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Alhuneafat L, Ghanem F, Nandy S, Khan S, Puttur A, Jabri A, Haddad A, Ramu B, Sabol B, Schultz J, Carlson S. Examining maternal and fetal outcomes across various subtypes of hypertension during pregnancy. INTERNATIONAL JOURNAL OF CARDIOLOGY. CARDIOVASCULAR RISK AND PREVENTION 2025; 25:200413. [PMID: 40343146 PMCID: PMC12059398 DOI: 10.1016/j.ijcrp.2025.200413] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/23/2024] [Revised: 04/01/2025] [Accepted: 04/22/2025] [Indexed: 05/11/2025]
Abstract
Introduction Hypertensive disorders of pregnancy (HDP) are a leading cause of maternal morbidity and mortality worldwide. It includes chronic hypertension (CH), gestational hypertension (GH), preeclampsia (PRE), and CH with superimposed preeclampsia (SPE).We aim to assess in-hospital maternal and fetal outcomes of women in each of these groups in comparison to normotensive controls. Methods Study sample included women in the National Inpatient Sample dataset from 2016 to 2020 who were categorized into the 4 groups of HDP as described above. They were compared to normotensive pregnancies for maternal and fetal outcomes using regression analysis after adjusting for age, race, C-section status, and comorbidities. Results The study dataset from October 2015-December 2020 included 19,089,780 delivery admissions with 2,771,809 (14.5 %) of patients affected by HDP. The HDP groups were distributed as follows: GH - 38 %, PRE - 32 %, SPE - 11 %, and CH - 19 %. Women with PRE, SPE, and CH had significantly higher rates of mortality, circulatory shock, peripartum cardiomyopathy, acute kidney injury, preterm labor, stillbirth, and cerebrovascular events as compared to normotensive patients, while GH did not. Specifically, maternal mortality was highest in the SPE group (adjusted odds ratio [aOR] 3.16), followed by PRE (aOR 2.91) and CH (aOR 2.42). Additionally, all HDP groups had higher rates of small for gestational age and significant bleeding as compared to normotensive patients. Conclusions Pregnant patients with CH, PRE, and SPE experience higher rates of adverse maternal and fetal outcomes during their delivery admission when compared to normotensive patients. Understanding the graded risk differences across HDP subtypes may enable more tailored interventions, optimizing maternal and fetal outcomes for those at highest risk.
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Affiliation(s)
- Laith Alhuneafat
- Division of Cardiovascular Disease, University of Minnesota, Minneapolis, MN, USA
| | - Fares Ghanem
- Department of Cardiovascular Medicine, Southern Illinois University, Springfield, IL, USA
| | - Sneha Nandy
- Division of Cardiovascular Disease, University of Minnesota, Minneapolis, MN, USA
| | - Sana Khan
- Department of Medicine, Allegheny Health Network, Pittsburgh, PA, USA
| | - Anushree Puttur
- Department of Medicine, Allegheny Health Network, Pittsburgh, PA, USA
| | - Ahmad Jabri
- Department of Cardiovascular Disease, Henry Ford Health System, Detroit, MI, USA
| | - Alaq Haddad
- School of Public Health, Harvard University, Boston, MA, USA
| | - Bhavadharini Ramu
- Division of Cardiovascular Disease, University of Minnesota, Minneapolis, MN, USA
| | - Bethany Sabol
- Department of Maternal-Fetal Medicine, University of Minnesota, Minneapolis, MN, USA
| | - Jessica Schultz
- Division of Cardiovascular Disease, University of Minnesota, Minneapolis, MN, USA
| | - Selma Carlson
- Division of Cardiovascular Disease, University of Minnesota, Minneapolis, MN, USA
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Paydar K, Sheikhtaheri A. Prediction of pregnancy outcomes in women with systemic lupus erythematosus before pregnancy: Application of machine learning models. Heliyon 2025; 11:e42679. [PMID: 40040993 PMCID: PMC11876896 DOI: 10.1016/j.heliyon.2025.e42679] [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: 08/30/2023] [Revised: 02/11/2025] [Accepted: 02/12/2025] [Indexed: 03/06/2025] Open
Abstract
Introduction Fetal loss is possible during pregnancy in women with systemic lupus erythematosus (SLE). Predicting pregnancy outcomes for women with SLE can be an effective aid in providing consultation and treatment services. Therefore, this study aimed to develop a machine-learning model that could predict pregnancy outcomes before pregnancy in women with SLE. Methods The data of all pregnant women referred to the rheumatology center of Shariati Hospital and a specialized rheumatology clinic since 1980 were retrospectively collected from their medical records. Data collection was done by gathering 26 variables that affect pregnancy outcomes. Then, we used standard algorithms to select important features that affect pregnancy outcomes before pregnancy (11 different feature sets). A variety of machine learning algorithms were trained using both imbalanced and balanced datasets in Clementine and Weka software. Finally, the model with a higher area under the receiver operating characteristic curve (AUC) and F-score was selected to predict pregnancy outcomes. Results Out of 149 pregnancies, 46 pregnancies resulted in spontaneous abortion, while 103 pregnancies resulted in live birth. Compared with other models, the Chi-square automatic interaction detection (CHAID) decision tree was selected as the best-performing model with higher accuracy (93.5 %), specificity (92.9 %), sensitivity (93.8 %), precision (97 %), F-score (0.95), and AUC (0.96). Conclusion By using the CHAID decision tree to predict the outcome of pregnancy in women with SLE and extracted rules, it is possible to use appropriate methods that prevent spontaneous abortion and also provide timely consultation to women with SLE for making decisions to become pregnant.
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Affiliation(s)
| | - Abbas Sheikhtaheri
- Health Management and Economics Research Center, Health Management Research Institute, Iran University of Medical Sciences, Tehran, Iran
- Department of Health Information Management, School of Health Management and Information Sciences, Iran University of Medical Sciences, Tehran, Iran
- Digital Health and Artificial Intelligence in Medicine Research Unit, Iran University of Medical Sciences, Tehran, Iran
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Moiz A, Zolotarova T, Eisenberg MJ. Outpatient management of essential hypertension: a review based on the latest clinical guidelines. Ann Med 2024; 56:2338242. [PMID: 38604225 PMCID: PMC11011233 DOI: 10.1080/07853890.2024.2338242] [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: 08/29/2023] [Accepted: 03/15/2024] [Indexed: 04/13/2024] Open
Abstract
Background: Essential hypertension, a prevalent cardiovascular condition, poses a significant health burden worldwide. Based on the latest American clinical guidelines, half of adults in the United States have hypertension. Of these, only about a half are treated and about a quarter are adequately controlled for hypertension. Given its impact on morbidity and mortality, ensuring effective management of high blood pressure is crucial to reduce associated risks and improve patient outcomes.Objective: This review aims to provide a comprehensive and up-to-date summary of the latest cardiology guidelines and evidence-based research on essential hypertension, with a focus on guiding outpatient clinical practice.Methods: The review evaluates both non-pharmacological approaches and pharmacological interventions to offer clinicians practical insights. Notably, it emphasizes the importance of individualized treatment plans tailored to patients' specific risk profiles and comorbidities.Results: By consolidating the latest advancements in hypertension management, this review provides clinicians with an up-to-date reference, offering a nuanced understanding of treatment goals and strategies.Conclusion: Through the incorporation of evidence-based recommendations, healthcare practitioners can optimize patient care, mitigate potential complications, and improve overall outcomes in essential hypertension.
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Affiliation(s)
- Areesha Moiz
- Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Canada
| | - Tetiana Zolotarova
- Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Canada
| | - Mark J. Eisenberg
- Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Canada
- Department of Medicine and Health Sciences, McGill University, Montreal, Canada
- Departments of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Canada
- Division of Cardiology, Jewish General Hospital, McGill University, Montreal, Canada
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Pinto-Souza CC, Kaihara JNS, Nunes PR, Mastella MH, Rossini BC, Cavecci-Mendonça B, Cavalli RDC, dos Santos LD, Sandrim VC. Different Proteomic Profiles Regarding Antihypertensive Therapy in Preeclampsia Pregnant. Int J Mol Sci 2024; 25:8738. [PMID: 39201423 PMCID: PMC11354552 DOI: 10.3390/ijms25168738] [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: 06/25/2024] [Revised: 07/22/2024] [Accepted: 08/07/2024] [Indexed: 09/02/2024] Open
Abstract
Preeclampsia (PE) is a hypertensive pregnancy syndrome associated with target organ damage and increased cardiovascular risks, necessitating antihypertensive therapy. However, approximately 40% of patients are nonresponsive to treatment, which results in worse clinical outcomes. This study aimed to compare circulating proteomic profiles and identify differentially expressed proteins among 10 responsive (R-PE), 10 nonresponsive (NR-PE) patients, and 10 healthy pregnant controls (HP). We also explored correlations between these proteins and clinical data. Plasma protein relative quantification was performed using mass spectrometry, followed by bioinformatics analyses with the UniProt database, PatternLab for Proteomics 4.0, and MetaboAnalyst software (version 6.0). Considering a fold change of 1.5, four proteins were differentially expressed between NR-PE and R-PE: one upregulated (fibronectin) and three downregulated (pregnancy-specific beta-1-glycoprotein 1, complement C4B, and complement C4A). Between NR-PE and HP, six proteins were differentially expressed: two upregulated (clusterin and plasmin heavy chain A) and four downregulated (apolipoprotein L1, heparin cofactor II, complement C4B, and haptoglobin-related protein). Three proteins were differentially expressed between R-PE and HP: one downregulated (transthyretin) and two upregulated (apolipoprotein C1 and hemoglobin subunit beta). These findings suggest a complex interplay of these proteins involved in inflammatory, immune, and metabolic processes with antihypertensive therapy responsiveness and PE pathophysiology.
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Affiliation(s)
- Caroline C. Pinto-Souza
- Department of Biophysics and Pharmacology, Institute of Biosciences of Botucatu (IBB), São Paulo State University (UNESP), Botucatu 18618-689, SP, Brazil; (C.C.P.-S.); (J.N.S.K.); (P.R.N.); (M.H.M.)
| | - Julyane N. S. Kaihara
- Department of Biophysics and Pharmacology, Institute of Biosciences of Botucatu (IBB), São Paulo State University (UNESP), Botucatu 18618-689, SP, Brazil; (C.C.P.-S.); (J.N.S.K.); (P.R.N.); (M.H.M.)
| | - Priscila R. Nunes
- Department of Biophysics and Pharmacology, Institute of Biosciences of Botucatu (IBB), São Paulo State University (UNESP), Botucatu 18618-689, SP, Brazil; (C.C.P.-S.); (J.N.S.K.); (P.R.N.); (M.H.M.)
| | - Moises H. Mastella
- Department of Biophysics and Pharmacology, Institute of Biosciences of Botucatu (IBB), São Paulo State University (UNESP), Botucatu 18618-689, SP, Brazil; (C.C.P.-S.); (J.N.S.K.); (P.R.N.); (M.H.M.)
| | - Bruno C. Rossini
- Biotechnology Institute (IBTEC), São Paulo State University (UNESP), Botucatu 18618-687, SP, Brazil; (B.C.R.); (B.C.-M.); (L.D.d.S.)
| | - Bruna Cavecci-Mendonça
- Biotechnology Institute (IBTEC), São Paulo State University (UNESP), Botucatu 18618-687, SP, Brazil; (B.C.R.); (B.C.-M.); (L.D.d.S.)
- Center for the Study of Venoms and Venomous Animals (CEVAP), São Paulo State University (UNESP), Botucatu 18619-002, SP, Brazil
| | - Ricardo de Carvalho Cavalli
- Department of Gynecology and Obstetrics, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo (USP), Ribeirao Preto 14049-900, SP, Brazil;
| | - Lucilene D. dos Santos
- Biotechnology Institute (IBTEC), São Paulo State University (UNESP), Botucatu 18618-687, SP, Brazil; (B.C.R.); (B.C.-M.); (L.D.d.S.)
| | - Valeria C. Sandrim
- Department of Biophysics and Pharmacology, Institute of Biosciences of Botucatu (IBB), São Paulo State University (UNESP), Botucatu 18618-689, SP, Brazil; (C.C.P.-S.); (J.N.S.K.); (P.R.N.); (M.H.M.)
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Thomopoulos C, Hitij JB, De Backer T, Gkaliagkousi E, Kreutz R, Lopez-Sublet M, Marketou M, Mihailidou AS, Olszanecka A, Pechère-Bertschi A, Pérez MP, Persu A, Piani F, Socrates T, Stolarz-Skrzypek K, Cífková R. Management of hypertensive disorders in pregnancy: a Position Statement of the European Society of Hypertension Working Group 'Hypertension in Women'. J Hypertens 2024; 42:1109-1132. [PMID: 38690949 DOI: 10.1097/hjh.0000000000003739] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/03/2024]
Abstract
Hypertensive disorders in pregnancy (HDP), remain the leading cause of adverse maternal, fetal, and neonatal outcomes. Epidemiological factors, comorbidities, assisted reproduction techniques, placental disorders, and genetic predisposition determine the burden of the disease. The pathophysiological substrate and the clinical presentation of HDP are multifarious. The latter and the lack of well designed clinical trials in the field explain the absence of consensus on disease management among relevant international societies. Thus, the usual clinical management of HDP is largely empirical. The current position statement of the Working Group 'Hypertension in Women' of the European Society of Hypertension (ESH) aims to employ the current evidence for the management of HDP, discuss the recommendations made in the 2023 ESH guidelines for the management of hypertension, and shed light on controversial issues in the field to stimulate future research.
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Affiliation(s)
- Costas Thomopoulos
- Department of Cardiology, General Hospital of Athens 'Laiko', Athens, Greece
| | - Jana Brguljan Hitij
- Department of Hypertension, University Medical Centre Ljubljana, Medical University Ljubljana, Slovenia
| | - Tine De Backer
- Cardiovascular Center & Clinical Pharmacology, University Hospital Gent, Belgium
| | - Eugenia Gkaliagkousi
- 3rd Department of Internal Medicine, Papageorgiou Hospital Faculty of Medicine, Aristotle University of Thessaloniki, Greece
| | - Reinhold Kreutz
- Charite-Universitätsmedizin Berlin, Institute of Clinical Pharmacology and Toxicology, Berlin, Germany
| | - Marilucy Lopez-Sublet
- AP-HP, Hopital Avicenne, Centre d'Excellence Europeen en Hypertension Arterielle, Service de Medecine Interne, INSERM UMR 942 MASCOT, Paris 13-Universite Paris Nord, Bobigny, FCRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists)
| | - Maria Marketou
- School of Medicine, University of Crete, Heraklion, Greece
| | - Anastasia S Mihailidou
- Department of Cardiology and Kolling Institute, Royal North Shore Hospital, St Leonards
- Faculty of Medicine and Health Sciences, Macquarie University, Sydney, New South Wales, Australia
| | - Agnieszka Olszanecka
- 1st Department of Cardiology, Interventional Electrocardiology, and Hypertension, Jagiellonian University Medical College, Krakow, Poland
| | | | - Mariana Paula Pérez
- Department of Hypertension. Hospital de Agudos J. M. Ramos Mejía, Buenos Aires, Argentina
| | - Alexandre Persu
- Division of Cardiology, Cliniques Universitaires Saint-Luc and Pole of Cardiovascular Research, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, Brussels, Belgium
| | - Federica Piani
- Hypertension and Cardiovascular Risk Research Center, Medical and Surgical Sciences Department, Alma Mater Studiorum University of Bologna, Bologna, Italy
| | - Thenral Socrates
- Medical Outpatient and Hypertension Clinic, ESH Hypertension Centre of Excellence University Hospital Basel, Basel, Switzerland
| | - Katarzyna Stolarz-Skrzypek
- 1st Department of Cardiology, Interventional Electrocardiology, and Hypertension, Jagiellonian University Medical College, Krakow, Poland
| | - Renata Cífková
- Center for Cardiovascular Prevention, Charles University in Prague, First Faculty of Medicine and Thomayer University Hospital
- Department of Medicine II, Charles University in Prague, First Faculty of Medicine, Prague, Czech Republic
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6
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Kuklina EV, Merritt RK, Wright JS, Vaughan AS, Coronado F. Hypertension in Pregnancy: Current Challenges and Future Opportunities for Surveillance and Research. J Womens Health (Larchmt) 2024; 33:553-562. [PMID: 38529887 PMCID: PMC11260429 DOI: 10.1089/jwh.2023.1072] [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] [Indexed: 03/27/2024] Open
Abstract
Hypertension in pregnancy (HP) includes eclampsia/preeclampsia, chronic hypertension, superimposed preeclampsia, and gestational hypertension. In the United States, HP prevalence doubled over the last three decades, based on birth certificate data. In 2019, the estimated percent of births with a history of HP varied from 10.1% to 15.9% for birth certificate data and hospital discharge records, respectively. The use of electronic medical records may result in identifying an additional third to half of undiagnosed cases of HP. Individuals with gestational hypertension or preeclampsia are at 3.5 times higher risk of progressing to chronic hypertension and from 1.7 to 2.8 times higher risk of developing cardiovascular disease (CVD) after childbirth compared with individuals without these conditions. Interventions to identify and address CVD risk factors among individuals with HP are most effective if started during the first 6 weeks postpartum and implemented during the first year after childbirth. Providing access to affordable health care during the first 12 months after delivery may ensure healthy longevity for individuals with HP. Average attendance rates for postpartum visits in the United States are 72.1%, but the rates vary significantly (from 24.9% to 96.5%). Moreover, even among individuals with CVD risk factors who attend postpartum visits, approximately 40% do not receive counseling on a healthy lifestyle. In the United States, as of the end of September 2023, 38 states and the District of Columbia have extended Medicaid coverage eligibility, eight states plan to implement it, and two states proposed a limited coverage extension from 2 to 12 months after childbirth. Currently, data gaps exist in national health surveillance and health systems to identify and monitor HP. Using multiple data sources, incorporating electronic medical record data algorithms, and standardizing data definitions can improve surveillance, provide opportunities to better track progress, and may help in developing targeted policy recommendations.
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Affiliation(s)
- Elena V Kuklina
- Division for Heart Disease and Stroke Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
| | - Robert K Merritt
- Division for Heart Disease and Stroke Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
| | - Janet S Wright
- Division for Heart Disease and Stroke Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
| | - Adam S Vaughan
- Division for Heart Disease and Stroke Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
| | - Fátima Coronado
- Division for Heart Disease and Stroke Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
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7
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Esposito M, Gatto M, Cipolla MJ, Bernstein IM, Mandalà M. Dilation of Pregnant Rat Uterine Arteries with Phenols from Extra Virgin Olive Oil Is Endothelium-Dependent and Involves Calcium and Potassium Channels. Cells 2024; 13:619. [PMID: 38607058 PMCID: PMC11011993 DOI: 10.3390/cells13070619] [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: 03/08/2024] [Revised: 03/27/2024] [Accepted: 03/29/2024] [Indexed: 04/13/2024] Open
Abstract
During pregnancy, uterine vasculature undergoes significant circumferential growth to increase uterine blood flow, vital for the growing feto-placental unit. However, this process is often compromised in conditions like maternal high blood pressure, particularly in preeclampsia (PE), leading to fetal growth impairment. Currently, there is no cure for PE, partly due to the adverse effects of anti-hypertensive drugs on maternal and fetal health. This study aimed to investigate the vasodilator effect of extra virgin olive oil (EVOO) phenols on the reproductive vasculature, potentially benefiting both mother and fetus. Isolated uterine arteries (UAs) from pregnant rats were tested with EVOO phenols in a pressurized myograph. To elucidate the underlying mechanisms, additional experiments were conducted with specific inhibitors: L-NAME/L-NNA (10-4 M) for nitric oxide synthases, ODQ (10-5 M) for guanylate cyclase, Verapamil (10-5 M) for the L-type calcium channel, Ryanodine (10-5 M) + 2-APB (3 × 10-5 M) for ryanodine and the inositol triphosphate receptors, respectively, and Paxilline (10-5 M) for the large-conductance calcium-activated potassium channel. The results indicated that EVOO-phenols activate Ca2+ signaling pathways, generating nitric oxide, inducing vasodilation via cGMP and BKCa2+ signals in smooth muscle cells. This study suggests the potential use of EVOO phenols to prevent utero-placental blood flow restriction, offering a promising avenue for managing PE.
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Affiliation(s)
- Milena Esposito
- Department of Biology, Ecology & Earth Science, University of Calabria, 87036 Arcavacata di Rende, CS, Italy; (M.E.); (M.G.)
| | - Mariacarmela Gatto
- Department of Biology, Ecology & Earth Science, University of Calabria, 87036 Arcavacata di Rende, CS, Italy; (M.E.); (M.G.)
| | - Marilyn J. Cipolla
- Department of Obstetrics, Gynecology and Reproductive Sciences, University of Vermont, Larner College of Medicine, Burlington, VT 05405, USA;
- Department of Neurological Sciences, University of Vermont, Larner College of Medicine, Burlington, VT 05405, USA;
| | - Ira M. Bernstein
- Department of Neurological Sciences, University of Vermont, Larner College of Medicine, Burlington, VT 05405, USA;
| | - Maurizio Mandalà
- Department of Biology, Ecology & Earth Science, University of Calabria, 87036 Arcavacata di Rende, CS, Italy; (M.E.); (M.G.)
- Department of Obstetrics, Gynecology and Reproductive Sciences, University of Vermont, Larner College of Medicine, Burlington, VT 05405, USA;
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Elgendy MM, Cortez J, Saker F, Acun C, Matar RB, Mohamed MA, Aly H. Acute kidney injury in infants with hypoxic-ischemic encephalopathy. Pediatr Nephrol 2024; 39:1271-1277. [PMID: 37947899 DOI: 10.1007/s00467-023-06214-3] [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: 08/09/2023] [Revised: 10/24/2023] [Accepted: 10/24/2023] [Indexed: 11/12/2023]
Abstract
BACKGROUND This study aimed to investigate the prevalence of acute kidney injury (AKI) in infants with varying degrees of hypoxic-ischemic encephalopathy (HIE) and its associated outcomes, including mortality and length of stay (LOS). METHODS The study used the National Inpatient Sample (NIS) dataset from 2010 to 2018. Regression analysis was used to control confounding variables. RESULTS Of 31,220,784 infants included in the study, 30,130 (0.1%) had HIE. The prevalence of AKI was significantly higher in infants with HIE (9.0%) compared to those without (0.04%), with an adjusted odds ratio (aOR) of 77.6 (CI:70.1-85.7, p < 0.001), with the highest prevalence of AKI in infants with severe HIE (19.7%), aOR:130 (CI: 107-159), p < 0.001). Infants with AKI had a higher mortality rate compared to those without AKI in those diagnosed with any degree of HIE (28.9% vs. 8.8%), aOR 3.5 (CI: 3.2-3.9, p < 0.001), particularly among those with severe HIE, aOR:1.4 (1.2-1.6, p < 0.001). CONCLUSIONS HIE is associated with an increased prevalence of AKI. Infants with severe HIE had the highest prevalence of AKI and associated mortality. The study highlights the need for close monitoring and early detection of AKI in infants with HIE, particularly those with severe HIE, to ameliorate the associated adverse outcomes.
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Affiliation(s)
- Marwa M Elgendy
- Department of Pediatrics & Neonatology, University of Florida College of Medicine-Jacksonville, Jacksonville, FL, USA.
| | - Josef Cortez
- Division of Neonatology, University of Florida College of Medicine - Jacksonville, Jacksonville, FL, USA
| | - Firas Saker
- Department of Neonatology, Cleveland Clinic Children's, Cleveland, OH, USA
| | - Ceyda Acun
- Department of Neonatology, Cleveland Clinic Children's, Cleveland, OH, USA
| | - Raed Bou Matar
- Center for Pediatric Nephrology, Cleveland Clinic Children's, Cleveland, OH, USA
| | - Mohamed A Mohamed
- Department of Neonatology, Cleveland Clinic Children's, Cleveland, OH, USA
| | - Hany Aly
- Department of Neonatology, Cleveland Clinic Children's, Cleveland, OH, USA
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9
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Sharma DD, Chandresh NR, Javed A, Girgis P, Zeeshan M, Fatima SS, Arab TT, Gopidasan S, Daddala VC, Vaghasiya KV, Soofia A, Mylavarapu M. The Management of Preeclampsia: A Comprehensive Review of Current Practices and Future Directions. Cureus 2024; 16:e51512. [PMID: 38304688 PMCID: PMC10832549 DOI: 10.7759/cureus.51512] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/01/2024] [Indexed: 02/03/2024] Open
Abstract
Preeclampsia (PE) is a disease in pregnancy that is characterized by new-onset hypertension end-organ dysfunction, often occurring after 20 weeks of gestation. Risk factors include a prior history of PE, diabetes, kidney disease, obesity, and high maternal age at pregnancy. Current treatment and management guidelines focus on the management of high blood pressure and any potential complications. The only known curative treatment is termination of pregnancy (either induction of delivery or cesarean section). However, the current guidelines and recommendations lack adequate prediction markers and are unable to prevent maternal and fetal mortality. There also exists a need for multidisciplinary collaborative action in view of the quality of life and psycho-educational counseling.
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Affiliation(s)
- Dhruvikumari D Sharma
- Biochemistry, Spartan Health Sciences University, Vieux Fort, LCA
- Medicine, Avalon University School of Medicine, Willemstad, CUW
| | | | - Ayesha Javed
- Gynecology, Hearts International Hospital, Rawalpindi, Rawalpindi, PAK
| | - Peter Girgis
- Internal Medicine, Ross University School of Medicine, Bridgetown, BRB
| | - Madiha Zeeshan
- Internal Medicine, Fatima Jinnah Medical University, Lahore, PAK
| | - Syeda Simrah Fatima
- Internal Medicine, Rajarajeswari Medical College and Hospital, Bangalore, IND
| | - Taneen T Arab
- Family Medicine, Saint James School of Medicine, Chicago, USA
| | - Sreeja Gopidasan
- Internal Medicine, American International School of Medicine, George Town, GUY
| | | | - Kalgi V Vaghasiya
- College of Medicine, Community Health Center (CHC) Vartej, Vartej, IND
| | - Ameena Soofia
- Internal Medicine, Shadan Institute of Medical Sciences, Hyderabad, IND
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Bhat AD, Keasler PM, Kolluru L, Dombrowski MM, Palanisamy A, Singh PM. Treatment of acute-onset hypertension in pregnancy: A network meta-analysis of randomized controlled trials comparing anti-hypertensives and route of administration. Pregnancy Hypertens 2023; 34:74-82. [PMID: 37857042 DOI: 10.1016/j.preghy.2023.10.005] [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: 03/07/2023] [Revised: 07/03/2023] [Accepted: 10/06/2023] [Indexed: 10/21/2023]
Abstract
BACKGROUND Consensus on the relative efficacy of available antihypertensive agents used in pregnancy is lacking. OBJECTIVE To compare treatment success with antihypertensives and categorize by route of administration. SEARCH STRATEGY MEDLINE, Embase, PubMed, Web of Science, Scopus, CINAHL, and clinicaltrials.gov were searched without date restriction. DATA COLLECTION Peer-reviewed randomized controlled trials (RCTs) comparing pharmacologic agents used to treat hypertension in parturients were included. Evaluated treatment groups included IV-labetalol (BBIV), IV-hydralazine (DIV), oral-nifedipine (CCBPO), sublingual nifedipine (CCBSL), IV-calcium channel blocker (nonspecific)(CCBIV), IV-nitroglycerine (NTG), epoprostenol infusion (PRO), IV-ketanserin (5HT2B), IV-diazoxide (BZO), oral-nifedipine + methyldopa (CCBAG), oral-methyl-dopa (AAG), and oral prazosin (ABPO). ANALYSIS Seventy-four studies (8324 patients) were eligible post PRISMA guidelines screening. Results were pooled using a Bayesian-approach for success of treatment (study defined target blood pressure), time to achieve target pressure, and neonatal intensive-care admissions. RESULTS Treatment success (primary outcome, 55 trials with 5518 patients) was analyzed. Surface under the cumulative ranking curve (SUCRA) was categorized for 13 drugs, CCBPO (0.84) followed by CCBSL (0.78) were most likely to be effective in achieving target blood pressure. After sub-grouping by presence/absence of preeclampsia, CCB-PO ranked highest for both [(0.82) vs. (0.77), respectively]. Serotonin antagonists (0.99) and nitroglycerin (0.88) ranked highest for time to target pressure. NICU admissions were lowest for alpha-2 agonists (0.89), followed by BB PO (0.82) and hydralazine IV (0.49). CONCLUSION Oral calcium-channel blockers ranked highest for treatment success. Ketanserin achieved target blood pressure fastest, warranting additional research. The results should be interpreted with caution as SUCRA values may not indicate whether the differences between interventions have clinically meaningful effect sizes.
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Affiliation(s)
- Adithya D Bhat
- Department of Anesthesiology, Washington University School of Medicine in St. Louis, MO, USA
| | - Paige M Keasler
- Department of Anesthesiology, Washington University School of Medicine in St. Louis, MO, USA; Department of Anesthesiology, University of Washington Medical Center, WA, USA
| | - Lavanya Kolluru
- University of Missouri-Kansas City School of Medicine, MO, USA
| | - Michael M Dombrowski
- Department of Obstetrics and Gynecology, Washington University School of Medicine in St. Louis, MO, USA
| | - Arvind Palanisamy
- Department of Anesthesiology, Washington University School of Medicine in St. Louis, MO, USA
| | - Preet Mohinder Singh
- Department of Anesthesiology, Washington University School of Medicine in St. Louis, MO, USA.
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11
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Barry MJ, Nicholson WK, Silverstein M, Cabana MD, Chelmow D, Coker TR, Davis EM, Donahue KE, Jaén CR, Li L, Ogedegbe G, Rao G, Ruiz JM, Stevermer J, Tsevat J, Underwood SM, Wong JB. Screening for Hypertensive Disorders of Pregnancy: US Preventive Services Task Force Final Recommendation Statement. JAMA 2023; 330:1074-1082. [PMID: 37721605 DOI: 10.1001/jama.2023.16991] [Citation(s) in RCA: 30] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 09/19/2023]
Abstract
Importance Hypertensive disorders of pregnancy are among the leading causes of maternal morbidity and mortality in the US. The rate of hypertensive disorders of pregnancy has been increasing from approximately 500 cases per 10 000 deliveries in 1993 to 1021 cases per 10 000 deliveries in 2016 to 2017. Objective The US Preventive Services Task Force (USPSTF) commissioned a systematic review to evaluate the benefits and harms of screening for hypertensive disorders of pregnancy. Population Pregnant persons without a known diagnosis of a hypertensive disorder of pregnancy or chronic hypertension. Evidence Assessment The USPSTF concludes with moderate certainty that screening for hypertensive disorders in pregnancy with blood pressure measurements has substantial net benefit. Recommendation The USPSTF recommends screening for hypertensive disorders in pregnant persons with blood pressure measurements throughout pregnancy. (B recommendation).
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Affiliation(s)
| | | | | | | | | | | | - Esa M Davis
- University of Maryland School of Medicine, Baltimore
| | | | | | - Li Li
- University of Virginia, Charlottesville
| | | | - Goutham Rao
- Case Western Reserve University, Cleveland, Ohio
| | | | | | - Joel Tsevat
- University of Texas Health Science Center, San Antonio
| | | | - John B Wong
- Tufts University School of Medicine, Boston, Massachusetts
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12
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Ehikioya E, Okobi OE, Beeko MAE, Abanga R, Abah NNI, Briggs L, Nwimo PN, Beeko PKA, Nwachukwu OB, Okoroafor CC. Comparing Intravenous Labetalol and Intravenous Hydralazine for Managing Severe Gestational Hypertension. Cureus 2023; 15:e42332. [PMID: 37614273 PMCID: PMC10443893 DOI: 10.7759/cureus.42332] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/23/2023] [Indexed: 08/25/2023] Open
Abstract
Background Hypertensive disorders of pregnancy are the leading causes of both maternal morbidity and maternal mortality. Hypertensive disorders are acute obstetric emergencies, which refer to various life-threatening medical challenges known to develop during pregnancy, labor, and delivery, requiring urgent attention to reduce blood pressure (BP) for the benefit of the affected mothers and infants. Hydralazine and labetalol have been widely used as the first-line medications in the management of severe hypertension during pregnancy. However, the choice between these two drugs lacks clear evidence regarding their safety and superiority. Several studies have attempted to study intravenous (IV) labetalol versus hydralazine, but very few such comparison studies have been conducted in Africa. Objective To compare the effectiveness of IV labetalol and IV hydralazine in reducing systolic and diastolic BP in pregnant women with severe hypertension. Also, to determine the time required for hydralazine and labetalol to lower BP to ≤150/100 mmHg, the number of doses needed for each drug, and evaluating maternal and perinatal outcomes. Study design This study employed an open-label randomized clinical trial design conducted in the labor, delivery, and antenatal ward of the Central and Stella Obasanjo Hospital in Benin City. A total of 120 women with severe pregnancy-induced hypertension were randomly assigned to two groups: Group X, consisting of 60 pregnant women, received IV hydralazine at a slow rate of 5 mg for five minutes, repeated every 20 minutes (maximum of five doses) until a blood pressure of ≤150/100 mmHg was achieved. Group Y, also consisting of 60 pregnant women, received IV labetalol in escalating doses of 25, 50, 75, 75, and 75 mg (maximum of 300 mg) every 20 minutes until the blood pressure reached ≤150/100 mmHg. Statistical analysis was performed using SPSS version 23 (IBM Inc., Armonk, New York). Result IV hydralazine achieved the target BP in an average time of 45.80 +/- 25.17 minutes, while IV labetalol took an average of 72.67 +/- 41.80 minutes (p=0.001). The number of doses required to reach the target BP differed significantly between the two drugs. Hydralazine required an average of 1.72 +/- 0.904 doses, whereas labetalol required an average of 3.72 +/- 1.782 doses (p=0.0001). While 45% of women in the hydralazine group attained the target BP with a single dose of hydralazine, only 31.1% of women in the labetalol group were able to attain the target BP with a single dose of labetalol (p=0.02). Overall, target BP was achieved in 55 out of 60 women (91.7%) who were randomized to receive IV hydralazine, whereas 45 out of 60 women (75%) who received IV labetalol achieved the target blood pressure. While hydralazine demonstrated more favorable results in terms of achieving target blood pressure, there were higher incidences of maternal adverse effects in the hydralazine group compared to the labetalol group. However, these adverse effects were not severe enough to warrant discontinuation of the medication. Conclusion IV hydralazine showed faster achievement of the target BP and a lower number of doses required compared to IV labetalol. Additionally, a higher percentage of women in the hydralazine group achieved the target BP with a single dose. However, there were more maternal adverse effects associated with hydralazine, although they were not severe. Perinatal outcomes did not differ significantly between the two groups.
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Affiliation(s)
| | - Okelue E Okobi
- Family Medicine, Medficient Health Systems, Laurel, USA
- Family Medicine, Lakeside Medical Center, Belle Glade, USA
| | | | - Rafia Abanga
- Obstetrics and Gynecology, Weija Gbawe Municipal Hospital, Accra, GHA
| | | | - Lilian Briggs
- Internal Medicine, Grodno State Medical University, Belarus, AUS
| | - Patience N Nwimo
- Internal Medicine, First Foundation Medical Clinic, Loganville, USA
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13
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Buxton MA, Heydarzadeh S, Gronlund CJ, Castillo-Castrejon M, Godines-Enriquez MS, O’Neill MS, Vadillo-Ortega F. Associations between Air Pollution Exposure and Blood Pressure during Pregnancy among PRINCESA Cohort Participants. TOXICS 2023; 11:424. [PMID: 37235239 PMCID: PMC10222039 DOI: 10.3390/toxics11050424] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/31/2022] [Revised: 04/12/2023] [Accepted: 04/19/2023] [Indexed: 05/28/2023]
Abstract
High blood pressure (BP) is a risk factor for hypertensive disease during pregnancy. Exposure to multiple toxic air pollutants can affect BP in pregnancy but has been rarely studied. We evaluated trimester-specific associations between air pollution exposure and systolic (SBP) and diastolic BP (DBP). Ozone (O3), sulfur dioxide (SO2), carbon monoxide (CO), nitrogen dioxide (NO2), and particulate matter less than 10 and 2.5 μm in aerodynamic diameter (PM10, PM2.5) in the Pregnancy Research on Inflammation, Nutrition, & City Environment: Systematic Analyses (PRINCESA) study. Multipollutant generalized linear regression models with each pollutant and O3 were fit. Due to nonlinear pollution/BP associations, results are presented for "below the median" or "above the median", where the beta estimate is the change in BP at a pollutant's median versus BP at the pollutant's minimum or maximum, respectively. Associations varied across trimesters and pollutants, and deleterious associations (higher blood pressure with higher pollution) were found only at pollutant values below the median: for SBP with NO2 in the second and third trimesters, and PM2.5 during the third trimester, and for DBP, PM2.5, and NO2 in the second and third trimesters. Findings suggest that minimizing prenatal exposure to air pollution may reduce the risks of changes in BP.
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Affiliation(s)
- Miatta A. Buxton
- Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI 48109, USA; (S.H.); (C.J.G.); (M.S.O.)
| | - Safa Heydarzadeh
- Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI 48109, USA; (S.H.); (C.J.G.); (M.S.O.)
| | - Carina J. Gronlund
- Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI 48109, USA; (S.H.); (C.J.G.); (M.S.O.)
- Institute for Social Research, Survey Research Center, University of Michigan, Ann Arbor, MI 48104, USA
| | - Marisol Castillo-Castrejon
- Department of Pathology, Stephenson Cancer Center, Harold Hamm Diabetes Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
| | | | - Marie S. O’Neill
- Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI 48109, USA; (S.H.); (C.J.G.); (M.S.O.)
- Department of Environmental Health Sciences, School of Public Health, University of Michigan, Ann Arbor, MI 48109, USA;
| | - Felipe Vadillo-Ortega
- Department of Environmental Health Sciences, School of Public Health, University of Michigan, Ann Arbor, MI 48109, USA;
- Unidad de Vinculación Científica de la Facultad de Medicina, Universidad Nacional Autónoma de México en el Instituto Nacional de Medicina Genómica, Mexico City 14610, Mexico
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Chang KJ, Seow KM, Chen KH. Preeclampsia: Recent Advances in Predicting, Preventing, and Managing the Maternal and Fetal Life-Threatening Condition. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2023; 20:2994. [PMID: 36833689 PMCID: PMC9962022 DOI: 10.3390/ijerph20042994] [Citation(s) in RCA: 70] [Impact Index Per Article: 35.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/29/2022] [Revised: 02/04/2023] [Accepted: 02/06/2023] [Indexed: 06/12/2023]
Abstract
Preeclampsia accounts for one of the most common documented gestational complications, with a prevalence of approximately 2 to 15% of all pregnancies. Defined as gestational hypertension after 20 weeks of pregnancy and coexisting proteinuria or generalized edema, and certain forms of organ damage, it is life-threatening for both the mother and the fetus, in terms of increasing the rate of mortality and morbidity. Preeclamptic pregnancies are strongly associated with significantly higher medical costs. The maternal costs are related to the extra utility of the healthcare system, more resources used during hospitalization, and likely more surgical spending due to an elevated rate of cesarean deliveries. The infant costs also contribute to a large percentage of the expenses as the babies are prone to preterm deliveries and relevant or causative adverse events. Preeclampsia imposes a considerable financial burden on our societies. It is important for healthcare providers and policy-makers to recognize this phenomenon and allocate enough economic budgets and medical and social resources accordingly. The true cellular and molecular mechanisms underlying preeclampsia remain largely unexplained, which is assumed to be a two-stage process of impaired uteroplacental perfusion with or without prior defective trophoblast invasion (stage 1), followed by general endothelial dysfunction and vascular inflammation that lead to systemic organ damages (stage 2). Risk factors for preeclampsia including race, advanced maternal age, obesity, nulliparity, multi-fetal pregnancy, and co-existing medical disorders, can serve as warnings or markers that call for enhanced surveillance of maternal and fetal well-being. Doppler ultrasonography and biomarkers including the mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI), and serum pregnancy-associated plasma protein A (PAPP-A) can be used for the prediction of preeclampsia. For women perceived as high-risk individuals for developing preeclampsia, the administration of low-dose aspirin on a daily basis since early pregnancy has proven to be the most effective way to prevent preeclampsia. For preeclamptic females, relevant information, counseling, and suggestions should be provided to facilitate timely intervention or specialty referral. In pregnancies complicated with preeclampsia, closer monitoring and antepartum surveillance including the Doppler ultrasound blood flow study, biophysical profile, non-stress test, and oxytocin challenge test can be arranged. If the results are unfavorable, early intervention and aggressive therapy should be considered. Affected females should have access to higher levels of obstetric units and neonatal institutes. Before, during, and after delivery, monitoring and preparation should be intensified for affected gravidas to avoid serious complications of preeclampsia. In severe cases, delivery of the fetus and the placenta is the ultimate solution to treat preeclampsia. The current review is a summary of recent advances regarding the knowledge of preeclampsia. However, the detailed etiology, pathophysiology, and effect of preeclampsia seem complicated, and further research to address the primary etiology and pathophysiology underlying the clinical manifestations and outcomes is warranted.
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Affiliation(s)
- Kai-Jung Chang
- Department of Obstetrics and Gynecology, Taipei Tzu-Chi Hospital, The Buddhist Tzu-Chi Medical Foundation, Taipei 231, Taiwan
| | - Kok-Min Seow
- Department of Obstetrics and Gynecology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei 111, Taiwan
- Department of Obstetrics and Gynecology, National Yang-Ming Chiao-Tung University, Taipei 112, Taiwan
| | - Kuo-Hu Chen
- Department of Obstetrics and Gynecology, Taipei Tzu-Chi Hospital, The Buddhist Tzu-Chi Medical Foundation, Taipei 231, Taiwan
- School of Medicine, Tzu-Chi University, Hualien 970, Taiwan
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15
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Abstract
Although men are at higher risk of stroke throughout most of their lifespan, the incidence of stroke in women climbs with age, increasing after menopause and rising sharply after 85 years. This, combined with women's longer life expectancy, results in most of the stroke deaths occurring in women. In addition to accounting for a larger proportion of strokes, women may also suffer a survival disadvantage, which may be due to several factors. In many families, women are the primary caretakers. When they become disabled, there may be limited options to care for them. Others suggest that some of the disparities in stroke outcomes in women may be related to age, pre-stroke functional status, and comorbidities. Regardless of the cause, the increased disability and post-stroke care requirements of women, particularly in our aging population, highlight the importance of determining successful strategies for stroke prevention, acute stroke treatments, optimization of stroke rehabilitation, and effective secondary prevention measures in women.
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16
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Comparative efficacy and safety of oral nifedipine with other antihypertensive medications in the management of hypertensive disorders of pregnancy: a systematic review and meta-analysis of randomized controlled trials. J Hypertens 2022; 40:1876-1886. [PMID: 35969195 DOI: 10.1097/hjh.0000000000003233] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
BACKGROUND Hypertensive disorders of pregnancy are the most frequently occurring medical condition during pregnancy, resulting in fetal and/or maternal morbidity and mortality. This meta-analysis compared the efficacy and safety of nifedipine with other antihypertensive medications used in hypertensive disorders of pregnancy. METHODOLOGY A comprehensive search was performed using PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), and Google Scholar. The meta-analysis was carried out using Review Manager Software, and the pooled effect estimate was generated as standardized mean difference and odds ratio with 95% confidence interval and two-sided P -value. RESULTS The meta-analysis was comprised of 22 randomized control trials with 2595 participants. It was found that meantime and number of doses required to achieve target blood pressure were lower in the nifedipine group ( P < 0.05). Even though it is statistically insignificant, fetal APGAR (Appearance, Pulse, Grimace, Activity, and Respiration) scores less than seven favors nifedipine intervention. Furthermore, none of the fetal or maternal secondary outcomes were found significant. CONCLUSION Nifedipine was found to be more effective than other antihypertensive medications to reduce blood pressure, particularly in patients with severe hypertension. However, future clinical studies, including real-world data are necessary to establish the safety profile of nifedipine concerning the fetal outcomes in hypertensive pregnant women.
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17
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Allen LB, Mirnics K. Metoprolol Inhibits Developmental Brain Sterol Biosynthesis in Mice. Biomolecules 2022; 12:1211. [PMID: 36139049 PMCID: PMC9496459 DOI: 10.3390/biom12091211] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2022] [Revised: 08/26/2022] [Accepted: 08/28/2022] [Indexed: 12/29/2022] Open
Abstract
De novo sterol synthesis is a critical homeostatic mechanism in the brain that begins during early embryonic development and continues throughout life. Multiple medications have sterol-biosynthesis-inhibiting side effects, with potentially detrimental effects on brain health. Using LC-MS/MS, we investigated the effects of six commonly used beta-blockers on brain sterol biosynthesis in vitro using cell lines. Two beta-blockers, metoprolol (MTP) and nebivolol, showed extreme elevations of the highly oxidizable cholesterol precursor 7-dehydrocholesterol (7-DHC) in vitro across multiple cell lines. We followed up on the MTP findings using a maternal exposure model in mice. We found that 7-DHC was significantly elevated in all maternal brain regions analyzed as well as in the heart, liver and brain of the maternally exposed offspring. Since DHCR7-inhibiting/7-DHC elevating compounds can be considered teratogens, these findings suggest that MTP utilization during pregnancy might be detrimental for the development of offspring, and alternative beta-blockers should be considered.
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Affiliation(s)
- Luke B. Allen
- Munroe-Meyer Institute for Genetics and Rehabilitation, University of Nebraska Medical Center, Omaha, NE 68105, USA
- Department of Biochemistry and Molecular Biology, College of Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA
| | - Károly Mirnics
- Munroe-Meyer Institute for Genetics and Rehabilitation, University of Nebraska Medical Center, Omaha, NE 68105, USA
- Department of Biochemistry and Molecular Biology, College of Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA
- Department of Pharmacology and Experimental Neuroscience, College of Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA
- Department of Psychiatry, College of Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA
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18
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Luizon MR, Pinto-Souza CC, Coeli-Lacchini F, Lacchini R, Cavalli RC, Sandrim VC. ARG2 single-nucleotide polymorphism rs3742879 affects plasma arginase 2 levels, nitric oxide formation and antihypertensive therapy response in preeclampsia. Pharmacogenomics 2022; 23:713-722. [PMID: 35971863 DOI: 10.2217/pgs-2022-0079] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Aim: This work examined whether ARG1 (rs2781659, rs2781667, rs2246012 and rs17599586) and ARG2 (rs3742879 and rs10483801) single-nucleotide polymorphisms (SNPs) are associated with antihypertensive therapy responsiveness in preeclampsia (PE) and their effects on arginase isoforms and nitrite concentrations in responsive and nonresponsive patients. Methods: SNP genotypes were determined by TaqMan assays. Plasma arginase levels were measured by ELISA and nitrite concentrations were measured using an ozone-based chemiluminescence assay. Results: The G allele for ARG2 rs3742879 (A>G) was less frequent in nonresponsive compared with responsive patients (15.5% vs 24.7%) and the G carriers of the nonresponsive subgroup had lower arginase 2 (9.2 ± 7.5 ng/ml vs 19.1 ± 17.3 ng/ml) and higher nitrite concentrations (110.2 ± 52.8 nM vs 78.5 ± 37.9 nM) than carriers of the AA genotype (all p < 0.05). Conclusion: ARG2 SNP rs3742879 is associated with diminished arginase 2 levels and increased nitric oxide formation in nonresponsive PE patients.
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Affiliation(s)
- Marcelo R Luizon
- Department of Genetics, Ecology & Evolution, Institute of Biological Sciences, Federal University of Minas Gerais (UFMG), Belo Horizonte, MG, 31270-901, Brazil
| | - Caroline C Pinto-Souza
- Department of Biophysics & Pharmacology, Institute of Biosciences of Botucatu, Universidade Estadual Paulista (UNESP), Distrito Rubiao Junior, Botucatu, Sao Paulo, 18618-689, Brazil
| | - Fernanda Coeli-Lacchini
- Department of Clinical Analyses, Toxicology & Food Science, School of Pharmaceutical Sciences of Ribeirao Preto, University of Sao Paulo (USP), Ribeirao Preto, Sao Paulo, 14040-903, Brazil
| | - Riccardo Lacchini
- Department of Psychiatric Nursing & Human Sciences, Ribeirao Preto School of Nursing, University of Sao Paulo (USP), Ribeirao Preto, Sao Paulo, 14049-900, Brazil
| | - Ricardo C Cavalli
- Department of Gynecology & Obstetrics, University of Sao Paulo (USP), Ribeirao Preto, Sao Paulo, 14049-900, Brazil
| | - Valeria C Sandrim
- Department of Biophysics & Pharmacology, Institute of Biosciences of Botucatu, Universidade Estadual Paulista (UNESP), Distrito Rubiao Junior, Botucatu, Sao Paulo, 18618-689, Brazil
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19
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Flavonoids exert potential in the management of hypertensive disorders in pregnancy. Pregnancy Hypertens 2022; 29:72-85. [DOI: 10.1016/j.preghy.2022.06.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2022] [Accepted: 06/29/2022] [Indexed: 11/19/2022]
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Greatorex B, Colebourn C, Ormerod O. Echocardiographic assessment and critical care management of peri-partum women with unexpected left ventricular failure. J Intensive Care Soc 2022; 23:210-221. [PMID: 35615233 PMCID: PMC9125437 DOI: 10.1177/1751143720978862] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2023] Open
Abstract
Introduction Cardiac disease remains the largest single cause of maternal death. Whilst uncommon, left ventricular failure during pregnancy and delivery can be devastating to both mother and child. Echocardiography can play a significant role in rapidly establishing a diagnosis, guiding initial therapy and then monitoring response. Clinical vignettes The history, presentation and management of three cases of peri-partum left ventricular failure is examined: stress cardiomyopathy in a 34 year old with twins, left ventricular dysfunction secondary to pre-eclampsia in a 22 year old with a singleton pregnancy and a true peri-partum cardiomyopathy in a 42 year old with IVF twins. The defining risk factors, presenting characteristics and echocardiographical findings for each pathology are highlighted. Conclusion Echocardiography is playing an increasingly important role in the immediate assessment and management of left ventricular failure. This is especially true in the peri-partum woman, where establishing the correct therapy is both challenging and crucial due to the significant cardiovascular changes that occur around the time of delivery. To this end we believe that echocardiography should be rapidly available to guide the management of these patients by a multidisciplinary team made up of obstetricians, cardiologists, anaesthetists and intensive care physicians.
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Affiliation(s)
- Ben Greatorex
- Department of Anaesthesia and
Intensive Care, Raigmore Hospital, NHS Highlands, Inverness, UK
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Mannemuddhu SS, Macumber I, Samuels JA, Flynn JT, South AM. When Hypertension Grows Up: Implications for Transitioning Care of Adolescents and Young Adults With Hypertension From Pediatric to Adult Health Care Providers. Adv Chronic Kidney Dis 2022; 29:263-274. [PMID: 36084973 DOI: 10.1053/j.ackd.2021.11.005] [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: 07/15/2021] [Revised: 11/01/2021] [Accepted: 11/15/2021] [Indexed: 11/11/2022]
Abstract
Hypertension (HTN) is an important cause of morbidity and mortality in children as well as adults. HTN and related adverse cardiovascular health develop and progress on a continuum across an individual's life course. Pediatric HTN, or even isolated elevated blood pressure as a child, increases the risk of sustained HTN and cardiovascular disease in later adulthood. Transitioning the care of adolescents and young adults who have HTN is an important but unmet health care need that could potentially have a dramatic effect on mitigating the risk of cardiovascular disease in adulthood. However, very little has been published about the transition process in this population, and considerable gaps in the field remain. We discuss the epidemiology, etiology, and management approach in youth with HTN and how they differ from adults. We contextualize HTN and cardiovascular health on a continuum across the life course. We discuss key considerations for the transition process for adolescents and young adults with HTN including the major barriers that exist. Finally, we review key immediate health care needs that are particularly important around the time of the transfer of care.
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Affiliation(s)
- Sai Sudha Mannemuddhu
- East Tennessee Children's Hospital, Knoxville, TN; Department of Medicine, University of Tennessee Health Science Center-College of Medicine, Knoxville, TN
| | - Ian Macumber
- Department of Pediatrics, Keck School of Medicine, Division of Nephrology, Children's Hospital Los Angeles, Los Angeles, CA
| | - Joshua A Samuels
- Department of Pediatrics, Pediatric Nephrology & Hypertension, McGovern Medical School at the University of Texas Health Science Center, Houston, TX
| | - Joseph T Flynn
- Department of Pediatrics, University of Washington, Division of Nephrology, Seattle Children's Hospital, Seattle, WA.
| | - Andrew M South
- Department of Pediatrics, Section of Nephrology, Wake Forest School of Medicine and Brenner Children's Hospital, Winston Salem, NC; Division of Public Health Sciences, Department of Epidemiology and Prevention, Wake Forest School of Medicine, Winston Salem, NC; Cardiovascular Sciences Center, Wake Forest School of Medicine, Winston Salem, NC
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Cantarutti A, Porcu G, Locatelli A, Corrao G. Association between hypertensive medication during pregnancy and risk of several maternal and neonatal outcomes in women with chronic hypertension: a population-based study. Expert Rev Clin Pharmacol 2022; 15:637-645. [PMID: 35485218 DOI: 10.1080/17512433.2022.2072292] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
BACKGROUND Several studies have reported an association between perinatal complications and the severity of the hypertensive disease. The increasing number of pregnancies complicated by hypertension and the small assurance about the perinatal effects of hypertensive drug use during pregnancy involves the need of studying the better management of hypertensive mothers. OBJECTIVE To evaluate the association between maternal use of antihypertensive drugs and maternal and neonatal outcomes in women with chronic hypertension. STUDY DESIGN We conducted a population-based study including all deliveries of hypertensive women that occurred between 2007-2017 in the Lombardy region, Italy. We evaluated the risk of several maternal and neonatal outcomes among women who filled antihypertensive prescriptions within the 20th week of gestation. Propensity score stratification was used to account for key potential confounders. RESULTS Out of 5,553 pregnancies, 2,138 were exposed to antihypertensive treatment. With respect to no-users, users of antihypertensive drugs showed an increased risk of preeclampsia (RR:1.68, 95%CI:1.42-1.99), low birth weight (1.30,1.14-1.48), and preterm birth (1.25,1.11-1.42). These results were consistent in a range of sensitivity and subgroup analyses. CONCLUSION Early exposure to antihypertensive drugs in the first 20 weeks of gestation was associated with an increased risk of preeclampsia, low birth weight, and preterm birth.
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Affiliation(s)
- Anna Cantarutti
- National Centre for Healthcare Research and Pharmacoepidemiology, Department of Statistics and Quantitative Methods, University of Milano-Bicocca, 20126 Milan, Italy.,Department of Statistics and Quantitative Methods, Division of Biostatistics, Epidemiology and Public Health, Laboratory of Healthcare Research and Pharmacoepidemiology, University of Milano-Bicocca, Milan, Italy
| | - Gloria Porcu
- National Centre for Healthcare Research and Pharmacoepidemiology, Department of Statistics and Quantitative Methods, University of Milano-Bicocca, 20126 Milan, Italy.,Department of Statistics and Quantitative Methods, Division of Biostatistics, Epidemiology and Public Health, Laboratory of Healthcare Research and Pharmacoepidemiology, University of Milano-Bicocca, Milan, Italy
| | - Anna Locatelli
- Department of Medicine and Surgery, University of Milano-Bicocca, Milano, Italy.,Department of Obstetrics and Gynecology, Ospedale San Gerardo, Monza, Italy
| | - Giovanni Corrao
- National Centre for Healthcare Research and Pharmacoepidemiology, Department of Statistics and Quantitative Methods, University of Milano-Bicocca, 20126 Milan, Italy.,Department of Statistics and Quantitative Methods, Division of Biostatistics, Epidemiology and Public Health, Laboratory of Healthcare Research and Pharmacoepidemiology, University of Milano-Bicocca, Milan, Italy
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Godoy DA, Robba C, Paiva WS, Rabinstein AA. Acute Intracranial Hypertension During Pregnancy: Special Considerations and Management Adjustments. Neurocrit Care 2022; 36:302-316. [PMID: 34494211 PMCID: PMC8423073 DOI: 10.1007/s12028-021-01333-x] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2021] [Accepted: 08/12/2021] [Indexed: 12/19/2022]
Abstract
Pregnancy is associated with a number of pathophysiological changes (including modification of vascular resistance, increased vascular permeability, and coagulative disorders) that can lead to specific (eclampsia, preeclampsia) or not specific (intracranial hemorrhage) neurological complications. In addition to these disorders, pregnancy can affect numerous preexisting neurologic conditions, including epilepsy, brain tumors, and intracerebral bleeding from cerebral aneurysm or arteriovenous malformations. Intracranial complications related to pregnancy can expose patients to a high risk of intracranial hypertension (IHT). Unfortunately, at present, the therapeutic measures that are generally adopted for the control of elevated intracranial pressure (ICP) in the general population have not been examined in pregnant patients, and their efficacy and safety for the mother and the fetus is still unknown. In addition, no specific guidelines for the application of the staircase approach, including escalating treatments with increasing intensity of level, for the management of IHT exist for this population. Although some of basic measures can be considered safe even in pregnant patients (management of stable hemodynamic and respiratory function, optimization of systemic physiology), some other interventions, such as hyperventilation, osmotic therapy, hypothermia, barbiturates, and decompressive craniectomy, can lead to specific concerns for the safety of both mother and fetus. The aim of this review is to summarize the neurological pathophysiological changes occurring during pregnancy and explore the effects of the possible therapeutic interventions applied to the general population for the management of IHT during pregnancy, taking into consideration ethical and clinical concerns as well as the decision for the timing of treatment and delivery.
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Affiliation(s)
- Daniel Agustin Godoy
- Neurointensive Care Unit, Sanatorio Pasteur, Catamarca, Argentina.
- Intensive Care, Hospital Carlos Malbran, Catamarca, Argentina.
| | - Chiara Robba
- Anesthesia and Intensive Care, San Martino Policlinico Hospital, Investigational Research for Critical Care for Oncology and Neurosciences, Genoa, Italy
| | - Wellingson Silva Paiva
- Division of Neurological Surgery, University of Sao Paulo Medical School, Sao Paulo, Brazil
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24
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Lumsden RH, Pagidipati N. Management of cardiovascular risk factors during pregnancy. Heart 2022; 108:1438-1444. [DOI: 10.1136/heartjnl-2021-319606] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/24/2021] [Accepted: 12/02/2021] [Indexed: 11/04/2022] Open
Abstract
Cardiovascular (CV) risk factors are rising among women of reproductive age. Obesity, hyperlipidaemia, diabetes, and hypertension are associated with adverse pregnancy outcomes and increased CV disease (CVD) risk following pregnancy. Pre-conception counselling and longitudinal postpartum follow-up with ongoing CV risk factor screening are critical for early CVD prevention, though significant racial/ethnic disparities in access to care result in significant gaps. This review summarises the recommended management of CV risk factors during and after pregnancy. For obesity, prevention of excessive weight gain is critical. Except in rare cases, lipid-lowering therapies for women with hyperlipidaemia should be stopped before pregnancy. Women with diabetes in pregnancy should maintain tight glucose control, with hemolgobin A1c (HbA1c) <6.5% to prevent congenital abnormalities. Hypertensive disorders of pregnancy are associated with high maternal and neonatal morbidity and require long-term follow-up to prevent future CVD. Finally, this review highlights the lack of clinical trials informing optimal treatment strategies of CV risk factors during and after pregnancy. Further research is needed to better understand how to improve long-term CV health among this high-risk population.
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Hussein H, Shamsipour M, Yunesian M, Hassanvand MS, Assan A, Fotouhi A. Prevalence and Predictors of Pre-Existing Hypertension among Prenatal Women: A Cross-Sectional Study in Ghana. IRANIAN JOURNAL OF PUBLIC HEALTH 2021; 50:1266-1274. [PMID: 34540748 PMCID: PMC8410977 DOI: 10.18502/ijph.v50i6.6428] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 05/15/2020] [Accepted: 08/22/2020] [Indexed: 11/24/2022]
Abstract
Background We aimed to assess prevalence and predictors of pre-existing hypertension in pregnant women in three districts of Northern region, Ghana. Methods This cross-sectional study was conducted among 1626 women in the third trimester of pregnancy across four antenatal centers in 2018. A questionnaire was used to collect medical information including weight and height. We used descriptive statistics to characterize all qualitative variables and performed logistic regression analyses to estimate association of hypertension and other risk factors. Results We included 1626 women; mean age standard deviation (SD) of pregnant women was 27.4 (5.1) years. About 4.5% (95% confidence interval [CI]: 3.6-5.7) of pregnant women reported they had earlier been diagnosed of having hypertension by a doctor or midwife, before pregnancy. Obese pregnant women had 2.9 times increased adjusted odds of having hypertension relative to non-obese pregnant women (Odds Ratio (OR))=2.9, 95% [CI]: 1.39-5.85, P=0.004). Further, gestational diabetes was a predictor of pre-existing hypertension at an increased odds of 4.9 times relative to those without gestational diabetes (OR= 4.9, CI: 0.92-26.75, P=0.061). Women with two or more children had 3.2 times the adjusted odds of having hypertension (OR=3.2 CI: 1.59-6.69, P=0.001). Conclusion Although the prevalence pre-existing hypertension was not too high, obesity, gestational diabetes and number of children were independent predictors of pre-existing hypertension in pregnant women.
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Affiliation(s)
- Hawawu Hussein
- Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.,Ho Teaching Hospital, Research, Policy Coordination, Planning & Budgeting, Monitoring & Evaluation Directorate, HO, Ghana
| | - Mansour Shamsipour
- Department of Research Methodology and Data Analysis, Institute for Environmental Research, Tehran University of Medical Sciences, Tehran, Iran.,Center for Air Pollution Research (CAPR), Institute for Environmental Research (IER), Tehran University of Medical Sciences, Tehran, Iran
| | - Masud Yunesian
- Department of Research Methodology and Data Analysis, Institute for Environmental Research, Tehran University of Medical Sciences, Tehran, Iran.,Department of Environmental Health Engineering, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohammad Sadegh Hassanvand
- Center for Air Pollution Research (CAPR), Institute for Environmental Research (IER), Tehran University of Medical Sciences, Tehran, Iran.,Department of Environmental Health Engineering, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Abraham Assan
- Global Policy and Advocacy Network (GLOOPLAN), Accra, Ghana
| | - Akbar Fotouhi
- Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
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26
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Cerritelli F, Frasch MG, Antonelli MC, Viglione C, Vecchi S, Chiera M, Manzotti A. A Review on the Vagus Nerve and Autonomic Nervous System During Fetal Development: Searching for Critical Windows. Front Neurosci 2021; 15:721605. [PMID: 34616274 PMCID: PMC8488382 DOI: 10.3389/fnins.2021.721605] [Citation(s) in RCA: 50] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2021] [Accepted: 08/19/2021] [Indexed: 12/17/2022] Open
Abstract
The autonomic nervous system (ANS) is one of the main biological systems that regulates the body's physiology. Autonomic nervous system regulatory capacity begins before birth as the sympathetic and parasympathetic activity contributes significantly to the fetus' development. In particular, several studies have shown how vagus nerve is involved in many vital processes during fetal, perinatal, and postnatal life: from the regulation of inflammation through the anti-inflammatory cholinergic pathway, which may affect the functioning of each organ, to the production of hormones involved in bioenergetic metabolism. In addition, the vagus nerve has been recognized as the primary afferent pathway capable of transmitting information to the brain from every organ of the body. Therefore, this hypothesis paper aims to review the development of ANS during fetal and perinatal life, focusing particularly on the vagus nerve, to identify possible "critical windows" that could impact its maturation. These "critical windows" could help clinicians know when to monitor fetuses to effectively assess the developmental status of both ANS and specifically the vagus nerve. In addition, this paper will focus on which factors-i.e., fetal characteristics and behaviors, maternal lifestyle and pathologies, placental health and dysfunction, labor, incubator conditions, and drug exposure-may have an impact on the development of the vagus during the above-mentioned "critical window" and how. This analysis could help clinicians and stakeholders define precise guidelines for improving the management of fetuses and newborns, particularly to reduce the potential adverse environmental impacts on ANS development that may lead to persistent long-term consequences. Since the development of ANS and the vagus influence have been shown to be reflected in cardiac variability, this paper will rely in particular on studies using fetal heart rate variability (fHRV) to monitor the continued growth and health of both animal and human fetuses. In fact, fHRV is a non-invasive marker whose changes have been associated with ANS development, vagal modulation, systemic and neurological inflammatory reactions, and even fetal distress during labor.
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Affiliation(s)
- Francesco Cerritelli
- Research and Assistance for Infants to Support Experience Lab, Foundation Center for Osteopathic Medicine Collaboration, Pescara, Italy
| | - Martin G. Frasch
- Department of Obstetrics and Gynecology and Center on Human Development and Disability, University of Washington, Seattle, WA, United States
| | - Marta C. Antonelli
- Facultad de Medicina, Instituto de Biología Celular y Neurociencia “Prof. E. De Robertis”, Universidad de Buenos Aires, Buenos Aires, Argentina
- Department of Obstetrics and Gynecology, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany
| | - Chiara Viglione
- Research and Assistance for Infants to Support Experience Lab, Foundation Center for Osteopathic Medicine Collaboration, Pescara, Italy
| | - Stefano Vecchi
- Research and Assistance for Infants to Support Experience Lab, Foundation Center for Osteopathic Medicine Collaboration, Pescara, Italy
| | - Marco Chiera
- Research and Assistance for Infants to Support Experience Lab, Foundation Center for Osteopathic Medicine Collaboration, Pescara, Italy
| | - Andrea Manzotti
- Research and Assistance for Infants to Support Experience Lab, Foundation Center for Osteopathic Medicine Collaboration, Pescara, Italy
- Department of Pediatrics, Division of Neonatology, “V. Buzzi” Children's Hospital, Azienda Socio-Sanitaria Territoriale Fatebenefratelli Sacco, Milan, Italy
- Research Department, Istituto Osteopatia Milano, Milan, Italy
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Khosla J, Golamari R, Cai A, Benson J, Aronow WS, Jain R, Jain R. Evidence-based management of arrhythmogenic right ventricular cardiomyopathy in pregnancy. Future Cardiol 2021; 17:693-703. [PMID: 33089714 DOI: 10.2217/fca-2020-0127] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2020] [Accepted: 09/16/2020] [Indexed: 11/21/2022] Open
Abstract
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetic disorder resulting in fibrofatty replacement of the myocardium. Genetic mutations in genes encoding for desmosome proteins result in a ventricular myocardium prone to arrhythmias and heart failure. Although ARVC is known for a few decades, most of the outcomes in pregnancy are reported recently. Pregnancy leads to significant physiological changes with excess mechanical stress on the myocardium. All the retrospective studies suggest that pregnancy is well tolerated in these patients despite the high risk of arrhythmias and heart failure. Our review focuses on the most up-to-date evidence on the management of ARVC patients during the antepartum and postpartum period.
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Affiliation(s)
- Jagjit Khosla
- Department of Internal Medicine, Westchester Medical Center, Valhalla, New York, NY 10595, USA
| | - Reshma Golamari
- Penn State Health Milton S Hershey Medical Center, Hershey, PA 17033, USA
| | - Alice Cai
- Penn State University College of Medicine, PA 17033, USA
| | - Jamal Benson
- Penn State University College of Medicine, PA 17033, USA
| | - Wilbert S Aronow
- Department of Cardiology, Westchester Medical Center, Valhalla, NY 10595, USA
| | - Rahul Jain
- Department of Cardiology, Indiana University, IN 46202, USA
| | - Rohit Jain
- Penn State Health Milton S Hershey Medical Center, Hershey, PA 17033, USA
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28
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Pereira DA, Sandrim VC, Palei AC, Amaral LM, Belo VA, Lacchini R, Cavalli RC, Tanus-Santos JE, Luizon MR. NAMPT single-nucleotide polymorphism rs1319501 and visfatin/NAMPT affect nitric oxide formation, sFlt-1 and antihypertensive therapy response in preeclampsia. Pharmacogenomics 2021; 22:451-464. [PMID: 33944612 DOI: 10.2217/pgs-2021-0006] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Aim: We examined the relationships between visfatin/NAMPT and nitrite concentrations (a marker of nitric oxide [NO] formation) or sFlt-1 levels in 205 patients with preeclampsia (PE) responsive or nonresponsive to antihypertensive therapy, and whether NAMPT SNPs rs1319501 and rs3801266 affect nitrite concentrations in PE and 206 healthy pregnant women. Patients & methods: Circulating visfatin/NAMPT and sFlt-1 levels were measured by ELISA, and nitrite concentrations by using an ozone-based chemiluminescence assay. Results: In nonresponsive PE patients, visfatin/NAMPT levels were inversely related to nitrite concentrations and positively related to sFlt-1 levels. NAMPT SNP rs1319501 affected nitrite concentrations in nonresponsive PE patients and was tightly linked with NAMPT functional SNPs in Europeans. Conclusion: NAMPT SNP rs1319501 and visfatin/NAMPT affect NO formation, sFlt-1 levels and antihypertensive therapy response in PE.
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Affiliation(s)
- Daniela A Pereira
- Graduate Program in Genetics, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
| | - Valeria C Sandrim
- Department of Biophysics & Pharmacology, Institute of Biosciences, Universidade Estadual Paulista (UNESP), Botucatu, São Paulo, Brazil
| | - Ana C Palei
- Department of Surgery, University of Mississippi Medical Center, Jackson, MS 392164, USA
| | - Lorena M Amaral
- Department of Pharmacology & Toxicology, University of Mississippi Medical Center, Jackson, MS 392164, USA
| | - Vanessa A Belo
- Graduate Program in Genetics, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
| | - Riccardo Lacchini
- Department of Psychiatric Nursing & Human Sciences, Ribeirao Preto College of Nursing, University of Sao Paulo, Ribeirao Preto, São Paulo, Brazil
| | - Ricardo C Cavalli
- Department of Gynecology & Obstetrics, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, São Paulo, Brazil
| | - Jose E Tanus-Santos
- Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, São Paulo, Brazil
| | - Marcelo R Luizon
- Graduate Program in Genetics, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.,Department of Genetics, Ecology & Evolution, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
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29
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Larkin BP, Saad S, Glastras SJ, Nguyen LT, Hou M, Chen H, Wang R, Pollock CA. Low-dose hydralazine during gestation reduces renal fibrosis in rodent offspring exposed to maternal high fat diet. PLoS One 2021; 16:e0248854. [PMID: 33735324 PMCID: PMC7971884 DOI: 10.1371/journal.pone.0248854] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2020] [Accepted: 03/08/2021] [Indexed: 11/18/2022] Open
Abstract
BACKGROUND Maternal high fat diet (HFD) promotes chronic kidney disease (CKD) in offspring. This is in accordance with the theory of fetal programming, which suggests adverse conditions occurring in utero predispose offspring to chronic conditions later in life. DNA methylation has been proposed as a key mechanism by which fetal programming occurs and is implicated in CKD progression. DNA demethylating drugs may interrupt the fetal programming of CKD by maternal obesity. Hydralazine, an antihypertensive agent, demethylates DNA at low doses which do not reduce blood pressure. We used a mouse model of maternal obesity to determine whether gestational administration of low-dose hydralazine to mothers can prevent CKD in offspring. METHODS C57BL/6 dams received HFD or chow from 6 weeks prior to mating and were administered subcutaneous hydralazine (5mg/kg) or saline thrice weekly during gestation. Male offspring were weaned to chow and were sacrificed at either postnatal week 9 or week 32. Biometric and metabolic parameters, renal global DNA methylation, renal structural and functional changes and markers of fibrosis, oxidative stress and inflammation were measured in offspring at weeks 9 and 32. RESULTS In week 9 offspring, maternal HFD consumption did not significantly alter anthropometric or metabolic parameters, or renal global DNA methylation. Week 32 offspring had increased renal global DNA methylation, together with albuminuria, glomerulosclerosis, renal fibrosis and oxidative stress. Administration of low-dose hydralazine to obese mothers during gestation reduced renal global DNA methylation and renal fibrotic markers in week 32 offspring. CONCLUSION Gestational hydralazine reduced renal global DNA methylation in offspring of obese mothers and attenuated maternal obesity-induced renal fibrosis. These data support the use of low-dose hydralazine as a demethylating agent to prevent CKD arising in offspring due to maternal HFD consumption.
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Affiliation(s)
- Benjamin P. Larkin
- Renal Research Laboratory, Kolling Institute of Medical Research, University of Sydney, Sydney, Australia
| | - Sonia Saad
- Renal Research Laboratory, Kolling Institute of Medical Research, University of Sydney, Sydney, Australia
- School of Life Sciences, Faculty of Science, University of Technology Sydney, Sydney, Australia
| | - Sarah J. Glastras
- Renal Research Laboratory, Kolling Institute of Medical Research, University of Sydney, Sydney, Australia
- Department of Diabetes, Endocrinology and Metabolism, Royal North Shore Hospital, Sydney, Australia
| | - Long T. Nguyen
- Renal Research Laboratory, Kolling Institute of Medical Research, University of Sydney, Sydney, Australia
| | - Miao Hou
- Department of Cardiology, Children’s Hospital of Soochow University, Suzhou, Jiangsu, China
| | - Hui Chen
- School of Life Sciences, Faculty of Science, University of Technology Sydney, Sydney, Australia
| | - Rosy Wang
- Renal Research Laboratory, Kolling Institute of Medical Research, University of Sydney, Sydney, Australia
| | - Carol A. Pollock
- Renal Research Laboratory, Kolling Institute of Medical Research, University of Sydney, Sydney, Australia
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Bertozzi-Matheus M, Bueno-Pereira TO, Viana-Mattioli S, Carlström M, Cavalli RDC, Sandrim VC. Different profiles of circulating arginase 2 in subtypes of preeclampsia pregnant women. Clin Biochem 2021; 92:25-33. [PMID: 33713637 DOI: 10.1016/j.clinbiochem.2021.03.002] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2020] [Revised: 03/01/2021] [Accepted: 03/02/2021] [Indexed: 01/12/2023]
Abstract
BACKGROUND AND AIMS Preeclampsia (PE) is a gestational hypertensive disease responsible for high maternal and fetal morbidity and mortality. The increase in blood pressure is associated with a decrease in the bioavailability of nitric oxide (NO). Arginase interferes with NO production consuming L-arginine, a substrate required by endothelial NO synthase to NO formation. No previous study has quantified the circulating levels of the two arginase isoforms (arginase 1 and arginase 2) in the plasma of pregnant women with PE. Therefore, our objective is to evaluate these plasma levels in healthy pregnant women and PE with or without severe features and who respond or not to antihypertensive therapy. METHODS We compared 29 healthy pregnant women with 56 pregnant women with PE, who were also divided into with severe features (n = 24) or without severe features (n = 32) and into responsive (n = 29) or nonresponsive to antihypertensive therapy (n = 27). We quantified the plasmatic expression of arginase 1 and arginase 2 by ELISA kits. RESULTS While similar levels of arginase 1 were found among groups, lower arginase 2 plasma levels were found in PE without severe features and responsive to antihypertensive drugs when compared to healthy pregnant women. There was no difference between arginase 2 levels in PE with severe features and nonresponsive group when compared to healthy pregnant women. CONCLUSION This shows different circulation profiles of arginase 2 among groups, suggesting the existence of mechanisms of arginase 2 modulation in pregnant women with PE associated with the severity of the disease and responsiveness to antihypertensive treatment.
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Affiliation(s)
- Mariana Bertozzi-Matheus
- Department of Biophysics and Pharmacology, Institute of Biosciences of Botucatu, Universidade Estadual Paulista, Distrito Rubiao Junior, Botucatu, São Paulo 18680-000, Brazil
| | - Thaina Omia Bueno-Pereira
- Department of Biophysics and Pharmacology, Institute of Biosciences of Botucatu, Universidade Estadual Paulista, Distrito Rubiao Junior, Botucatu, São Paulo 18680-000, Brazil
| | - Sarah Viana-Mattioli
- Department of Biophysics and Pharmacology, Institute of Biosciences of Botucatu, Universidade Estadual Paulista, Distrito Rubiao Junior, Botucatu, São Paulo 18680-000, Brazil
| | - Mattias Carlström
- Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm 17177, Sweden
| | - Ricardo de Carvalho Cavalli
- Department of Gynecology and Obstetrics, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, Sao Paulo 14049-900, Brazil
| | - Valeria Cristina Sandrim
- Department of Biophysics and Pharmacology, Institute of Biosciences of Botucatu, Universidade Estadual Paulista, Distrito Rubiao Junior, Botucatu, São Paulo 18680-000, Brazil.
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31
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Gumusoglu SB, Chilukuri ASS, Hing BWQ, Scroggins SM, Kundu S, Sandgren JA, Santillan MK, Santillan DA, Grobe JL, Stevens HE. Altered offspring neurodevelopment in an arginine vasopressin preeclampsia model. Transl Psychiatry 2021; 11:79. [PMID: 33510137 PMCID: PMC7844013 DOI: 10.1038/s41398-021-01205-0] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2020] [Revised: 12/17/2020] [Accepted: 01/08/2021] [Indexed: 12/18/2022] Open
Abstract
Preeclampsia is a severe gestational hypertensive condition linked to child neuropsychiatric disorders, although underlying mechanisms are unclear. We used a recently developed, clinically relevant animal model of preeclampsia to assess offspring. C57BL/6J mouse dams were chronically infused with arginine vasopressin (AVP) or saline (24 ng/h) throughout pregnancy. Adult offspring were behaviorally tested (Y-maze, open field, rotarod, social approach, and elevated plus maze). Offspring brain was assessed histologically and by RNA sequencing. Preeclampsia-exposed adult males exhibited increased anxiety-like behavior and social approach while adult females exhibited impaired procedural learning. Adult AVP-exposed males had reduced total neocortical volume. Adult AVP-exposed females had increased caudate-putamen volume, increased caudate-putamen cell number, and decreased excitatory synapse density in hippocampal dentate gyrus (DG), CA1, and CA3. At postnatal day 7 (P7), AVP-exposed male and female offspring both had smaller neocortex. At P7, AVP-exposed males also had smaller caudate-putamen volume, while females had increased caudate-putamen volume relative to neocortical size. Similar to P7, E18 AVP-exposed offspring had smaller dorsal forebrain, mainly in reduced intermediate, subventricular, and ventricular zone volume, particularly in males. Decreased volume was not accounted for by cell size or cerebrovascular vessel diameter changes. E18 cortical RNAseq revealed 49 differentially-expressed genes in male AVP-exposed offspring, over-representing cytoplasmic translation processes. In females, 31 genes were differentially-expressed, over-representing collagen-related and epithelial regulation pathways. Gene expression changes in E18 AVP-exposed placenta indicated potential underlying mechanisms. Deficits in behavior and forebrain development in this AVP-based preeclampsia model were distinctly different in males and females, implicating different neurobiological bases.
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Affiliation(s)
- Serena Banu Gumusoglu
- Interdisciplinary Neuroscience Graduate Program, University of Iowa, Iowa City, IA, USA.
- Department of Psychiatry, Carver College of Medicine, University of Iowa, Iowa City, IA, USA.
- Iowa Neuroscience Institute, University of Iowa, Iowa City, IA, USA.
| | - Akanksha Sri Satya Chilukuri
- Department of Psychiatry, Carver College of Medicine, University of Iowa, Iowa City, IA, USA
- Iowa Neuroscience Institute, University of Iowa, Iowa City, IA, USA
| | - Benjamin Wen Qing Hing
- Department of Psychiatry, Carver College of Medicine, University of Iowa, Iowa City, IA, USA
- Iowa Neuroscience Institute, University of Iowa, Iowa City, IA, USA
- Molecular Physiology and Biophysics, Carver College of Medicine, University of Iowa, Iowa City, IA, USA
| | - Sabrina Marie Scroggins
- Department of Obstetrics and Gynecology, Carver College of Medicine, University of Iowa, Iowa City, IA, USA
| | - Sreelekha Kundu
- Department of Psychiatry, Carver College of Medicine, University of Iowa, Iowa City, IA, USA
- Iowa Neuroscience Institute, University of Iowa, Iowa City, IA, USA
| | - Jeremy Anton Sandgren
- Department of Pharmacology, Carver College of Medicine, University of Iowa, Iowa City, IA, USA
| | - Mark Kharim Santillan
- Department of Obstetrics and Gynecology, Carver College of Medicine, University of Iowa, Iowa City, IA, USA
| | - Donna Ann Santillan
- Department of Obstetrics and Gynecology, Carver College of Medicine, University of Iowa, Iowa City, IA, USA
| | - Justin Lewis Grobe
- Department of Physiology, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Hanna Elizabeth Stevens
- Interdisciplinary Neuroscience Graduate Program, University of Iowa, Iowa City, IA, USA
- Department of Psychiatry, Carver College of Medicine, University of Iowa, Iowa City, IA, USA
- Iowa Neuroscience Institute, University of Iowa, Iowa City, IA, USA
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Cotta Filho CK, Oliveira-Paula GH, Rondon Pereira VC, Lacchini R. Clinically relevant endothelial nitric oxide synthase polymorphisms and their impact on drug response. Expert Opin Drug Metab Toxicol 2020; 16:927-951. [DOI: 10.1080/17425255.2020.1804857] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Affiliation(s)
| | | | | | - Riccardo Lacchini
- Department of Psychiatric Nursing and Human Sciences, University of Sao Paulo, Ribeirao Preto, Brazil
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Chera-Aree P, Tengtrakulcharoen P, Leetheeragul J, Sampaojarean U, Surasereewong S, Wataganara T. Clinical Experiences of Intravenous Hydralazine and Labetalol for Acute Treatment of Severe Hypertension in Pregnant Thai Women. J Clin Pharmacol 2020; 60:1662-1670. [PMID: 32598488 DOI: 10.1002/jcph.1685] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2020] [Accepted: 06/04/2020] [Indexed: 12/28/2022]
Abstract
Response to acute treatment of severe hypertension during pregnancy in Asian women was not known. Labor and delivery checklists of Thai women treated with intravenous hydralazine or labetalol for systolic blood pressure (SBP) ≥ 160 or diastolic blood pressure (DBP) ≥ 110 mm Hg from January 2011 to December 2013 were reviewed as parts of an audit. Primary outcome was prompt achievement of SBP 140-150 and DBP 90-100 mm Hg after the first bolus. Secondary outcomes were medication-related undesired effects. The mean ± standard deviation age and prevalence of chronic hypertension in hydralazine (n = 62) versus labetalol (n = 64) groups were 32.5 ± 6 versus 29.9 ± 6.8 years and 50% versus 21.9%, respectively (P < .05). Magnesium sulfate was promptly administered on admission to every woman to prevent seizure. Targeted blood pressure was timely achieved in 41.9% and 67.2% of the hydralazine and labetalol groups, respectively (P < .05). Nonreassuring fetal heart rate occurred in 51.6% and 32.8% of the hydralazine and labetalol groups, respectively (P = .05). The prevalence of cesarean section and Apgar score < 7 were not significantly different (P > .05). Real-life clinical experiences suggested significant advantages of intravenous labetalol over hydralazine in pregnant women with severe hypertension.
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Affiliation(s)
- Pattraporn Chera-Aree
- Department of Obstetrics and Gynecology, Faculty of Medicine Siriraj Hospital, Bangkok, Thailand
| | | | - Jarunee Leetheeragul
- Department of Obstetrics and Gynecology, Faculty of Medicine Siriraj Hospital, Bangkok, Thailand
| | - Urai Sampaojarean
- Department of Obstetrics and Gynecology, Faculty of Medicine Siriraj Hospital, Bangkok, Thailand
| | - Supitchaya Surasereewong
- Department of Obstetrics and Gynecology, Faculty of Medicine Siriraj Hospital, Bangkok, Thailand
| | - Tuangsit Wataganara
- Department of Obstetrics and Gynecology, Faculty of Medicine Siriraj Hospital, Bangkok, Thailand
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Avila WS, Alexandre ERG, Castro MLD, Lucena AJGD, Marques-Santos C, Freire CMV, Rossi EG, Campanharo FF, Rivera IR, Costa MENC, Rivera MAM, Carvalho RCMD, Abzaid A, Moron AF, Ramos AIDO, Albuquerque CJDM, Feio CMA, Born D, Silva FBD, Nani FS, Tarasoutchi F, Costa Junior JDR, Melo Filho JXD, Katz L, Almeida MCC, Grinberg M, Amorim MMRD, Melo NRD, Medeiros OOD, Pomerantzeff PMA, Braga SLN, Cristino SC, Martinez TLDR, Leal TDCAT. Brazilian Cardiology Society Statement for Management of Pregnancy and Family Planning in Women with Heart Disease - 2020. Arq Bras Cardiol 2020; 114:849-942. [PMID: 32491078 PMCID: PMC8386991 DOI: 10.36660/abc.20200406] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Affiliation(s)
- Walkiria Samuel Avila
- Instituto do Coração (Incor) do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP),São Paulo, SP - Brasil
| | | | - Marildes Luiza de Castro
- Hospital das Clínicas da Faculdade de Medicina da Universidade Federal de Minas gerais (UFMG),Belo Horizonte, MG - Brasil
| | | | - Celi Marques-Santos
- Universidade Tiradentes,Aracaju, SE - Brasil
- Hospital São Lucas, Rede D'Or Aracaju,Aracaju, SE - Brasil
| | | | - Eduardo Giusti Rossi
- Instituto do Coração (Incor) do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP),São Paulo, SP - Brasil
| | - Felipe Favorette Campanharo
- Universidade Federal de São Paulo (UNIFESP), Escola Paulista de Medicina (EPM),São Paulo, SP - Brasil
- Hospital Israelita Albert Einstein,São Paulo, SP - Brasil
| | | | - Maria Elizabeth Navegantes Caetano Costa
- Cardio Diagnóstico,Belém, PA - Brasil
- Centro Universitário Metropolitano da Amazônia (UNIFAMAZ),Belém, PA - Brasil
- Centro Universitário do Estado Pará (CESUPA),Belém, PA - Brasil
| | | | | | - Alexandre Abzaid
- Instituto do Coração (Incor) do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP),São Paulo, SP - Brasil
| | - Antonio Fernandes Moron
- Universidade Federal de São Paulo (UNIFESP), Escola Paulista de Medicina (EPM),São Paulo, SP - Brasil
| | | | - Carlos Japhet da Mata Albuquerque
- Instituto de Medicina Integral Professor Fernando Figueira (IMIP), Recife, PE – Brazil
- Hospital Barão de Lucena, Recife, PE – Brazil
- Hospital EMCOR, Recife, PE – Brazil
- Diagnósticos do Coração LTDA, Recife, PE – Brazil
| | | | - Daniel Born
- Universidade Federal de São Paulo (UNIFESP), Escola Paulista de Medicina (EPM),São Paulo, SP - Brasil
| | | | - Fernando Souza Nani
- Instituto do Coração (Incor) do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP),São Paulo, SP - Brasil
| | - Flavio Tarasoutchi
- Instituto do Coração (Incor) do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP),São Paulo, SP - Brasil
| | - José de Ribamar Costa Junior
- Hospital do Coração (HCor),São Paulo, SP - Brasil
- Instituto Dante Pazzanese de Cardiologia,São Paulo, SP - Brasil
| | | | - Leila Katz
- Instituto de Medicina Integral Professor Fernando Figueira (IMIP), Recife, PE – Brazil
| | | | - Max Grinberg
- Instituto do Coração (Incor) do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP),São Paulo, SP - Brasil
| | | | - Nilson Roberto de Melo
- Departamento de Obstetrícia e Ginecologia da Faculdade de Medicina da Universidade de São Paulo (USP), São Paulo, SP – Brazil
| | | | - Pablo Maria Alberto Pomerantzeff
- Instituto do Coração (Incor) do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP),São Paulo, SP - Brasil
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Brussé IA, Kluivers ACM, Zambrano MD, Shetler K, Miller EC. Neuro-obstetrics: A multidisciplinary approach to care of women with neurologic disease. HANDBOOK OF CLINICAL NEUROLOGY 2020; 171:143-160. [PMID: 32736747 DOI: 10.1016/b978-0-444-64239-4.00007-2] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
The term "neuro-obstetrics" refers to a multidisciplinary approach to the care of pregnant women with neurologic comorbidities, both preconceptionally and throughout pregnancy. General preconception care should be offered to all women, including women with neurologic disease. Women with neurologic comorbidities should also be offered specialist preconception care by an obstetrician who consults with a neurologist, anesthesiologist, and if indicated clinical geneticist and/or other specialists. In women with neurologic comorbidities, neurologic sequelae may influence the course of the pregnancy and delivery. Also, pregnancy may influence the severity of the neurologic condition, depending on the type of disease. Physiologic adaptations during pregnancy and altered pharmacokinetics may cause altered blood serum levels of drugs, leading to decreased or increased drug effects. When administering drugs to a woman who wishes to conceive, it is important to consider possible teratogenic effects and possible secretion in breast milk. Tailoring medication regimens should be considered, preferably preconceptionally. In this chapter, we review general principles of neuro-obstetric care, as well as some specific considerations for neurologists, obstetricians, and anesthesiologists caring for pregnant women with common neurologic conditions.
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Affiliation(s)
- Ingrid A Brussé
- Department of Obstetrics and Gynecology, Division of Obstetrics and Fetal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands.
| | - Anna C M Kluivers
- Department of Obstetrics and Gynecology, Division of Obstetrics and Fetal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands
| | - Maria D Zambrano
- Department of Neurology, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, United States
| | - Kara Shetler
- Department of Neurology, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, United States
| | - Eliza C Miller
- Department of Neurology, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, United States; NewYork-Presbyterian Hospital, Columbia University Irving Medical Center, New York, NY, United States
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Mogos MF, Jones LM, Robinson NS, Whitehead AO, Piscotty R, Goba GK. Prevalence, Correlates, and Outcomes of Co-Occurring Depression and Hypertensive Disorders of Pregnancy. J Womens Health (Larchmt) 2019; 28:1460-1467. [DOI: 10.1089/jwh.2018.7144] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Affiliation(s)
- Mulubrhan F. Mogos
- Department of Women, Children and Family Health Science, College of Nursing, University of Illinois at Chicago, Chicago, Illinois
| | - Lenette M. Jones
- Department of Health Behavior and Biological Sciences, University of Michigan, Ann Arbor, Michigan
| | - Nadia S. Robinson
- Department of Biobehavioral Health Science, University of Illinois at Chicago, Chicago, Illinois
| | | | - Ronald Piscotty
- Department of Organizational Systems and Adult Health, University of Maryland Baltimore, Baltimore, Maryland
| | - Gelila K. Goba
- Department of Obstetrics and Gynecology, University of Illinois at Chicago, Chicago, Illinois
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Use of Prescribed Psychotropics during Pregnancy: A Systematic Review of Pregnancy, Neonatal, and Childhood Outcomes. Brain Sci 2019; 9:brainsci9090235. [PMID: 31540060 PMCID: PMC6770670 DOI: 10.3390/brainsci9090235] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2019] [Revised: 09/03/2019] [Accepted: 09/09/2019] [Indexed: 12/27/2022] Open
Abstract
This paper reviews the findings from preclinical animal and human clinical research investigating maternal/fetal, neonatal, and child neurodevelopmental outcomes following prenatal exposure to psychotropic drugs. Evidence for the risks associated with prenatal exposure was examined, including teratogenicity, neurodevelopmental effects, neonatal toxicity, and long-term neurobehavioral consequences (i.e., behavioral teratogenicity). We conducted a comprehensive review of the recent results and conclusions of original research and reviews, respectively, which have investigated the short- and long-term impact of drugs commonly prescribed to pregnant women for psychological disorders, including mood, anxiety, and sleep disorders. Because mental illness in the mother is not a benign event, and may itself pose significant risks to both mother and child, simply discontinuing or avoiding medication use during pregnancy may not be possible. Therefore, prenatal exposure to psychotropic drugs is a major public health concern. Decisions regarding drug choice, dose, and duration should be made carefully, by balancing severity, chronicity, and co-morbidity of the mental illness, disorder, or condition against the potential risk for adverse outcomes due to drug exposure. Globally, maternal mental health problems are considered as a major public health challenge, which requires a stronger focus on mental health services that will benefit both mother and child. More preclinical and clinical research is needed in order to make well-informed decisions, understanding the risks associated with the use of psychotropic medications during pregnancy.
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Raichand S, Pearson SA, Zoega H, Buckley NA, Havard A. Utilisation of teratogenic medicines before and during pregnancy in Australian women. Aust N Z J Obstet Gynaecol 2019; 60:218-224. [PMID: 31397495 DOI: 10.1111/ajo.13044] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2019] [Accepted: 07/06/2019] [Indexed: 01/28/2023]
Abstract
BACKGROUND Given the potential hazards of teratogenic medicines, to a fetus exposed in utero, monitoring their use around pregnancy is imperative. AIM To measure utilisation of teratogenic medicines (Therapeutic Goods Administration's category D or X) in women who gave birth in New South Wales, Australia, during pregnancy and the 24 months prior. MATERIALS AND METHODS We used linked population-based datasets including dispensing and perinatal data for all deliveries in NSW between 2005 and 2012. We included pregnancies among concessional beneficiaries only, with complete ascertainment of dispensing claims. Pre-pregnancy and during-pregnancy periods were based on birth dates and gestational age. We determined prevalence of exposure using percent of pregnancies in which women had at least one dispensed teratogenic medicine in three-month time periods. RESULTS The study included 191 588 pregnancies (145 419 women). Prevalence of exposure to D/X medicines anytime during pregnancy was 2.0% (<20 pregnancies category X), decreasing from pre-pregnancy (3.8-6.0%) to first trimester (1.5%), further decreasing in second and third trimesters (0.8% and 0.6% respectively). We observed large reductions in antibiotic prevalence but only modest reductions for psychotropics and antilipidemic agents (all category D). Our results suggest higher use of potentially teratogenic medicines (category D) than those strictly contraindicated for use (category X), during pregnancy. Overall, use was higher in the first trimester than the rest of pregnancy. The high prevalence of potentially contraindicated psychotropics in all three trimesters may suggest a higher benefit-to-risk ratio and warrants future research focusing on the reasons for their prescribing to pregnant women.
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Affiliation(s)
- Smriti Raichand
- Centre for Big Data Research in Health (CBDRH), University of New South Wales, Sydney, New South Wales, Australia
| | - Sallie-Anne Pearson
- Centre for Big Data Research in Health (CBDRH), University of New South Wales, Sydney, New South Wales, Australia
| | - Helga Zoega
- Centre for Big Data Research in Health (CBDRH), University of New South Wales, Sydney, New South Wales, Australia.,Centre of Public Health Sciences, Faculty of Medicine, University of Iceland, Reykjavik, Iceland
| | - Nicholas A Buckley
- Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia
| | - Alys Havard
- Centre for Big Data Research in Health (CBDRH), University of New South Wales, Sydney, New South Wales, Australia
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Prenatal Exercise and Pre-gestational Diseases: A Systematic Review and Meta-analysis. JOURNAL OF OBSTETRICS AND GYNAECOLOGY CANADA 2019; 41:1134-1143.e17. [DOI: 10.1016/j.jogc.2018.10.007] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2018] [Revised: 10/04/2018] [Indexed: 12/13/2022]
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Tamargo J, Caballero R, Delpón E. Pharmacotherapy for hypertension in pregnant patients: special considerations. Expert Opin Pharmacother 2019; 20:963-982. [PMID: 30943045 DOI: 10.1080/14656566.2019.1594773] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
Abstract
INTRODUCTION Hypertensive disorders of pregnancy (HDP) represent a major cause of maternal, fetal and neonatal morbidity and mortality and identifies women at risk for cardiovascular and other chronic diseases later in life. When antihypertensive drugs are used during pregnancy, their benefit and harm to both mother and fetus should be evaluated. AREAS COVERED This review summarizes the pharmacological characteristics of the recommended antihypertensive drugs and their impact on mother and fetus when administered during pregnancy and/or post-partum. Drugs were identified using MEDLINE and the main international Guidelines for the management of HDP. EXPERT OPINION Although there is a consensus that severe hypertension should be treated, treatment of mild hypertension without end-organ damage (140-159/90-109 mmHg) remains controversial and there is no agreement on when to initiate therapy, blood pressure targets or recommended drugs in the absence of robust evidence for the superiority of one drug over others. Furthermore, the long-term outcomes of in-utero antihypertensive exposure remain uncertain. Therefore, evidence-based data regarding the treatment of HDP is lacking and well designed randomized clinical trials are needed to resolve all these controversial issues related to the management of HDP.
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Affiliation(s)
- Juan Tamargo
- a Department of Pharmacology and Toxicology, School of Medicine , Instituto de Investigación Sanitaria Gregorio Marañón, Universidad Complutense, CIBERCV , Madrid , Spain
| | - Ricardo Caballero
- a Department of Pharmacology and Toxicology, School of Medicine , Instituto de Investigación Sanitaria Gregorio Marañón, Universidad Complutense, CIBERCV , Madrid , Spain
| | - Eva Delpón
- a Department of Pharmacology and Toxicology, School of Medicine , Instituto de Investigación Sanitaria Gregorio Marañón, Universidad Complutense, CIBERCV , Madrid , Spain
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Michita RT, Kaminski VDL, Chies JAB. Genetic Variants in Preeclampsia: Lessons From Studies in Latin-American Populations. Front Physiol 2018; 9:1771. [PMID: 30618791 PMCID: PMC6302048 DOI: 10.3389/fphys.2018.01771] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2018] [Accepted: 11/23/2018] [Indexed: 12/13/2022] Open
Abstract
Placental vascularization is a tightly regulated physiological process in which the maternal immune system plays a fundamental role. Vascularization of the maternal-placental interface involves a wide range of mechanisms primarily orchestrated by the fetal extravillous trophoblast and maternal immune cells. In a healthy pregnancy, an immune cross-talk between the mother and fetal cells results in the secretion of immunomodulatory mediators, apoptosis of specific cells, cellular differentiation/proliferation, angiogenesis, and vasculogenesis, altogether favoring a suitable microenvironment for the developing embryo. In the context of vasculopathy underlying common pregnancy disorders, it is believed that inefficient invasion of extravillous trophoblast cells in the endometrium leads to a poor placental blood supply, which, in turn, leads to decreased secretion of angiogenic factors, hypoxia, and inflammation commonly associated with preterm delivery, intrauterine growth restriction, and preeclampsia. In this review, we will focus on studies published by Latin American research groups, providing an extensive review of the role of genetic variants from candidate genes involved in a broad spectrum of biological processes underlying the pathophysiology of preeclampsia. In addition, we will discuss how these studies contribute to fill gaps in the current understanding of preeclampsia. Finally, we discuss some trending topics from important fields associated with pregnancy vascular disorders (e.g., epigenetics, transplantation biology, and non-coding RNAs) and underscore their possible implications in the pathophysiology of preeclampsia. As a result, these efforts are expected to give an overview of the extent of scientific research produced in Latin America and encourage multicentric collaborations by highlighted regional research groups involved in preeclampsia investigation.
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Affiliation(s)
- Rafael Tomoya Michita
- Immunogenetics Laboratory, Department of Genetics, Biosciences Institute, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
| | - Valéria de Lima Kaminski
- Immunogenetics Laboratory, Department of Genetics, Biosciences Institute, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
| | - José Artur Bogo Chies
- Immunogenetics Laboratory, Department of Genetics, Biosciences Institute, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
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Fisher SC, Van Zutphen AR, Werler MM, Romitti PA, Cunniff C, Browne ML, National Birth Defects Prevention Study. Maternal antihypertensive medication use and selected birth defects in the National Birth Defects Prevention Study. Birth Defects Res 2018; 110:1433-1442. [PMID: 30260586 PMCID: PMC10064868 DOI: 10.1002/bdr2.1372] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2018] [Revised: 06/25/2018] [Accepted: 06/26/2018] [Indexed: 11/06/2022]
Abstract
BACKGROUND There are limited data on the relationship between antihypertensive medication use in early pregnancy and risk of birth defects. METHODS Using data from the National Birth Defects Prevention Study, we examined associations between specific antihypertensive medication classes and 28 noncardiac birth defects. We analyzed self-reported data on 17,038 case and 11,477 control pregnancies with estimated delivery dates during 1997-2011. We used multivariable logistic regression to estimate odds ratios (ORs) and 95% confidence intervals, adjusted for maternal age, race/ethnicity, body mass index, parity, pregestational diabetes, and study site, for associations between individual birth defects and antihypertensive medication use during the first trimester of pregnancy. We compared risk among women reporting early pregnancy antihypertensive medication use to normotensive women. RESULTS Hypertensive women who reported early pregnancy antihypertensive medication use were more likely to be at least 35 years old, non-Hispanic Black, obese, multiparous, and to report pregestational diabetes than normotensive women. Compared to normotensive women, early pregnancy antihypertensive medication use was associated with increased risk of small intestinal atresia (adjusted OR 2.4, 95% CI 1.2-4.7) and anencephaly (adjusted OR 1.9, 95% CI 1.0-3.5). Risk of these defects was not specific to any particular medication class. CONCLUSIONS Maternal antihypertensive medication use was not associated with the majority of birth defects we analyzed, but was associated with an increased risk for some birth defects. Because we cannot entirely rule out confounding by the underlying hypertension and most ORs were based on small numbers, the increased risks observed should be interpreted with caution.
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Affiliation(s)
- Sarah C. Fisher
- Congenital Malformations Registry, New York State Department of Health, Albany, NY
| | - Alissa R. Van Zutphen
- Congenital Malformations Registry, New York State Department of Health, Albany, NY
- Department of Epidemiology and Biostatistics, School of Public Health, University at Albany, Rensselaer, NY
| | - Martha M. Werler
- Department of Epidemiology, School of Public Health, Boston University, Boston, MA
| | - Paul A. Romitti
- Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, IA
| | | | - Marilyn L. Browne
- Congenital Malformations Registry, New York State Department of Health, Albany, NY
- Department of Epidemiology and Biostatistics, School of Public Health, University at Albany, Rensselaer, NY
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Abstract
PURPOSE Hypertensive disorders of pregnancy are increasing in prevalence and associated with significant maternal and perinatal morbidity and mortality. RECENT FINDINGS Increased emphasis has been placed recently on the use of out-of-office (i.e., home and ambulatory) blood pressure (BP) monitoring to diagnose and manage hypertension in the general population. Current guidelines offer limited recommendations on the use of out-of-office BP monitoring during pregnancy and postpartum. This review will discuss the recent literature on BP measurement outside of the office and its use for screening, diagnosis, and treatment in pregnancy and postpartum, and will illuminate areas for future research.
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Soo JY, Wiese MD, Berry MJ, McMillen IC, Morrison JL. Intrauterine growth restriction may reduce hepatic drug metabolism in the early neonatal period. Pharmacol Res 2018; 134:68-78. [PMID: 29890254 DOI: 10.1016/j.phrs.2018.06.003] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2018] [Revised: 05/23/2018] [Accepted: 06/04/2018] [Indexed: 11/26/2022]
Abstract
The effects of intrauterine growth restriction (IUGR) extend well into postnatal life. IUGR is associated with an increased risk of adverse health outcomes, which often leads to greater medication usage. Many medications require hepatic metabolism for activation or clearance, but hepatic function may be altered in IUGR fetuses. Using a sheep model of IUGR, we determined the impact of IUGR on hepatic drug metabolism and drug transporter expression, both important mediators of fetal drug exposure, in late gestation and in neonatal life. In the late gestation fetus, IUGR decreased the gene expression of uptake drug transporter OATPC and increased P-glycoprotein protein expression in the liver, but there was no change in the activity of the drug metabolising enzymes CYP3A4 or CYP2D6. In contrast, at 3 weeks of age, CYP3A4 activity was reduced in the livers of lambs born with low birth weight (LBW), indicating that LBW results in changes to drug metabolising capacity in neonatal life. Together, these results suggest that IUGR may reduce hepatic drug metabolism in fetal and neonatal life through different mechanisms.
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Affiliation(s)
- Jia Yin Soo
- Early Origins of Adult Health Research Group, Adelaide, SA, 5001, Australia; School of Pharmacy & Medical Sciences, Sansom Institute for Health Research, University of South Australia, Adelaide, SA, 5001, Australia
| | - Michael D Wiese
- School of Pharmacy & Medical Sciences, Sansom Institute for Health Research, University of South Australia, Adelaide, SA, 5001, Australia
| | - Mary J Berry
- Centre for Translational Physiology, Wellington, New Zealand; Department of Paediatrics and Child Health, University of Otago, Wellington, New Zealand
| | | | - Janna L Morrison
- Early Origins of Adult Health Research Group, Adelaide, SA, 5001, Australia; School of Pharmacy & Medical Sciences, Sansom Institute for Health Research, University of South Australia, Adelaide, SA, 5001, Australia.
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Soo JY, Wiese MD, Berry MJ, Morrison JL. Does poor fetal growth influence the extent of fetal exposure to maternal medications? Pharmacol Res 2018; 130:74-84. [DOI: 10.1016/j.phrs.2018.02.001] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/30/2017] [Revised: 12/18/2017] [Accepted: 02/01/2018] [Indexed: 10/18/2022]
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Müller-Deile J, Schröder P, Beverly-Staggs L, Hiss R, Fiedler J, Nyström J, Thum T, Haller H, Schiffer M. Overexpression of preeclampsia induced microRNA-26a-5p leads to proteinuria in zebrafish. Sci Rep 2018; 8:3621. [PMID: 29483572 PMCID: PMC5827519 DOI: 10.1038/s41598-018-22070-w] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2017] [Accepted: 02/16/2018] [Indexed: 12/16/2022] Open
Abstract
So far the pathomechanism of preeclampsia in pregnancy is focussed on increased circulating levels of soluble fms-like tyrosin kinase-1 (sFLT-1) that neutralizes glomerular VEGF-A expression and prevents its signaling at the glomerular endothelium. As a result of changed glomerular VEGF-A levels endotheliosis and podocyte foot process effacement are typical morphological features of preeclampsia. Recently, microRNA-26a-5p (miR-26a-5p) was described to be also upregulated in the preeclamptic placenta. We found that miR-26a-5p targets VEGF-A expression by means of PIK3C2α in cultured human podocytes and that miR-26a-5p overexpression in zebrafish causes proteinuria, edema, glomerular endotheliosis and podocyte foot process effacement. Interestingly, recombinant zebrafish Vegf-Aa protein could rescue glomerular changes induced by miR-26a-5p. In a small pilot study, preeclamptic patients with podocyte damage identified by podocyturia, expressed significantly more urinary miR-26a-5p compared to healthy controls. Thus, functional and ultrastructural glomerular changes after miR-26a-5p overexpression can resemble the findings seen in preeclampsia and indicate a potential pathophysiological role of miR-26a-5p in addition to sFLT-1 in this disease.
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Affiliation(s)
- Janina Müller-Deile
- Department of Medicine/Nephrology, Hannover Medical School, Hannover, Germany. .,Mount Desert Island Biological Laboratory, Salisbury Cove, Maine, USA.
| | - Patricia Schröder
- Mount Desert Island Biological Laboratory, Salisbury Cove, Maine, USA
| | | | - Rebecca Hiss
- Department of Medicine/Nephrology, Hannover Medical School, Hannover, Germany
| | - Jan Fiedler
- Institute of Molecular and Translational Therapeutic Strategies, Hannover Medical School, Hannover, Germany
| | - Jenny Nyström
- Department of Physiology, Institute of Neuroscience and Physiology, the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Thomas Thum
- Institute of Molecular and Translational Therapeutic Strategies, Hannover Medical School, Hannover, Germany
| | - Hermann Haller
- Department of Medicine/Nephrology, Hannover Medical School, Hannover, Germany.,Mount Desert Island Biological Laboratory, Salisbury Cove, Maine, USA
| | - Mario Schiffer
- Department of Medicine/Nephrology, Hannover Medical School, Hannover, Germany.,Mount Desert Island Biological Laboratory, Salisbury Cove, Maine, USA
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48
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Fitton CA, Steiner MF, Aucott L, Pell JP, Mackay DF, Fleming M, McLay JS. In-utero exposure to antihypertensive medication and neonatal and child health outcomes: a systematic review. J Hypertens 2017; 35:2123-2137. [PMID: 28661961 PMCID: PMC5625961 DOI: 10.1097/hjh.0000000000001456] [Citation(s) in RCA: 52] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2017] [Revised: 05/30/2017] [Accepted: 06/01/2017] [Indexed: 11/30/2022]
Abstract
BACKGROUND Although medication is generally avoided wherever possible during pregnancy, pharmacotherapy is required for the treatment of pregnancy associated hypertension, which remains a leading cause of maternal and fetal morbidity and mortality. The long-term effects to the child of in-utero exposure to antihypertensive agents remains largely unknown. OBJECTIVE The aim of this study was to systematically review published studies on adverse outcomes to the child associated with in-utero exposure to antihypertensive medications. METHODS OVID, Scopus, EBSCO Collections, the Cochrane Library, and Web of Science databases were searched for relevant publications published between January 1950 and October 2016 and a total of 688 potentially eligible studies were identified. RESULTS Following review, 47 primary studies were eligible for inclusion. The Critical Appraisal Skills Programme checklist was used to assess study quality. Five studies were of excellent quality; the remainder were either mediocre or poor. Increased risk of low birth weight, low size for gestational age, preterm birth, and congenital defects following in-utero exposure to all antihypertensive agents were identified. Two studies reported an increased risk of attention deficit hyperactivity disorder following exposure to labetalol, and an increased risk of sleep disorders following exposure to methyldopa and clonidine. CONCLUSION The current systematic review demonstrates a paucity of relevant published high-quality studies. A small number of studies suggest possible increased risk of adverse child health outcomes; however, most published studies have methodological weaknesses and/or lacked statistical power thus preventing any firm conclusions being drawn.
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Affiliation(s)
- Catherine A. Fitton
- The Department of Child Health, University of Aberdeen, Royal Aberdeen Children's Hospital, Aberdeen
| | - Markus F.C. Steiner
- The Department of Child Health, University of Aberdeen, Royal Aberdeen Children's Hospital, Aberdeen
| | - Lorna Aucott
- The Department of Child Health, University of Aberdeen, Royal Aberdeen Children's Hospital, Aberdeen
| | - Jill P. Pell
- Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK
| | - Daniel F. Mackay
- Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK
| | - Michael Fleming
- Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK
| | - James S. McLay
- The Department of Child Health, University of Aberdeen, Royal Aberdeen Children's Hospital, Aberdeen
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Agra KF, Pontes IEA, da Silva JR, Figueiroa JN, Clough GF, Alves JGB. Impaired neurovascular reactivity in the microvasculature of pregnant women with preeclampsia. Microcirculation 2017; 24. [DOI: 10.1111/micc.12383] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2017] [Accepted: 05/08/2017] [Indexed: 01/24/2023]
Affiliation(s)
- Karine Ferreira Agra
- Department of Mother and Child Health; Instituto de Medicina Integral Prof. Fernando Figueira-IMIP; Recife Brazil
| | | | - José Roberto da Silva
- Department of Mother and Child Health; Instituto de Medicina Integral Prof. Fernando Figueira-IMIP; Recife Brazil
| | - José Natal Figueiroa
- Department of Mother and Child Health; Instituto de Medicina Integral Prof. Fernando Figueira-IMIP; Recife Brazil
| | | | - João Guilherme Bezerra Alves
- Department of Mother and Child Health; Instituto de Medicina Integral Prof. Fernando Figueira-IMIP; Recife Brazil
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50
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Meiri H, Osol G, Cetin I, Gizurarson S, Huppertz B. Personalized Therapy Against Preeclampsia by Replenishing Placental Protein 13 (PP13) Targeted to Patients With Impaired PP13 Molecule or Function. Comput Struct Biotechnol J 2017; 15:433-446. [PMID: 29034064 PMCID: PMC5633742 DOI: 10.1016/j.csbj.2017.09.002] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2017] [Revised: 08/27/2017] [Accepted: 09/12/2017] [Indexed: 12/16/2022] Open
Abstract
Hypertensive disorders affect about one third of all people aged 20 and above, and are treated with anti-hypertensive drugs. Preeclampsia (PE) is one form of such disorders that only develops during pregnancy. It affects ten million pregnant women globally and additionally causes fetal loss and major newborn disabilities. The syndrome's origin is multifactorial, and anti-hypertensive drugs are ineffective in treating it. Biomarkers are helpful for predict its development. Generic drugs, such as low dose aspirin, were proven effective in preventing preterm PE. However, it does not cure the majority of cases and many studies are underway for fighting PE with extended use of additional generic drugs, or through new drug development programs. This review focuses on placental protein 13 (PP13). This protein is only expressed in the placenta. Impaired PP13 DNA structure and/or its reduced mRNA expression leads to lower blood PP13 level that predict a higher risk of developing PE. Two polymorphic PP13 variants have been identified: (1) The promoter PP13 variant with an "A/A" genotype in the -98 position (versus "A/C" or "C/C"). Having the "A/A" genotype is coupled to lower PP13 expression, mainly during placental syncytiotrophoblast differentiation and, if associated with obesity and history of previous preeclampsia, it accurately predicts higher risk for developing the disorder. (2) A thymidine deletion at position 221 causes a frame shift in the open reading frame, and the formation of an early stop codon resulting in the formation of DelT221, a truncated variant of PP13. In pregnant rodents, both short- and long- term replenishment of PP13 causes reversible hypotension and vasodilation of uterine vessels. Long-term exposure is also accompanied by the development of larger placentas and newborns. Also, only w/t PP13 is capable of inducing leukocyte apoptosis, providing maternal immune tolerance to pregnancy. Based on published data, we propose a targeted PP13 therapy to fight PE, and consider the design and conduct of animal studies to explore this hypothesis. Accordingly, a new targeted therapy can be implemented in humans combining prediction and prevention.
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Affiliation(s)
- Hamutal Meiri
- Hy Laboratories, Rehovot, and TeleMarpe, Tel Aviv, Israel
| | - George Osol
- Department of Obstetrics, Gynecology and Reproductive Sciences, University of Vermont, Burlington, VT, USA
| | - Irene Cetin
- Department of Obstetrics and Gynecology, University of Milano, Italy
- Department of Mother and Child, Hospital Luigi Sacco, and Center for Fetal Research “Giorgio Pardi”, Milano, Italy
| | - Sveinbjörn Gizurarson
- Faculty of Pharmaceutical Sciences, School of Health Science, University of Iceland, Reykjavik, Iceland
| | - Berthold Huppertz
- Institute of Cell Biology, Histology and Embryology & Biobank Graz, Medical University of Graz, Graz, Austria
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