Clinical ScienceProphylactic vitamin D in healthy infants: assessing the need
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.
References (60)
- et al.
Estimation of optimal serum concentrations of 25-hydroxyvitamin D for multiple health outcomes
Am J Clin Nutr
(2006) - et al.
Maternal intake of vitamin D during pregnancy and risk of recurrent wheeze in children at 3 y of age
Am J Clin Nutr
(2007) Circulating 25-hydroxyvitamin D levels indicative of vitamin sufficiency: implications for establishing a new effective DRI for vitamin D
J Nutr
(2005)- et al.
Circulating vitamin D3 and 25-hydroxyvitamin D in humans: an important tool to define adequate nutritional vitamin D status
J Steroid Biochem Mol Biol
(2007) - et al.
Dietary recommendations for vitamin D: a critical need for functional end points to establish an estimated average requirement
J Nutr
(2005) - et al.
Nutritional rickets in childhood: analysis of 62 cases
Med Clin
(2003) - et al.
Symptomatic hypocalcaemia due to nutritional rickets. A presentation of two cases
An Pediatr
(2010) - et al.
Higher prevalence of vitamin D deficiency in mothers of rachitic than nonrachitic children
J Pediatr
(2005) - et al.
Bone mineral content, serum vitamin D metabolite concentrations, and ultraviolet B light exposure in infants fed human milk with and without vitamin D2 supplements
J Pediatr
(1989) - et al.
Nutritional status of vitamin D and the effect of vitamin D supplementation in Korean breast-fed infants
J Korean Med Sci
(2010)
Vitamin intakes from supplements and fortified food in German children and adolescents: results from the DONALD study
J Nutr
25-Hydroxyvitamin D, cholesterol, and ultraviolet irradiation
Metabolism
Bone mineral content and serum 25-hydroxyvitamin D concentrations in breast-fed infants with and without supplemental vitamin D: one year follow-up
J Pediatr
The effects of seasonal variation of 25-hydroxyvitamin D and fat mass on a diagnosis of vitamin D sufficiency
Am J Clin Nutr
Seasonal variation of 1-25-dihydroxyvitamin D and its association with body mass index and age
J Steroid Biochem Mol Biol
Geographic location and vitamin D synthesis
Mol Aspects Med
Serum 25-hydroxyvitamin D status of adolescents and adults in two subpopulations from NHANES III
Bone
Differences in bone mineral status between urban and rural chinese men and women
Bone
Resurrection of vitamin D deficiency and rickets
J Clin Invest
Vitamin D supplementation in early childhood and risk of type 1 diabetes: a systematic review and meta-analysis
Arch Dis Child
Vitamin D serum levels and allergic rhinitis
Allergy
Hypovitaminosis D in obese children and adolescents: relationship with adiposity, insulin sensitivity, ethnicity, and season
Metabolism
Vitamin D deficiency
N Engl J Med
Vitamin D deficiency in children and its management: review of current knowledge and recommendations
Pediatrics
Effectiveness and safety of vitamin d in relation to bone health
Evidence report/technology assessment no 158
Hypovitaminosis D among healthy children in the United States
Arch Pediatr Adolesc Med
Nutritional rickets with normal circulating 25-hydroxyvitamin D: a call for reexamining the role of dietary calcium intake in North American infants
J Clin Endocrinol Metab
Dietary reference intakes for calcium, phosphorus, magnesium, vitamin D, and fluoride
Vitamin D
Committee to review dietary references intakes for vitamin D and calcium. Food and Nutrition Board
Cited by (28)
Current opinion on the role of vitamin D supplementation in respiratory infections and asthma/COPD exacerbations: A need to establish publication guidelines for overcoming the unpublished data
2022, Clinical NutritionCitation Excerpt :De Gruijl et al. [117], Baris et al. [125], Dhungel and Alam [144], Babar et al. [150], Somnath et al. [147] and Di Mauro et al. [155] were unblinded for both participants and personnel and hence these RCTs were rated as some concerns for bias associated with deviations from intended intervention. Finally, Aloia and Li-Ng [107], Alonso et al. [114], Tran et al. [95] and Grant et al. [96] were considered at high risk of bias in selection of the reported result. Overall, a total of eight RCTs were rated as high risk of bias [95,96,107,110,112,114,144,150], five RCTs were rated as some concerns [117,135,143,149,155] and the remaining 52 RCTs were rated as low risk of bias.
Vitamin D reduces respiratory tract infections frequency
2017, Journal of PediatricsHypovitaminosis D and associated factors in 4-year old children in northern Spain
2017, Anales de PediatriaWorld Allergy Organization-McMaster University Guidelines for Allergic Disease Prevention (GLAD-P): Vitamin D
2016, World Allergy Organization JournalCitation Excerpt :We found no systematic review addressing this question. We found 5 randomized trials that investigated vitamin D supplementation in infants but none reported allergy outcomes [38–42]. One RCT [42] could not be meta-analyzed because it reported mean values without measures of dispersion.
Vitamin D deficiency at pediatric intensive care admission
2014, Jornal de PediatriaCitation Excerpt :Many confounding factors (hemodilution, interstitial extravasation, decreased synthesis of binding proteins, renal wasting of 25(OH)vitD, pH, underlying disease, season of the year, age, and dietary supplementation, among others) influence vitamin D status during critical illness.17 To date, there is no consensus regarding the optimal definitions of vitamin D deficiency, nor the threshold levels to define health benefits.17,18 Therefore, this study aimed to investigate whether vitamin D deficiency is highly prevalent in patients admitted to a PICU.
Health and vitamin D: An incomplete puzzle
2012, Anales de Pediatria
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.