140 - META-ANALYSIS OF PRENATAL RISK FACTORS FOR CONGENITAL HEART DISEASE: PART 2 - MATERNAL ALCOHOL AND MEDICATION, ASSISTED REPRODUCTIVE TECHNOLOGIES, AND FAMILIAL AND FETAL FACTORS.

Background: Understanding the etiology of congenital heart diseases (CHDs) is challenging due to multifactorial and often elusive causes, along with insufficient evidence on quantitative effects of prenatal risk factors. Currently, there is no comprehensive systematic review encompassing all CHD risk factors. This two-part study aims to address these gaps by conducting a systematic review and meta-analysis on all CHD risk factors. Part 2 explores maternal alcohol and medication use, use of assisted reproductive technologies (ART), and familial and fetal factors.

METHODS AND RESULTS: Relevant studies were identified using a search strategy encompassing the concepts of CHD and prenatal risk factors across PubMed, MEDLINE and Scopus. Included articles (1) were peer-reviewed, (2) quantified association between CHD and risk factors, and (3) were published between 1989 and 2022. Pooled odds ratios (OR) and their 95% confidence interval (CI) were calculated using a random effects model.

151 articles met the inclusion criteria. Associations were found between all CHDs and extracardiac anomalies (OR 3.41, 95% CI 1.72-6.77) and increased nuchal translucency (OR 6.87, 95% CI 2.42-19.53). An association was also found between severe CHDs and increased and very increased nuchal translucency (OR 5.93, 95% CI 3.39-10.36 and OR 21.43, 95% CI 8.28-55.44, respectively). Associations were found between all CHDs and antidepressant use (OR 1.22, 95% CI 1.07-1.38) and antihypertensive use (OR 2.07, 95% CI 1.80-2.38). There was a positive association between severe CHDs and lithium use, but with a very wide confidence interval encompassing the null effect. There was no association between all CHDs and maternal alcohol use. Associations were found between all CHDs and family history of CHD (OR 2.85, 95% CI 2.20-3.69). There was weak positive association with all CHD and the use of ART, but with wide confidence intervals (the association was statistically significant only for severe CHDs: OR 1.98, 95% CI 1.30-3.02). There were insufficient data to evaluate associations between CHDs and the presence of a single umbilical artery, anticonvulsant use and vitamin A use.


Conclusion: There were associations between CHDs and maternal exposure to antidepressants and antihypertensives, extracardiac anomalies, increased nuchal translucency, and family history of CHD. Effect sizes were larger for fetal factors, whereas maternal exposures and familial factors had modest associations. Interestingly, data was scarce and sometimes inconclusive for some risks factor commonly cited as being associated with CHD risk, such as lithium use, the presence of a single umbilical artery, anticonvulsant use, and vitamin A use.