Background: The association between educational attainment (EA) and offspring birth weight (BW) has been reported by several traditional epidemiological studies. However, evidence for this association tends to be mixed and confounded. This study aimed to investigate the causal association between EA of parents and offspring BW.Methods: Here, we carried out a two-sample bidirectional Mendelian randomization (MR) analysis to examine the causal association between EA of males (n = 131,695) and females (n = 162,028) and offspring BW using genetic instruments. Summary statistics of EA associated single nucleotide polymorphisms (SNPs) were extracted from a GWAS incorporating 293,723 individuals of European descent performed by the Social Science Genetic Association Consortium (SSGAC), and the effects of these SNPs on offspring BW were estimated using a GWAS meta-analysis of 86,577 participants of European descent from 25 studies. Univariable MR analyses were conducted using the inverse-variance weighted (IVW) method and four other methods. Further sensitivity analyses were carried out to test the viability of the results. Multivariable MR was used to examine the confounders between the exposure and outcome.Results: The result shows evidence that the offspring BW is positively causally affected by female EA. Each one standard deviation (SD) increase in female EA was associated with 0.24 SD higher of offspring BW (95% confidence interval [CI], 0.10 to 0.37, p < 0.001 for the IVW method). Similarly, change in offspring BW was 0.21 SD (95% CI: 0.07 to 0.34, p = 2.82 × 10–3) per one SD higher in male EA. No causal effect of BW on EA was found by any of the five methods. The causal association between female EA and offspring BW maintained after adjusting for alcoholic drinks per week and BMI. The effect of male EA on offspring BW was attenuated when we adjusted for BMI and alcoholic drinks per week using multivariable MR analysis.Conclusion: Our study indicated that female EA is positively causally associated with offspring BW. The association between male EA and offspring BW may be confounded by alcoholic drinks per week and BMI.
Background: Macrosomia is a serious public health problem worldwide, the underlying etiology and mechanism of macrosomia born to healthy mothers are still unclear. Abnormal lipid transport during pregnancy exerts potential and adverse impacts on fetus, our study aimed to assess associations between macrosomia and placental expression levels of lipid transport-related genes and umbilical cord blood lipid concentrations in healthy pregnancy.Methods: We conducted a case-control study of 38 macrosomia and 39 normal-birth-weight newborns in healthy pregnancy. Cord blood lipid levels were measured by automatic biochemical analyzer, mRNA and protein expression levels of placental lipid transport-related factors were determined by real-time polymerase chain reaction and western blot, respectively. Results: The single factor analysis showed that placental mRNA and protein expression levels of PPARα, PPARγ, FABPpm, LXRα, FABP3, FABP4 and FAT/CD36 were significantly higher and cord blood total cholesterol, low-density lipoprotein cholesterol, and non-esterified fatty acid (NEFA) concentrations were significantly lower in macrosomia group. Further analysis found that placental PPARγ, FABP4 and FABP3 mRNA expression levels were positively correlated with high-density lipoprotein cholesterol, NEFA and triglycerides concentrations in macrosomia cord blood, respectively. After multivariate adjustment, the logistic regression analysis showed that high placental PPARα (AOR=3.022; 95%CI:1.032-8.853) and FAT/CD36 (AOR=2.989; 95%CI:1.029-8.679) expression increased the risk of delivering macrosomia. Conclusions: The increase of PPARα and FAT/CD36 mRNA expression levels is associated with the occurrence of macrosomia, suggesting that they may be important regulators during placental lipid transport in macrosomia.
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