Am J Perinatol
DOI: 10.1055/a-2097-2098
Original Article

Post Hoc Analysis of National Institute of Child Health and Human Development Vitamin-D Pregnancy Cohort and The Role of Functional Vitamin-D Deficiency in Pregnancy

Shellie Davis
1   Division of Neonatology, Department of Pediatrics, Medical University of South Carolina, Charleston, South Carolina
Elliott Lyles
2   College of Osteopathic Medicine, Edward Via College of Osteopathic Medicine-Carolinas, Spartanburg, South Carolina
Judy R. Shary
1   Division of Neonatology, Department of Pediatrics, Medical University of South Carolina, Charleston, South Carolina
Myla Ebeling
1   Division of Neonatology, Department of Pediatrics, Medical University of South Carolina, Charleston, South Carolina
Susan G. Reed
1   Division of Neonatology, Department of Pediatrics, Medical University of South Carolina, Charleston, South Carolina
John E. Baatz
1   Division of Neonatology, Department of Pediatrics, Medical University of South Carolina, Charleston, South Carolina
Bruce W. Hollis
1   Division of Neonatology, Department of Pediatrics, Medical University of South Carolina, Charleston, South Carolina
Carol L. Wagner
1   Division of Neonatology, Department of Pediatrics, Medical University of South Carolina, Charleston, South Carolina
› Author Affiliations
Funding This study was funded National Institute of Children's Health and Human Development Grant number R01 HD47511, National Institutes of Health Grant Number RR01070, and the South Carolina Clinical and Translational Research (SCTR) Institute, with an academic home at the Medical University of South Carolina, and NIH/NCRR Grant Number UL1 RR029882, U.S. Department of Health and Human Services and National Center for Advancing Translational Sciences, RR01070 and UL1 RR029882.


Objective Our objective was to conduct a secondary, post hoc analysis of the National Institute of Child Health and Human Development (NICHD) vitamin D (vitD) pregnancy study by Hollis et al, which reported on the effect of vitD supplementation in pregnant women and determine the potential interaction between intact parathyroid hormone (iPTH) concentrations, vitD status, and various comorbidities associated with pregnancy. Women with low 25-hydroxy vitamin D (25(OH)D) concentrations and high iPTH concentrations during pregnancy, known as functional vitamin-D deficiency (FVDD), were more likely to acquire complications also affecting their neonates.

Study Design This post hoc analysis of data collected from a diverse group of pregnant women participating in the NICHD vitD pregnancy study was applied to investigate the applicability of the concept of FVDD in pregnancy (Hemmingway, 2018) in identifying potential risks for certain comorbidities of pregnancy. This analysis defines FVDD as maternal serum 25(OH)D concentrations below 20 ng/mL and iPTH concentrations above 65 pg/mL creating a definitive ratio number, 0.308, to classify mothers as having FVDD prior to delivery (PTD). Statistical analyses were performed using SAS 9.4 (Cary, NC).

Results In total, 281 women (85 African American, 115 Hispanic, and 81 Caucasian) with 25(OH)D and iPTH concentrations measured at monthly visits were included in this analysis. No statistically significant association was found between mothers classified as having FVDD at baseline or 1-month PTD and hypertensive disorders of pregnancy, infection, or admittance to the neonatal intensive care unit. When combining all comorbidities of pregnancy in this cohort, results showed those with FVDD at baseline, 24 weeks' gestation, and 1-month PTD were more likely to experience a comorbidity (p = 0.001; p = 0.001; p = 0.004, respectively). Those with FVDD 1-month PTD were 7.1 times (confidence interval [CI]: 1.71–29.81) more likely to have preterm birth (<37 weeks) than women without FVDD.

Conclusion Participants were more likely to have experienced preterm birth if they met the criteria for FVDD. This study supports the importance of FVDD during pregnancy.

Key Points

  • Functional vitamin D deficiency (FVDD) is defined as the ratio of 25(OH)D divided by iPTH concentration ≤0.308.

  • At a minimum, it is recommended that vitamin D status be kept in the healthy range based on current recommendations for pregnant individuals.

  • FVDD is a more sensitive predictor of pregnancy risk than 25(OH)D alone.

  • FVDD identified those with greater risk of preterm birth in this cohort.

Publication History

Received: 09 January 2023

Accepted: 19 May 2023

Accepted Manuscript online:
22 May 2023

Article published online:
28 June 2023

© 2023. Thieme. All rights reserved.

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