Maternal Versus Infant Vitamin D Supplementation During Lactation: A Randomized Controlled Trial

PEDIATRICS Volume 136, number 4, October 2015

Bruce W. Hollis, Carol L. Wagner, Cynthia R. Howard, Myla Ebeling, Judy R. Shary, Pamela G. Smith, Sarah N. Taylor, Kristen Morella, Ruth A. Lawrence, Thomas C. Hulsey.

OBJECTIVE: Compare effectiveness of maternal vitamin D3 supplementation with 6400 IU per day alone to maternal and infant supplementation with 400 IU per day.

METHODS: Exclusively lactating women living in Charleston, SC, or Rochester, NY, at 4 to 6 weeks postpartum were randomized to either 400, 2400, or 6400 IU vitamin D3/day for 6 months. Breastfeeding infants in 400 IU group received oral 400 IU vitamin D3/day; infants in 2400 and 6400 IU groups received 0 IU/day (placebo). Vitamin D de ficiency was defined as 25-hydroxy-vitamin D (25(OH)D) < 50 nmol/L.  2400 IU group ended in 2009 as greater infant deficiency occurred. Maternal serum vitamin D, 25(OH)D, calcium, and phosphorus concentrations and urinary calcium/creatinine ratios were measured at baseline then monthly, and infant blood parameters were measured at baseline and months 4 and 7.

RESULTS: Of the 334 mother-infant pairs in 400 IU and 6400 IU groups at enrollment, 216 (64.7%) were still breastfeeding at visit 1; 148 (44.3%) continued full breastfeeding to 4 months and 95 (28.4%) to 7 months. Vitamin D deficiency in breastfeeding infants was greatly affected by race. Compared with 400 IU vitamin D3 per day, 6400 IU/day safely and significantly increased maternal vitamin D and 25(OH)D from baseline (P < 0.0001). Compared with breastfeeding infant 25(OH)D in the 400 IU group receiving supplement, infants in the 6400 IU group whose mothers only received supplement did not differ.

CONCLUSIONS: Maternal vitamin D supplementation with 6400 IU/day safely supplies breast milk with adequate vitamin D to satisfy her nursing infant’s requirement and offers an alternate strategy to direct infant supplementation.

 

Vitamin D and multiple health outcomes: umbrella review of systematic reviews and meta-analyses of observational studies and randomised trials.

Theodoratou E, Tzoulaki I, Zgaga L, et al. V BMJ. 2014 Apr 1;348:g2035. 

doi:10.1136/bmj.g2035. (Review)

OBJECTIVE: To evaluate the breadth, validity, and presence of biases of the associations of vitamin D with diverse outcomes.
DESIGN: Umbrella review of the evidence across systematic reviews and meta-analyses of observational studies of plasma 25-hydroxyvitamin D or 1,25-dihydroxyvitamin D concentrations and randomised controlled trials of vitamin D supplementation.
DATA SOURCES: Medline, Embase, and screening of citations and references. ELIGIBILITY CRITERIA: Three types of studies were eligible for the umbrella review: systematic reviews and meta-analyses that examined observational associations between circulating vitamin D concentrations and any clinical outcome; and meta-analyses of randomised controlled trials assessing supplementation with vitamin D or active compounds (both established and newer compounds of vitamin D).
RESULTS: 107 systematic literature reviews and 74 meta-analyses of observational studies of plasma vitamin D concentrations and 87 meta-analyses of randomised controlled trials of vitamin D supplementation were identified. The relation between vitamin D and 137 outcomes has been explored, covering a wide range of skeletal, malignant, cardiovascular, autoimmune, infectious, metabolic, and other diseases. Ten outcomes were examined by both meta-analyses of observational studies and meta-analyses of randomised controlled trials, but the direction of the effect and level of statistical significance was concordant only for birth weight (maternal vitamin D status or supplementation). On the basis of the available evidence, an association between vitamin D concentrations and birth weight, dental caries in children, maternal vitamin D concentrations at term, and parathyroid hormone concentrations in patients with chronic kidney disease requiring dialysis is probable, but further studies and better designed trials are needed to draw firmer conclusions. In contrast to previous reports, evidence does not support the argument that vitamin D only supplementation increases bone mineral density or reduces the risk of fractures or falls in older people.
CONCLUSIONS: Despite a few hundred systematic reviews and meta-analyses, highly convincing evidence of a clear role of vitamin D does not exist for any outcome, but associations with a selection of outcomes are probable.

Trial of Daily Vitamin D Supplementation in Preterm Infants

1. Chandra Kumar Natarajan, DM^a, 
2. M. Jeeva Sankar, DM^a,
3. Ramesh Agarwal, DM^a, 
4. O. Tejo Pratap, DM^a, 
5. Vandana Jain, MD^b,
6. Nandita Gupta, PhD^c, 
7. Arun Kumar Gupta, MD^d, 
8. Ashok K. Deorari, MD^a, 
9. Vinod K. Paul, MD^a, and 
10. Vishnubhatla Sreenivas, PhD^e
11. Pediatrics. 2014 Mar;133(3):e628-34. doi: 10.1542/peds.2012-3395. Epub 2014 Feb 10.
    
    
    OBJECTIVE: To compare the effect of 800 vs 400 IU of daily oral vitamin D₃on the prevalence of vitamin D deficiency (VDD) at 40 weeks’ postmenstrual age (PMA) in preterm infants of 28 to 34 weeks’ gestation.
    METHODS: In this randomized double-blind trial, we allocated eligible infants to receive either 800 or 400 IU of vitamin D₃ per day (n = 48 in both groups). 
    RESULTS: Prevalence of VDD in the 800-IU group was significantly lower than in the 400-IU group at 40 weeks (38.1% vs 66.7%; relative risk: 0.57; 95% confidence interval: 0.37–0.88) and at 3 months’ CA (12.5% vs 35%; relative risk: 0.36; 95% confidence interval: 0.14–0.90). One infant (2.4%) in the 800-IU group had vitamin D excess (100–150 ng/mL). Bone mineral content (mean ± SD: 79.6 ± 16.8 vs 84.7 ± 20.7 g; P = .27) and bone mineral density (0.152 ± 0.019 vs 0.158 ± 0.021 g/cm²; P = .26) were not different between the 2 groups.
    CONCLUSIONS: Daily supplementation with 800 IU of vitamin D reduces the prevalence of VDD at 40 weeks’ PMA and at 3 months’ CA in preterm infants without showing any improvement in bone mineralization. However, there is a possibility that this dose may occasionally result in vitamin D excess

Vitamin D supplementation reduces the risk of acute otitis media in otitis-prone children.

Pediatr Infect Dis J. 2013 Oct;32(10):1055-60. doi: 10.1097/INF.0b013e31829be0b0. 
Marchisio P, Consonni D, Baggi E, Zampiero A, Bianchini S, Terranova L, Tirelli S, Esposito S, Principi N.

BACKGROUND:

The aim of this study was to evaluate whether a deficit in vitamin D (VD) is associated with an increased risk of recurrent acute otitis media (AOM) and whether VD supplementation is effective in reducing the number of AOM episodes in otitis-prone children.

METHODS:

A total of 116 children with a history of recurrent AOM (≥3 episodes in preceding 6 months or ≥4 episodes in preceding 12 months) were prospectively and blindly randomized to receive oral VD 1000 IU/d or placebo for 4 months. Episodes of AOM were monitored for 6 months.

RESULTS:

Fifty-eight children received placebo and 58 with similar characteristics were treated with VD. The number of children experiencing ≥1 AOM episode during the study period was significantly lower in the treatment group (26 versus 38; P = 0.03). There was a marked difference in the number of children who developed uncomplicated AOM (P < 0.001), but no difference in the number of children with ≥1 episode of spontaneous otorrhea. The likelihood of AOM was significantly reduced in the patients whose serum VD concentrations were ≥30 ng/mL.

CONCLUSIONS:

VD hypovitaminosis is common in children with recurrent AOM and associated with an increase in the occurrence of AOM when serum 25(OH)D levels are < 30 ng/mL. The administration of VD in a dosage of 1000 IU/d restores serum values of ≥30 ng/mL in most cases and is associated with a significant reduction in the risk of uncomplicated AOM.

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Vitamin D in the Healthy European Paediatric Population.

J Pediatr Gastroenterol Nutr. 2013 Jun;56(6):692-701

Braegger C, Campoy C, Colomb V, Decsi T, Domellof M, Fewtrell M, Hojsak I, Mihatsch W, Molgaard C, Shamir R, Turck D, van Goudoever J; on Behalf of the ESPGHAN Committee on Nutrition.

Source

*Division of Gastroenterology and Nutrition, University Children's Hospital Zurich, Zurich, Switzerland †Department of Paediatrics, University of Granada, Granada, Spain ‡Hospital Necker, Paris, France §Department of Paediatrics, University of Pecs, Hungary ||Department of Clinical Sciences, Paediatrics, Umeå University, Umeå, Sweden ¶MRC Childhood Nutrition Research Centre, UCL Institute of Child Health, London, UK #Children's Hospital Zagreb, Zagreb, Croatia **Department of Paediatrics, Deaconry Hospital, Schwaebisch Hall, Germany ††Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Frederiksberg C, Denmark ‡‡Schneider Children's Medical Centre of Israel, Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv, Israel §§Jeanne de Flandre Children's Hospital, Lille University Faculty of Medicine, Lille, France ||||Paediatrics, VU University Medical Center Amsterdam Netherlands and Paediatrics, Emma Children's Hospital-AMC, Amsterdam, the Netherlands. 1Dr Walter Mihatsch is the Secretary of the Committee. 2Dr Johannes van Goudoever is the Chairperson of the Committee.

ABSTRACT: In recent years, reports suggesting a resurgence of vitamin D deficiency in the Western world, combined with various proposed health benefits for vitamin D supplementation, have resulted in increased interest from health care professionals, the media, and the public. The aim of this position paper is to summarise the published data on vitamin D intake and prevalence of vitamin D deficiency in the healthy European paediatric population, to discuss the health benefits of vitamin D and to provide recommendations for the prevention of vitamin D deficiency in this population. Vitamin D plays a key role in calcium and phosphate metabolism and is essential for bone health. There is insufficient evidence from interventional studies to support vitamin D supplementation for other health benefits in infants, children, and adolescents. The pragmatic use of a serum concentration >50 nmol/L to indicate sufficiency and a serum concentration <25 sigue="">

Randomized trial of vitamin D supplementation to prevent seasonal influenza A in schoolchildren.

Randomized trial of vitamin D supplementation to prevent seasonal influenza A in schoolchildren.
Am J Clin Nutr. 2010 Mar 10. [Epub ahead of print]

Randomized trial of vitamin D supplementation to prevent seasonal influenza A in schoolchildren.
Urashima M, Segawa T, Okazaki M, Kurihara M, Wada Y, Ida H.

Division of Molecular Epidemiology Jikei University School of Medicine Minato-ku Tokyo Japan.

Abstract
BACKGROUND: To our knowledge, no rigorously designed clinical trials have evaluated the relation between vitamin D and physician-diagnosed seasonal influenza. OBJECTIVE: We investigated the effect of vitamin D supplements on the incidence of seasonal influenza A in schoolchildren. DESIGN: From December 2008 through March 2009, we conducted a randomized, double-blind, placebo-controlled trial comparing vitamin D(3) supplements (1200 IU/d) with placebo in schoolchildren. The primary outcome was the incidence of influenza A, diagnosed with influenza antigen testing with a nasopharyngeal swab specimen. RESULTS: Influenza A occurred in 18 of 167 (10.8%) children in the vitamin D(3) group compared with 31 of 167 (18.6%) children in the placebo group [relative risk (RR), 0.58; 95% CI: 0.34, 0.99; P = 0.04]. The reduction in influenza A was more prominent in children who had not been taking other vitamin D supplements (RR: 0.36; 95% CI: 0.17, 0.79; P = 0.006) and who started nursery school after age 3 y (RR: 0.36; 95% CI: 0.17, 0.78; P = 0.005). In children with a previous diagnosis of asthma, asthma attacks as a secondary outcome occurred in 2 children receiving vitamin D(3) compared with 12 children receiving placebo (RR: 0.17; 95% CI: 0.04, 0.73; P = 0.006). CONCLUSION: This study suggests that vitamin D(3) supplementation during the winter may reduce the incidence of influenza A, especially in specific subgroups of schoolchildren. This trial was registered at https://center.umin.ac.jp as UMIN000001373.