e-Library of Evidence for Nutrition Actions (eLENA)

Interventions for the prevention of nutritional rickets in term born children

Systematic review summary

This document has been produced by the World Health Organization. It is a summary of findings and some data from the systematic review may therefore not be included. Please refer to the original publication for a complete review of findings.

Original publication
Lerch C, Meissner T. Interventions for the prevention of nutritional rickets in term born children. Cochrane Database of Systematic Reviews 2007, Issue 4. Art. No.: CD006164. DOI: 10.1002/14651858.CD006164.pub2.

Key findings

  • Few (4) studies were identified for inclusion in the review, three of which were randomized controlled trials
  • Vitamin D supplementation, with or without calcium and nutritional counselling, compared with no treatment reduced the risk of nutritional rickets in children up to three years of age in two trials, and in the other two trials no cases of rickets occurred in either treatment group
  • Although current evidence is limited, it appears that vitamin D and/or calcium supplementation should be offered to groups at high risk of nutritional rickets

1. Objectives

To assess the effects of various interventions on the prevention of nutritional rickets in term born children

2. How studies were identified

The following databases were searched in August 2006:

  • CENTRAL (The Cochrane Library 2006, Issue 3)
  • MEDLINE
  • EMBASE
  • LILACS
  • mRCT

Reference lists of identified studies were searched and researchers in the area were also contacted.

3. Criteria for including studies in the review

3.1 Study type

Randomized, quasi-randomized and non-randomized controlled clinical trials and prospective cohort studies

3.2 Study participants

Healthy term born children or children with diseases not increasing the risk of developing rickets

3.3 Interventions

Interventions used for the prevention of nutritional rickets, such as vitamin D or calcium supplementation (tablets, liquids or fortified foods), advice to increase sunlight exposure or combinations of these interventions, compared to no intervention or placebo

3.4 Primary outcomes
  • Occurrence of rickets (diagnosed clinically or radiologically)
  • Adverse events

(Studies in which rickets was diagnosed solely on biochemical data were excluded)

3.5 Secondary outcomes

Secondary outcomes included all-cause mortality, quality of life (preferably measured using a validated instrument) and costs

4. Main results

4.1 Included studies

Four trials, enrolling 1758 children, were included in this review.

  • Three studies were randomized controlled trials and one study was a controlled clinical trial
  • Two studies investigated vitamin D supplementation versus placebo or no treatment, one study compared parental nutritional counselling and vitamin D and calcium supplementation versus no treatment, and one study evaluated fortified milks (vitamin D and calcium or calcium alone) versus no treatment
  • Age at inclusion ranged from one month to 15 years, and length of follow-up ranged from six to 30 months
4.2 Study settings
  • China (2 studies), France and Turkey
  • Three studies were community-based, recruiting from villages (China), schools (China) and the community (Turkey)
  • One study recruited hospital patients (France) who were free from diseases that increase the risk of rickets
4.3 Effect of intervention on primary outcomes

4.3.1 How the data were analysed

Interventions used for the prevention of nutritional rickets were compared to no intervention or placebo. Provided they were available and sufficiently similar, data were to be summarised statistically in meta-analysis.

Subgroup analyses were to be conducted only if significant differences between treatment groups were observed for primary outcomes, and were intended primarily for exploring heterogeneity. The following subgroup analyses were planned:

  • Infants with fair skin; infants with intermediate or dark skin living in an area with high UV-B irradiation; and infants with intermediate or dark skin living in an area with low UV-B irradiation
  • Breast milk nutrition during infancy
  • Veiling of the mother during pregnancy and breastfeeding
  • Mode of administration of the intervention

4.3.2 Summary of effects

Occurrence of rickets
Two studies reported no occurrence of rickets in either the intervention or control group. In one study set in rural Turkey of 676 children aged three to 36 months, those receiving 400 International Units (IU) of vitamin D per day for 12 months were less likely to develop rickets than those receiving no treatment (relative risk (RR) 0.04, 95% confidence interval (CI) [0 to 0.71]). In another study in rural China of 229 children aged six to 30 months, the treatment group (supplemented with vitamin D 300 IU/day and calcium 378 mg/day, and parental nutrition counselling) were also less likely to develop rickets than those receiving no treatment (RR 0.76, 95% CI [0.61 to 0.95]). Data were not pooled for meta-analysis.

Adverse events
Adverse events were investigated in one study of 66 children, in which no hypercalcaemia was observed.

No included studies reported data on mortality, quality of life or costs. No subgroup analyses were performed due to lack of sufficient data.

5. Additional author observations*

Due to the paucity of trials included in this study and clinical heterogeneity in nutritional rickets, a quantitative data synthesis was not performed. However, considering the high frequency of nutritional rickets and the likely favourable risk-benefit ratio, it may be reasonable to offer preventive interventions (vitamin D and calcium) to children up to two years of age.

Further trials investigating the prevention of nutritional rickets should be conducted in different countries, different age groups and in children of different ethnic origin. Adverse effects of these interventions should also be examined.

*The authors of the systematic review alone are responsible for the views expressed in this section.