Maternal Hypertension During Pregnancy and the Risk of Congenital Heart Defects in Offspring: A Systematic Review and Meta-analysis

Abstract

Maternal hypertension is common during pregnancy, and multiple studies have reported on an association between maternal hypertension and congenital heart defects (CHDs) in offspring; however, there is variability in the quality of these studies. A systematic review and meta-analysis was conducted on the associations between untreated and treated maternal hypertension and the risk of CHDs, evaluating CHDs overall as well as specific CHD subtypes. A systematic search of peer-reviewed articles published before August 2013 identified 16 studies evaluating the associations between untreated and treated maternal hypertension and CHDs. Summary relative risk (RR) estimates were calculated using fixed-effects models and random-effects models. Significant associations were observed between maternal hypertension and overall CHDs, for both treated [RR 2.0; 95 % confidence interval (CI) 1.5, 2.7] and untreated (RR 1.4; 95 % CI 1.2, 1.7) hypertension, as well as for overall hypertension regardless of treatment status (RR 1.8; 95 % CI 1.5, 2.2). The magnitude of effect was similar for the majority of CHD sub-types evaluated. The effects were also similar among women with hypertension who used one of multiple specific hypertension medications. There was no evidence of publication bias, and our results were robust to several factors considered in sensitivity analyses (e.g., source of exposure data, adjustment for potential confounders, and study design). Maternal hypertension was associated with CHDs. By understanding the specific mechanisms involved, appropriate strategies may be developed to reduce this risk, in order to prevent CHDs.

Pregnancy Outcome After First Trimester Use of Methyldopa

“…25 Some studies have discussed an increased risk for cardiac defects in treated and untreated pregnancies with hypertension. [26][27][28][29][30] The small number of major birth defects in our study does not allow further analysis with regard to other organ systems like urogenital malformations that were previously reported to be associated with antihypertensive treatment. 31 However, there is no distinct pattern of congenital anomalies among exposed neonates, neither in our prospective cohort nor among our retrospective reports.…”

British Association for Psychopharmacology consensus guidance on the use of psychotropic medication preconception, in pregnancy and postpartum 2017

“…This association may therefore reflect a physiological effect of lowering the maternal blood pressure rather than a drug-specific teratogenic effect, or may be causally related to the underlying maternal hypertension (Ramakrishnan et al, 2015).…”

Gestational stress induces the unfolded protein response, resulting in heart defects

“…Epidemiological studies have identified significant environmental risk factors for human CHD, including maternal exposures to alcohol, isotretinoin, thalidomide, antiseizure medications, antiretroviral medications, environmental teratogens and infectious agents. Embryo hypoxia is another well-recognized risk factor caused by smoking, living at high altitude, maternal diabetes, high body mass index, hypertension or prescription medications (Watkins et al, 2003;Jenkins et al, 2007;Zheng et al, 2013;Webster et al, 2014;Ornoy et al, 2015;Ramakrishnan et al, 2015;Sullivan et al, 2015). The specific effects of environment on embryonic development have been studied by exposing pregnant animals to a variety of conditions.…”