Maternal vitamin D status, fetal growth patterns, and adverse pregnancy outcomes in a multisite prospective pregnancy cohort

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2025
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American English
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Abstract

Background: Few studies have examined maternal vitamin D status and fetal growth patterns across gestation. Furthermore, time points in pregnancy at which maternal vitamin D status is most critical for optimal fetal growth and pregnancy outcomes are uncertain.

Objectives: Our objective was to examine whether first and second trimester maternal vitamin D status are associated with fetal growth patterns and pregnancy outcomes.

Methods: We conducted a secondary analysis using data and samples from a multisite prospective cohort study of nulliparous pregnant females in the United States. We measured serum 25-hydroxyvitamin D (25(OH)D) for 351 participants at 6-13 and 16-21 weeks of gestation. Fetal growth was measured by ultrasound at 16-21 and 22-29 weeks of gestation, and neonatal anthropometric measures at birth. We constructed fetal growth curves using length, weight, and head circumference z-scores, and calculated risk of preterm birth (<37 wk) and small for gestational age (SGA). We examined outcomes across 25(OH)D concentrations assessed continuously, using Institute of Medicine (IOM) cutoffs (<50 compared with ≥50 nmol/L), and using exploratory cutoffs (<40, 40-59.9, 60-79.9, ≥80 nmol/L).

Results: Vitamin D insufficiency (25(OH)D <50 nmol/L) was prevalent in 20% of participants in the first trimester. Each 10 nmol/L increase in first trimester 25(OH)D was associated with a 0.05 [95% confidence interval (CI): 0.01, 0.10] increase in length-for-age z-score but was not associated with weight or head circumference. There were no differences in risk of preterm birth or SGA using IOM cutoffs; participants with first trimester 25(OH)D <40 compared with ≥80 nmol/L had 4.35 (95% CI: 1.14, 16.55) times risk of preterm birth. Second trimester 25(OH)D was not associated with fetal growth patterns or with pregnancy outcomes.

Conclusions: First trimester 25(OH)D is positively associated with linear growth. Low first trimester 25(OH)D (<40 nmol/L) is associated with a higher risk of preterm birth. Second trimester 25(OH)D is not associated with fetal growth or pregnancy outcomes assessed.

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Beck C, Blue NR, Silver RM, et al. Maternal vitamin D status, fetal growth patterns, and adverse pregnancy outcomes in a multisite prospective pregnancy cohort. Am J Clin Nutr. 2025;121(2):376-384. doi:10.1016/j.ajcnut.2024.11.018
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The American Journal of Clinical Nutrition
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