25-Hydroxyvitamin D Deficiency in the First Trimester Is Associated with Increased Obstetric Complications despite Standard Supplementation during Pregnancy

BACKGROUND: Vitamin D deficiency during pregnancy has been linked to adverse maternal-fetal outcomes. However, it remains unclear whether standard supplementation mitigates risks equally in patients with differing baseline 25-hydroxyvitamin D [25(OH)D3] levels.

OBJECTIVES: The objective of this study was to determine whether differences exist in obstetric outcomes and pregnancy-related disorders among patients with different levels of 25(OH)D3 in the first trimester who receive standard supplementation.

DESIGN: This retrospective comparative cohort study involves pregnant women aged 16-50 years who received prenatal care at a semiprivate hospital in Northeastern México between January 2022 and December 2024.

PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants were grouped based on first-trimester serum 25(OH)D3 levels (≥30 ng/mL vs. <30 ng/mL), all receiving standard 25(OH)D3 supplementation (4,000 IU/day). For comparisons between groups, we performed independent samples t-tests or Mann-Whitney U tests for quantitative variables and chi-square tests for qualitative variables. A multivariate logistic regression analysis was conducted to identify predictors of adverse obstetric outcomes.

RESULTS: A total of 303 women (mean [standard deviation] age 29.3 [5.4] years) were analyzed, divided almost equally between first-trimester 25(OH)D3 deficient group (n = 151) and the sufficient group (n = 152), with similar baseline characteristics. Although insufficient 25(OH)D3 women reached sufficiency during the second and third trimesters, sufficient women maintained significantly higher serum 25(OH)D3 levels throughout pregnancy (p < 0.001) and had lower rates of preeclampsia (1.3% vs. 10.6%, p < 0.001), gestational diabetes (8.6% vs. 24.5%, p < 0.001), preterm labor (0% vs. 5.3%, p = 0.003), urinary tract infections (4.6% vs. 14.6%, p = 0.003), and bacterial vaginosis (3.9% vs. 13.2%, p = 0.004). Logistic regression confirmed first-trimester 25(OH)D3 sufficiency as independently protective against adverse outcomes (OR = 0.21, 95% CI: 0.10-0.43, p < 0.001).

CONCLUSIONS: First-trimester 25(OH)D3 sufficiency was associated with reduced risk of obstetric complications, compared with women with insufficiency, even when the last achieved sufficiency in the second and third trimester. These findings highlight the importance of early screening and support the need for personalized supplementation strategies before conception to optimize maternal-fetal outcomes.