Nilgün Köksal

Possible Neuroprotective Effects of Magnesium Sulfate and Melatonin as Both Pre- and Post-Treatment in a Neonatal Hypoxic-Ischemic Rat Model

Background: Perinatal hypoxia-ischemia is a major cause of mortality and long-term neurological deficits. Objectives: The objective of this study was to compare the effects of two neuroprotective agents; magnesium sulfate and melatonin, administered alone or in combination, on brain infarct volume and TUNEL positivity in a neonatal hypoxic-ischemic (HI) rat model. Methods: After being anesthetized, 7-day-old pups (n = 80) underwent ischemia followed by exposure to hypoxia for 2 h. The pups were then divided equally and randomly into 4 groups in order to receive the vehicle (saline, control group), magnesium sulfate, melatonin or a combination of magnesium sulfate and melatonin. Treatments were administered intraperitoneally three times; the first being just before ischemia, the second after hypoxia and the third 24 h after the second dose. The pups were sacrificed on postnatal day 10, their brains harvested and evaluated for infarct volume and neuronal apoptosis. Results: Percent infarcted brain volume was significantly reduced in pups receiving the drugs (either magnesium sulfate, melatonin or their combination) compared with those receiving the vehicle. In addition, TUNEL staining showed markedly reduced numbers of TUNEL-positive cells per unit area in the CA1, CA3 and dentate gyrus regions of the hippocampus and in the cortex. However, no statistically significant differences were found regarding percent infarcted brain volume and number of TUNEL-positive cells among the drug-treated groups. Conclusions: Magnesium sulfate and melatonin, two agents acting at different stages of HI brain damage, administered either alone or in combination, significantly reduced the percent infarcted brain volume and TUNEL positivity, suggesting that these agents may confer a possible benefit in the treatment of infants with HI encephalopathy.

Increased incidence of bronchopulmonary dysplasia in preterm infants exposed to preeclampsia.

Objective: The aims of the study were to determine the effect of preeclampsia on bronchopulmonary dysplasia (BPD) development in preterm infants and to investigate the possible association between BPD severity and preeclampsia. Methods: The study group involved preterm infants (≤32 gestational week) born to a preeclamptic mother with no co-existing medical condition, whereas the comparison group involved preterm infants born to a normotensive mother. BPD was defined as requirement for supplemental oxygen for the first 28 days of life and classified as mild, moderate and severe. Results: There were a total of 117 and 215 premature infants that were born to a preeclamptic mother and a normotensive mother, respectively. The incidence of BPD in preterm infants born to preeclamptic mothers (38.5%) was significantly higher than those born to normotensive mothers (19.5%). Frequencies of moderate and severe BPD were significantly higher in the infants born to preeclamptic mothers. Moderate and severe BPD was also significantly higher in infants born to a mother with severe preeclampsia compared with a mother with mild preeclampsia. In logistic regression model, preeclampsia was found to be predictive of BPD. Conclusions: Preeclampsia was found to be an important risk factor for BPD development in preterm infants. The incidence of both moderate and severe BPD was significantly higher in infants born to preeclamptic mothers. These findings might be associated with altered angiogenesis in the preeclamptic mother which might be shared by the fetus.

The progression of maternal RSV antibodies in the offspring

The concentrations of maternal anti-RSV IgG antibodies were followed in 49 healthy newborns over the first six months of life. At birth, 41 mothers (83%) tested positive for anti-RSV IgG and all of their babies carried maternal anti-RSV IgG. Anti-RSV IgG positivity dropped to 73% at 1 month, 6% at 3 months, and 2% at 6 months. Between 3 and 6 months, 8% did acquire RSV infection, half of them as acute bronchiolitis and half as non-specific respiratory infection. All of the patients who acquired clinical RSV disease had an antibody concentration of <20 RU/ml which may be the cut off value for protection.

Comparison of the efficacy of serum amyloid A, C-reactive protein, and procalcitonin in the diagnosis and follow-up of necrotizing enterocolitis in premature infants

PURPOSE The aim of this study was to compare the efficacy of serum amyloid A (SAA) with that of C-reactive protein (CRP), and procalcitonin (PCT) in diagnosis and follow-up of necrotizing enterocolitis (NEC) in preterm infants. METHODS A total of 152 infants were enrolled into this observational study. The infants were classified into 3 groups: group 1 (58 infants with NEC and sepsis), group 2 (54 infants with only sepsis), and group 3 (40 infants with neither sepsis nor NEC, or control group). The data including whole blood count, CRP, PCT, SAA, and cultures that were obtained at diagnosis (0 hour), at 24 and 48 hours, and at 7 and 10 days were evaluated. RESULTS A total of 58 infants had a diagnosis of NEC. Mean CRP (7.4 ± 5.2 mg/dL) and SAA (46.2 ± 41.3 mg/dL) values of infants in group 1 at 0 hour were significantly higher than those in groups 2 and 3. Although the area under the curve of CRP was higher at 0 hour in infants with NEC, there were no significant differences between groups with respect to the areas under the curve of SAA, CRP, and PCT at all measurement times. Levels of SAA decreased earlier than CRP and PCT in the follow-up of NEC (mean SAA levels were 45.8 ± 45.2, 21.9 ± 16.6, 10.1 ± 8.3, and 7.9 ± 5.1 mg/dL at evaluation times, respectively). Levels of CRP and SAA of infants with NEC stages II and III were significantly higher than those with only sepsis and/or NEC stage I. CONCLUSIONS Serum amyloid A, CRP, and PCT all are accurate and reliable markers in diagnosis of NEC, in addition to clinical and radiographic findings. Higher CRP and SAA levels might indicate advanced stage of NEC. Serial measurements of SAA, CRP, and PCT, either alone or in combination, can be used safely in the diagnosis and follow-up of NEC.

Culture-proven neonatal sepsis in preterm infants in a neonatal intensive care unit over a 7 year period: coagulase-negative Staphylococcus as the predominant pathogen.

The aim of this study was to determine the causative agents in early, late‐ and very late‐onset sepsis in preterm infants. The demographic features, risk factors, clinical and laboratory findings in sepsis types were also defined.

Maternal preeclampsia is associated with increased risk of necrotizing enterocolitis in preterm infants.

BACKGROUND Necrotizing enterocolitis (NEC) is an important cause of mortality and morbidity in preterm infants. AIMS To evaluate the effect of maternal preeclampsia on the development and severity of NEC in premature infants. STUDY DESIGN Prospective observational study in a tertiary neonatal intensive care unit. SUBJECTS The preterm infants of ≤ 37 gestational age who were consecutively hospitalized were enrolled. The study group contained preterm infants born to a preeclamptic mother and the comparison group contained preterm infants born to a normotensive mother. OUTCOME MEASURES The primary outcome was to determine the association between preeclampsia and NEC. RESULTS A total of 88 infants had NEC diagnosis. The incidence of NEC in infants born to preeclamptic mothers (22.9%) was significantly higher compared with those born to normotensive mothers (14.6%). According to NEC stages, NEC was more advanced in preeclamptic mother infants. NEC developed significantly earlier in infants with NEC in the study group. The duration of NEC was also significantly longer in infants born to preeclamptic mothers. In multiple logistic regression model, preeclampsia was found to be predictive of NEC with an odds ratio of 1.74 (95% confidence interval 0.64-0.92). CONCLUSIONS Maternal preeclampsia may be an important risk factor for the development of NEC in premature infants as NEC incidence and severity of NEC were found to be significantly higher in premature infants born to preeclamptic mothers. The onset of NEC was significantly earlier and duration of NEC was longer in these infants.

Neonatal outcomes of premature infants born to preeclamptic mothers

OBJECTIVE Only limited studies with conflicting results are available on neonatal morbidity and mortality in infants born to preeclamptic mothers. The objective of this study was to evaluate neonatal morbidity and mortality in premature infants born to preeclamptic mothers. METHODS Premature infants who were admitted to Uludag University, School of Medicine, Neonatal Intensive Care Unit between June 2006 and December 2007 were included in this study. The infants were evaluated according to their demographic characteristics and neonatal morbidities. RESULTS Fifty-one infants born to preeclamptic mothers (study group) and 33 gestational age- and gender-matched infants born to normotensive mothers (control group) were included in this study. No statistical difference was found between the two groups in terms of demographic characteristics. However, frequency of neutropenia, duration of mechanical ventilation, and neonatal sepsis rates were found to be significantly higher in the study group compared with those of the control group. Although the rates of other neonatal morbidities such as bronchopulmonary dysplasia, retinopathy of prematurity, intraventricular hemorrhage and necrotising enterocolitis were found to be higher in the study group, the difference was not statistically significant. Mortality rates were also found to be similar in both groups. CONCLUSIONS The infants born to preeclamptic mothers had significantly higher rates of neutropenia and sepsis. There were no significant difference in terms of other neonatal morbidities and neonatal mortality between the study and the control group.

Meropenem in neonatal severe infections due to multiresistant gram-negative bacteria.

Recently, new broad spectrum carbapenem has been investigated on a world-wide scale for the treatment of moderate to severe infections. In the neonatal intensive care units the extensive use of third generation cephalosporins for therapy of neonatal sepsis may lead to rapid emergence of multiresistant gram-negative organisms. We report the use of meropenem in 35 infants with severe infections due toAcinetobacter baumanii andKlebsiella pneumoniae. All gram negative bacteria were resistant to ampicillin, amoxicillin, ticarcilin, cefazoline, cefotaxime, ceftazidime, ceftriaxone and aminoglycosides. Eighty two percent of the cases (29/35) were born prematurely. Assisted ventilation was needed in 85.7 % (30/35). All infants deteriorated during their conventional treatment and were changed to meropenem monotherapy. Six percent (2/35) died. The incidence of drug-related adverse events (mostly a slight increase in liver enzymes) was 8.5 %. No adverse effects such as diarrhea, vomiting, rash, glossitis, oral or diaper area moniliasis, thrombocytosis, thrombocytopenia, eosinophilia and seizures were observed. At the end of therapy, overall satisfactory clinical and bacterial response was obtained in 33/35 (94.3%) of the newboms treated with meropenem. Clinical and bacterial response rates for meropenem were 100% for sepsis and 87.5% for nosocomial pneumonia. This report suggests that meropenem may be a useful antimicrobial agent in neonatal infections caused by multiresistant gram negative bacilli. Further studies are needed to confirm these results : Meropenem, newborn, sepsis and nosocomial infection.

Risk factors for intraventricular haemorrhage in very low birth weight infants.

Objective: In a prospective study at Uludag University Hospital, 120 premature infants with birthweights of 1500 g or less were screened for intraventricular hemorrhage (IVH) using cranial ultrasound. With the purpose of studying the incidence of IVH, the associated risk factors for these neonates were considered.Methods : We studied all the very low birth weight infants admitted in our neonatal unit. We examined the following variables as risk factors for IVH: sex, birth weight, gestational age, Apgar score, mechanichal ventilation, hypercapnia, use of antenatal steroids, tocolytic drugs, vaginalversus cesarean section delivery, and inbornversus outborn status, vasopressor infusion (any vasoactive drug such as dopamine, dobutamine, or epinephrine) not associated with resuscitation, and surfactant administration.Results :The incidence of IVH was 15% (18/120), 50% grade I (9/18), 17% grade II (3/18), 11 % grade III (2/18), and 22% grade IV (4/18). IVH occurred mainly in the first week of life (78%; 14/18). The significant risk factors for IVH were found to be prematurity, outborn status, low 5 minute Apgar score, vaginal delivery, hypercapnia, mechanical ventilation, hypotension, and use of vasopressors on the day of admission. Significant protective factors against IVH included antenatal steroid therapy, cesarean section, magnesium sulfate tocolysis, increasing gestational age, and increasing birth weight.Conclusion: Our results concur with the notion that a tertiary center is the optimal location for delivery of the high risk neonate. Transportation of infantsin utero to a perinatal center specializing in high risk-deliveries results in a decreased incidence of IVH when compared to infants transported postnatally. Aggressive resuscitation, with avoidance of hypercarbia, and rapid restoration of hypovolemia could potentially reduce the incidence of PVH/IVH

Neuroprotective effects of melatonin administered alone or in combination with topiramate in neonatal hypoxic-ischemic rat model.

PURPOSE The objective of this study was to compare the effects of two neuroprotective agents; melatonin, a free radical scavenger and topiramate, AMPA/kainate receptor antagonist, administered alone or in combination in neonatal hypoxic-ischemic model. METHODS After being anesthetized, 7-day-old pups underwent ischemia followed by exposure to hypoxia. The pups were divided into 4 groups in order to receive the vehicle, melatonin, topiramate and combination of topiramate and melatonin. These were administered intraperitoneally for three times; the first before ischemia, the second after hypoxia and the third 24 hours after the second dose. After sacrification, infarct volume and apoptosis were evaluated. RESULTS Percent infarcted brain volume was significantly reduced in rats which received drugs compared with those which received the vehicle. The number of TUNEL positive cells per unit area in hippocampus and cortex were markedly reduced in drug treated groups compared with control group. No significant differences were found regarding percent infarcted brain volume and number of TUNEL positive cells among drug-treated groups. CONCLUSIONS Melatonin and topiramate, administered either alone or in combination significantly reduced the percent infarcted brain volume and number of TUNEL positive cells suggesting that these agents may confer benefit in treatment of infants with hypoxic-ischemic encephalopathy.