Low vitamin D in first trimester linked to higher preterm birth risk and reduced fetal length

By Dr. Priyom Bose, Ph.D. Reviewed by Danielle Ellis, B.Sc. Feb 7 2025

Findings suggest early pregnancy may be a critical window for maternal vitamin D in supporting fetal growth and reducing preterm birth risk Study: Maternal vitamin D status, fetal growth patterns, and adverse pregnancy outcomes in a multisite prospective pregnancy cohort. Image Credit: MVelishchuk/Shutterstock.com

A recent American Journal of Clinical Nutrition study investigated whether first and second-trimester maternal vitamin D levels are associated with fetal growth and pregnancy outcomes. Vitamin D status and pregnancy outcome

In an American survey, approximately 28% of pregnant or lactating women exhibited vitamin D deficiency. Several studies have indicated that inadequate maternal vitamin D status, i.e., below 50 nmol/L may lead to adverse pregnancy outcomes for both infant and mother. Vitamin D deficiency has been associated with an increased risk of gestational diabetes mellitus, preterm birth, and preeclampsia.

Vitamin D plays an important role in early pregnancy; for example, it is involved in the production of vascular endothelial growth factor and placental growth factor. These pro-angiogenic factors are crucial to regulating early vascularization of the placenta. Furthermore, vitamin D is extremely important for bone health and formation. Previous studies have associated maternal vitamin D status with birth weight and skeletal development.

Not many studies have investigated whether vitamin D status influences fetal growth patterns across gestation. Previous research has presented contradictory evidence on the efficacy of vitamin D supplements on improvement in maternal and neonatal outcomes. Therefore, it is important to assess the effects of vitamin D supplementation at different time points during pregnancy on maternal outcomes and fetal growth patterns.   About the study

The current longitudinal, observational study investigated the associations between first and second-trimester vitamin D status and fetal growth pattern, including gestational age at birth, small for gestational age (SGA), and risk of preterm birth.

All relevant data was obtained from a multicenter prospective cohort study- the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be (nuMoM2b). This US-based study included 10,038 nulliparous pregnant females. Pregnancy data and biospecimens were collected from participants in their first trimester, early second trimester, late second/early third trimester, and at delivery.

Since 25-hydroxyvitamin D (25(OH)D) was not originally measured for the nuMoM2b cohort. A total of 351 nuMoM2b participants were randomly selected to measure f25(OH)D for the current study. Fetal growth was measured by ultrasound at 16–21 and 22–29 weeks of gestation. In addition, neonatal anthropometric estimates were measured at birth. Fetal growth curves were constructed based on length, weight, and head circumference z-scores. Study findings

The mean age of the participants was 27.9 years, the mean length of gestation was 38.8 weeks, and the mean body mass index (BMI) was 26.6. Approximately 50% of the cohort had a bachelor’s degree, and the majority of them were non-Hispanic White. In comparison to older participants, younger women were more inclined to have vitamin D deficiency. Related StoriesVitamin D supplements during pregnancy strengthen children's bonesVitamin D may lower blood pressure in older people with obesityLow vitamin D associated with increased depression risk in pregnancy and after birth

Interestingly, participants who had a bachelor’s degree were found to be less likely to be vitamin D deficient, i.e., 25(OH)D <50 nmol/L. These participants exhibited a higher inclination to use multivitamin supplements. The mean 25(OH)D concentrations in the first and second trimesters were 68.1 nmol/L and 78.0 nmol/L, respectively.

In the first trimester, 20% of females had 25(OH)D concentrations below 50 nmol/L, while the majority exhibited 25(OH)D concentrations above 50 nmol/L. In the second trimester, 13% of females exhibited vitamin D deficiency, while 87% had 25(OH)D concentrations ≥50 nmol/L.

96% of the cohort had fetal growth measures for all three-time points, while the remaining 4% had measures for only two-time points. In the first trimester, associations between 25(OH)D and linear fetal growth were observed. However, vitamin D concentration was not associated with either weight or head circumference in adjusted models.

In the first trimester, each 10 nmol/L increase in 25(OH)D was associated with a 0.05 increase in length z-score after adjustment for confounders. Using Institute of Medicine (IOM) insufficiency cutoffs (<50 compared with ≥50 nmol/L), second trimester 25(OH)D was not associated with fetal growth trajectories for length, weight, or head circumference after adjusting for confounders.

Approximately 6% of the infants were born SGA, and 8% were born preterm. The current study assessed first trimester 25(OH)D continuously or by using IOM binary cutoffs; 25(OH)D concentration was not associated with risk for SGA or preterm birth.

In comparison with women with 25(OH)D >80 nmol/L, those with first trimester 25(OH)D levels below 40 nmol/L were found to be at 4.35 times higher risk of delivering a preterm infant, on average 1.17 weeks earlier. Second trimester 25(OH)D was not associated with SGA or preterm birth. Conclusions

The current study observed that first-trimester maternal vitamin D status is robustly associated with fetal growth patterns. Vitamin D deficiency in the first trimester was associated with a higher risk of shorter mean length of gestation and preterm birth. However, in the second trimester, vitamin D status was not associated with adverse pregnancy outcomes or changes in fetal growth patterns. In the future, researchers must uncover the mechanism by which vitamin D contributes to fetal growth. Journal reference: Beck, C. et al. (2025) Maternal Vitamin D Status, Fetal Growth Patterns, and Adverse Pregnancy Outcomes in a Multisite Prospective Pregnancy Cohort. The American Journal of Clinical Nutrition. 121(2), pp. 376-384. doi: https://doi.org/10.1016/j.ajcnut.2024.11.018.