Clinical Review

Vitamin D and pregnancy: 9 things you need to know

OBG Manag. 2011 August;23(8):30-36

References

1. Dror DK, Allen LH. Vitamin D inadequacy in pregnancy: biology outcomes, and interventions. Nutr Rev. 2010;68(8):465-477.

2. Verstuyf A, Carmeliet G, Bouillon R, Mathieu C. Vitamin D: a pleiotropic hormone. Kidney Int. 2010;78(2):140-145.

3. Merewood A, Mehta SD, Chen TC, Bauchner H, Holick MF. Association between vitamin D deficiency and primary cesarean section. J Clin Endocrinol Metab. 2009;94(3):940-945.

4. Bodnar LM, Krohn MA, Simhan HN. Maternal vitamin D deficiency is associated with bacterial vaginosis in the first trimester of pregnancy. J Nutr. 2009;139(6):1157-1161.

5. Robinson CJ, Alanis MC, Wagner CL, Hollis BW, Johnson DD. Plasma 25-hydroxyvitamin D levels in early-onset severe preeclampsia. Am J Obstet Gynecol. 2010;203(4):366.e1-6.

6. Lau SL, Gunton JE, Athayde NP, Byth K, Cheung NW. Serum 25-hydroxyvitamin D and glycated haemoglobin levels in women with gestational diabetes mellitus. Med J Aust. 2011;194(7):334-337.

7. Mulligan ML, Felton SK, Riek AE, Bernal-Mizrachi C. Implications of vitamin D deficiency in pregnancy and lactation. Am J Obstet Gynecol. 2010;202(5):429.e1-9.

8. Hollis BW. Vitamin D requirement during pregnancy and lactation. J Bone Miner Res. 2007;22 (suppl 2):V39-44.

9. Johnson DD, Wagner CL, Hulsey TC, McNeil RB, Ebeling M, Hollis BW. Vitamin D deficiency and insufficiency is common during pregnancy. Am J Perinatol. 2010;28(1):7-12.

10. Bodnar LM, Simhan HN, Powers RW, Frank MP, Cooperstein E, Roberts JM. High prevalence of vitamin D insufficiency in black and white pregnant women residing in the northern United States and their neonates. J Nutr. 2007;137(2):447-452.

11. Ginde AA, Sullivan AF, Mansbach JM, Camargo CA, Jr. Vitamin D insufficiency in pregnant and nonpregnant women of childbearing age in the United States. Am J Obstet Gynecol. 2010;202(5):436.e1-8.

12. ACOG Committee Opinion No. 495: Vitamin D: Screening and supplementation during pregnancy. Obstet Gynecol. 2011;118(1):197-198.

13. Wagner CL, Greer FR. American Academy of Pediatrics Section on Breastfeeding; American Academy of Pediatrics Committee on Nutrition. Prevention of rickets and vitamin D deficiency in infants children, and adolescents. Pediatrics. 2008;122(5):1142-1152.

14. Yu CK, Sykes L, Sethi M, Teoh TG, Robinson S. Vitamin D deficiency and supplementation during pregnancy. Clin Endocrinol (Oxf). 2009;70(5):685-690.

15. Jones G. Pharmacokinetics of vitamin D toxicity. Am J Clin Nutr. 2008;88(2):582S-586S.

16. Hathcock JN, Shao A, Vieth R, Heaney R. Risk assessment for vitamin D. Am J Clin Nutr. 2007;85(1):6-18.

17. Hollis BW. Vitamin D requirement during pregnancy and lactation. J Bone Miner Res. 2007;22 (suppl 2):V39-44.

TABLE 2

When (and with how much “D”) to treat pregnant patients

If the 25-OHD level is…	…then supplement with*
<20 ng/mL	50,000 IU oral vitamin D weekly for 12 weeks
20–32 ng/mL	2,000–4,000 IU oral vitamin D daily (~15,000–30,000 IU weekly)
>32 ng/mL	No action needed
*Assuming that the patient will continue taking a prenatal vitamin containing 400 IU/tablet.

8. How should you treat vitamin D deficiency in pregnancy?

Here, again, there is a lack of solid evidence. No guidelines exist for pregnant patients. In its Commitee Opinion, ACOG points out that higher-dose regimens have not been studied in pregnancy, but cites studies using up to 4,000 IU daily.¹² The question becomes: Can guidelines that have been established for nonpregnant patients be used safely in pregnancy?

Although there is no evidence-based consensus, physiology and previous studies suggest that they can.

In one study, pregnant women were given doses as high as 200,000 IU in the third trimester to treat vitamin D deficiency.¹⁴ That investigation produced two key findings:

There were no signs or symptoms of toxicity in patients or newborns, demonstrating that a single dose of a large amount of vitamin D can be administered safely.
Despite the treatment, many of the women in this study remained deficient, indicating that continued supplementation would be required beyond the initial dose.

Although the dosage administered in this study seems like a large amount, it should be viewed in context: a Caucasian female can produce 50,000 IU of vitamin D from 30 minutes of sun exposure at midday.¹⁴

The IOM acknowledged that it underestimated the amount of vitamin D that can be taken safely and increased its upper limit of normal to 4,000 IU daily. Note that this upper limit is for people who are presumed to have a normal level to begin with. Therefore, it would be expected that a deficiency would require a greater amount for treatment.

As for treatment, both daily and weekly regimens are acceptable. Because vitamin D is fat-soluble, a daily dose of 1,000 IU is equivalent to a weekly dose of 7,000 IU. Many patients prefer the convenience of weekly dosing, which can also improve compliance.

See TABLE 2 for a proposed guideline on how to treat a pregnant patient, based on the 25-OHD level.

9. Can a person get too much vitamin D?

Vitamin D is fat-soluble. Should you worry about toxicity?

Because there is such a wide normal range for vitamin D, a person would have to be taking massive amounts of the nutrient for a substantial time before hypervitaminosis and a potential impact on calcium metabolism occur. Pharmacokinetic data demonstrate that toxicity may not occur until a vitamin D level of 300 ng/mL or higher is reached, which is three times the upper limit of normal for most reference ranges.¹⁵ A 2007 review found no cases of toxicity reported in the literature at a total serum level below 200 ng/mL (twice the normal limit) or a dose of less than 30,000 IU/day.¹⁶

Last words

Many questions and research opportunities remain regarding optimal vitamin D levels and supplementation in pregnancy, as well as the impact of vitamin D not only on pregnancy-related outcomes but on neonatal and infant health. One thing is certain: No one can argue that a nutritionally deficient state is preferred in pregnancy for maternal or fetal health. As advocates for women’s health, it behooves us to address this situation for the benefit of our patients and their children.

How do you manage the vitamin D requirements of pregnant and nonpregnant patients? Do you agree with the IOM that a vitamin D level of 20 ng/mL is sufficient for most individuals? Do you routinely measure the vitamin D level of your patients? Do you recommend vitamin D supplementation in pregnancy?
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NEWS FROM THE MEDICAL LITERATURE

Study finds vitamin D supplementation in pregnancy to be safe and effective

Daily 4,000-IU vitamin D supplementation from 12 to 16 weeks of gestation is safe and effective in achieving vitamin D sufficiency in pregnant women and their neonates, according to a study published in the July 2011 issue of the Journal of Bone and Mineral Research.

Bruce W. Hollis, PhD, from the Medical University of South Carolina in Charleston, and colleagues assessed the need, safety, and effectiveness of vitamin D supplementation in 350 women with singleton pregnancies at 12 to 16 weeks of gestation. Participants were randomly assigned to receive 400 IU, 2,000 IU, or 4,000 IU vitamin D₃ daily until delivery. The outcomes studied included maternal/neonatal circulating serum vitamin D (25-OHD) levels at delivery, achieving 25-OHD of 80 nmol/L or more, and achieving 25-OHD concentration for maximal 1,25-dihydroxycholecalciferol (1,25-OH2D) production.

The investigators found that the percentage of participants who achieved vitamin D sufficiency was significantly different between groups, with the 4,000-IU group having the highest percentage. Within 1 month of delivery, the relative risk (RR) of achieving 25-OHD of 80 nmol/L or more differed significantly between the 2,000-IU versus 400-IU groups and 4,000-IU versus 400-IU groups (RR, 1.52 and 1.60, respectively). There was no significant difference between the 2,000-IU and 4,000-IU groups. Circulatory 25-OHD directly influenced 1,25-OH2D levels throughout pregnancy, with maximal production of 1,25-OH2D in the 4,000-IU group. Vitamin D supplementation was not associated with adverse events, and safety measures were similar between the groups.

“A daily vitamin D dose of 4,000 IU was associated with improved vitamin D status throughout pregnancy, one month prior, and at delivery in both mother and neonate,” the authors write.

One of the study authors disclosed financial ties with the Diasorin Corporation.