Salih Kalay

Severe vitamin D deficiency among pregnant women and their newborns in Turkey.

Abstract Objectives: Vitamin D deficiency is an important health problem in pregnant women and their infants in sunny countries. Low socio-economic status (LSES), covered dressing style, pregnancies in winter season and having dark skin are the major risk factors for vitamin D deficiency. The present study evaluated serum 25-hydroxyvitamin D3 [25(OH)D3] concentrations in pregnant women and in their newborns and determined the risk factors in LSES cities in Turkey. Methods: Ninety-seven pregnant women and their newborns were included in the study between December 2012 and February 2013. All of the pregnant women had irregular follow-up or had received no antenatal care, were pregnant during summer, had presented to the hospital after 37 weeks of gestation (WG) and had received no vitamin D supplementation. A detailed history was obtained, which included mothers’ age, number of births and dressing sytle. Maternal and cord blood samples were taken to measure 25(OH)D3 levels. Results: All of the pregnant women were predominantly LSES, had covered dressing style and none of them had received vit D3 supplementation during pregnancy. The mean serum 25(OH)D3 level and mean cord blood level of of 97 mothers were 4.97 ± 3.27 ng/ml and 4.29 ± 2.44 ng/ml, respectively. There was a strong positive correlation between maternal serum and umbilical cord 25(OH)D3 levels (r: 0.735, p < 0.05). Ninety-five mothers had serum 25(OH)D3 below 20 ng/ml and all cord blood serum 25(OH)D3 levels were below 20 ng/ml. Level of 25(OH)D3 was not correlated with mother age, WG or newborn weight. Serum 25(OH)D3 concentrations in primigravida and multigravida were 3.71 ± 1.88 and 5.2 ± 3.4 ng/ml, respectively, with a significant difference between them (p < 0.05). Conclusion: Severe vitamin D deficiency is common in reproductive women and their newborns in LSES cities of Turkey. Covered dressing style, not receiving any vitamin D supplementation and primigravida women are at greatest risk. Vitamin D supplementation campaigns which should cover pregnant women and the newborn to prevent maternal and perinatal vitamin D deficiency should be implemented especially in risk areas.

The Effects of Intraperitoneal Pentoxifylline Treatment in Rat Pups With Hypoxic-Ischemic Encephalopathy

BACKGROUND The aim of this study was to evaluate the effects of postischemic treatment with pentoxifylline on the cytokine gene expressions and neuronal apoptosis in neonatal rat model of hypoxic-ischemic encephalopathy. METHODS Seven-day-old Wistar rat pups (n = 40) of either sex, delivered spontaneously, were used in this experimental study. Control group (n = 8): after median neck incision was made, neither ligation nor hypoxia was performed, ischemia group (n = 16): 0.5 mL of saline was injected intraperitoneally immediately after hypoxia. Pentoxifylline and ischemia groups (n = 16): the rat pups were administered intraperitoneally 60 mg/kg of pentoxifylline immediately after hypoxia. Eight rats from ischemia and pentoxifylline + ischemia groups were sacrificed 4 and 24 hours after drug administration. Control group mice were decapitated 4 hours after hypoxia. Caspase-3 activity, interleukin-1β, and tumor necrosis factor-α messenger RNA expression levels were studied in the left half of the brain. RESULTS Induction of cerebral ischemia increased tumor necrosis factor-α and interleukin-1β messenger RNA expression levels significantly at 4 hours and 24 hours following ischemia in the left ischemic hemispheres in the ischemia group as compared with the control group. Systemic administration of pentoxifylline immediately after hypoxic-ischemic encephalopathy significantly reduced the tumor necrosis factor-α and interleukin-1β messenger RNA expression levels in ischemic tissue as compared with the ischemia group. Caspase-3 activities in the left half of the brains of ischemia group were found to be increased significantly as compared with control group. Caspase-3 activities in the brains of pentoxifylline + ischemia groups were significantly lower than in that of ischemia group. CONCLUSIONS Based on the significantly lower interleukin-1β and tumor necrosis factor-α gene expression measured after 4 and 24 hours and significantly reduced caspase-3 activity measured colorimetrically in the animals treated with pentoxifylline, our findings suggest that pentoxifylline may reduce brain damage due to hypoxic-ischemic injury.

Possible autosomal recessive inheritance in an infant with acrofacial dysostosis similar to nager syndrome

The acrofacial dysostosis syndromes, which are characterized by malformations of the craniofacial region and limbs, are a clinically heterogeneous group of disorders. Based primarily on the of the pattern of limb defects two major groups have emerged: Nager syndrome with predominantly preaxial malformations plus mandibulofacial dysostosis (severe micrognathia and malar hypoplasia) and Miller syndrome with postaxial malformations plus mandibulofacial dysostosis. Among these syndromes, Nager syndrome is a rare condition but the most common form of acrofacial dysostosis. Most cases are sporadic, while autosomal dominant and autosomal recessive inheritance patterns have been reported. Recently, heterozygous mutations in the SF3B4 gene on chromosome 1q12–q21 were found to be responsible for a subset of sporadic and autosomal dominant cases. We present a female infant born to consanguineous parents with craniofacial features resembling Nager syndrome and a unilateral preaxial limb malformation. Mutation analysis of coding exons of SF3B4 did not identify any mutations. This couple also had a deceased child who had similar clinical features. We conclude that, the presence of consanguinity and absence of mutation in SF3B4, provides evidence in support of a recessive form of Nager syndrome.

Role of immunoglobulin in neuronal apoptosis in a neonatal rat model of hypoxic ischemic brain injury

The objective of the present study was to evaluate the neuroprotective effects of immunoglobulin (Ig) in a neonatal hypoxic ischemic (HI) rat model. Seven-day-old rat pups were randomly assigned to control, hypoxia and hypoxia + Ig groups. The rats in the hypoxia +Ig group were intraperitoneally administered 1 g/kg Ig once, immediately after hypoxia. Saline was administered to the rats in the hypoxia group at the same time point. Eight rats from each of the Ig + hypoxia and hypoxia groups were sacrificed by decapitation 4 and 24 h following the administration of Ig or saline. The rats of the control group were sacrificed at the 4 h time-point. Caspase-3 activity, as well as IL-1β, IL-6 and TNF-α mRNA expression levels, were studied in the left ischemic hemispheres. Induction of cerebral ischemia increased the TNF-α, IL-6 and IL-1β mRNA expression levels significantly at 4 and 24 h in the left ischemic hemispheres in the hypoxia group compared with those in the control group. The systemic administration of Ig following HI encephalopathy significantly reduced the TNF-α, IL-6 and IL-1β mRNA expression levels in the ischemic tissue in the Ig + hypoxia group compared with those in the hypoxia group. In the hypoxia group, caspase-3 activity in the left half of the brain was found to be significantly increased compared with that in the control group. Caspase-3 activity in the Ig + hypoxia group was significantly lower than that in the hypoxia group. The observations of the present study indicate that Ig administration may be an efficient treatment approach for reducing cerebral apoptosis associated with hypoxic ischemia.

The role of VEGF and its soluble receptor VEGFR-1 in preterm newborns of preeclamptic mothers with RDS

Abstract Objective: We measured vascular endothelial growth factor (VEGF) and soluble VEGF receptor 1(sVEGFR-1) concentrations in cord blood and tracheal aspirate fluid (TAF) in order to investigate the role of them in lung maturation and the severity of respiratory distress syndrome (RDS) in preterm newborns, born to preeclamptic mothers. Methods: Newborns were divided into two groups as preterms born to preeclamptic mothers and preterms born to healthy mothers. They were also divided into two groups as severe RDS (sRDS) and mild RDS (mRDS) according to the need of surfactant and extent or type of ventilatory support. The concentrations of VEGF and sVEGFR-1 in cord blood and TAF (only in preterms with sRDS) were assayed by standardized enzyme-linked immunosorbent assay. Results: When the patients were evaluated as sRDS and mRDS, cord blood VEGF and VEGF/sVEGFR-1 concentrations of preterms with sRDS were significantly lower than the concentrations of preterms with mRDS. Conversely, cord blood sVEGFR-1 concentrations of preterms with sRDS were significantly higher than the concentrations of preterms with mRDS. VEGF and sVEGFR-1 concentrations in TAF could be compared only between sRDS preterms, born to preeclampsia (+) and (−) mothers. No statistical significance was detected between the two groups when sVEGFR-1, VEGF and VEGF/sVEGFR-1 concentrations in TAF were compared. Conclusion: Preeclampsia seems not to have an important effect on VEGF and sVEGFR-1 concentrations of preterm newborns both in cord blood and in TAF. Low VEGF and high sVEGFR-1 concentrations seem to be associated with the severity of RDS irrespective of preeclampsia, suggesting that VEGF may be one of the main components of lung maturation.

Levels of ischemia-modified albumin in transient tachypnea of the newborn.

AIM The aim of the article is to evaluate ischemia-modified albumin (IMA) levels in infants with transient tachypnea of the newborn (TTN) and to find out its relation to the disease severity. Patients and METHODS Infants with > 37 weeks of gestation, without any respiratory and cardiac symptoms and without any maternal health problems, and diagnosed as TTN were allocated as the study group. Patients with obvious retractions, grunting, hypercarbia (Pco 2 > 60 mm Hg) or hypoxia (oxygen saturation < 88% with Fio 2 of 0.60) were managed with nasal continuous positive airway pressure (CPAP). During the postnatal 0 to 24 hours, blood samples were collected in 2 mL for IMA. RESULTS A total of 47 patients were diagnosed TTN, and allocated as the study group. Of the 47 patients, 43 patients without respiratory symptoms were enrolled as the control group. IMA levels in TTN were found to be significantly higher (p < 0.05). In addition, IMA levels were significantly increased in the nasal CPAP group versus supplemental oxygen therapy groups (p < 0.05). IMA levels were determined to be significantly higher in the > 3 days of oxygen therapy group (p < 0.05). IMA levels with a cutoff point of 0.87 ABSU, sensitivity of 81.1% and specificity of 69.8% predicted TTN (area under the curve [AUC] = 0.85; p < 0.05). IMA levels with > 0.98 ABSU, 78% sensitivity, and 86% specificity indicated the prediction of CPAP requirement (AUC = 0.86; p < 0.05). CONCLUSION IMA levels were significantly higher in infants with diagnosed TTN. Therefore, IMA may be used as a new marker for predicting TTN and disease severity.

Is the strength of direct antiglobulin test important for the duration of phototherapy

Abstract The purpose of this study was to evaluate the relationship between the grades of positivity of the direct antiglobulin test (DAT) and their effects on the duration of phototherapy for neonatal jaundice. DAT reactions of blood samples were graded as (1+), (2+), (3+) and (4+). DAT was positive in 80 neonates who were exposed to phototherapy due to jaundice. Patients with positive DAT reactions are classified in the study as follows: 34 newborns were DAT (1+), 18 newborns were DAT (2+), 16 newborns were DAT (3+) and 12 newborns were DAT (4+). We found that higher grades of positivity of DAT are associated with extended duration of phototherapy (r = 0.436, p < 0.05). Additionally, DAT (4+) reactions are more predictive for a prolonged duration of phototherapy requirement than the other grades (p < 0.0001).

Reliable and powerful laboratory markers of cobalamin deficiency in the newborn: plasma and urinary methylmalonic acid.

Abstract Background: Diagnosing cobalamin deficiency is critical, given the high prevalence of cobalamin deficiency particularly in developing countries. Measuring serum cobalamin levels is of limited diagnostic sensitivity, in other words its specificity and sensitivity are low. The present study investigated the changes in the levels of metabolic markers – plasma homocysteine, plasma methylmalonic acid (MMA) and urinary MMA – of cobalamin metabolism. Methods: Plasma cobalamin and serum folic acid were studied in 206 pregnant women over the last four prenatal weeks. Plasma cobalamin, folic acid, homocysteine, MMA from umbilical cord blood and urinary MMA in newborns were studied. Results: Plasma cobalamin values were low in 66% of the mothers. There was a positive correlation between maternal and neonatal plasma cobalamin values (r = 0.72, p < 0.001). B12 was strongly inversely associated with plasma MMA, urine MMA and plasma homocysteine. To predict cobalamin deficiency, sensitivities of plasma MMA, urinary MMA and homocysteine were 96.4%, 95.6% and 88.2%, respectively. And positive predictive values (PPV) were 96.2%, 96.9% and 86% for plasma MMA, urinary MMA and plasma homocysteine levels, respectively. Conclusion: Plasma MMA and urinary MMA B12 are the most robust markers of cobalamin deficiency. As a non-invasive method, urinary MMA is a sensitive method in demonstrating cobalamin deficiency in the newborn.

Pentoxifylline therapy attenuates intestinal injury in rat pups with hypoxic ischemic encephalopathy

Abstract Aim: The aim of this study was to evaluate the effects of post-ischemic pentoxifylline (PTX) therapy on the gut injury in neonatal rat model of hypoxic ischemic encephalopathy (HIE). Methods: Seven-day-old Wistar rat pups (n = 24) of either sex, delivered spontaneously, were used in this experimental study. Seven-day-old rat pups were randomly divided into three groups. Control group (n = 8): after median neck incision was made, neither ligation nor hypoxia was performed. Hypoxia group (n = 8): 0.5 ml of saline was injected intraperitoneally immediately after hypoxia. Pentoxifylline + Hypoxia group (n = 8): the rat pups were administered intraperitoneally 60 mg/kg of PTX immediately after hypoxia. Eight rats from all groups were sacrificed 24 h after drug administration. The ischemic injury was scored at least six sections at three different levels using histopathologic injury scores (HIS). Results: Induction of hypoxia/reoxygenation (H/R) increased mean HIS levels significantly at 24 h in the intestinal tissue samples in the hypoxia group as compared with the control group. Induction of H/R decreased means HIS levels significantly at 24 h in the intestinal tissue samples in the PTX + hypoxia group as compared with the hypoxia group. Conclusion: In this experimental study, PTX significantly attenuated H/R-induced intestinal injury in neonatal rat model of HIE. These findings indicate that PTX can reduce the intestinal H/R injury.

Neonatal hyperbilirubinemia in a Turkish cohort: association of vitamin B12.

Background Deficiency of vitamin B12 (VitB12) causes failure of erytrocyte maturation leading to cell lysis. Red blood cell lysis causes excess heme production that ends with hyperbilirubinemia. In this study, we aimed to evaluate the role of VitB12 in neonatal hyperbilirubinemia (NNH) with prolonged jaundice and to compare patients with control group who did not develop hyperbilirubinemia. Methods A total of 20 patients (M/F = 13/7) with jaundice and 20 healthy controls (M/F = 11/9) were included in the study. Results The mean indirect bilirubin level of patient group was 9.91 ± 1.90 mg/dL (6.71 - 15.2 mg/dL) and control group was 3.18 ± 1.24 mg/dL (1.16 - 4.96 mg/dL). The mean VitB12 level of patient group was 119.9 ± 43.9 ng/L (42.35 - 178 ng/L) and the control group was 286.17 ± 97.43 ng/L (207.90 - 624.10 ng/L). There was a statistically significant difference in terms of VitB12 level (< 0.001) between the study groups. Conclusion To our knowledge, this study is the first study showing that low VitB12 level has been observed as a risk factor in NNH for the first time in the literature. We suggest that prophylactic use of VitB12 by pregnant women so will greatly benefit to prevent VitB12 deficiency and its complications in the first years of life such as NNH.