Maternal Vitamin D Status and Spontaneous Preterm Birth by Placental Histology in the US Collaborative Perinatal Project

Lisa M. Bodnar; Mark A. Klebanoff; Alison D. Gernand; Robert W. Platt; W. Tony Parks; Janet M. Catov; Hyagriv N. Simhan.


Am J Epidemiol. 2014;179(2):168-176. 

In This Article

Abstract and Introduction


The objective of this study was to determine the association between maternal 25-hydroxyvitamin D (25(OH)D) and the risk of spontaneous preterm birth (sPTB) before 35 weeks' gestation. A random subcohort from the US Collaborative Perinatal Project (1959–1965) was sampled (n = 2,629) and augmented with all remaining cases of sPTB before 35 weeks' gestation for a total of 767 cases. Banked serum samples collected at 26 weeks' gestation or earlier were assayed for 25(OH)D. Constructs for vascular histology and inflammatory histology were developed from placental pathology examinations. There was no relationship between 25(OH)D and sPTB among white women. Among nonwhite mothers, serum 25(OH)D levels of 30–<50, 50–<75, and ≥75 nmol/L were associated with reductions of 1.0–1.6 cases of sPTB per 100 live births and 20%–30% reductions in risk of sPTB compared with 25(OH)D levels less than 30 nmol/L after adjustment for prepregnancy body mass index (weight (kg)/height (m)2), season, and other confounders. This association was driven by inflammation-mediated cases of sPTB and sPTB cases without placental lesions. A sensitivity analysis for unmeasured confounding by exercise, fish intake, and skin color suggested some bias away from the null in the conventional results, but conclusions were generally supported. The vitamin D–sPTB relationship should be examined in modern cohorts with detailed data on skin pigmentation and other covariates.


Preterm birth is the most important problem in modern obstetrics. In 2010, more than 1 million infants born preterm (at less than 37 weeks of gestation) died worldwide, making it the second leading cause of death in children under the age of 5 years.[1] Preterm infants who survive are at risk of chronic lung disease, deafness, blindness or other visual impairment, and learning and cognitive disabilities.[1] The 12% rate of preterm birth in the United States ranks 131st of 184 countries, behind many developing nations.[1] The past 3 decades in the United States have seen little decline in preterm births, including the earliest deliveries, which cause the most morbidity and mortality.[2,3] Identifying potential targets for preterm birth prevention is a public health priority.[1,3]

Recently, maternal vitamin D deficiency has been linked to adverse pregnancy outcomes, including preeclampsia and fetal growth restriction,[4] and also may be important in preterm birth. Vitamin D is a prohormone that is either ingested orally or produced photochemically in the skin. It affects established physiological pathways in the pathogenesis of preterm birth, including inflammation, immunomodulation, and transcription of genes involved in placental function.[5–7] Vitamin D deficiency is common in pregnant women and, like preterm birth,[2] is substantially more frequent among non-Hispanic black mothers.[8,9] Nevertheless, little research has been done to explore the relationship between maternal vitamin D status and the risk of preterm birth.

Our objective was to determine the association between maternal vitamin D deficiency at 26 weeks' gestation or earlier and the risk of spontaneous preterm birth (sPTB) before 35 weeks overall and by placental histology.