integrating HHs into MHC programs can be the immediate call for action while averting male adolescents' school dropouts can be the long-term strategy.
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Affiliation(s)
- Md Mahabubur Rahman
- Health Systems and Population Studies Division, icddr,b, GPO Box 128, Dhaka, 1000, Bangladesh
| | - Md Tazvir Amin
- Health Systems and Population Studies Division, icddr,b, GPO Box 128, Dhaka, 1000, Bangladesh.
| | - Zannatul Ferdous
- Institute of Health Economics, Administrative Building (Ground Floor), University of Dhaka, Dhaka, 1000, Bangladesh
| | - Hridoy Patwary
- Maternal and Child Health Division, icddr,b., GPO Box 128, Dhaka, 1000, Bangladesh
| | - M Moinuddin Haider
- Health Systems and Population Studies Division, icddr,b, GPO Box 128, Dhaka, 1000, Bangladesh
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Zibugu D, Gubbels JS, Namugenyi C, Asiimwe JB, Gerards S. Impact of the Timed and Targeted Counselling Model on Maternal Health Continuum of Care Outcomes in Northern Uganda: Protocol of a Quasi-Experimental Study. Methods Protoc 2024; 7:98. [PMID: 39728618 DOI: 10.3390/mps7060098] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2024] [Revised: 12/01/2024] [Accepted: 12/03/2024] [Indexed: 12/28/2024] Open
Abstract
BACKGROUND About 287,000 women died globally during their pregnancy journey in 2020, yet most of these deaths could have been prevented. In Uganda, studies show that using Community Health Worker (CHW) visits to households with a pregnant woman can support the prevention of adverse maternal and neonatal outcomes. One such intervention is through the timed and targeted counselling (ttC) approach, where CHWs deliver tailored messages to mothers and their male caregivers at key stages of pregnancy. This study aims to evaluate the impact of the ttC approach on maternal health in Northern Uganda. The main outcomes include antenatal care attendance, advised place of delivery, and postnatal care visit. METHODS We will employ a cross-sectional quasi-experimental design, with retrospective data to compare an intervention group (where ttC is implemented) to a control group (without intervention) using the propensity score matching (PSM) technique applying a 1:1 ratio with a caliper width of 20% of the standard deviation to estimate the average treatment effects. Adjusted odds ratios after generating matched pairs will be reported with 95% confidence intervals with Rosenbaum sensitivity analysis carried out for robustness. DISCUSSION These findings can be used to modify the implementation of the ttC approach, thereby enhancing its efficiency and effectiveness.
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Affiliation(s)
- Douglas Zibugu
- Department of Health Promotion, NUTRIM Institute of Nutrition and Translational Research in Metabolism, Maastricht University, 6211 LK Maastricht, The Netherlands
| | - Jessica S Gubbels
- Department of Health Promotion, NUTRIM Institute of Nutrition and Translational Research in Metabolism, Maastricht University, 6211 LK Maastricht, The Netherlands
| | | | - John Bosco Asiimwe
- School of Statistics and Planning, Makerere University, Kampala 7062, Uganda
| | - Sanne Gerards
- Department of Health Promotion, NUTRIM Institute of Nutrition and Translational Research in Metabolism, Maastricht University, 6211 LK Maastricht, The Netherlands
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Ngadaya E, Manu A, Mmweteni M, Burengelo D, Philbert D, Kagaruki G, Isangula K, Senkoro M, Kimaro G, Kahwa A, Mazige F, Bundala F, Iriya N, Donard F, Kitinya C, Minja V, Nyakairo F, Gupta G, Pearson L, Kim M, Mfinanga S, Baker U, Hailegebriel TD. Management of possible serious bacterial infections in young infants where referral is not possible in the context of existing health system structure in Mbeya, Tanzania: Experience and lessons from the end line assessment. PLoS One 2024; 19:e0310259. [PMID: 39636929 PMCID: PMC11620348 DOI: 10.1371/journal.pone.0310259] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2022] [Accepted: 08/27/2024] [Indexed: 12/07/2024] Open
Abstract
Severe bacterial infections (SBIs) are a leading cause of neonatal deaths in low- and middle-income countries. World Health Organization's (WHO's) guideline for outpatient management of danger signs indicating possible serious bacterial infections (PSBI) when referral is not possible was adopted by three pilot district councils in Mbeya Region, in Tanzania (Busekelo, Kyela and Mbarali Districts) in 2018 (the PSBI project). This study documented changes in practice during the PSBI project, and lessons learned. A cross-sectional study was conducted using both qualitative and quantitative data collection methods between July 2021 and January 2022, post-implementation. The study participants comprised stakeholders, health workers, community health workers, and mothers/fathers/caregivers who had a young infant with PSBI. Study tools included record review, quantitative, in-depth, and key informant interviews. Quantitative data were analysed using STATA version 15 (STATACorp Inc., TX, USA), whereas qualitative data were analysed using a framework analysis approach. Our assessment showed that 2,228 young infants (0-59 days old) from the three districts were classified as having PSBI. The majority, 1,607 (72.1%) had fast breathing as the only danger sign, while 621 (27.9%) were classified as having severe illness. All 621 young infants with severe illness were counselled and offered referral to a higher-level health facility; however, only 174 of them (28%) accepted the referral. The remaining 447 severely ill infants, for whom referral was not possible, were treated at the primary health facilities with gentamicin injection and amoxicillin dispersible tablets (DT). When referral is not feasible, outpatient treatment for young infants with signs of PSBI is possible within existing health system in Tanzania, based on experience after this pilot project. However, successful scale-up of outpatient management for PSBI will require commitments from government and key stakeholders to strengthen healthcare systems.
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Affiliation(s)
- Esther Ngadaya
- National Institute for Medical Research-Muhimbili Centre, Dar es Salaam, Tanzania
| | - Alexander Manu
- University of Ghana School of Public Health, Accra, Ghana
- London School of Hygiene and Tropical Medicine, London, United Kingdom
| | | | - Dorica Burengelo
- National Institute for Medical Research-Muhimbili Centre, Dar es Salaam, Tanzania
| | - Doreen Philbert
- National Institute for Medical Research-Muhimbili Centre, Dar es Salaam, Tanzania
| | - Gibson Kagaruki
- National Institute for Medical Research-Muhimbili Centre, Dar es Salaam, Tanzania
| | - Kahabi Isangula
- University of Ghana School of Public Health, Accra, Ghana
- Aga Khan University, Dar es Salaam, Tanzania
| | - Mbazi Senkoro
- National Institute for Medical Research-Muhimbili Centre, Dar es Salaam, Tanzania
| | - Godfather Kimaro
- National Institute for Medical Research-Muhimbili Centre, Dar es Salaam, Tanzania
| | - Amos Kahwa
- National Institute for Medical Research-Muhimbili Centre, Dar es Salaam, Tanzania
| | | | | | | | - Francis Donard
- National Institute for Medical Research-Muhimbili Centre, Dar es Salaam, Tanzania
| | - Caritas Kitinya
- National Institute for Medical Research-Muhimbili Centre, Dar es Salaam, Tanzania
| | - Victor Minja
- National Institute for Medical Research-Muhimbili Centre, Dar es Salaam, Tanzania
| | - Festo Nyakairo
- National Institute for Medical Research-Muhimbili Centre, Dar es Salaam, Tanzania
| | - Gagan Gupta
- UNICEF Headquarters, New York, New York, United States of America
| | - Luwei Pearson
- UNICEF Headquarters, New York, New York, United States of America
| | - Minjoon Kim
- UNICEF Headquarters, New York, New York, United States of America
| | - Sayoki Mfinanga
- National Institute for Medical Research-Muhimbili Centre, Dar es Salaam, Tanzania
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Sebina I, Bidgood C, Stalley F, Hartel G, Stark T, Callaway L, Amoako A, Lehner C, Dekker Nitert M, Phipps S. Pre-pregnancy obesity is associated with an altered maternal metabolome and reduced Flt3L expression in preterm birth. Sci Rep 2024; 14:30027. [PMID: 39627409 PMCID: PMC11615298 DOI: 10.1038/s41598-024-81194-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2024] [Accepted: 11/25/2024] [Indexed: 12/06/2024] Open
Abstract
Mechanisms linking pre-pregnancy obesity to increased preterm birth risk are unclear. Here, we examined the impact of pre-pregnancy obesity on metabolites, Fms-related tyrosine kinase 3 ligand (Flt3L), and proinflammatory cytokine profiles in preterm birth. We used cytokine bead array, ELISA and Gas Chromatography-Mass Spectrometry (GC-MS) to determine cytokine and metabolite profiles in maternal and cord blood samples from 124 pregnant women in Australia, who gave birth at term (n = 86) or preterm (n = 38). Besides the expected variations in birth weight and gestational age, all demographic characteristics, including pre-pregnancy body mass index, were similar between the term and preterm birth groups. Mothers in the preterm birth group had reduced Flt3L (P = 0.002) and elevated IL-6 (P = 0.002) compared with term birthing mothers. Among mothers who gave birth preterm, those with pre-pregnancy obesity had lower Flt3L levels (P = 0.02) compared with lean mothers. Flt3L and IL-6 were similar in cord blood across both groups, but TNFα levels (P = 0.02) were reduced in preterm newborns. Metabolomic analysis revealed significant shifts in essential metabolites in women with pre-pregnancy obesity, some of which were linked to preterm births. Our findings suggest that maternal pre-pregnancy obesity alters the metabolome and reduces Flt3L expression, potentially increasing risk of preterm birth.
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Affiliation(s)
- Ismail Sebina
- Infection and Inflammation Program, QIMR Berghofer Medical Research Institute, Herston, QLD, 4006, Australia.
- Faculty of Medicine, The University of Queensland, Brisbane, QLD, 4072, Australia.
- School of Biomedical Sciences, Queensland University of Technology, Brisbane, 4000, QLD, Australia.
| | - Charles Bidgood
- School of Biomedical Sciences, Queensland University of Technology, Brisbane, 4000, QLD, Australia
| | - Felicity Stalley
- Women's and Newborn Services, Royal Brisbane and Women's Hospital, Herston, QLD, 4006, Australia
| | - Gunter Hartel
- Statistics Unit, QIMR Berghofer Medical Research Institute, Herston, QLD, 4006, Australia
- School of Public Health, The University of Queensland, Brisbane, QLD, Australia
| | - Terra Stark
- Metabolomics Australia (Queensland Node), The University of Queensland, Brisbane, QLD, 4072, Australia
| | - Leonie Callaway
- Faculty of Medicine, The University of Queensland, Brisbane, QLD, 4072, Australia
- Women's and Newborn Services, Royal Brisbane and Women's Hospital, Herston, QLD, 4006, Australia
| | - Akwasi Amoako
- Faculty of Medicine, The University of Queensland, Brisbane, QLD, 4072, Australia
- Women's and Newborn Services, Royal Brisbane and Women's Hospital, Herston, QLD, 4006, Australia
| | - Christoph Lehner
- Faculty of Medicine, The University of Queensland, Brisbane, QLD, 4072, Australia
- Women's and Newborn Services, Royal Brisbane and Women's Hospital, Herston, QLD, 4006, Australia
| | - Marloes Dekker Nitert
- School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, QLD, 4072, Australia
| | - Simon Phipps
- Infection and Inflammation Program, QIMR Berghofer Medical Research Institute, Herston, QLD, 4006, Australia
- Faculty of Medicine, The University of Queensland, Brisbane, QLD, 4072, Australia
- School of Biomedical Sciences, Queensland University of Technology, Brisbane, 4000, QLD, Australia
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Dai Z, Zhong X, Chen Q, Chen Y, Pan S, Ye H, Tang X. Identification of Neonatal Factors Predicting Pre-Discharge Mortality in Extremely Preterm or Extremely Low Birth Weight Infants: A Historical Cohort Study. CHILDREN (BASEL, SWITZERLAND) 2024; 11:1453. [PMID: 39767882 PMCID: PMC11674047 DOI: 10.3390/children11121453] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/16/2024] [Revised: 11/24/2024] [Accepted: 11/26/2024] [Indexed: 01/11/2025]
Abstract
BACKGROUND/OBJECTIVES This study identified early neonatal factors predicting pre-discharge mortality among extremely preterm infants (EPIs) or extremely low birth weight infants (ELBWIs) in China, where data are scarce. METHODS We conducted a retrospective analysis of 211 (92 deaths) neonates born <28 weeks of gestation or with a birth weight <1000 g, admitted to University Affiliated Hospitals from 2013 to 2024 in Guangzhou, China. Data on 26 neonatal factors before the first 24 h of life and pre-discharge mortality were collected. LASSO-Cox regression was employed to screen predictive factors, followed by stepwise Cox regression to develop the final mortality prediction model. The model's performance was evaluated using the area under the curve (AUC) of the receiver operating characteristic, calibration curves, and decision curve analysis. RESULTS The LASSO-Cox model identified 13 predictors that showed strong predictive accuracy (AUC: 0.806/0.864 in the training/validation sets), with sensitivity and specificity rates above 70%. Among them, six predictors remained significant in the final stepwise Cox model and generated similar predictive accuracy (AUC: 0.830; 95% CI: 0.775-0.885). Besides the well-established predictors (e.g., gestational age, 5 min Apgar scores, and multiplicity), this study highlights the predictive value of the maximum FiO2. It emphasizes the significance of the early use of additional doses of surfactant and umbilical vein catheterization (UVC) in reducing mortality. CONCLUSIONS We identified six significant predictors for pre-discharge mortality. The findings highlighted the modifiable factors (FiO2, surfactant, and UVC) as crucial neonatal factors for predicting mortality risk in EPIs or ELBWIs, and offer valuable guidance for early clinical management.
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Affiliation(s)
- Zhenyuan Dai
- Department of Pediatrics, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, China; (Z.D.); (X.Z.); (Q.C.); (S.P.); (H.Y.)
| | - Xiaobing Zhong
- Department of Pediatrics, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, China; (Z.D.); (X.Z.); (Q.C.); (S.P.); (H.Y.)
| | - Qian Chen
- Department of Pediatrics, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, China; (Z.D.); (X.Z.); (Q.C.); (S.P.); (H.Y.)
| | - Yuming Chen
- Department of Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China;
| | - Sinian Pan
- Department of Pediatrics, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, China; (Z.D.); (X.Z.); (Q.C.); (S.P.); (H.Y.)
| | - Huiqing Ye
- Department of Pediatrics, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, China; (Z.D.); (X.Z.); (Q.C.); (S.P.); (H.Y.)
| | - Xinyi Tang
- Department of Pediatrics, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, China; (Z.D.); (X.Z.); (Q.C.); (S.P.); (H.Y.)
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Azhar M, Yasin R, Hanif S, Bughio SA, Das JK, Bhutta ZA. Nutritional Management of Low Birth Weight and Preterm Infants in Low- and Low Middle-Income Countries. Neonatology 2024; 122:209-223. [PMID: 39591949 PMCID: PMC11875417 DOI: 10.1159/000542154] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/13/2024] [Accepted: 10/17/2024] [Indexed: 11/28/2024]
Abstract
INTRODUCTION Preterm and low birth weight (LBW) infants are at an increased risk of morbidity and mortality compared with their term counterparts, with more than 20 million LBW infants born each year, the majority in lower middle-income countries (LMICs). Given the increased vulnerability and higher nutritional needs of these infants, optimizing feeding strategies may play a crucial role in improving their health outcomes. METHODS We updated evidence of Every Newborn Series published in The Lancet 2014 by identifying relevant systematic reviews, extracting low-income country (LIC) and LMIC data, and conducting revised meta-analysis for these contexts. RESULTS We found 15 reviews; the evidence showed that early initiation of enteral feeding reduced neonatal mortality overall, but not in LIC/LMIC settings. Breastfeeding promotion interventions increased the prevalence of early initiation of breastfeeding and exclusive breastfeeding at 3 and 6 months of age in LMIC settings. There was an increased risk of neonatal mortality with formula milk in LIC/LMIC settings. Despite contributing to greater weight gain, there was a higher risk of necrotizing enterocolitis with formula milk overall. Breast milk fortification and nutrient-enriched formula improved growth outcomes. Iron and vitamin A supplementation reduced anemia and mortality rates (LMIC), respectively. The evidence also suggested that benefits of various different micronutrient supplementation interventions such as zinc, calcium/phosphorous, and vitamin D, outweigh the risks since our review demonstrates little to no adverse effects deriving from their supplementation, particularly for a breastfed preterm and/or LBW infant. CONCLUSION Early adequate nutritional support of preterm or LBW infant is paramount to averse adverse health outcomes, contribute to normal growth, resistance to infection, and optimal development. Breast milk feeding and micronutrient supplementation are crucial to reduce diarrhea incidence and mortality respectively while feed fortification or nutrient-enriched formula, when breast milk is not available, to enhance better growth especially in LMICs where there is higher population of growth restriction and stunting. This review also highlights need for randomized trials in LMICs at large scale to further strengthen the evidence. INTRODUCTION Preterm and low birth weight (LBW) infants are at an increased risk of morbidity and mortality compared with their term counterparts, with more than 20 million LBW infants born each year, the majority in lower middle-income countries (LMICs). Given the increased vulnerability and higher nutritional needs of these infants, optimizing feeding strategies may play a crucial role in improving their health outcomes. METHODS We updated evidence of Every Newborn Series published in The Lancet 2014 by identifying relevant systematic reviews, extracting low-income country (LIC) and LMIC data, and conducting revised meta-analysis for these contexts. RESULTS We found 15 reviews; the evidence showed that early initiation of enteral feeding reduced neonatal mortality overall, but not in LIC/LMIC settings. Breastfeeding promotion interventions increased the prevalence of early initiation of breastfeeding and exclusive breastfeeding at 3 and 6 months of age in LMIC settings. There was an increased risk of neonatal mortality with formula milk in LIC/LMIC settings. Despite contributing to greater weight gain, there was a higher risk of necrotizing enterocolitis with formula milk overall. Breast milk fortification and nutrient-enriched formula improved growth outcomes. Iron and vitamin A supplementation reduced anemia and mortality rates (LMIC), respectively. The evidence also suggested that benefits of various different micronutrient supplementation interventions such as zinc, calcium/phosphorous, and vitamin D, outweigh the risks since our review demonstrates little to no adverse effects deriving from their supplementation, particularly for a breastfed preterm and/or LBW infant. CONCLUSION Early adequate nutritional support of preterm or LBW infant is paramount to averse adverse health outcomes, contribute to normal growth, resistance to infection, and optimal development. Breast milk feeding and micronutrient supplementation are crucial to reduce diarrhea incidence and mortality respectively while feed fortification or nutrient-enriched formula, when breast milk is not available, to enhance better growth especially in LMICs where there is higher population of growth restriction and stunting. This review also highlights need for randomized trials in LMICs at large scale to further strengthen the evidence.
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Affiliation(s)
- Maha Azhar
- Institute for Global Health and Development, The Aga Khan University, Karachi, Pakistan
| | - Rahima Yasin
- Institute for Global Health and Development, The Aga Khan University, Karachi, Pakistan
| | - Sawera Hanif
- Institute for Global Health and Development, The Aga Khan University, Karachi, Pakistan
| | - Sharib Afzal Bughio
- Institute for Global Health and Development, The Aga Khan University, Karachi, Pakistan
| | - Jai K. Das
- Institute for Global Health and Development, The Aga Khan University, Karachi, Pakistan
- Division of Women and Child Health, The Aga Khan University, Karachi, Pakistan
| | - Zulfiqar A. Bhutta
- Institute for Global Health and Development, The Aga Khan University, Karachi, Pakistan
- Center for Global Child Health, Hospital for Sick Children, Toronto, ON, Canada
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Muralidharan O, Rehman S, Sihota D, Harrison L, Vaivada T, Bhutta ZA. Post-Asphyxial Aftercare and Management of Neonates in Low- and Middle-Income Countries: A Systematic Evidence Synthesis. Neonatology 2024; 122:84-105. [PMID: 39536730 PMCID: PMC11875422 DOI: 10.1159/000541862] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2024] [Accepted: 10/02/2024] [Indexed: 11/16/2024]
Abstract
INTRODUCTION Effective post-resuscitation care is crucial for improving outcomes in neonates post-asphyxia. This review aimed to provide a comprehensive overview of post-asphyxial aftercare strategies and forms part of a supplement describing an extensive synthesis of effective newborn interventions in low- and middle-income countries (LMICs). METHODS Evidence was generated by performing de novo reviews, updates to reviews via systematic searches, and reanalyses of studies conducted in LMICs from existing reviews. RESULTS Sixty-one trials recruiting 5,046 term infants post-asphyxia were included across all intervention domains. Limited studies were available from LMICs related to fluid restriction, antiseizure medications, and early interventions to improve developmental outcomes. Our reanalysis of whole-body cooling trials in LMICs found effects on neonatal mortality and mortality or neurological disability in infancy differed significantly based on the care center and type of cooling device used. Pharmacological therapies for neuroprotection evaluated in 27 trials in middle-income countries had varied effects in neonates with encephalopathy. Majority of the trials (60%) focused on magnesium sulfate therapy and showed significant improvements in short-term mortality and morbidities. CONCLUSION The sample sizes of included trials were relatively small, and the certainty of evidence ranged from very low to moderate. Evidence on long-term survival and neurodevelopmental outcomes was limited. Further research on promising neuroprotective therapies and factors affecting their implementation in low-resource contexts is required. To reduce the high burden related to asphyxia in LMICs, this review underscores the need for a paradigm shift toward prevention, and strategies that emphasize improving antenatal and obstetric care. INTRODUCTION Effective post-resuscitation care is crucial for improving outcomes in neonates post-asphyxia. This review aimed to provide a comprehensive overview of post-asphyxial aftercare strategies and forms part of a supplement describing an extensive synthesis of effective newborn interventions in low- and middle-income countries (LMICs). METHODS Evidence was generated by performing de novo reviews, updates to reviews via systematic searches, and reanalyses of studies conducted in LMICs from existing reviews. RESULTS Sixty-one trials recruiting 5,046 term infants post-asphyxia were included across all intervention domains. Limited studies were available from LMICs related to fluid restriction, antiseizure medications, and early interventions to improve developmental outcomes. Our reanalysis of whole-body cooling trials in LMICs found effects on neonatal mortality and mortality or neurological disability in infancy differed significantly based on the care center and type of cooling device used. Pharmacological therapies for neuroprotection evaluated in 27 trials in middle-income countries had varied effects in neonates with encephalopathy. Majority of the trials (60%) focused on magnesium sulfate therapy and showed significant improvements in short-term mortality and morbidities. CONCLUSION The sample sizes of included trials were relatively small, and the certainty of evidence ranged from very low to moderate. Evidence on long-term survival and neurodevelopmental outcomes was limited. Further research on promising neuroprotective therapies and factors affecting their implementation in low-resource contexts is required. To reduce the high burden related to asphyxia in LMICs, this review underscores the need for a paradigm shift toward prevention, and strategies that emphasize improving antenatal and obstetric care.
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Affiliation(s)
- Oviya Muralidharan
- Centre for Global Child Health, The Hospital for Sick Children, Toronto, ON, Canada
| | - Sarah Rehman
- Centre for Global Child Health, The Hospital for Sick Children, Toronto, ON, Canada
| | - Davneet Sihota
- Centre for Global Child Health, The Hospital for Sick Children, Toronto, ON, Canada
| | - Leila Harrison
- Centre for Global Child Health, The Hospital for Sick Children, Toronto, ON, Canada
| | - Tyler Vaivada
- Centre for Global Child Health, The Hospital for Sick Children, Toronto, ON, Canada
| | - Zulfiqar A. Bhutta
- Centre for Global Child Health, The Hospital for Sick Children, Toronto, ON, Canada
- Center of Excellence in Women and Child Health, The Aga Khan University, Karachi, Pakistan
- Institute for Global Health and Development, The Aga Khan University, Karachi, Pakistan
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