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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.

Objective: To assess the association of conventional semen parameters and sperm DNA fragmentation with risk of recurrent spontaneous abortion (RSA). Design: Systematic review and meta-analysis. Setting: Not applicable. Patient(s): Total 1,690 male partners of women with RSA, and 1,337 male partners of fertile control women. Intervention(s): Case-control or cohort studies were determined by searching PubMed, Google Scholar, Cochrane Libraries, China Biology Medicine disc, Chinese Scientific Journals Fulltext Database, China National Knowledge Infrastructure, and Wanfang Database. RSA was defined as two or more previous pregnancy losses. The fertile women refer to the reproductive women who have had at least a normal pregnancy history and no history of abortion. Main Outcome Measure(s): This study included eight outcome measures: semen volume(ml), semen pH value, sperm density(10 6 /ml), sperm viability (%), sperm progressive motility rate (%), normal sperm morphology rate (%), sperm deformity rate(%), sperm DNA fragmentation index (DFI) (%). The summary measures were reported as standardized mean difference (SMD) with 95% confidence interval (CI). Result(s): Finally, twenty-four studies were included for analysis. Overall, male partners of women with RSA had a significantly lower level of sperm density (SMD = -0.53, 95%CI: – 0.75 to –0.30), sperm viability (SMD = -1.03, 95%CI: – 1.52 to –0.54), sperm progressive motility rate (SMD = -0.76, 95%CI:-1.06 – -0.46), and normal sperm morphology rate (SMD =  –0.56, 95%CI: – 0.99 to –0.12), and had a significantly higher rate of sperm deformity rate (SMD = 1.29, 95%CI: 0.60 – 1.97), and sperm DFI (SMD = 1.60, 95%CI: 1.04 to 2.17), when compared with the reference group. However, there were no statistically significant differences for semen volume (SMD = -0.03, 95%CI: -0.14 – 0.08) and semen pH value (SMD =  –0.23, 95% CI: –0.50 to 0.05) among 2 groups. Conclusion(s): The results of this analysis support an association of sperm density, sperm viability, sperm progressive motility rate, normal sperm morphology rate, sperm deformity rate, as well as sperm DFI with RSA. However, given the significant heterogeneity between studies and the lack of more detailed data on the subjects, further large-scale prospective studies are needed.

Background. Congenital heart disease (CHD) is one of the most common birth defects among newborns, accounting for a large proportion of infant mortality worldwide. However, the mechanisms remain largely undefinable. This study aimed to investigate the association of CHD in offspring of mothers with diabetes mellitus (DM) and single nucleotide polymorphisms (SNPs) of NKX2.5. Methods and Results. A case-control study of 620 mothers of CHD patients and 620 mothers of healthy children admitted to Hunan Children’s Hospital from November 2017 to December 2019 was conducted. We collected the mothers’ information by questionnaire and detected children’s NKX2.5 variants with a MassARRAY system. The interaction coefficient (γ) was used to quantify the estimated gene-environment interactions. Univariate and multivariate analyses both showed that the infants had a higher risk of CHD if their mothers had a history of DM, including gestational DM (GDM) during this pregnancy (adjusted odds ratio [aOR=4.98]), GDM in previous pregnancies (aOR=4.30), and pregestational DM (PGDM) in the 3 months before this pregnancy (aOR=6.78). Polymorphisms of the NKX2.5 gene at rs11802669 (C/C vs. T/T: aOR=4.97; C/T vs. T/T: aOR=2.15) and rs2277923 (T/T vs. C/C, aOR=1.74; T/C vs. C/C, aOR=1.61) were significantly associated with the risk of CHD in offspring. In addition, significant interactions between maternal DM and NKX2.5 genetic variants at rs11802669 (aOR=8.12) and rs2277923 (aOR=17.72) affecting the development of CHD were found. Conclusions. These results suggest that maternal DM, NKX2.5 genetic variants, and their interactions are significantly associated with the risk of CHD in offspring.

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