Maternal Reproductive History and the Risk of Congenital Heart Defects in Offspring: A Systematic Review and Meta-analysis

Abstract

Epidemiological studies have reported conflicting results on the association of congenital heart defect (CHD) risk in offspring with a maternal history of prior pregnancies and abortions, but no meta-analysis has been reported. We searched MEDLINE and EMBASE from their inception to April 14, 2014, for relevant studies that assessed the association between maternal reproductive history and CHD risk. Two authors independently assessed eligibility and extracted data. Fixed-effects or random-effects models were used to calculate the pooled odds ratios (ORs). Among 1,599 references, 17 case-control studies and one nested case-control study were included in this meta-analysis. The summary OR for the ever versus nulligravidity was 1.18 (95% CI 1.03-1.34). A dose-response analysis also indicated a positive effect of maternal gravidity on CHD risk, and the summary OR for each increment in number of pregnancies was 1.13 (95% CI 1.08-1.18). A history of abortion was associated with a 24% higher risk of CHD, OR = 1.24 (95% CI 1.11-1.38). When stratified by abortion category, CHD risk increased by 18 and 58% with a history of spontaneous abortion and induced abortion, respectively. The summary OR for each increment of one abortion was 1.28 (95% CI 1.18-1.40). In summary, this study provides evidence that increased maternal gravidity was positively associated with a risk of CHDs in offspring. Meanwhile, our results demonstrate a positive association of any history of abortion with an increased risk of CHDs.

Acute alcohol exposure during mouse gastrulation alters lipid metabolism in placental and heart development: Folate prevention

“…Of interest, a meta‐analysis that assessed the association between maternal reproductive history and CHD risk, the study provided evidence that a history of abortion was associated with a 24% higher risk of CHD. When defined by abortion category, CHD risk increased by 18% and 58% with a history of spontaneous abortion and induced abortion, respectively (Feng et al, ).…”

Changes in the Maternal Risk Factors of Congenital Heart Disease in Chinese Population: A Meta-analysis

“…Maternal stress caused by negative life events during pregnancy would lead to increased secretion of plasma adrenocorticotrophin, β-endorphin, glucocorticoids, and catecholamines, which may lead to changes in the fetal neurotransmitter systems and transcriptional mechanisms [40,58]. Abnormal childbearing history, such as previous abortions, may result in some residual effects that may affect the development of subsequent embryo [59,60]. In addition, the causes of previous abnormal pregnancies, such as genetic factors, uterine factors, maternal chronic diseases, etc., if not removed, will still affect subsequent embryonic development [60].…”

“…Abnormal childbearing history, such as previous abortions, may result in some residual effects that may affect the development of subsequent embryo [59,60]. In addition, the causes of previous abnormal pregnancies, such as genetic factors, uterine factors, maternal chronic diseases, etc., if not removed, will still affect subsequent embryonic development [60].…”

Congenital heart diseases and parental occupational exposure in a Hungarian case‐control study in 1997 to 2002

“…The etiology of approximately 20% of CHDs can be linked to known causes, while the rest of cases are the result of complex interactions between genetic, lifestyle, and environmental factors 4,5 . Previous studies explored that maternal antibiotic use (adjusted odds ratio [aOR] = 3.96; 95% CI: 1.78‐8.79), maternal alcohol consumption (aOR = 2.14; 95% CI: 1.64‐2.80), age (aOR = 1.94; 95% CI: 1.12‐3.34), past induced abortion (aOR = 1.58; 95% CI: 1.12‐2.22), education of parents (aOR = 1.47; 95% CI: 1.28‐1.69), the use of assisted reproduction techniques for conception (aOR = 1.45; 95% CI: 1.20‐1.76), higher maternal body mass index (aOR = 1.32; 95% CI: 1.21‐1.43), parity (aOR = 1.18; 95% CI: 1.03‐1.34), and maternal smoking (aOR = 1.11; 95% CI: 1.02‐1.21) may all increase the risk of CHDs, while maternal folate intake (aOR = 0.42; 95% CI: 0.21‐0.86) may have a protective effect 6‐11 . Other studies have also confirmed occupation of parents as a possible causative factor for the development of CHDs.…”