Nihat Demir

Clinical and neurological findings of severe vitamin B12 deficiency in infancy and importance of early diagnosis and treatment.

Nutritional vitamin B12 deficiency among children in developing countries may lead to a severe clinical status. In this article, the clinical manifestations of vitamin B12 deficiency and the consequences of delay in its diagnosis have been evaluated.

The levels of vitamın B12, folate and homocysteine in mothers and their babies with neural tube defects

Abstract The aim of the present study was to determine the serum levels of vitamin B12, folate, and homocysteine (Hcy) in mothers and their babies, and to assess the association between these levels and neural tube defect (NTD). The study group included 92 baby-mother pairs, where the babies had NTD, and the control group included 102 pairs, where the babies had no NTD, from May 2012 to May 2015. Plasma vitamin B12, folate, and Hcy levels of the babies and mothers were measured, and compared with each other. NTD was diagnosed in 2.6% of our babies. The vitamin B12 levels in the mothers and the babies in the study group were determined as 166.2 ± 63.7 pg/mL and 240.3 ± 120.3 pg/mL, and in the control group as 1 9 0 ± 80.2 pg/mL and 299.5 ± 151.4 pg/mL, respectively. There was a significant difference between the two groups in terms of both the mothers’ and the babies’ vitamin B12 levels (p = 0.024 and p = 0.003, respectively). The plasma folate levels of the mothers in the study group (5.2 ± 3 ng/mL) were significantly lower than control group (6.4 ± 4.3 ng/mL, p = 0.032).The plasma Hcy level of the mothers in the study group (9.3 ± 3.8 μmol/L) was significantly higher than the control group (7 ± 3.8 μmol/L, p < 0.001). High plasma Hcy levels and low plasma folate and vitamin B12 levels are risk factors for NTD. Our results show that the risk for NTD can be decreased by fortification of mothers-to-be, particularly in rural areas with folate and vitamin B12 deficiency, which would lower the plasma Hcy level.

Dermatological findings of vitamin B12 deficiency and resolving time of these symptoms

Abstract Aim: The mucocutaneous changes observed during vitamin B12 deficiency in children have been published only as case studies and small case series. In this study, we aimed to demonstrate the frequency of mucocutaneous changes (particularly hyperpigmentation) seen during vitamin B12 deficiency and resolving time of these symptoms with vitamin B12 treatment. Material and methods: This prospective study was conducted at the pediatrics outpatient clinic of Harran and Yuzuncu Yil University Faculty of Medicine, among 57 patients, aged between 6 and 24 months, who were diagnosed with vitamin B12 deficiency following various examinations and tests. A detailed examination was performed in respect to skin and mucosal findings. Patients with vitamin B12 deficiency were administered intramuscular cyanocobalamin. Prospective examination was continued, and resolving time of symptoms after treatment was recorded. Results: The mean age of the patients enrolled in the study was found to be 12.75 ± 4.75. Hyperpigmentation was reported in 49 (85.96%) patients enrolled in the study; atrophic glossitis in 40 (70.17%), brittle and matt hair in 13 (22.80%), skin lesions (particularly diaper dermatitis) in eight (15.78%) and cheilosis in four (7.01%) patients. Three months after the treatment initiation, hyperpigmentation improved in 87.75%, atrophic glossitis in 97.5% and brittle and matt hair in 92.3% of the patients. Five patients (8.77%) with continuing pigmentation by the end of sixth months were considered as nonresponsive to the treatment. Conclusion: Deficiency of vitamin B12 should be considered in the differential diagnosis of infants who present with skin and mucosal lesions.

A study on the effects of pica and iron-deficiency anemia on oxidative stress, antioxidant capacity and trace elements

Pica is defined as developmentally inappropriate consumption of nonnutritive substances for at least 1 month. There are a few studies on serum trace element levels of patients with pica. The literature contains contracting data on the levels of oxidative stress and antioxidant levels in patients with iron-deficiency anemia (IDA). The effect of pica on oxidative stress and antioxidant capacity has not been investigated yet. The present study evaluated the effects of pica and IDA on oxidative stress and antioxidant capacity as well as on the levels of trace elements including serum zinc and selenium in 47 children with IDA plus pica, 22 children with IDA only and 21 nonanemic children as controls. The results demonstrated significantly lower levels of serum selenium and zinc in pica and IDA groups compared to the control group. Total oxidant levels were highest in the pica group and consistently, the lowest total antioxidant capacity was observed again in the pica group. Comparison of pica and IDA groups yielded significantly lower levels of total antioxidant levels and significantly higher oxidative stress index in the pica group. Consequently, it is thought that the detrimental effects of pica within the organism were mediated by adverse impacts on antioxidant capacity and oxidative stress. These effects should be kept in mind while managing patients with pica.

Brain Malformations Associated With Knobloch Syndrome—Review of Literature, Expanding Clinical Spectrum, and Identification of Novel Mutations

BACKGROUND Knobloch syndrome is a rare, autosomal recessive, developmental disorder characterized by stereotyped ocular abnormalities with or without occipital skull deformities (encephalocele, bone defects, and cutis aplasia). Although there is clear heterogeneity in clinical presentation, central nervous system malformations, aside from the characteristic encephalocele, have not typically been considered a component of the disease phenotype. METHODS Four patients originally presented for genetic evaluation of symptomatic structural brain malformations. Whole-genome genotyping, whole-exome sequencing, and confirmatory Sanger sequencing were performed. Using immunohistochemical analysis, we investigated the protein expression pattern of COL18A1 in the mid-fetal and adult human cerebral cortex and then analyzed the spatial and temporal changes in the expression pattern of COL18A1 during human cortical development using the Human Brain Transcriptome database. RESULTS We identified two novel homozygous deleterious frame-shift mutations in the COL18A1 gene. On further investigation of these patients and their families, we found that many exhibited certain characteristics of Knobloch syndrome, including pronounced ocular defects. Our data strongly support an important role for COL18A1 in brain development, and this report contributes to an enhanced characterization of the brain malformations that can result from deficiencies of collagen XVIII. CONCLUSIONS This case series highlights the diagnostic power and clinical utility of whole-exome sequencing technology-allowing clinicians and physician scientists to better understand the pathophysiology and presentations of rare diseases. We suggest that patients who are clinically diagnosed with Knobloch syndrome and/or found to have COL18A1 mutations via genetic screening should be investigated for potential structural brain abnormalities even in the absence of an encephalocele.

The relationship between mother and infant plasma trace element and heavy metal levels and the risk of neural tube defect in infants

Abstract Objective: To determine levels of trace elements [copper (Cu), zinc (Zn), selenium (Se), and cobalt (Co)] and heavy metals [arsenic (As), mercury (Hg), lead (Pb), and cadmium (Cd)] in the plasma of mothers and infants and investigate the relationship between those levels and neural tube defects (NTD). Methods: A total of 100 neonates diagnosed with NTD and placed in the Neonatal Intensive Care Unit of Yuzuncu Yil University, Turkey between May 2013 and December 2016 comprised the study group. The control group consisted of 70 healthy neonates not diagnosed with NTD or any other congenital anomalies. For both the groups, mother and infant plasma levels of Cu, Zn, Co, Cd, Se, Hg, As, and Pb were measured and compared. Plasma levels of Cu, Zn, Co, Cd, Se, Hg, As, and Pb were measured and compared between two groups of mothers and infants. Findings: Mother and infant plasma levels of trace elements Zn and Se were determined to be significantly lower in the study group compared with the control group, while Cu levels were significant elevated in the study group (all p values < .05). Plasma levels of heavy metals As, Pb, and Cd were found to be significantly higher in the NTD control group (p < .05 for all). There was no association between maternal infection, maternal smoking status, history of miscarriage, or history of NTD with the development of NTD (p > .05). Differences in maternal age, birth weight, length of gestation, and infant gender for the two groups were also determined not to be statistically significant. Results: High plasma levels of heavy metals As, Pb, and Cd and trace element Cu were identified as risk factors for the development of NTD. At the same time, low plasma levels of trace elements Zn and Se were also found to be risk factors for NTD. However, no association between Hg and Co plasma levels and increased risk for the development of NTD was observed. This study, while being the most comprehensive case study to date investigating the relationship between heavy metals and trace element levels and increased risk of NTD, nonetheless highlights the need for further research in order to make definite statements regarding this relationship.

Is platelet mass a more significant indicator than platelet count of closure of patent ductus arteriosus

Abstract Background: The purpose of this study was to evaluate whether or not platelet mass contributes to closure of patent ductus arteriosus (PDA) in premature newborns. Study design and subjects: This retrospective study included 115 preterm newborns with hemodynamically significant PDA (hPDA) and 120 newborns without PDA. The newborns’ platelet count, mean platelet volume (MPV) and platelet distribution width (PDW) were noted from their files and the platelet mass (platelet count plus MPV/103) was calculated. Patients with congenital abnormality, persistent pulmonary hypertension or sepsis were not included in the study. Results: Platelet count and PDW were found to not be risk factors for closure of hPDA (p > 0.05), but both high platelet mass (OR 1.25; 95% CI 1.12–1.41) and MPV (OR 1.87; 95% CI 2.52–3.85) were determined to be independent risk factors for hPDA. Conclusions: Platelet mass may be a more significant indicator than platelet count of closure of hPDA in preterm newborns.

The Use of Acute Peritoneal Dialysis in Critically Ill Newborns

Background To evaluate the efficacy, complications, and mortality rate of acute peritoneal dialysis (APD) in critically ill newborns. Material/Methods The study included 31 newborns treated in our center between May 2012 and December 2014. Results The mean birth weight, duration of peritoneal dialysis, and gestational age of the patients were determined as 2155.2±032.2 g (580–3900 g), 4 days (1–20 days), and 34 weeks (24–40 weeks), respectively. The main reasons for APD were sepsis (35.5%), postoperative cardiac surgery (16%), hypoxic ischemic encephalopathy (13%), salting of the newborn (9.7%), congenital metabolic disorders (6.1%), congenital renal diseases (6.5%), nonimmune hydrops fetalis (6.5%), and acute kidney injury (AKI) due to severe dehydration (3.2%). APD-related complications were observed in 48.4% of the patients. The complications encountered were catheter leakages in nine patients, catheter obstruction in three patients, peritonitis in two patients, and intestinal perforation in one patient. The general mortality rate was 54.8%, however, the mortality rate in premature newborns was 81.3%. Conclusions APD can be an effective, simple, safe, and important therapy for renal replacement in many neonatal diseases and it can be an appropriate treatment, where necessary, for newborns. Although it may cause some complications, they are not common. However, it should be used carefully, especially in premature newborns who are vulnerable and have a high mortality risk. The recommendation of APD therapy in such cases needs to be verified by further studies in larger patient populations.

Efficacy and safety of rectal ibuprofen for patent ductus arteriosus closure in very low birth weight preterm infants

Abstract Background: To compare rectal ibuprofen with oral ibuprofen for the closure of hemodynamically significant patent ductus arteriosus (hsPDA) in very low birth weight (VLBW) preterm infants. Study design and subjects: In a prospective, randomized study, 72 VLBW infants who had hsPDA received either rectal or oral ibuprofen. The plasma concentration of ibuprofen and renal functions were determined in both groups by the high-performance liquid chromatography (HPLC) method and cystatin-C (cys-C), respectively. Results: The hsPDA closure rate of the group that received rectal ibuprofen was similar to oral ibuprofen (86.1% versus 83.3%) after the first course of the treatment (p = 0.745). A statistically significant difference was identified between the mean plasma cys-C levels before and after treatment in both the rectal and oral ibuprofen groups (p = 0.004 and p< 0.001, respectively). The mean plasma ibuprofen concentration was similar in both groups after the first dose (rectal 44.06 ± 12.4; oral, 48.28 ± 22.8) and the third dose (rectal, 45.34 ± 24.3; oral, 48.94 ± 24.8) (p > 0.05 for all values). Conclusions: Rectal ibuprofen is as effective as oral ibuprofen for hsPDA closure in VLBW infants. The rise in the cys-C level with rectal and oral treatment shows that patients with borderline renal function should be evaluated and followed closely.

The importance of administration of early surfactant and nasal continuous positive airway pressure in newborns with respiratory distress syndrome

AIM Mechanical ventilation is an invasive method and causes to important problems in the respiratory tract and lung parenchyma. The objective of our study was to investigate if administration of early surfactant and nasal continuous positive airway pressure (nCPAP) was superior to delayed surfactant administration and mechanical ventilation. MATERIAL AND METHODS The study was conducted in the Van 100th Year University, Medical Faculty Hospital, Neonatal Intensive Care Unit. One hundred and nine infants with respiratory distrss syndrome (RDS) with a gestational age of 32 weeks and/or below were included in the study. Surfactant was given to 61 infants in the delivery room or intensive care unit and subsequently nCPAP was administered. Surfactant was administered in 48 infants in the control group and mechanical ventilation was inititated subsequently. Informed consent was obtained from the relatives of all patients and ethics committee approval was also obtained (Approval number: 03.02.2011/15). RESULTS There was no statistically significant difference between the two groups in terms of gestational age, birth weight, gender, height and head circumference measurements (p>0.05). The mean hospitalization time in the patients in the study group was 24.4±17.8 days, whereas the mean time of nCPAP was 28.4 (4-120) hours. In the study group, intracranial hemorrhage was found with a rate of 27.85%, bronchopulmonary dysplasia was found with a rate of 4.91%, pneumothorax was found with a rate of 3.27%, necrotizing enterocolitis was found with a rate of 3.27%, patent ductus arteriosus was found with a rate of 16.39, sepsis was found with a rate of 22.95% and retinopathy of prematurity was found with a rate of 1.63%. No statistically significant difference was found between the study and control groups in terms of the rates of complications. During the follow-up period, 17 (27.86%) patients were lost. The length of stay on mechanical ventilation in the study group was found to be statistically significantly shorter compared to the control group (p<0.05). CONCLUSIONS In our study, it was observed that administration of early surfactant and nCPAP in treatment of preterm newborns with a diagnosis of RDS markedly decreased the lenght of stay on mechanical ventilation, but had no significant impact on morbidity and mortality.