Vitamin D Deficiency and Insufficiency isCommon during PregnancyDonna 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 Caucasianwomen at <14 weeks of gestation; 25 hydroxyvitamin D levels (25(OH)D) levels weremeasured by radioimmunoassay. The mean 25(OH)D levels in African-American,Hispanic, and Caucasian pregnant women were 15.5� 7.2 (standard deviation),24.1� 8.7, 29.0� 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/Lor <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 forvitamin D deficiency or insufficiency. African-American women and Hispanic womenwere more likely to have vitamin D insufficiency and deficiency than Caucasian women.Furthermore, primigravid women were more at risk for vitamin D insufficiency. This studydemonstrates widespread vitamin D deficiency and insufficiency in pregnant females livingat a southern latitude. African-Americans are at greatest risk.

KEYWORDS: Hypovitaminosis D, pregnancy, vitamin D

With the identification of increasing numbersof children with rickets in the United States in the1990s, the medical community exhibited a renewedinterest in vitamin D deficiency and vitamin D research.1

One of the initial studies to assess the vitamin D status ofwomen of reproductive age used samples collected in theNutrition Examination Survey (NHANES III) from1988 through 1994 to measure 25 hydroxyvitamin Dlevels (25(OH)D). Forty-two percent of African-American and 4% of Caucasian females were found to

have vitamin D deficiency defined as less than37.5 nmol/L (<15 ng/mL).2 Follow-up data fromNHANES in 2000 to 2004 demonstrated that vitaminD concentrations in the population have not improved.3

Because women of reproductive age are deficient invitamin D, it was reasoned that pregnant women alsoare likely to be deficient.

Evaluation of vitamin D status of pregnantwomen has been primarily done outside of the UnitedStates in populations that are at significant risk for

1Division of Maternal Fetal Medicine, Department of Obstetrics andGynecology, Medical University of South Carolina; 2Division ofPediatric Nutrition, Department of Pediatrics, Children’s ResearchInstitution; 3Division of Pediatric Epidemiology, Department ofPediatrics, Rutledge Tower, Charleston, South Carolina; 4Departmentof Biostatistics, Mayo Clinic, Jacksonville, Florida.

Address for correspondence and reprint requests: Donna D.Johnson, M.D., Division of Maternal Fetal Medicine, Department ofObstetrics and Gynecology, Medical University of South Carolina,

96 Jonathan Lucas Street, CSB 634, Charleston, SC 29425-0619(e-mail: johnsodo@musc.edu).

Am J Perinatol. Copyright # by Thieme Medical Publishers, Inc.,333 Seventh Avenue, New York, NY 10001, USA. Tel: +1(212)584-4662.

Received: January 27, 2010. Accepted after revision: May 10, 2010.DOI: http://dx.doi.org/10.1055/s-0030-1262505.ISSN 0735-1631.

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vitamin D deficiency, such as immigrants with dark skinpigmentation living at very northern latitudes or womenwho wear clothing that covers most of the body surfacedue to religious and cultural preferences.4–12 In a largeEuropean study of 358 pregnant women, 8% of Westernand 73% of Turkish, Moroccan, and other non-West-erners were vitamin D deficient, defined as <25 nmol/L(<10 ng/mL). This study was conducted in The Hague,Netherlands. This city lies at the 52 degrees northlatitude and is 3 degrees north of the most northernlatitude of the vast majority of mainland United States.The intensity of the sun is greatest at the equator anddecreases at increasing latitudes.13 So, pregnant womenin the United States would be expected to be lessdeficient than the Netherlands cohort because the sunis more intense, especially during the summer months,and few American women wear clothing that fully coversthem.

A study of a pregnant cohort of 200 Caucasianand 200 African-American pregnant women wasrecently conducted in Pittsburgh, Pennsylvania (40degrees north latitude). Vitamin D levels were meas-ured at 4 to 21 weeks and at delivery. Five percent ofCaucasian females and 29% of African-Americanfemales were found to be vitamin D deficient asdefined by a 25(OH)D level <37.5 nmol/L (<15ng/mL). Forty-two percent of Caucasians and 54%of African-Americans were found to have vitamin Dinsufficiency (25(OH)D 37.5 to 80 nmol/L; 15 to 32ng/mL). Overall, only 53% of Caucasians and 17% ofAfrican-Americans had adequate vitamin D levels(>80 nmol/L or >32 ng/mL).14 Thus, despite beingcloser to the equator, vitamin D deficiency or insuffi-ciency in pregnant women is also prevalent in theUnited States.

What then accounts for this high prevalence ofvitamin D deficiency and insufficiency? Vitamin D isobtained from diet, dietary supplements, and sunlight.Few foods naturally contain vitamin D. In developedcountries, some foods are fortified with vitamin D. Theamount that food is fortified with vitamin D and theamount of vitamin D in the typical dietary supplement(400 IU) is inadequate to correct vitamin D deficiency.13

Cutaneous synthesis is the most important source ofvitamin D. Regardless of the latitude, any process thatreduces or blocks absorption of ultraviolet B radiationwill decrease the amount of vitamin D synthesized. Forexample, the darker skin pigmentation commonly seenin African-Americans decreases the amount of vitaminD synthesized.15 Not surprisingly, a racial disparity invitamin D levels and deficiency has long been recog-nized. Although pregnant African-American and Cau-casian females have been studied, very little is knownabout the pregnant Hispanic population. The objectiveof this observational study was to compare the baselinevitamin D levels of African-American, Hispanic,

and Caucasian pregnant women enrolled in a vitaminD supplementation trial and to report cumulativeincidence of vitamin D deficiency (<20 ng/mL or<50 nmol/L), insufficiency (�20 ng/mL and <32 ng/mLor �50 nmol/L and <80 nmol/L), and sufficiency(�32 ng/mL or >80 nmol/L) in these three groups ata southern (32.7 degrees north) latitude.

METHODSApproval for this study was granted by the MedicalUniversity of South Carolina’s Institutional ReviewBoard for Human Subjects, HR No. 10727 and theGeneral Clinical Research Center (Protocol #670). Pa-tients from Charleston, South Carolina, who were lessthan 14 weeks of pregnancy were recruited and gaveconsent over a 5-year period. Patients with diseasesassociated with defects in vitamin D such as sarcoid,renal disease, uncontrolled thyroid disease, or para-thyroid disease were excluded from the study. Inaddition, patients with chronic hypertension and dia-betes were excluded as patients with these diseases havea higher incidence of adverse pregnancy outcomes. Thevitamin D levels were obtained as baseline data duringa large randomized clinical trial in which women wererandomized to receive different amounts of vitamin Dsupplementation during pregnancy. The primary ob-jective of the trial was to determine the safety ofhigher-dose vitamin D supplementation in pregnancy.Race was self-reported and classified as non-Hispanicor Hispanic black, Hispanic white, or non-Hispanicwhite. Throughout this article, the classifications arereferred to as African-American, Hispanic, and Cau-casian. Demographic information was obtained at thefirst patient encounter. Prepregnancy maternal weightwas self-reported. Maternal height was measured atthe first clinical visit. This information was used tocalculate maternal prepregnancy body mass index(BMI) in kg/m2.

Whole blood was collected in serum separatortubes and centrifuged. Serum was collected and thenstored at �808C and analyzed in batches. Total circulat-ing 25(OH)D levels were measured using radioimmuno-assay as previously described.16 The detection limit ofthe assay is 2.8 mg/L. The assay precision (coefficientof variation) was less than 7%.17 Laboratory personnelwere blinded to sociodemographic data of the subject,including race/ethnicity.

Subjects were classified using the followingdefinitions. If their level of 25(OH)D was less than<20 ng/mL (<50 nmol/L), the subjects were classifiedas vitamin D deficient. If their levels were �20 but<32 ng/mL (�50 nmol/L and <80 nmol/L), the sub-jects were classified as insufficient. Only subjects withserum levels of 25(OH)D �32 ng/mL (�80 nmol/L)were classified as having sufficient vitamin D levels.17–19

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Data were analyzed using SAS for Windowsversion 9.1. Categorical variables were analyzed usingchi-square and continuous variables were analyzed usinganalysis of variance. A p value less than 0.05 definedsignificance. Multivariate analysis of the three categoriesof vitamin D was conducted with multinomial logisticregression using Proc Logistic in SAS. This procedureallows the modeling of the dependent variable as athree-group categorical variable (vitamin D <20 ng/mL[<50 nmol/L], vitamin D �20 to <32 ng/mL[�50 nmol/L and <80 nmol/L], vitamin D �32 ng/mL[�80 nmol/L]) as a function of the independent variablesage, parity, ethnicity, obesity (BMI >30), and sunlightexposure. The results of this analysis present an odds ratioand 95% confidence interval for the association of eachindependent variable with the two categories of vitaminD deficiency (<20 ng/mL or <50 nmol/L) and vitaminD insufficiency (20 to 32 ng/mL or >50 nmol/L and<80 nmol/L), considering vitamin D sufficiency(�32 ng/mL or �80 nmol/L) as the reference category.

RESULTSDemographic data are presented in Table 1. Caucasianwomen were older than either African-Americans orHispanics. Caucasians and Hispanics were more likely tobe primigravid than African-Americans. More African-Americans were obese than either Caucasians or His-panic women. The average gestational age at enrollmentwas less than 12 weeks in all groups, but Hispanicwomen were enrolled at an earlier gestational age thanthe other two groups. Samples were drawn as frequentlyin the spring and summer compared with fall and winter.

The mean 25(OH)D levels in African-Americans, Hispanics, and Caucasians were 15.5�7.2(standard deviation), 24.1�8.7, 29.0�8.5 ng/mL, re-spectively. The range for African-Americans was 2.4 to43.5 ng/mL, for Hispanics was 6.2 to 52.9 ng/mL, andfor Caucasians was 9.3 to 69.0 ng/mL. Forty-one percent(200/494) of all pregnant women were deficient, andan additional 41% (204/494) were insufficient. Overall,82% of this cohort had vitamin D levels <32 ng/mL(<80 nmol/L). Figure 1 displays vitamin D deficiency,insufficiency, and sufficiency by race. More African-

Americans were deficient than either Hispanics or Cau-casians. Ninety-seven percent (149/154) of African-Americans, 81% (157/194) of Hispanics, and 67% (98/146) of Caucasians were insufficient or deficient. MoreCaucasians had normal vitamin D levels than the othertwo groups; of those two groups, Hispanics were morelikely than African-Americans to have normal vitamin Dlevels.

Table 2 presents the results of the logistic regres-sion modeling for vitamin D deficiency, insufficiency,and sufficiency. Controlling for these potential con-founders (maternal age, parity, race, BMI �30, andenrollment during summer months), African-Americanand Hispanic women were persistently at greater risk foreither vitamin D deficiency or insufficiency than Cau-casians. Of the included covariables, only primigravidwomen were significantly at risk for vitamin D insuffi-ciency.

DISCUSSIONThis study clearly demonstrates a high incidence ofvitamin D deficiency and insufficiency and in womenduring their first trimester of pregnancy in a city in theUnited States with high UV index. The incidence ofvitamin D deficiency and insufficiency in this population

Table 1 Demographics by Ethnicity

Demographics

African-American

(n¼ 154)

Hispanic

(n¼ 189)

Caucasian

(n¼ 146) p Value

Maternal age (mean, SD)* 25.3�4.9 24.8� 4.8 30.1�5.4 <0.001

Gestational age (mean, SD)* 11.6�2.3 9.5�2.1 10.7�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.yChi-square.BMI, body mass index; SD, standard deviation.

Figure 1 Vitamin D deficiency (<20 ng/mL or <50 nmol/L,

black bar) is more common in African-Americans, and vitamin

D sufficiency (�32 ng/mL or �80 nmol/L, white bar) is more

common in the Caucasian population.

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is higher than or similar to the incidence reported inother studies conducted in an adult population whensimilar definitions for vitamin D deficiency, insuffi-ciency, and sufficiency is used.14 Skin pigmentation,and thus race and ethnicity, influence the amount ofvitamin D synthesis from sun exposure. Persons withdarker skin synthesize less vitamin D for a given ex-posure and are, not surprisingly, more prone to vitaminD deficiency.15 In the U.S. study conducted in Pitts-burgh, Pennsylvania, 83% of blacks and 47% of whiteshad insufficient or deficient vitamin D levels.14 Thisobservation is consistent in our population where 97% ofAfrican-Americans and 67% of Caucasians had vitaminD deficiency or insufficiency. Because Hispanics havedarker pigmentation than Caucasians and generallylighter pigmentation than blacks, the expected frequencyof vitamin D deficiency or insufficiency in pregnantHispanics should be greater than Caucasians but lessthan African-Americans. Indeed, this observation hasbeen made in the general population and was alsoconfirmed in our pregnancy population.3 In fact, race/ethnicity is the variable most strongly associated withvitamin D levels in our population.

Seasonality has long been recognized as an im-portant modulator of vitamin D status. Subjects havehigher 25(OH)D levels in the summer than inthe winter.13 For example, above 35 degrees northlatitude (Atlanta, Georgia), little or no vitamin D canbe produced from November to February.13 In ourstudy, seasonality was not a significant covariable inour population. Others have noted no impact of season-ality on 25(OH)D levels in their population.12 Severalexplanations are possible. We did not examine the

amount of time outside and the use of sunscreens inthis study. Because of the heat index, subjects mayspend less time outside in the summer compared withthe other seasons. Also, African-Americans have asmaller increase in vitamin D levels than Caucasianswith the same amount of sun exposure.20 Finally, ourpopulation may have been so deficient that the amountof sun exposure did not significantly impact their levels.In Florida, female subjects only experience a 13%increase in their 25(OH)D levels between winter andsummer.21

Obesity is also a known risk factor for vitamin Ddeficiency.22–25 The etiology of this association is un-clear. Several hypotheses have been proposed. Peoplewith a higher BMI may avoid sunbathing or adiposetissue may sequester vitamin D.23 Also, obesity may notaffect the vitamin D status of all races equally.23,25 In ourcohort, we defined obese patients (BMI �30) and non-obese patient (BMI �30) and using this cut-point forobesity in our cohort, obesity was not a risk factor fordeficient or insufficient vitamin D levels. Others havecompared obese patients (BMI �30) to patients withnormal weight (BMI �25).22,24 In our study, includingthe overweight individuals may have blunted the effectof obesity on vitamin D levels.

In our study, primigravid subjects were morelikely to have deficient or insufficient vitamin D levelsthan multiparous subjects. In most studies, parity has notbeen examined in relationship to vitamin D. In thelargest U.S. study, the majority of blood samples wereobtained only from primigravid women and all of theirpatients were nulliparous (i.e., had not delivered a child>20 weeks).14 In the largest European trial with

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

32þ 1.00 (ref) — —

BMI, body mass index; CI, confidence interval.

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358 subjects, parity was not significant.12 Parity wasspecifically studied in 86 Saudi pregnant women; how-ever, the authors compared patients who were para 5 tosubjects who were para 4 or less, and in this comparison,parity did not affect vitamin D levels.26 In our popula-tion, primigravid women may have different habits thanmultiparous women. We did not examine the relation-ship of parity to diet, sun exposure, and supplementationuse in this analysis.

There is no consensus on the optimal levels of25(OH)D. Most experts agree that vitamin D deficiencyis <20 ng/mL (50 nmol/L), and this is the definition weused in our population.13 We chose to define vitamin Dinsufficiency as <32 ng/mL (80 nmol/L). Recent datasuggest that a cutoff of <32 ng/mL (80 nmol/L) is moreappropriate based on the measurement of specific bio-markers that increase or decrease with changes in25(OH)D levels, such as parathyroid hormone, calciumabsorptions, and bone mineral density.18,27,28 Becausethe fetus is entirely dependent on maternal stores forvitamin D, adequate vitamin D levels during pregnancyare essential. The vitamin D level in the fetus is �50 to60% of maternal concentrations.29 Several small studiessuggest that inadequate vitamin D intake may be asso-ciated with adverse pregnancy outcomes, such as intra-uterine growth restriction and preeclampsia.30,31

However, currently there are no randomized trials thatexamine the affect on maternal or fetal outcomes usingthe cutoffs used in this study.

In summary, the incidence of vitamin D is defi-ciency and insufficiency is very high in early pregnancy ina southern city in the United States. Our findings aresimilar to other pregnant populations in the UnitedStates and Europe. As in the nonpregnant population,African-American women are the most severely affectedfollowed by Hispanics and then Caucasians.3 Moreresearch is necessary to determine the optimal vitaminD levels during pregnancy and adequate vitamin Dsupplementation in pregnant females.

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