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Circulating 25-Hydroxyvitamin D Levels During Pregnancy and Risk of Congenital Heart Diseases: Multivariable and
Karen Christina Walker1, Ina O Specht1,2, Vibeke Hjortdal3
1The Parker Institute, Research Unit for Dietary studies Bispebjerg and Frederiksberg Hospital Frederiksberg Denmark.
Journal of the American Heart Association
|May 2, 2025
Summary
Maternal vitamin D levels during pregnancy do not appear to causally impact offspring congenital heart disease (CHD) risk. This study found no robust evidence linking 25-hydroxyvitamin D (25(OH)D) to CHD prevention.
Area of Science:
- Reproductive Health
- Pediatrics
- Nutritional Science
Background:
- Congenital heart disease (CHD) prevention is crucial, necessitating identification of modifiable risk factors.
- Previous research suggested a link between maternal 25-hydroxyvitamin D (25(OH)D) and offspring CHD, but with methodological limitations.
- This study addresses these limitations by investigating the association using advanced analytical methods.
Purpose of the Study:
- To examine the relationship between maternal 25-hydroxyvitamin D (25(OH)D) levels during pregnancy and the risk of congenital heart disease (CHD) in offspring.
- To differentiate between observational associations and potential causal effects using multivariable regression (MVR) and Mendelian randomization (MR) analyses.
Main Methods:
- Utilized data from three large cohorts: ALSPAC, BiB, and MoBa (N=8722 for MVR, N=74,953 for MR).
- Employed multivariable regression (MVR) adjusted for key confounders and one-sample Mendelian randomization (MR) using a genetic risk score for 25(OH)D.
- Conducted meta-analysis of pooled results and examined consistency between MVR and MR findings.
Main Results:
- Pooled MVR analysis indicated a potential inverse association between maternal 25(OH)D and CHD risk, though confidence intervals were wide and included the null.
- Mendelian randomization analysis, designed to infer causality, did not support a significant relationship between genetically predicted 25(OH)D and CHD risk.
- Results from MVR and MR analyses showed a lack of robust evidence for a causal link.
Conclusions:
- This study found no robust evidence to support a causal effect of maternal 25-hydroxyvitamin D (25(OH)D) levels during pregnancy on offspring congenital heart disease (CHD) risk.
- The findings suggest that vitamin D supplementation during pregnancy may not be a viable strategy for CHD prevention based on current evidence.
- Further research may be needed to explore other potential risk factors or refine the understanding of vitamin D's role in fetal development.
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