This study found that vitamin D deficiency and insufficiency are common among pregnant women in the United States, especially for African American and Hispanic women. The study measured vitamin D levels in 154 African American, 194 Hispanic, and 146 Caucasian pregnant women early in their pregnancies. It found that 97% of African American women, 81% of Hispanic women, and 67% of Caucasian women had insufficient or deficient vitamin D levels. African American women were the most likely to have deficiency, while Caucasian women were the most likely to have sufficient levels. Race was identified as the most important risk factor for deficiency or insufficiency.

1. Vitamin D Deficiency and Insufficiency is
Common during Pregnancy
Donna D. Johnson, M.D.,1 Carol L. Wagner, M.D.,2 Thomas C. Hulsey, D.Sc.,3
Rebecca B. McNeil, Ph.D.,4 Myla Ebeling, R.A.,3 and Bruce W. Hollis, Ph.D.2
ABSTRACT
The objective was to determine the incidence of vitamin D deficiency, insuffi-
ciency, and sufficiency in African-American, Hispanic, and Caucasian pregnant women.
Blood samples were taken from 154 African-American, 194 Hispanic, and 146 Caucasian
women at <14 weeks of gestation; 25 hydroxyvitamin D levels (25(OH)D) levels were
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measured by radioimmunoassay. The mean 25(OH)D levels in African-American,
Hispanic, and Caucasian pregnant women were 15.5 Æ 7.2 (standard deviation),
24.1 Æ 8.7, 29.0 Æ 8.5 ng/mL, respectively. Ninety-seven percent of African-Americans,
81% of Hispanics, and 67% of Caucasians were deficient (25(OH)D levels <20 ng/mL or
<50 nmol/L) or insufficient (25(OH)D levels !20 ng/mL or <32 ng/mL or !50 nmol/L
or <80 nmol/L). Of these pregnant women, 82% had vitamin D levels <32 ng/mL
(<80 ng/mL). In logistic regression models, race was the most important risk factor for
vitamin D deficiency or insufficiency. African-American women and Hispanic women
were more likely to have vitamin D insufficiency and deficiency than Caucasian women.
Furthermore, primigravid women were more at risk for vitamin D insufficiency. This study
demonstrates widespread vitamin D deficiency and insufficiency in pregnant females living
at a southern latitude. African-Americans are at greatest risk.
KEYWORDS: Hypovitaminosis D, pregnancy, vitamin D
W ith the identification of increasing numbers have vitamin D deficiency defined as less than
of children with rickets in the United States in the 37.5 nmol/L (<15 ng/mL).2 Follow-up data from
1990s, the medical community exhibited a renewed NHANES in 2000 to 2004 demonstrated that vitamin
interest in vitamin D deficiency and vitamin D research.1 D concentrations in the population have not improved.3
One of the initial studies to assess the vitamin D status of Because women of reproductive age are deficient in
women of reproductive age used samples collected in the vitamin D, it was reasoned that pregnant women also
Nutrition Examination Survey (NHANES III) from are likely to be deficient.
1988 through 1994 to measure 25 hydroxyvitamin D Evaluation of vitamin D status of pregnant
levels (25(OH)D). Forty-two percent of African- women has been primarily done outside of the United
American and 4% of Caucasian females were found to States in populations that are at significant risk for
1
Division of Maternal Fetal Medicine, Department of Obstetrics and 96 Jonathan Lucas Street, CSB 634, Charleston, SC 29425-0619
Gynecology, Medical University of South Carolina; 2Division of (e-mail: johnsodo@musc.edu).
Pediatric Nutrition, Department of Pediatrics, Children’s Research Am J Perinatol. Copyright # by Thieme Medical Publishers, Inc.,
Institution; 3Division of Pediatric Epidemiology, Department of 333 Seventh Avenue, New York, NY 10001, USA. Tel: +1(212)
Pediatrics, Rutledge Tower, Charleston, South Carolina; 4Department 584-4662.
of Biostatistics, Mayo Clinic, Jacksonville, Florida. Received: January 27, 2010. Accepted after revision: May 10, 2010.
Address for correspondence and reprint requests: Donna D. DOI: http://dx.doi.org/10.1055/s-0030-1262505.
Johnson, M.D., Division of Maternal Fetal Medicine, Department of ISSN 0735-1631.
Obstetrics and Gynecology, Medical University of South Carolina,

2. AMERICAN JOURNAL OF PERINATOLOGY
vitamin D deficiency, such as immigrants with dark skin and Caucasian pregnant women enrolled in a vitamin
pigmentation living at very northern latitudes or women D supplementation trial and to report cumulative
who wear clothing that covers most of the body surface incidence of vitamin D deficiency (<20 ng/mL or
due to religious and cultural preferences.4–12 In a large <50 nmol/L), insufficiency (!20 ng/mL and <32 ng/mL
European study of 358 pregnant women, 8% of Western or !50 nmol/L and <80 nmol/L), and sufficiency
and 73% of Turkish, Moroccan, and other non-West- (!32 ng/mL or >80 nmol/L) in these three groups at
erners were vitamin D deficient, defined as <25 nmol/L a southern (32.7 degrees north) latitude.
(<10 ng/mL). This study was conducted in The Hague,
Netherlands. This city lies at the 52 degrees north
latitude and is 3 degrees north of the most northern METHODS
latitude of the vast majority of mainland United States. Approval for this study was granted by the Medical
The intensity of the sun is greatest at the equator and University of South Carolina’s Institutional Review
decreases at increasing latitudes.13 So, pregnant women Board for Human Subjects, HR No. 10727 and the
in the United States would be expected to be less General Clinical Research Center (Protocol #670). Pa-
deficient than the Netherlands cohort because the sun tients from Charleston, South Carolina, who were less
is more intense, especially during the summer months, than 14 weeks of pregnancy were recruited and gave
and few American women wear clothing that fully covers consent over a 5-year period. Patients with diseases
them. associated with defects in vitamin D such as sarcoid,
A study of a pregnant cohort of 200 Caucasian renal disease, uncontrolled thyroid disease, or para-
and 200 African-American pregnant women was thyroid disease were excluded from the study. In
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recently conducted in Pittsburgh, Pennsylvania (40 addition, patients with chronic hypertension and dia-
degrees north latitude). Vitamin D levels were meas- betes were excluded as patients with these diseases have
ured at 4 to 21 weeks and at delivery. Five percent of a higher incidence of adverse pregnancy outcomes. The
Caucasian females and 29% of African-American vitamin D levels were obtained as baseline data during
females were found to be vitamin D deficient as a large randomized clinical trial in which women were
defined by a 25(OH)D level <37.5 nmol/L (<15 randomized to receive different amounts of vitamin D
ng/mL). Forty-two percent of Caucasians and 54% supplementation during pregnancy. The primary ob-
of African-Americans were found to have vitamin D jective of the trial was to determine the safety of
insufficiency (25(OH)D 37.5 to 80 nmol/L; 15 to 32 higher-dose vitamin D supplementation in pregnancy.
ng/mL). Overall, only 53% of Caucasians and 17% of Race was self-reported and classified as non-Hispanic
African-Americans had adequate vitamin D levels or Hispanic black, Hispanic white, or non-Hispanic
(>80 nmol/L or >32 ng/mL).14 Thus, despite being white. Throughout this article, the classifications are
closer to the equator, vitamin D deficiency or insuffi- referred to as African-American, Hispanic, and Cau-
ciency in pregnant women is also prevalent in the casian. Demographic information was obtained at the
United States. first patient encounter. Prepregnancy maternal weight
What then accounts for this high prevalence of was self-reported. Maternal height was measured at
vitamin D deficiency and insufficiency? Vitamin D is the first clinical visit. This information was used to
obtained from diet, dietary supplements, and sunlight. calculate maternal prepregnancy body mass index
Few foods naturally contain vitamin D. In developed (BMI) in kg/m2.
countries, some foods are fortified with vitamin D. The Whole blood was collected in serum separator
amount that food is fortified with vitamin D and the tubes and centrifuged. Serum was collected and then
amount of vitamin D in the typical dietary supplement stored at À808C and analyzed in batches. Total circulat-
(400 IU) is inadequate to correct vitamin D deficiency.13 ing 25(OH)D levels were measured using radioimmuno-
Cutaneous synthesis is the most important source of assay as previously described.16 The detection limit of
vitamin D. Regardless of the latitude, any process that the assay is 2.8 mg/L. The assay precision (coefficient
reduces or blocks absorption of ultraviolet B radiation of variation) was less than 7%.17 Laboratory personnel
will decrease the amount of vitamin D synthesized. For were blinded to sociodemographic data of the subject,
example, the darker skin pigmentation commonly seen including race/ethnicity.
in African-Americans decreases the amount of vitamin Subjects were classified using the following
D synthesized.15 Not surprisingly, a racial disparity in definitions. If their level of 25(OH)D was less than
vitamin D levels and deficiency has long been recog- <20 ng/mL (<50 nmol/L), the subjects were classified
nized. Although pregnant African-American and Cau- as vitamin D deficient. If their levels were !20 but
casian females have been studied, very little is known <32 ng/mL (!50 nmol/L and <80 nmol/L), the sub-
about the pregnant Hispanic population. The objective jects were classified as insufficient. Only subjects with
of this observational study was to compare the baseline serum levels of 25(OH)D !32 ng/mL (!80 nmol/L)
vitamin D levels of African-American, Hispanic, were classified as having sufficient vitamin D levels.17–19

3. VITAMIN D DEFICIENCY AND INSUFFICIENCY/JOHNSON ET AL
Table 1 Demographics by Ethnicity
African-American Hispanic Caucasian
Demographics (n ¼ 154) (n ¼ 189) (n ¼ 146) p Value
Maternal age (mean, SD)* 25.3 Æ 4.9 24.8 Æ 4.8 30.1 Æ 5.4 <0.001
Gestational age (mean, SD)* 11.6 Æ 2.3 9.5 Æ 2.1 10.7 Æ 1.8 <0.001
Primigravida, n (%)y 28 (20%) 58 (36%) 52 (40%) <0.001
BMI !30, n (%)y 64 (52%) 32 (22%) 23 (21%) <0.0001
Season (April through September)y 69 (44%) 101 (53%) 60 (41%) NS
*Analysis of variance.
y
Chi-square.
BMI, body mass index; SD, standard deviation.
Data were analyzed using SAS for Windows Americans were deficient than either Hispanics or Cau-
version 9.1. Categorical variables were analyzed using casians. Ninety-seven percent (149/154) of African-
chi-square and continuous variables were analyzed using Americans, 81% (157/194) of Hispanics, and 67% (98/
analysis of variance. A p value less than 0.05 defined 146) of Caucasians were insufficient or deficient. More
significance. Multivariate analysis of the three categories Caucasians had normal vitamin D levels than the other
of vitamin D was conducted with multinomial logistic two groups; of those two groups, Hispanics were more
regression using Proc Logistic in SAS. This procedure likely than African-Americans to have normal vitamin D
allows the modeling of the dependent variable as a levels.
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three-group categorical variable (vitamin D <20 ng/mL Table 2 presents the results of the logistic regres-
[<50 nmol/L], vitamin D !20 to <32 ng/mL sion modeling for vitamin D deficiency, insufficiency,
[!50 nmol/L and <80 nmol/L], vitamin D !32 ng/mL and sufficiency. Controlling for these potential con-
[!80 nmol/L]) as a function of the independent variables founders (maternal age, parity, race, BMI !30, and
age, parity, ethnicity, obesity (BMI >30), and sunlight enrollment during summer months), African-American
exposure. The results of this analysis present an odds ratio and Hispanic women were persistently at greater risk for
and 95% confidence interval for the association of each either vitamin D deficiency or insufficiency than Cau-
independent variable with the two categories of vitamin casians. Of the included covariables, only primigravid
D deficiency (<20 ng/mL or <50 nmol/L) and vitamin women were significantly at risk for vitamin D insuffi-
D insufficiency (20 to 32 ng/mL or >50 nmol/L and ciency.
<80 nmol/L), considering vitamin D sufficiency
(!32 ng/mL or !80 nmol/L) as the reference category.
DISCUSSION
This study clearly demonstrates a high incidence of
RESULTS vitamin D deficiency and insufficiency and in women
Demographic data are presented in Table 1. Caucasian during their first trimester of pregnancy in a city in the
women were older than either African-Americans or United States with high UV index. The incidence of
Hispanics. Caucasians and Hispanics were more likely to vitamin D deficiency and insufficiency in this population
be primigravid than African-Americans. More African-
Americans were obese than either Caucasians or His-
panic women. The average gestational age at enrollment
was less than 12 weeks in all groups, but Hispanic
women were enrolled at an earlier gestational age than
the other two groups. Samples were drawn as frequently
in the spring and summer compared with fall and winter.
The mean 25(OH)D levels in African-
Americans, Hispanics, and Caucasians were 15.5Æ7.2
(standard deviation), 24.1Æ8.7, 29.0Æ8.5 ng/mL, re-
spectively. The range for African-Americans was 2.4 to
43.5 ng/mL, for Hispanics was 6.2 to 52.9 ng/mL, and
for Caucasians was 9.3 to 69.0 ng/mL. Forty-one percent
(200/494) of all pregnant women were deficient, and
an additional 41% (204/494) were insufficient. Overall, Figure 1 Vitamin D deficiency (<20 ng/mL or <50 nmol/L,
82% of this cohort had vitamin D levels <32 ng/mL black bar) is more common in African-Americans, and vitamin
(<80 nmol/L). Figure 1 displays vitamin D deficiency, D sufficiency (!32 ng/mL or !80 nmol/L, white bar) is more
insufficiency, and sufficiency by race. More African- common in the Caucasian population.

4. AMERICAN JOURNAL OF PERINATOLOGY
Table 2 Multinomial Logistic Regression Model for Vitamin D Levels
Variable Vitamin D Group Odds Ratio 95% CI p Value
Age <25 y <20 1.38 0.62–3.06 0.43
20–31 0.86 0.41–1.81 0.70
32þ 1.00 (ref) — –—
Primigravida <20 2.17 0.95–4.97 0.07
20–31 3.18 1.56–6.49 0.001
32þ 1.00 (ref) — —
Black (versus white) <20 54.98 16.37–184.62 <0.0001
20–31 3.24 1.04–10.07 0.04
32þ 1.00 (ref) — —
Hispanic (versus white) <20 5.25 2.10–13.17 0.004
20–31 2.06 1.03–4.11 0.04
32þ 1.00 (ref) — —
Obese (BMI !30) <20 1.87 0.81–4.28 0.14
20–31 1.66 0.78–3.52 0.19
32þ 1.00 (ref) — —
Summer months <20 0.80 0.39–1.61 0.52
20–31 0.94 0.51–1.73 0.83
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32þ 1.00 (ref) — —
BMI, body mass index; CI, confidence interval.
is higher than or similar to the incidence reported in amount of time outside and the use of sunscreens in
other studies conducted in an adult population when this study. Because of the heat index, subjects may
similar definitions for vitamin D deficiency, insuffi- spend less time outside in the summer compared with
ciency, and sufficiency is used.14 Skin pigmentation, the other seasons. Also, African-Americans have a
and thus race and ethnicity, influence the amount of smaller increase in vitamin D levels than Caucasians
vitamin D synthesis from sun exposure. Persons with with the same amount of sun exposure.20 Finally, our
darker skin synthesize less vitamin D for a given ex- population may have been so deficient that the amount
posure and are, not surprisingly, more prone to vitamin of sun exposure did not significantly impact their levels.
D deficiency.15 In the U.S. study conducted in Pitts- In Florida, female subjects only experience a 13%
burgh, Pennsylvania, 83% of blacks and 47% of whites increase in their 25(OH)D levels between winter and
had insufficient or deficient vitamin D levels.14 This summer.21
observation is consistent in our population where 97% of Obesity is also a known risk factor for vitamin D
African-Americans and 67% of Caucasians had vitamin deficiency.22–25 The etiology of this association is un-
D deficiency or insufficiency. Because Hispanics have clear. Several hypotheses have been proposed. People
darker pigmentation than Caucasians and generally with a higher BMI may avoid sunbathing or adipose
lighter pigmentation than blacks, the expected frequency tissue may sequester vitamin D.23 Also, obesity may not
of vitamin D deficiency or insufficiency in pregnant affect the vitamin D status of all races equally.23,25 In our
Hispanics should be greater than Caucasians but less cohort, we defined obese patients (BMI !30) and non-
than African-Americans. Indeed, this observation has obese patient (BMI 30) and using this cut-point for
been made in the general population and was also obesity in our cohort, obesity was not a risk factor for
confirmed in our pregnancy population.3 In fact, race/ deficient or insufficient vitamin D levels. Others have
ethnicity is the variable most strongly associated with compared obese patients (BMI !30) to patients with
vitamin D levels in our population. normal weight (BMI 25).22,24 In our study, including
Seasonality has long been recognized as an im- the overweight individuals may have blunted the effect
portant modulator of vitamin D status. Subjects have of obesity on vitamin D levels.
higher 25(OH)D levels in the summer than in In our study, primigravid subjects were more
the winter.13 For example, above 35 degrees north likely to have deficient or insufficient vitamin D levels
latitude (Atlanta, Georgia), little or no vitamin D can than multiparous subjects. In most studies, parity has not
be produced from November to February.13 In our been examined in relationship to vitamin D. In the
study, seasonality was not a significant covariable in largest U.S. study, the majority of blood samples were
our population. Others have noted no impact of season- obtained only from primigravid women and all of their
ality on 25(OH)D levels in their population.12 Several patients were nulliparous (i.e., had not delivered a child
explanations are possible. We did not examine the >20 weeks).14 In the largest European trial with

5. VITAMIN D DEFICIENCY AND INSUFFICIENCY/JOHNSON ET AL
358 subjects, parity was not significant.12 Parity was Saudi mothers and their neonates. Pediatr Res 1984;18:
specifically studied in 86 Saudi pregnant women; how- 739–741
ever, the authors compared patients who were para 5 to 5. Brooke OG, Brown IR, Cleeve HJ, Sood A. Observations on
the vitamin D state of pregnant Asian women in London. Br
subjects who were para 4 or less, and in this comparison,
J Obstet Gynaecol 1981;88:18–26
parity did not affect vitamin D levels.26 In our popula- 6. ´
Mallet E, Gugi B, Brunelle P, Henocq A, Basuyau JP,
¨
tion, primigravid women may have different habits than Lemeur H. Vitamin D supplementation in pregnancy: a
multiparous women. We did not examine the relation- controlled trial of two methods. Obstet Gynecol 1986;68:
ship of parity to diet, sun exposure, and supplementation 300–304
use in this analysis. 7. Brunvand L, Haug E. Vitamin D deficiency amongst
There is no consensus on the optimal levels of Pakistani women in Oslo. Acta Obstet Gynecol Scand 1993;
72:264–268
25(OH)D. Most experts agree that vitamin D deficiency
8. ˘ ˘ ¨
Pehlivan I, Hatun S, Aydogan M, Babaoglu K, Gokalp AS.
is <20 ng/mL (50 nmol/L), and this is the definition we Maternal vitamin D deficiency and vitamin D supplementa-
used in our population.13 We chose to define vitamin D tion in healthy infants. Turk J Pediatr 2003;45:315–320
insufficiency as <32 ng/mL (80 nmol/L). Recent data 9. O’Riordan MN, Kiely M, Higgins JR, Cashman KD.
suggest that a cutoff of <32 ng/mL (80 nmol/L) is more Prevalence of suboptimal vitamin D status during pregnancy.
appropriate based on the measurement of specific bio- Ir Med J 2008;101:240, 242–243
markers that increase or decrease with changes in 10. Datta S, Alfaham M, Davies DP, et al. Vitamin D deficiency
in pregnant women from a non-European ethnic minority
25(OH)D levels, such as parathyroid hormone, calcium
population—an interventional study. BJOG 2002;109:
absorptions, and bone mineral density.18,27,28 Because 905–908
the fetus is entirely dependent on maternal stores for
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11. Serenius F, Elidrissy AT, Dandona P. Vitamin D nutrition in
vitamin D, adequate vitamin D levels during pregnancy pregnant women at term and in newly born babies in Saudi
are essential. The vitamin D level in the fetus is $50 to Arabia. J Clin Pathol 1984;37:444–447
60% of maternal concentrations.29 Several small studies 12. van der Meer IM, Karamali NS, Boeke AJP, et al. High
suggest that inadequate vitamin D intake may be asso- prevalence of vitamin D deficiency in pregnant non-Western
women in The Hague, Netherlands. Am J Clin Nutr 2006;
ciated with adverse pregnancy outcomes, such as intra-
84:350–353; quiz 468–469
uterine growth restriction and preeclampsia.30,31 13. Holick MF. Vitamin D deficiency. N Engl J Med 2007;
However, currently there are no randomized trials that 357:266–281
examine the affect on maternal or fetal outcomes using 14. Bodnar LM, Simhan HN, Powers RW, Frank MP,
the cutoffs used in this study. Cooperstein E, Roberts JM. High prevalence of vitamin D
In summary, the incidence of vitamin D is defi- insufficiency in black and white pregnant women residing in
ciency and insufficiency is very high in early pregnancy in the northern United States and their neonates. J Nutr
2007;137:447–452
a southern city in the United States. Our findings are
15. Matsuoka LY, Wortsman J, Haddad JG, Kolm P, Hollis
similar to other pregnant populations in the United BW. Racial pigmentation and the cutaneous synthesis of
States and Europe. As in the nonpregnant population, vitamin D. Arch Dermatol 1991;127:536–538
African-American women are the most severely affected 16. Hollis BW. Comparison of equilibrium and disequilibrium
followed by Hispanics and then Caucasians.3 More assay conditions for ergocalciferol, cholecalciferol and their
research is necessary to determine the optimal vitamin major metabolites. J Steroid Biochem 1984;21:81–86
D levels during pregnancy and adequate vitamin D 17. Hollis BW, Kamerud JQ, Selvaag SR, Lorenz JD, Napoli JL.
Determination of vitamin D status by radioimmunoassay
supplementation in pregnant females.
with an 125I-labeled tracer. Clin Chem 1993;39:529–533
18. Hollis BW. Circulating 25-hydroxyvitamin D levels indica-
tive of vitamin D sufficiency: implications for establishing a
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