Vitamin D deficiency in children Dr. Rim El-Rifai Consultant Paediatrician Queen Mary’s Hospital for Children

Dangers of Vitamin D deficiency: DOH February 2012 Up to ¼ of the population has low levels of Vitamin D in their blood The majority of pregnant women do not take Vitamin D supplements People on lower income can get supplements through the Healthy Start Scheme

Vitamin D A prohormone essential for normal absorption of calcium from the gut It occurs Naturally in the body following exposure to UVB sunlight, the body can also synthesize it (from cholesterol) A group of fat-soluble Secosteroids In humans, it can be ingested as cholecalciferol (vitamin D3) or ergocalciferol (vitamin D2)

25-hydroxy vitamin D The 25-hydroxy vitamin D test is the most accurate way to measure vitamin D level. In the kidney, 25-hydroxy vitamin D changes into an active form of the vitamin.

Synthesis of Vitamin D In the skin 7-dehydrocholseterol is converted to vitamin D3 In the liver vitamin D is converted to 25- hydroxycholecalciferol, or 25-hydroxyvitamin D (Calcidiol) —abbreviated 25(OH)D: the specific vitamin D metabolite measured in serum to determine a vitamin D status. Part of the calcidiol is converted by the kidneys to 1, 25- dihydroxy vitamin D3 (Calcitriol), the biologically active form of vitamin D. Calcitriol circulates in the blood, regulating the concentration of Calcium and Phosphate in the bloodstream and promoting the healthy growth and remodeling of bone. Calcidiol is also converted to calcitriol outside of the kidneys for other purposes, such as the proliferation, differentiation and apoptosis of cells; calcitriol also affects neuromuscular function and inflammation.[

Vitamin D deficiency in Children in the UK ADCH 2007 Survey of Paediatricians in the West Midlands in 2001 24 cases of Vit D deficiency under 5 years of age Overall incidence 7.5 per 100 000 11/24 had bowed legs, presented at around 18 months 6 had hypocalcemic seizures at 6 weeks of age 4 had gross motor delay at 17.7 months of age All were black African or African-Caribbean Majority were beastfed 50% of those with convulsions were formula fed suggesting inadequate Vit D content in formula milk Advised: need to supplement vulnerable groups including pregnant women

Vitamin D deficiency rickets among children in Canada Paediatricians surveyed between 2002-2004 104 confirmed cases in the study period Overall annual incidence 2.9 cases per 100 000 Mean age at diagnosis 1.4 yrs 65% lived in urban areas 89% had intermediate or darker skin 94% were breastfed None of the breast fed babies had received a supplement according to guidelines (400 IU/day) Maternal risk factors included: limited sun exposure, lack of Vit D from diet, lack of Vitamin supplementation during pregnancy and lactation

AMERICAN ACADEMY OF PEDIATRICS Prevention of Rickets and Vitamin D Deficiency: New Guidelines for Vitamin D Intake, April 2003 Cases of rickets in infants attributable to inadequate vitamin D intake and decreased exposure to sunlight continue to be reported in the United States. A state of deficiency occurs months before rickets is obvious on physical examination. Also, it is acknowledged that most vitamin D in older children and adolescents is supplied by sunlight exposure. However, dermatologists and cancer experts advise caution in exposure to sun, especially in childhood, and recommend regular use of sunscreens. Sunscreens markedly decrease vitamin D production in the skin.

People at risk of Vit D deficiency all pregnant and breastfeeding women, especially teenagers and young women infants and young children under 5 years of age older people aged 65 years and over people who have low or no exposure to the sun, for example those who cover their skin for cultural reasons, who are housebound or confined indoors for long periods people who have darker skin, for example people of African, African-Caribbean and South Asian origin

Presentation Extremely variable and dependent on: age Severity of deficiency Underlying causes Ranges from Biochemical to severe bony disease

Rickets in 1st year of life The most rapidly growing bones are : skull, upper limbs and ribs Craniotabes Widening on cranial sutures Frontal bossing Enlarged swollen epiphyses: particularly wrists Bulging of costo-chondral joints (Rachitic Rosary) Harrison’s sulcus Irritability Hypotonia

Bowing of legs Frontal bossing

Rachitic Rosary

Enlarged Swollen Epiphyses

Rickets after the first year Genu Varum, Genu Valgum Abnormal dentition with enamel hypoplasia Bone pain Proxymal myopathy

Genu Valgum and Genu Varum

Severe Rickets In severe cases resulting from low Calcium: Tetany Laryngeal stridor Paraesthesiae Convulsions Respiratory failure

Association of subclinical vitamin D deficiency with severe acute lower respiratory infection in children Study of 150 hospitalized Indian children in 2004 Subclinical vitamin D deficiency and non-exclusive breast feeding in the first 4 months of age: significant risk factors for severe acute lower respiratory infections in Indian children

Causes of Vitamin D deficiency Poor dietary intake most common in Asian population Reduced synthesis from sun exposure Genetic: Vitamin D dependent rickets: AR Hypophosphataemic Rickets: x-linked dominany Malabsorption: Coeliac disease, Cystic Fibrosis Renal disease (low 1,25 dihydroxy vitamin D- the most active form) Liver Disease Medications such as Anticonvulsants induce hepatic enzymes

Calciopenic: Low Ca Dietary calcium and vitamin D deficiency Malabsorption Lack of sun light Hepatic disease Anticonvulsant treatment Renal disease 1-α hydroxylase deficiency End organ resistance to vitamin D

Phosphopenic:low PO4 Fanconi Syndrome X-linked hypoposphataemic rickets Renal tubular acidosis Ocul-cerebro-renal syndrome (Lowe syndrome) Osteopenia of prematurity

Biochemical Hypocalcaemia Hypophosphataemia Elevated Alkaline Phosphatase Low 1,25 – Dihydroxy vitamin D Serum Parathyroid Hormone level may be high

Radiologically Widening of growth plate Fraying, Cupping, and Widening of metaphyses Pseudo fractures Signs of secondary hyperparathyroidism : subperiosteal erosion

Other investigations Depending on underlying cause: Acidosis Aminoaciduria Chronic renal failure anaemia

Treatment Calcium, phosphate and vitamin D given in varying combinations Underlying abnormalities need to be treated (coeliac disease) Growth needs to be monitored In hypophsphataemic rickets large doses of Vitamin D are required In 1α hydroxylase deficiency or end-organ resistance to vitamin D, 1,25- dihydroxy-cholecalciferol is usually required in significant doses Regular renal USS is important

Treatment Vitamin D 1,000 to 5,000 μg IV/ day until normal alkaline phosphatase Then 10 μg / day and 500 ml/ day of milk for calcium requirements Exposure to sunlight Dietary source: oily fish, fortified margarine

Dietary sources Oily fish Eggs Infant formula Some cereals, dairy products, low fat speads have a small amounts added Difficult to get sufficient Vitamin D from diet alone

Breast feeding and Vitamin D Infants who are breastfed but do not receive supplemental vitamin D or adequate sunlight exposure are at increased risk of developing vitamin D deficiency or rickets. Human milk typically contains a vitamin D concentration of 25 IU/L or less. The recommended adequate intake of vitamin D cannot be met with human milk as the sole source of vitamin D for the breastfeeding infant.

Formulas and Vitamin D All infant formulas must have a minimum vitamin D concentration of 40 IU/100 kcal (258 IU/L of a 20- kcal/oz formula) and a maximum vitamin D concentration of 100 IU/100 kcal (666 IU/L of a 20- kcal/oz formula). All formulas sold have at least 400 IU/L. If an infant is ingesting at least 500 mL per day of formula (vitamin D concentration of 400 IU/L), he or she will receive the recommended vitamin D intake of 200 IU per day.

Sunlight Exposure Decreased sunlight exposure occurs: Skin Cancer: during the winter and other seasons and when sunlight is attenuated by clouds, air pollution Lifestyles or cultural practices: decreased time spent outdoors increase the amount of body surface area covered by clothing when outdoors. individuals with darker skin pigmentation by the use of sunscreens. Skin Cancer: age at which direct sunlight exposure is initiated is more important than the total sunlight exposure over a lifetime in determining the risk of skin cancer. AAP guidelines for decreasing exposure: infants younger than 6 months should be kept out of direct sunlight, children’s activities that minimize sunlight exposure should be selected, protective clothing as well as sunscreens should be used.

Chief Medical Officers: “A significant proportion of people in the UK probably have inadequate levels of vitamin D in their blood. “People at risk of vitamin D deficiency, including pregnant women and children under 5, are already advised to take daily supplements”. DOH February 2012

National Pharmacy Association Fact sheet prepared with assistance of DOH in March 2012 Providing advice on the prevention of vitamin D Deficiency in the at risk groups http://www.npa.co.uk/resources/information-leaflets- and-factsheets/clinical/preventing-vitamin-d-deficiency- in-at-risk-groups/

NPA Recommendations Daily vitamin D supplementation should be taken by: All pregnant and breastfeeding women Breastfed infants from one month of age if mother did not take vit D supplements through pregnancy All children aged 6 mon- 5 years (except who receive more than 500 ml of formula milk, which is fortified with Vit D) People aged 65 and over People who are not exposed to much sun People with darker skins Medical conditions (GI, renal, liver) Medication (Carbamazepine, phenytoin, primidone, barbiturates, some anti-HIV medicines

NPA Supplementation guidance Patient Class Daily supplementation dose of vitamin D Pregnant or breastfeeding 10 micrograms (440 iu) Breastfed infants from one month of age if mother did not take vitamin D supplementation during pregnancy Babies may need supplementation in the form of vitamin drops containing vitamin D Children aged 6 mon to 5 yrs drinking 500 ml or more of formula milk None required Children 6 mon to 5 yrs NOT drinking 500 ml of formula milk Vitamin drops containing vitamin D Aged 65 years or all ages with limited exposure to sun 10 micrograms (400 iu)

prognosis Excellent in most children Dependent on compliance with treatment Less certain in hypophospahtaemic rickets and severe deformities of the limbs may result