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Limited data are available on pregnant women with COVID-19 and their neonates. We aimed to evaluate the epidemiological and clinical characteristics of newborns born to women infected with COVID-19. A multicenter cohort study was conducted among newborns born to mothers with COVID-19 in 34 neonatal intensive care units (NICUs) in Turkey. Pregnant women (n = 125) who had a positive RT-PCR test and their newborns were enrolled. Cesarean section, prematurity, and low-birthweight infant rates were 71.2%, 26.4%, and 12.8%, respectively. Eight of 125 mothers (6.4%) were admitted to an intensive care unit for mechanical ventilation, among whom six died (4.8%). Majority of the newborns (86.4%) were followed in isolation rooms in the NICU. Four of 120 newborns (3.3%) had a positive RT-PCR test result. Although samples taken on the first day were negative, one neonate became positive on the second day and the other two on the fifth day. Sample from deep tracheal aspirate was positive on the first day in an intubated case.Conclusion: COVID-19 in pregnant women has important impacts on perinatal and neonatal outcomes. Maternal mortality, higher rates of preterm birth and cesarean section, suspected risk of vertical transmission, and low rate of breastfeeding show that family support should be a part of the care in the NICU.Trial registration: ClinicalTrials.gov identifier: NCT04401540What is Known:• The common property of previous reports was the conclusions on maternal outcomes, rather than neonatal outcomes.• Published data showed similar outcomes between COVID-19 pregnant women and others.What is New:• Higher maternal mortality, higher rates of preterm birth and cesarean section, suspected risk of vertical transmission especially in a case with deep tracheal aspiration during the intubation, and the possible role of maternal disease severity on the outcomes are remarkable findings of this study.• In contrast to recommendation for breastfeeding, parents’ preference to formula and expressed breast milk due to anxiety and lack of information shows that family support should be a part of the care in the NICU.

Background/Objectives: The optimal rate of enteral feeding advancement in preterm infants remains uncertain despite decades of clinical research. This uncertainty arises from concerns that rapid feeding progression may increase the risk of feeding intolerance and necrotizing enterocolitis (NEC), two major causes of morbidity and mortality in this population. The feeding rate may also influence intestinal oxygenation due to mesenteric hemodynamic changes during feeding. This study aimed to evaluate whether the rate of enteral feeding advancement (slow vs. rapid) affects intestinal oxygenation and its association with feeding intolerance (FI) or necrotizing enterocolitis in very low birth weight preterm infants. Methods: This prospective, randomized, two-center study included infants born at 28–32 weeks of gestation. Group 1 received slow advancement (20 mL/kg/day) and Group 2 rapid advancement (30 mL/kg/day) of enteral feeds. Splanchnic (srSO2) and cerebral (crSO2) oxygenation were monitored daily using the FDA-approved INVOS NIRS device during feeding periods (08:00–16:00). Monitoring was performed during minimal enteral nutrition (Phase 1), advancement phases (Phase 2), and for two days after achieving full enteral feeding (Phase 3). The splanchnic-to-cerebral oxygenation ratio (SCOR) was also calculated. Percentage changes in srSO2 and SCOR during and after feeding were calculated from baseline (prefeeding) values and analyzed. Results: Sixty infants were enrolled. Mean gestational age and birth weight were 29.76 ± 1.33 weeks and 1375.05 ± 271.19 g, respectively. Group 2 achieved full enteral feeding significantly earlier (p = 0.001), with no other demographic differences between groups. No cases of NEC were observed. Feeding intolerance occurred in 14 infants (23.3%): 8 in Group 1 and 6 in Group 2 (p = 0.192). Both groups exhibited increased srSO2 and SCOR during feeding; however, the between-group differences were not statistically significant (Phase 2 srSO2 and SCOR: p = 0.07, 0.08; Phase 3 srSO2 and SCOR: p = 0.069, 0.071). However, the percentage change from baseline in srSO2 and SCOR during and after feeding was significantly greater in Group 2 during the advancement and full enteral feeding phases (Phase 2 srSO2 and SCOR: p = 0.03, 0.022; Phase 3 srSO2 and SCOR: p = 0.015, 0.048). Infants with feeding intolerance demonstrated significantly lower srSO2 and SCOR values compared to tolerant infants, and this reduction persisted even after reaching full enteral feeding. ROC analysis suggested gestational age < 30 weeks, birth weight < 1180 g, srSO2 < 52, and SCOR < 0.6 were associated with feeding intolerance. Conclusions: Intermittent bolus feeding increased intestinal oxygenation, with a more pronounced effect in the rapid advancement group. No difference in gastrointestinal adverse outcomes was observed between groups. Lower intestinal oxygenation was associated with feeding intolerance, and the suggested predictive criteria may help guide individualized feeding strategies.

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. 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. 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. 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.

Objectives: In the neonatal period, 25% of cases with critical congenital heart disease (CCHD) require surgical or interventional palliative and corrective procedures. Prenatal diagnosis and timely intervention can positively impact neonatal mortality and morbidity. This study evaluated the effects of perinatal follow-up on the management of CCHD. Methods: The study was conducted on term neonates diagnosed with CCHD, who were monitored in the neonatology and pediatric cardiac intensive care unit between 1 January 2023 and 1 January 2024. The cases were categorized into CCHD with prenatal follow-up (Group I), CCHD born without follow-up at our hospital (Group II), and CCHD accepted from external centers (Group III). Neonatal mortality and morbidity outcomes of these cases that underwent surgical or interventional procedures were statistically evaluated. Results: During the study period, there were 280 neonatal cases (50% male). Among these cases, 30% were in Group I (n = 84), 20% in Group II (n = 56), and 50% in Group III (n = 140). The cesarean section rate was higher in Group I compared to the other groups (80% vs. 52% vs. 45%), and the preoperative lactate levels were lower (0.9 vs. 1.7 vs. 2.1). The anatomical diagnoses, ventricular physiology, operation time, and interventional procedure time were similar. After interventional or surgical procedures, morbidity (22% vs. 25% vs. 36%) and mortality rates (6% vs. 9% vs. 18%) were lower in Group I and Group II compared to Group III. Conclusions: All infants diagnosed with CCHD before birth should be delivered in a tertiary heart center, which positively contributes to neonatal mortality and morbidity. More effort is needed to improve prenatal screening programs.

Background/Objectives: Caffeine citrate represents the standard pharmacological intervention for apnea of prematurity (AOP) and episodes of intermittent hypoxia (IH). Despite its widespread use, consensus regarding the necessity of routine serum monitoring, optimal dosing protocols, and precise clinical indications remains elusive. The primary objective of this investigation was to evaluate the longitudinal trajectory of serum caffeine concentrations in preterm infants and to analyze their correlation with the incidence of AOP and IH episodes. Furthermore, we sought to determine whether blood caffeine concentrations varied significantly across gestational ages throughout the postnatal period. Methods: This multicenter, prospective observational study enrolled preterm infants with a gestational age of ≤30 weeks. Participants were administered a standard loading dose of caffeine citrate within the first 24 h of life, followed by a standardized maintenance regimen. Serum caffeine levels were quantified on a weekly basis. The cohort was stratified into two distinct groups based on gestational age: Group 1 (23–27 weeks) and Group 2 (28–30 weeks). Results: The study yielded 588 serum caffeine measurements from a cohort of 104 preterm infants, characterized by a median gestational age of 28 weeks (range: 23–30 weeks) and a mean birth weight of 1034 ± 296 g. Statistical analysis revealed no significant disparities in serum caffeine concentrations across gestational age groups (p > 0.05). Notably, during the third week of life, infants with apneic episodes demonstrated significantly lower caffeine levels than those without apnea (p = 0.016). Furthermore, a significant negative correlation was identified between serum caffeine concentrations and the frequency of IH episodes during the third, fourth, and fifth weeks of life across multiple oxygen saturation thresholds. Conclusions: While serum caffeine concentrations in preterm infants did not vary significantly with gestational age, lower levels were associated with a higher incidence of AOP and IH episodes. These results suggest that while routine monitoring or dose adjustment based solely on gestational age may not be warranted, maintaining adequate serum levels is critical for symptom management. Future research should prioritize randomized controlled trials with expanded sample sizes, extended follow-up periods, and a rigorous analysis of adverse effects.

To achieve gas exchange goals and mitigate lung injury, infants who fail with conventional ventilation (CV) are generally switched to high-frequency oscillatory ventilation (HFOV). Although preferred in many neonatal intensive care units (NICUs), research on this type of rescue HFOV has not been reported recently. An online registry database for a multicenter, prospective study was set to evaluate factors affecting the response of newborn infants to rescue HFOV treatment. The study population consisted of 372 infants with CV failure after at least 4 hours of treatment in 23 participating NICUs. Patients were grouped according to their final outcome as survived (Group S) or as died or received extracorporeal membrane oxygenation (ECMO) (Group D/E). Patients' demographic characteristics and underlying diseases in addition to their ventilator settings, arterial blood gas (ABG) analysis results at 0, 1, 4, and 24 hours, type of device, ventilation duration, and complications were compared between groups. HFOV as rescue treatment was successful in 58.1% of patients. Demographic and treatment parameters were not different between groups, except that infants in Group D/E had lower birthweight (BW) (1655 ± 1091 vs. 1858 ± 1027 g, p = 0.006), a higher initial FiO2 setting (83% vs. 72%, p < 0.001), and a higher rate of nitric oxide exposure (21.8% vs. 11.1%, p = 0.004) in comparison to infants who survived (Group S). The initial cut-offs for a successful response on ABG were defined as pH >7.065 (OR: 19.74, 95% CI 4.83-80.6, p < 0.001), HCO3 >16.35 mmol/L (OR: 1.06, 95% CI 1.01-1.1, p = 0.006), and lactate level <3.75 mmol/L (OR: 1.09%95 CI 1.01-1.16, p = 0.006). Rescue HFOV duration was associated with retinopathy of prematurity (p = 0.005) and moderate or severe chronic lung disease (p < 0.001), but not with patent ductus arteriosus or intraventricular hemorrhage, in survivors (p > 0.05). Rescue HFOV as defined for this population was successful in more than half of the patients with CV failure. Although the response was not associated with gestational age, underlying disease, device used, or initial MV settings, it seemed to be more effective in patients with higher BW and those not requiring nitric oxide. Initial pH, HCO3, and lactate levels on ABG may be used as predictors of a response to rescue HFOV.

Histone acetylation and deacetylation may play a role in the pathogenesis of inflammatory lung diseases. We evaluated the preventive effect of valproic acid (VPA), a histone deacetylase (HDAC) inhibitor, on neonatal hyperoxic lung injury. Forty newborn rat pups were randomized in normoxia, normoxia+VPA, hyperoxia and hyperoxia+VPA groups. Pups in the normoxia and normoxia+VPA groups were kept in room air and received daily saline and VPA (30 mg/kg) injections, respectively, while those in hyperoxia and hyperoxia+VPA groups were exposed to 95% O2 and received daily saline and VPA (30 mg/kg) injections for 10 days, respectively. Growth, histopathological, biochemical and molecular biological indicators of lung injury, apoptosis, inflammation, fibrosis and histone acetylation were evaluated. VPA treatment during hyperoxia significantly improved weight gain, histopathologic grade, radial alveolar count and lamellar body membrane protein expression, while it decreased number of TUNEL(+) cells and active Caspase-3 expression. Expressions of TGFβ3 and phospho-SMAD2 proteins and levels of tissue proinflammatory cytokines as well as lipid peroxidation biomarkers were reduced, while anti-oxidative enzyme activities were enhanced by VPA treatment. VPA administration also reduced HDAC activity while increasing acetylated H3 and H4 protein expressions. The present study shows for the first time that VPA treatment ameliorates lung damage in a neonatal rat model of hyperoxic lung injury. The preventive effect of VPA involves HDAC inhibition.

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Background Fetal growth restriction (FGR) is a major cause of perinatal morbidity and mortality. In patients with absent end-diastolic flow (AEDF) in the umbilical artery, placental insufficiency is typically severe, and adverse neonatal outcomes are common. The modified myocardial performance index (Mod-MPI) provides a noninvasive assessment of global fetal cardiac function; however, its relationship with Doppler findings and perinatal outcomes in patients with FGR remains under investigation. Methods This prospective observational study included 217 singleton pregnancies between 24 + 0 and 36 + 0 weeks of gestation. Among these, 103 fetuses were diagnosed with FGR and subdivided on the basis of the presence ( n  = 47) or absence ( n  = 56) of AEDF. The control group included 114 gestational age-matched fetuses with normal growth and Doppler findings. Left ventricular Mod-MPI and cardiac time intervals were measured via a standardized pulsed-wave Doppler technique on the basis of valvular motion timing. The mitral inflow E- and A-wave velocities were also recorded. Perinatal outcomes such as gestational age at delivery, birth weight, 5-minute Apgar score, and NICU admission were compared. Results Although the mean Mod-MPI values were not significantly different between the groups ( p  = 0.38), AEDF-positive fetuses had shorter ejection times and significantly lower mitral E and A velocities ( p  < 0.001). These findings indicate impaired diastolic function. Compared with other groups, AEDF-positive fetuses were delivered earlier, had lower birth weights, and had higher NICU admission rates ( p  < 0.01). Conclusions In fetuses with FGR, the presence of AEDF is associated with early signs of cardiac dysfunction and poor perinatal outcomes. While the mean Mod-MPI may not differ markedly, its components reflect significant hemodynamic compromise. Mod-MPI may be a useful adjunct for monitoring fetal well-being in cases of severe placental insufficiency.

Background This study aimed to investigate the prenatal features, genetic findings, and perinatal outcomes of fetuses with congenital anomalies of the kidney and urinary tract (CAKUT), with a particular focus on associations with additional structural or chromosomal abnormalities. Methods A retrospective cohort analysis was conducted on 277 fetuses diagnosed with CAKUT between December 2020 and December 2024 at a tertiary center. Data on anomaly subtypes, associated findings, genetic testing, pregnancy outcomes, and postnatal follow-up were evaluated. Logistic regression was used to identify predictors of termination. Results Urinary tract dilatation was the most frequent anomaly (28.2%), followed by multicystic dysplastic kidney (11.6%) and bilateral renal agenesis (11.2%). Extrarenal anomalies were present in 33.9% of fetuses, primarily involving the CNS. Genetic testing was performed in 48.4%; chromosomal abnormalities were found in 17.3%, most commonly trisomy 21 (5.8%). Termination was significantly associated with early diagnosis (adjusted OR = 0.82; p  < 0.001), oligohydramnios (OR = 4.94; p  < 0.001), CNS (OR = 3.74; p  = 0.001), and cardiac anomalies (OR = 4.21; p  = 0.002). Neonatal death occurred in 29.2% of cases, and mortality was higher in non-isolated anomalies (60% vs. 32.9%, p  < 0.001). Conclusions Fetuses with CAKUT, particularly those with early diagnosis or coexisting anomalies, carry a higher risk of adverse outcomes. Prenatal detection, coupled with comprehensive genetic and structural evaluation, is essential for informed counseling and postnatal planning.