Confusion regarding the importance of specific ethnic groups receiving correct advice on vitamin supplementation and sunshine could partly be behind this worrying recent trend, believesJacqui Lowdon
Rickets is a childhood disease that causes a softening of the bones, potentially leading to fractures and deformity. Eighty years ago it was thought to have largely been eradicated from the UK. However a recent increase in cases of rickets, not just in Britain but around the world, has proven this isn't the case. Today the disease affects children from all types of socio-economic backgrounds, not just the poorer ones, and it is primarily caused by low levels of vitamin D and certain foods. In January 2011 the government's chief medical officer Dame Sally Davies recommended all children aged six months to five should be given vitamin D supplements, particularly during winter months when natural sunshine is limited.
The irony is that the advice in recent years for children to wear a high factor sunscreen and remain covered up while playing outdoors are partly felt to be behind the reason for its re-emergence. Parents and health professionals alike were shocked when it was revealed that a school girl living on the Isle of Wight developed rickets precisely because of her mother's vigilance at following sun safety rules. NICE, in their latest report (Jan 2011) stated that: "Exposure to the sun has a number of benefits. For example, it increases people's sense of wellbeing, allows them to synthesise vitamin D and provides opportunities for physical activity. " A tendency for children to stay indoors and watch TV or play on computer games, rather than play outside when the sun is shining, is arguably also another contributing factor.
_ A lack of vitamin D is the prime cause of rickets
_ A good diet and sunshine are key to preventing rickets
_ Although certain ethnic groups are at greater risk, children of all ethnic groups are at risk if their diet doesn't include sufficient levels of vitamin D
_ British children don't receive a lot of sunshine during the winter months, so a good diet is vital and vitamin supplementation may also be necessary
_ It's vital that children living in Scotland and the north of England take the supplements as they spend fewer months of the year with sufficient sunshine
_ Good dietary sources of vitamin D include oily fish (such as salmon and fresh tuna), eggs and fortified margarine, cereals, milk and orange juice
_ It's now recommended that pregnant and breastfeeding mums take vitamin D supplementation as any deficiency in levels they have will have an adverse effect on the baby's own level of vitamin D
_ New government recommendations advise limited exposure to sunshine and all children under five to receive vitamin D supplementation
Nearly 35 years ago, nutritional rickets was thought to have all but disappeared in the UK. However, concerns have recently been raised about a resurgence of rickets and vitamin D deficiency among infants and children, from all corners of the globe1,2,3 not just the UK. The reports have emerged from countries with limited sunshine (like Canada, New Zealand, the UK and the USA4,5,6,7), as well as those with sunnier climes such as Australia, Saudi Arabia and Ethiopia8,9, In some instances, though, it appears that malnutrition10, may be the main contributing factor. This is despite a clear understanding of predisposing factors and preventative strategies.
What is rickets?
The osteoid tissue of bone mineralises if there is a sufficient supply of the minerals, calcium and phosphate. Osteomalacia results when there is an insufficient amount of these minerals. In children, where the bone is still growing and is unfused, this manifests itself as rickets.
What causes it? Nutritional rickets is a multifactorial condition and has multiple risk factors11 (see Table 1).
The main form of nutritional rickets is calcipenic rickets, although changes in phosphate also occur. It is caused by a deficiency of either calcium, vitamin D, or both. Although nutritional calcium deficiency has been proposed as an important factor12, it is vitamin D deficiency that has historically been the major cause of morbidity13 Other dietary factors include nutritional deficiency associated with macrobiotic diets14, vegetarian diets15,16, strict vegan diets17 or "health food" milk alternative diets18.
Diagnostic symptoms and features
Nutritional rickets has multiple clinical presentations and is age-dependant. The main symptoms and features are listed in Table 2. Three diagnostic critera are usually used to diagnose vitamin D deficiency rickets (Table 3). Once recognised, it is relatively easy to treat. However, the belief that nutritional rickets has been eliminated from developed countries, can prevent swift recognition and slow down the diagnostic process. The failure to diagnose rickets quickly is a cause for concern as there is significant potential for morbidity and mortality, including hypocalcaemic seizures, faltering growth, serious infections, and chronic problems with growth and skeletal deformity. In surveys of "at risk" populations, a significant proportion have exhibited subclinical vitamin D deficiency19. Radiological evidence of rickets is not always present in these patients7,20 leading to diagnostic confusion, such as with hypoparathyroidism or pseudohypoparathyroidism, unless the possibility of vitamin D deficiency is considered21,22. Diagnosis of rickets will be based on symptoms (Table 3), blood tests, and possibly, an X-ray of wrists and knees. Blood tests will include calcium, phosphorous, vitamin D as well as the enzyme alkaline phosphatise and the parathyroid hormone (a hormone that increases blood calcium levels). In nutritional rickets, the biochemical findings would include: normal or decreased calcium blood level and normal, decreased or increased blood phosphate level, as well as increased alkaline phosphate blood level, increased parathyroid hormone level or both. In vitamin D deficiency rickets 25-hydroxyvitamin blood levels are decreased. A bone densitometry scan, which measures the calcium content of bone and highlights any possible fractures, may also be carried out.
Prevalence of rickets
Rickets has been reported in UK infants and children, especially amongst Asian populations. In infants with fair skin, nutritional rickets is mostly due to pure vitamin D deficiency, but there is little data for incidence or prevalence. In a West Midlands study23, where the overall incidence was 7.5% per 100,000 children under five years, only one of 24 children with rickets (defined by radiological changes or hypocalcaemic convulsions) was classified as "white". This approximates to an incidence of 0.4 per annum per 100,000 children under five years. In infants with intermediate or dark skin living indigenously, nutritional rickets may be due to a calcium or vitamin D deficiency. For example, in Tibet, 66% of children over 24 months demonstrated clinical features of rickets24.
A third group comprises of children of immigrants or immigrated infants. The West Midlands study demonstrated an incidence of 38% per annum per 100 for children of south Asian ethnic origin and 95% for children of black African or African-Caribbean ethnic origin for children under the age of five years.
Prevalence of vitamin D deficiency
However there is additional worrying evidence of vitamin D deficiency in UK infants and children, which can have a detrimental effect on bone mineral mass. The international (and UK) benchmark for vitamin D deficiency has been set at <25nmol/l 25(OH)D (25, dihydroxyvitamin D3) (Table 4). This low level has been reported in UK infants, children, adolescents and adults, particularly during the winter months25,26. There is increasing evidence that even mild vitamin D insufficiency can have a detrimental effect on bone mineral mass in children and adolescent girls27,28. In the UK, adolescents have the highest prevalence of low vitamin D status, deficiency and insufficiency amongst the younger population. This is a critical time for the acquisition of optimal bone mass, which will determine bone quality in later life. For children and adolescents, levels below 50nmol/l 25(OH)D have been associated with lower bone mineral content (BMC) and mass28,29,30. However, compared to Caucasian children of a similar age, young children from Asian and Afro-Caribbean families are at higher risk31,32. A population study33 demonstrated that 20-34% of Asian children from three ethnic groups had vitamin D levels below 25nmol/l (low status) compared to 1% in a national survey34. Table 5 summarises vitamin D status in the UK.
Treatment of vitamin D deficiency is usually straightforward, consisting of oral supplementation with the vitamin. Shaw and Pal35 recommend 3,000 units daily for infants under six months and 6,000 units for older children. However, a number of infants have presented with vitamin D deficiency despite being fed with formula milks fortified with vitamin D, or who have been given vitamin supplements in recommended amounts (400 units daily). It appears that whilst 400 units per day of vitamin D is sufficient to prevent deficiency in replete individuals it may not be sufficient to correct any deficiencies at birth, where the mothers are also vitamin D deficient36,37,38,39.
An alternative, equally effective treatment is to administer a single large dose of vitamin D (300,000 to 600,000 units), either orally or parenterally40. This is particularly useful if there are concerns regarding treatment adherence. Large doses have to be given initially to mimic the supraphysiological rise in 1,25- (OH)2D, which occurs naturally at the start of treatment with vitamin D41,42. A poor response often results from the use of "physiological" doses, and does not address the underlying issue of vitamin D deficiency. If the presenting symptom is hypocalcaemia initial treatment will be with calcium supplementation, by intravenous infusion if necessary. Oral calcium supplements, as well as vitamin D, increases the rate of recovery43.
Prevention: getting it right from the start
Lifetime bone health starts right at the beginning, with the foetus, and this is influenced by the mother. Vitamin D deficiency during late pregnancy has been associated with a deficit in the accrual of bone mineral in the child, as has been demonstrated at nine years of age30. As vitamin D deficiency is well known to occur in otherwise healthy, pregnant women44, this is of particular concern.
Human milk contains little vitamin D45,46,47, approximately 0.5μg (20 IU)/litre. It relies completely on maternal vitamin D status, achieved either by UV exposure or oral supplementation48,49,50,51. Lactating mothers with low vitamin D levels will therefore provide their babies with even less than mothers who are vitamin D sufficient. This will impact on the baby's vitamin D status as well as on bone health in childhood30,52. Where breast milk is the sole source of nutrition without vitamin D supplementation, its low vitamin D content increases the infant's risk of of vitamin D deficiency38,39,53,54. A high prevalence of vitamin D deficiency among breastfed infants is also consistently being reported54. One observational study showed up to 95% of children with vitamin D deficient rickets had been breastfed10, highlighting the importance of adequate vitamin D supplementation for both mother and child.
The early years An association between premature infants supplemented with vitamin D during the first year of life and an increase in whole bone mass at 12 years of age was demonstrated in a retrospective cohort study56.
The importance of vitamin D supplementsIn order to halt the escalating prevalence of rickets in the UK19, vitamin D supplementation for pregnant and breastfeeding mothers has been highlighted by the Department of Health, as well infants and children up to the age of five years (DoH 1998). The Healthy Start vitamins, recently launched in the UK (see www.healthystart.nhs.uk), are available free of charge to those qualifying for the Healthy Start scheme. These vitamins are:
_ Vitamin D drops for infants and children - vitamins A, C and D, with 7.5 μg of vitamin D. Free of charge up to their fourth birthday
_ Supplements for women who are pregnant or breastfeeding - vitamins C, D and folic acid,with 10 μg (400 IU) of vitamin D Table 6 lists those who are at high risk of vitamin D deficiency and Table 7 lists the main factors affecting an individual's vitamin D status.
Nutritional rickets has always been with us, so technically speaking it's not making a comeback, it's merely increasing in frequency again. This is partly due to it being recognised with its different presentations, but also mainly because vitamin D supplementation is no longer regarded as essential for "at risk" individuals. The clinical cases of vitamin D deficiency almost certainly represent the "tip of the iceberg". It's now time to highlight the need for a national campaign, promoting the awareness of the risks of vitamin D deficiency, especially amongst the atrisk groups in the UK. Education programmes are also required both for health professionals and for pregnant and breastfeeding mothers. Consideration should also be given to screening "at-risk" groups, if these increasing trends are to be reversed. Despite global warming and resultant increase in sunshine, this is one iceberg that's not melting.
Jacqui Lowdon MSc, BSc, PGCE (HE),RD Paediatric Dietitian Royal Manchester Children's Hospital