Post-hoc analysis of vitamin D status and reduced risk of preterm birth in two vitamin D pregnancy cohorts compared with South Carolina March of Dimes 2009–2011 rates

BACKGROUND Two vitamin D pregnancy supplementation trials were recently undertaken in South Carolina: The NICHD (n=346) and Thrasher Research Fund (TRF, n=163) studies. The findings suggest increased dosages of supplemental vitamin D were associated with improved health outcomes of both mother and newborn, including risk of preterm birth (<37 weeks gestation). How that risk was associated with 25(OH)D serum concentration, a better indicator of vitamin D status than dosage, by race/ethnic group and the potential impact in the community was not previously explored. While a recent IOM report suggested a concentration of 20 ng/mL should be targeted, more recent work suggests optimal conversion of 25(OH)D-1,25(OH)2D takes place at 40 ng/mL in pregnant women. OBJECTIVE Post-hoc analysis of the relationship between 25(OH)D concentration and preterm birth rates in the NICHD and TRF studies with comparison to Charleston County, South Carolina March of Dimes (CC-MOD) published rates of preterm birth to assess potential risk reduction in the community. METHODS Using the combined cohort datasets (n=509), preterm birth rates both for the overall population and for the subpopulations achieving 25(OH)D concentrations of ≤20 ng/mL, >20 to <40 ng/mL, and ≥40 ng/mL were calculated; subpopulations broken down by race/ethnicity were also examined. Log-binomial regression was used to test if an association between 25(OH)D serum concentration and preterm birth was present when adjusted for covariates; locally weighted regression (LOESS) was used to explore the relationship between 25(OH)D concentration and gestational age (weeks) at delivery in more detail. These rates were compared with 2009-2011 CC-MOD data to assess potential risk reductions in preterm birth. RESULTS Women with serum 25(OH)D concentrations ≥40 ng/mL (n=233) had a 57% lower risk of preterm birth compared to those with concentrations ≤20 ng/mL [n=82; RR=0.43, 95% confidence interval (CI)=0.22,0.83]; this lower risk was essentially unchanged after adjusting for covariates (RR=0.41, 95% CI=0.20,0.86). The fitted LOESS curve shows gestation week at birth initially rising steadily with increasing 25(OH)D and then plateauing at ∼40 ng/mL. Broken down by race/ethnicity, there was a 79% lower risk of preterm birth among Hispanic women with 25(OH)D concentrations ≥40 ng/mL (n=92) compared to those with 25(OH)D concentrations ≤20 ng/mL (n=29; RR=0.21, 95% CI=0.06,0.69) and a 45% lower risk among Black women (n=52 and n=50; RR=0.55, 95% CI=0.17,1.76). There were too few white women with low 25(OH)D concentrations for assessment (n=3). Differences by race/ethnicity were not statistically significant with 25(OH)D included as a covariate. Compared to the CC-MOD reference group, women with serum concentrations ≥40 ng/mL in the combined cohort had a 46% lower rate of preterm birth overall (n=233, p=0.004) with a 66% lower rate among Hispanic women (n=92, p=0.01) and a 58% lower rate among black women (n=52, p=0.04). CONCLUSIONS In this post-hoc analysis, achieving a 25(OH)D serum concentration ≥40 ng/mL significantly decreased the risk of preterm birth compared to ≤20 ng/mL. These findings suggest the importance of raising 25(OH)D levels substantially above 20 ng/mL; reaching 40 ng/mL during pregnancy would reduce the risk of preterm birth and achieve the maximal production of the active hormone.