Neonatal Resuscitation Practices in Turkey: A Survey of the Turkish Neonatal Society and the Union of European Neonatal and Perinatal Societies.

OBJECTIVE: Optimal care in the delivery room is important to decrease neonatal morbidity and mortality. We aimed to evaluate neonatal resuscitation practices in Turkish centers. MATERIALS AND METHODS: A cross-sectional survey consisted of a 91-item questionnaire focused on delivery room practices in neonatal resuscitation and was sent to 50 Turkish centers. Hospitals with <2500 and those with ≥2500 births/year were compared. RESULTS: In 2018, approximately 240 000 births occurred at participating hospitals with a median of 2630 births/year. Participating hospitals were able to provide nasal continuous-positiveairway-pressure/high-flow nasal cannula, mechanical ventilation, high-frequency oscillatory ventilation, inhaled nitric oxide, and therapeutic hypothermia similarly. Antenatal counseling was routinely performed on parents at 56% of all centers. A resuscitation team was present at 72% of deliveries. Umbilical cord management for both term and preterm infants was similar between centers. The rate of delayed cord clamping was approximately 60% in term and late preterm infants. Thermal management for preterm infants (<32 weeks) was similar. Hospitals had appropriate equipment with similar rates of interventions and management, except conti nuous-positive-airway-pressure and positive-end-expiratory-pressure levels (cmH2O) used in preterm infants (P = .021, and P = .032). Ethical and educational aspects were also similar. CONCLUSIONS: This survey provided information on neonatal resuscitation practices in a sample of hospitals from all regions of Turkey and allowed us to see weaknesses in some fields. Although adherence to the guidelines was high among centers, further implementations are required in the areas of antenatal counseling, cord management, and circulation assessment in the delivery room.

Relationship between placental autophagy and inflammasome activities with morbidity of extremely preterm infants.

BACKGROUND: The placenta is the major regulatory element of the in-utero environment, and alterations in placental cellular functions in infection, inflammation, and hypoxemia lead to adverse preterm birth outcomes. The importance of regulation of autophagy and inflammasome activities has been shown in the pathogenesis of morbidities in immature animal models. This study aimed to determine the relationship between placental autophagy and inflammasome activities with morbidity in extremely preterm infants. METHODS: Premature infants born between 24th to 29th gestational weeks were evaluated prospectively. Placental LC3B and NLRP3 immunostainings were performed to assess autophagy and inflammasome activities. Preterm morbidities including respiratory distress syndrome (RDS), patent ductus ateriosus: (PDA), intraventricular hemorrhage (IVH), necrotizing enterocolitis (NEC), periventricular leukomalacia (PVL), sepsis, bronchopulmonary dysplasia (BPD), retinopathy of prematurity (ROP) and mortality were evaluated. RESULTS: Fifty-nine infants with a mean gestational age of 26.9 ± 1.5 weeks were included. Anti-LC3B staining scores were moderate or intense positive in 75% of the placentas. Anti-LC3B activity was not associated with the existance of evaluated neonatal morbidities or mortality. Autophagy and inflammasome coexistence were demonstrated in 35 placentas (59.3%). Anti-NLRP3 staining score was moderate or intensely positive in 75% of the placentas. Infants with BPD had a lower rate of positive anti -NLRP3 staining than infants without BPD (42.9 vs 57.1%, p=0.048). Infants who had hemodynamic significant patent ductus arteriosus (hsPDA) and surgical- NEC showed significantly intense anti-NLRP3 staining compared to infants who did not (18.8% vs 0%, p= 0.027 and 33% vs 7.5%, p=0.048 respectively). CONCLUSIONS: The results showed that autophagy and inflammatory activities were present in varying amounts in the placenta of preterm infants. Association of decreased or increased rates of inflammasome activities with certain diseases such as BPD, hsPDA and surgical-NEC indicates the role of the intrauterin inflammatory process and the importance of critical balance in inflammation. Because of the complex pathophysiology of preterm morbidities, placental autophagy and inflammasome activities seem worthy of further investigation.

A novel Mecom gene mutation associated with amegakaryocytic thrombocytopenia in a premature infant.

BACKGROUND: Hereditary bone marrow failure syndromes are a category of biologically different syndromes that can cause cytopenia in at least one hematopoietic cell lineage. CASE: We present a 29-week-old male infant who had a low Apgar Score, advanced delivery room resuscitation, widespread petechial rash, and ecchymoses at birth, without any dysmorphic features. Initial laboratory tests revealed bicytopenia (platelet count 7x10 3 /uL, hemoglobin of 3.9 g/dL, neutrophil 2.0x103 /uL) with findings of disseminated intravasculer coagulation (DIC). Imaging studies demonstrated accompanying left-sided congenital pulmonary airway malformation. On the second postnatal week pancytopenia occurred and the bone marrow findings were consistent with congenital amegakaryocytic thrombocytopenia. Further evaluations for differential diagnosis of pancitopenia were performed and the results of congenital viral infections, metabolic and immunologic tests were negative. While supportive treatments were in progress, haploidentical bone marrow transplantation (BMT) was performed from the father at 84th day due to unavailability of HLA-matched relative or nonrelative donor. Whole exome sequencing revealed a novel heterozygous frameshift variation (c.1242dupT [p. Thr538fs]) in exon 8 of the MECOM gene and validated by Sanger sequencing. No variation was detected in the parents genetic analysis. CONCLUSIONS: In this report, we present a patient with congenital bone marrow failure successfully treated with haploidentic BMT and describe a novel, de novo pathogenic variant in MECOM gene.

Pathophysiologically Based Ventilatory Management of Severe Bronchopulmonary Dysplasia.

Both "new" and "old" bronchopulmonary dysplasia features overlap in preterm infants with severe bronchopulmonary dysplasia. The optimal ventilation strategy for infants with severe bronchopulmonary dysplasia has not been clarified yet. Principally, the lung is a multi-com- partmental heterogeneous tissue with regionally varying compliance and resistance. Generally, 2 critical strategical errors are common while ventilating infants with established bronchopulmonary dysplasia: (i) ventilatory management as if they are still in the acute phase of respiratory distress syndrome and (ii) early extubation attempts with the aim of reducing ventilator-induced lung injury. Considering the heterogeneous character of bronchopulmo- nary dysplasia, although there is no unique formulation for optimal ventilation, the most physi- ologically appropriate ventilation mode may be the combined mode of volume-guaranteed synchronized intermittent mechanical ventilation and pressure support ventilation. With the volume-guaranteed synchronized intermittent mechanical ventilation mode, slow compart- ments of the lung with high resistance and low compliance can be adequately ventilated, while fast compartments having relatively normal resistance and compliance can be venti- lated well with the pressure support ventilation mode. The following settings are advisable: frequency = 12-20 breaths per minute, tidal volume = 10-15 mL/min, positive end expiratory pressure = 7-12 cmH2O, and inspiratory to expiratory time ratio = 1 : 5. Higher oxygen satura- tions such as 92%-95% should be targeted to avoid subsequent pulmonary hypertension. In conclusion, there is no evidence-based ventilation recommendation for infants with severe bronchopulmonary dysplasia. However, given the changing pattern of the disease and the underlying pathophysiology, these infants should not be ventilated as if they were in the acute phase of respiratory distress syndrome.

Comparison of isotonic and hypotonic intravenous fluids in term newborns: is it time to quit hypotonic fluids.

OBJECTIVE: Hypotonic fluids have been traditionally used in newborns. National Institute for Health and Clinical Excellence-2015 (NICE) fluid therapy guideline recommends the use of isotonic fluids as maintenance fluid therapy in term newborns. However, there is no clear evidence supporting this recommendation. This study aims to compare isotonic (5% dextrose in 0.9% sodium chloride (NaCl)) and hypotonic (5% dextrose in 0.45% NaCl) parenteral fluid therapies in hospitalized term newborns with regard to changes in plasma Na (pNa) and complications related with fluid therapy. METHODS: This was a retrospective cohort study performed in a tertiary university hospital NICU between January 2016 and April 2018. Term newborns who were initially isonatremic or mildly dysnatremic (pNa <130 or >155 meq/L) and receiving fluid therapy for maintenance or replacement therapy after 48th postnatal hours were eligible for the study. Infants having specific diagnoses requiring extraordinary fluids were excluded. The primary outcome evaluated was the change in mean plasma Na (ΔpNa meq/L/h) at 24 h or at the end of intravenous (i.v.) fluid therapy. Secondary outcomes evaluated were the risk of hyponatremia, hypernatremia, and adverse events attributable to fluid administration. RESULTS: Among the 108 included newborns, 57 received hypotonic fluid (5% dextrose solution in 0.45% NaCl) and the remaining received isotonic fluid (5% dextrose solution in 0.9% NaCl) therapy. The hypotonic fluid group showed a greater ΔpNa compared to the isotonic group (0.48 ± 0.28 vs. 0.27 ± 0.21 meq/L/h, p = .001). The risk of experiencing unsafe plasma Na decrease in the hypotonic fluid group (ΔpNa >0.5 meq/L/h) was higher than the isotonic fluid group (odd ratio: 8.46; 95% confidence interval (CI): 2.3-30.06). Six mildly hypernatremic babies between 48 and 72 h of postnatal age showed insufficient Na reduction despite the appropriate amount of fluid. No significant difference was found between the two groups in terms of other outcomes. CONCLUSION: The results of this study suggested that as maintenance or replacement fluid therapy in the newborn, hypotonic fluids, even 5% dextrose in 0.45% NaCl, can lead to unsafe plasma Na decreases in term newborns, while isotonic fluids are safe when started after the first few days of life. Although the results parallel NICE guidelines, before making recommendations regarding the removal of hypotonic fluids entirely from clinical practice in term newborns following the renal adaptation period; larger randomized controlled studies involving a wide range of babies are needed.

The role of MRI-based texture analysis to predict the severity of brain injury in neonates with perinatal asphyxia.

OBJECTIVE: To evaluate the efficacy of the MRI-based texture analysis (TA) of the basal ganglia and thalami to distinguish moderate-to-severe hypoxic-ischemic encephalopathy (HIE) from mild HIE in neonates. METHODS: This study included 68 neonates (15 with mild, 20 with moderate-to-severe HIE, and 33 control) were born at 37 gestational weeks or later and underwent MRI in first 10 days after birth. The basal ganglia and thalami were delineated for TA on the apparent diffusion coefficient (ADC) maps, T1-, and T2 weighted images. The basal ganglia, thalami, and the posterior limb of the internal capsule (PLIC) were also evaluated visually on diffusion-weighted imaging and T1 weighted sequence. Receiver operating characteristic curve and logistic regression analyses were used. RESULTS: Totally, 56 texture features for the basal ganglia and 46 features for the thalami were significantly different between the HIE groups on the ADC maps, T2-, and T2 weighted sequences. Using a Histogram_entropy log-10 value as >1.8 from the basal ganglia on the ADC maps (p < 0.001; OR, 266) and the absence of hyperintensity of the PLIC on T1 weighted images (p = 0.012; OR, 17.11) were found as independent predictors for moderate-to-severe HIE. Using only a Histogram_entropy log-10 value had an equal diagnostic yield when compared to its combination with other texture features and imaging findings. CONCLUSION: The Histogram_entropy log-10 value can be used as an indicator to differentiate from moderate-to-severe to mild HIE. ADVANCES IN KNOWLEDGE: MRI-based TA may provide quantitative findings to indicate different stages in neonates with perinatal asphyxia.

Current factors affecting the risk of omphalitis in newborns: A prospective case-control study.

AIM: We aimed to determine the current factors affecting the development of omphalitis in our region. MATERIALS AND METHODS: This prospective case-control study included term and late preterm newborns admitted to the newborn outpatient clinic or paediatric emergency service between 2014 and 2015. One hundred newborns with omphalitis and age-matched 100 newborns as a control group were included. The perinatal, postnatal, and sociocultural characteristics of newborns were evaluated and the factors that could influence the development of omphalitis were determined. RESULTS: Younger maternal age and primiparity, lower maternal education, and lower maternal hand washing habits were the significant risk factors of omphalitis development. Using non-cotton clothes were the most important risk factor amongst all factors as it increases the omphalitis risk up to 13 times. The frequency of omphalitis was significantly higher in warm months when microorganisms were able to colonise and reproduce compared with the colder months. CONCLUSION: Results suggested that community-based interventions promoting the improvement of neonatal care should emphasise simple and low-cost interventions such as hand washing habit of mothers, caring for the umbilical cord, and using cotton clothes for babies. This study also confirms the safety of dry cord care at the time of birth and afterwards. However, broadscale multicentric studies are needed to protect against omphalitis.

Epigenetic Programming Through Breast Milk and Its Impact on Milk-Siblings Mating.

BACKGROUND: The epigenetic effects of transmission of certain regulatory molecules, such as miRNAs, through maternal milk on future generations, are still unknown and have not been fully understood yet. We hypothesized that breastfeeding regularly by adoptive-mother may cause transmission of miRNAs as epigenetic regulating factors to the infant, and the marriage of milk-siblings may cause various pathologies in the future generations. RESULTS: A cross-fostering model using a/a and A vy /a mice had been established. F2 milk-sibling and F2 control groups were obtained from mating of milk-siblings or unrelated mice. Randomized selected animals in the both F2 groups were sacrificed for miRNA expression studies and the remainings were followed for phenotypic changes (coat color, obesity, hyperglycemia, liver pathology, and life span). The lifespan in the F2 milk-sibling group was shorter than the control group (387 vs 590 days, p = 0.011) and they were more obese during the aging period. Histopathological examination of liver tissues revealed abnormal findings in F2 milk-sibling group. In order to understand the epigenetic mechanisms leading to these phenotypic changes, we analyzed miRNA expression differences between offspring of milk-sibling and control matings and focused on the signaling pathways regulating lifespan and metabolism. Bioinformatic analysis demonstrated that differentially expressed miRNAs were associated with pathways regulating metabolism, survival, and cancer development such as the PI3K-Akt, ErbB, mTOR, and MAPK, insulin signaling pathways. We further analyzed the expression patterns of miR-186-5p, miR-141-3p, miR-345-5p, and miR-34c-5p and their candidate target genes Mapk8, Gsk3b, and Ppargc1a in ovarian and liver tissues. CONCLUSION: Our findings support for the first time that the factors modifying the epigenetic mechanisms may be transmitted by breast milk and these epigenetic interactions may be transferred transgenerationally. Results also suggested hereditary epigenetic effects of cross-fostering on future generations and the impact of mother-infant dyad on epigenetic programming.

An Observational, Prospective, Multicenter, Registry-Based Cohort Study Comparing Conservative and Medical Management for Patent Ductus Arteriosus.

No consensus has been reached on which patent ductus arteriosus (PDAs) in preterm infants require treatment and if so, how, and when they should be treated. A prospective, multicenter, cohort study was conducted to compare the effects of conservative approaches and medical treatment options on ductal closure at discharge, surgical ligation, prematurity-related morbidities, and mortality. Infants between 240/7 and 286/7 weeks of gestation from 24 neonatal intensive care units were enrolled. Data on PDA management and patients' clinical characteristics were recorded prospectively. Patients with moderate-to-large PDA were compared. Among the 1,193 enrolled infants (26.7 ± 1.4 weeks and 926 ± 243 g), 649 (54%) had no or small PDA, whereas 544 (46%) had moderate-to-large PDA. One hundred thirty (24%) infants with moderate-to-large PDA were managed conservatively, in contrast to 414 (76%) who received medical treatment. Eighty (62%) of 130 infants who were managed conservatively did not receive any rescue treatment and the PDA closure rate was 53% at discharge. There were no differences in the rates of late-onset sepsis, necrotizing enterocolitis (NEC), retinopathy of prematurity, intraventricular hemorrhage (≥Grade 3), surgical ligation, and presence of PDA at discharge between conservatively-managed and medically-treated infants (p > 0.05). Multivariate analysis including perinatal factors showed that medical treatment was associated with increased risk for mortality (OR 1.68, 95% Cl 1.01-2.80, p = 0.046), but decreased risk for BPD or death (BPD/death) (OR 0.59, 95%Cl 0.37-0.92, p = 0.022). The preferred treatment options were ibuprofen (intravenous 36%, oral 31%), and paracetamol (intravenous 26%, oral 7%). Infants who were treated with oral paracetamol had higher rates of NEC and mortality in comparison to other treatment options. Infants treated before postnatal day 7 had higher rates of mortality and BPD/death than infants who were conservatively managed or treated beyond day 7 (p = 0.009 and 0.007, respectively). In preterm infants born at <29 weeks of gestation with moderate-to-large PDA, medical treatment did not show any reduction in the rates of open PDA at discharge, surgical or prematurity-related secondary outcomes. In addition to the high incidence of spontaneous closure of PDA in the first week of life, early treatment (<7 days) was associated with higher rates of mortality and BPD/death.

Endotracheal Surfactant Combined With Budesonide for Neonatal ARDS.

Acute respiratory distress syndrome (ARDS) is a clinical condition characterized by acute diffuse inflammatory lung injury and severe hypoxemia. In 2017, the Montreux Consensus defined diagnostic criteria for ARDS in the neonatal period. The management of ARDS includes strict adherence to lung-protective ventilation strategies and therapeutic agents to improve gas exchange. We report two similar cases of premature infants with gestational ages of 23 and 24 weeks diagnosed with neonatal ARDS according to the Montreux definition. These patients developed acute worsening of oxygenation on the 30th and 28th day of life, respectively, while they were ventilated on volume-guarantee assist/control mode. Chest X-rays revealed bilateral diffuse opacity, there were no cardiogenic origins for pulmonary edema, and their oxygenation indexes were >8. Both cases fulfilled the neonatal ARDS criteria and the patients' clinical conditions were associated with late onset neonatal sepsis. After lung recruitment maneuver, the infants began HFO volume-guarantee ventilation and received surfactant treatment. Since they showed a poor short-term response, intratracheal surfactant of 100 mg/kg plus budesonide of 0.25 mg/kg were administered and their oxygenation indexes were reduced stepwise. Both patients survived and were discharged home with spontaneous breathing of room air. Neonatal ARDS is generally an underdiagnosed condition associated with sepsis, pneumonia, and meconium aspiration. Impaired surfactant activity and reduced lung compliance play important roles in its pathophysiology. To our knowledge, this is the first case report indicating the possible therapeutic role of budesonide plus surfactant in ARDS treatment. Since ARDS is an entity not recognized in newborns, we want to emphasize neonatal ARDS diagnosis and underline that the combination of budesonide and surfactant may be a novel therapeutic option in the treatment of ARDS.

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.

Is European Medicines Agency (EMA) sepsis criteria accurate for neonatal sepsis diagnosis or do we need new criteria?

BACKGROUND: Currently, there is a lack of clear definition for neonatal sepsis. The Pediatric Committee of the European Medicines Agency (EMA) developed consensus criteria to ensure a standardization for neonatal sepsis definition. However, there is no evidence supporting the accuracy of the EMA sepsis criteria in neonatal sepsis diagnosis. The main objective of this study was to evaluate the diagnostic accuracy of EMA sepsis criteria for proven neonatal sepsis. METHODS: A multicenter prospective cohort study was conducted from October 2015 to November 2018. Infants with a gestational age over 34th weeks, diagnosed with clinical sepsis and received antibiotics according to the EMA criteria or experienced neonatologists' opinion were included. Blood culture or multiplex real time-PCR or 16S-rRNA positive infants were accepted as "proven sepsis". The predictive performance of EMA criteria for proven sepsis was evaluated by sensitivity, specificity, accuracy, and area under the curve measures of receiver operator characteristic curves. Data-mining methods were used for further analysis. RESULTS: Among the 245 included infants, the EMA criteria were positive in 97 infants (39.6%), while proven sepsis was diagnosed in 113 infants (46.1%). The sensitivity, specificity, and accuracy of the EMA criteria for proven sepsis were 44.2% (95%CI: 34.9-53.9), 64.4% (95%CI: 55.6-72.5), 55.1% (95%CI: 46.6-59.4) respectively. None of the clinical and laboratory parameters had sufficient performance individually in terms of sensitivity, specificity and accuracy measures. The diagnostic performance was similar when different clinical findings were added to the EMA sepsis criteria or assessment of the score was interpreted in different ways. CONCLUSIONS: Results highlighted that clinician opinion and standard laboratory tests are limited in the neonatal sepsis diagnosis. The EMA criteria also did not efficiently meet the diagnostic accuracy measures for neonatal sepsis. A predictive sepsis definition and rapid bedside point-of care tests are urgently needed.

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.

Comparison of INTERGROWTH-21 and Fenton growth standards to assess size at birth and extrauterine growth in very preterm infants.

AIM: This study aimed to compare the recently published prescriptive INTERGROWTH-21st standards with commonly used intrauterine based Fenton growth standards in terms of birth size classification and extrauterine growth restriction (EUGR) incidence in a sample of very preterm infants. METHODS: The anthropometric measures of preterm infants born before 32 weeks of gestation at the Dokuz Eylul University Hospital during the period from January 2012 to February 2016 were obtained at birth, at the 36th gestational weeks or at the time of discharge. Birth and growth data were presented as percentiles according to the two reference standards. RESULTS: A total of 248 infants with mean gestational age of 29.1 ± 2.1 weeks were included. The small for gestational age (SGA) rate was significantly higher (12 versus 15%, p = .004) and the EUGR rate was significantly lower (40.2 versus 31.5%, p < .001) with the INTERGROWTH-21st charts compared with the Fentons'. Twenty-four per cent of the infants who were accepted as SGA according to the INTERGROWTH-21st standards were appropriate for gestational age (AGA) according to the Fenton preterm growth charts. However, these newly identified SGA infants according to the Intergrowth-21st standards did not have increased risks of early morbidities. Furthermore, 77% of the cases who had EUGR due to the Fenton standards were categorized as EUGR when evaluated using the INTERGROWTH-21st standards. CONCLUSIONS: Results indicated that almost one out of every five cases assessed as EUGR according to Fenton standards was within the normal interval according to Intergrowth standards. On the contrary, one out of every four cases assessed as SGA according to the INTERGROWTH-21st standards was within the normal interval according to Fentons'. These differences observed with INTERGROWTH-21st standards may affect in-hospital and postdischarge nutrition plan of these vulnerable infants. However, new standards are needed to be evaluated against currently used ones before they are implemented and further studies should be conducted to evaluate the functional impact of these differences on long-term outcomes including neurologic and cardio-metabolic morbidities.

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.