Razi Journal of Medical Sciences

en بررسی تأثیر سدیم والپروات بر وزن، شاخص توده بدنی، اسید اوریک، ویتامین D3، انسولین خون و لیپیدهای سرم در کودکان Study the effect of sodium valproate on weight, body mass index, uric acid, vitamin D3, blood insulin and serum lipid profile in children اعصاب کودکان Pediatric Neurology پژوهشي Research زمینه و هدف: با توجه به شیوع بالای صرع و استفاده از والپروات سدیم به عنوان داروی ضد صرع که به طور گسترده در این بیماران تجویز می‌شود، شناخت دقیق عوارض جانبی آن و تأثیرات آن بر سطح لیپیدهای سرم<a name="_Hlk67868315">،</a> آنزیم‌های کبد<a name="_Hlk67867954">،</a> اسید اوریک و آزمایشات عملکرد تیروئید، به خصوص در مواردی که نیاز به درمان طولانی مدت دارند ضروری به نظر می‌رسد. هدف از این مطالعه بررسی تأثیرات والپروات سدیم بر وزن<a name="_Hlk67868609">،</a> شاخص توده بدن (BMI)، ویتامین D3، انسولین خون، سطح اسید اوریک و لیپیدهای سرم در کودکان مبتلا به صرع تازه تشخیص داده شده بود. روش کار: این مطالعه آینده نگر بر روی 30 کودک 3 تا 8 ساله انجام شد که از صرع تازه تشخیص داده شده رنج می‌بردند و والپروات سدیم را به عنوان مونوتراپی دریافت می‌کردند. داده‌ها شامل اطلاعات دموگرافیک (سن ، جنس ، قد ، وزن و دور کمر و اندازه مفصل ران) و همچنین مشخصات بالینی مانند آنزیم‌های کبدی، سطح لیپیدهای سرم است. آزمایش تیروئید، قند خون ناشتا، سطح اسید اوریک و سطح انسولین خون کودکان قبل و شش ماه پس از مصرف سدیم والپروات، مورد بررسی قرار گرفتند. یافته‌ها: میانگین وزن کودکان قبل و شش ماه پس از شروع درمان با والپروات سدیم به ترتیب 99/2 ± 54/18 و 93/3 ± 13/21 (کیلوگرم) بود. این اختلاف از نظر آماری معنی دار بود (005/0 = P). همچنین، میانگین وزن باscore  Z در کودکان قبل و بعد از مصرف والپروات سدیم به ترتیب 293/2- و 497/2- بود که از نظر آماری نیز معنی دار بود. علاوه بر افزایش وزن، بعد از مصرف والپروات دور شکم و باسن نیز افزایش قابل توجهی مشاهده شد، در حالی که افزایش میانگین BMI قبل و بعد از تجویز والپروات از نظر آماری معنی دار نبود (114/0 = P). همچنین، والپروات سدیم به طور قابل توجهی سطح ALT را افزایش داد (046/0 = P). این در حالی است که والپروات سدیم هیچ تأثیری بر سایر آزمایش های عملکرد کبد (AST)، هورمون‌های تیروئید (TSH ، T4)، قند خون ناشتا (FBS)، سطح اسید اوریک، 25 OH Vit-D3 و سطح انسولین خون کودکان نداشت (05/0 >P). نتیجه‌گیری: با توجه به یافته‌های مطالعه، والپروات سدیم داروی مناسبی برای کودکان 3 تا 8 سال است اما مصرف این دارو احتمال چاقی را در کودکان افزایش می‌دهد. با توجه به افزایش قابل توجه آنزیم ALT در این مطالعه، توصیه می‌شود آنزیم‌های کبد قبل، یک و شش ماه پس از شروع درمان بررسی شوند زیرا می‌تواند از عوارض جانبی دائمی برگشت ناپذیر این دارو جلوگیری کند. Background & Aims: According to the high prevalence of epilepsy and the using of sodium valproate as an antiepileptic drug widely given in these patients, accurate recognition of its side effects and its effects on serum lipids profile, liver enzymes, uric acid level, and thyroid function tests, especially in cases that need long-term treatment seems essential. Sodium valproate is a broad-spectrum drug that has been frequently prescribed as a first-line anticonvulsant since 1970. Similar to other anticonvulsant drugs, sodium valproate comes with some side effects, including transient and harmless outcomes such as weight gain, transient drowsiness, hair loss, hand and arm tremors at rest and activity, reversible thrombocytopenia, and moderate (about 3 times) increase in gamma-glutamyl transferase, as well as harmful complications such as hepatotoxicity, encephalopathy, coagulation disorders, pancreatitis, and bone marrow suppression. Also, sodium valproate interacts with other drugs such as phenobarbital, phenytoin (PHT), carbamazepine, lamotrigine, felbamate, rifampin, ethosuximide, and primidone. It generally confers suitable therapeutic properties, and whether it is used or prohibited or its modification due to negative side effects should be decided individually for each patient. Obesity or an increase in adipose tissue is defined using the body mass index (BMI), where the body weight (kg) is divided by the square of the body height (m). In a child over 2, obesity is defined as a BMI at or above the 95th percentile, and a BMI at the 85th to 95th percentile means that the person is overweight. On the other hand, serum concentrations of specific lipids and lipoproteins in young adults are serious risk factors for the development of cardiovascular disease during life. Several data showed that increased total cholesterol, elevated triglyceride (TG) and LDL-C, and decreased HDL-C levels, cause cardiovascular disease. Therefore, the assessment of variations in serum lipid profile levels following the consumption of anticonvulsants may help select the safest drug to prevent cardiovascular complications in patients. As we know, the complications of sodium valproate may be higher in children than adult. The aim of this study was to evaluate the effects of sodium valproate on weight, body mass index (BMI), vitamin D3, blood insulin, uric acid level, and serum lipids profile in children with newly diagnosed epilepsy. Methods: This prospective study was performed on 30 children between 3 and 8 years of age who admitted to the pediatric ward of Rassol-e-Akram Hospital in Tehran during 2018-2019, suffered from newly diagnosed epilepsy and received sodium valproate as monotherapy to control of seizures. In this study, patients had no metabolic disease or underlying chromosomal condition, obesity, failure to thrive (FTT), or congenital anomalies were included in the study. All patients with, underlying conditions such as chronic hepatic, heart, renal, and metabolic diseases, diabetes, chromosomal disease, obesity, FTT, congenital anomalies, progressive neurological disease, gastrointestinal diseases, coagulation disorders and developmental delay were excluded from the study. Data include demographic information (age, sex, height, weight and waist and hip circumference of children), as well as clinical characteristics such as liver enzymes (ALT, AST, ALK-P), serum lipids level (TG, TC, HDL-C, LDL-C), thyroid tests (TSH, T4), fasting blood sugar (FBS), Uric Acid level, 25 OH Vitamin D3 (Vit-D3) and blood insulin level of children before and six months after the consumption of sodium valproate, were examined Results: The mean weight of children before and six months after the start of sodium valproate treatment was 18.54±2.99 and 21.13±3.93 (kg), respectively. This difference was statistically significant (P=0.005). Also, the mean weight Z-score of children before and after taking sodium valproate was respectively -2.497 and -2.293, that was statistically significant too. In addition to weight gain, there was also a significant increase in the abdominal and hip circumference of children after taking valproate, whereas the increase in mean BMI before and after valproate administration was not statistically significant (P=0.114). Mean values of weight, body mass index, and circumference of the abdomen and hips of children before and after taking sodium valproate were compared individually in girls and boys. However, mean weight gain, as well as the increase in the waist and hip circumference, had no relationship with gender (P> 0.05). Paraclinical features such as hepatic enzymes (ALT, AST, ALK-P), lipids profile (TG, TC, HDL-C, LDL.C), thyroid tests (TSH, T4), fasting blood sugar (FBS), the concentration of uric acid, 25 OH Vitamin D3, and the content of blood insulin level before and after consuming sodium valproate were measured individually in boys and girls. Also, sodium valproate significantly increased ALT level (P=0.046). This is while sodium valproate had no effect on other liver function markers (AST), thyroid hormones (TSH, T4), fasting blood sugar (FBS), uric acid level, 25 OH Vit-D3, and the children's blood insulin levels (P> 0.05). Conclusion: This study was carried out in 2018 on 30 children aged 3 to 8 years who were admitted in the pediatric ward of Rasool-e- Akram Hospital with newly diagnosed epilepsy and were treated with sodium valproate to control their seizures. In this study, factors including gender, age, weight, height, and size of waist and hip, as well as hepatic enzymes (AST, ALT), and the results of laboratory testing of lipid profiles, uric acid level, thyroid hormones, vitamin D3 level, and fasting blood sugar were recorded before and 6 months after consuming sodium valproate for each patient. According to the findings of this study, it can be said that sodium valproate is a good and safe drug for children between 3 and 8 years of age, but it should be noted that taking this drug increases the chance of obesity in children. Weight gain following the consumption of sodium valproate was observed in all children in this study. The main side effect of this drug is weight gain. In addition to weight gain, a significant increase was observed in the size of the abdomen and hips of children after taking this drug. Due to the normal serum level of insulin, uric acid and lipids, it seems that the role of sodium valproate in children weight gain is more result of increased appetite than metabolic and hormonal changes. Also, the result of significant increase in ALT enzyme level, in this study, recommended that liver enzymes should be checked before, one and six months after starting treatment as it can prevent the irreversible permanent side effects of this drug.   چاقی, سدیم والپورات, کودکان, صرع Obesity, Sodium Valproate, Children, Epilepsy 49 59 http://rjms.iums.ac.ir/browse.php?a_code=A-10-5947-1&slc_lang=en&sid=1 Farzad Sina فرزاد سینا sina.f@iums.ac.ir 3900319475328460061117 3900319475328460061117 No Assistant Professor of Nourology, Fellowship of Epilepsy, Firoozgar Hospital, Iran University of Medical Science, Tehran, Iran استادیار، متخصص مغز و اعصاب، فلوشیپ صرع، بیمارستان فیروزگر، دانشگاه علوم پزشکی ایران، تهران، ایران Mohammad Vafaee Shahi محمد وفایی شاهی vafaeeshahi.m@iums.ac.ir 3900319475328460061118 3900319475328460061118 Yes Iran University of Medical Sciences, Tehran, Iran دانشگاه علوم پزشکی ایران، تهران، ایران Fahimeh Soheilipour فهیمه سهیلی پور soheilipour.f@iums.ac.ir 3900319475328460061119 3900319475328460061119 No Associate Professor of Pediatric Endocrinology, Minimally Invasive Surgery Research Center, Department of Pediatric Endocrinology, Aliasghar Children Hospital, School of Medicine, Iran University of Medical Sciences,Tehran, Iran دانشیار، فوق تخصص غدد و متابولیسم کودکان، مرکز تحقیقات جراحی های کم تهاجمی، گروه کودکان، دانشکده پزشکی، بیمارستان حضرت علی اصغر، دانشگاه علوم پزشکی ایران، تهران، ایران Parisa Mohagheghi پریسا محققی pmohagh@yahoo.com 3900319475328460061120 3900319475328460061120 No Pediatric Resident, Rasool Akram Complex Hospital, Iran University of Medical Sciences, Tehran, Iran دانشیار، فوق تخصص نوزادان، بیمارستان حضرت رسول اکرم، دانشگاه علوم پزشکی ایران، تهران، ایران Aina Riahi آینا ریاحی ainariahi@yahoo.com 3900319475328460061121 3900319475328460061121 No Pediatrician, Minimally Invasive Surgery Research Center, Iran University of Medical Science, Tehran, Iran متخصص کودکان، مرکز تحقیقات کم تهاجمی چاقی، دانشگاه علوم پزشکی ایران، تهران، ایران Nafiseh Borqei نفیسه برقعی nborqei@yahoo.com 3900319475328460061122 3900319475328460061122 No Pediatric Resident, Rasool Akram Complex Hospital, Iran University of Medical Sciences, Tehran, Iran دستیار تخصصی کودکان، بیمارستان حضرت رسول اکرم، دانشگاه علوم پزشکی ایران، تهران، ایران Atefeh Talebi عاطفه طالبی a_talebi5855@yahoo.com 3900319475328460061123 3900319475328460061123 No Biostatistician, Colorectal Research Center, Iran University of Medical Science, Tehran, Iran متخصص آمار، مرکز تحقیقات کولورکتال، دانشگاه علوم پزشکی ایران، تهران، ایران