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  • 1. Widespread Vitamin D Deficiency in UrbanMassachusetts Newborns and Their Mothers WHAT’S KNOWN ON THIS SUBJECT: Vitamin D deficiency seems AUTHORS: Anne Merewood, MPH, IBCLC,a Supriya D. to be more widespread than has been previously understood, and Mehta, PhD, MHS,b Xena Grossman, RD, MS,a Tai C. Chen, newborns and their mothers are at high risk. PhD,c Jeffrey S. Mathieu, MS,c Michael F. Holick, PhD, MD,c and Howard Bauchner, MDa a WHAT THIS STUDY ADDS: Information about predisposing Division of General Pediatrics, Boston Medical Center, and factors for vitamin D deficiency in newborns and mothers and Boston University School of Medicine, Boston, Massachusetts; bDivision of Epidemiology and Biostatistics, University of Illinois about the relationship between maternal and infant vitamin D Chicago School of Public Health, Chicago, Illinois; cDivision of status. The results also suggest that prenatal vitamins are not Endocrinology, Diabetes and Nutrition, Department of Medicine, adequate sources of vitamin D for pregnant women. Boston University School of Medicine, Boston, Massachusetts KEY WORDS vitamin D, newborns, urban, minority health, pregnancy, birth ABBREVIATIONS 25(OH)D—25-hydroxyvitamin Dabstract WIC—Supplemental Nutrition Program for Women, Infants, and ChildrenOBJECTIVE: To determine vitamin D status and associated factors in a CI— confidence intervalcohort of newly delivered infants and their mothers in Boston, aOR—adjusted odds ratioMassachusetts. www.pediatrics.org/cgi/doi/10.1542/peds.2009-2158PATIENTS AND METHODS: Enrollment in this cross-sectional study took doi:10.1542/peds.2009-2158place from 2005 to 2007 in an urban Boston teaching hospital with 2500 Accepted for publication Jan 14, 2010births per year. A questionnaire and medical-record data were used to Address correspondence to Anne Merewood, MPH, IBCLC,identify variables that are potentially associated with vitamin D deficiency Division of General Pediatrics, Boston Medical Center, 88 E(25-hydroxyvitamin D [25(OH)D] Ͻ 20 ng/mL). Infant and maternal blood Newton St, Vose 3, Boston, MA 02118. E-mail:was obtained by venipuncture within 72 hours of birth. The main outcome anne.merewood@bmc.orgmeasure was infant and maternal 25(OH)D status, assessed by competi- PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275).tive protein binding. Copyright © 2010 by the American Academy of PediatricsRESULTS: We enrolled 459 healthy mother/infant pairs. After subsequent FINANCIAL DISCLOSURE: The authors have indicated they haveexclusions, analyses were performed on 376 newborns and 433 women. no financial relationships relevant to this article to disclose.The median infant 25(OH)D level was 17.2 ng/mL (95% confidence interval[CI]: 16.0 –18.8; range: Ͻ5.0 to 60.8 ng/mL). The median maternal 25(OH)Dlevel was 24.8 ng/mL (95% CI: 23.2–25.8; range: Ͻ5.0 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 Ͻ 20 ng/mL); 38.0% of the infants and 23.1% of the mothers wereseverely deficient (25[OH]D Ͻ 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 Ն35 (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 Ն5 times perweek in the third trimester was protective for mothers (aOR: 0.37 [95% CI:0.20 – 0.69]). Despite this, Ͼ30% 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;125:640–647640 MEREWOOD et al Downloaded from www.pediatrics.org. Provided by Siu School Of Medicine on March 25, 2010
  • 2. ARTICLESIn 1898, 80% of inpatient children English, Spanish, or French; was white, Skin color was categorized as “light,”younger than 2 years of age at a Bos- black, or Hispanic (because of insuffi- “medium,” and “dark” according toton, Massachusetts, hospital showed cient numbers of potential subjects categories derived from the Fitz-physical signs of rickets.1 The disease, from other races/ethnicities); was not patrick et al skin-type matrix.17 Be-ubiquitous in industrialized nations in using illegal drugs; and had no history cause race/ethnicity is not necessarilythe early 20th century, virtually disap- of parathyroid, renal, or liver disease. an accurate measure of skin color,peared after its causal pathway was Race was self-identified through the analyses were conducted according torecognized and the hormone “vitamin” enrollment questionnaire. Pairs were skin color as well as by race/ethnicity.D was added to milk for population- ineligible if the infant was premature,level supplementation.2 Recent re- had a congenital anomaly, or was ad- Diagnostic Testports, however, have suggested that mitted to the NICU or if the mother had Serum 25-hydroxyvitamin D (25[OH]D),rickets is reemerging1,3 and demon- spent more than half the pregnancy accepted as the indicator of vitamin Dstrated that vitamin D deficiency outside the greater Boston area (be- status in individuals, was measured byis widespread in industrialized na- cause of the potential for different competitive protein binding as de-tions.1,4–8 In 2008, the American Acad- sunlight-exposure levels from women scribed by Chen et al.18 The competitiveemy of Pediatrics issued new guide- who were pregnant in Boston). The protein-binding assay that was per-lines for vitamin D intake in children, study was approved by the Boston Uni- formed used the vitamin D– bindingfrom infancy through adolescence, versity Medical Center institutional re- protein that recognizes 25(OH)D3and called for an increase in previous view board. equally as well as 25(OH)D2. This assaysupplementation recommendations.9 After signing informed-consent forms, was validated previously by liquidVitamin D deficiency has been associ- women completed a questionnaire on chromatography tandem mass spec-ated with a broader range of adverse demographic, lifestyle, and behavioral troscopy.19 The lower limit of detectionhealth outcomes than was previously factors; additional data were obtained was 5 ng/mL, and the intraassay andacknowledged7,10,11 and seems to be from the medical record. Before dis- interassay coefficients of variationprevalent in women of childbearing charge from the hospital, a blood sam- were 5.0% to 10% and 10% to 15%, re-age and young children.12–15 The goal of ple was obtained by venipuncture from spectively. The reference range was 20our study was to examine vitamin D the mother and infant. to 100 ng/mL. Serum was frozen atstatus in mothers and newborns in Variables assumed to be pertinent to Ϫ80°C and stored, and tests were runBoston and to determine factors that vitamin D status included season of in batches approximately every 2were associated with vitamin D defi- birth (vitamin D is made primarily by weeks.ciency in that population, such as the skin in sunlight, and research re-prenatal-vitamin use. Although dark- sults have suggested that sunlight is Statistical Analysesskinned people who live in the inner only intense enough between Marchcity are at the highest risk of defi- We conducted 2 separate analyses to and October, in Boston, to produce vi-ciency, few studies have examined examine risks for vitamin D deficiency tamin D316); use of prenatal vitaminsinfants and their mothers in this in infants and their mothers. The out- (most of which contain 400 IU per dailypopulation. come was vitamin D deficiency (dichot- dose); maternal prepregnancy BMI omized as Ͻ20 vs Ն20 ng/mL) and (obtained from the medical record);METHODS was examined separately for new- milk consumption; clothing habits; andThe study was conducted at an urban other measures of sunlight exposure. borns and mothers. Newborns andBoston teaching hospital with 2500 Numerous questions were asked to as- mothers with 25(OH)D levels below thebirths per year and a primarily low- sess clothing habits. For example, level of detection (Ͻ5 ng/mL) wereincome black and Hispanic population. women were asked to recall for each categorized as being at Ͻ20 ng/mLBetween January 2005 and December trimester how frequently they went for models examining predictors of2007, women were screened for eligi- outside in clothing that revealed their deficiency.bility and approached in the maternity legs from below the knees and their Explanatory variables in the infantservice; those who agreed to partici- arms from the shoulders down. Other model were season of birth, mother’spate were enrolled within 72 hours of measures to determine sunlight expo- skin color and 25(OH)D status, mater-the birth of their child. Mother/infant sure included reported use of sun- nal sociodemographics, gestationalpairs were eligible if the mother spoke screen and time spent in the sun. age, birth weight and length, gender,PEDIATRICS Volume 125, Number 4, April 2010 641 Downloaded from www.pediatrics.org. Provided by Siu School Of Medicine on March 25, 2010
  • 3. Apgar score, and mother’s sun expo- analysis at a P value of Ͻ.20. In addi- women; because we were indepen-sure and prenatal-vitamin use. tion, we used the generalized estimat- dently interested in a woman’s sta-Explanatory variables in the maternal ing equations (GEE) extension of gener- tus at the time of delivery, womenmodel were maternal sociodemo- alized linear models to account for the were not excluded from maternalgraphics (age, educational attainment, within-subject correlation among the analyses because their infant’smarital status, employment status, repeated measures, assuming bino- blood was not available.health insurance, Supplemental Nutri- mial distributions with log link. None of The median infant 25(OH)D level wastion Program for Women, Infants, and the repeated-measure variables were 17.2 ng/mL (95% confidence intervalChildren [WIC] status, and place of statistically significant in GEE20 except [CI]: 16.0 –18.8; range: Ͻ5.0 to 60.8 ng/birth), parity, mode of delivery, hospi- for vitamin use. In addition, variables mL). The median maternal 25(OH)Dtalization, bed rest, weight gain during that assessed sun exposure had low level was 24.8 ng/mL (95% CI:pregnancy, BMI, and skin color (light, correlation between the first and third 23.2–25.8; range: Ͻ5.0 to 79.2 ng/mL).medium, or dark). For each trimester trimesters (r Ͻ 0.27, all measures), According to the standard of Ͻ20of pregnancy, we examined prenatal- which was expected because of sea- ng/mL as deficient,14 58.0% of the in-vitamin use and sun exposure (fre- sonal variation in weather. The fants and 35.8% of the mothers werequency and duration of time spent out- correlation between first- and third- vitamin D deficient. With a 25(OH)Dside, sun-protective-factor use). Intake trimester vitamin use was 0.38. There- level Ͻ 15 ng/mL as a marker of severeof foods high in vitamin D content, in- fore, composite variables were cre- deficiency, 38% of the infants andcluding vitamin D–fortified milk and ated as needed, and standard logistic regression modeling was used to iden- 23.1% of the mothers were severely vi-orange juice, cod liver oil, certain tify factors associated with maternal tamin D deficient.fish, fortified cereals, and eggs, wasascertained from a food-frequency and infant vitamin D deficiency. Infant Vitamin D Statusquestionnaire. Variables significant at the P Ͻ .20 level in exploratory analysis were ex- In bivariate analyses, variables associ-We estimated a sample size of 417 in- amined by univariate logistic regres- ated with infant vitamin D status atfants and mothers to observe a 20% sion. Variables significant at the P Ͻ birth included season of birth and thedifference in the proportion of infantsand mothers with vitamin D deficiency .20 level by likelihood-ratio testing mother’s vitamin D status, skin color,according to race and season with were entered into a multivariable lo- use of prenatal vitamins, and clothing80% power (2-sided test of signifi- gistic regression model by using for- habits (Table 1). Although duration ofcance: ␣ ϭ .017 for multiple compari- ward stepwise entry. Wald-test P val- sun exposure was statistically signifi-sons). The racial makeup of the popu- ues are presented for the final cantly associated with maternal vita-lation was known in advance, and we multivariable model. Data were ana- min D status, it was not associatedassumed that births would be evenly lyzed by using Stata/SE 9.2 for Win- with infant vitamin D status. After mul-distributed over the seasons. However, dows (Stata Corp, College Station, TX). tivariable logistic regression, risk fac-to further ensure that equal numbers tors for infant vitamin D deficiency thatof individuals of the desired races RESULTS remained statistically significant in-were enrolled in the desired season, We enrolled 458 mother/infant pairs cluded maternal deficiency (adjustedwe tracked enrollment over the course between January 1, 2005, and Decem- odds ratio [aOR]: 5.28 [95% CI: 2.90 –of the study. When numbers of individ- ber 31, 2007. Of these, 12 pairs were 9.62]), winter birth (aOR: 3.86 [95% CI:uals of specific races were not evenly later excluded for the following rea- 1.74 – 8.55]), black race (aOR: 3.36distributed, we proactively enrolled to sons: 1 spent Ͼ7 months of the preg- [95% CI: 1.37– 8.25]), and a maternalmeet the desired quota. nancy outside of the United States, 2 BMI of Ն35 (aOR: 2.78 [95% CI: 1.18 –Differences between explanatory vari- withdrew consent, and for 9 pairs we 6.55]). Maternal use of prenatal vita-ables and the outcome were assessed failed to obtain either infant or mater- mins Ն5 days/week during at least theby ␹2 test for categorical variables. In nal blood samples. In addition, 70 en- second and third trimesters (com-cross-sectional analysis, there were rolled infants and 13 women were pared with use of prenatal vitaminsno first-trimester variables regarding subsequently excluded because of Ͻ5 days week in at least 2 trimesters)sun exposure and vitamin use that failure to obtain an adequate blood was protective of vitamin D deficiencywere associated with infant or mater- sample. Thus, analyses were per- in the infant (aOR: 0.30 [95% CI: 0.16 –nal vitamin D status in exploratory formed on 376 newborns and 433 0.56]) (Table 2).642 MEREWOOD et al Downloaded from www.pediatrics.org. Provided by Siu School Of Medicine on March 25, 2010
  • 4. ARTICLESMaternal Vitamin D Status TABLE 1 Factors Associated With Infant 25(OH)D Status Variable Total (N ϭ 376), Infant 25(OH)D Status PVariables associated with maternal vi- n (%)tamin D status in bivariate analysis in- Ն20 ng/mL Ͻ20 ng/mL (n ϭ 158), (n ϭ 218),cluded season of birth, skin color, bed n (%) n (%)rest during pregnancy, use of vitamins Maternal 25(OH)D, ng/mL Ͻ.001in the third trimester, drinking milk, Ն20 230 (63.4) 129 (56.1) 101 (43.9)and time spent outside (Table 3). Use Ͻ20 133 (36.6) 24 (18.0) 109 (82.0) Type of delivery .29of prenatal vitamins in the first and Vaginal 284 (75.5) 115 (40.5) 169 (59.5)second trimesters was not associated Cesarean 92 (24.5) 43 (46.7) 49 (53.3)with vitamin D status, nor was con- Infant gender .24 Female 192 (51.1) 75 (39.1) 117 (60.9)sumption of vitamin D–fortified orange Male 184 (48.9) 83 (45.1) 101 (54.9)juice, cod liver oil, fish, or fortified ce- Season of birthreals (data not shown). Women who Summer 97 (25.8) 54 (55.7) 43 (44.3) Ͻ.001reported consuming eggs had a lower Fall 89 (23.7) 38 (42.7) 51 (57.3) Winter 88 (23.4) 18 (20.5) 70 (79.5)prevalence of vitamin D deficiency; Spring 102 (27.1) 48 (47.1) 54 (52.9)however, egg consumption was less Maternal race/ethnicitya .002common among US-born mothers and White 40 (10.6) 25 (62.5) 15 (37.5) Hispanic 195 (51.9) 87 (44.6) 108 (55.4)those who took vitamins less fre- Black 141 (37.5) 46 (32.6) 95 (67.4)quently during the third trimester. Maternal skin color .02 Light 124 (33.0) 64 (51.6) 60 (48.4)In multivariable logistic regression, Medium 129 (34.3) 51 (39.5) 78 (60.5)the strongest predictor of vitamin D Dark 123 (32.7) 43 (35.0) 80 (65.0)deficiency was giving birth in winter Maternal age, y .08 Ͻ20 40 (10.6) 11 (27.5) 29 (72.5)compared with summer (aOR: 4.78 20 to Ͻ30 221 (58.8) 92 (41.6) 129 (58.4)[95% CI: 2.39 –9.55]). Other statistically 30–43 115 (30.6) 55 (47.8) 60 (52.2)significant risk factors for maternal de- Maternal place of birth .33ficiency were dark skin color (aOR: 2.74 Non-US born 244 (64.9) 107 (43.9) 137 (56.1) US born 132 (35.1) 51 (38.6) 81 (61.4)[95% CI: 1.53– 4.88]), fall birth (aOR: 2.73 Maternal education .54[95% CI: 1.41–5.32]); and being born in Less than high school 156 (41.6) 63 (40.4) 93 (59.6)the United States (aOR: 2.03 [95% CI: 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)1.25–3.30]). Frequent vitamin use in the WIC recipient .18third trimester, drinking milk during No 56 (14.9) 28 (50.0) 28 (50.0)pregnancy, and spending at least 1 hour/ Yes 319 (85.1) 129 (40.4) 190 (59.6) Maternal health insurance .92day outside during the second or third Public 331 (88.7) 139 (42.0) 192 (58.0)trimesters were protective against vita- Private, self-pay 42 (11.3) 18 (42.9) 24 (57.1)min D deficiency (Table 4). Maternal bed rest during pregnancy .38 No 342 (91.4) 145 (42.4) 197 (57.6) Yes 32 (8.6) 11 (34.4) 21 (65.6)DISCUSSION Frequency of prenatal-vitamin use in first trimester .002We found that, in a population of Ͻ5 d/wk 118 (32.2) 35 (29.7) 83 (70.3) Ն5 d/wk 248 (67.8) 119 (48.0) 129 (52.0)largely Hispanic and black urban Frequency of prenatal-vitamin use in second .001mothers and newborns, vitamin D de- trimesterficiency was present in 58% of the new- Ͻ5 d/wk 84 (22.8) 21 (25.0) 63 (75.0) Ն5 d/wk 285 (77.2) 136 (47.7) 149 (52.3)borns and 35.8% of the mothers, and Frequency of prenatal-vitamin use in third Ͻ.001severe deficiency was present in 38% trimesterof the infants and 23.1% of the moth- Ͻ5 d/wk 92 (24.9) 23 (25.0) 69 (75.0) Ն5 d/wk 278 (75.1) 134 (48.2) 144 (51.8)ers. Maternal and infant status were Frequency of prenatal-vitamin useb Ͻ.001closely associated, and winter birth as Ͻ5 d/wk in Ͼ1 trimester 84 (24.1) 20 (23.8) 64 (76.2)well as a BMI of Ն35 were risk factors Ն5 d/wk during at least second and third 264 (75.9) 129 (48.9) 135 (51.1)for mothers and infants. These results trimesterare consistent with findings fromother studies.21,22PEDIATRICS Volume 125, Number 4, April 2010 643 Downloaded from www.pediatrics.org. Provided by Siu School Of Medicine on March 25, 2010
  • 5. TABLE 1 Continued D. Although maternal vitamin D status Variable Total (N ϭ 376), Infant 25(OH)D Status P was an important factor in predicting n (%) Ն20 ng/mL Ͻ20 ng/mL infant vitamin D status, the correlation (n ϭ 158), (n ϭ 218), between maternal and infant vitamin D n (%) n (%) deficiency is not 1-to-1: 18% of the in-Mother ever drank milk during pregnancy .01 No 51 (13.6) 13 (25.5) 38 (74.5) fants born to vitamin D– deficient Yes 324 (86.4) 144 (44.4) 180 (55.6) mothers were not deficient, whereasMaternal employment status during pregnancy .37 44% of the infants born to vitamin No/part-time 264 (70.6) 114 (43.2) 150 (56.8) Full-time 110 (29.4) 42 (38.2) 68 (61.8) D–replete mothers were deficient. ForMaternal frequency of exposing arms or legs Ͻ.001 example, a maternal BMI of Ͼ35 was during third trimester associated with increased risk of defi- 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) ciency in the infants but not in theMaternal smoking status .34 mothers, which suggests that obesity Never/before pregnancy 333 (88.6) 137 (41.1) 196 (58.9) During pregnancy 43 (11.4) 21 (48.8) 22 (51.2) may possibly impede transference ofAny maternal alcohol during pregnancy .86 micronutrients during pregnancy; this No 355 (94.7) 149 (42.0) 206 (58.0) is a novel association that is worth ad- Yes 20 (5.3) 8 (40.0) 12 (60.0)Any maternal medical problem .10 ditional examination. No 281 (74.7) 125 (44.5) 156 (55.5) We were able to identify modifiable fac- Yes 95 (25.3) 33 (34.7) 62 (65.3)Maternal BMI .001 tors that could decrease risk. For in- Ͻ35 327 (87.0) 148 (45.3) 179 (54.7) fants, the strongest association ob- Ն35 49 (13.0) 10 (20.4) 39 (79.6) served was with maternal deficiency,GED indicates General Educational Development.a Maternal race and skin color were highly correlated (0.76). Therefore, only 1 of these variables was entered in multivariate which implies that improved vitamin Dregression. Maternal race/ethnicity was chosen, because it explained a greater amount of variance than did skin color. status in mothers will have beneficialb 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 created effects on infants. Frequent prenatal-to summarize use over all trimesters. vitamin use reduced the infant’s risk of deficiency if the mother took themTABLE 2 Results of Univariate and Multivariate Logistic Regression for Risks for Infant 25(OH)D throughout the second and third tri- Deficiency at Term mesters. Third-trimester vitamin use Variable Crude OR (95% CI) aOR (95% CI) alone may not be sufficient to reduceMaternal 25(OH)D, ng/mL infant deficiency; rather, a longer Ն20 Referent Referent duration of use may be needed for Ͻ20 5.80 (3.47–9.69) 5.28 (2.90–9.62)Season of birth adequate stores. Although prenatal- Summer Referent Referent vitamin use Ն5 times per week in the Fall 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) third trimester was protective for Spring 1.41 (0.81–2.47) 1.14 (0.58–2.21) women, Ͼ30% of the women who tookMaternal race/ethnicity the prenatal vitamin this often were White Referent Referent Hispanic 2.07 (1.03–4.16) 2.47 (1.05–5.80) still vitamin D deficient at the time of Black 3.44 (1.66–7.15) 3.36 (1.37–8.25) birth. One possible explanation for thisFrequency of prenatal-vitamin use result is that the prenatal vitamin does Ͻ5 d/wk in Ͼ1 trimester Referent Referent Ն5 d/wk during at least the second and third trimesters 0.33 (0.19–0.57) 0.30 (0.16–0.56) not contain enough vitamin D to affectMaternal BMI an apparent chronic deficiency in Ͻ35 Referent Referent these women of childbearing age. For Ն35 3.22 (1.56–6.68) 2.78 (1.18–6.55) the mothers, drinking milk and spendingAll 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, time outside were protective of vitamin Dand maternal medical problem. deficiency. Although a BMI of Ն35 was a risk factor for both mothers and infants,Although sun exposure was protective ferred to their infants, which suggests when compared with a BMI of Ͻ35, theof vitamin D deficiency in the mothers, that other factors may influence risk of deficiency did not increase pro-this protective effect was not trans- maternal-fetal transference of vitamin portionally with increased BMI and was644 MEREWOOD et al Downloaded from www.pediatrics.org. Provided by Siu School Of Medicine on March 25, 2010
  • 6. ARTICLESnot evident at lower categorizations of TABLE 3 Factors Associated With Maternal 25(OH)D StatusBMI (data not shown). Variable Total, n (%) Maternal 25(OH)D Status PThe rates of deficiency in this study, Ն20 ng/mL Ͻ20 ng/mL (n ϭ 278), (n ϭ 155),especially in infants, were particularly n (%) n (%)high. The use of 20 ng/mL as an indica- Season of birth Ͻ.001tor of deficiency is now standard in Summer 112 (25.9) 91 (81.3) 21 (18.7)adult populations. We used it in our in- Fall 105 (24.3) 66 (62.9) 39 (37.1)fant population, because it is the clini- Winter 99 (22.9) 45 (45.5) 54 (54.4) Spring 117 (27.0) 76 (65.0) 41 (35.0)cally accepted standard used in hospi- Maternal race/ethnicitya .001tals in our area, including our own; Black 164 (37.9) 87 (53.0) 77 (47.0)children with a 25(OH)D level of Ͻ20 White 46 (10.6) 35 (76.1) 11 (23.9) Hispanic 223 (51.5) 156 (70.0 67 (30.0)ng/mL are treated for deficiency. Re- Maternal skin color Ͻ.001cently, using Ͻ20 ng/mL as deficient in Light 140 (32.3) 107 (76.4) 33 (23.6)a Boston population of infants and us- Medium 146 (33.7) 92 (63.0) 54 (37.0) Dark 147 (34.0) 79 (53.7) 68 (46.3)ing a comparable assay, Gordon et al14 Maternal age, y Ͼ.999found a 12% rate of deficiency. How- Ͻ20 53 (12.2) 34 (64.2) 19 (35.8)ever, we suggest that our rates were 20 to Ͻ30 254 (58.7) 163 (64.2) 91 (35.8) 30–43 126 (29.1) 81 (64.3) 45 (35.7)higher because we measured new- Place of birth .001born levels, whereas Gordon et al in- Non-US born 280 (64.7) 196 (70.0) 84 (30.0)cluded infants and older infants up to 1 US born 153 (35.3) 82 (53.6) 71 (46.4)year of age. Newborn status is related Education .008 Less than high school 179 (41.4) 129 (72.1) 50 (27.9)to maternal status and likely changes High school graduate/GED 133 (30.8) 82 (61.7) 51 (38.3)in the first year of life. More than high school 120 (27.8) 66 (55.0) 54 (45.0) WIC recipient .25A recent review by the American Acad- No 69 (16.0) 40 (58.0) 29 (42.0)emy of Pediatrics suggested that ade- Yes 363 (84.0) 237 (65.3) 126 (34.7)quate vitamin D status is important for Health insurance .15 Public 379 (88.1) 247 (65.2) 132 (34.8)a range of developmental factors in in- Private, self-pay 51 (11.9) 28 (54.9) 23 (45.1)fants and children, including skeletal Bed rest in pregnancy .004development, higher birth weight, and No 388 (90.0) 257 (66.2) 131 (33.8)improved bone-mineral content and Yes 43 (10.0) 19 (44.2) 24 (55.8) Frequency of prenatal-vitamin use in third trimester .001bone mass in children at 9 years of Never or Ͻ1 d/wk 67 (15.7) 34 (50.7) 33 (49.3)age.9 In addition, we recently re- 1–4 d/wk 41 (9.6) 20 (48.8) 21 (51.2)ported an association between ma- Ն5 d/wk 319 (74.7) 221 (69.3) 98 (30.7) Maternal calcium supplement .81ternal vitamin D deficiency at birth Never 196 (64.1) 110 (35.9)and an elevated risk of primary ce- Sometimes 53 (62.4) 32 (37.6)sarean delivery.23 This is consistent Often 28 (68.3) 13 (31.7) Ever drank milk during pregnancy .004with data of the impact of vitamin D No 57 (13.2) 27 (47.4) 30 (52.6)deficiency on skeletal and smooth Yes 374 (86.8) 250 (66.8) 124 (33.2)muscle function. Employment status during pregnancy .03 No/part-time 304 (70.7) 204 (67.1) 100 (32.9)It should be noted that skin color was Full-time 126 (29.3) 71 (56.3) 55 (46.7)a risk for deficiency in mothers, Average time spent outside during second or third .03whereas race/ethnicity was a statisti- trimestersb Ͻ1 h/d in second and third trimesters 199 (48.0) 118 (59.3) 81 (40.7)cally clearer risk for deficiency in in- Ն1 h/d in second or third trimester 216 (52.0) 150 (69.4) 66 (30.6)fants. It is possible that the variable Frequency of exposing arms or legs during third Ͻ.001race/ethnicity includes unmeasured trimesterc 0–4 d/wk 228 (52.9) 128 (56.1) 100 (43.9)confounders that have important bear- 5–7 d/wk 203 (47.1) 149 (73.4) 54 (26.6)ing on infant vitamin D status but not Ever used sunscreen .61on maternal vitamin D status. No 282 (65.4) 183 (64.9) 99 (35.1) Yes 149 (34.6) 93 (62.4) 56 (37.6)We acknowledge some limitations.Data regarding variables in pregnancyPEDIATRICS Volume 125, Number 4, April 2010 645 Downloaded from www.pediatrics.org. Provided by Siu School Of Medicine on March 25, 2010
  • 7. TABLE 3 Continued size needed (376 vs 417) because of Variable Total, n (%) Maternal 25(OH)D Status P difficulty obtaining blood samples. Ն20 ng/mL Ͻ20 ng/mL Baseline values of 25(OH)D were miss- (n ϭ 278), (n ϭ 155), ing for some infants; however, this was n (%) n (%) a result of inevitable difficulties draw-Smoking status .008 Never/before pregnancy 386 (89.2) 256 (66.3) 130 (33.7) ing blood on young infants and was not During pregnancy 47 (10.8) 22 (46.8) 25 (53.2) associated with the mother’s 25(OH)DAny alcohol during pregnancy .99 level, skin color, or season of birth (re- No 407 (94.2) (64.1) 146 (35.9) Yes 25 (5.8) 16 (64.0) 9 (36.0) sults not shown).Maternal BMI .01 In addition, although children with a Ͻ35 380 (87.8) 252 (66.3) 128 (33.7) Ն35 53 (12.2) 26 (49.1) 27 (50.9) 25(OH)D level of Ͻ20 ng/mL areGED indicates General Educational Development. treated with supplementation in thea Maternal race and skin color were highly correlated (0.76). Therefore, only 1 of these variables was entered in multivariate clinical setting, biomarkers of vitaminregression. 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), so D deficiency in young children particu-they were combined into a single variable. larly are lacking. A need for researchc 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 in to determine validity of commonly ac-keeping with the pattern seen in the third trimester of decreasing prevalence of vitamin D deficiency with increasing time cepted measures of deficiency hasspent outside). been identified.21,24TABLE 4 Results of Univariate and Multivariate Logistic Regression for Risks for Maternal 25(OH)D CONCLUSIONS Deficiency at Term Variable Crude OR (95% CI) aOR (95% CI) We found that more than half of theSeason of birth infants and approximately one third of Summer Referent Referent the mothers who gave birth in this Bos- Fall 2.56 (1.38–4.75) 2.73 (1.41–5.32) ton study were vitamin D deficient at 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) the time of delivery. Although prenatal-Maternal skin color vitamin use was protective for both Light Referent Referent infants and mothers, considerable Medium 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) proportions of infants and mothers re-Maternal place of birth mained deficient even when prenatal Non-US born Referent Referent vitamins were taken regularly. It is US born 2.02 (1.34–3.04) 2.03 (1.25–3.30) time to rethink our approach to ensur-Frequency of prenatal-vitamin use in third trimester Never or Ͻ1 d/wk Referent Referent ing vitamin D sufficiency in newborns 1–4 d/wk 1.08 (0.50–2.35) 0.79 (0.32–1.91) and their mothers. Ն5 d/wk 0.46 (0.27–0.78) 0.37 (0.20–0.69)Ever drank milk during pregnancy No Referent Referent ACKNOWLEDGMENTS Yes 0.45 (0.25–0.78) 0.45 (0.24–0.87)Time spent outside in second and third trimester This work was funded by Health Re- Ͻ1 h/d second and third trimester Referent Referent sources and Services Administration/ Ն1 h/d second or third trimester 0.64 (0.43–0.96) 0.55 (0.34–0.87) Bureau of Maternal and Child HealthAll parameter estimates were adjusted for the other covariates presented. Variables entered from univariate analysis that grant R40 MC03620-01-00 and US De-were not statistically significant in multivariate analysis were maternal race (correlated with skin color ͓r ϭ 0.66͔), bed restduring pregnancy, smoking during pregnancy, educational attainment, BMI, and employment status. partment of Agriculture/Cooperative State Research, Education, and Exten- sion Service grant 2005-35200-15260were collected retrospectively. We did min D levels at the time they were and supported by grant M01-RR00533not have dietary intake of vitamin D questioned, knowledge of the study from the General Clinical Researchand calcium, only the frequency or topic may have influenced some re- Centers Program of the National Cen-amount of consumption. Although sponses. The number of infants ana- ter for Research Resources, Nationalmothers were unaware of their vita- lyzed was 90% of the estimated sample Institutes of Health.646 MEREWOOD et al Downloaded from www.pediatrics.org. Provided by Siu School Of Medicine on March 25, 2010
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