Pediatric Neurology 52 (2015) 160e164
Contents lists available at ScienceDirect
Pediatric Neurology journal homepage: www.elsevier.com/locate/pnu
Original Article
Vitamin D Supplementation in Children With Epilepsy and Intellectual Disability Francesca M. Snoeijen-Schouwenaars MD a, *,1, Kaily C. van Deursen d,1, In Y. Tan MD a, Pauline Verschuure PhD e, Marian H. Majoie PhD b, c a
Department of Residential Care, Kempenhaeghe Department of Neurology, Academic Center for Epileptology Kempenhaeghe c Department of Neurology, Maastricht University Medical Center d Faculty of Health, Medicine and Life Sciences, Maastricht University e Laboratory for Clinical Chemistry & Pharmacology, Kempenhaeghe b
abstract BACKGROUND: Children with epilepsy and intellectual disability have an increased risk of vitamin D deficiency. In
this patient group, it is neither clear which factors are associated with the level of 25-hydroxyvitamin D nor what the therapeutic results are when Dutch guidelines are followed. METHODS: This retrospective study included 30 patients who, in October 2012, were residents of the children’s wards of a tertiary epilepsy center in The Netherlands (Kempenhaeghe). From November 2012 onward they received cholecalciferol supplementation in doses that met or exceeded Dutch guidelines. At baseline, after 6, and 15 months, serum 25-hydroxyvitamin D concentration was measured. RESULTS: At baseline, the vitamin D status in 11 (36.7%) residents was found to be deficient, in 10 (33.3%) to be insufficient and in 9 (30.0%) sufficient. Supplementation dose, diet, body mass index, intellectual disability, and mobility were significantly associated with baseline 25-hydroxyvitamin D concentrations. The mean 25-hydroxyvitamin D concentration increased significantly from 57.40 22.00 nmol/L at baseline to 89.47 26.77 nmol/L after 15 months (P < 0.001). In spite of supplementation ranging from 400 to 1200 IU/day, 64% of the residents in the deficient category and 30% of those with an insufficient level at baseline failed to attain a sufficient vitamin D status after 15 months. CONCLUSIONS: Not all residents reached a sufficient vitamin D status after supplementation at least equal to the amount recommended by the Dutch guidelines. In a high-risk population, such as our residents, we advise monitoring 25-hydroxyvitamin D concentrations, adjusting supplementation accordingly and following patients to ensure they reach sufficiency. Keywords: vitamin D, supplementation, children, epilepsy, intellectual disability
Pediatr Neurol 2015; 52: 160-164 Ó 2015 Elsevier Inc. All rights reserved.
Introduction
Vitamin D has an important role in bone metabolism. Vitamin D deficiency, which is common in the general population, can induce rickets, a lower peak bone mass,
Article History: Received June 11, 2014; Accepted in final form October 1, 2014 * Communications should be addressed to: Dr. SnoeijenSchouwenaars, Sterkselseweg 65; 5590 AB Heeze the Netherlands. E-mail address: [email protected] 1
Both authors were equally responsible for the work described in this paper. 0887-8994/$ - see front matter Ó 2015 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.pediatrneurol.2014.10.001
osteomalacia, and osteoporosis resulting in a higher fracture risk.1-5 Furthermore, it can cause muscle weakness,1,2 and a lack of vitamin D is associated with various chronic diseases, such as multiple sclerosis, diabetes mellitus, cardiometabolic diseases, and cancer.1-5 Factors associated with vitamin D deficiency are pigmented skin, winter season, inadequate exposure to sunshine, obesity, older age, and several chronic diseases influencing vitamin D metabolism.1,2,5,6 In The Netherlands, the recommendations on vitamin D supplementation made by the Dutch Health Council should be followed,7 although the exact definition of what constitutes a sufficient vitamin D status is still a matter of discussion.8-12
F.M. Snoeijen-Schouwenaars et al. / Pediatric Neurology 52 (2015) 160e164
Children with epilepsy are at increased risk of poor bone health. They often have additional risk factors for vitamin D deficiency.13-17 Enzyme-inducing antiepileptic drugs cause an increased catabolism of vitamin D. Nonenzyme-inducing antiepileptic drugs, polytherapy, longterm use of antiepileptic drugs, intellectual disability, and impaired mobility are also associated with vitamin D deficiency.13,14,17-24 The optimal strategy for preventing and treating a deficiency in this high-risk population is not clear.14,15,25 Only a few studies have investigated the effects of supplementation in children with epilepsy. It seems that the effect in these children differs from that in healthy children.26-31 We investigated the factors that are associated with serum 25-hydroxyvitamin D (25-(OH) D) concentrations in children with epilepsy and intellectual disability. We will also determine whether supplementation in doses which were at least equal to the amount recommended by the guidelines leads to a sufficient vitamin D status in all these children after 6 and 15 months. Materials and Methods
161
Results Patient characteristics
We included 30 of the 36 residents of the children’s wards of the epilepsy center. Six were excluded because follow-up was incomplete (two died, four moved). Patient characteristics are listed in Table 1. All those included are aged between 5 and 22 years, are Caucasian, and have unimpaired renal function. Baseline vitamin D
At baseline, the vitamin D status of 11 (36.7%) residents was deficient, of 10 (33.3%) was insufficient, and of 9 (30.0%), sufficient. The residents received standard care at baseline. This means that most residents (n ¼ 23, 76.7%) already received vitamin D supplementation, up to a maximum of 400 IU/day. Baseline 25-(OH)D concentrations differed significantly between subgroups of supplementation dose, diet, BMI, severity of intellectual disability, and mobility (Table 2). Univariate analysis showed no significant correlation of 25-(OH)D with age, duration of antiepileptic
Patient selection and intervention We selected all residents of the children’s wards of a tertiary epilepsy center in The Netherlands (Kempenhaeghe) in October 2012. They had been diagnosed with epilepsy and intellectual disability. Those in whom follow-up of vitamin D status was incomplete were excluded. Up to November 2012, residents received standard care. From November 2012 onward, they all received supplementary vitamin D at doses that were at least equivalent to the dose recommended by the Dutch Health Council. Doses were prescribed by either the physician for people with an intellectual disability or the pediatrician, depending on the individual results of the 25-(OH)D serum concentration. All vitamin D preparations contained cholecalciferol.
Data collection This study was a retrospective cohort study. We retrieved the following information from the electronic patient files: gender, age, body mass index (BMI) using Dutch BMI-tables according to age for boys and girls,32 mobility using Barthel index for walking, severity of intellectual disability using intelligence quotient, creatinine, supplementation dose of vitamin D, antiepileptic drug use, and data about epilepsy. The caregivers completed a questionnaire about the amount of sun exposure, skin type, and diet. Sun exposure and skin type were analyzed using the same definitions as the Dutch guidelines.7 Serum 25-(OH)D concentration was measured by routine automated analysis. The samples were collected for routine blood monitoring in the autumn of 2012 (baseline), spring of 2013 (6 months), and at the end of winter, 2014 (15 months). We defined a 25-(OH)D concentration of 75 nmol/L or more as “sufficient” vitamin D status, of 50 to 75 nmol/L as “insufficient,” and of less than 50 nmol/L as “deficient.”
Statistical analysis To describe continuous variables we used mean (standard deviation) for normally distributed variables and median (minimummaximum) for not normally distributed variables. We used numbers (percentages) to describe categorical variables. Paired t test, unpaired t test, analysis of variance, correlation, and linear and multiple regression, or nonparametric equivalents (Wilcoxon singed rank test, MannWhitney test, Kruskal-Wallis test) were applied to the data using SPSS, version 21 (IBM Corp, Armonk, NY). The level of significance was a P value of
Contents lists available at ScienceDirect
Pediatric Neurology journal homepage: www.elsevier.com/locate/pnu
Original Article
Vitamin D Supplementation in Children With Epilepsy and Intellectual Disability Francesca M. Snoeijen-Schouwenaars MD a, *,1, Kaily C. van Deursen d,1, In Y. Tan MD a, Pauline Verschuure PhD e, Marian H. Majoie PhD b, c a
Department of Residential Care, Kempenhaeghe Department of Neurology, Academic Center for Epileptology Kempenhaeghe c Department of Neurology, Maastricht University Medical Center d Faculty of Health, Medicine and Life Sciences, Maastricht University e Laboratory for Clinical Chemistry & Pharmacology, Kempenhaeghe b
abstract BACKGROUND: Children with epilepsy and intellectual disability have an increased risk of vitamin D deficiency. In
this patient group, it is neither clear which factors are associated with the level of 25-hydroxyvitamin D nor what the therapeutic results are when Dutch guidelines are followed. METHODS: This retrospective study included 30 patients who, in October 2012, were residents of the children’s wards of a tertiary epilepsy center in The Netherlands (Kempenhaeghe). From November 2012 onward they received cholecalciferol supplementation in doses that met or exceeded Dutch guidelines. At baseline, after 6, and 15 months, serum 25-hydroxyvitamin D concentration was measured. RESULTS: At baseline, the vitamin D status in 11 (36.7%) residents was found to be deficient, in 10 (33.3%) to be insufficient and in 9 (30.0%) sufficient. Supplementation dose, diet, body mass index, intellectual disability, and mobility were significantly associated with baseline 25-hydroxyvitamin D concentrations. The mean 25-hydroxyvitamin D concentration increased significantly from 57.40 22.00 nmol/L at baseline to 89.47 26.77 nmol/L after 15 months (P < 0.001). In spite of supplementation ranging from 400 to 1200 IU/day, 64% of the residents in the deficient category and 30% of those with an insufficient level at baseline failed to attain a sufficient vitamin D status after 15 months. CONCLUSIONS: Not all residents reached a sufficient vitamin D status after supplementation at least equal to the amount recommended by the Dutch guidelines. In a high-risk population, such as our residents, we advise monitoring 25-hydroxyvitamin D concentrations, adjusting supplementation accordingly and following patients to ensure they reach sufficiency. Keywords: vitamin D, supplementation, children, epilepsy, intellectual disability
Pediatr Neurol 2015; 52: 160-164 Ó 2015 Elsevier Inc. All rights reserved.
Introduction
Vitamin D has an important role in bone metabolism. Vitamin D deficiency, which is common in the general population, can induce rickets, a lower peak bone mass,
Article History: Received June 11, 2014; Accepted in final form October 1, 2014 * Communications should be addressed to: Dr. SnoeijenSchouwenaars, Sterkselseweg 65; 5590 AB Heeze the Netherlands. E-mail address: [email protected] 1
Both authors were equally responsible for the work described in this paper. 0887-8994/$ - see front matter Ó 2015 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.pediatrneurol.2014.10.001
osteomalacia, and osteoporosis resulting in a higher fracture risk.1-5 Furthermore, it can cause muscle weakness,1,2 and a lack of vitamin D is associated with various chronic diseases, such as multiple sclerosis, diabetes mellitus, cardiometabolic diseases, and cancer.1-5 Factors associated with vitamin D deficiency are pigmented skin, winter season, inadequate exposure to sunshine, obesity, older age, and several chronic diseases influencing vitamin D metabolism.1,2,5,6 In The Netherlands, the recommendations on vitamin D supplementation made by the Dutch Health Council should be followed,7 although the exact definition of what constitutes a sufficient vitamin D status is still a matter of discussion.8-12
F.M. Snoeijen-Schouwenaars et al. / Pediatric Neurology 52 (2015) 160e164
Children with epilepsy are at increased risk of poor bone health. They often have additional risk factors for vitamin D deficiency.13-17 Enzyme-inducing antiepileptic drugs cause an increased catabolism of vitamin D. Nonenzyme-inducing antiepileptic drugs, polytherapy, longterm use of antiepileptic drugs, intellectual disability, and impaired mobility are also associated with vitamin D deficiency.13,14,17-24 The optimal strategy for preventing and treating a deficiency in this high-risk population is not clear.14,15,25 Only a few studies have investigated the effects of supplementation in children with epilepsy. It seems that the effect in these children differs from that in healthy children.26-31 We investigated the factors that are associated with serum 25-hydroxyvitamin D (25-(OH) D) concentrations in children with epilepsy and intellectual disability. We will also determine whether supplementation in doses which were at least equal to the amount recommended by the guidelines leads to a sufficient vitamin D status in all these children after 6 and 15 months. Materials and Methods
161
Results Patient characteristics
We included 30 of the 36 residents of the children’s wards of the epilepsy center. Six were excluded because follow-up was incomplete (two died, four moved). Patient characteristics are listed in Table 1. All those included are aged between 5 and 22 years, are Caucasian, and have unimpaired renal function. Baseline vitamin D
At baseline, the vitamin D status of 11 (36.7%) residents was deficient, of 10 (33.3%) was insufficient, and of 9 (30.0%), sufficient. The residents received standard care at baseline. This means that most residents (n ¼ 23, 76.7%) already received vitamin D supplementation, up to a maximum of 400 IU/day. Baseline 25-(OH)D concentrations differed significantly between subgroups of supplementation dose, diet, BMI, severity of intellectual disability, and mobility (Table 2). Univariate analysis showed no significant correlation of 25-(OH)D with age, duration of antiepileptic
Patient selection and intervention We selected all residents of the children’s wards of a tertiary epilepsy center in The Netherlands (Kempenhaeghe) in October 2012. They had been diagnosed with epilepsy and intellectual disability. Those in whom follow-up of vitamin D status was incomplete were excluded. Up to November 2012, residents received standard care. From November 2012 onward, they all received supplementary vitamin D at doses that were at least equivalent to the dose recommended by the Dutch Health Council. Doses were prescribed by either the physician for people with an intellectual disability or the pediatrician, depending on the individual results of the 25-(OH)D serum concentration. All vitamin D preparations contained cholecalciferol.
Data collection This study was a retrospective cohort study. We retrieved the following information from the electronic patient files: gender, age, body mass index (BMI) using Dutch BMI-tables according to age for boys and girls,32 mobility using Barthel index for walking, severity of intellectual disability using intelligence quotient, creatinine, supplementation dose of vitamin D, antiepileptic drug use, and data about epilepsy. The caregivers completed a questionnaire about the amount of sun exposure, skin type, and diet. Sun exposure and skin type were analyzed using the same definitions as the Dutch guidelines.7 Serum 25-(OH)D concentration was measured by routine automated analysis. The samples were collected for routine blood monitoring in the autumn of 2012 (baseline), spring of 2013 (6 months), and at the end of winter, 2014 (15 months). We defined a 25-(OH)D concentration of 75 nmol/L or more as “sufficient” vitamin D status, of 50 to 75 nmol/L as “insufficient,” and of less than 50 nmol/L as “deficient.”
Statistical analysis To describe continuous variables we used mean (standard deviation) for normally distributed variables and median (minimummaximum) for not normally distributed variables. We used numbers (percentages) to describe categorical variables. Paired t test, unpaired t test, analysis of variance, correlation, and linear and multiple regression, or nonparametric equivalents (Wilcoxon singed rank test, MannWhitney test, Kruskal-Wallis test) were applied to the data using SPSS, version 21 (IBM Corp, Armonk, NY). The level of significance was a P value of
