Association of maternal MTHFD1 and MTHFD2 gene polymorphisms with congenital heart disease in offspring / 中国当代儿科杂志

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.

Association between Maternal Drug Use and Cytochrome P450 Genetic Polymorphisms and the Risk of Congenital Heart Defects in Offspring / 生物医学与环境科学（英文）

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.

Association between maternal reduced folate carrier gene polymorphisms and congenital heart disease in offspring: a case-control study / 中国当代儿科杂志

OBJECTIVE@#To study the association between maternal reduced folate carrier (@*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 @*RESULTS@#After control for confounding factors, the multivariate logistic regression analysis showed that maternal @*CONCLUSIONS@#Maternal

Risk factors for preterm birth: a prospective cohort study / 中国当代儿科杂志

OBJECTIVES@#To investigate the incidence of preterm birth and risk factors for preterm birth.@*METHODS@#A prospective cohort study was performed for the pregnant women in early pregnancy and their spouses, who underwent prenatal examination for the first time in Hunan Provincial Maternal and Child Health Care Hospital from May 2014 to December 2016 and decided to be hospitalized for delivery. A questionnaire survey was performed to collect exposure information possibly related to preterm birth. The hospital's medical record system was used for information verification and to record the pregnancy outcome. A multivariate logistic regression analysis was used to investigate the risk factors for preterm birth.@*RESULTS@#A total of 6 764 pregnant women with complete data were included, and the incidence rate of preterm birth was 17.09%. The multivariate logistic regression analysis showed that a history of adverse pregnancy outcomes, eating areca nut before pregnancy, a history of pregnancy complications, a history of hepatitis, no folate supplementation during pregnancy, medication during pregnancy, active smoking and passive smoking during pregnancy, drinking during pregnancy, unbalanced diet during pregnancy, high-intensity physical activity during pregnancy, and natural conception after treatment of infertility or assisted conception as the way of conception were risk factors for preterm birth (@*CONCLUSIONS@#There are many risk factors for preterm birth. Special attention should be paid to the life behaviors of pregnant women during pregnancy, and health education should be strengthened for pregnant women and their spouses to develop good living habits and reduce the incidence of preterm births.

Epidemiological characteristics and spatial epidemiology of hand-foot-mouth disease in Hunan Province, China, from 2008 to 2019 / 中国当代儿科杂志

OBJECTIVES@#To investigate the epidemic situation of hand-foot-mouth disease (HFMD) in Hunan Province, China, from 2008 to 2019, as well as its spatial autocorrelation characteristics and spatial-temporal clustering, and to provide a reference for the prevention and control of HFMD in Hunan Province.@*METHODS@#Spatial autocorrelation and spatial-temporal clustering analyses were used to analyze the monitoring data of HFMD in Hunan Province from 2008 to 2019.@*RESULTS@#The epidemic situation of HFMD in Hunan Province from 2008 to 2019 showed obvious seasonal distribution, with a low incidence rate in January to March and a high incidence rate in April to July. As for population distribution, children aged 0-5 years had the highest number of HFMD cases and accounted for 95.89% (1 460 391/1 522 910) of all cases, with a mean annual incidence rate of 2 197.784/100 000, and scattered children had the highest number of cases and accounted for 82.59% (1 257 739/1 522 910) of all cases. The global spatial autocorrelation analysis showed that the onset of HFMD in Hunan Province showed a significant clustering distribution, and the local spatial autocorrelation analysis showed that the high clustering areas of HFMD were mainly the districts and counties of Changsha, Zhuzhou, and Yueyang cities. Time-space scanning showed that clustering time was mainly April to July; the cases were clustered in the northeast of Hunan Province from 2008 to 2010 and in the central part of Hunan Province from 2011 to 2019.@*CONCLUSIONS@#The high incidence rate of HFMD is observed in April to July in Hunan Province. Children under 5 years of age are at a high risk of this disease. Spatial-temporal clustering is observed for the epidemic of HFMD, mainly clustered in the northeastern and central areas of Hunan Province. It is suggested that the results may be used as guidance to determine the key areas for HFMD prevention and control in Hunan Province and optimize the allocation of health resources.

Risk factors of congenital malformations and its impacts on adverse pregnancy outcomes: A prospective cohort study / 中华疾病控制杂志

Objective To explore risk factors of congenital malformations (CMs) and to evaluate its impacts on adverse pregnancy outcomes (APOs). Methods A prospective cohort study was conducted among pregnant women who received the first antenatal care from March 2013 to February 2016 in the reproductive center, obstetrics clinics, infertility clinics and ultrasound department of Hunan Provincial Maternal and Child Health Hospital. Corresponding information from pregnant women and their spouses were collected. Univariate and multivariate Logistic regression were used to screen possible risk factors of CMs and evaluate the impacts of CMs on other APOs. Results The study showed that women had history of non-standard BMI, smoking, hepatitis, pregnancy-related complications, gestational diabetes mellitus, infertility and using assisted reproductive technology before pregnancy; had no folic acid taking, active and passive smoking, drinking, uneven diet, high intensity physical activity during pregnancy increased the risk of CMs in offspring. Furthermore, the history of spouse smoking and eating betel nut also increased the risk of CMs in offspring. CMs might increase the risk of preterm birth, very preterm birth, low birth weight, very low birth weight, and perinatal mortality. Conclusions There are many risk factors of CMs. Knowing these risk factors, and giving them optimal prevention strategies and effective intervention measures are important measures in preventing the occurrence of CMs and other APOs.

Association of single nucleotide polymorphisms of transcription factors with congenital heart diseases in the Chinese population: a Meta analysis / 中国当代儿科杂志

<p><b>OBJECTIVE</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSIONS</b>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.</p>