Clinical opinionObstetricsImplications of vitamin D deficiency in pregnancy and lactation
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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
References (115)
- et al.
High prevalence of vitamin D insufficiency in black and white pregnant women residing in the northern United States and their neonates
J Nutr
(2007) - et al.
Evidence that vitamin D3 increases serum 25-hydroxyvitamin D more efficiently than does vitamin D2
Am J Clin Nutr
(1998) - et al.
An evaluation of the vitamin D3 content in fish: is the vitamin D content adequate to satisfy the dietary requirement for vitamin D?
J Steroid Biochem Mol Biol
(2007) - et al.
Photometabolism of 7-dehydrocholesterol to previtamin D3 in skin
Biochem Biophys Res Commun
(1977) How to define normal values for serum concentrations of 25-hydroxyvitamin D? An overview
- et al.
The ontogeny of 25-hydroxyvitamin D(3) 1alpha-hydroxylase expression in human placenta and decidua
Am J Pathol
(2002) McCollum Award Lecture, 1994: vitamin D: new horizons for the 21st century
Am J Clin Nutr
(1994)In utero physiology: role in nutrient delivery and fetal development for calcium, phosphorus, and vitamin D
Am J Clin Nutr
(2007)- et al.
A longitudinal study of calcium homeostasis during human pregnancy and lactation and after resumption of menses
Am J Clin Nutr
(1998) - et al.
Calcium homeostasis and bone metabolism during pregnancy, lactation, and postweaning: a longitudinal study
Am J Clin Nutr
(1995)
Pregnancy as state of physiologic absorptive hypercalciuria
Am J Med
Calcium metabolism in normal pregnancy: a longitudinal study
Am J Obstet Gynecol
Vitamin D and barrier function: a novel role for extra-renal 1 alpha-hydroxylase
Mol Cell Endocrinol
Vitamin D in pregnancy and lactation: maternal, fetal, and neonatal outcomes from human and animal studies
Am J Clin Nutr
Effect of prolactin on vitamin D metabolism
Mol Cell Endocrinol
Maternal plasma osteoprotegerin concentration in normal pregnancy
Am J Obstet Gynecol
Acute effect of estradiol on the renal vitamin D hydroxylases in Japanese quail
Biochem Pharmacol
Circulating vitamin D3 and 25-hydroxyvitamin D in humans: an important tool to define adequate nutritional vitamin D status
J Steroid Biochem Mol Biol
Circulating 25-hydroxyvitamin D levels indicative of vitamin D sufficiency: implications for establishing a new effective dietary intake recommendation for vitamin D
J Nutr
Vitamin D deficiency during pregnancy: an ongoing epidemic
Am J Clin Nutr
High prevalence of vitamin D deficiency among pregnant women and their newborns in northern India
Am J Clin Nutr
Perinatal vitamin D metabolismIII. Factors influencing late gestational human serum 25-hydroxyvitamin D
Am J Obstet Gynecol
Hypovitaminosis D prevalence and determinants among African American and white women of reproductive age: third National Health and Nutrition Examination Survey, 1988-1994
Am J Clin Nutr
Pregnancy-related mortality from preeclampsia and eclampsia
Obstet Gynecol
World Health Organization randomized trial of calcium supplementation among low calcium intake pregnant women
Am J Obstet Gynecol
Vitamin D intake during pregnancy: association with maternal characteristics and infant birth weight
Early Hum Dev
Milk consumption during pregnancy is associated with increased infant size at birth: prospective cohort study
Am J Clin Nutr
Prospective study of vitamin D supplementation and rickets in China
J Pediatr
Maternal vitamin D status during pregnancy and childhood bone mass at age 9 years: a longitudinal study
Lancet
Human perinatal vitamin D metabolism: I, 25-hydroxyvitamin D in maternal and cord blood
J Pediatr
Vitamin D and its metabolites in human and bovine milk
J Nutr
Hypocalcemic focal seizures in a one-month-old infant of a mother with a low circulating level of vitamin D
Brain Dev
Vitamin D requirements during lactation: high-dose maternal supplementation as therapy to prevent hypovitaminosis D for both the mother and the nursing infant
Am J Clin Nutr
Is vitamin D deficiency to blame for the asthma epidemic?
J Allergy Clin Immunol
Vitamin D receptor expression by the lung micro-environment is required for maximal induction of lung inflammation
Arch Biochem Biophys
Vitamin D status, 1,25-dihydroxyvitamin D3, and the immune system
Am J Clin Nutr
Prevention of rickets and vitamin D deficiency in infants, children, and adolescents
Pediatrics
Vitamin D deficiency
N Engl J Med
Vitamin D2 is as effective as vitamin D3 in maintaining circulating concentrations of 25-hydroxyvitamin D
J Clin Endocrinol Metab
Dietary reference intakes (DRIs): recommended intakes for individuals
Effect of UV-B exposure on the concentration of vitamin D2 in sliced shiitake mushroom (Lentinus edodes) and white button mushroom (Agaricus bisporus)
J Agric Food Chem
Sunlight regulates the cutaneous production of vitamin D3 by causing its photodegradation
J Clin Endocrinol Metab
Unique biosynthesis by kidney of a biological active vitamin D metabolite
Nature
Human prostate cells synthesize 1,25-dihydroxyvitamin D3 from 25-hydroxyvitamin D3
Cancer Epidemiol Biomarkers Prev
Expression of 25-hydroxyvitamin D3-1alpha-hydroxylase in the human kidney
J Am Soc Nephrol
Extrarenal expression of 25-hydroxyvitamin d(3)-1 alpha-hydroxylase
J Clin Endocrinol Metab
Vitamin D
Am J Physiol Renal Physiol
Influence of season and latitude on the cutaneous synthesis of vitamin D3: exposure to winter sunlight in Boston and Edmonton will not promote vitamin D3 synthesis in human skin
J Clin Endocrinol Metab
Regulation of metabolism of 25-hydroxycholecalciferol by kidney tissue in vitro by dietary calcium
Nat New Biol
A detailed assessment of alterations in bone turnover, calcium homeostasis, and bone density in normal pregnancy
J Bone Miner Res
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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.