Research Article: Maternal 25(OH)D concentrations ≥40 ng/mL associated with 60% lower preterm birth risk among general obstetrical patients at an urban medical center

Date Published: July 24, 2017

Publisher: Public Library of Science

Author(s): Sharon L. McDonnell, Keith A. Baggerly, Carole A. Baggerly, Jennifer L. Aliano, Christine B. French, Leo L. Baggerly, Myla D. Ebeling, Charles S. Rittenberg, Christopher G. Goodier, Julio F. Mateus Niño, Rebecca J. Wineland, Roger B. Newman, Bruce W. Hollis, Carol L. Wagner, Cheryl S. Rosenfeld.


Given the high rate of preterm birth (PTB) nationwide and data from RCTs demonstrating risk reduction with vitamin D supplementation, the Medical University of South Carolina (MUSC) implemented a new standard of care for pregnant women to receive vitamin D testing and supplementation.

To determine if the reported inverse relationship between maternal 25(OH)D and PTB risk could be replicated at MUSC, an urban medical center treating a large, diverse population.

Medical record data were obtained for pregnant patients aged 18–45 years between September 2015 and December 2016. During this time, a protocol that included 25(OH)D testing at first prenatal visit with recommended follow-up testing was initiated. Free vitamin D supplements were offered and the treatment goal was ≥40 ng/mL. PTB rates (<37 weeks) were calculated, and logistic regression and locally weighted regression (LOESS) were used to explore the association between 25(OH)D and PTB. Subgroup analyses were also conducted. Among women with a live, singleton birth and at least one 25(OH)D test during pregnancy (N = 1,064), the overall PTB rate was 13%. The LOESS curve showed gestational age rising with increasing 25(OH)D. Women with 25(OH)D ≥40 ng/mL had a 62% lower risk of PTB compared to those <20 ng/mL (p<0.0001). After adjusting for socioeconomic variables, this lower risk remained (OR = 0.41, p = 0.002). Similar decreases in PTB risk were observed for PTB subtypes (spontaneous: 58%, p = 0.02; indicated: 61%, p = 0.006), by race/ethnicity (white: 65%, p = 0.03; non-white: 68%, p = 0.008), and among women with a prior PTB (80%, p = 0.02). Among women with initial 25(OH)D <40 ng/mL, PTB rates were 60% lower for those with ≥40 vs. <40 ng/mL on a follow-up test (p = 0.006); 38% for whites (p = 0.33) and 78% for non-whites (p = 0.01). Maternal 25(OH)D concentrations ≥40 ng/mL were associated with substantial reduction in PTB risk in a large, diverse population of women.

Partial Text

There were 15 million preterm births (PTB) (<37 weeks) worldwide and more than 1 million infant deaths from PTB complications in 2010 [1]. PTB rates ranged from 5% to 18% around the world and the rate in the United States was disproportionately high (12%) compared to other developed counties [1]. Substantial racial disparities in PTB rates have also been found in the United States: 18% among African Americans, 12% among Hispanics, and 11% among whites in 2009 [2]. Since PTB is the leading cause of neonatal death and multiple short and long term health problems [3], it is critical to identify modifiable maternal risk factors that could significantly reduce PTB risk at the population level. For this study, following IRB approval (HR#Pro00020570), de-identified medical record data were obtained for all pregnant women aged 18–45 years who received a 25(OH)D test and delivered at MUSC between September 2015 and December 2016. During this time, a protocol was instituted which included routine 25(OH)D testing at each patient’s first prenatal visit. Follow-up testing was recommended between 24–28 weeks and prior to delivery by provider request. Testing increased in May 2016 when the initial 25(OH)D test was automated as part of initial prenatal screening. Total circulating 25(OH)D (ng/mL) was measured using standardized methodology for LC/MS analysis in a MUSC Clinical Laboratory Improvement Amendments (CLIA)-certified clinical laboratory. Between September 2015 and December 2016, delivery information was available for 1,064 women with at least one 25(OH)D test result during pregnancy. The characteristics of this cohort are found in Table 1. We found a clear association between maternal 25(OH)D concentration and PTB risk in the general obstetrical population at an urban medical center treating a large, diverse population of women. Women with a 25(OH)D concentration of ≥40 ng/mL had a 62% lower risk of PTB compared to those with concentrations <20 ng/mL. Similar or greater magnitudes of decreased risk were observed for PTB subtypes, race/ethnic groups, and among women with a prior PTB. Additionally, among women with low initial 25(OH)D concentrations (<40 ng/mL), PTB rates were significantly lower (60%) for those who achieved ≥40 ng/mL on a follow-up test vs. those who did not, especially for non-white women (78%).   Source:


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