Journal
JOURNAL OF HYPERTENSION
Volume 35, Issue 11, Pages 2123-2137Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/HJH.0000000000001456
Keywords
adverse drug event; antihypertensive agents; child health; drug exposure in pregnancy; female; hypertension; in-utero exposure; pharmacovigilance; preeclampsia; pregnancy-induced hypertension
Categories
Funding
- Farr Institute at Scotland
- Arthritis Research UK
- British Heart Foundation
- Cancer Research UK
- Economic and Social Research Council
- Engineering and Physical Sciences Research Council
- Medical Research Council
- National Institute of Health Research
- National Institute for Social Care and Health Research (Welsh Assembly Government)
- Chief Scientist Office (Scottish Government Health Directorates)
- Wellcome Trust, (MRC) [MR/K007017/1]
- MRC [MR/M501633/1, MR/K007017/1, MR/M501633/2] Funding Source: UKRI
- Medical Research Council [MR/K007017/1, MC_PC_13040, MR/M501633/2, MR/M501633/1] Funding Source: researchfish
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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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