Clinical opinion
Obstetrics
Implications of vitamin D deficiency in pregnancy and lactation

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Vitamin D is an essential fat soluble vitamin and a key modulator of calcium metabolism in children and adults. Because calcium demands increase in the third trimester of pregnancy, vitamin D status becomes crucial for maternal health, fetal skeletal growth, and optimal maternal and fetal outcomes. Vitamin D deficiency is common in pregnant women (5-50%) and in breastfed infants (10-56%), despite the widespread use of prenatal vitamins, because these are inadequate to maintain normal vitamin D levels (≥32 ng/mL). Adverse health outcomes such as preeclampsia, low birthweight, neonatal hypocalcemia, poor postnatal growth, bone fragility, and increased incidence of autoimmune diseases have been linked to low vitamin D levels during pregnancy and infancy. Studies are underway to establish the recommended daily doses of vitamin D in pregnant women. This review discusses vitamin D metabolism and the implications of vitamin D deficiency in pregnancy and lactation.

Section snippets

Vitamin D physiologic components

Vitamin D is a prohormone that is derived from cholesterol. The nutritional forms of vitamin D include D3 (cholecalciferol), which is generated in the skin of humans and animals, and vitamin D2 (ergocalciferol), which is derived from plants; both forms can be absorbed in the gut and used by humans. Controversy exists as to whether D2 or D3 is more effective in maintaining circulating levels of vitamin D in nonpregnant individuals, and specific data during pregnancy is unknown.4, 5 In this

Vitamin D and calcium metabolism in pregnancy

During pregnancy and lactation, significant changes in maternal vitamin D and calcium metabolism occur to provide the calcium that is needed for fetal bone mineral accretion. During the first trimester, the fetus accumulates 2-3 mg/d in the skeleton; however, this rate of accumulation doubles in the last trimester.21 The body of a pregnant woman adapts to fetal requirements by increasing calcium absorption in early pregnancy, with maximal absorption in the last trimester.22, 23 Along with the

Classification of vitamin D status

Vitamin D status is usually estimated by measuring the level of plasma 25(OH)D. Evidence of 25(OH)D concentrations of 44-70 ng/mL observed in healthy outdoor workers (such as farmers and lifeguards) suggest an optimal healthy level that is far above the levels that are reported to prevent rickets and osteomalacia.45, 46 Studies that have evaluated the correlation between vitamin D levels and intestinal calcium absorption, maximal PTH suppression, bone fracture prevention, and bone turnover have

Prevalence of vitamin D deficiency in pregnancy

Vitamin D deficiency during pregnancy is a worldwide epidemic; studies have reported a prevalence that ranges from 18-84%, depending on the country of residence and local clothing customs.50, 51, 52, 53, 54 In the United States, vitamin D deficiency is estimated to occur in 5-50% of pregnant women.55, 56 African American women have a much higher risk of vitamin D deficiency, compared with other women because of increased skin pigmentation and low dietary intake.57 Bodnar et al3 reported the

Maternal effects of vitamin D deficiency

Preeclampsia and hypertensive disorders complicate 3-10% of pregnancies in the United States and contribute to maternal and neonatal morbidity and deaths.58, 59 Previous studies have shown that women with preeclampsia have lower urinary calcium excretion, lower ionized calcium levels, higher PTH levels, and lower 1,25 (OH)2 D levels, compared with normotensive pregnant control subjects.60 Low plasma calcium levels induce several common mechanisms that are associated with hypertension, such as

Infant size

Several studies have reported an association between infant size and vitamin D status. In a study in 449 Iranian pregnant women, higher mean birth length was found at delivery in babies from mothers who received the recommended dietary allowance of calcium and vitamin D. The incidence of low birthweight was significantly lower in newborn infants from mothers who received the recommended doses of calcium and vitamin D.69 In 2251 pregnant women from the Camden study, a prospective analysis of the

Vitamin D deficiency during lactation

In the first 6-8 weeks of postnatal life, the vitamin D status of a neonate is dependent largely on vitamin D that is acquired through placental transfer in utero, as evidenced by the direct linear relationship between maternal and cord blood levels of 25(OH)D.84 In most infants, vitamin D stores acquired from the mother are depleted by approximately 8 weeks of age.85 Thereafter, vitamin D is derived from diet, sunlight, and supplementation. In general, formula-fed babies receive adequate

Asthma

Multiple biologic actions suggest a correlation between vitamin D deficiency and the asthma epidemic.96 Vitamin D signaling pathways and receptor polymorphisms97, 98, 99 may have effects on Th1-Th2 imbalance,97, 100, 101 smooth muscle contraction,102, 103 airway inflammation, prostaglandin regulation, and airway remodeling, all of which can impact asthma control. In animal models, vitamin D regulates lung growth in utero.104 Clinical studies indicate an inverse association between vitamin D

Recommendations for monitoring and replacement

Vitamin D is important to maternal health, fetal development, and postnatal life. Current prenatal care does not include the monitoring of vitamin D levels, which is an unfortunate oversight because deficiency is easily treated. On average, daily vitamin D supplements of 1000-2000 IU cost $1-2 per month. Women with ≥1 risk factors for vitamin D deficiency (Table 2) should have a plasma 25(OH)D level drawn at the beginning of gestation and at mid pregnancy. The recommended target range for

Comment

Recent evidence demonstrates that the prevalence of vitamin D deficiency in the general population and in women of child-bearing age is surprisingly high. However, the influence of vitamin D deficiency on calcium metabolism during pregnancy has not been well-characterized. Vitamin D deficiency is known to be associated with an increased prevalence of preeclampsia, which a common cause of increased mortality rates in pregnancy. In children, it is also associated with small infant size and the

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    Cite this article as: Mulligan ML, Felton SK, Riek AE, et al. Implications of vitamin D deficiency in pregnancy and lactation. Am J Obstet Gynecol 2010;202:429.e1-9.

    Financial support was provided by the American Diabetes Association (Grant 7-08-CR-08); Washington University; the Diabetes Research and Training Center (Grant P60 DK20579); and the David M. and Paula L. Kipnis Scholar in Medicine, Washington University School of Medicine.

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