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ÖZET Bu çalışma en az iki yıl süreyle karbamazepin veya valproik asit alan epileptik hastalarda, osteoporozu ve oluşum mekanizmasını aydınlatmak, antiepileptik iîaçlann kümülatif dozları ile osteoporoz oluşma süresi arasındaki ilişkinin araştırılması planlandı. Çalışma Erciyes Üniversitesi Tıp Fakültesi Pediatrik Nöroloji Departmanında Mart 2003 ile Ağustos 2003 tarihleri arasında takip ve tedavi edilmekte olan, prepubertal dönemde olup mental-motor retardasyonu olmayan, osteoporoza sebep olabileceği bilinen herhangi bir kronik hastalığı ve ilaç kullanımı olmayan 66 hasta üzerinde yapıldı. Valproik asit kullanan 33 hasta grup I (17 erkek, 16 kız hasta ortalama 8.22+1.83 yıl yaş), karbamazepin kullanan 33 hasta grup II (20 erkek, 13 kız hasta ortalama 9.73 ±1.62 yıl yaş ) şeklinde oluştu. Hastaların kemik mineral dansitesi (KMD) 'ni belirlemek üzere dual enerji X-Ray absorbsiyometri (DEXA) çekildi ve KMD ile ilişkisi olduğu bilinen biyokimyasal ve hormonal parametreler çalışıldı. Kesitsel nitelikteki çalışmamızda benzer yaş ve cinsiyette 16 vaka kontrol grubu ( 9'u erkek, 7'si kız hasta ortalama 8.22+1.83 yıl yaş) olarak oluşturuldu. Karbamazepin ve valproik asit kullanan hastalarda kemik mineral dansitesinin önemli oranda azaldığı tespit edildi. Karbamazepin kullanan grupta,ortalama 35.52 ±12.84 ay süre ve 19478.6+6301.34 mg/kg kümülatif dozda kemik mineral dansitesinin önemli oranda düştüğü saptandı. Aynı grupta serum 25 OH vitamin D düzeyi düşük, serum ALP ve PTH düzeyleri ise yüksek bulundu. Karbamazepinin karaciğer mikrozomal enzim indüksiyonu yoluyla serum 25 OH vitamin D düzeyini düşürdüğü ve bu durumun osteopeni ve osteoporozdan sorumlu olabileceği kanaatine varıldı. Valproik asitin, ortalama 33.72+15.00 ay süre ve 22852.4+12477.4 mg/kg kümülatif dozda kullanımının kemik mineral dansitesinde önemli oranda düşme yaptığı görüldü. Bu gruptaki ortalama 25 OH vitamin D düzeyi kontrol grubuyla benzer bulundu. Serum ALP düzeyleri kontrol grubuna göre yüksek bulunmasına rağmen, aralarında fark istatiksel olarak anlamlı bulunmadı. Bu gruptaki 7 hastada serum PTH düzeylerinde patolojik yüksek değer tespit edildi. Ayrıca kemik mineral dansitesi ile serum PTH düzeyleri arasında anlamlı negatif korelasyon saptandı. Bu bulgular valproik asitin bilinmeyen bir mekanizmayla sekonder hiperparatiroidiye yol açtığı ve kemik rezorbsiyonuna neden olduğu şeklinde yorumlandı. Her iki grupta, düşük serum insülin benzeri büyüme faktörü (IGF-I) ve insülin benzeri büyüme faktörü bağlayıcı protein (IGFBP 3) düzeyleri ile düşük kemik mineral dansitesi arasında ilişki saptanmadı. Bu nedenle valproik asit ve karbamazepinin belirtilen kullanım sürelerinde büyüme hormonu nörodisfonksiyonu (BHNSD)'na neden olmadığı sonucuna varıldı. Ayrıca idrarda kalsiyum atılımı yüksek olmadığından, sekonder hiperparatiroidi ile idrar kalsiyum atılımı arasında bir ilişki kurulamadı. Son zamanlardaki antikonvuîzan ilaçların sitokin ve büyüme faktörlerinin saîımmını arttırdığı yönündeki çalışmaların ışığında, bu ilaçların kemik metabolizmasına olan etkilerinin daha iyi anlaşılabilmesi için, kemik biyopsisi, kemik yıkım belirleyicileri, sitokinler ve büyüme faktörlerinin birlikte değerlendirilmesinin uygun olacağı kanaatine varıldı. ABSTRACT The effects of at least two years valproic acid and carbamazepine therapy on bone mineral status were evaluated in a cross-sectional and retrospective study. Ambulatory epileptic patients were divided into two groups. Thirty three patients (groupl; 17 boys, 16 girls, mean age: 8.76+1.99 years) received valproic acid and thirty three patients received carbamazepine (group II; 20 boys, 13 girls, mean age: 9.72±1.62 years). The control group consisted of 16 healthy children (9 boys, 7 girls, mean age: 8.22+1.83 years), who were age and sex matched with patient groups. All subjects were under the care of Erciyes University Department of Pediatric Neurology. Children with metabolic bone disease, growth and neurological impairment or sign of malnutrition and any chronic disease were excluded from the study. Bone mineral density values at lumbar spine in both the carbamezapine (mean 35.52+12.84 months long term and 19478.6+6301.3 mg/kg cumulative dose) and valproic acid (mean 33.72+15.00 months long term and 22852.4+Î 2477.4 mg/kg cumulative dose) groups were significantly different from that of the control group. Parathyroid hormone concentrations were increased, while (Bone Mineral Density) BMD was decreased in group I. Osteoporosis and osteopenia occurred in spite of normal mean levels of serum 25 OH vitamin D. The lack ofrelationship between serum levels of 25 OH vitamin D and BMD suggested that osteopenia and osteoporosis were independent effect of valproic acid on vitamin D metabolism. The incidence of elevated PTH levels (7 patients, 21.2%) was greatest in valproic acid group comparing with control group (one patient, 4.5%) and serum PTH levels showed a negative correlation with BMD L1-L4 vertebra Z score measurements (r= -0.615, p< 0.01) in spite of mean serum PTH levels were not significantly different from control group. These findings suggested that valproic acid therapy results in a hyperparathyroid state. Urinary calcium levels were not significantly different from that of the control group. We proposed that this hyperparathyroid state may be cause of osteopenia and osteoporosis in patients receiving valproic acid therapy, but the mechanism of hyperparathyroid state was remain unclear. Serum levels of 250H vitamin D were significantly decreased and ALP, PTH levels were significantly increased in patients receiving carbamazepine therapy. Serum levels of 25 OH vitamin D showed a positive correlation with BMD L1-L4 vertebra Z score measurements (r= 0.798, p< 0.01). These findings confirm that anticonvulsant drugs which induce the liver microsomal enzyme system alter vitamin D metabolism and cause osteopenia or osteoporosis. The results of present study suggest that children treated chronically with carbamazepine drag should be maintained on vitamin D supplementation. Because of serum IGF-I and IGFBP3 levels were not significantly associated with BMD in all subjects, we concluded that valproic acid and carbamazepine monotherapy don't cause BHND. Recent studies showed that antiepileptic drugs influence the immune system by increasing interleukin and growth factor which were known to cause bone resorption. In order to explain the effect of anticonvulsant drugs on bone metabolism; bone resorption markers, interleukin and growth factors must be studied additionally with bone biopsy evaluation. 96

Beken, Serdar/0000-0002-8609-2684; BAS, AHMET YAGMUR/0000-0002-1329-2167; Bulbul, Ali/0000-0002-3510-3056; Karatekin, Guner/0000-0001-7112-0323, WOS: 000534242500056, PubMed: 31851725, Objective To investigate the early neonatal outcomes of very-low-birth-weight (VLBW) infants discharged home from neonatal intensive care units (NICUs) in Turkey. Material and methods A prospective cohort study was performed between April 1, 2016 and April 30, 2017. the study included VLBW infants admitted to level III NICUs. Perinatal and neonatal data of all infants born with a birth weight of.1500 g were collected for infants who survived. Results Data from 69 NICUs were obtained. the mean birth weight and gestational age were 1137 +/- 245 g and 29 +/- 2.4 weeks, respectively. During the study period, 78% of VLBW infants survived to discharge and 48% of survived infants had no major neonatal morbidity. VLBW infants who survived were evaluated in terms of major morbidities: bronchopulmonary dysplasia was detected in 23.7% of infants, necrotizing enterocolitis in 9.1%, blood culture proven late-onset sepsis (LOS) in 21.1%, blood culture negative LOS in 21.3%, severe intraventricular hemorrhage in 5.4% and severe retinopathy of prematurity in 11.1%. Hemodynamically significant patent ductus arteriosus was diagnosed in 24.8% of infants. Antenatal steroids were administered to 42.9% of mothers. Conclusion the present investigation is the first multicenter study to include epidemiological information on VLBW infants in Turkey. Morbidity rate in VLBW infants is a serious concern and higher than those in developed countries. Implementation of oxygen therapy with appropriate monitoring, better antenatal and neonatal care and control of sepsis may reduce the prevalence of neonatal morbidities. Therefore, monitoring standards of neonatal care and implementing quality improvement projects across the country are essential for improving neonatal outcomes in Turkish NICUs., Turkish Neonatal Society [2-2016]; Turkish Neonatal Society, This study was supported by the Turkish Neonatal Society, http://www.neonatology.org.tr, number 2-2016, received by AYB. Turkish Neonatal Society funded the study's online registry system. the funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Background To evaluate the prevalence, risk factors and treatment of retinopathy of prematurity (ROP) in Turkey and to establish screening criteria for this condition., Methods A prospective cohort study (TR-ROP) was performed between 1 April 2016 and 30 April 2017 in 69 neonatal intensive care units (NICUs). Infants with a birth weight (BW)=1500 g or gestational age (GA) 1500 g or GA> 32 weeks with an unstable clinical course were included in the study. Predictors for the development of ROP were determined by logistic regression analyses., Results The TR-ROP study included 6115 infants: 4964 (81%) with a GA 32 weeks. Overall, 27% had any stage of ROP and 6.7% had severe ROP. A lower BW, smaller GA, total days on oxygen, late-onset sepsis, frequency of red blood cell transfusions and relative weight gain were identified as independent risk factors for severe ROP in infants with a BW=1500 g. Of all infants, 414 needed treatment and 395 (95.4%) of the treated infants had a BW, Conclusions Screening of infants with a GA