title: 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.
abstract: 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.
authors.affiliation: Medical University of South Carolina Children's Hospital, Charleston, SC, USA. Electronic address: wagnercl@musc.edu.
authors.forename: C L
authors.initials: CL
authors.lastname: Wagner
authors.affiliation: GrassrootsHealth, Encinitas, CA, USA.
authors.forename: C
authors.initials: C
authors.lastname: Baggerly
authors.affiliation: GrassrootsHealth, Encinitas, CA, USA.
authors.forename: S
authors.initials: S
authors.lastname: McDonnell
authors.affiliation: Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: K A
authors.initials: KA
authors.lastname: Baggerly
authors.affiliation: GrassrootsHealth, Encinitas, CA, USA.
authors.forename: C B
authors.initials: CB
authors.lastname: French
authors.affiliation: GrassrootsHealth, Encinitas, CA, USA.
authors.forename: L
authors.initials: L
authors.lastname: Baggerly
authors.affiliation: Eau Claire Cooperative Health Centers, Columbia, SC, USA.
authors.forename: S A
authors.initials: SA
authors.lastname: Hamilton
authors.affiliation: Medical University of South Carolina Children's Hospital, Charleston, SC, USA.
authors.forename: B W
authors.initials: BW
authors.lastname: Hollis
mesh_terms: D000293:Adolescent; D000328:Adult; D001741:Black or African American; D002986:Clinical Trials as Topic; D015331:Cohort Studies; D019587:Dietary Supplements; D005260:Female; D006630:Hispanic or Latino; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D007752:Obstetric Labor, Premature / Q000097:blood* / Q000453:epidemiology / Q000208:ethnology / Q000517:prevention & control; D011247:Pregnancy; D012044:Regression Analysis; D012306:Risk; D013022:South Carolina; D014807:Vitamin D / Q000097:blood*; D014808:Vitamin D Deficiency / Q000097:blood* / Q000453:epidemiology / Q000208:ethnology / Q000517:prevention & control; D044465:White People
chemical_list: D014807:Vitamin D
keywords: Cholecalciferol; March of Dimes; Pregnancy health outcomes; Preterm birth; Vitamin D