孕期循环25-羟维生素D水平与先天性心脏病风险：使用3个出生队列的多变量和孟德尔随机化分析

Circulating 25-Hydroxyvitamin D Levels During Pregnancy and Risk of Congenital Heart Diseases: Multivariable and Mendelian Randomization Analyses Using 3 Birth Cohorts.

作者信息

Walker Karen Christina, Specht Ina O, Hjortdal Vibeke, Christesen Henrik T, Heitmann Berit L, Santorelli Gillian, West Jane, Magnus Per, Njølstad Pål R, Corfield Elizabeth C, Havdahl Alexandra, Magnus Maria, Taylor Kurt, Lawlor Deborah A

机构信息

The Parker Institute, Research Unit for Dietary studies Bispebjerg and Frederiksberg Hospital Frederiksberg Denmark.

The Research Unit for General Practice and Section of General Practice, Department of Public Health University of Copenhagen Denmark.

出版信息

J Am Heart Assoc. 2025 May 6;14(9):e036273. doi: 10.1161/JAHA.124.036273. Epub 2025 May 2.

DOI:10.1161/JAHA.124.036273

PMID:40314341

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12184255/

Abstract

BACKGROUND

Identifying modifiable risk factors for congenital heart disease (CHD) is important for prevention. Previous studies have reported associations between 25-hydroxyvitamin D (25(OH)D) in pregnancy and CHD in the offspring. However, these studies contain important methodological limitations. We aimed to investigate 25(OH)D levels during pregnancy in relation to offspring risk of CHD using both multivariable regression (MVR) analysis and Mendelian randomization (MR) analysis.

METHODS

Data from the ALSPAC (Avon Longitudinal Study of Parents and Children), BiB (Born in Bradford), and MoBa (Norwegian Mother, Father and Child Cohort) studies (N=8722 (77 cases) for MVR analysis, N=74 953 (646 cases) for MR) were used. MVR analysis was adjusted for offspring sex, maternal age, education, body mass index, smoking, alcohol consumption, and parity. One sample MR was performed with weighted genetic risk score for 25(OH)D based on published genome-wide significant genetic variants. Sensitivity analyses explored the relevance and validity of the genetic risk score. Results were pooled across the 3 cohorts in a meta-analysis with random effects and consistency between results from the MVR and MR was examined.

RESULTS

Pooled results from the adjusted MVR suggested higher maternal pregnancy 25(OH)D associated with lower CHD risk, though the CIs were wide and included the null (odds ratio [OR], 0.79 [95% CI, 0.53, 1.06] per 1 SD higher 25(OH)D). By contrast precise MR results did not support a causal relationship (OR, 0.99 [95% CI, 0.91, 1.07] per 1 SD higher 25(OH)D genetic risk score).

CONCLUSIONS

We did not find robust evidence supporting an effect of maternal pregnancy 25(OH)D levels on offspring CHD.

摘要

背景

确定先天性心脏病（CHD）的可改变风险因素对预防至关重要。先前的研究报道了孕期25-羟维生素D（25(OH)D）与后代CHD之间的关联。然而，这些研究存在重要的方法学局限性。我们旨在使用多变量回归（MVR）分析和孟德尔随机化（MR）分析来研究孕期25(OH)D水平与后代患CHD风险的关系。

方法

使用了来自ALSPAC（阿冯父母与儿童纵向研究）、BiB（布拉德福德出生队列）和MoBa（挪威母亲、父亲和儿童队列）研究的数据（MVR分析n = 8722（77例），MR分析n = 74953（646例））。MVR分析对后代性别、母亲年龄、教育程度、体重指数、吸烟、饮酒和产次进行了调整。基于已发表的全基因组显著遗传变异，对25(OH)D进行了单样本MR加权遗传风险评分。敏感性分析探讨了遗传风险评分的相关性和有效性。在随机效应的荟萃分析中汇总了3个队列的结果，并检验了MVR和MR结果之间的一致性。

结果

调整后的MVR汇总结果表明，母亲孕期25(OH)D水平越高，CHD风险越低，尽管置信区间较宽且包含无效值（每增加1个标准差25(OH)D，优势比[OR]为0.79[95%置信区间，0.53，1.06]）。相比之下，精确的MR结果不支持因果关系（每增加1个标准差25(OH)D遗传风险评分，OR为0.99[95%置信区间，0.91，1.07]）。