Genetic evidence linking retinol to birth weight: A two-sample Mendelian randomization study

Area of Science:

• Nutritional Epidemiology
• Maternal and Child Health
• Genetic Epidemiology

Background:

• Dietary antioxidant vitamins are crucial for maternal and fetal health.
• Previous observational studies suggest links between vitamins and pregnancy outcomes, but causal evidence is limited.
• Mendelian randomization (MR) offers a robust approach to infer causality using genetic variants.

Purpose of the Study:

• To investigate the potential causal effects of dietary antioxidant vitamins (retinol, vitamin C, carotene, vitamin E) on key pregnancy outcomes.
• Specifically examining associations with miscarriage, preterm labor, and birth weight.
• To provide evidence-based recommendations for prenatal vitamin supplementation.

Main Methods:

• Employed Mendelian randomization (MR) analysis using single-nucleotide polymorphisms (SNPs) as instrumental variables.
• Utilized summary statistics from large-scale genome-wide association studies (GWASs) for pregnancy outcomes.
• Applied inverse-variance weighted (IVW) method with sensitivity analyses (MR-RAPS, maximum likelihood) to ensure result robustness.

Main Results:

• A significant causal effect of retinol on birth weight was identified (β=0.091, P=0.028), supported by sensitivity analyses.
• No statistically significant causal associations were found between retinol and miscarriage or preterm labor.
• Carotene, vitamin E, and vitamin C showed no significant causal links to miscarriage, preterm labor, or birth weight.

Conclusions:

• Retinol intake has a causal impact on birth weight, highlighting the importance of adequate vitamin A levels during pregnancy.
• Maintaining normal retinol levels may be a viable strategy to prevent low birth weight.
• Monitoring and supplementing vitamin A in deficient pregnant women could improve overall pregnancy outcomes.