Preterm birth, a significant global health concern, has been associated with alterations in the gut microbiota. However, the causal nature of this relationship remains uncertain due to the limitations inherent in observational studies.

To investigate the potential causal relationship between gut microbiota imbalances and preterm birth.

We conducted a two-sample Mendelian randomization (MR) study using genome-wide association study (GWAS) data from the MiBioGen consortium focusing on microbiota and preterm birth. Single nucleotide polymorphisms (SNPs) associated with the microbiota were selected as instrumental variables. The inverse variance weighting (IVW) method was used to estimate causality. We confirmed pleiotropy and identified and excluded outlier SNPs using MR-PRESSO and MR-Egger regression. Cochran's Q test was applied to assess heterogeneity among SNPs, and a leave-one-out analysis was performed to evaluate the influence of individual SNPs on overall estimates.

Our findings provide evidence for a causal link between specific components of the gut microbiota and preterm birth, with the identification of relevant metabolites.

This study highlights the causal role of gut microbiota imbalances in preterm birth, offering novel insights into the development of preterm birth and potential targets for prevention strategies.

This study aimed to identify differentially expressed non-coding RNAs (ncRNAs) associated with preterm birth (PTB) and determine biological pathways being influenced in the context of PTB. We processed cell-free RNA sequencing data and identified seventeen differentially expressed (DE) ncRNAs that could be involved in the onset of PTB. Per the validation via customized RT-qPCR, the recorded variations in expressions of eleven ncRNAs were concordant with the in-silico analyses. The results of this study provide insights into the role of DE ncRNAs and their impact on pregnancy-related biological pathways that could lead to PTB. Further studies are required to elucidate the precise mechanisms by which these DE ncRNAs contribute to adverse pregnancy outcomes (APOs) and their potential as diagnostic biomarkers.

Preterm birth remains a leading cause of neonatal morbidity and mortality. Cerclage for short cervical length ≤25 mm in patients with singleton pregnancies with a history of spontaneous preterm birth is associated with decreased neonatal morbidity/mortality. Both vaginal progesterone and cerclage individually have level 1 evidence supporting benefit in the prevention of preterm birth in pregnancies complicated by short cervical length. However, there is a paucity of level 1 evidence regarding the potential benefit of cerclage with progesterone relative to progesterone alone for short cervical length ≤25 mm in patients with singleton pregnancies without a history of spontaneous preterm birth.

This study aimed to conduct a pragmatic randomized controlled trial to evaluate the additional benefit of cerclage with vaginal progesterone relative to vaginal progesterone alone in patients with singleton pregnancies without prior spontaneous preterm birth and with a current midtrimester transvaginal ultrasound cervical length ≤25 mm.

This was a multicenter international randomized controlled trial conducted from September 2017 to September 2023, involving 4 sites in the United States and Italy. Patients with singleton pregnancies without prior spontaneous preterm birth received transvaginal ultrasound cervical length (universal) screening during the midtrimester anatomy ultrasound examination as part of routine care. Inclusion criteria included transvaginal ultrasound cervical length ≤25 mm at 18 0/7 to 23 6/7 weeks. Exclusion criteria included current or planned cerclage, cervical dilation, symptoms of labor, infection, bleeding, and rupture of membranes at screening. Participants were randomized in a 1:1 ratio to cerclage with vaginal progesterone (200-mg vaginal progesterone daily) or vaginal progesterone alone. Randomization was stratified by study site and transvaginal ultrasound cervical length ≤15 mm. The primary outcome was preterm birth <35 weeks, assessed using intention-to-treat analysis. Secondary outcomes included preterm birth <37, 32, 28, and 24 weeks, gestational age at delivery, latency to delivery, and neonatal outcomes. Categorical variables were compared using the Pearson chi-square test and relative risk estimates with 95% confidence intervals. Continuous variables were compared using the Mann-Whitney U test. Latency to delivery and gestational age at delivery were also compared using Kaplan-Meier survival curves. Planned enrollment was set at N=206 on the basis of an estimated 0.54 relative risk with cerclage and a 34% incidence of preterm birth with standard care. The trial was registered on ClinicalTrials.gov (NCT03251729) on June 22, 2017.

Enrollment ran from September 22, 2017 to October 31, 2023, and was halted early because of lagging enrollment. A total of 93 participants were randomized; 3 were excluded because of withdrawal (n=1) and loss to follow-up (n=2). Of the 90 participants included in the intention-to-treat analysis, 43 were assigned to cerclage and progesterone and 47 to progesterone alone. Overall, 40 participants (40.4%) had a transvaginal ultrasound cervical length ≤15 mm. There was no significant difference in the primary outcome of preterm birth <35 weeks between those randomized to cerclage with progesterone vs progesterone alone (16.3% vs 23.4%; relative risk, 0.70 [0.30-1.63]). Those randomized to cerclage with progesterone had significantly increased latency from randomization to delivery (median difference, 13 [5-20] days; P=.01) and a significantly later gestational age at delivery (median difference, 1.0 [0.2-1.7] weeks; P=.035). A Kaplan-Meier survival curve also demonstrated increased latency to delivery and gestational age at delivery for cerclage with progesterone compared with progesterone alone (Mantel-Cox log-rank P<.001 and P=.003, respectively). These findings persisted within both subgroups of cervical length ≤15 mm and 16 to 25 mm.

In singleton gestations without a prior spontaneous preterm birth and a transvaginal ultrasound cervical length ≤25 mm before 24 weeks, cerclage with progesterone was not found to significantly reduce the preterm birth rate compared with progesterone alone. However, cerclage and progesterone did result in a significantly longer latency from randomization to delivery and a significantly later gestational age at delivery, compared to progesterone alone. These results suggest the potential benefit of cerclage and progesterone relative to progesterone alone in patients with singleton pregnancies without a prior spontaneous preterm birth and a short cervical length ≤25 mm before 24 weeks. This trial was halted early, and these findings should be confirmed in a larger trial or meta-analysis. El resumen está disponible en Español al final del artículo.

Premature infants are highly susceptible to infections that can lead to sepsis with life-threatening organ dysfunctions. The clinical practice of high parenteral glucose supply in preterm infants can exacerbate infection outcomes through excessive glycolysis-induced inflammatory response. This in turn can affect the health of vital preterm organs, including the brain and kidneys. We hypothesized that reduced parenteral glucose supply to infected preterm newborns may help protect against pathology in these two key organs.

Cesarean-delivered preterm pigs were nourished with high or low parenteral glucose levels (21 % vs. 5 %), infused with Staphylococcus epidermidis or saline, and monitored in heated, oxygenated incubators until 22 h. Blood, brain, and kidney samples were collected for histological, immunohistological, q-PCR, ELISA, and biochemical analyses.

Infection led to multiple pathological changes (e.g. edema), increased inflammation and tissue injury (indicated by gene expression data) in both brain and kidneys of preterm piglets. Reduced glucose supply in infected animals alleviated histopathological manifestations in the brain, and reduced neuroinflammation with enhanced M2 microglial phenotype. Reduced glucose supply also decreased plasma creatinine, and the severity of renal edema, tubular vacuolization and dilatation. Multiple genes related to innate and Th1 immunity in both organs were dampened by reduced glucose supply. Correlation analysis showed that renal inflammation was more closely connected to systemic inflammation compared to neuroinflammation.

Reduced glucose supply can reduce renal and neuro-inflammation during neonatal infection, thereby protecting brain and kidney health in infected preterm neonates.

Increasingly, pregnant women with HIV (WHIV) initiate antiretroviral therapy (ART) before conception. We assessed the risk of adverse perinatal outcomes among pregnant WHIV initiating ART preconception or antenatally, compared with women without HIV or ART-naive WHIV.

Systematic review and meta-analysis.

We searched PubMed, EMBASE, CINAHL, and Global Health for studies published between 1 January 1980 and 14 July 2023. We assessed the association of preconception/antenatal ART initiation with preterm birth (PTB), very PTB (VPTB), spontaneous PTB (sPTB), low birthweight (LBW), very LBW (VLBW), small for gestational age (SGA), very SGA (VSGA), stillbirth and neonatal death (NND). Data were analysed using random effects meta-analyses. Quality assessments, subgroup and sensitivity analyses were conducted. PROSPERO registration: CRD42021248987.

Thirty-one cohort studies were eligible, including 199 156 women in 19 countries. WHIV with preconception ART were associated with increased risk of PTB [risk ratio (RR) 1.55; 95% confidence interval (CI) 1.27-1.90], VPTB (RR 2.14, 95% CI 1.02-4.47), LBW (RR 2.19, 95% CI 1.32-3.63), VLBW (RR 3.34, 95% CI 1.08-10.35), SGA (RR 1.92, 95% CI 1.01-3.66), and VSGA (RR 2.79, 95% CI 1.04-7.47), compared with women without HIV. WHIV with antenatal ART were associated with increased risk of PTB (RR 1.35, 95% CI 1.15-1.58), LBW (RR 2.16, 95% CI 1.39-3.34), VLBW (RR 1.97, 95% CI 1.01-3.84), SGA (RR 1.77, 95% CI 1.10-2.84), and VSGA (RR 1.21, 95% CI 1.09-1.33), compared with women without HIV. Compared to ART-naive WHIV, WHIV with preconception or antenatal ART were associated with increased risk of SGA (preconception: RR 1.40, 95% CI 1.12-1.73; antenatal: RR 1.39, 95% CI 1.11-1.74) and VSGA (preconception: RR 2.44, 95% CI 1.63-3.66; antenatal: RR 2.24, 95% CI 1.48-3.40).

Among WHIV, both preconception and antenatal initiation of ART are associated with increased risks of adverse perinatal outcomes, compared to women without HIV and ART-naive WHIV.

Birth asphyxia is one of the leading causes of death for neonates worldwide. Lack of an objective cost effective test to predict poor newborn outcomes at birth affects the ability to respond appropriately. This study determined predictive values of umbilical cord arterial lactate in relation to adverse neonatal outcomes.

This was a cross-sectional analytical study conducted between March 2018 and March 2019 at two hospitals in Northern Uganda. A total of 2655 women admitted for birth and their newborns were recruited. At birth, umbilical cord arterial blood was tested for lactate using the Nova Biomedical StatStrip Xpress meter. Apgar scores were assessed at 5 min by trained research midwives. Area under the receiver operator characteristics curve (AUROC) was calculated relating umbilical arterial lactate (UAL) levels and four outcomes. We modeled the best lactate cutoff level associated with the highest AUROC for the four outcomes.

The estimated AUROC for lactate was: 88.42% for Apgar score <7 at 5 min, 83.35% for resuscitation with bag and mask, 84.55% for oxygen therapy after resuscitation and 87.72% for admission to neonatal care unit. The UAL cutoff value of 5.5 mmol/L was associated with the best AUROC of between 75.81% to 81.75% for the four adverse outcomes with no significant differences when adjusted for infectious disease parameters. The sensitivity, specificity, PPV, and NPV were; 78.95%, 86.48%, 23.54%, and 98.73% for Apgar scores <7 at 5 min, 64.40%, 88.11%, 36.59%, and 95.87% for resuscitation with bag and mask, 67.17%, 87.20%, 30.23%, and 96.99% for oxygen therapy after resuscitation, and 77.17%, 86.15%, 22.27%, and 98.65% for admission to the special care unit, respectively.

Umbilical cord lactate point-of-care (POC) estimate of ≥5.5 mmol/L predicts adverse neonatal outcomes. This test may be used to trigger early interventions and intensified neonatal care complementing the clinical Apgar score assessment in settings like Uganda.

Influenza A viruses continue to pose a serious threat to public health and economic stability. To investigate the role of C1RL-AS1 in influenza A virus (IAV) pneumonia. Using RT-qPCR analysis, we determined C1RL-AS1 expression levels in children with IAV-infected pneumonia and A549 cells. C1RL-AS1 expression levels in children were subjected to ROC analysis. C1RL-AS1 was knocked down to investigate its role in IAV-infected A549 cells, including effects on viral nucleoprotein (NP) production, cell survival, and apoptosis. Downstream miRNAs of C1RL-AS1 were predicted and validated. MiR-16-5p target genes were predicted and validated. C1RL-AS1 was up-regulated in IAV-infected children and A549 cells. C1RL-AS1 expression levels distinguished children with IAV pneumonia from healthy children. Knockdown of C1RL-AS1 attenuated viral NP production, promoted A549 cell survival, and inhibited apoptosis. MiR-16-5p was a downstream C1RL-AS1 miRNA. miR-16-5p counteracted the anti-IAV infection effect brought about by C1RL-AS1 knockdown. LAMP3 was a miR-16-5p target gene associated with pneumonia. LAMP3 restored the cellular effects brought about by C1RL-AS1/miR-16-5p co-knockdown. C1RL-AS1 is a possible diagnostic factor for IAV pneumonia in children. C1RL-AS1 may participate in IAV pneumonia by sponging miR-16-5p and then moderating LAMP3.

Respiratory tract infections with viral pathogens are frequently identified using the World Health Organization (WHO) case definition of severe acute respiratory infection (SARI), defined as fever of ≥38°Celsius, cough, onset within 10 days, and hospitalization. While there is extensive research in adults, less is known about the WHO SARI case definition performance in children and youth. We aimed to determine the performance of the WHO SARI and modified case definitions in identifying viral respiratory tract infections in hospitalized children and youth.

Retrospective observational cross-sectional study of hospitalized children (0-18 years) with an acute respiratory infection and who received a respiratory viral test at two large Canadian children's hospitals from July 2022 to June 2023. The WHO SARI and modified SARI case definitions were evaluated overall, by virus and age, with reporting of sensitivity and specificity.

There were 2333 hospital admissions, with a median age of 2.4 years (IQR 0.8-5.0). 78% (n = 1828) had one or more viruses identified, most commonly respiratory syncytial virus (30%, n = 709). The WHO SARI definition had a sensitivity of 58% and specificity of 49% for identifying infections with a microbiologically confirmed virus. For Influenza only, the sensitivity was 71% and specificity 44%. The lowest sensitivity was among young children <3 months (28%) and 3 to <6 months (45%). Modified SARI definitions had similarly poor performance, with trade-offs of sensitivity and specificity.

The widely implemented WHO SARI case definition has sub-optimal performance among children and youth hospitalized with acute respiratory infections. Public health surveillance based on these case definitions may inadequately detect and monitor known and emerging infections, highlighting the need to develop an accurate and reliable SARI case definition for children and youth globally.

Public Health Agency of Canada, SickKids Foundation, BC Children's Hospital.

This study aimed to investigate the perceived safety during the transfer process of infants from a Neonatal Intensive Care Unit (NICU) to a regional level II department. It sought to identify stakeholder agreements and divergences on safety and to determine the facilitators and barriers to achieving a high level of perceived safety.

This study employed a mixed-method cohort design and action research approach grounded in Safety-II principles.

The study focused on transfers from a single Dutch university hospital NICU to multiple regional level II neonatology departments.

Surveys were administered to parents and care professionals, including NICU staff, level II department staff, and ambulance personnel. The surveys consisted of both quantitative and open-ended questions. Data were analysed quantitatively and qualitatively, incorporating Safety-I and Safety-II perspectives, to assess the perceived safety and identify facilitators and barriers.

A total of 46 transfers were evaluated by 239 stakeholders. The overall perception of safety was positive among all stakeholder groups. There were no significant differences in the overall level of perceived safety between parents and care professionals. However, stakeholder perceptions varied significantly across transfer phases. Qualitative analysis revealed facilitators and barriers related to timing, parental participation and information exchange.

This study indicated consistently positive safety perceptions among parents and care professionals. Effective communication, parental participation and optimal timing were identified as crucial for enhancing safety perceptions during transfers.

Kangaroo mother care (KMC) is recognized as an effective intervention for promoting growth and neurodevelopment in preterm infants, particularly in resource-limited settings. It addresses critical neonatal care needs by facilitating skin-to-skin contact and breastfeeding.

This meta-analysis evaluates the impact of KMC on growth parameters and neurobehavioral development in preterm infants, while considering evidence quality.

Six databases were searched for studies published in English, covering studies up to the year 2024. Additionally, citation tracking was used to identify relevant studies.

Out of 953 studies initially identified, 17 studies met the inclusion criteria and were reviewed for the meta-analysis.

Data were abstracted and assessed for quality and validity using standardized guidelines, applied independently by multiple observers.

KMC significantly improved the weight, head circumference, and body length of preterm infants. Gestational age was found to influence outcomes: with increasing gestational age, head circumference growth slowed, while body length showed more rapid gains. KMC also demonstrated positive effects on neurodevelopmental and brain growth indicators.

Clinically, nurses can support parents in initiating and maintaining kangaroo care, helping to enhance parental involvement during the NICU stay. While its benefits for health and neurodevelopment are well-established, further research is needed to explore its application at home. Higher-quality evidence is required to validate these findings and support broader clinical adoption in various healthcare settings.

Violence against women and children is a global issue with profound impacts on health and well-being. Intimate partner violence (IPV) and violent discipline often coexist within households, yet the impact of their co-occurrence on child health remains understudied, particularly in low- and middle-income countries (LMICs) like the Philippines.

This study sought to assess the independent and joint associations of IPV and violent discipline within households on child morbidity outcomes.

Using data from 6414 mother-child pairs from the 2022 Philippine National Demographic and Health Survey, logistic regression models were used to analyze the independent and joint associations between past-year maternal IPV, past-month violent child discipline and child morbidity (acute respiratory infection (ARI), fever and diarrhea in the past two weeks). Stratified analyses were performed by household wealth.

About 16 % of the mothers experienced IPV in the past year, 62 % of children experienced violent discipline in the past month, and 12 % of families experienced both. In the two weeks preceding the survey, fever was the most prevalent symptom of child illness (10.5 %), followed by diarrhea (5.8 %) and ARI (1.3 %). IPV and violent discipline were independently associated with increased risks of ARI, fever, and diarrhea in children under five. Their co-occurrence further heightened the risk of child morbidity (ARI aOR: 3.5, 95 % CI 1.7-7.1, fever aOR: 2.5, 95 % CI: 1.8-3.3, and diarrhea aOR: 2.5, 95 % CI 1.8-3.5), and these associations were consistent between poor and wealthy households.

These findings call for comprehensive interventions, such as parenting and community-based programs that aim to address family violence, including IPV and violent discipline, to mitigate impacts on child health in LMICs.

Teratogens play a crucial role in the development of birth defects, making effective screening vital for prevention and management. This study aimed to develop an optimized zebrafish embryo-based platform for teratogenicity screening and further evaluate its findings with established clinical and animal data. Zebrafish embryos [6-8hours post-fertilization (hpf)] were exposed to 19 different test solutions, including nine known teratogens and ten non-teratogens, in 96-well plates, and mortality and morphological abnormalities were assessed at 48, 72, and 96 hpf. The half-lethal concentration (LC50) and half-effective concentration (EC50) were calculated from the counts of dead and abnormal embryos, respectively. The teratogenicity index (TI), defined as LC50 / EC50, was used to classify the chemicals. Of the tested compounds, eight were identified as teratogenic, nine as non-teratogenic, and two outliers due to solubility constraints in this assessment. Notably, extending the exposure duration to 96 hpf provided a more accurate assessment of teratogenicity compared to shorter exposures. Eight teratogenic substances exhibited a TI greater than 3, while (-)-thalidomide did not yield a definitive TI due to low solubility. Among the non-teratogenic chemicals, nine had a TI below 3, with ajmaline also lacking a precise TI due to solubility constraints. These findings suggest that using a 6-8 hpf to 96 hpf exposure window and establishing a TI threshold of 3 can facilitate reliable teratogenicity risk assessment. Furthermore, the phenotypes observed in zebrafish embryos were consistent with typical teratogenic malformations documented in clinical and animal studies. This study demonstrates that the refined zebrafish embryo teratogenicity testing method coupled with the TI, can be an effective tool for assessing teratogenic risk.

To study the incidence and disease burden of congenital birth defects in children under five in China from 1990 to 2021 and to predict the incidence of congenital birth defects in this population from 2022 to 2036, providing a reference for the prevention of congenital birth defects in children.

Using the Global Burden of Disease Study 2021 (GBD 2021) database, the incidence and disability-adjusted life years (DALY) were employed to describe the disease burden. The Joinpoint regression model was used to analyze the trends in incidence and DALY rates of congenital birth defects in children under five. A grey prediction model GM(1,1) was applied to fit the trend of incidence rates of congenital birth defects in this age group and to predict the incidence from 2022 to 2036.

In 2021, the incidence rate of congenital birth defects among children under five in China was 737.28 per 100 000. Among these, congenital musculoskeletal and limb deformities had the highest incidence rate at 307.15 per 100 000, followed by congenital heart defects (223.53 per 100 000), congenital urinary and genital tract malformations (74.99 per 100 000), and congenital gastrointestinal malformations (62.61 per 100 000). From 1990 to 2021, the incidence rate and DALY rate of congenital birth defects in children under five in China decreased at an average annual rate of 1.73% and 5.42%, respectively. The prediction analysis indicated a decreasing trend in the incidence of congenital birth defects among children under five in China from 2022 to 2036, with the incidence rate dropping from 892.36 per 100 000 in 2022 to 783.35 per 100 000 in 2036.

The incidence and disease burden of congenital birth defects in children under five in China showed a significant declining trend from 1990 to 2021. It is predicted that this incidence will continue to decrease until 2036.

The association between interpregnancy interval (IPI) after vaginal delivery and preterm birth (PTB) in singleton has not been elucidated. The aim of this study is to investigate the association between interpregnancy interval after vaginal delivery and preterm birth.

Birth data from the 2022 National Vital Statistics System (NVSS) were selected, and multinomial logistic regression models were used to determine the odds ratios (OR) and 95% confidence intervals (95% CI) for the association between IPI after vaginal delivery and PTB. A restricted cubic spline (RCS) model with multivariate adjustment was constructed with a 4-node OR curve to check for possible non-linear relationships. Threshold effect analysis was conducted using two-piecewise linear regression and a likelihood ratio test.

The study included a total of 1,517,106 subjects, with an average age of 30.56 ± 5.29 years. 113,613 subjects had PTB, while 1,403,493 did not. Compared to the reference group (18-23 months), IPI of ≤ 11 months and ≥ 24 months were associated with an increased risk of PTB. The RCS curve observed a J-shaped association between the IPI after vaginal delivery and PTB (P < 0.001), with the lowest point of PTB risk occurring at approximately 23 months. The effect values for < 23 months and ≥ 23 months were 0.975 (95% CI: 0.974 ~ 0.977, P < 0.001) and 1.006 (95% CI: 1.005 ~ 1.006, P < 0.001), respectively. The results of sensitivity analyses remained stable.

In patients with a history of vaginal delivery, a J-shaped non-linear relationship was found between the IPI and the risk of PTB. IPIs of ≤ 11 months and ≥ 24 months were associated with an increased risk of PTB.

Armed conflict can be described as human development in reverse. In addition to the direct consequences of violence, there are numerous ways in which armed conflict may have indirect effects on people's health and well-being. Studies give varying results, and health impacts seem to differ from context to context. We aimed to determine how conflict intensity is associated with health outcomes, accounting for existing vulnerabilities and the functioning of healthcare services in countries experiencing armed conflict.

This study is based on panel data on conflict intensity, vulnerability, healthcare service functioning, and health outcomes in 42 conflict-affected countries between 2000 and 2019 and uses fixed-effects panel regression analysis to determine the associations between conflict intensity and health outcomes.

Conflict intensity was positively associated with the health outcomes included in this study. As the conflict intensity increased, the mortality and prevalence of these outcomes also increased, although this increase was not statistically significant for half the outcomes (8/16). After adjusting for the vulnerabilities and functioning of healthcare services, this positive association became significant for all health outcomes. Vulnerability and functioning of healthcare services were strong predictors of outcomes. Subgroup analysis revealed that conflict intensity was more significantly associated with outcomes in countries with high and medium vulnerability scores.

Existing vulnerabilities and healthcare system conditions are known to impact health outcomes. The association between conflict intensity and health outcomes strengthens when existing vulnerabilities and the state of healthcare services are considered. This underscores the importance of incorporating strategies to address socioeconomic inequities and strengthen healthcare system capacity in interventions for conflict-affected regions. This also raises additional concerns for long-term negative health effects related to the increasing trend of attacks on health care in contemporary conflicts.

Avoidable mortality (AM) refers to deaths preventable through effective prevention measures or timely medical treatment, and reducing AM is crucial for improving child survival rates. We conducted an analysis of the situation and temporal trends of AM among under-five (U5) children in China.

Data were extracted from the China Death Surveillance Dataset. The Joinpoint regression and multivariate linear regression were used.

The AM rate among U5 children decreased from 233.99/100,000 in 2004 to 34.54/100,000 in 2021, with an average annual percentage change of -10.72% (-11.90%, -9.98%). The proportion of AM generally showed a downward trend, with urban-rural disparities observed particularly evident by year-end 2021. Perinatal mortality is declining at an average rate of 9.75% per year, the proportion of perinatal deaths to all deaths has not changed significantly, and even the proportion of deaths caused by birth injury and suffocation has increased (annual percent change: 0.95%, 95% CI:0.39% to 1.59%). For boys and girls aged 1-5 years, the leading causes of death are drowning and land transport accidents, respectively, with the incidence of drowning in rural areas being higher than in urban areas.

China has reduced AM in U5 children, but rural areas still need targeted interventions to address preventable deaths and achieve Sustainable Development Goals.

Avoidable mortality among children under-five in China decreased by an average of 10.72% between 2004 and 2021, with urban-rural differences. Perinatal mortality declined by 9.75% annually, but the proportion of perinatal deaths remained stable, while deaths from birth injury and suffocation increased. For boys aged 1-5 years, drowning is the leading avoidable cause of death, while for girls, it is land transport accidents, with drowning more prevalent in rural areas. Increasing health technicians in rural areas may narrow the rural-urban gap, with targeted interventions needed for birth injury and suffocation, drowning, and land transport accidents.

A key target of the 2030 Sustainable Development Goals is to eliminate preventable deaths in newborns and children under 5. This study aimed to estimate the effect of time of birth on early neonatal mortality (ENM) and low Apgar scores at 5 min (LA5) in newborns.

A retrospective cohort study was conducted using vital statistics data on live births, maternal morbidity, congenital defects and perinatal mortality in Cauca-Colombia (2017-2021) excluding out-of-hospital, multiple and major defect cases. A directed acyclic graph was constructed to define the confounder adjustment set. Multivariable logistic, linear and propensity score models evaluated the effect of birth timing on neonatal outcomes, estimating crude and adjusted incidence rate ratios (IRRa).

We assessed 65 182 live births, finding similar baseline characteristics for daytime and night-time births. ENM was 0.2% (95% CI 0.19% to 0.26%) at 7 days of follow-up, absolute mortality difference 0.1% (95% CI -0.01% to 0.12%). Night-time births increased the incidence of ENM in the primary analysis IRRa 1.27 (95% CI 0.90 to 1.82), in the secondary IRRa 1.45 (95% CI 0.94 to 2.20), and in the primary and secondary sensitivity analysis, respectively, IRRa 1.48 (95% CI 1.06 to 2.07) and 1.70 (95% CI 1.16 to 2.59). LA5 was present in 0.7% (95% CI 0.60% to 0.72%) of birth, with absolute LA5 difference 0.1% (95% CI -0.02% to 0.22%). Night-time births increased the incidence of LA5 in the primary analysis IRRa 1.31 (95% CI 1.00 to 1.49), in the secondary IRRa 1.44 (95% CI 1.13 to 1.83), and in the primary and secondary sensitivity analysis, respectively, IRRa 1.31 (95% CI 1.08 to 1.59) and IRRa 1.54 (95% CI 1.23 to 1.92).

Birth at night-time is associated with worse neonatal outcomes, ENM and low Apgar scores in Colombia's diverse population, highlighting the need for optimised prenatal care, revised work schedules and improved referral systems in maternal health.

We investigated the association between maternal leukocyte telomere length (LTL) in the immediate postpartum period and moderate to late preterm birth (32- < 37 weeks) among Latinas, a population at high risk for preterm birth.

Maternal LTL was measured using quantitative polymerase chain reaction at delivery in a prospective San Francisco primarily Latina birth cohort. Logistic regression models were used to investigate the association between postpartum maternal LTL and preterm birth. Maternal LTL was analyzed as a continuous predictor.

Out of 194 participants, 23 (11.9%) had preterm delivery. Longer postnatal maternal LTL was associated with preterm birth (crude OR 4.68; 95% confidence interval (CI) 1.07, 20.6, p = 0.039; adjusted OR 12.8, 95% CI 1.83, 99.9, p = 0.010). Age-stratified analysis showed that being under 35 years increased the effect size of the association between maternal LTL and preterm birth (adjusted OR 32.5, 95% CI 2.58, 597, p < 0.01).

Latina mothers with moderate to late preterm infants had longer LTL in the immediate postpartum period compared to those with term infants. This association was stronger for mothers under the age of 35 years. LTL may serve as a biomarker to better understand the pathophysiology and risk of preterm birth and could inform targeted interventions for prevention and early detection. Future studies are needed to understand physiological changes in maternal LTL from the prenatal to postnatal period in relation to birth outcomes.

Preparations of Bryophyllum pinnatum have been used as a well-tolerated treatment of preterm labor, initially in anthroposophic hospitals and, more recently, also in conventional settings. In vitro studies with human myometrial cells have shown that B. pinnatum leaf press juice inhibits both intracellular Ca2 + signaling and the activation of inflammatory pathways induced by the relevant hormone oxytocin. However, the compounds responsible for these inhibitory effects and the potential involvement of related signaling pathways remain unknown. In the present study, we aim to address these knowledge gaps. In vitro experiments were conducted in hTERT-C3 human myometrial cells, using alamarBlue assay, fluorescent intracellular Ca2+ assay, ELISA, proteomics and real-time PCR. Contractility studies were conducted in an ex vivo organ bath model using human myometrial tissue. No single compound from B. pinnatum leaves mimicked the inhibitory effect of the whole leaf press juice on OT-induced Ca2+ signaling. However, a bufadienolide-enriched fraction and the bufadienolides bersaldegenin-1,3,5-acetate, bryophyllin A and bersaldegenin-3-acetate, but not bersaldegenin-1-acetate, reduced OT-induced COX-2 expression and attenuated NFκB activation. That the juice can inhibit prostaglandin F2α-induced contractions was shown in the myometrium bath model. Proteomics analysis revealed that the leaf juice reduced expression of various extracellular matrix proteins. Cell viability assays showed that the various inhibitory effects cannot be attributed to cytotoxicity. Taken together, these results further support investigations on the use of B. pinnatum as a well-tolerated candidate for long-term treatment of preterm labor.

The global rise of hybrid Escherichia coli (E. coli) is a major public health concern, as enhanced virulence from multiple pathotypes complicates the traditional E. coli classification system and challenges clinical diagnostics. Hybrid strains are particularly concerning as they can infect both intestinal and extraintestinal sites, complicating treatment and increasing the risk of severe disease. This study analyzed virulence-associated genes (VAGs) in 13 E. coli isolates from fecal samples of patients with symptoms of gastrointestinal (GI) infection in Norwegian hospitals and clinics. Whole genome sequencing (WGS) was conducted using Oxford Nanopore's MinION and Illumina's MiSeq platforms. Eleven strains harbored molecular diagnostic markers of atypical enteropathogenic E. coli (aEPEC), enteroinvasive E. coli (EIEC), Shiga toxin-producing E. coli (STEC), enterotoxigenic E. coli (ETEC), or typical enteropathogenic E. coli (tEPEC). Two of those isolates were identified as triple intestinal hybrids with molecular diagnostic markers for aEPEC, EIEC, and STEC. Notably, two isolates lacked any IPEC-specific molecular diagnostic markers, yet were suspected of causing the patient's GI infection. Furthermore, genes associated with extraintestinal pathogenic E. coli (ExPEC)-including adhesins, toxins, protectins, siderophores, iron acquisition systems, and invasins-were identified in all the isolates. Thus, most of the isolates were classified as hybrid aEPEC/ExPEC, STEC/ExPEC, tEPEC/ExPEC, or aEPEC/EIEC/STEC/ExPEC. These findings emphasize the genomic plasticity of E. coli and highlight the need to revise the classification system for enteric pathogens.

To comprehensively assess the prevalence and years lived with disability (YLDs) of preterm-associated developmental intellectual disability (PDID) in children and adolescents born preterm (CABP) from 1990 to 2021.

Using data from the Global Burden of Disease 2021, the burden of PDID in CABP (0-19 years) at global, regional and national levels was assessed by joinpoint regression, age-period-cohort (A-P-C) analysis, and cross-country health inequality analysis.

Globally, there were 12,114,153 prevalent cases and 915,937 YLDs of PDID in CABP in 2021, with much higher values in males than in females. Moreover, the prevalent cases and YLDs demonstrated significant increasing trends, whereas only the age-standardized rate of prevalence showed a slight decline from 1990 to 2021 worldwide, with a slight increase in the proportion of severe cases. The age subgroup analysis showed a significant reduction in the burden of PDID in children aged <5 years. The A-P-C analysis found that, in contrast to middle to high-sociodemographic index (SDI) regions, the risk of PDID was highest in children aged <5 years, and that period and cohort effects were unfavourable in low-SDI regions. The results of cross-country health inequality analysis showed that the burden of PDID in CABP was concentrated in low-SDI countries, while SDI-related inequalities generally decreased between 1990 and 2021.

Overall, the global burden of PDID in CABP has increased from 1990 to 2021, while the burden in children under 5 years of age has decreased globally. Despite reduced health inequalities, low-SDI regions still bear a significant burden.

Precisely timed immune adaptations, observed in the maternal circulation, underpin the notion of an immune clock of human pregnancy that supports its successful progression and completion at delivery. This immune clock is divided into three immunological phases, with the first phase starting at the time of conception and implantation, shifting into the second phase that supports homeostasis and tolerance throughout pregnancy, and culminating in the last phase of labor and parturition. Disruptions of this immune clock are reported in pregnancy complications such as spontaneous preterm birth. However, our understanding of the immune clock preceding spontaneous preterm birth remains scattered. In this review, we describe the chronology of maternal immune cell adaptations during healthy pregnancies and highlight its disruption in spontaneous preterm birth. With a focus on single-cell cytometric, proteomic and transcriptomic approaches, we review recent studies of term and spontaneous preterm pregnancies and discuss the need for future prospective studies aimed at tracking pregnancies longitudinally on a multi-omic scale. Such studies will be critical in determining whether spontaneous preterm pregnancies progress at an accelerated pace or follow a preterm-intrinsic pattern when compared to those delivered at term.

The occurrence of preterm birth is correlated with the potential emergence of disabilities in children. Early intervention programs are designed to promote better developmental outcomes. These interventions employ family-centered methodologies, wherein parents are instructed to facilitate neurodevelopment, thereby promoting heightened involvement of the child in their daily activities. The objective of this investigation was to evaluate the efficacy of early family-based interventions on motor, cognitive, and language development. A systematic review and meta-analysis was conducted utilizing the databases PubMed, Medline, PEDro, Scopus, CINAHL Complete, SciELO, and Open Grey. The search terms utilized included NDT (neuro-developmental treatment), Bobath, neurodevelopmental therapy, parents administered, family administered, physical therapy modalities, early intervention (educational), early intervention, premature infant, preterm, and premature. Randomized clinical trials and observational studies written in English or Spanish were taken into consideration. The initial search resulted in 420 articles. After removing duplicates and applying the selection criteria, 12 articles were selected for the systematic review and 5 articles were selected for the meta-analysis. The meta-analysis revealed a significant association between early intervention and enhanced cognitive function (p = 0.01) in this study. Additionally, the meta-analysis indicated improvements resulting from early family-based intervention (p = 0.02) in motor function. Early motor interventions that emphasize parent involvement and education in neurodevelopment show significant outcomes in motor and cognitive areas at 2 years of age in very premature or extremely premature infants. However, inconclusive effects have been found in the language area, which is the least studied domain. Due to the methodological heterogeneity observed, further research is needed to establish conclusive decisions regarding the administration of these interventions and the determination of key evaluation periods.

Criteria air pollutant exposure impacts human health through various pathways. Preterm birth (PTB) is one of the major adverse birth outcomes (ABO) associated with such exposure. Although numerous global and regional studies have been conducted on this issue, few have recently investigated the impact of major criteria air pollutant exposure on PTBs in Bangladesh, one of the world's most polluted countries with the highest relative PTB rate. In this study, we retrieved high-resolution criteria air pollution data from recent studies and regionally scaled it to 10 km × 10 km resolution. We incorporated the MERRA-2 model, satellite measurements, and exposure-response modeling to quantify the impacts of CO, O3, PM2.5, SO2, and NO2 exposure on PTBs in Bangladesh from 2015 to 2019. We observed the highest all-source CO, O3, PM2.5, SO2, and NO2 exposure in 2018 at 272.8 μg/m3, 88.2 ppbv, 62.9 μg/m3, 20.5 μg/m3, and 11.6 ppbv, respectively. These exposures were associated with 0.18 million [95% confidence interval (95%CI): 0.08-0.29 million] to 0.20 million [95%CI: 0.08-0.32 million] annual total PTBs among 4.3 million annual total live births, indicating an alarming 4.4-4.9% PTB rate exclusively attributable to the exposure to these five criteria air pollutants. Within these PTB estimates, our study found that combined CO, O3, and PM2.5 exposure caused the majority (94.7-95.8%) of the total PTBs, with hotspots in the central and southern regions of Bangladesh. This study provides quantitative evidence of the PTB incidence caused by major criteria air pollutant exposure and discusses the urgency of the targeted reduction of pollutants as well as source control to reduce the risks of PTBs, which is critical for the overall well-being of the overpopulated and underrepresented women and children of Bangladesh.

Neonatal mortality is high in middle- and low-income countries, including Tanzania. Most of these deaths are preventable and linked to suboptimal quality of care. In this study, we assessed neonatal resuscitation skills acquisition after a 1-day Helping Babies Breathe (HBB) simulation training using improved tools and associated factors among healthcare providers in 12 facilities in Tanzania.

A cross-sectional study was conducted among healthcare providers working in the labor wards in selected health facilities. The training was conducted in situ using the HBB second edition curriculum with improved simulation tools (Neonatalie Live simulator, NeoBeat heart rate meter, and Upright resuscitator). After training, skills acquisition was evaluated using Objectively Structured Clinical Evaluation. Participants who scored an average of 75% or above were considered passing. Descriptive statistics were used to determine the proportion of staff who passed the evaluation by different demographic categories. One-way analysis of variance was used to compare mean scores among demographic categories. Factors associated with neonatal resuscitation skills acquisition were analyzed using modified Poisson regression.

A total of 481 participants were enrolled in the study. Among these, 420 (87.3%) passed the skills evaluation on the first attempt. The overall mean skills score was 92.4%. In bivariable analysis, health facility level, region, age, and experience working in the labor ward were associated with passing skills evaluation on the first attempt. However, after controlling other variables in a multivariable model, none of the factors showed a statistically significant association.

In-situ, HBB simulation training using improved training tools effectively imparts neonatal resuscitation skills among healthcare providers. Participants learned skills similarly regardless of their different demographic characteristics, including level of education and working experience. Due to its potential to impart skills, frequent simulation training using improved tools may be considered for scaling up in other health facilities.

Data on the birth prevalence of congenital anomalies in low- and middle-income countries report wide variations in prevalence estimates. We conducted a scoping review to identify the sources of bias in studies reporting birth prevalence of congenital anomalies in World Health Organization South-East Asia region (SEAR) countries.

PubMed and Google Scholar databases were screened for relevant literature. Data on study characteristics and sources of bias was extracted. A narrative synthesis of the data is reported using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews checklist. A checklist for reporting studies on birth prevalence of congenital anomalies (CD-Checklist) was developed.

The literature search retrieved 47 articles. Birth prevalence varied from 0.21% to 9.68%. Sampling bias was evident as studies were single hospital studies, lacked relevant description of sample, did not justify sample size or describe the process of sampling. Information bias was identified as studies did not mention classification system used, and failed to clearly distinguish between number of malformations and babies with malformations. Observer and reporting bias were noted.

Several sources of bias introduce variations in birth prevalence reports of congenital anomalies in SEAR countries. A checklist (CD-Checklist) has been suggested which can guide investigators to minimize the risk of bias in studies.

Birth asphyxia is the second leading cause of neonatal mortality worldwide, including in Ethiopia, and remains a significant public health concern. Despite the availability of national data on neonatal mortality in Ethiopia, there remains a gap in understanding the specific incidence and predictors of mortality among asphyxiated neonates. To address this information gap, this meta-analysis was conducted to assess the incidence and predictors of mortality among asphyxiated neonates in Ethiopia.

This systematic review and meta-analysis was conducted in accordance with the PRISMA guidelines. Relevant studies were identified through various databases, including PubMed, CINAHL, Scopus, EMBASE, and Google Scholar. Data analysis of pooled estimates for mortality incidence and its predictors was performed via STATA 17 software with the DerSimonian and Laird model. Heterogeneity was assessed via Cochrane's Q-test and the I² statistic. Additionally, publication bias was evaluated through funnel plots, Egger's test, and Doi plots.

Out of 68 identified studies, only 10 met the eligibility criteria, including a total of 4,866 participants. The pooled incidence rate of birth asphyxia mortality was 4 per 100 person-days (95% CI: 3-5), which was 35,754 person-days of observation. Furthermore, predictors of birth asphyxia mortality included: pregnancy complications (HR 1.52, 95% CI: 1.41-1.64), labor complications (HR 1.29, 95% CI: 1.15-1.44), severe hypoxic-ischemic encephalopathy (HR 1.67, 95% CI: 1.51-1.85), neonatal seizures (HR 1.23, 95% CI: 1.11-1.38), and comorbidities in neonates (HR 1.31, 95% CI: 1.24-1.39).

In the current study, the pooled incidence of birth asphyxia mortality was high, falling short of the Sustainable Development Goals target and highlighting the need for immediate intervention. Additionally, pregnancy and labor complications, severe hypoxic-ischemic encephalopathy, neonatal seizures, and neonatal comorbidities were identified as predictors of birth asphyxia mortality. These findings underscore the urgent need to enhance early detection and intervention for pregnancy- and labor-related complications, as well as severe neonatal complications related to asphyxia, in to reduce mortality.

Preterm delivery is the leading cause of neonatal morbidity and mortality. This study performed a systematic review and meta-analysis to compare the efficacy of transdermal nitroglycerin and oral nifedipine in managing preterm labor.

A comprehensive search was conducted across multiple MEDLINE, Scopus, Web of Science, and the Cochrane Central Register of Controlled Trials for the randomized controlled trials comparing the effectiveness of nitroglycerin vs. nifedipine in the management of preterm labor. Primary outcomes were the prolongation of pregnancy and gestational age at delivery, while secondary outcomes included maternal side effects and neonatal outcomes. Statistical analyses were performed using RevMan 5.4 electronic databases, includingsoftware.

Eighteen studies were included. The meta-analysis revealed no significant difference between nitroglycerin and nifedipine in prolonging pregnancy for 48 h (RR = 0.93, 95% CI 0.81-1.07, p = 0.3), 7 days (RR = 0.99, 95% CI 0.88-1.11, p = 0.88), or beyond 7 days (RR = 0.92, 95% CI 0.76-1.1, p = 0.36). Both treatments showed no significant advantage in prolonging gestational age at delivery (MD = 0.25, 95% CI -0.61-1.12, p = 0.58). Nitroglycerin was associated with an increased risk of headache (RR = 2.23, 95% CI 1.23-4.05, p = 0.009), while nifedipine was linked to higher rates of tachycardia (RR = 0.51, 95% CI 0.38-0.69, p < 0.00001) and palpitations (R = 0.45, 95% CI 0.27-0.73, p = 0.001). No significant differences were observed in neonatal outcomes, including birth weight (MD = -44.28, 95% CI -266.80-178.24, p = 0.70) and NICU admission rates (RR = 0.99, 95% CI 0.61-1.59, p = 0.96).

Nitroglycerin and nifedipine demonstrate similar efficacy in prolonging pregnancy and influencing neonatal outcomes, though their side effect profiles differ. Nifedipine is associated with more tachycardia and palpitations, while nitroglycerin causes more headaches. Further high-quality studies are required due to current evidence's low to very low certainty.

Preterm birth (PTB) is a major cause of neonatal morbidity and mortality worldwide. Effective use of tocolytic agents may improve perinatal outcomes. This study aims to compare the effectiveness and safety of nifedipine and magnesium sulfate in the treatment of PTB.

A systematic review and meta-analysis.

China National Knowledge Infrastructure, China Science and Technology Journal Database, WanFang, PubMed, Embase, Web of Science and Cochrane were searched from inception to 1 December 2024.

We included randomised controlled trials (RCTs) and cohort studies that compare the efficacy and safety of magnesium sulfate versus nifedipine in treating PTB.

Two researchers independently screened studies and extracted data. Risk of bias was assessed using the Cochrane risk-of-bias assessment tool for RCTs and the modified Newcastle-Ottawa Scale for non-randomised studies. Meta-analysis was conducted using Review Manager V.5.4.

In all, 50 articles were included in this review, comprising 6072 cases (n=3014 for the magnesium sulfate group; n=3058 for the nifedipine group). Compared with the magnesium sulfate group, the nifedipine group was more favourable in terms of time to onset of action and prolongation of days of gestation, as well as higher neonatal 1 min Apgar scores. The use of magnesium sulfate was associated with a higher incidence of maternal side effects, specifically tachycardia, flushing, palpitations, dizziness and nausea. In addition, the magnesium sulfate group also showed a higher incidence of neonatal respiratory distress syndrome than the nifedipine group.

Compared with magnesium sulfate, nifedipine is more effective with a faster onset of action and a longer prolonging pregnancy. Additionally, nifedipine may be safer for fewer maternal side effects and better neonatal outcomes. Further studies are needed to confirm the long-term safety and efficacy of these treatments.

Intravenous epinephrine administration is preferred during neonatal resuscitation, but may not always be rapidly administered due to lack of equipment or trained staff. We aimed to compare the time to return of spontaneous circulation (ROSC) and post-ROSC haemodynamics between intravenous, endotracheal (ET) and intranasal (IN) epinephrine in severely asphyxic, bradycardic newborn lambs.

After instrumentation, severe asphyxia (heart rate <60 bpm, blood pressure ~10 mm Hg) was induced by clamping the cord in near-term lambs. Resuscitation was initiated with ventilation followed by chest compressions. Lambs were randomly assigned to receive intravenous (0.02 mg/kg), ET (0.1 mg/kg) or IN (0.1 mg/kg) epinephrine. If ROSC was not achieved after three allocated treatment doses, rescue intravenous epinephrine was administered. After ROSC, lambs were ventilated for 60 min.

ROSC in response to allocated treatment occurred in 8/8 (100%) intravenous lambs, 4/7 (57%) ET lambs and 5/7 (71%) IN lambs. Mean (SD) time to ROSC was 173 (32) seconds in the intravenous group, 360 (211) seconds in the ET group and 401 (175) seconds in the IN group (p<0.05 intravenous vs IN). Blood pressure and cerebral oxygen delivery were highest in the intravenous group immediately post-ROSC (p<0.05), whereas the ET group sustained the highest blood pressure over the 60-min observation (p<0.05).

Our study supports neonatal resuscitation guidelines, highlighting intravenous administration as the most effective route for epinephrine. ET and IN epinephrine should only be considered when intravenous access is delayed or not feasible.

Preterm infants (PTIs) require hospitalization in different levels of neonatal care units (NCUs) for their survival and developmental needs. The quality of care provided at NCUs significantly influences infant outcomes and parents' experiences. Parents' experience of received support and care of PTIs is one of the indicators for determining the quality of care at NCUs. The study aims to investigate parents' perspectives on the PTIs care and support received from nurses in NCUs of Nepal.

A descriptive phenomenological study was conducted within the NCUs of three public tertiary hospitals in Kathmandu, Nepal. In-depth interviews were conducted among 25 purposively selected parents, (both mothers and fathers) of low-birthweight PTIs admitted to the NCUs. Data was collected from November 2019 to February 2020. The data were meticulously analyzed using the Colaizzi method.

The exploration of parents' experiences identified three main theme areas: (1) Care and support, (2) Initial involvement in PTI care, and (3) Outcome of care involvement. Parents appreciated competent and affectionate PTI care as well as informational support. However, they had varied experiences with communication, emotional support, and opportunities for infant-parent attachment. Guidance and support for PTI care from nurses and peer-parents proved instrumental in mitigating uncertainties related to initial care learning and involvement in PTI care. Parents' involvement in hands on care of their PTIs boosted infant-parent attachment, empowered for care giving, and provided emotional solace.

Findings indicate that parents have positive experience with PTI care provided by nurses and their involvement in hands-on care of their PTIs. However, there are gaps in support expectations of parents including communication, emotional support, and care guidance. Findings have important implications for nurses, pediatricians, and policymakers for the enhancement of neonatal care practice by incorporating parental support and parents' involvement in hands on care of PTI across NCUs in Nepal.

The infant respiratory microbiome is derived largely from the mother and is associated with downstream health and disease. Manipulating maternal respiratory flora peripartum to influence the infant microbiome has not previously been investigated. Neisseria lactamica is a harmless pharyngeal commensal that correlates inversely with Neisseria meningitidis carriage and disease. Intranasal N lactamica inoculation is a safe and well characterised controlled human infection model (CHIM) in non-pregnant healthy adults. We hypothesised that N lactamica inoculation in pregnancy induces mother-to-infant N lactamica transmission postnatally.

In this single-arm trial, 21 healthy pregnant female participants aged 18 years or older were inoculated at 36-38 weeks' gestation with 105 colony-forming units of N lactamica Y92-1009 at University Hospital Southampton Clinical Research Facility, Southampton, UK. N lactamica selective culture, genome sequencing, and serological testing were performed on maternal and infant oral, nasopharyngeal, breastmilk, and serum samples over 15 weeks postpartum. Seven female participants naturally colonised with N lactamica at baseline were followed up, but not inoculated. Oral samples were obtained from 12 cohabiting siblings younger than 5 years. The primary endpoint was infant N lactamica colonisation. This study was registered with ClinicalTrials.gov, NCT04784845, and is now complete.

Between Oct 25, 2021, and March 7, 2022, 31 adult female participants (median age 33·5 years [range 23·1-39·9]; 26 [84%] were White, British) were screened and enrolled, of whom seven were already colonised with N lactamica. After exclusion of three participants, 21 participants were inoculated, of whom 15 (71%) became N lactamica-colonised, and no sustained N lactamica Y92-1009 transmission to their infants was observed. Conversely, non-Y92-1009 N lactamica strain sharing was observed in four (57%) of seven uninoculated mother-sibling pairs, and Moraxella catarrhalis strain sharing in nine (38%) of 24 mother-infant pairs completing the study. Anti-N lactamica serum IgG titres increased in seven (88%) of eight N lactamica Y92-1009-colonised female participants, but none of their infants (where paired sera were available). There were no serious adverse reactions to the inoculum.

As the world's first perinatal CHIM, this trial demonstrates that this model in pregnancy is feasible, and that N lactamica Y92-1009 can safely and efficiently colonise pregnant individuals. Lack of sustained mother-to-infant N lactamica transmission, despite evidence supporting mother-to-infant M catarrhalis and sibling-to-mother N lactamica transmission, challenges conventional perceptions of infants as passive recipients of maternal microbes, suggesting that respiratory commensal transmission is selective and microbe-specific.

Medical Research Council and National Institute for Health Research Southampton Biomedical Research Centre.

Adolescent pregnancy is associated with adverse outcomes, and although there has been a global decline in the incidence of teenage pregnancies and neonatal deaths, the absolute number remains significant. This study aimed to evaluate temporal trends in live births and neonatal deaths from adolescent mothers, as well as to identify the effect of adolescent pregnancy on neonatal death.

This is a population-based study of all live births from mothers residing in Sao Paulo state, Brazil, between 2004 and 2020. The Prais-Winsten model was used to analyze annual trends for live births from adolescent mothers, neonatal mortality rates, and the percentage of neonatal deaths within specific demographic groups. The Kaplan-Meier survival curve evaluated the time to neonatal death. A Poisson regression model was utilized to identify maternal and neonatal characteristics associated with the risk of neonatal death.

The present study encompassed a total of 9,870,181 live births, with 14.4% occurring to adolescent mothers. There were 75,504 neonatal deaths, with 14,159 (18.8%) of those occurring in the neonates born to adolescent mothers. The annual percentage change in live births to adolescent mothers decreased by -3.03% (95%CI: -4.12% to -1.93%). The neonatal mortality rates showed a declining trend within both adolescent and non-adolescent mothers. Infants born to adolescent mothers had a higher probability of neonatal death and an earlier age of death when compared to non-adolescent mothers' infants. Poisson multiple regression analysis indicated an elevated risk of neonatal death for seven tested variables (adolescent mothers, inadequate prenatal care, multiple gestation, non-hospital delivery, low birth weight, male sex and congenital anomalies) and a reduction on risk of death for neonates born from cesarean section.

The study showed a reduction in live births to adolescent mothers and neonatal deaths among adolescent mothers from 2004 to 2020 in the state of Sao Paulo. Was also shown a risk association between been born to adolescent mothers and neonatal death.

With the continuous improvement in perinatal care, the number of viable preterm infants is gradually increasing, along with the rise in preterm-related diseases such as necrotizing enterocolitis, bronchopulmonary dysplasia, perinatal brain injury, retinopathy of prematurity, and sepsis. Due to the unique pathophysiology of preterm infants, diagnosing and treating these diseases has become particularly challenging, significantly affecting their survival rate and long-term quality of life. Extracellular vesicles (EVs), as key mediators of intercellular communication, play an important regulatory role in the pathophysiology of these diseases. Because of their biological characteristics, EVs could serve as biomarkers and potential therapeutic agents for preterm-related diseases. This review summarizes the biological properties of EVs, their relationship with preterm-related diseases, and their prospects for diagnosis and treatment. EVs face unique challenges and opportunities for clinical applications.

Due to the scarcity of published data on growth among children with severe diarrhoea requiring readmission during post-discharge follow-up, we aimed to investigate the potential impact of post-discharge readmission at day-90 follow-up on growth in diarrheal children aged 2-23 months.

We performed a secondary analysis using Bangladesh site data from the Antibiotic for Children with Diarrhea (ABCD) trial, a multi-country, randomised, double-blind, placebo-controlled study conducted from July 2017 to July 2019. Children aged 2-23 months who had severe diarrhoea defined as having acute diarrhoea with some/severe dehydration, or severe stunting, or moderate wasting, were admitted to the facility. In this analysis, we classified children who were re-hospitalised within a 90-day post-discharge follow-up period as cases and randomly selected controls who did not require re-hospitalisation, matching them by similar ages and sexes in a 1:3 ratio. We gathered anthropometric data on enrolment and day 90 follow-up. The outcome variables were changes in nutritional indicators height-for-age (ΔHAZ), weight-for-age (ΔWAZ), weight-for-height (ΔWHZ), and mid-upper arm circumference (ΔMUAC). We assessed for growth changes at day 90 post-discharge follow-up using multivariate linear regression.

Among 1431 diarrhoeal children enrolled, we identified 145 cases and 435 controls. In terms of the baseline admission characteristics, the cases were less likely to be immunised (81% vs. 72%; P = 0.031), vomit (11% vs. 22%; P = 0.001), and have dehydrating diarrhoea (26% vs. 36%; P = 0.026) than the controls. After adjusting for potential covariates, the cases had a significant reduction in growth than the controls at 90 days of post-discharge follow-up, according to anthropometric indices: ΔHAZ (β = -0.11; 95% confidence interval (CI) = -0.21, -0.01; P = 0.029), ΔWAZ (β = -0.24; 95% CI = -0.35, -0.14; P < 0.001), ΔWHZ (β = -0.25; 95% CI = -0.39, -0.12; P < 0.001), and ΔMUAC (for children 6-23 months, β = -0.17; 95% CI = -0.29, -0.04; P = 0.011).

Diarrhoeal children aged 2-23 months requiring readmission during the 90-day post-discharge follow-up period had a significant deterioration of ponderal and linear growth, compared with those who did not require readmission. This finding underscores the importance of early identification of children with risks of post-discharge readmission and designing a package of post-discharge trials, including social and nutritional interventions that may help to reduce post-discharge readmissions as well as subsequent growth faltering.

To evaluate the uterocervical angle in the second trimester in singleton pregnancies as a predictor of spontaneous preterm labour.

An observational cohort study was carried out from March 2022 to May 2023, including consecutively selected patients with singleton pregnancies who underwent routine examinations between 18.0 and 23.6 weeks to analyse the risk of prematurity. The uterocervical angle (UCA) measurement was added to the transvaginal ultrasonographic analysis of the cervix. Birth-related outcomes were prospectively collected.

patients were evaluated. The occurrence of spontaneous preterm birth (sPTB) before 37 weeks was 12%, with 50 patients. An association was observed between a more obtuse uterocervical angle and the occurrence of birth before 37 weeks, with the area under the curve of 0.636 (p=0.003; 95% CI: 0.546-0.726). The cutoff point of 77.2 degrees demonstrated a sensitivity of 80% and specificity of 29.4% (p=0.003), a positive predictive value of 13.6%, and a negative predictive value of 91.3%, with a positive likelihood ratio of 1.13 and negative 0.88.

The measurement of UCA in the second trimester of pregnancy is associated with the occurrence of sPTB. The result corroborates recent literature conclusions that UCA is a relatively recent predictor of sPTB. New evidence in different populations may contribute to its possible incorporation into prematurity risk assessment.

Preterm birth (PTB) refers to the delivery of a baby before the completion of 37 weeks of gestation. It is a significant global health issue with implications for both mothers and neonates. The placenta is a transient organ crucial in the sustenance of pregnancy until parturition; its dysfunction is associated with different adverse pregnancy outcomes, including PTB. We conducted a nested case-control study of 40 placental tissue samples from preterm and term deliveries to study their comparative protein profiles. Label-free quantitation (LFQ) revealed 23 differentially expressed proteins (DEPs). Aldo-keto reductase-B1 (AKR1B1) protein expression profile exhibited a declining trajectory with an increasing period of gestation (POG). Immunoblotting and immunohistochemistry analyses of placental samples also revealed elevated protein levels in extreme preterm samples. AKR1B1 is a functional Prostaglandin F synthase responsible for the synthesis of Prostaglandin-F2α, a prostanoid that is elevated during parturition and involved in cervical ripening, membrane rupture, myometrial contraction, and inflammation. Hence, our finding supports the idea that elevated AKR1B1 levels play a significant role in the pathology of preterm birth by amplifying Prostaglandin-F2α synthesis in the placental milieu and can be further explored as a potential predictor of this condition. Data are available via ProteomeXchange with the identifier PXD043480.

Acute lower respiratory infections (ALRIs) remain the leading causes of repeated hospitalisations among young disadvantaged Australian and New Zealand First Nations and Timorese children. Severe (hospitalised) and recurrent ALRIs in the first years of life are associated with future chronic lung diseases (eg, bronchiectasis) and impaired lung function. Despite the high burden and long-term consequences of severe ALRIs, clinical, evidence-based and feasible interventions (other than vaccine programmes) that reduce ALRI hospitalisations in children are limited. This randomised controlled trial (RCT) will address this unmet need by trialling a commonly prescribed macrolide antibiotic (azithromycin) for 6-12 months. Long-term azithromycin was chosen as it reduces ALRI rates by 50% in Australian and New Zealand First Nations children with chronic suppurative lung disease or bronchiectasis. The aim of this multicentre, international, double-blind, placebo-containing RCT is to determine whether 6-12 months of weekly azithromycin administered to Australian and New Zealand First Nations and Timorese children after their hospitalisation with an ALRI reduces subsequent ALRIs compared with placebo. Our primary hypothesis is that children receiving long-term azithromycin will have fewer medically attended ALRIs over the intervention period than those receiving placebo.

We will recruit 160 Australian and New Zealand First Nations and Timorese children aged <2 years to a parallel, superiority RCT across four hospitals from three countries (Australia, New Zealand and Timor-Leste). The primary outcome is the rate of medically attended ALRIs during the intervention period. The secondary outcomes are the rates and proportions of children with ALRI-related hospitalisation, chronic symptoms/signs suggestive of underlying chronic suppurative lung disease or bronchiectasis, serious adverse events, and antimicrobial resistance in the upper airways, and cost-effectiveness analyses.

The Human Research Ethics Committees of the Northern Territory Department of Health and Menzies School of Health Research (Australia), Health and Disability Ethics Committee (New Zealand) and the Institute National of Health-Research Technical Committee (Timor-Leste) approved this study. The study outcomes will be disseminated to academic and medical communities via international peer-reviewed journals and conference presentations, and findings reported to health departments and consumer-based health organisations.

Australia New Zealand Clinical Trial Registry ACTRN12619000456156.

Managing fluid and electrolytes in extremely low gestational age neonates (ELGANs) is often challenging because of their distinctive fluid physiology. Most of the fluid loss in the first week of life is trans-epidermal due to the immature barrier function of the skin. ELGANs also have a developmental tendency for exaggerated diuresis and natriuresis. Allowing an initial weight loss of 6-12% promotes physiological extracellular contraction. Also, restricted fluid intake in the first week of life may decrease the incidence of bronchopulmonary dysplasia, patent ductus arteriosus, and necrotizing enterocolitis. A protocol-based approach for fluid management in ELGANs, developed based on physiology and available evidence, is the best strategy. Based on the estimated dermal and renal losses and desired weight change, the authors recommend initiating total fluids on the first day of life at 100 mL/kg/d in neonates at 26-27 wk gestation and 110 mL/kg/d at 24-25 wk gestation. The subsequent fluid rate is determined based on rigorous monitoring of weight, urine output, and serum sodium, with a typical daily increment in fluids of 10-20 mL/kg and a maximum fluid rate of 150-160 mL/kg/d in 26-27 wk and 160-180 mL/kg/d in 24-25 wk gestation neonates by day 7 of life. Fluid strategy should ideally be revised every 12 h in the first few days of life. A humidified incubator is the ideal care environment to minimize trans-epidermal losses. Since most of these recommendations are not based on concrete evidence from trials, it is advisable to periodically audit the outcomes and devise a unit-specific fluid strategy.