This study aimed to examine the risk of macrosomia and large for gestational age (LGA) births in relation to maternal pre-pregnancy body mass index (BMI) status mediated through gestational diabetes mellitus (GDM). This prospective study included 34,104 singleton pregnancies at 8–14 weeks of gestation. The interesting outcomes were macrosomia (≥4000 g) and LGA (≥90th percentile). Mediation analyses were conducted using log-binomial regression adjusted for age, education, parity, fetal sex, and gestational weight gain. The proportion mediated was estimated based on the risk difference scale, and the E-value was utilized to assess potential confounders. Overall, 15.9% of women had GDM, and there were 4.0% macrosomia and 9.9% LGA births. The proportion mediated by GDM on macrosomia was up to 40% among obese women, and the estimate of the total effect was 6.18 (95% CI: 5.26–7.26), of the natural direct effect was 4.10 (95% CI: 3.35–4.99), and of the natural indirect effect was 1.51 (95% CI: 1.31–1.76). Likewise, among overweight women, the proportion mediated by GDM on macrosomia was up to 40%. Furthermore, consistent findings were evident for the outcome of LGA births. Pre-pregnancy overweight/obesity increased the risk of macrosomia and LGA births independently and partly mediated by GDM.

The purpose of this study is to investigate whether the link between pre-pregnancy overweight/obesity and risk of macrosomia is mediated by both gestational diabetes mellitus (GDM) and high maternal triglyceride (mTG) levels. This prospective study finally included 29,415 singleton term pregnancies. The outcome of interest was macrosomia (≥4000 g). High mTG levels were denoted as values ≥90th percentile. GDM was diagnosed using a standard 75 g 2 h oral glucose tolerance test. The mediation analysis was conducted using log-binomial regression while controlling for maternal age, education, parity, gestational weight gain, gestational hypertension, smoking, drinking and infant sex. Overall, 15.9% of pregnant women were diagnosed with GDM, and 4.3% were macrosomia. Mediation analysis suggested that overweight had a total effect of 0.009 (95% CI, 0.006–0.013) on macrosomia, with a direct effect of 0.008 (95% CI, 0.004–0.012) and an indirect effect of 0.001 (95% CI, 0.001–0.002), with an estimated proportion of 11.1% mediated by GDM and high mTG levels together. Furthermore, we also discovered a total effect of obesity on macrosomia of 0.038 (95% CI, 0.030–0.047), consisting of a direct effect of 0.037 (95% CI, 0.028–0.045) and an indirect effect of 0.002 (95% CI, 0.001–0.002), with an estimated proportion of 5.3% mediated by GDM and high mTG levels combined. Both GDM and high mTG levels enhanced the risk of macrosomia independently and served as significant mediators in the relationship between pre-pregnancy overweight/obesity and macrosomia.

Preeclampsia (PE) is a common and serious pregnancy-specific disorder, which is closely linked with adverse maternal and neonatal outcomes. This study aimed to evaluate whether maternal pre-pregnancy body mass index (BMI) and gestational weight gain (GWG) was associated with preeclampsia and its phenotypes. In this prospective study, 32,531 women with singleton pregnancies were finally included. Compared with women with normal pre-pregnancy BMI, women with overweight and obesity were at increased risk of PE (RR = 1.62, 95%CI: 1.57–1.66; RR = 2.04, 95%CI: 1.97–2.11, respectively), while those who were underweight had a lower risk of PE (RR = 0.84, 95%CI: 0.81–0.88). When compared with women who gained adequate GWG, pregnant women with inadequate GWG and excessive GWG had an increased risk of PE (RR = 1.15, 95%CI: 1.12–1.19; RR = 1.56, 95%CI: 1.52–1.60, respectively). The observed increased risk was generally similar for mild-, severe-, early- and late-onset PE, and the reduced risk was similar for severe- and late-onset PE. No significant interactions between GWG and pre-pregnancy BMI on the risk of PE were identified (p-interaction > 0.05). In conclusion, pre-pregnancy overweight or obesity and excessive GWG have established risk factors for PE, and that the potential risk may vary according to PE phenotypes. Moreover, the synergistic effect that may exist between pre-pregnancy BMI and GWG.

This study aimed at examining the risk of macrosomia, in relation to maternal pre-pregnancy overweight/obesity mediated via high maternal triglyceride (mTG) levels. In this prospective study, 24,730 singleton term non-diabetic pregnancies were finally included. Serum mTG levels were measured using fasting blood samples that were collected after 28 weeks of gestation. High mTG levels were defined as values ≥ the 90th percentile. The outcome of interest was macrosomia (≥4000 g). Log-binomial regression was used to assess the mediation path between overweight/obesity, high mTG levels, and macrosomia. The mediation analysis found a total effect of overweight on macrosomia of 0.006 (95% CI, 0.001–0.010), including a direct effect of 0.005 (95% CI, 0.001, 0.009) and indirect effect of 0.001 (95% CI, 0.000–0.001), with an estimated proportion of 11.1% mediated by high mTG levels. Additionally, we also found a total effect of obesity on macrosomia of 0.026 (95% CI, 0.018–0.036), including a direct effect of 0.025 (95% CI, 0.017–0.036) and indirect effect of 0.001 (95% CI, 0.000–0.001), with an estimated proportion of 3.8% mediated by high mTG levels. In conclusion, non-diabetic women with overweight or obesity had an increased risk of macrosomia, and this positive association was partly mediated by high mTG levels.

This study attempted to learn the association between maternal betaine-homocysteine methyltransferase (BHMT) gene polymorphisms, maternal dietary habits, and their interactions with the risk of ventricular septal defects (VSD) in offspring. A total of 426 mothers of VSD children and 740 control mothers were included in the study. Logistic regression was used to evaluate the level of associations and interaction effects. Our study suggested that mothers reporting excessive intake of smoked foods (aOR = 2.44, 95%CI: 1.89–3.13), barbecued foods (aOR = 1.86, 95%CI: 1.39–2.48), fried foods (aOR = 1.93, 95%CI: 1.51–2.46), and pickled vegetables (aOR = 2.50, 95%CI: 1.92–3.25) were at a significantly higher risk of VSD in offspring, instead, mothers reporting regular intake of fresh fruits (aOR = 0.47, 95%CI: 0.36–0.62), fish and shrimp (aOR = 0.35, 95%CI: 0.28–0.44), fresh eggs, (aOR = 0.56, 95%CI: 0.45–0.71), beans (aOR = 0.68, 95%CI: 0.56–0.83), and milk products (aOR = 0.67, 95%CI: 0.56–0.80) were at a lower risk of VSD in offspring. In addition, maternal BHMT gene polymorphisms at rs1316753 (CG vs. CC: aOR = 2.01, 95%CI: 1.43–2.83) and rs1915706 (CT vs. TT: (aOR = 1.81, 95%CI: 1.33–2.46) were significantly associated with increased risk of VSD in offspring. Furthermore, a significant interaction between BHMT polymorphisms and maternal bean intake was identified in the study. In conclusion, Maternal BHMT polymorphisms at rs1316753 and rs1915706, dietary habits as well as their interaction were observed to be significantly associated with the risk of VSD in offspring.