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Objectives: To explore the associations of parental smoking and alcohol consumption during the periconceptional period and their interactions with risk of congenital heart disease (CHD) in offspring., Methods: The parents of children with simple CHD aged 0 to 1 year ( n =683) were recruited as the case group, while the parents of healthy children aged 0 to 1 year ( n =740) served as the control group. A case-control study was conducted, and a questionnaire was used to collect information on perinatal exposures. After controlling for relevant confounding factors using multivariate logistic regression analysis and propensity score matching, the associations of parental smoking and alcohol consumption during the periconceptional period and their interactions with CHD were examined, as well as the cumulative effects of smoking and drinking on CHD risk., Results: Maternal active smoking ( OR =2.91, 95% CI : 1.60-5.30), passive smoking ( OR =1.94, 95% CI : 1.56-2.42), and alcohol consumption ( OR =2.59, 95% CI : 1.89-3.54), as well as paternal smoking ( OR =1.52; 95% CI : 1.22-1.90) and drinking ( OR =1.48, 95% CI : 1.19-1.84), were associated with an increased risk of CHD in offspring. There was no interaction between parental smoking and drinking behaviors during the periconceptional period concerning the risk of CHD in offspring ( P >0.05). The more parents' smoking and drinking behaviors during the perinatal pregnancy, the higher the risk of CHD in their offspring ( OR =1.50, 95% CI : 1.36-1.65)., Conclusions: Parental smoking and alcohol consumption during the periconceptional period are associated with the occurrence of CHD in offspring, and there is a cumulative effect on CHD risk, suggesting that reducing tobacco and alcohol exposure during the periconceptional period may lower the incidence of CHD.

Objectives: To study the association of maternal methylenetetrahydrofolate dehydrogenase 1 ( MTHFD1 ) and methylenetetrahydrofolate dehydrogenase 2 ( MTHFD2 ) gene polymorphisms with congenital heart disease (CHD) in offspring., Methods: A hospital-based case-control study was conducted. The mothers of 683 children with CHD alone who attended Hunan Children's Hospital, from November 2017 to March 2020 were enrolled as the case group, and the mothers of 740 healthy children who attended the same hospital during the same period and did not have any deformity were enrolled as the control group. A questionnaire survey was performed to collect related exposure data, and then venous blood samples (5 mL) were collected from the mothers to detect MTHFD1 and MTHFD2 gene polymorphisms. A multivariate logistic regression analysis was used to evaluate the association of MTHFD1 and MTHFD2 gene polymorphisms with CHD. The four-gamete test in Haploview 4.2 software was used to construct haplotypes and evaluate the association between haplotypes and CHD. The generalized multifactor dimensionality reduction method and logistic regression analysis were used to examine gene-gene interaction and its association with CHD., Results: The multivariate logistic regression analysis showed that maternal MTHFD1 gene polymorphisms at rs11849530 (GA vs AA: OR =1.49; GG vs AA: OR =2.04) andat rs1256142 (GA vs GG: OR =2.34; AA vs GG: OR =3.25) significantly increased the risk of CHD in offspring ( P <0.05), while maternal MTHFD1 gene polymorphisms at rs1950902 (AA vs GG: OR =0.57) and MTHFD2 gene polymorphisms at rs1095966 (CA vs CC: OR =0.68) significantly reduced the risk of CHD in offspring ( P <0.05). The haplotypes of G-G-G ( OR =1.86) and G-A-G ( OR =1.35) in mothers significantly increased the risk of CHD in offspring ( P <0.05). The gene-gene interaction analyses showed that the first-order interaction between MTHFD1 rs1950902 and MTHFD1 rs2236222 and the second-order interaction involving MTHFD1 rs1950902, MTHFD1 rs1256142, and MTHFD2 rs1095966 might be associated with risk of CHD ( P <0.05)., Conclusions: Maternal MTHFD1 and MTHFD2 gene polymorphisms and their haplotypes, as well as the interaction between MTHFD1 rs1950902 and MTHFD1 rs2236222 and between MTHFD1 rs1950902, MTHFD1 rs1256142, and MTHFD2 rs1095966, are associated with the risk of CHD in offspring.

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 CYP450 genetic 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., (Copyright © 2022 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.)

Objective: To study the association between maternal reduced folate carrier ( RFC ) gene polymorphisms and congenital heart disease (CHD) in offspring., Methods: A hospital-based case-control study was conducted. The mothers of 683 infants with CHD who attended the Department of Cardiothoracic Surgery, Hunan Children's Hospital, from November 2017 to March 2020 were enrolled as the case group. The mothers of 740 healthy infants without any deformity who attended the hospital during the same period of time were enrolled as the control group. A questionnaire survey was performed to collect the exposure data of subjects. Venous blood samples of 5 mL were collected from the mothers for genetic polymorphism detection. A multivariate logistic regression analysis was used to evaluate the association of RFC gene polymorphisms and their haplotypes with CHD. A generalized multifactor dimensionality reduction method was used to analyze gene-gene interactions., Results: After control for confounding factors, the multivariate logistic regression analysis showed that maternal RFC gene polymorphisms at rs2236484 (AG vs AA: OR =1.91, 95% CI :1.45-2.51; GG vs AA: OR =1.96, 95% CI :1.40-2.75) and rs2330183 (CT vs CC: OR =1.39, 95% CI :1.06-1.83) were significantly associated with the risk of CHD in offspring. The haplotypes of G-G ( OR =1.21, 95% CI :1.03-1.41) and T-G ( OR =1.25, 95% CI :1.07-1.46) in mothers significantly increased the risk of CHD in offspring. The interaction analysis showed significant gene-gene interactions between different SNPs of the RFC gene in CHD ( P < 0.05)., Conclusions: Maternal RFC gene polymorphisms and interactions between different SNPs are significantly associated with the risk of CHD in offspring.

Objective: To study the association of maternal diabetes mellitus (DM), uncoupling protein 2 (UCP2) gene polymorphisms, and their interaction with the risk of congenital heart disease (CHD) in offspring., Methods: A hospital-based case-control study was conducted. A total of 464 mothers of children with CHD alone who were diagnosed in Hunan Children's Hospital from March 2018 to August 2019 were enrolled as the case group. A total of 504 mothers of healthy children who were hospitalized during the same period and did not have any deformity were enrolled as the control group. A questionnaire survey was performed to collect the information on exposure. Venous blood samples (5 mL) were collected from the mothers to detect UCP2 gene polymorphisms. A multivariate logistic regression analysis was used to investigate the association of maternal DM, UCP2 gene polymorphisms, and their interaction with CHD in offspring., Results: After control for confounding factors, the multivariate logistic regression analysis showed that mothers with gestational DM (OR=2.96, 95%CI: 1.57-5.59), a history of gestational DM (OR=3.16, 95%CI: 1.59-6.28), and pregestational DM (OR=4.52, 95%CI: 2.41-8.50) significantly increased the risk of CHD in offspring (P<0.05). The polymorphisms of the UCP2 gene at rs659366 (T/C vs C/C: OR=1.49, 95%CI: 1.02-2.16; T/T vs C/C: OR=2.77, 95%CI: 1.67-4.62) and rs660339 (A/A vs G/G: OR=2.19, 95%CI: 1.34-3.58) were significantly associated with risk of CHD in offspring (P<0.05). The interaction analysis showed an interaction between the polymorphisms of the UCP2 gene at rs659366 and rs660339 and maternal DM in the development of CHD (P<0.05)., Conclusions: Maternal DM, UCP2 gene polymorphisms, and their interaction are associated with the development of CHD in offspring.

Objective: To study the association of single nucleotide polymorphisms (SNPs) of transcription factors (NKX2.5, GATA4, TBX5, and FOG2) with congenital heart disease (CHD) in the Chinese population., Methods: PubMed, Google Scholar, CNKI, Wanfang Data, and Weipu Data were searched for articles on the association of SNPs of target genes with CHD in the Chinese population. If one locus was mentioned in at least two articles, the random or fixed effect model was used to perform a pooled analysis of study results and to calculate the pooled OR and its 95%CI. If a locus was mentioned in only one article, related data were extracted from this article to analyze the association between the SNPs of this locus and CHD., Results: Twenty-three articles were included. The Meta analysis showed that there were significant differences between the CHD and control groups in the genotype and allele frequencies of GATA4 rs1139244 and rs867858 and the genotype frequency of GATA4 rs904018, while there were no significant differences in the SNPs of the other genetic loci between the two groups. The single-article analysis showed that there were significant differences between the two groups in the allele frequencies of NKX2.5 rs118026695/rs703752, GATA4 rs884662/rs12825/rs12458/rs3203358/rs4841588, and TBX5 rs6489956. There were no significant differences in the SNPs of FOG2 locus between the two groups., Conclusions: The SNPs of some loci in NKX2.5, GATA4, and TBX5 are associated with CHD in the Chinese population, but the association between the SNPs of FOG2 locus and the development of CHD has not been found yet.