Vita D Defic Mothers Newborns Merewood Pediatrics 2010

Widespread Vitamin D Deficiency in UrbanMassachusetts Newborns and Their Mothers

WHAT’S KNOWN ON THIS SUBJECT: Vitamin D deficiency seemsto be more widespread than has been previously understood, andnewborns and their mothers are at high risk.

WHAT THIS STUDY ADDS: Information about predisposingfactors for vitamin D deficiency in newborns and mothers andabout the relationship between maternal and infant vitamin Dstatus. The results also suggest that prenatal vitamins are notadequate sources of vitamin D for pregnant women.

abstractOBJECTIVE: To determine vitamin D status and associated factors in acohort of newly delivered infants and their mothers in Boston,Massachusetts.

PATIENTS AND METHODS: Enrollment in this cross-sectional study tookplace from 2005 to 2007 in an urban Boston teaching hospital with 2500births per year. A questionnaire and medical-record data were used toidentify variables that are potentially associated with vitamin D deficiency(25-hydroxyvitamin D [25(OH)D] � 20 ng/mL). Infant and maternal bloodwas obtained by venipuncture within 72 hours of birth. The main outcomemeasure was infant and maternal 25(OH)D status, assessed by competi-tive protein binding.

RESULTS: We enrolled 459 healthy mother/infant pairs. After subsequentexclusions, analyses were performed on 376 newborns and 433 women.The median infant 25(OH)D level was 17.2 ng/mL (95% confidence interval[CI]: 16.0–18.8; range:�5.0 to 60.8 ng/mL). The median maternal 25(OH)Dlevel was 24.8 ng/mL (95% CI: 23.2–25.8; range:�5.0 to 79.2 ng/mL). Over-all, 58.0% of the infants and 35.8% of the mothers were vitamin D deficient(25[OH]D� 20 ng/mL); 38.0% of the infants and 23.1% of themothers wereseverely deficient (25[OH]D� 15 ng/mL). Risk factors for infant vitamin Ddeficiency included maternal deficiency (adjusted odds ratio [aOR]: 5.28[95% CI: 2.90–9.62]), winter birth (aOR: 3.86 [95% CI: 1.74–8.55]), blackrace (aOR: 3.36 [95% CI: 1.37–8.25]), and a maternal BMI of�35 (aOR: 2.78[95% CI: 1.18–6.55]). Maternal prenatal-vitamin use throughout the sec-ond and third trimesters was protective against infant deficiency (aOR:0.30 [95% CI: 0.16–0.56]). Similarly, prenatal-vitamin use of�5 times perweek in the third trimester was protective for mothers (aOR: 0.37 [95% CI:0.20–0.69]). Despite this,�30% of the women who took prenatal vitaminswere still vitamin D deficient at the time of birth.

CONCLUSIONS: A high proportion of infants and their mothers in NewEngland were vitamin D deficient. Prenatal vitamins may not containenough vitamin D to ensure replete status at the time of birth. Pediatrics2010;125:640–647

AUTHORS: Anne Merewood, MPH, IBCLC,a Supriya D.Mehta, PhD, MHS,b Xena Grossman, RD, MS,a Tai C. Chen,PhD,c Jeffrey S. Mathieu, MS,c Michael F. Holick, PhD, MD,c

and Howard Bauchner, MDa

aDivision of General Pediatrics, Boston Medical Center, andBoston University School of Medicine, Boston, Massachusetts;bDivision of Epidemiology and Biostatistics, University of IllinoisChicago School of Public Health, Chicago, Illinois; cDivision ofEndocrinology, Diabetes and Nutrition, Department of Medicine,Boston University School of Medicine, Boston, Massachusetts

KEY WORDSvitamin D, newborns, urban, minority health, pregnancy, birth

ABBREVIATIONS25(OH)D—25-hydroxyvitamin DWIC—Supplemental Nutrition Program for Women, Infants, andChildrenCI—confidence intervalaOR—adjusted odds ratio

www.pediatrics.org/cgi/doi/10.1542/peds.2009-2158

doi:10.1542/peds.2009-2158

Accepted for publication Jan 14, 2010

Address correspondence to Anne Merewood, MPH, IBCLC,Division of General Pediatrics, Boston Medical Center, 88 ENewton St, Vose 3, Boston, MA 02118. E-mail:[email protected]

PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275).

Copyright © 2010 by the American Academy of Pediatrics

FINANCIAL DISCLOSURE: The authors have indicated they haveno financial relationships relevant to this article to disclose.

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In 1898, 80% of inpatient childrenyounger than 2 years of age at a Bos-ton, Massachusetts, hospital showedphysical signs of rickets.1 The disease,ubiquitous in industrialized nations inthe early 20th century, virtually disap-peared after its causal pathway wasrecognized and the hormone “vitamin”D was added to milk for population-level supplementation.2 Recent re-ports, however, have suggested thatrickets is reemerging1,3 and demon-strated that vitamin D deficiencyis widespread in industrialized na-tions.1,4–8 In 2008, the American Acad-emy of Pediatrics issued new guide-lines for vitamin D intake in children,from infancy through adolescence,and called for an increase in previoussupplementation recommendations.9

Vitamin D deficiency has been associ-ated with a broader range of adversehealth outcomes than was previouslyacknowledged7,10,11 and seems to beprevalent in women of childbearingage and young children.12–15 The goal ofour study was to examine vitamin Dstatus in mothers and newborns inBoston and to determine factors thatwere associated with vitamin D defi-ciency in that population, such asprenatal-vitamin use. Although dark-skinned people who live in the innercity are at the highest risk of defi-ciency, few studies have examinedinfants and their mothers in thispopulation.

METHODS

The study was conducted at an urbanBoston teaching hospital with 2500births per year and a primarily low-income black and Hispanic population.Between January 2005 and December2007, women were screened for eligi-bility and approached in the maternityservice; those who agreed to partici-pate were enrolled within 72 hours ofthe birth of their child. Mother/infantpairs were eligible if the mother spoke

English, Spanish, or French; was white,black, or Hispanic (because of insuffi-cient numbers of potential subjectsfrom other races/ethnicities); was notusing illegal drugs; and had no historyof parathyroid, renal, or liver disease.Race was self-identified through theenrollment questionnaire. Pairs wereineligible if the infant was premature,had a congenital anomaly, or was ad-mitted to the NICU or if the mother hadspent more than half the pregnancyoutside the greater Boston area (be-cause of the potential for differentsunlight-exposure levels from womenwho were pregnant in Boston). Thestudy was approved by the Boston Uni-versity Medical Center institutional re-view board.

After signing informed-consent forms,women completed a questionnaire ondemographic, lifestyle, and behavioralfactors; additional data were obtainedfrom the medical record. Before dis-charge from the hospital, a blood sam-ple was obtained by venipuncture fromthe mother and infant.

Variables assumed to be pertinent tovitamin D status included season ofbirth (vitamin D is made primarily bythe skin in sunlight, and research re-sults have suggested that sunlight isonly intense enough between Marchand October, in Boston, to produce vi-tamin D316); use of prenatal vitamins(most of which contain 400 IU per dailydose); maternal prepregnancy BMI(obtained from the medical record);milk consumption; clothing habits; andother measures of sunlight exposure.Numerous questions were asked to as-sess clothing habits. For example,women were asked to recall for eachtrimester how frequently they wentoutside in clothing that revealed theirlegs from below the knees and theirarms from the shoulders down. Othermeasures to determine sunlight expo-sure included reported use of sun-screen and time spent in the sun.

Skin color was categorized as “light,”“medium,” and “dark” according tocategories derived from the Fitz-patrick et al skin-type matrix.17 Be-cause race/ethnicity is not necessarilyan accurate measure of skin color,analyses were conducted according toskin color as well as by race/ethnicity.

Diagnostic Test

Serum 25-hydroxyvitamin D (25[OH]D),accepted as the indicator of vitamin Dstatus in individuals, was measured bycompetitive protein binding as de-scribed by Chen et al.18 The competitiveprotein-binding assay that was per-formed used the vitamin D–bindingprotein that recognizes 25(OH)D3equally as well as 25(OH)D2. This assaywas validated previously by liquidchromatography tandem mass spec-troscopy.19 The lower limit of detectionwas 5 ng/mL, and the intraassay andinterassay coefficients of variationwere 5.0% to 10% and 10% to 15%, re-spectively. The reference range was 20to 100 ng/mL. Serum was frozen at�80°C and stored, and tests were runin batches approximately every 2weeks.

Statistical Analyses

We conducted 2 separate analyses toexamine risks for vitamin D deficiencyin infants and their mothers. The out-come was vitamin D deficiency (dichot-omized as �20 vs �20 ng/mL) andwas examined separately for new-borns and mothers. Newborns andmothers with 25(OH)D levels below thelevel of detection (�5 ng/mL) werecategorized as being at �20 ng/mLfor models examining predictors ofdeficiency.

Explanatory variables in the infantmodel were season of birth, mother’sskin color and 25(OH)D status, mater-nal sociodemographics, gestationalage, birth weight and length, gender,

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Apgar score, and mother’s sun expo-sure and prenatal-vitamin use.

Explanatory variables in the maternalmodel were maternal sociodemo-graphics (age, educational attainment,marital status, employment status,health insurance, Supplemental Nutri-tion Program for Women, Infants, andChildren [WIC] status, and place ofbirth), parity, mode of delivery, hospi-talization, bed rest, weight gain duringpregnancy, BMI, and skin color (light,medium, or dark). For each trimesterof pregnancy, we examined prenatal-vitamin use and sun exposure (fre-quency and duration of time spent out-side, sun-protective-factor use). Intakeof foods high in vitamin D content, in-cluding vitamin D–fortified milk andorange juice, cod liver oil, certainfish, fortified cereals, and eggs, wasascertained from a food-frequencyquestionnaire.

We estimated a sample size of 417 in-fants and mothers to observe a 20%difference in the proportion of infantsand mothers with vitamin D deficiencyaccording to race and season with80% power (2-sided test of signifi-cance: � � .017 for multiple compari-sons). The racial makeup of the popu-lation was known in advance, and weassumed that births would be evenlydistributed over the seasons. However,to further ensure that equal numbersof individuals of the desired raceswere enrolled in the desired season,we tracked enrollment over the courseof the study. When numbers of individ-uals of specific races were not evenlydistributed, we proactively enrolled tomeet the desired quota.

Differences between explanatory vari-ables and the outcome were assessedby �2 test for categorical variables. Incross-sectional analysis, there wereno first-trimester variables regardingsun exposure and vitamin use thatwere associated with infant or mater-nal vitamin D status in exploratory

analysis at a P value of �.20. In addi-tion, we used the generalized estimat-ing equations (GEE) extension of gener-alized linear models to account for thewithin-subject correlation among therepeated measures, assuming bino-mial distributions with log link. None ofthe repeated-measure variables werestatistically significant in GEE20 exceptfor vitamin use. In addition, variablesthat assessed sun exposure had lowcorrelation between the first and thirdtrimesters (r � 0.27, all measures),which was expected because of sea-sonal variation in weather. Thecorrelation between first- and third-trimester vitamin use was 0.38. There-fore, composite variables were cre-ated as needed, and standard logisticregression modeling was used to iden-tify factors associated with maternaland infant vitamin D deficiency.

Variables significant at the P � .20level in exploratory analysis were ex-amined by univariate logistic regres-sion. Variables significant at the P �.20 level by likelihood-ratio testingwere entered into a multivariable lo-gistic regression model by using for-ward stepwise entry. Wald-test P val-ues are presented for the finalmultivariable model. Data were ana-lyzed by using Stata/SE 9.2 for Win-dows (Stata Corp, College Station, TX).

RESULTS

We enrolled 458 mother/infant pairsbetween January 1, 2005, and Decem-ber 31, 2007. Of these, 12 pairs werelater excluded for the following rea-sons: 1 spent �7 months of the preg-nancy outside of the United States, 2withdrew consent, and for 9 pairs wefailed to obtain either infant or mater-nal blood samples. In addition, 70 en-rolled infants and 13 women weresubsequently excluded because offailure to obtain an adequate bloodsample. Thus, analyses were per-formed on 376 newborns and 433

women; because we were indepen-dently interested in a woman’s sta-tus at the time of delivery, womenwere not excluded from maternalanalyses because their infant’sblood was not available.

The median infant 25(OH)D level was17.2 ng/mL (95% confidence interval[CI]: 16.0–18.8; range:�5.0 to 60.8 ng/mL). The median maternal 25(OH)Dlevel was 24.8 ng/mL (95% CI:23.2–25.8; range: �5.0 to 79.2 ng/mL).According to the standard of �20ng/mL as deficient,14 58.0% of the in-fants and 35.8% of the mothers werevitamin D deficient. With a 25(OH)Dlevel� 15 ng/mL as amarker of severedeficiency, 38% of the infants and23.1% of the mothers were severely vi-tamin D deficient.

Infant Vitamin D Status

In bivariate analyses, variables associ-ated with infant vitamin D status atbirth included season of birth and themother’s vitamin D status, skin color,use of prenatal vitamins, and clothinghabits (Table 1). Although duration ofsun exposure was statistically signifi-cantly associated with maternal vita-min D status, it was not associatedwith infant vitamin D status. After mul-tivariable logistic regression, risk fac-tors for infant vitamin D deficiency thatremained statistically significant in-cluded maternal deficiency (adjustedodds ratio [aOR]: 5.28 [95% CI: 2.90–9.62]), winter birth (aOR: 3.86 [95% CI:1.74–8.55]), black race (aOR: 3.36[95% CI: 1.37–8.25]), and a maternalBMI of �35 (aOR: 2.78 [95% CI: 1.18–6.55]). Maternal use of prenatal vita-mins�5 days/week during at least thesecond and third trimesters (com-pared with use of prenatal vitamins�5 days week in at least 2 trimesters)was protective of vitamin D deficiencyin the infant (aOR: 0.30 [95% CI: 0.16–0.56]) (Table 2).



Maternal Vitamin D Status

Variables associated with maternal vi-tamin D status in bivariate analysis in-cluded season of birth, skin color, bedrest during pregnancy, use of vitaminsin the third trimester, drinking milk,and time spent outside (Table 3). Useof prenatal vitamins in the first andsecond trimesters was not associatedwith vitamin D status, nor was con-sumption of vitamin D–fortified orangejuice, cod liver oil, fish, or fortified ce-reals (data not shown). Women whoreported consuming eggs had a lowerprevalence of vitamin D deficiency;however, egg consumption was lesscommon among US-born mothers andthose who took vitamins less fre-quently during the third trimester.

In multivariable logistic regression,the strongest predictor of vitamin Ddeficiency was giving birth in wintercompared with summer (aOR: 4.78[95% CI: 2.39–9.55]). Other statisticallysignificant risk factors for maternal de-ficiency were dark skin color (aOR: 2.74[95% CI: 1.53–4.88]), fall birth (aOR: 2.73[95% CI: 1.41–5.32]); and being born inthe United States (aOR: 2.03 [95% CI:1.25–3.30]). Frequent vitamin use in thethird trimester, drinking milk duringpregnancy, andspendingat least 1hour/day outside during the second or thirdtrimesters were protective against vita-min D deficiency (Table 4).

DISCUSSION

We found that, in a population oflargely Hispanic and black urbanmothers and newborns, vitamin D de-ficiency was present in 58% of the new-borns and 35.8% of the mothers, andsevere deficiency was present in 38%of the infants and 23.1% of the moth-ers. Maternal and infant status wereclosely associated, and winter birth aswell as a BMI of�35 were risk factorsfor mothers and infants. These resultsare consistent with findings fromother studies.21,22

TABLE 1 Factors Associated With Infant 25(OH)D Status

Variable Total (N� 376),n (%)

Infant 25(OH)D Status P

�20 ng/mL(n� 158),n (%)

�20 ng/mL(n� 218),n (%)

Maternal 25(OH)D, ng/mL �.001�20 230 (63.4) 129 (56.1) 101 (43.9)�20 133 (36.6) 24 (18.0) 109 (82.0)Type of delivery .29Vaginal 284 (75.5) 115 (40.5) 169 (59.5)Cesarean 92 (24.5) 43 (46.7) 49 (53.3)Infant gender .24Female 192 (51.1) 75 (39.1) 117 (60.9)Male 184 (48.9) 83 (45.1) 101 (54.9)Season of birthSummer 97 (25.8) 54 (55.7) 43 (44.3) �.001Fall 89 (23.7) 38 (42.7) 51 (57.3)Winter 88 (23.4) 18 (20.5) 70 (79.5)Spring 102 (27.1) 48 (47.1) 54 (52.9)Maternal race/ethnicitya .002White 40 (10.6) 25 (62.5) 15 (37.5)Hispanic 195 (51.9) 87 (44.6) 108 (55.4)Black 141 (37.5) 46 (32.6) 95 (67.4)Maternal skin color .02Light 124 (33.0) 64 (51.6) 60 (48.4)Medium 129 (34.3) 51 (39.5) 78 (60.5)Dark 123 (32.7) 43 (35.0) 80 (65.0)Maternal age, y .08

�20 40 (10.6) 11 (27.5) 29 (72.5)20 to�30 221 (58.8) 92 (41.6) 129 (58.4)30–43 115 (30.6) 55 (47.8) 60 (52.2)Maternal place of birth .33Non-US born 244 (64.9) 107 (43.9) 137 (56.1)US born 132 (35.1) 51 (38.6) 81 (61.4)Maternal education .54Less than high school 156 (41.6) 63 (40.4) 93 (59.6)High school graduate/GED 111 (29.6) 44 (39.6) 67 (60.4)More than high school 108 (28.8) 50 (46.3) 58 (53.7)WIC recipient .18No 56 (14.9) 28 (50.0) 28 (50.0)Yes 319 (85.1) 129 (40.4) 190 (59.6)Maternal health insurance .92Public 331 (88.7) 139 (42.0) 192 (58.0)Private, self-pay 42 (11.3) 18 (42.9) 24 (57.1)Maternal bed rest during pregnancy .38No 342 (91.4) 145 (42.4) 197 (57.6)Yes 32 (8.6) 11 (34.4) 21 (65.6)Frequency of prenatal-vitamin use in first trimester .002

�5 d/wk 118 (32.2) 35 (29.7) 83 (70.3)�5 d/wk 248 (67.8) 119 (48.0) 129 (52.0)Frequency of prenatal-vitamin use in secondtrimester

.001

�5 d/wk 84 (22.8) 21 (25.0) 63 (75.0)�5 d/wk 285 (77.2) 136 (47.7) 149 (52.3)Frequency of prenatal-vitamin use in thirdtrimester

�.001

�5 d/wk 92 (24.9) 23 (25.0) 69 (75.0)�5 d/wk 278 (75.1) 134 (48.2) 144 (51.8)Frequency of prenatal-vitamin useb �.001

�5 d/wk in�1 trimester 84 (24.1) 20 (23.8) 64 (76.2)�5 d/wk during at least second and thirdtrimester

264 (75.9) 129 (48.9) 135 (51.1)

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Although sun exposure was protectiveof vitamin D deficiency in the mothers,this protective effect was not trans-

ferred to their infants, which suggeststhat other factors may influencematernal-fetal transference of vitamin

D. Although maternal vitamin D statuswas an important factor in predictinginfant vitamin D status, the correlationbetweenmaternal and infant vitamin Ddeficiency is not 1-to-1: 18% of the in-fants born to vitamin D–deficientmothers were not deficient, whereas44% of the infants born to vitaminD–replete mothers were deficient. Forexample, a maternal BMI of �35 wasassociated with increased risk of defi-ciency in the infants but not in themothers, which suggests that obesitymay possibly impede transference ofmicronutrients during pregnancy; thisis a novel association that is worth ad-ditional examination.

Wewere able to identifymodifiable fac-tors that could decrease risk. For in-fants, the strongest association ob-served was with maternal deficiency,which implies that improved vitamin Dstatus in mothers will have beneficialeffects on infants. Frequent prenatal-vitamin use reduced the infant’s risk ofdeficiency if the mother took themthroughout the second and third tri-mesters. Third-trimester vitamin usealone may not be sufficient to reduceinfant deficiency; rather, a longerduration of use may be needed foradequate stores. Although prenatal-vitamin use �5 times per week in thethird trimester was protective forwomen,�30% of the women who tookthe prenatal vitamin this often werestill vitamin D deficient at the time ofbirth. One possible explanation for thisresult is that the prenatal vitamin doesnot contain enough vitamin D to affectan apparent chronic deficiency inthese women of childbearing age. Forthemothers, drinkingmilk andspendingtimeoutsidewereprotectiveof vitaminDdeficiency. Although a BMI of�35 was arisk factor for bothmothers and infants,when compared with a BMI of�35, therisk of deficiency did not increase pro-portionally with increased BMI and was

TABLE 1 Continued

Variable Total (N� 376),n (%)

Infant 25(OH)D Status P

�20 ng/mL(n� 158),n (%)

�20 ng/mL(n� 218),n (%)

Mother ever drank milk during pregnancy .01No 51 (13.6) 13 (25.5) 38 (74.5)Yes 324 (86.4) 144 (44.4) 180 (55.6)Maternal employment status during pregnancy .37No/part-time 264 (70.6) 114 (43.2) 150 (56.8)Full-time 110 (29.4) 42 (38.2) 68 (61.8)Maternal frequency of exposing arms or legsduring third trimester

�.001

0–4 d/wk 197 (52.7) 66 (33.5) 131 (66.5)5–7 d/wk 177 (47.3) 91 (51.4) 86 (48.6)Maternal smoking status .34Never/before pregnancy 333 (88.6) 137 (41.1) 196 (58.9)During pregnancy 43 (11.4) 21 (48.8) 22 (51.2)Any maternal alcohol during pregnancy .86No 355 (94.7) 149 (42.0) 206 (58.0)Yes 20 (5.3) 8 (40.0) 12 (60.0)Any maternal medical problem .10No 281 (74.7) 125 (44.5) 156 (55.5)Yes 95 (25.3) 33 (34.7) 62 (65.3)Maternal BMI .001

�35 327 (87.0) 148 (45.3) 179 (54.7)�35 49 (13.0) 10 (20.4) 39 (79.6)

GED indicates General Educational Development.a Maternal race and skin color were highly correlated (0.76). Therefore, only 1 of these variables was entered inmultivariateregression. Maternal race/ethnicity was chosen, because it explained a greater amount of variance than did skin color.b Frequency of vitamin use in the first trimester was correlated with the second (0.51) and third (0.38) trimesters, andsecond-trimester vitamin use was correlated with third-trimester use (0.76). Therefore, a composite variable was createdto summarize use over all trimesters.

TABLE 2 Results of Univariate and Multivariate Logistic Regression for Risks for Infant 25(OH)DDeficiency at Term

Variable Crude OR (95% CI) aOR (95% CI)

Maternal 25(OH)D, ng/mL�20 Referent Referent�20 5.80 (3.47–9.69) 5.28 (2.90–9.62)Season of birthSummer Referent ReferentFall 1.69 (0.94–3.01) 1.66 (0.82–3.34)Winter 4.88 (2.54–9.40) 3.86 (1.74–8.55)Spring 1.41 (0.81–2.47) 1.14 (0.58–2.21)Maternal race/ethnicityWhite Referent ReferentHispanic 2.07 (1.03–4.16) 2.47 (1.05–5.80)Black 3.44 (1.66–7.15) 3.36 (1.37–8.25)Frequency of prenatal-vitamin use

�5 d/wk in�1 trimester Referent Referent�5 d/wk during at least the second and third trimesters 0.33 (0.19–0.57) 0.30 (0.16–0.56)Maternal BMI

�35 Referent Referent�35 3.22 (1.56–6.68) 2.78 (1.18–6.55)

All parameter estimates were adjusted for other covariates presented. Variables entered from univariate analysis thatwere not statistically significant in multivariate analysis were maternal age, clothing, ever drinking milk during pregnancy,and maternal medical problem.



not evident at lower categorizations ofBMI (data not shown).

The rates of deficiency in this study,especially in infants, were particularlyhigh. The use of 20 ng/mL as an indica-tor of deficiency is now standard inadult populations. We used it in our in-fant population, because it is the clini-cally accepted standard used in hospi-tals in our area, including our own;children with a 25(OH)D level of �20ng/mL are treated for deficiency. Re-cently, using�20 ng/mL as deficient ina Boston population of infants and us-ing a comparable assay, Gordon et al14

found a 12% rate of deficiency. How-ever, we suggest that our rates werehigher because we measured new-born levels, whereas Gordon et al in-cluded infants and older infants up to 1year of age. Newborn status is relatedto maternal status and likely changesin the first year of life.

A recent review by the American Acad-emy of Pediatrics suggested that ade-quate vitamin D status is important fora range of developmental factors in in-fants and children, including skeletaldevelopment, higher birth weight, andimproved bone-mineral content andbone mass in children at 9 years ofage.9 In addition, we recently re-ported an association between ma-ternal vitamin D deficiency at birthand an elevated risk of primary ce-sarean delivery.23 This is consistentwith data of the impact of vitamin Ddeficiency on skeletal and smoothmuscle function.

It should be noted that skin color wasa risk for deficiency in mothers,whereas race/ethnicity was a statisti-cally clearer risk for deficiency in in-fants. It is possible that the variablerace/ethnicity includes unmeasuredconfounders that have important bear-ing on infant vitamin D status but noton maternal vitamin D status.

We acknowledge some limitations.Data regarding variables in pregnancy

TABLE 3 Factors Associated With Maternal 25(OH)D Status

Variable Total, n (%) Maternal 25(OH)D Status P

�20 ng/mL(n� 278),n (%)

�20 ng/mL(n� 155),n (%)

Season of birth �.001Summer 112 (25.9) 91 (81.3) 21 (18.7)Fall 105 (24.3) 66 (62.9) 39 (37.1)Winter 99 (22.9) 45 (45.5) 54 (54.4)Spring 117 (27.0) 76 (65.0) 41 (35.0)Maternal race/ethnicitya .001Black 164 (37.9) 87 (53.0) 77 (47.0)White 46 (10.6) 35 (76.1) 11 (23.9)Hispanic 223 (51.5) 156 (70.0 67 (30.0)Maternal skin color �.001Light 140 (32.3) 107 (76.4) 33 (23.6)Medium 146 (33.7) 92 (63.0) 54 (37.0)Dark 147 (34.0) 79 (53.7) 68 (46.3)Maternal age, y �.999

�20 53 (12.2) 34 (64.2) 19 (35.8)20 to�30 254 (58.7) 163 (64.2) 91 (35.8)30–43 126 (29.1) 81 (64.3) 45 (35.7)Place of birth .001Non-US born 280 (64.7) 196 (70.0) 84 (30.0)US born 153 (35.3) 82 (53.6) 71 (46.4)Education .008Less than high school 179 (41.4) 129 (72.1) 50 (27.9)High school graduate/GED 133 (30.8) 82 (61.7) 51 (38.3)More than high school 120 (27.8) 66 (55.0) 54 (45.0)WIC recipient .25No 69 (16.0) 40 (58.0) 29 (42.0)Yes 363 (84.0) 237 (65.3) 126 (34.7)Health insurance .15Public 379 (88.1) 247 (65.2) 132 (34.8)Private, self-pay 51 (11.9) 28 (54.9) 23 (45.1)Bed rest in pregnancy .004No 388 (90.0) 257 (66.2) 131 (33.8)Yes 43 (10.0) 19 (44.2) 24 (55.8)Frequency of prenatal-vitamin use in third trimester .001Never or�1 d/wk 67 (15.7) 34 (50.7) 33 (49.3)1–4 d/wk 41 (9.6) 20 (48.8) 21 (51.2)�5 d/wk 319 (74.7) 221 (69.3) 98 (30.7)Maternal calcium supplement .81Never 196 (64.1) 110 (35.9)Sometimes 53 (62.4) 32 (37.6)Often 28 (68.3) 13 (31.7)Ever drank milk during pregnancy .004No 57 (13.2) 27 (47.4) 30 (52.6)Yes 374 (86.8) 250 (66.8) 124 (33.2)Employment status during pregnancy .03No/part-time 304 (70.7) 204 (67.1) 100 (32.9)Full-time 126 (29.3) 71 (56.3) 55 (46.7)Average time spent outside during second or thirdtrimestersb

.03

�1 h/d in second and third trimesters 199 (48.0) 118 (59.3) 81 (40.7)�1 h/d in second or third trimester 216 (52.0) 150 (69.4) 66 (30.6)Frequency of exposing arms or legs during thirdtrimesterc

�.001

0–4 d/wk 228 (52.9) 128 (56.1) 100 (43.9)5–7 d/wk 203 (47.1) 149 (73.4) 54 (26.6)Ever used sunscreen .61No 282 (65.4) 183 (64.9) 99 (35.1)Yes 149 (34.6) 93 (62.4) 56 (37.6)

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were collected retrospectively. We didnot have dietary intake of vitamin Dand calcium, only the frequency oramount of consumption. Althoughmothers were unaware of their vita-

min D levels at the time they werequestioned, knowledge of the studytopic may have influenced some re-sponses. The number of infants ana-lyzed was 90% of the estimated sample

size needed (376 vs 417) because ofdifficulty obtaining blood samples.Baseline values of 25(OH)D were miss-ing for some infants; however, this wasa result of inevitable difficulties draw-ing blood on young infants and was notassociated with the mother’s 25(OH)Dlevel, skin color, or season of birth (re-sults not shown).

In addition, although children with a25(OH)D level of �20 ng/mL aretreated with supplementation in theclinical setting, biomarkers of vitaminD deficiency in young children particu-larly are lacking. A need for researchto determine validity of commonly ac-cepted measures of deficiency hasbeen identified.21,24

CONCLUSIONS

We found that more than half of theinfants and approximately one third ofthemothers who gave birth in this Bos-ton study were vitamin D deficient atthe time of delivery. Although prenatal-vitamin use was protective for bothinfants and mothers, considerableproportions of infants and mothers re-mained deficient even when prenatalvitamins were taken regularly. It istime to rethink our approach to ensur-ing vitamin D sufficiency in newbornsand their mothers.

ACKNOWLEDGMENTSThis work was funded by Health Re-sources and Services Administration/Bureau of Maternal and Child Healthgrant R40 MC03620-01-00 and US De-partment of Agriculture/CooperativeState Research, Education, and Exten-sion Service grant 2005-35200-15260and supported by grant M01-RR00533from the General Clinical ResearchCenters Program of the National Cen-ter for Research Resources, NationalInstitutes of Health.

TABLE 3 Continued

Variable Total, n (%) Maternal 25(OH)D Status P

�20 ng/mL(n� 278),n (%)

�20 ng/mL(n� 155),n (%)

Smoking status .008Never/before pregnancy 386 (89.2) 256 (66.3) 130 (33.7)During pregnancy 47 (10.8) 22 (46.8) 25 (53.2)Any alcohol during pregnancy .99No 407 (94.2) (64.1) 146 (35.9)Yes 25 (5.8) 16 (64.0) 9 (36.0)Maternal BMI .01

�35 380 (87.8) 252 (66.3) 128 (33.7)�35 53 (12.2) 26 (49.1) 27 (50.9)

GED indicates General Educational Development.a Maternal race and skin color were highly correlated (0.76). Therefore, only 1 of these variables was entered inmultivariateregression. Maternal race/ethnicity was chosen, because it explained a greater amount of variance than did skin color.b The average amount of time spent outside daily was highly correlated between the second and third trimesters (0.76), sothey were combined into a single variable.c Frequency of exposing arms and legs during the first and second trimesters differed significantly according to themother’s 25(OH)D status. However, the direction of association was clearly confounded by season (ie, results were not inkeeping with the pattern seen in the third trimester of decreasing prevalence of vitamin D deficiency with increasing timespent outside).

TABLE 4 Results of Univariate and Multivariate Logistic Regression for Risks for Maternal 25(OH)DDeficiency at Term

Variable Crude OR (95% CI) aOR (95% CI)

Season of birthSummer Referent ReferentFall 2.56 (1.38–4.75) 2.73 (1.41–5.32)Winter 5.20 (2.80–9.64) 4.78 (2.39–9.55)Spring 2.34 (1.27–4.29) 1.87 (0.96–3.65)Maternal skin colorLight Referent ReferentMedium 1.90 (1.14–3.18) 2.46 (1.36–4.42)Dark 2.79 (1.68–4.63) 2.74 (1.53–4.88)Maternal place of birthNon-US born Referent ReferentUS born 2.02 (1.34–3.04) 2.03 (1.25–3.30)Frequency of prenatal-vitamin use in third trimesterNever or�1 d/wk Referent Referent1–4 d/wk 1.08 (0.50–2.35) 0.79 (0.32–1.91)�5 d/wk 0.46 (0.27–0.78) 0.37 (0.20–0.69)Ever drank milk during pregnancyNo Referent ReferentYes 0.45 (0.25–0.78) 0.45 (0.24–0.87)Time spent outside in second and third trimester

�1 h/d second and third trimester Referent Referent�1 h/d second or third trimester 0.64 (0.43–0.96) 0.55 (0.34–0.87)

All parameter estimates were adjusted for the other covariates presented. Variables entered from univariate analysis thatwere not statistically significant inmultivariate analysis werematernal race (correlatedwith skin color �r� 0.66�), bed restduring pregnancy, smoking during pregnancy, educational attainment, BMI, and employment status.



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