Vitamin D deficiency in pregnancy and the risk of preterm birth: a nested case-control study

Abstract Background: Each year, an estimated 15 million babies are born preterm. Micronutrient deficiencies, including vitamin D deficiency, are common in many low- and middle-income countries (LMICs), and these conditions are often associated with adverse pregnancy outcomes. Bangladesh experiences a high prevalence of vitamin D deficiency. The country also has a high preterm birth (PTB) rate. Using data from a population-based pregnancy cohort, we estimated the burden of vitamin D deficiency during pregnancy and its effect on PTB. Methods: Pregnant women (N=3,000) were enrolled after ultrasound confirmation of gestational age at 8-19 weeks of gestation. Trained health workers prospectively collected detailed phenotypic and epidemiological data at scheduled home visits. Trained phlebotomists collected maternal blood samples at enrollment and at 24 -28 weeks of gestation. Aliquots of serum were stored at -800 C. We conducted a nested case-control study, with all PTB (n=262) and a random sample of term births (n=668). We used the following data: vitamin D concentrations of 24-28 weeks maternal blood samples, ultrasound-determined gestational age, data on pregnancy outcomes, and other PTB risk factors data. PTB was defined as the birth of a baby <37 weeks of gestation. Women were categorized as vitamin D deficient (lowest quartile of 25(OH)D; <=30.18 nmol/L) or not deficient (upper-three quartiles of 25(OH)D; >30.18 nmol/L). We used logistic regression to determine the effect of vitamin D deficiency on PTB, adjusting for potential confounders. Results: The median and interquartile range of serum 25(OH)D was 38.0 nmol/L; 30.18 to 48.52 (nmol/L). After adjusting for co-variates, serum 25(OH)D deficiency was significantly associated with PTB [adjusted odds ratio (aOR) = 1.47, 95% confidence interval (CI) = 1.06 – 2.04]. The risk of PTB was also higher in primiparous women (aOR = 1.54, 95% CI = 1.12 – 2.12), passive smokers (aOR = 1.55, 95% CI = 1.06 – 2.26), and those who didn’t receive iron supplementation during pregnancy (aOR, 95% CI: 0.59, 0.41- 0.83). Conclusion: Vitamin D deficiency is common in Bangladeshi pregnant women, and these women experience an increased risk of PTB. Improving maternal vitamin D status during pregnancy may significantly reduce the risk of PTB.