Early Immunomodulatory Effects of Different Natural Surfactant Preparations in Preterms With Respiratory Distress.

Background: Respiratory distress syndrome (RDS) is the most common respiratory disease in premature infants. Exogenous natural surfactant preparations are used in the treatment of RDS. In recent years, it has become increasingly evident that surfactant plays an immunoregulatory role. Objectives: The aim of this study was to evaluate cytokine and chemokine response following three different regimens of natural surfactant treatment in preterm newborns with RDS. Methods: Premature newborns below 32 weeks of gestation who were intubated for RDS and given early surfactant rescue therapy were included in the study. Newborns were randomly divided into three groups and Beractant 100 mg/kg (B-100), Poractant alfa 100 mg/kg (Pα-100) and Poractant alfa 200 mg/kg (Pα-200) were administered intratracheally. Blood samples and transtracheal aspirates (TA) were collected just before and 4-6 h after the surfactant treatment. Total eosinophil count, inducible T Cell alpha chemoattractant (ITaC), macrophage inflammatory protein 3 beta (MIP3b), interleukins (IL) 5, 8, 9, 10, 13, immunoglobulin E (IgE), interferon gamma (IFN-γ), eotaxin and tumor necrosis factor beta-1 (TGF-ß1) were measured from blood and tracheal aspirate samples. Results: A total of 45 infants, 15 in each group, were included in the study. Mean gestational age, birth weight, antenatal, demographic and clinical characteristics of the study groups were similar. IFNγ concentration and eosinophil counts in TA decreased after surfactant replacement in all groups, especially in the infants treated with Pα-100 and Pα-200. Eotaxin, TGF beta and IL-8 concentrations in TA increased significantly in the infants treated with Pα-100 and Pα-200. IL-9 levels in TA decreased in the B-100 group but increased in the Pα-100 and Pα-200 groups. Blood levels of cytokines and chemokines showed significantly decreased levels of ITaC and MIP3b only in the B-100 group, but no significant change was observed in the Pα-100 and Pα-200 groups. Conclusion: In our study, the different immunomodulatory effects of natural surfactant preparations on newborn lung is proven. We found that Poractant α, one of the natural surfactant preparations, shifted the lung immune system toward TH2.

Can urinary biomarkers predict acute kidney injury in newborns with critical congenital heart disease?

BACKGROUND: Congenital heart disease (CHD) is the most common congenital malformation group and is the leading cause of newborn mortality in developed countries. Most of the infants with CHD develop preoperative or postoperative acute kidney injury (AKI). Acute kidney injury may develop before the serum creatinine rise and oliguria. Urinary biomarkers such as kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), interleukin (IL)-18, and cystatin C may predict AKI in patients with critical CHD (CCHD) before the serum creatinine rise. In this study, we aimed to determine the AKI incidence among newborn patients with CCHD and investigate the predictivity of urinary biomarkers for AKI. METHODS: Newborns with a gestational age >34 weeks and birth weight >1500 g with a diagnosis of CCHD were enrolled in the study. Blood and urine samples were collected at birth, during the first 24-48 h, and in the preoperative and postoperative periods. RESULTS: A total of 53 CCHD patients requiring surgery during the neonatal period were enrolled in the study. The 24-48 h KIM-1 levels of the cases with exitus were higher (P = 0.007). The 24-48 h cystatin C and preoperative NGAL levels were higher in patients with postoperative AKI (P = 0.02). DISCUSSION: In newborns with CCHD, high KIM-1 levels may predict mortality, whereas high cystatin C and preoperative NGAL levels may be indicative of AKI. These biomarkers deserve further investigation in larger study populations.

Mannose-binding lectin may affect pregnancy outcome.

Mannose-binding lectin (MBL) is a component of the innate immune system and acts as a complement activator through the lectin pathway. Genetic variations of MBL and low MBL levels cause several infection problems, which may also be related to pregnancy problems. We aimed to investigate the role of MBL gene codon 54 polymorphism and serum MBL levels in pregnancy problems and premature delivery. In this prospective study, MBL gene codon 54 polymorphism and serum MBL levels were studied in 45 mothers who delivered earlier than 35 gestational weeks. The frequency of MBL gene codon 54 variant allele B was much higher (homozygous 4.4% and heterozygous 33.3%) in the study group mothers than the previously reported frequency in the healthy Turkish population (homozygous 2-6%, heterozygous 12-20%). MBL variant allele B frequency was closely related to low MBL levels (<0.1 µg/ml), vaginitis and increased IL-6 levels. The median MBL levels were lower than the critical level of 0.1 µg/ ml in study mothers who had recurrent miscarriage, infertility, preeclampsia, gestational diabetes mellitus, preterm premature rupture of membranes with duration of longer than 72 hours, tocolysis, histological chorioamnionitis, urinary tract infection and vaginitis. MBL gene codon 54 variant allele B is related to low serum MBL levels, increased IL-6 levels, genitourinary infections and may cause pregnancy-related problems such as infertility, recurrent miscarriage and preterm delivery.

Perforated appendicitis after intravenous immunoglobulin therapy in a term neonate with haemolytic jaundice.

Neonatal appendicitis is a rare clinical condition that may cause high morbidity and mortality if diagnosis is delayed. There is usually an underlying disease; it can also be a localized form of necrotizing enterocolitis. Here, we present a term neonate who was treated with intravenous immunoglobulin because of severe isoimmune hemolytic jaundice. The patient developed abdominal symptoms within 10 hours of therapy, was diagnosed with acute perforated appendicitis and completely recovered after surgery.

Cord blood and consecutive chitotriosidase activity: Relationship to prematurity and early prognosis.

BACKGROUND: The aim of this study was to investigate the relationship between plasma chitotriosidase activity, an inflammatory protein secreted mainly from macrophages, and neonatal morbidity and mortality in premature infants. METHODS: Cord blood chitotriosidase activity was studied in healthy control infants (53 term, group 1; 26 late preterm [33-37 gestational weeks], group 2) and 35 preterm infants (≤ 32 weeks; group 3). In group 3, consecutive samples at 3 h, 24 h, 72 h, 7 days, 14 days, and 36 weeks after conception were also analyzed. Group 3 was also evaluated for mortality, respiratory treatment and bronchopulmonary dysplasia (BPD), patent ductus arteriosus (PDA), intraventricular hemorrhage (IVH) and retinopathy of prematurity (ROP) and necrotizing enterocolitis (NEC). RESULTS: Cord blood chitotriosidase activity was positively correlated with gestational age and birthweight. SNAPPE-II score was correlated with chitotriosidase activity at 24 h. Consecutive chitotriosidase activity for group 3 was non-significantly higher in infants who died in the early neonatal period. Higher chitotriosidase activity was observed in mechanically ventilated infants than infants treated with non-invasive assisted ventilation. BPD, PDA, IVH and ROP, but not NEC, were related to higher chitotriosidase activity, being significant at some of the time points. CONCLUSION: Neonatal stress such as invasive ventilation may create a risk for the development of BPD, PDA, IVH, and ROP by increasing macrophage activation in preterm infants as reflected in the higher chitotriosidase activity. High chitotriosidase activity may also be associated with disease severity and mortality.

Association of vitamin D receptor gene polymorphisms and bronchopulmonary dysplasia.

BACKGROUND: Vitamin D and its receptor (VDR) have important roles in perinatal lung development. The aim of this study was to investigate the relationship between VDR gene polymorphism and bronchopulmonary dysplasia (BPD) in preterm infants. METHODS: VDR Fok I, Bsm I, Apa I, and Taq I polymorphisms were genotyped using restriction fragment length polymorphism in 109 preterm infants (47 with BPD, 62 without BPD). RESULTS: In univariate analysis, Ff (odds ratio (OR) = 3.937, P = 0.022, 95% confidence interval (CI) = 1.22-12.69) and ff (OR = 5.23, P = 0.004, 95% CI = 1.69-16.23) genotypes of Fok I were associated with the increased risk of BPD; whereas tt genotype of Taq 1 was associated with a protective effect against BPD (OR = 0.30, P = 0.04, 95% CI = 0.09-0.94). In multivariate logistic regression analysis, variant Fok 1 genotype increased risk of BPD (OR = 4.11, 95% CI = 1.08-15.68, P = 0.038) independent of patent ductus arteriosus, sepsis, mechanical ventilation, and surfactant treatment. Taq 1, Bsm 1, and Apa 1 polymorphisms did not have any effect. CONCLUSION: After adjusting for multiple confounders, VDR Fok 1 polymorphism was associated with the increased frequency of BPD. Further studies are needed to assess the contribution of VDR signaling to the pathogenesis of BPD and to determine if VDR polymorphisms may be suitable for identifying infants at high risk for BPD.

The effect of inhaled nitric oxide therapy on thromboelastogram in newborns with persistent pulmonary hypertension.

UNLABELLED: Studies about the effects of inhaled nitric oxide (iNO) on bleeding time and platelet aggregation in newborns are limited in number and have inconclusive results. Thromboelastogram (TEG) shows the combined effects of coagulation factors and platelet functions. In this preliminary study, we aimed to evaluate the effects of iNO on coagulation using TEG in newborns with persistent pulmonary hypertension (PPH). TEG assays were performed in 10 term infants receiving iNO treatment for PPH and 32 healthy term infants. Samples of the iNO group were collected before and during iNO. Clot reaction time (R), clot kinetics (K), maximum amplitude (MA), and alpha angle were obtained from the TEG tracing. TEG-R values were statistically higher during iNO treatment (7.75 ± 3.34) when compared to the values before iNO (4.83 ± 1.38) and the healthy controls (3.75 ± 0.98). The alpha angle was lower in iNO treated infants at both periods (before iNO, 55.33 ± 8.58; during iNO, 42.90 ± 18.34) compared to the control group (64.95 ± 6.88). MA values before iNO treatment were the lowest (44.43 ± 14.09) and improved with the iNO treatment (48.40 ± 9.49) despite still being lower compared to the controls (53.67 ± 5.56). CONCLUSION: Both PPH and iNO may negatively effect in vitro coagulation tests. Therefore, newborns with PPH requiring iNO treatment should be closely monitored for coagulation problems.

Medical closure of patent ductus arteriosus does not reduce mortality and development of bronchopulmonary dysplasia in preterm infants.

BACKGROUND: Although, patent ductus arteriosus (PDA) is associated with significant morbidity due to hemodynamic instability in preterm infants, the effect of ductus closure on mortality and morbidity is a controversial issue. The aim is to evaluate the efficacy of oral and intravenous (IV) ibuprofen treatment on ductal closure and effects on mortality and bronchoplumonary dysplasia. MATERIALS AND METHODS: The medical records of 292 premature infants treated at Ege University Neonatal Intensive Care Unit were retrospectively evaluated. Patients were classified into 3 groups as; No PDA, hemodynamically insignificant PDA (hiPDA) and hemodynamically significant PDA (hsPDA) according to the presence and hemodynamical significance of PDA by echocardiography. hsPDA group was treated with IV or oral ibuprofen. RESULTS: Patent ductus arteriosus was diagnosed by routine echocardiography in 145 patients, of whom 78 (53.7%) had hsPDA. All 65 infants with hiPDA had spontaneous PDA closure. Echocardiographic measurements were similar to those patients treated with oral or IV ibuprofen, as in the response rate to treatment without serious adverse effects. The presence of respiratory distress syndrome, surfactant therapy, late sepsis, bronchopulmonary dysplasia (BPD) and mortality rates were significantly higher in patients with hsPDA. However, with stepwise logistic regression; 5(th) min Apgar score (odds ratio [OR], 1.321, 95% confidence interval [CI], 1.063-1.641, P = 0.012) and gestational age (OR, 1.422, 95% CI, 1.212-1.662, P < 0.001) were the only significant variables associated with mortality. Gestational age (OR, 0.680, 95% CI, 0.531-0.871, P = 0.002) was the only significant variable associated with BPD shown with logistic regression. CONCLUSION: Ibuprofen treatment is effective for hsPDA closure with minimal side effects. HiPDA can close spontaneously; therefore treatment decision should be individualized. However, medical treatment of PDA does not reduce mortality and BPD.

Cardiovascular consequences of bronchopulmonary dysplasia in prematurely born preschool children.

BACKGROUND: A limited number of studies have reported various short-term cardiovascular changes in bronchopulmonary dysplasia (BPD) patients in the postsurfactant era. Little is known about the course of these changes in children with BPD. OBJECTIVES: It was the aim of this study to investigate cardiovascular consequences of BPD at preschool ages and to find out possible risk factors related to cardiovascular sequelae. METHODS: Prematurely born children with (n = 21) and without BPD (n = 20) were evaluated with conventional and myocardial tissue Doppler echocardiography at the age of 2-4 years. RESULTS: BPD patients had a decreased pulmonary artery acceleration time and higher left and right ventricular myocardial performance indexes, consistent with higher pulmonary pressures and impaired biventricular systolic and diastolic functions at preschool ages. Low birth weight, disease severity and postnatal cumulative steroid dose were related to these changes. CONCLUSION: Negative effects of BPD on global cardiac performances of both ventricles and pulmonary arterial pressure persist up to preschool ages.

Role of digoxin-like immunoreactive substance in the pathogenesis of transient tachypnea of newborn.

BACKGROUND: Transient tachypnea of newborn (TTN) is usually observed in term or near-term infants. It constitutes an important part of the respiratory distress cases observed in the neonatal intensive care unit (NICU). AIM: This paper examines the effects of digoxin-like immunoreactive substance (DLIS) on fluid and ion balance, hemodynamic and echocardiographic parameters of neonates with TTN. METHODS: Plasma DLIS, Na(+), K(+), urea, creatinine, serum and urine osmolarity, urine FeNa(+), 24-hour urine output, echocardiographic investigation and mean blood pressure, and clinical parameters of disease severity were recorded in TTN group and compared with control on the 1st and 7th days of their lives. RESULTS: Plasma DLIS levels were statistically higher in TTN group (0.66 ± 0.37 ng/mL) compared to control group (0.24 ± 0.20 ng/mL) both on the 1st day (P < 0.01) and the 7th day (P < 0.05). For TTN group, significant correlation was found between plasma DLIS levels and maximum respiratory rate, duration of tachypnea, and length of hospitalization on the 1st day. Plasma DLIS levels were correlated negatively with serum osmolarity levels. Plasma DLIS levels were positively correlated with urine output, urinary FeNa(+) levels, cardiac output, left ventricles end diastolic diameters, and right ventricles end diastolic diameters. CONCLUSIONS: Increased DLIS levels were correlated with disease severity in cases with TTN. This increase may be a primary or secondary event in the disease progress. It may help reduce the fluid overload due to already disturbed cardiac functions in patients by increasing urine output and natriuresis; however it may also contribute to disease pathogenesis, by inhibiting alveolar Na(+)-K(+)-ATPase which further decreases fetal alveolar fluid resorption.

Histological chorioamnionitis: effects on premature delivery and neonatal prognosis.

BACKGROUND: Chorioamnionitis is closely related to premature birth and has negative effects on neonatal morbidity and mortality. METHODS: In this prospective study, 43 mothers who delivered earlier than 35 gestational weeks and their 57 infants were evaluated clinically and with laboratory findings. Placentas and umbilical cords were investigated histopathologically for chorioamnionitis and funisitis. RESULTS: The overall frequency of clinical and histological chorioamnionitis (HCA) was 8.3% and 23.2%, respectively. The frequency of HCA was 47.3% and 83.3% in mothers delivered <32 weeks and <30 weeks, respectively. Maternal demographic and clinical findings and also leukocyte and C-reactive protein values were not indicative of HCA. Infants of mothers with HCA had significantly lower Apgar scores together with higher SNAP-PE-II and CRIB scores. These infants had increased mechanical ventilator and surfactant requirements, higher incidences of patent ductus arteriosus, early sepsis, and bronchopulmonary dysplasia, and higher mortality rates. The effect of HCA on neonatal morbidity and mortality was more prominent than the effect of low birthweight and lower gestational age. CONCLUSION: Chorioamnionitis not only causes premature deliveries, but is also associated with neonatal complications and increased mortality. Clinical findings and infectious markers in mother or infant do not predict the diagnosis of histological chorioamnionitis. Therefore, placental histopathology may have a role in predicting neonatal outcome in premature deliveries, especially those below 30 weeks.

Neonatal status epilepticus controlled with levetiracetam at Sturge Weber syndrome.

Sturge-Weber syndrome is a rare, sporadic, congenital neurocutaneous syndrome characterized by facial cutaneous vascular malformation, leptomeningeal angioma and eye abnormalities. Seizures develop during the first year of life, may become refractory to multiple anticonvulsants and status epilepticus may develop. A rare subtype of Sturge-Weber syndrome with bilateral facial vascular malformation, unilateral cerebral involvement and neonatal status epilepticus is reported here. Neonatal status epilepticus was successfully controlled with intravenous levetiracetam infusion.

Serial intravesical pressure measurements can predict the presence and the severity of necrotizing enterocolitis.

BACKGROUND AND AIMS: Necrotizing enterocolitis (NEC) which is accompanied with gastrointestinal ulceration and necrosis is one of the most important problems of preterm infants in neonatal intensive care unit (NICU). Increased intra-abdominal pressure (IAP) is detected among most of the pediatric patients hospitalized in intensive care unit and undergoing surgery or trauma. This pathology, namely, abdominal compartment syndrome, causes ischemia and hypoperfusion of abdominal organs. Recently, the effect of increased IAP on NEC is under focus and this increase is thought to be related with the onset of NEC by leading to intestinal ischemia and necrosis. In this study, we aimed to investigate if serial intravesical pressure (IVP) measurements as an indirect indicator of IAP may help to early diagnosis in NEC and to decision for surgery besides to predict the mortality of NEC. MATERIAL AND METHOD: A total number of 61 preterm infants with a birth weight of ≤ 1,500 g hospitalized in NICU were included to the study. IVP values were measured by the same nurse twice daily during their hospitalization through urinary catheter. The IVP values of the preterm infants with and without NEC were compared. RESULTS: Totally 61 premature infants included in the study were grouped as follows: group 0, the control group without NEC (n = 38); group 1, medically treated NEC patients (n = 14); and group 2, NEC patients undergoing surgery (n = 9). The median IVP measurements of group 0 were lower than the other groups (p = 0.001). No statistically significant difference in IVP measurements was detected between group 1 and group 2 (p = 0.155). A 10% of increase in IVP measurement was significant in predicting the development of NEC with consecutive serial measurements. The mean IVP measurements were higher in infants with NEC who died during their follow-up at NICU compared with NEC patients who survived (p = 0.043). CONCLUSION: Serial IVP measurements may help for early diagnosis and surgery decision of NEC and high IVP levels also may predict mortality in cases with NEC.

Association between bronchopulmonary dysplasia and MBL2 and IL1-RN polymorphisms.

BACKGROUND: The imbalance between pro-inflammatory and anti-inflammatory cytokines may play a role in the development of bronchopulmonary dysplasia (BPD) in preterm infants. Mannose binding lectin (MBL) codon 54 and interleukin 1 receptor antagonist gene (IL1-RN) polymorphisms cause genetic predisposition to increased risk of infection and inflammation, therefore may increase the risk of BPD. The aim of this study was to investigate the relationship between MBL, IL1-RN gene polymorphisms and BPD development in preterm infants. METHODS: MBL codon 54 and IL1-RN polymorphisms were studied in 71 infants who were born at <32 weeks of gestation, with the diagnosis of BPD (group 1) and in a control group of preterm infants without BPD (group 2). RESULTS: IL1-RN and MBL2 variant genes were closely associated with increased risk of BPD (both P < 0.001) together with significantly lower birthweight (P < 0.001 and P = 0.001, respectively), lower 5 min Apgar scores (P = 0.009 for both genes) and increased neonatal infection rate (P < 0.001 and P < 0.009, respectively). The IL1 RN 1/1 genotype was protective (odds ratio [OR], 0.075; 95% confidence interval [CI]: 0.019-0.76) while the IL1-RN 2/2 genotype increased the risk for BPD (OR, 11.7; 95%CI: 1.3-103.6). The MBL-AA genotype was protective against BPD (OR, 0.066; 95%CI: 0.02-0.2) whereas the MBL-BB genotype increased the susceptibility for the development of BPD (OR, 23.8; 95%CI: 2.8-200.6). CONCLUSION: MBL and IL 1 RN polymorphisms are closely related to low birthweight and increase the risk of neonatal sepsis and BPD development in preterm infants.

Comparison of oral and intravenous Ibuprofen for medical closure of patent ductus arteriosus: which one is better?

OBJECTIVE: Intravenous ibuprofen is an expensive drug that is being used currently for treating and preventing patent ductus arteriosus. Although oral ibuprofen is much cheaper, there is limited data published about its safety and efficacy. The aim of this study was to compare two forms of ibuprofen in terms of safety and efficacy in closure of patent ductus arteriosus. DESIGN: This is a single-center retrospective study. SETTING: Data were collected from patients' files of preterm infants who were hospitalized at the Neonatal Intensive Care Unit of Dr. Behcet Uz Children's Hospital between April 2009 and June 2010. PATIENTS: Six hundred sixty infants were evaluated by echocardiography between 24 and 48 postnatal hours. Clinically and hemodynamically significant ductus arteriosus was defined in 66 infants with gestational age less than 32 weeks and birth weight less than 1500 g. INTERVENTIONS: Oral or intravenous ibuprofen (loading dose: 10 mg/kg on day 1, followed by maintenance dose: 5 mg/kg on days 2 and 3) was administered. OUTCOME MEASURES: Treatment success was defined as a completely closed duct without reopening on follow-up. Drug-associated renal, gastrointestinal, cerebral, hematological, and metabolic side effects were monitored and compared between treatment groups. RESULTS: Ductal closure rates were 100% and 97.6%, respectively, in the oral and intravenous groups. Hypernatremia was the remarkable side effect in the intravenous group, whereas bronchopulmonary dysplasia and septicemia were prominent in the oral group. No statistically significant difference could be demonstrated between the groups in terms of mortality rates. CONCLUSION: Oral ibuprofen therapy is as efficacious as intravenous ibuprofen with some concerns about increased sepsis and bronchopulmonary dysplasia incidence. However, comprehensive and large-scale pharmacokinetic studies are required in order to prove this efficacy. On the other hand, intravenous ibuprofen still remains to be the drug of choice for patent ductus arteriosus but only with meticulous control of serum sodium levels in smaller infants.

Desferrioxamine treatment of iron overload secondary to RH isoimmunization and intrauterine transfusion in a newborn infant.

Intrauterine transfusion is the standard of care in the management of severe Rh isoimmunization. Desferrioxamine has been used for the treatment of iron overload secondary to hemolysis and intrauterine transfusions in Rh isoimmunization cases. Here, we report a preterm infant born at 34 weeks of gestational age who had formerly received intrauterine transfusions for Rhesus hemolytic disease and presented with severe hyperferritinemia and elevated liver enzymes in the first week of life. Desferrioxamine treatment was started due to a ferritin level of 28,800 ng/ml and continued for 13 weeks. Although the treatment was successful, we observed resistant leukopenia which resolved after the cessation of treatment. In conclusion, iron overload secondary to intrauterine transfusions can be treated successfully with desferrioxamine; however, neonatologists must be aware of the possible side effects of this drug which has been used in only a limited number of newborns.

Mannose-binding lectin gene polymorphism and early neonatal outcome in preterm infants.

BACKGROUND: Mannose-binding lectin (MBL) as a component of innate immunity plays an important role in preterm infants in whom adaptive immunity is not sufficiently developed. Polymorphisms in immunoregulatory genes influence the response to infection and subsequent inflammation. Infection and inflammation have been implicated in the mechanisms responsible for many of the diseases in the preterm newborns. OBJECTIVES: The aim of the study was to investigate the relationship between MBL gene polymorphism and early neonatal outcome in preterm infants. METHODS: Codon 54 and 57 polymorphisms in MBL2 gene were genotyped in 99 preterm infants admitted to the Neonatal Intensive Care Unit at Ege University Children's Hospital. RESULTS: Overall frequencies of sepsis and early-onset sepsis were higher in the group of infants with MBL polymorphism when compared to infants with wild-type MBL genotype (p = 0.008, 0.009, respectively). Maximum Tollner sepsis score in the first 3 days of life was higher for the infants with variant MBL genotype (p = 0.0278). More infants in the variant MBL group had significant patent ductus arteriosus when compared to infants with wild-type MBL (27.8 vs. 9.5% respectively, p = 0.037). CONCLUSION: MBL gene polymorphism was associated with increased frequency of clinical sepsis particularly with early neonatal sepsis and also with higher Tollner sepsis scores and increased frequency of patent ductus arteriosus in infants. Overall mortality and incidence of culture proven sepsis, respiratory distress syndrome, bronchopulmonary dysplasia, intraventricular hemorrhage, periventricular leukomalacia and necrotizing enterocolitis were not found to be related to MBL genotype.

Investigation of maternal melatonin effect on the hippocampal formation of newborn rat model of intrauterine cortical dysplasia.

OBJECTIVES: Cortical dysplasia is a cortical malformation resulting from any developmental defects during different periods of development. This study aims to investigate the hippocampal histopathological alterations in the neonates with cortical dysplasia due to the prenatal exposure to carmustine (1,3-bis (2-chloroethyl)-1-nitrosourea; BCNU) and the possible effects of prophylaxis with melatonin, a neuroprotective agent. METHODS: Wistar albino female rats were randomly divided into four experimental groups; control, melatonin-treated, BCNU-exposed and BCNU-exposed+melatonin-treated. Light microscopy and immunohistochemistry were carried out on the newborn hippocampus. RESULTS: Histopathology of hippocampus from the control and melatonin-treated groups showed continuity of migration and maturation as pathognomonic signs of the normal newborn hippocampus. Hippocampal cortex from the newborns exposed in utero to BCNU showed the histology of early embryonic hippocampal formation with immunohistochemical increase in the number of nestin positive cells and decreases in the immunoreactivity of glial fibrillary acidic protein (GFAP) and synaptophysin. These findings indicate a significant delay in hippocampal maturation, migration, and synaptogenesis. Intrauterine treatment of BCNU-exposed rats with melatonin resulted in histopathological features almost similar to control group. CONCLUSION: It has been concluded that cortical dysplasia induced by intrauterine BCNU administration results in delayed hippocampal maturation, which is successfully restored by intrauterine melatonin treatment.

Titration of betaine therapy to optimize therapy in an infant with 5,10-methylenetetrahydrofolate reductase deficiency.

Betaine therapy was given for 2 years to a 2-year-old boy with 5,10-methylenetetrahydrofolate reductase deficiency. Used as a methyl donor to lower homocysteine levels through methylation of methionine, betaine has been reported to be effective in treating homocystinuria. Satisfactory biochemical and clinical responses were obtained with the following regimen: betaine started in the newborn period at increasing doses to reach 1 g given six times a day. It is suggested that frequent administration of a moderate dose may provide clinical and biochemical benefit.

Value of biochemical markers for outcome in term infants with asphyxia.

The aim of this study was to define the predictive values of serum and cerebrospinal fluid concentrations of interleukin-6 and neuron-specific enolase and urinary uric acid/creatinine ratio for outcome in term infants with perinatal asphyxia. All biochemical markers were measured simultaneously within the 24-72 hours of life in 21 infants. The infants were monitored with a standardized neurologic and developmental evaluation protocol over the 2 years of life. The overall outcome at 2 years of age was categorized as "favorable" or "adverse". According to Sarnat and Sarnat classification, 12 infants had mild encephalopathy and 9 infants had moderate to severe encephalopathy. Seven of 9 (78%) infants with moderate to severe encephalopathy had adverse outcome. However, all infants with mild encephalopathy had favorable outcome. Interleukin-6 and neuron specific enolase levels in cerebrospinal fluid and serum interleukin-6 levels were significantly correlated with the degree of encephalopathy, as well as the outcome. Interleukin-6 in cerebrospinal fluid (cutoff value, 25.9 pg/mL) had the highest predictive value among the biochemical markers. The predictive factors identified in this study should be examined for their ability in a fresh clinical sample in the neonatal intensive care unit before these markers can be applied to the routine clinical of infants with perinatal asphyxia.