RESUMO
【Objective】 To investigate the association of maternal medication during early pregnancy and cytochrome P450 (CYP450) genetic polymorphisms with the risk of congenital heart disease (CHD) in offspring. 【Methods】 We selected 127 pregnant women with CHD fetuses as the observation group and 132 pregnant women with non-CHD fetuses as the control group. Their characteristics and medication history were investigated, and CYP450 polymorphisms were detected. Logistic regression analysis was used to assess the association between maternal medication, CYP450 gene variations, and offspring CHD risk. 【Results】 The risk of CHD in offspring was higher in the observation group with maternal use of ovulation induction drugs, antihypertensive drugs, antibiotics, antidepressants, miscarriage prevention drugs, and traditional Chinese medicine (P<0.05). The A/T and T/T genotypes in rs1065852 and the C/G and G/G genotypes in rs16947 increased the risk of CHD in offspring compared to their respective genotypes. The risk of CHDs in offspring increased with the presence of risk genotypes (A/T or T/T) at the rs1065852 locus of the maternal CYP450 gene and early pregnancy medication use (P<0.05); the same was observed for risk genotypes (C/G or G/G) at the rs16947 locus (P<0.05). 【Conclusion】 Maternal medication during early pregnancy may be associated with offspring CHD, and the rs1065852 and rs16947 loci of CYP450 are significantly related to the risk of CHD in offspring.
RESUMO
OBJECTIVE@#This study aimed to assess the associations between maternal drug use, cytochrome P450 ( CYP450) genetic polymorphisms, and their interactions with the risk of congenital heart defects (CHDs) in offspring.@*METHODS@#A case-control study involving 569 mothers of CHD cases and 652 controls was conducted from November 2017 to January 2020.@*RESULTS@#After adjusting for potential confounding factors, the results show that mothers who used ovulatory drugs (adjusted odds ratio [a OR] = 2.12; 95% confidence interval [ CI]: 1.08-4.16), antidepressants (a OR = 2.56; 95% CI: 1.36-4.82), antiabortifacients (a OR = 1.55; 95% CI: 1.00-2.40), or traditional Chinese drugs (a OR = 1.97; 95% CI: 1.26-3.09) during pregnancy were at a significantly higher risk of CHDs in offspring. Maternal CYP450 genetic polymorphisms at rs1065852 (A/T vs. A/A: OR = 1.53, 95% CI: 1.10-2.14; T/T vs. A/A: OR = 1.57, 95% CI: 1.07-2.31) and rs16947 (G/G vs. C/C: OR = 3.41, 95% CI: 1.82-6.39) were also significantly associated with the risk of CHDs in offspring. Additionally, significant interactions were observed between the CYP450genetic variants and drug use on the development of CHDs.@*CONCLUSIONS@#In those of Chinese descent, ovulatory drugs, antidepressants, antiabortifacients, and traditional Chinese medicines may be associated with the risk of CHDs in offspring. Maternal CYP450 genes may regulate the effects of maternal drug exposure on fetal heart development.