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.
J Steroid Biochem Mol Biol. 2015 Nov 7. pii: S0960-0760(15)30124-2. doi: 10.1016/j.jsbmb.2015.10.022. [Epub ahead of print]
Wagner CL1, Baggerly C2, McDonnell S2, Baggerly KA3, French CB2, Baggerly L2, Hamilton SA4, Hollis BW5.
Note that most of the benefit was to women of color - who typically have low vitamin D levels
1 Medical University of South Carolina Children's Hospital, Charleston, SC, United States. Electronic address: wagnercl@musc.edu.
2 GrassrootsHealth, Encinitas, CA, United States.
3 Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States.
4 Eau Claire Cooperative Health Centers, Columbia, SC, United States.
5 Medical University of South Carolina Children's Hospital, Charleston, SC, United States.
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 to 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 2009-2011CC-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.
Copyright © 2015. Published by Elsevier Ltd.
PMID: 26554936
- - - - - - - - - - -
- Notice the moderate and very preterms- poor response to 4,000 IU of Vitamin D by several women (black squares)
- Suspect that these poor responses could have been avoided if more vitamin D and/or cofactors which increase the response had been give to high-risk women - such as obese
Fig. 1. 25(OH)D concentration within 6 weeks of delivery by gestational age (weeks) at birth (NICHD & TRF, N = 509).
Term birth is 37 weeks of gestation; late preterm birth is 34 to <37 weeks; moderately preterm is 32 to <34 weeks; and very preterm is <32 weeks.
White circles represent women assigned to the control group (400 IU/day);
gray triangles represent women assigned to the 2000 IU/day treatment group; and
solid black squares represent women assigned to the 4000 IU/day treatment group.
Black line represents fitted LOESS curve.
Download the PDF from VitaminDWiki
See also VitaminDWiki
Healthy pregnancies need lots of vitamin D has the following summary
Most were taking 2,000 to 7,000 IU daily for >50% of pregnancy
Click on hyperlinks for details
Problem | Vit. D Reduces | Evidence |
| 0. Chance of not conceiving | 3.4 times | Observe |
| 1. Miscarriage | 2.5 times | Observe |
| 2. Pre-eclampsia | 3.6 times | RCT |
| 3. Gestational Diabetes | 3 times | RCT |
| 4. Good 2nd trimester sleep quality | 3.5 times | Observe |
| 5. Premature birth | 2 times | RCT |
| 6. C-section - unplanned | 1.6 times | Observe |
| Stillbirth - OMEGA-3 | 4 times | RCT - Omega-3 |
| 7. Depression AFTER pregnancy | 1.4 times | RCT |
| 8. Small for Gestational Age | 1.6 times | meta-analysis |
| 9. Infant height, weight, head size within normal limits | RCT | |
| 10. Childhood Wheezing | 1.3 times | RCT |
| 11. Additional child is Autistic | 4 times | Intervention |
| 12.Young adult Multiple Sclerosis | 1.9 times | Observe |
| 13. Preeclampsia in young adult | 3.5 times | RCT |
| 14. Good motor skills @ age 3 | 1.4 times | Observe |
| 15. Childhood Mite allergy | 5 times | RCT |
| 16. Childhood Respiratory Tract visits | 2.5 times | RCT |
RCT = Randomized Controlled Trial
Intervention during Pregnancy studies on VitaminDWiki
- 3X reduction in preemie Bronchopulmonary Dysplasia if add tiny amount of Vitamin D – meta-analysis June 2024
- 4,000 IU of daily Vitamin D during pregnancy is good (Mongolia this time) – RCT Oct 2023
- Resulting childhood Asthma cut in half if 4,400 IU Vitamin D daily while pregnant - RCT April 2023
- 6,400 IU of Vitamin D is safe and effective during breastfeeding – RCT Dec, 2020
- Vitamin D during pregnancy – single 200,000 IU similar to daily 5,000 IU – April 2020
- Massive improvement in vaginal microbiome during pregnancy with Vitamin D – March 2019
- Autism risk reduced 2X by prenatal vitamins (Vitamin D or Folic) – Feb 2019
- Fetal bones helped a bit by 1,000 IU of vitamin D – RCT Feb 2019
- Adding 1,000 IU vitamin D while pregnant did not help much (no surprise) – RCT Jan 2019
- Pregnancies helped a lot by Vitamin D (injection then 50,000 IU monthly) – RCT May 2018
- 430 genes changed when 3,800 IU Vitamin D added in late second trimester – RCT May 2018
- 300,000 IU of Vitamin D is not enough during pregnancy – RCT May 2018
- Preeclampsia risk reduced 7X by 4,000 IU of Vitamin D daily – RCT March 2018
- Risk of infant Asthma cut in half if mother supplemented Vitamin D to get more than 30 ng – RCT Oct 2017
- Gestational diabetes 30 percent less likely if consumed more than 400 IU of vitamin D daily – Oct 2017
- Monthly 120,000 IU Vitamin D plus daily Calcium was great during pregnancies – RCT Sept 2017
- Preterm birth rate reduced by vitamin D – 78 percent if non-white, 39 percent if white – July 2017
- 1,000 IU of Vitamin D while pregnant helped a little bit (4,000 IU helps a lot) – RCT Dec 2016
- Preeclampsia recurrence reduced 2 X by 50,000 IU of vitamin D every two weeks – RCT July 2017
- Only a select group of women will get a modest benefit from 800 IU of vitamin D – Jan 2017
- Reduction of infant asthma may require good vitamin D when lung development starts (4 weeks) – March 2017
- Gestational diabetes treated by Vitamin D plus Omega-3 – RCT Feb 2017
- 3,800 IU Vitamin D during pregnancy did not help much – RCT Jan 2017
- 50,000 IU of vitamin D for 8 weeks of pregnancy raised most above 30 nanograms - RCT Jan 2017
- Gestational Diabetes reduce 3 times by 5,000 IU of Vitamin D – RCT Jan 2016
- Preeclampsia risk reduced by higher levels of vitamin D (VDAART 4,400 IU) - RCT Nov 2016
- Gestational Diabetes treated with 50,000 IU every two weeks – RCT Sept 2016
- Perinatal depression decreased 40 percent with just a few weeks of 2,000 IU of vitamin D – RCT Aug 2016
- Pregnancy – adding 35,000 IU Vitamin D weekly was nice, but not enough – RCT April 2016
- Vitamin D once during pregnancy reduced infant health care costs (300 times ROI) – RCT Dec 2015
- Autism rate in siblings reduced 4X by vitamin D: 5,000 IU during pregnancy, 1,000 IU to infants – Feb 2016
- Preterm birth rate reduced 57 percent by Vitamin D – Nov 2015
- Pregnancy supplemented with 2,000 IU vitamin D got most infants to more than 12 nanograms – Aug 2015
- Preeclampsia reduced by Vitamin D (50,000 IU bi-weekly) and Calcium – Oct 2015
- Clinical trials for pregnancy with Vitamin D intervention – 51 as of Sept 2015
- No multiple sclerosis relapses during pregnancy if 50,000 IU of Vitamin D weekly – RCT April 2015
- Wheezing reduced 35 percent if vitamin D added during pregnancy – April 2015
- 4,000 IU raised vitamin D levels during pregnancy – July 2014
- Pregnant mothers in Quatar needed more than weekly 50,000 IU Vitamin D – Nov 2013
- Gestational diabetes – Vitamin D and Calcium provided huge benefits – RCT March 2015
- Pregnancy helped by single dose of 60,000 IU of Vitamin D – RCT March 2015
- Gestational diabetes reduced by just two 50,000 IU doses of vitamin D – RCT Nov 2014
- Improved births with 2,000 IU vitamin D during pregnancy in India - RCT Feb 2015
- 50,000 IU of Vitamin D every 2 weeks reduced gestational diabetes – RCT Feb 2015
- Infant much healthier if Gestational Diabetic mother got 2 doses of vitamin D – RCT Nov 2014
- 2000 IU vitamin D during pregnancy and 800 IU to infant resulted in less use of antibiotics – RCT April 2014
- Gestational Diabetes reduced with 50,000 IU of vitamin D every 3 weeks and daily Calcium – RCT June 2014
- Gestational Diabetes reduced 40 percent by 5,000 IU of vitamin D – RCT April 2014
- 5,000 IU Vitamin D was not enough to reduce preeclampsia but did help future infant – RCT April 2014
- Breast milk resulted in 20 ng of vitamin D for infant if mother had taken 5,000 IU daily – RCT Dec 2013