Intravenous Levetiracetam for Treatment of Seizures in Term and Preterm Neonates.

CONTEXT: Seizures are the most frequent neurological disturbance in the neonatal period, and there are no evidence-based guidelines for the treatment of neonatal seizures. Here we report a study on the use of levetiracetam as second-line therapy in the treatment of seizures in term and preterm neonates. AIM: The aim of this study was to assess the efficacy and safety of levetiracetam for seizures of term and preterm neonates. SETTINGS AND DESIGN: We retrospectively analyzed data of the patients who had seizures and who were treated with levetiracetam as an add-on therapy to phenobarbital during the neonatal period. STATISTICAL ANALYSIS: The Statistical Package for the Social Sciences (SPSS) software, version 15.0 (SPSS, Chicago, Illinois), was used for statistical analysis. Continuous variables were expressed as mean values and standard deviations. RESULTS: Thirty-six patients (8 term and 28 preterm) received levetiracetam. Mean dose of levetiracetam was 31.67 ± 14.83mg/kg/day. Twenty-five of the patients (69.4%) were seizure free with levetiracetam treatment. Electroencephalography recordings improved in 28 (77.8%) of the patients after levetiracetam. No severe adverse effects were observed. CONCLUSION: Our data suggest that levetiracetam may be a safe and effective treatment for neonatal seizures, which are unresponsive to phenobarbital.

Volume Guarantee High-Frequency Oscillatory Ventilation in Preterm Infants With RDS: Tidal Volume and DCO2 Levels for Optimal Ventilation Using Open-Lung Strategies.

High frequency oscillatory ventilation with volume-guarantee (HFOV-VG) is a promising lung protective ventilator mode for the treatment of respiratory failure in newborns. However, indicators of optimal ventilation during HFOV-VG mode are not identified yet. In this study, we aimed to evaluate optimal high-frequency tidal volume (VThf) and the dissociation coefficient of CO2 (DCO2) levels to achieve normocapnia during HFOV-VG after lung recruitment in very low birthweight infants with respiratory distress syndrome (RDS). Preterm babies under the 32nd postmenstrual week with severe RDS that received HFOV-VG using open-lung strategy between January 2014 and January 2019 were retrospectively evaluated. All included patients were treated with the Dräger Babylog VN500 ventilator in the HFOV-VG mode. In total, 53 infants with a mean gestational age of 26.8 ± 2.3 weeks were evaluated. HFOV mean optimal airway pressure (MAPhf) level after lung recruitment was found to be 10.2 ± 1.7 mbar. Overall, the mean applied VThf per kg was 1.64 ± 0.25 mL/kg in the study sample. To provide normocapnia, the mean VThf was 1.61 ± 0.25 mL/kg and the mean DCO2corr was 29.84 ± 7.88 [mL/kg]2/s. No significant correlation was found between pCO2 levels with VThf (per kg) or DCO2corr levels. VThf levels to maintain normocarbia were significantly lower with 12 Hz frequency compared to 10 Hz frequency (1.50 ± 0.24 vs. 1.65 ± 0.25 mL/ kg, p < 0.001, respectively). A weak but significant positive correlation was found between mean airway pressure (MAPhf) and VThf levels. To our knowledge, this is the largest study to evaluate the optimal HFOV-VG settings in premature infants with RDS, using the open-lung strategy. According to the results, a specific set of numbers could not be recommended to achieve normocarbia. Following the trend of each patient and small adjustments according to the closely monitored pCO2 levels seems logical.

Evaluation of health-related quality of life and affecting factors in child with enuresis.

BACKGROUND: Enuresis is a common problem in children and distressing condition that can have an impact on the child's behavior and on their emotional and social life. Health-related quality of life (HRQoL) is defined as an individual's perception of the impact of the disease and treatment. OBJECTIVE: The aim of this study was to evaluate the HRQoL in Turkish children with enuresis and to investigate the effect of independent sociodemographic and clinical variables on HRQoL in children with enuresis. STUDY DESING: 110 children with enuresis and their mothers and 120 healthy children and their mothers were included in the study. The German quality of life questionnaire (KINDL®) scales were used to assess the children's HRQoL. For comparing the data of children with enuresis and healthy children, a two-sided unpaired t-test and linear regression model were used. RESULT: The total HRQoL score for the children with enuresis group was 63.14 ± 21.98 and for the children in the control group was 75.6 ± 10.1 (P < 0.001). After adjusting for sex and age using the unstandardized coefficient of regression model, HRQoL score for the children with enuresis still remained statistically significant lower than that for healthy peers (64.21 ± vs 75.11 ± P < 0.001). The HRQoL subscale scores showed that children with enuresis had lower emotional well-being scores (64.23 ± 14.2 vs 78.9 ± 11.4, P < 0.001), self-esteem score (62.23 ± 11 vs 68.6 ± 17.4, P = 0.001), family relationship score (76.23 ± 2 vs 83.4 ± 12.2, P = 0.042), and friendship score (62.4 ± 13.2 vs 68.8 ± 15.3, P = 0.023) compared to the control group. When the effects of independent sociodemographic factors and clinical variables on HRQoL were evaluated, it was seen that the presence of lower urinary tract symptoms (LUTS) negatively affected total HRQoL score (59.89 ± 11.2 vs 69.29 ± 10.9 P = 0.028). Also the total HRQoL score was higher in treated children with enuresis than in nontreated children (65.96 ± 12.1 vs 55.27 ± 10.1 P = 0.032). Among the treated children, complete treatment response group had higher total HRQoL score compared to partial treatment response group and nonresponse group (respectively, 70.98 ± 9.7, 65.25 ± 10.1, 60.45 ± 10.9, P = 0.034, P = 0.01) (Summary Figure). Family income level affected total HRQoL score, low-income group had lower total HRQoL score compared to high-income group (62.17 ± 11.9 vs 69.25 ± 10 P = 0.039). DISCUSSION: This study demonstrated that enuresis negatively affects the HRQoL of children and most affected domains in HRQoL were self-esteem, emotional well-being, and their relationship for family and friends. Our presented study showed that HRQoL was lower in non-primary monosymptomatic nocturnal enuresis (non-PMNE) children, nontreated patients. Also there were higher HRQoL scores in patients who had a total or partial response to treatment. CONCLUSION: Our study may indicate that, low-income children with enuresis, nontreated enuretic children, and presence of LUTS should be considered as a risk group for low HRQoL.

Effects of maternal folic acid supplementation on airway remodeling and allergic airway disease development.

Objective: Maternal folic acid supplementation has been recommended prior to and during the first trimester of pregnancy to reduce the risk of infant neural tube defects. However, an uncertain relationship between folic acid supplementation during pregnancy and development of childhood asthma exists. Recent data show a methyl donor-rich diet could increase the risk of developing allergic airway disease through DNA methylation and aberrant gene transcription. This study evaluated the effect of folic acid supplementation during pregnancy on airway remodeling and allergic airway disease vulnerability in a mouse asthma model. Methods: BALB/c mice were divided into four groups according to gestational folic acid supplementation and postnatal ovalbumin (OVA) exposure: Group 1 (whole pregnancy folic acid supplementation + OVA-exposed group), Group 2 (first gestational week folic acid supplementation + OVA-exposed group), Group 3 (no folic acid supplementation + OVA-exposed group), and Group 4 (control group). Offspring were sacrificed on day 45 for immunohistological and ultrastructural tests. Results: In OVA challenged groups, folic acid supplementation led to a thicker epithelial and subepithelial smooth muscle layer than in the unsupplemented group. Moreover, folic acid supplementation during whole pregnancy (Group 1) was associated with a thicker epithelial and subepithelial smooth muscle layer than folic acid supplementation during the first week of pregnancy (Group 2), suggesting a duration-response relationship. Electron microscopic imaging revealed that structural changes including the loss of epithelial integrity, thickening of basement membrane, and subepithelial fibrosis were more prominent in the folic acid supplementation groups. Conclusions: This study suggested that maternal folic acid supplementation during pregnancy affects airway remodeling and increases the allergic responses induced by ovalbumin challenge in offspring. In addition, the effect size increased as the duration and cumulative dose increased.

The effects of perinatal steroid therapy on growth factor levels during different stages of the developing brain.

OBJECTIVE: Excess glucocorticoid (GC) exposure on the fetal brain during critical stages of development has considerable effects on the development of the central nervous system (CNS). This study thus aimed to evaluate the differential effects of GC exposure on critical growth factor levels during different stages of brain maturation. METHODS: For this purpose, forty-two rat pups were divided into six groups based on the timing of betamethasone administration. Rats in the treatment groups were exposed to intraperitoneal betamethasone injections beginning at different time points (postnatal days 1, 2, and 3). Rats in the placebo group received the same volume of 0.9% saline via the same fashion. Pups were sacrificed at 24 h following the final injection for determining the neuronal density and immunohistochemical evaluation of critical growth factors. RESULTS: In the groups treated with betamethasone on postnatal day 1 (P1) and P2, which correspond to 22-24 and 24-28 gestational weeks in humans, the neuronal count in the hippocampal regions was significantly lower than their control groups. However, if steroid therapy was administered on P3, corresponding to 28-32 weeks in humans, no difference was observed between the two groups. Growth factors were affected in different ways depending on the steroid administration time and evaluated region. CONCLUSIONS: The results suggest that the modulating effect of steroids on neuron count and growth factor response depends on the stage of brain development at the time of exposure. Therefore, this may be one of the key determinants affecting the deleterious and beneficial effects of GCs on the CNS.

Intranasal surfactant protein D as neuroprotective rescue in a neonatal rat model of periventricular leukomalacia.

BACKGROUND: Periventricular leukomalacia (PVL) is the leading cause of neurocognitive deficits in children with prematurity. We previously hypothesized that surfactant protein D (SPD) with its ability to bind toll-like receptors may have a possible ameliorating effect in PVL. METHODS: Three groups were defined as: LPS-administered and postnatal intranasal saline administered group, LPS-administered and postnatal intranasal SPD-treated group, and control group. Twenty-eight offspring rats were reared with their dams until their sacrifice for histological evaluation on day 7. RESULTS: A significant loss of brain weight occurred in the LPS group compared with controls. The postnatal intranasal SPD treatment significantly reduced the number of TUNEL-positive cells in the periventricular white matter as compared with the LPS-treated group. Compared with the control group, LPS injection in the rat brain significantly reduced the MBP-positive staining. Postnatal SPD treatment greatly prevented LPS-stimulated loss of MBP staining. CONCLUSIONS: Present study demonstrated a neuroprotective effect of SPD in a rat model of PVL. Our results offer future implications towards increasing our understanding about multifactorial mechanisms underlying periventricular leukomalacia and developing plausible therapeutic strategies in order to prevent neurocognitive deficits in preterm infants.

Nasal intermittent positive pressure ventilation with or without very early surfactant therapy for the primary treatment of respiratory distress syndrome.

AIM: Current evidence suggests that nasal intermittent positive pressure ventilation (NIPPV) as a primary treatment for RDS reduces the duration of invasive mechanical ventilation (MV) comparing with nasal continuous airway pressure (NCPAP). We aimed to evaluate whether very early surfactant treatment decreases the need for MV when used in premature infants treated with early NIPPV soon after birth. METHODS: The inclusion criteria of this prospective cohort study were a gestational age of 24-31(6/7) weeks and supplemental oxygen with the evidence of labored breathing within 60 min. Infants were stabilized on NCPAP and then continued with NIPPV, following early surfactant treatment, or were only put on NIPPV. Thirty infants in the NIPPV group and 29 infants in the NIPPV + SURFACTANT group met the inclusion criteria. Primary end-point was the need of MV in the first 72 h of life according to the predefined criteria. RESULTS: The failure rate was significantly lower in the NIPPV + SURFACTANT group compared with the NIPPV group (37.9% and 66.7% respectively, p < 0.05). All other results, including bronchopulmonary dysplasia and death, were similar between the groups. CONCLUSION: NIPPV failure was significantly lower when combined with surfactant treatment, which indicates the critical role of early surfactant treatment in reducing the need for invasive ventilation.

Impact of Volume Guarantee on High-Frequency Oscillatory Ventilation in Preterm Infants: A Randomized Crossover Clinical Trial.

BACKGROUND: High-frequency oscillatory ventilation (HFOV) with volume guarantee (VG) is a new ventilation mode that allows the clinician to set a mean tidal volume to be delivered. OBJECTIVE: This study aimed to investigate whether HFOV with a VG option may result in constant tidal volume delivery and less fluctuant CO2 levels compared to HFOV alone in premature infants with respiratory distress syndrome (RDS). METHODS: Inborn infants at less than 32 weeks of gestation with RDS requiring invasive mechanical ventilation were eligible. Patients were randomized to receive HFOV + VG or HFOV alone as the initial ventilator mode and then crossed over to the other mode. HFOV was performed with 'optimal lung volume strategy' during both of the periods. RESULTS: Twenty infants were evaluated. The mean high-frequency tidal volume (VThf) and CO2 diffusion coefficient (DCO2) were significantly higher in the HFOV + VG mode than HFOV alone. HFOV + VG maintains VThf within the target range more consistently than HFOV. The incidences of hypocarbia and hypercarbia were lower in HFOV with VG than HFOV alone. CONCLUSION: This is the first prospective, randomized, short-term crossover clinical study that compared HFOV with and without VG in infants with acute RDS. Because of the lower VThf fluctuation and lower incidences of out-of-target PCO2 levels, HFOV combined with VG seems to be feasible for preterm infants. However, the results should be interpreted with caution due to the small sample size and short-term crossover design of the study.

Bacillus Calmette-Guerín vaccination: a novel therapeutic approach to preventing hyperoxic lung injury.

OBJECTIVE: A growing body of evidence suggests that vaccinations play a role in the normal maturation of the immune system and in both the development and balance of immune regulatory pathways that can impact health later in life. This study aimed to evaluate the effects of Bacillus Calmette-Guerín (BCG) vaccine on the hyperoxia-induced neonatal rat lung injury. METHODS: Four groups were defined as hyperoxia-exposed BCG-vaccinated, hyperoxia-exposed placebo, room air-exposed control and room air-exposed BCG-vaccinated group. The validity of the hyperoxia-induced lung injury model used in this study was confirmed by histological and immunohistochemical test. Gene expression related with cytokine and growth factor was evaluated by real-time reverse transcription polymerase chain reaction. RESULT: The mean alveolar surface area and quantification of secondary crest formation in the oxygen-exposed placebo group was significantly lower than that of the oxygen-exposed BCG-vaccinated group. Compared to the oxygen-exposed placebo group, the oxygen-exposed BCG-vaccinated group showed a significantly decreased alveolar septal fibrosis and smooth muscle actin expression. The expression of genes VEGF, FGF-BP1, IL-13, and NFκB1 (p50) in the lungs of the hyperoxia-exposed BCG-vaccinated group was significantly higher than that of the hyperoxia-exposed placebo group. CONCLUSION: Results suggest that BCG vaccination can protect against neonatal hyperoxic lung injury. These benefits may be interpreted to coincide with its immunomodulatory effects on pro-inflammatory and anti-inflammatory cytokine balance and expression of growth factors.