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• W1907445240 abstract "Maternal vitamin D deficiency during pregnancy has been suggested as a risk factor for the development of childhood allergic disease and asthma.1Litonjua A.A. Weiss S.T. Is vitamin D deficiency to blame for the asthma epidemic?.J Allergy Clin Immunol. 2007; 120: 1031-1035Abstract Full Text Full Text PDF PubMed Scopus (373) Google Scholar The literature on maternal vitamin D status and asthma-related outcomes in children has been inconsistent. In 2007, higher maternal vitamin D intake during pregnancy was shown to be associated with a lower risk of wheezing illnesses by age 3 and 5 years.2Devereux G. Litonjua A.A. Turner S.W. Craig L.C. McNeill G. Martindale S. et al.Maternal vitamin D intake during pregnancy and early childhood wheezing.Am J Clin Nutr. 2007; 85: 853-859PubMed Google Scholar Two subsequent studies examining 25-hydroxyvitamin D (25[OH]D) in cord blood found lower levels of cord blood 25(OH)D to be related to allergic sensitization3Rothers J. Wright A.L. Stern D.A. Halonen M. Camargo Jr., C.A. Cord blood 25-hydroxyvitamin D levels are associated with aeroallergen sensitization in children from Tucson, Arizona.J Allergy Clin Immunol. 2011; 128 (e1091-5): 1093-1099Abstract Full Text Full Text PDF PubMed Scopus (148) Google Scholar and wheeze,4Camargo Jr., C.A. Ingham T. Wickens K. et al.Cord-blood 25-hydroxyvitamin D levels and risk of respiratory infection, wheezing, and asthma.Pediatrics. 2011; 127: e180-e187Crossref PubMed Scopus (411) Google Scholar but not asthma.3Rothers J. Wright A.L. Stern D.A. Halonen M. Camargo Jr., C.A. Cord blood 25-hydroxyvitamin D levels are associated with aeroallergen sensitization in children from Tucson, Arizona.J Allergy Clin Immunol. 2011; 128 (e1091-5): 1093-1099Abstract Full Text Full Text PDF PubMed Scopus (148) Google Scholar, 4Camargo Jr., C.A. Ingham T. Wickens K. et al.Cord-blood 25-hydroxyvitamin D levels and risk of respiratory infection, wheezing, and asthma.Pediatrics. 2011; 127: e180-e187Crossref PubMed Scopus (411) Google Scholar Of 10 observational studies, half of which assessed vitamin D status by estimating dietary intake using questionnaires and half of which measured 25(OH)D in maternal serum or cord blood, 5 found a significantly reduced risk of asthma or atopy among children of mothers with higher vitamin D status during pregnancy, 3 found increased asthma or atopy risk in this same population, and the remaining 2 studies found no relationship.5Harvey N.C. Holroyd C. Ntani G. Javaid K. Cooper P. Moon R. et al.Vitamin D supplementation in pregnancy: a systematic review.Health Technol Assess. 2014; 18: 1-190Crossref Scopus (226) Google Scholar In current analyses, we used an objective measure of vitamin D status—the concentration of plasma 25(OH)D in umbilical cord blood—in 2 US birth cohorts with widely divergent populations to examine the relationship of vitamin D status at birth with various atopic and asthma-related outcomes in children after 5 to 6 years of follow-up. The design, methods, and study populations of the Urban Environment and Childhood Asthma (URECA) study6Gern J.E. Visness C.M. Gergen P.J. Wood R.A. Bloomberg G.R. O'Connor G.T. et al.The Urban Environment and Childhood Asthma (URECA) birth cohort study: design, methods, and study population.BMC Pulm Med. 2009; 9: 17Crossref PubMed Scopus (74) Google Scholar and the Childhood Origins of Asthma (COAST) study7Lemanske Jr., R.F. The Childhood Origins of Asthma (COAST) study.Pediatr Allergy Immunol. 2002; 13: 38-43Crossref PubMed Scopus (177) Google Scholar have been previously reported in detail. Both studies were approved by institutional review boards at each participating institution, and written informed consent was obtained before enrollment. Although the 2 studies used similar enrollment criteria to select infants at high risk for asthma (ie, participants needed to have a mother or father with allergic rhinitis, eczema, and/or asthma), the study populations were very different. The URECA study enrolled pregnant women residing in low-income areas of 4 large inner cities (Baltimore, Boston, New York, and St Louis), whereas COAST enrolled pregnant women from Madison, Wisconsin, and surrounding communities. The URECA study enrolled 560 newborns, and the COAST study enrolled 288 newborns. Cord blood samples were collected using sterile procedures and transported to each center's laboratory on the day of collection. After separation by density gradient centrifugation, the plasma fraction, diluted with RPMI medium, was frozen at −80 C. Plasma 25(OH)D concentrations were successfully measured in 520 URECA samples and 258 COAST samples. Among these, follow-up data were available for 435 URECA children and all 258 COAST children. Wheezing symptoms in URECA children were captured by questionnaires administered every 3 months to the parent or the guardian. In COAST, wheezing was assessed by phone contacts during respiratory illnesses and by questionnaire at annual study visits. Allergen-specific IgE results and skin prick test results were available from study visits at age 3 and 5 years, respectively (see Table E1 in this article's Online Repository at www.jacionline.org). Current asthma was diagnosed in COAST at age 6 years on the basis of clinical criteria but has not yet been determined for the URECA children. Logistic regression was used to determine the association between a 10-ng/mL change in cord blood 25(OH)D concentrations and the atopic and wheeze outcomes. Models were controlled for race/ethnicity (URECA only) and season of birth. All statistical analyses were performed using SAS 9.2 and R 2.12.2 (SAS, Cary, NC). The 2 cohorts are very different demographically, reflecting their different target populations (Table I). Despite this, the prevalence of aeroallergen sensitization as assessed by serum-specific IgE level at age 3 years was similar in the 2 cohorts (28.4% in COAST vs 27.4% in URECA). However, the prevalence of at least 1 wheezing illness during the third year of life was higher in URECA than in COAST (38.6% in URECA vs 23.3% in COAST).Table ICharacteristics of participants in 2 US birth cohort studies (URECA, N = 435; COAST, N = 258)CharacteristicURECA (N = 435)COAST (N = 258)Mother's age at child's birth (y), median (range)23 (13-42)31 (17-43)Race or ethnicity of child (%) Hispanic20.23.1 African American70.34.3 White1.286.4 Mixed or other8.36.2Maternal education (%) Less than high school41.71.6 High school33.27.1 More than high school25.191.3Mother married (%)13.894.6Household income <$20,000 (%)68.35.6Type of delivery (%) Vaginal66.985.2 C-section33.114.8Male sex (%)50.856.2Gestational age (wk), median (range)39 (34-42)40 (37-40+)∗COAST values ≥40 were reported in a single category.Breast-fed at birth (%)56.590.3Breast-fed at 3 mo (%)24.372.5Maternal smoking (%) Pregnancy17.54.3 First year of life40.57.025(OH)D (ng/mL), median (range)20.1 (4.2-54.6)21.1 (4.0-77.7)Any wheeze at age 3 y (%)38.623.3 Single wheeze17.712.4 ≥2 wheeze20.910.8Atopy (%) Any positive IgE at age 3 y49.243.2 Any positive IgE to aeroallergen at age 3 y27.428.4 Any positive IgE to food allergen at age 3 y39.833.2 Any positive skin test result at age 3 y36.2NA Any positive skin test result at age 5 y44.049.5NA, Not applicable/available.∗ COAST values ≥40 were reported in a single category. Open table in a new tab NA, Not applicable/available. The median concentration of umbilical cord plasma 25(OH)D in URECA was 20.1 ng/mL and in COAST was 21.1 ng/mL (Table I). Table II shows that umbilical cord plasma 25(OH)D concentration was not associated with any of the atopic or wheeze outcomes examined in either cohort. We also examined 25(OH)D concentration as a continuous variable as well as used common cutoff points for adequacy of 20 and 30 ng/mL without finding any significant relationships to our outcomes.Table IIRelationship of cord blood 25(OH)D concentrations to wheezing and atopic outcomes in 2 US birth cohorts (URECA, N = 435; COAST, N = 258)CohortRR∗RR for 10-ng/mL increase in the concentration of 25(OH)D in cord blood, adjusting for race/ethnicity and season of birth. COAST models are adjusted for the season of birth only.95% CIP valueURECA Any wheeze in first year0.930.83-1.04.23 Recurrent wheeze at year 30.930.79-1.08.33 Any positive aeroallergen-specific IgE at year 30.940.78-1.13.48 Any positive food-specific IgE at year 31.080.94-1.25.26 Any positive skin test result at year 30.880.74-1.03.11 Any positive skin test result at year 51.060.93-1.19.39 Food allergic at years 1-5†Positive specific IgE to milk, egg, or peanut and clinical history of a reaction to that food at any time in the first 5 years of life.0.870.62-1.24.44COAST Any wheeze in first year0.940.76-1.16.56 Any wheeze in third year0.960.76-1.22.76 Any wheeze in the first 3 y0.940.81-1.08.37 Asthma at age 6 y0.990.81-1.22.93 Any positive aeroallergen-specific IgE at year 31.010.82-1.25.92 Any positive food-specific IgE at year 31.000.83-1.21.98 Any positive skin test result at year 50.980.85-1.13.81RR, Relative risk.∗ RR for 10-ng/mL increase in the concentration of 25(OH)D in cord blood, adjusting for race/ethnicity and season of birth. COAST models are adjusted for the season of birth only.† Positive specific IgE to milk, egg, or peanut and clinical history of a reaction to that food at any time in the first 5 years of life. Open table in a new tab RR, Relative risk. In summary, in both these high-risk birth cohorts—one of urban, largely minority, and low-income children, and one of largely suburban white children—cord blood concentrations of 25(OH)D were not associated with risk of asthma, wheeze, or atopic outcomes. Measures of vitamin D status at age 3 years were similarly unrelated to these outcomes (see Table E2 in this article's Online Repository at www.jacionline.org). Our study relies on a single measurement of vitamin D status during pregnancy. Because 25(OH)D concentrations can be highly variable, it is possible that cord blood concentrations, while reflecting vitamin D status at the end of pregnancy, may not fully reflect vitamin D exposure of the infant during critical time windows in pregnancy and development. The 2 studies did show a 4% to 7% reduction in the risk of wheeze outcomes, and it is also possible that they were underpowered to detect an effect of this magnitude. It was unexpected that the median 25(OH)D concentrations were similar in both cohorts, given that African American populations frequently are found to have lower concentrations.8Gergen P.J. Teach S.J. Mitchell H.E. Freishtat R.F. Calatroni A. Matsui E. et al.Lack of a relation between serum 25-hydroxyvitamin D concentrations and asthma in adolescents.Am J Clin Nutr. 2013; 97: 1228-1234Crossref PubMed Scopus (32) Google Scholar, 9Powe C.E. Evans M.K. Wenger J. Zonderman A.B. Berg A.H. Nalls M. et al.Vitamin D-binding protein and vitamin D status of black Americans and white Americans.N Engl J Med. 2013; 369: 1991-2000Crossref PubMed Scopus (805) Google Scholar This may be explained by both populations taking prenatal supplements or by the northern latitude of the COAST population. This study used an objective measure of vitamin D status during late pregnancy—25(OH)D concentrations in umbilical cord blood—rather than relying on estimates of vitamin D intake based on self-reported dietary information. Whether this is a good measure of vitamin D status in infancy is a matter of debate. Umbilical cord 25(OH)D levels have been shown to have some correlation to maternal levels, but not to maternal dietary intake apart from vitamin D supplementation. Bioavailable vitamin D may be a better measure of the biologically active component affecting allergic outcomes.9Powe C.E. Evans M.K. Wenger J. Zonderman A.B. Berg A.H. Nalls M. et al.Vitamin D-binding protein and vitamin D status of black Americans and white Americans.N Engl J Med. 2013; 369: 1991-2000Crossref PubMed Scopus (805) Google Scholar Recent analysis among older inner-city children and adolescents with asthma have also failed to show a relationship between 25(OH)D levels and asthma severity or allergic outcomes.8Gergen P.J. Teach S.J. Mitchell H.E. Freishtat R.F. Calatroni A. Matsui E. et al.Lack of a relation between serum 25-hydroxyvitamin D concentrations and asthma in adolescents.Am J Clin Nutr. 2013; 97: 1228-1234Crossref PubMed Scopus (32) Google Scholar, 10Bird J.A. Wang J. Visness C.M. Calatroni A. Sampson H.A. Gruchalla R. Winter birth in inner-city asthmatic children is associated with increased food allergen sensitization risk.J Allergy Clin Immunol. 2014; 134: 490-492Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar Although vitamin D supplementation of pregnant women to prevent asthma and allergic outcomes in their offspring would be a simple and inexpensive intervention, were it to prove to be effective, the current findings might temper the enthusiasm of vitamin D proponents. Two large-scale intervention trials are nearing completion and may provide more insight into this question (NCT00920621 and NCT00856947). Table E1Skin test and IgE panels for 2 US birth cohortsURECA skin test panel (years 3 and 5) • German cockroach • American and German cockroach mix • Aspergillus mix • Alternaria tenius • Dermatophagoides farina • Dermatophagoides pteronyssinus • Dog epithelia • Cat hair • Mouse epithelia • Penicillium notatum • Ragweed mix • Rat epithelia • Timothy grass • Tree pollen○ White oak (St Louis and Baltimore)○ Birch mix (Boston and New York)URECA IgE measurements (years 1, 2, 3, and 5) • Milk • Egg • Peanut • German cockroach • Dermatophagoides farina∗Not tested at age 1 y. • Dermatophagoides pteronyssinus∗Not tested at age 1 y. • Dog∗Not tested at age 1 y. • Cat∗Not tested at age 1 y. • Mouse∗Not tested at age 1 y. • Alternaria∗Not tested at age 1 y.COAST skin test panel (year 5) • American and German cockroach mix • Aspergillus fumigatus • Alterneria alternata • Cladosporium herbarum • Dermatophagoides farina • Dermatophagoides pteronyssinus • Grass (7-grass mix) • Cat (standardized) • Dog (mixed breeds) • Ragweed (giant and short mix) • Late fall pollen mix • Tree (Eastern 6-tree mix)COAST IgE measurements (year 3) • Milk • Egg • Peanut • Soy • Dermatophagoides farina • Dermatophagoides pteronyssinus • Dog • Cat • Alternaria alternate∗ Not tested at age 1 y. Open table in a new tab Table E2Relationship of 25(OH)D concentrations measured at age 3 years to wheezing and atopic outcomes in 2 US birth cohorts (URECA, N = 435; COAST, N = 258)CohortRR∗RR for 10-ng/mL increase in the concentration of 25(OH)D measured at age 3 years, adjusting for race/ethnicity and the season of birth. COAST models are adjusted for the season of birth only.95% CIP valueURECA Recurrent wheeze at year 31.060.85-1.33.58 Any positive aeroallergen-specific IgE at year 31.170.90-1.51.24 Any positive food-specific IgE at year 30.990.81-1.20.89 Any positive skin test result at year 31.120.91-1.39.28 Any positive skin test result at year 51.090.90-1.31.39 Food allergic at year 1-5†Positive specific IgE to milk, egg, or peanut and clinical history of a reaction to that food at any time in the first 5 years of life.1.000.61-1.63.99COAST Any wheeze in first year1.020.78-1.32.90 Any wheeze in third year1.080.79-1.48.64 Any wheeze in the first 3 y1.090.90-1.32.36 Asthma at age 6 y0.970.73-1.29.83 Any positive aeroallergen-specific IgE at year 31.120.87-1.44.36 Any positive food-specific IgE at year 30.990.78-1.26.93 Any positive skin test result at year 51.120.91-1.38.30RR, Relative risk.∗ RR for 10-ng/mL increase in the concentration of 25(OH)D measured at age 3 years, adjusting for race/ethnicity and the season of birth. COAST models are adjusted for the season of birth only.† Positive specific IgE to milk, egg, or peanut and clinical history of a reaction to that food at any time in the first 5 years of life. Open table in a new tab RR, Relative risk." @default.
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• W1907445240 title "Cord blood vitamin D concentrations are unrelated to atopy and wheeze in 2 diverse birth cohort studies" @default.
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