Question 2 What is the ideal dose of vitamin D supplementation for term neonates?
- Chike Onwuneme1,2,4,
- Aoife Carroll2,
- Roberta McCarthy1,
- Mark Kilbane3,
- Malachi McKenna3,
- Nuala Murphy2,
- Eleanor J Molloy1,4,5
- 1Department of Paediatrics, National Maternity Hospital, Dublin, Ireland
- 2Department of Endocrinology, Children's University Hospital Temple Street, Dublin, Ireland
- 3Metabolism Laboratory, St Vincent's University Hospital, Dublin, Ireland
- 4UCD School of Medicine and Medical Sciences, University College Dublin, Dublin, Ireland
- 5Department of Neonatology, National Maternity Hospital, Dublin, Ireland
- Correspondence to Chike Onwuneme, Department of Paediatrics, National Maternity Hospital, Holles Street, Dublin 2, Ireland;
- Received 25 January 2012
- Accepted 29 January 2012
During a well-baby check, a mother asked for the consultant's recommendation on the ideal dose and type of vitamin D formulation for her infant. She intends to breastfeed her baby exclusively. Her baby was born at 39 weeks gestation by spontaneous vaginal delivery.
Structured clinical question
In a normal term neonate [patient], what is the optimal dose of vitamin D supplementation [intervention] to prevent vitamin D deficiency and rickets [outcome]?
MEDLINE was searched via PubMed from 1990 to July 2011. The advanced search mode was used with the terms ‘vitamin D’ and ‘neonates’ and ‘supplementation’.
A search of the Cochrane Library was conducted using the search terms ‘vitamin D’ and ‘infants’.
Vitamin D is essential for good bone health and insufficient levels are linked to rickets in children.1 5 A resurgence of vitamin D insufficiency and nutritional rickets has been reported across many countries.1 Studies in infants and children are also exploring the association between vitamin D insufficiency and type 1 diabetes mellitus as well as inflammatory diseases.1 2 There are limited natural dietary sources of vitamin D and adequate sun exposure for the cutaneous synthesis of vitamin D is not easily determined for a given individual.3 Therefore, the recommendations to ensure adequate vitamin D status have been revised to cover all infants, including those who are exclusively breastfed.3
In Europe, very few foods are fortified with vitamin D and children are at especially high risk of deficiency.5 The most studied functional outcome of vitamin D deficiency in children has been the occurrence of vitamin D deficiency rickets.6 Insufficiency is defined as a vitamin D level <50 nmol/l and severe deficiency as a vitamin D level <25 nmol/l.3 4 Reports on children from around the world have not supported any absolute threshold level of vitamin D for the occurrence of rickets.6 Studies have shown that less than 200 IU/day of vitamin D will not maintain vitamin D concentrations at >50 nmol/l in infants.3 An intake of 400 IU/day of vitamin D has been shown to maintain serum vitamin D concentrations at >50 nmol/l in exclusively breastfed infants.3 7 9
Pittard et al in a randomised controlled trial demonstrated that in newborns, 400 IU/day of vitamin D3 maintains the serum concentration of vitamin D above the range classically associated with rickets (see table 2).7 A Cochrane Review found that 400 IU/day of vitamin D for 12 months prevented nutritional rickets in children aged 3–36 months in Turkey, and that 300 IU/day of vitamin D for at least the first 12 months reduced the risk of rickets by 24% in China. A randomised clinical trial by Shakiba et al in Iran found that administering 200 IU/day, 400 IU/day and a 2-monthly bolus injection of 50 000 IU vitamin D provides the ideal serum level (>50 nmol/l) of vitamin D and prevents nutritional rickets.9 However, self-limiting complications such as diarrhoea and agitation were reported in the bolus injection group. No other studies have shown added benefits for doses greater than 400 IU/day in infants or children. A randomised controlled trial by Siafarikas et al in Germany demonstrated that supplementation with 250 IU/day versus 500 IU/day of vitamin D3 for breastfed infants is sufficient (serum level >50 nmol/l) and prevents nutritional rickets in the summer and winter; there was no difference in serum vitamin D levels between the 250 IU/day and 500 IU/day groups.10
Clinical bottom line
▶ 200–250 IU/day of vitamin D3 provided to breastfed infants prevents nutritional rickets, but this may not apply to dark skinned infants as studies were conducted only in white children. (Grade B)
▶ 400 IU/day of vitamin D is not associated with adverse effects but has not been shown to be superior to 200–250 IU/day for the prevention of nutritional rickets. (Grade B)
The Institute of Medicine of the National Academies, the American Academy of Paediatrics, the Drug and Therapeutics Committee of the Lawson Wilkins Paediatric Endocrine Society, the Canadian Paediatric Society and the European Society for Paediatric Endocrinology recommend 400 IU/day of vitamin D supplementation for infants.3 11 12 However, the European Society for Paediatric Gastroenterology, Hepatology and Nutrition suggested 800–1000 IU/day for high-risk infants during the winter. The Irish Department of Health and Children and the Health Service Executive recommend that all infants from birth to 12 months, whether breastfed or formula fed, be given a daily supplement of 200 IU (5 µg) of vitamin D3.13 The UK Department of Health guidelines on vitamin D supplements in infants14 recommend that breastfed children should be given a daily vitamin D supplement from 6 months of age until the age of 5 years. However, children receiving less than 500 ml (a pint) of infant formula a day should also be given a daily vitamin D supplement. The recommended Healthy Start Children's vitamin drop in the UK15 contains 300 IU (7.5 µg) of vitamin D3.
Competing interests None.
Provenance and peer review Commissioned; internally peer reviewed.