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      The Longitudinal Trajectory of Vitamin D Status from Birth to Early Childhood on the Development of Food Sensitization

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          Abstract

          Background

          Increasing evidence supports the immunomodulatory effect of vitamin D on allergic diseases. The combined role of prenatal and postnatal vitamin D status in the development of food sensitization (FS) and food allergy remains under-studied.

          Methods

          460 children in the Boston Birth Cohort had plasma 25(OH)D measured at birth and early childhood, and were genotyped for rs2243250 (C-590T) in the IL4 gene. We defined FS as specific IgE ≥0.35kUA/L to any of eight common food allergens; and persistently low vitamin D status as cord blood 25(OH)D <11ng/ml and postnatal 25(OH)D <30ng/ml.

          Results

          We observed a moderate correlation between cord blood 25(OH)D at birth and venous blood 25(OH)D measured at 2–3 years (r=0.63), but a weak correlation at <1 year (r=0.28). There was no association between low vitamin D status and FS at any single time point alone. However, in combination, persistence of low vitamin D status at birth and early childhood increased the risk of FS (OR=2.03, 95%CI:1.02–4.04), particularly among children carrying the C allele of rs2243250 (OR=3.23, 95%CI:1.37–7.60).

          Conclusions

          Prenatal and early postnatal vitamin D levels, along with individual genetic susceptibility, should be considered in assessing the role of vitamin D in the development of FS and food allergy.

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          Most cited references22

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          Prevention of rickets and vitamin D deficiency in infants, children, and adolescents.

          Rickets in infants attributable to inadequate vitamin D intake and decreased exposure to sunlight continues to be reported in the United States. There are also concerns for vitamin D deficiency in older children and adolescents. Because there are limited natural dietary sources of vitamin D and adequate sunshine exposure for the cutaneous synthesis of vitamin D is not easily determined for a given individual and may increase the risk of skin cancer, the recommendations to ensure adequate vitamin D status have been revised to include all infants, including those who are exclusively breastfed and older children and adolescents. It is now recommended that all infants and children, including adolescents, have a minimum daily intake of 400 IU of vitamin D beginning soon after birth. The current recommendation replaces the previous recommendation of a minimum daily intake of 200 IU/day of vitamin D supplementation beginning in the first 2 months after birth and continuing through adolescence. These revised guidelines for vitamin D intake for healthy infants, children, and adolescents are based on evidence from new clinical trials and the historical precedence of safely giving 400 IU of vitamin D per day in the pediatric and adolescent population. New evidence supports a potential role for vitamin D in maintaining innate immunity and preventing diseases such as diabetes and cancer. The new data may eventually refine what constitutes vitamin D sufficiency or deficiency.
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            Maternal cigarette smoking, metabolic gene polymorphism, and infant birth weight.

            Little is known about genetic susceptibility to cigarette smoke in relation to adverse pregnancy outcomes. To investigate whether the association between maternal cigarette smoking and infant birth weight differs by polymorphisms of 2 maternal metabolic genes: CYP1A1 and GSTT1. Case-control study conducted in 1998-2000 among 741 mothers (174 ever smokers and 567 never smokers) who delivered singleton live births at Boston Medical Center. A total of 207 cases were preterm or low-birth-weight infants and 534 were non-low-birth-weight, full-term infants (control). Birth weight, gestation, fetal growth by smoking status and CYP1A1 MspI (AA vs Aa and aa, where Aa and aa were combined because of small numbers of aa and similar results), and GSTT1 (present vs absent) genotypes. Without consideration of genotype, continuous maternal smoking during pregnancy was associated with a mean reduction of 377 g (SE, 89 g) in birth weight (odds ratio [OR], 2.1; 95% confidence interval [CI], 1.2-3.7). When CYP1A1 genotype was considered, the estimated reduction in birth weight was 252 g (SE, 111 g) for the AA genotype group (n = 75; OR, 1.3; 95% CI, 0.6-2.6), but was 520 g (SE, 124 g) for the Aa/aa genotype group (n = 43 for Aa, n = 6 for aa; OR, 3.2; 95% CI, 1.6-6.4). When GSTT1 genotype was considered, the estimated reduction in birth weight was 285 g (SE, 99 g) (OR, 1.7; 95% CI, 0.9-3.2) and 642 g (SE, 154 g) (OR, 3.5; 95% CI, 1.5-8.3) for the present and absent genotype groups, respectively. When both CYP1A1 and GSTT1 genotypes were considered, the greatest reduction in birth weight was found among smoking mothers with the CYP1A1 Aa/aa and GSTT1 absent genotypes (-1285 g; SE, 234 g; P<.001). Among never smokers, genotype did not independently confer an adverse effect. A similar pattern emerged in analyses stratified by maternal ethnicity and in analyses for gestation. In our study, maternal CYP1A1 and GSTT1 genotypes modified the association between maternal cigarette smoking and infant birth weight, suggesting an interaction between metabolic genes and cigarette smoking.
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              Maternal vitamin D intake during pregnancy and early childhood wheezing.

              Maternal intake of vitamin D in pregnancy is a potentially modifiable but understudied risk factor for the development of asthma in children. We investigated whether maternal vitamin D intake in pregnancy is associated with decreased risks of wheezing symptoms in young children. Subjects were from a birth cohort recruited in utero with the primary objective of identifying associations between maternal diet during pregnancy and asthma and allergies in children. A random sample of 2000 healthy pregnant women was recruited while attending antenatal clinics at the Aberdeen Maternity Hospital, Scotland, at approximately 12 wk gestation. Maternal vitamin D intake was ascertained from a food-frequency questionnaire completed at 32 wk of gestation. The main outcome measures were wheezing symptoms, spirometry, bronchodilator response, atopic sensitization, and exhaled nitric oxide at 5 y. Respiratory details through 5 y and maternal food-frequency-questionnaire data were available for 1212 children. In models adjusted for potential confounders, including the children's vitamin D intake, a comparison of the highest and lowest quintiles of maternal total vitamin D intake conferred lower risks for ever wheeze [odds ratio (OR): 0.48; 95% CI: 0.25, 0.91], wheeze in the previous year (OR: 0.35; 95% CI: 0.15, 0.83), and persistent wheeze (OR: 0.33; 95% CI: 0.11, 0.98) in 5-y-old children. In addition, lower maternal total vitamin D intakes in pregnancy were also associated with decreased bronchodilator response (P = 0.04). No associations were observed between maternal vitamin D intakes and spirometry or exhaled nitric oxide concentrations. Increasing maternal vitamin D intakes during pregnancy may decrease the risk of wheeze symptoms in early childhood.
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                Author and article information

                Journal
                0100714
                6400
                Pediatr Res
                Pediatr. Res.
                Pediatric research
                0031-3998
                1530-0447
                11 April 2013
                24 June 2013
                September 2013
                01 March 2014
                : 74
                : 3
                : 321-326
                Affiliations
                [1 ]Mary Ann and J. Milburn Smith Child Health Research Program, Department of Pediatrics, Northwestern University Feinberg School of Medicine and Children's Hospital of Chicago Research Center, Chicago, IL, USA
                [2 ]Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
                [3 ]Biostatistics Research Core, Children’s Hospital of Chicago Research Center, Chicago, IL, USA
                [4 ]Center of Early Life Origins of Disease, Department of Population, Family and Reproductive Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA
                [5 ]Division of Biostatistics and Bioinformatics, Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Taiwan
                [6 ]Division of Kidney Disease, Department of Pediatrics, Northwestern University Feinberg School of Medicine and Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA
                [7 ]Department of Pediatrics, Boston University School of Medicine and Boston Medical Center, Boston, MA, USA
                [8 ]Division of Allergy-Immunology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
                [9 ]Division of Allergy and Immunology, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA
                Author notes
                [] Correspondence and reprint requests should be addressed to: Xin Liu, MD, PhD, Mary Ann and J. Milburn Smith Child Health Research Program, Children's Hospital of Chicago Research Center, Department of Pediatrics, Feinberg School of Medicine, Northwestern University, 225 E. Chicago Avenue, Box 157, Chicago, IL, USA, Telephone: 312-227-7025, Fax: 312-227-9523, xnliu@ 123456luriechildrens.org
                Article
                NIHMS447521
                10.1038/pr.2013.110
                3773018
                23797532
                7cc05d63-e354-42e4-996a-06cc6d2f1720

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                History
                Funding
                Funded by: National Institute of Allergy and Infectious Diseases Extramural Activities : NIAID
                Award ID: R21 AI087888 || AI
                Funded by: National Center for Research Resources : NCRR
                Award ID: KL2 RR025740 || RR
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                Pediatrics
                Pediatrics

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