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.
Although many studies shown that the risk of congenital heart disease (CHD) was closely related to genetic and environmental factors, the exact mechanism was still unclear. This study was to assess the association of maternal folic acid supplementation (FAS), the 5-methyltetrahydrofolate-homocysteine methyltransferase reductase (MTRR) gene polymorphisms in offspring and their interaction effects with the risk of CHD and its subtypes. A case-control study was conducted on 595 children with CHD and 605 healthy child controls. The multivariate logistic regression model was used to assess the association of maternal FAS, offspring MTRR gene polymorphisms and their interaction effects with CHD and its subtypes. This study shown that maternal FAS was significantly associated with a reduced risk of CHD (OR = 0.55, 95%CI: 0.36–0.83) and its subtypes including ASD (OR = 0.25, 95%CI: 0.14–0.45), VSD (OR = 0.42, 95%CI: 0.27–0.64), and CTD (OR = 0.23, 95%CI: 0.09–0.59) in offspring. Offspring MTRR gene polymorphisms at rs162048 (GG vs. AA: OR = 2.05, 95%CI: 1.35–3.13), rs1802059 (AA vs. GG: OR = 5.13, 95%CI: 2.15–12.23; GA vs. GG: OR = 1.81, 95%CI: 1.35–2.43), rs10380 (TT vs. CC: OR = 2.27, 95%CI: 1.20–4.31) and rs1801394 (GG vs. AA: OR = 1.58, 95%CI: 1.02–2.42) were significantly associated with the risk of CHD, and similar results were also found for three subtypes of CHD. Additionally, a statistically significant interaction effect between maternal FAS and offspring MTRR gene polymorphism at rs1802059 was observed (OR = 0.38, 95%CI: 0.15–0.94). Among children who had a variant genotype at rs1802059, the risk of CHD was significantly decreased when their mother used folate for this pregnancy compared with mothers not using folate. In those of Chinese descent, maternal FAS and offspring MTRR gene polymorphisms are significantly associated with the risk of CHD and its three subtypes. Furthermore, maternal FAS may help to offset some of risks of CHD due to offspring MTRR genetic variants. However, more studies with prospective designs and larger samples are needed to confirm our findings. Registration number: ChiCTR1800016635; Registration time: 14/06/2018.
Abstract Background Although many studies shown that the risk of congenital heart disease (CHD) was closely related to genetic and environmental factors, the exact mechanism was still unclear. This study was to assess the association of maternal folic acid supplementation (FAS), the 5-methyltetrahydrofolate-homocysteine methyltransferase reductase (MTRR) gene polymorphisms in offspring and their interactions with the risk of CHD and its subtypes. Methods A case-control study was conducted on 595 children with CHD and 605 healthy child controls. The multivariate logistic regression model was used to assess the association of maternal FAS, offspring MTRR gene polymorphisms and their interactions with CHD and its subtypes. Results This study shown that maternal FAS was significantly associated with a reduced risk of CHD (OR = 0.55, 95%CI: 0.36–0.83) and its subtypes including ASD (OR = 0.25, 95%CI: 0.14–0.45), VSD (OR = 0.42, 95%CI: 0.27–0.64), and CTD (OR = 0.23, 95%CI: 0.09–0.59) in offspring. Offspring MTRR gene polymorphisms at rs162048 (GG vs AA: OR = 2.05, 95%CI: 1.35–3.13), rs1802059 (AA vs GG: OR = 5.13, 95%CI: 2.15–12.23; GA vs GG: OR = 1.81, 95%CI: 1.35–2.43), rs10380 (TT vs CC: OR = 2.27, 95%CI: 1.20–4.31) and rs1801394 (GG vs AA: OR = 1.58, 95%CI: 1.02–2.42) were significantly associated with the risk of CHD, and similar results were also found for three subtypes of CHD. Additionally, a statistically significant interaction between maternal FAS and offspring MTRR gene polymorphism at rs1802059 was observed (OR = 0.38, 95%CI: 0.15–0.94). Among children who had a variant genotype at rs1802059, the risk of CHD was significantly decreased when their mother used folate for this pregnancy compared with mothers not using folate. Conclusions In those of Chinese descent, maternal FAS and offspring MTRR gene polymorphisms are significantly associated with the risk of CHD and its three subtypes. Furthermore, maternal FAS may help to offset some of risks of CHD due to offspring MTRR genetic variants. However, more studies with prospective designs and larger samples are needed to confirm our findings. Trial registration: Registration number: ChiCTR1800016635; Registration time: 14/06/2018.
Background The relationships between various obesity measures and hypertensive disorders of pregnancy (HDP) remain inadequately explored, and their causal links are not well understood. This study aims to clarify these associations and investigate the mediating role of triglycerides. Methods We conducted a comprehensive meta-analysis of observational studies alongside Mendelian randomisation (MR) analysis to assess the impact of 10 obesity measures on HDP risk. Additionally, we evaluated the mediating effect of triglycerides. Results Our meta-analysis revealed significant associations between maternal prepregnancy overweight/obesity and increased risks of gestational hypertension (GH) (overweight: OR=1.98, 95% CI 1.83 to 2.15; obesity: OR=3.77, 95% CI 3.45 to 4.13) and pre-eclampsia (overweight: OR=1.78, 95% CI 1.67 to 1.90; obesity: OR=3.46, 95% CI 3.16 to 3.79). Higher maternal waist circumference (WC) was also linked to increased pre-eclampsia risk (OR=1.45, 95% CI 1.14 to 1.83). MR analyses indicated that each 1-SD increase in genetically predicted obesity measures (whole body fat mass, body fat percentage, trunk fat mass, trunk fat percentage, body mass index, WC, hip circumference) was associated with higher risks of GH and pre-eclampsia. Triglycerides mediated 4.3%–14.1% of the total genetic effect of these obesity measures on GH and pre-eclampsia risks. Conclusions This study demonstrates that various obesity measures are causally linked to increased HDP risk and highlights the mediating role of triglycerides. These findings could inform clinical practices and public health strategies aimed at reducing HDP through targeted obesity and triglyceride management.
Previous studies predominantly focused on single types of congenital birth defects (CBDs) or specific national prevalence. This study adopts a holistic perspective to assess current trends and health inequalities in birth incidence rate of various types of CBDs, providing novel insights to inform public health policy formulation. Global, socio-demographic index (SDI) regional, and country-specific estimates incidence cases and rate at birth of CBDs from 1990 to 2021 were derived from the Global Burden of Disease (GBD) 2021. Joinpoint analysis and autoregressive integrated moving average predictive models were employed to evaluate temporal trends in the birth incidence rate of CBDs for the period 2022-2031. Additionally, analysis of associations and health inequalities were conducted to examine the relationship between SDI and the birth incidence rate of CBDs across countries. Globally, the birth incidence rate decreased from 5811.17/100k population in 1990 to 5563.72/100k population in 2021, with low SDI regions recording the lowest rate and cases. Joinpoint analysis revealed a global decrease in the birth incidence rate of CBDs (average annual percentage change, AAPC: -0.14%, 95%CI: -0.15% to -0.12%). The most significant decline was observed in neural tube defects (NTD) (AAPC: -1.35%, 95%CI: -1.42% to -1.28%). However, only birth incidence rate of orofacial clefts (OC) is projected to decrease globally the next decade. Within the five SDI regions, the birth incidence rate of OC is also projected to decrease probably. The analysis revealed negative correlations between congenital heart anomalies (CHA), NTD, and SDI, with NTD showing both absolute and relative health inequalities. Despite the general decline in overall birth incidence rate of CBDs, projections suggested a probable increasing trend for all types except OC. This underscores the necessity for enhanced surveillance and intervention measures. Furthermore, the successful prevention policies implemented for NTD could serve as effective models for addressing other types of CBDs, thereby improving the current global situation of CBDs.
Abstract Background Although current treatments are effective in dealing with congenital heart disease (CHD), non‐cardiac comorbidities such as attention‐deficit hyperactivity disorder (ADHD) have received widespread attention. The purpose of this systematic review and meta‐analysis is to assess the risk of ADHD associated with CHD. Methods The literature search was carried out systematically through eight different databases by the end of September 2022. Either a fixed‐ or a random‐effects model was used to calculate the overall combined risk estimates. The heterogeneity of the studies was assessed by the Cochran Q test and the I 2 statistic. Subgroup and sensitivity analyses were used to explore the potential sources of heterogeneity. Results Eleven studies were included in this study, which involved a total of 296 741 participants. Our study showed that the children with CHD were at a significantly increased risk of ADHD compared with the reference group ( OR = 2.98, 95% CI : 2.18–4.08). The results were moderately heterogeneous. These factors including study design, geographic region and study quality were identified as the first three of the most relevant heterogeneity moderators by subgroup analyses. Sensitivity analysis yielded consistent results. There was no evidence of publication bias. Conclusions The present study suggests that CHD children have a significantly higher risk of ADHD when compared with those without CHD. Early identification and intervention of ADHD is important to reduce its symptoms and adverse effects; therefore, clinicians should increase screening for ADHD in children with CHD and intervene promptly to reduce its effects whenever possible.
Objective To evaluate the prevalence and associated factors of undernutrition among children with congenital heart disease (CHD) who have not undergone surgeries in China. Methods This cross-sectional study included 734 CHD children along with their parents. The outcome of interest was undernutrition, including underweight, wasting, and stunting, defined as Z-scores ( i.e., weight-for-age, weight-for-height, and height-for-age ) ≤−2, according to the World Health Organization (WHO) growth standard. Exposures of interest, containing demographics, obstetric factors, maternal dietary factors, parents' life behaviors and habits, birth-related factors, cardiac-related factors, and preoperative factors, were analyzed using a multivariate logistic regression model to test their associations with undernutrition in CHD children. Results Overall, 36.1%, 29.7%, and 21.3% of cases were underweight, wasted, and stunted, respectively. Multivariate logistic regression indicated that underweight was associated with demographic factors (including parents' occupational status, family income, and maternal body mass index pre-pregnancy), low birth weight (OR = 4.60, 2.76–7.70), pulmonary hypertension (OR = 4.46, 3.09–6.43), and pneumonia (OR = 1.88, 1.28–2.76). Artificially-fed children were 2.34 (1.36–4.01) times more likely to be underweight. Occupied mothers (OR = 0.62, 0.44–0.88) and fathers (OR = 0.49, 0.26–0.92) served as protective factors, while mothers having gestational complications (OR = 1.56, 1.11–2.18) and exposed to noisy environment (OR = 1.64, 1.11–2.42) during this pregnancy, and pulmonary hypertension (OR = 3.21, 2.30–4.49) increased the chance of wasting in offspring. The odds of being stunted were greater in families with >2 children (OR = 1.88, 1.13–3.14), placental abruption during this pregnancy (OR = 25.15, 2.55–247.89), preterm births (OR = 1.84, 1.02–3.31), low birth weight (OR = 3.78, 2.16–6.62), pulmonary hypertension (OR = 2.35, 1.56–3.53) and pneumonia (OR = 1.93, 1.28–2.90). In subgroup analyses, the associations differed between patients with different feeding patterns (breastfeeding vs. non-breastfeeding), CHD classifications (cyanotic vs . acyanotic), and prematurity (preterm vs . non-preterm). Conclusion Undernutrition is common in preoperative CHD children. Familial demographics, maternal factors (including having gestational complications and exposure to noisy environment during pregnancy), and patient-related factors (encompassing preterm births, low birth weight, pulmonary hypertension, pneumonia, and feeding pattern) were found to contribute to undernutrition in CHD cases. However, associated factors among the three subgroups of distinct feeding patterns, CHD categorization, and prematurity exhibited varied outcomes, suggesting the necessity for targeted interventions.
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