The effect of maternal BMI, smoking and alcohol on congenital heart diseases: a Mendelian randomisation study

Abstract

Background Congenital heart diseases (CHDs) remain a significant cause of infant morbidity and mortality. Epidemiological studies have explored maternal risk factors for offspring CHDs, but few have used genetic epidemiology methods to improve causal inference. Methods Three birth cohorts, including 65,510 mother/offspring pairs (N = 562 CHD cases) were included. We used Mendelian randomisation (MR) analyses to explore the effects of genetically predicted maternal body mass index (BMI), smoking and alcohol on offspring CHDs. We generated genetic risk scores (GRS) using summary data from large-scale genome-wide association studies (GWAS) and validated the strength and relevance of the genetic instrument for exposure levels during pregnancy. Logistic regression was used to estimate the odds ratio (OR) of CHD per 1 standard deviation (SD) higher GRS. Results for the three cohorts were combined using random-effects meta-analyses. We performed several sensitivity analyses including multivariable MR to check the robustness of our findings. Results The GRSs associated with the exposures during pregnancy in all three cohorts. The associations of the GRS for maternal BMI with offspring CHD (pooled OR (95% confidence interval) per 1SD higher GRS: 0.95 (0.88, 1.03)), lifetime smoking (pooled OR: 1.01 (0.93, 1.09)) and alcoholic drinks per week (pooled OR: 1.06 (0.98, 1.15)) were close to the null. Sensitivity analyses yielded similar results. Conclusions Our results do not provide robust evidence of an effect of maternal BMI, smoking or alcohol on offspring CHDs. However, results were imprecise. Our findings need to be replicated, and highlight the need for more and larger studies with maternal and offspring genotype and offspring CHD data.

Association of Maternal Dietary Habits and Infant MTHFR Gene Polymorphisms with Ventricular Septal Defect in Offspring: A Case–Control Study

“…Other covariates were collected based on existing literature [28][29][30][31], including sex, maternal age at pregnancy, residence, last year's household income, maternal schooling years, pregestational BMI, history of adverse pregnancy outcomes, history of familial congenital malformations, consanguineous marriages, gestational hypertension during this pregnancy, gestational diabetes mellitus during this pregnancy, lifestyle factors during the first trimester of pregnancy (i.e., smoke and drink alcohols), pregestational folic acid supplementation, and pregestational exposure to antibiotics. A portion of the above questions were documented in the nationwide free prenatal health care system [32].…”

Research Progress of Maternal Metabolism on Cardiac Development and Function in Offspring

“…Similarly, a systematic review of 24 studies revealed a dose-dependent relationship between maternal overweight, mild and severe obesity, and the incidence of all types of CHDs in offspring [25]. However, a Mendelian randomization study did not demonstrate a causal association between maternal BMI and the incidence of CHDs in offspring [26]. The conflicting results of these studies suggest that the effect of maternal obesity on the offspring's heart remains uncertain, and additional robust evidence and analytical methods are necessary to control for potential confounding factors.…”

Imbalance of fetal growth factor levels in congenital heart disease pathology: a systematic review to investigate therapeutic potential

“…Acetaminophen and ibuprofen may successfully close the venous hole in the PDA and may be effective for treating other defects, such as VSD(8, 9); however, the most useful method for treating TOF is surgery. Changes in maternal factors during pregnancy can be useful both as a treatment and as a diagnostic method, as a lower concentration of folate in the mother's body during pregnancy is considered an indicator of a greater incidence of CHD (10,11). Reduction of growth factors is another change that can be introduced as the main pathology of CHD in addition to potential therapy.…”