Elsevier

Metabolism

Volume 60, Issue 12, December 2011, Pages 1719-1725
Metabolism

Clinical Science
Prophylactic vitamin D in healthy infants: assessing the need

https://doi.org/10.1016/j.metabol.2011.04.011Get rights and content

Abstract

The objective was to evaluate the need for vitamin D prophylaxis in healthy infants. This was a prospective and randomized study performed at primary care clinics. Eighty-eight full-term 1-month-old healthy infants were randomly assigned to receive (n = 41) or not (n = 47) 402 IU/d of vitamin D for 1 year. Primary outcome measures were serum 25-hydroxyvitamin D (25OHD) and parathyroid hormone (PTH) concentrations at 3, 6, and 12 months of age; secondary measures included data on feeding, habitat, season of birth, sun exposure, and physical examination. At 3 and 6 months of age, serum 25OHD levels (±SD) were significantly higher (P < .001) in the prophylaxis group. In the group without prophylaxis, serum 25OHD increased with age; and breast-fed infants aged 3 months had the lowest value (20.2 ± 9.4 ng/mL), which was significantly (P = .001) lower than that of formula-fed infants (35.0 ± 9.7 ng/mL). The PTH levels were not influenced by the prophylaxis or feeding. No influence of either the habitat or season of birth on serum 25OHD concentrations was demonstrated. No infant had clinical signs of vitamin D deficiency. Serum 25OHD and PTH concentrations were weakly but significantly correlated (r = −0.29, P = .009) at 3 months of age. Healthy infants without vitamin D prophylaxis had lower circulating concentrations of 25OHD at 3 and 6 months of age, the lowest value being found in 3-month breast-fed infants. The clinical relevance of these findings is probably negligible because serum 25OHD levels spontaneously increased with age and were not associated with high serum PTH. Clinical manifestations of rickets were not observed.

Introduction

Issues such as the actions of vitamin D not linked to mineral metabolism, the concern about the return of clinical rickets, and the high estimated prevalence of subclinical vitamin D deficiency have prompted the recent outburst of publications on vitamin D [1]. There is also a growing controversy on whether or not vitamin D exerts a protective role in the pathogenesis and progression of major diseases including diabetes mellitus, cancer, chronic kidney disease, and asthma [2], [3], [4], [5], [6].

A serum 25-hydroxyvitamin D (25OHD) concentration of 20 ng/mL is usually considered in adults as the threshold of vitamin D deficiency on the basis that serum parathyroid hormone (PTH) levels increase when serum 25OHD concentrations drop to less than this value [7], [8], [9]. However, there is no consensus on the definition of hypovitaminosis D in infants and children [7], [10], [11]; and estimates of its prevalence range widely from 1% to 78% [12]. Dietary Reference Intakes from the Institute of Medicine (1997) define vitamin D deficiency as a serum concentration of 25OHD less than 11 ng/mL [13], although other authors consider that the threshold of deficiency should take into account the dietary calcium intake [14].

The American Academy of Pediatrics revised its policy on vitamin D supplementation in 2008. The current recommended daily intake of vitamin D is 400 IU/d since the first few days of life for infants, children, and adolescents because this vitamin D dose has been shown to maintain serum 25OHD concentrations greater than 20 ng/mL in exclusively breast-fed infants [10].

In November 2010, the Institute of Medicine of the United States proposed new reference values for calcium and vitamin D that modify those issued in 1997 [15], which established an adequate intake for vitamin D of 200 IU/d, coinciding with other international organizations [16]. Following a review by a Food and Nutrition Board committee, the adequate intake for vitamin D in childhood and adolescence has now been established to be 400 IU/d [17]. This recommendation assumes that no vitamin D is synthesized in the skin.

The adequacy of human milk in providing vitamin D [10], [18], [19], [20], [21], [22], [23], [24], [25], [26], especially in dark-skinned infants and infants born to mothers deficient in vitamin D [27], [28], [29], [30], [31], is a matter of question. Serum 25OHD concentrations in the mother′s blood and cord blood have been shown to be consistently correlated with newborn′s serum 25OHD levels, but not with newborn′s serum calcium, phosphorus, and PTH concentrations [32]. Former studies showed lower serum 25OHD concentrations in breast-fed infants without vitamin D supplementation than in infants with vitamin D supplementation, although this difference was not associated with significant differences in PTH levels or bone mineral density [23], [24], [26], [33].

The policy of food fortification and vitamin D prophylaxis in infants varies according to country and even within the same country or region. In Spain, the infant formulas provide 1.0 to 1.8 µg/100 mL of vitamin D; and there are no uniform recommendations on the convenience of systematic vitamin D prophylaxis as well as its dosage and duration. The present study was designed to find out the differences in vitamin D status between 2 populations of healthy infants classified according to whether or not they were recommended vitamin D pharmacological prophylaxis in a poorly sunny geographical area located at a latitude of 43° north (N).

Section snippets

Design and participants

A clinical, prospective, randomized, and multicenter study was designed and approved by the Regional Ethics Committee of the Principality of Asturias. Informed consents were obtained from parents. Healthy term infants who were seen for a routine health visit in the first 15 days of life in the 11 participating primary health care centers of a community of northern Spain (latitude, 43°N) from February 2007 through February 2008 were enrolled in this study.

Infants were randomly assigned to a

Results

One hundred two infants were enrolled into the study; but the final sample included 88 infants, 41 in the vitamin D prophylaxis group and 47 in the group without vitamin D prophylaxis (Fig. 1). Demographic features of both groups of patients and main information collected in the questionnaires are shown in Table 1. Sun exposure time was not different between both groups. No clinical signs or symptoms of rickets were found in any child. Three infants from the prophylaxis group and 4 from the

Discussion

This study shows that healthy infants without vitamin D prophylaxis had lower serum concentrations of 25OHD at 3 and 6 months of age than those found in a group of infants receiving 402 IU/d of vitamin D, but no significant difference was found at 12 months of age. Likewise, the serum PTH concentrations were not different between both groups at any age. No infant showed clinical symptoms of rickets. The risk of subtle forms of hypovitaminosis D [12], [36], [37], [38], [39], [40] is leading to

Funding

Partly supported by grant FIS ECO8/00238 from the Instituto de Salud Carlos III and by the Fundación Nutrición y Crecimiento.

Acknowledgment

The authors are grateful to the infants and their families for their participation in the study; and all members of the Collaborative Group on Prophylaxis with Vitamin D.

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    Author contributions: Dr Alonso had full access to all of the data in the study and took responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Alonso, Rodríguez, Santos. Acquisition of data: Collaborative Group on Prophylaxis with Vitamin D in Asturias (Dr Ordoñez, Dr González-Posada, Dr Martínez, Dr Carballo, Dr Fernández Francés, and all authors of the manuscript). Analysis and interpretation of data: Coto, Alonso, Rodríguez, Santos. Drafting of the manuscript: Alonso, Rodríguez, Santos. Critical revision of the manuscript: Santos, Carvajal-Urueña. Statistical analysis: Rodríguez.

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