An observational, multicenter, registry-based cohort study of Turkish Neonatal Society in neonates with Hypoxic ischemic encephalopathy.

BACKGROUND: Hypoxic ischemic encephalopathy (HIE) is a significant cause of mortality and short- and long-term morbidities. Therapeutic hypothermia (TH) has been shown to be the standard care for HIE of infants ≥36 weeks gestational age (GA), as it has been demonstrated to reduce the rates of mortality, and adverse neurodevelopmental outcomes. This study aims to determine the incidence of HIE in our country, to assess the TH management in infants with HIE, and present short-term outcomes of these infants. METHODS: The Turkish Hypoxic Ischemic Encephalopathy Online Registry database was established for this multicenter, prospective, observational, nationally-based cohort study to evaluate the data of infants born at ≥34 weeks GA who displayed evidence of neonatal encephalopathy (NE) between March, 2020 and April 2022. RESULTS: The incidence of HIE among infants born at ≥36 weeks GA (n = 965) was 2.13 per 1000 live births (517:242440), and accounting for 1.55% (965:62062) of all neonatal intensive care unit admissions. The rates of mild, moderate and severe HIE were 25.5% (n = 246), 58.9% (n = 568), and 15.6% (n = 151), respectively. Infants with severe HIE had higher rates of abnormal magnetic resonance imaging (MRI) findings, and mortality (p<0.001). No significant difference in mortality and abnormal MRI results was found according to the time of TH initiation (<3 h, 3-6 h and >6 h) (p>0.05). TH was administered to 85 (34.5%) infants with mild HIE, and of those born of 34-35 weeks of GA, 67.4% (n = 31) received TH. A total of 58 (6%) deaths were reported with a higher mortality rate in infants born at 34-35 weeks of GA (OR 3.941, 95% Cl 1.446-10.7422, p = 0.007). CONCLUSION: The incidence of HIE remained similar over time with a reduction in mortality rate. The timing of TH initiation, whether <3 or 3-6 h, did not result in lower occurrences of brain lesions on MRI or mortality. An increasing number of infants with mild HIE and late preterm infants with HIE are receiving TH; however, the indications for TH require further clarification. Longer follow-up studies are necessary for this vulnerable population.

A Population Model of Time-Dependent Changes in Serum Creatinine in (Near)term Neonates with Hypoxic-Ischemic Encephalopathy During and After Therapeutic Hypothermia.

The objective was to apply a population model to describe the time course and variability of serum creatinine (sCr) in (near)term neonates with moderate to severe encephalopathy during and after therapeutic hypothermia (TH). The data consisted of sCr observations up to 10 days of postnatal age in neonates who underwent TH during the first 3 days after birth. Available covariates were birth weight (BWT), gestational age (GA), survival, and acute kidney injury (AKI). A previously published population model of sCr kinetics in neonates served as the base model. This model predicted not only sCr but also the glomerular filtration rate normalized by its value at birth (GFR/GFR0). The model was used to compare the TH neonates with a reference full term non-asphyxiated population of neonates. The estimates of the model parameters had good precision and showed high between subject variability. AKI influenced most of the estimated parameters denoting a strong impact on sCr kinetics and GFR. BWT and GA were not significant covariates. TH transiently increased [Formula: see text] in TH neonates over the first days compared to the reference group. Asphyxia impacted not only GFR, but also the [Formula: see text] synthesis rate. We also observed that AKI neonates exhibit a delayed onset of postnatal GFR increase and have a higher [Formula: see text] synthesis rate compared to no-AKI patients. Our findings show that the use of [Formula: see text] as marker of renal function in asphyxiated neonates treated with TH to guide dose selection for renally cleared drugs is challenging, while we captured the postnatal sCr patterns in this specific population.

Serum Creatinine Patterns in Neonates Treated with Therapeutic Hypothermia for Neonatal Encephalopathy.

INTRODUCTION: There is large variability in kidney function and injury in neonates with neonatal encephalopathy (NE) treated with therapeutic hypothermia (TH). Acute kidney injury (AKI) definitions that apply categorical approaches may lose valuable information about kidney function in individual patients. Centile serum creatinine (SCr) over postnatal age (PNA) may provide more valuable information in TH neonates. METHODS: Data from seven TH neonates and one non-TH-treated, non-NE control cohorts were pooled in a retrospective study. SCr centiles over PNA, and AKI incidence (definition: SCr ↑≥0.3 mg/dL within 48 h, or ↑ ≥1.5 fold vs. the lowest prior SCr within 7 days) and mortality were calculated. Repeated measurement linear models were applied to SCr trends, modeling SCr on PNA, birth weight or gestational age (GA), using heterogeneous autoregressive residual covariance structure and maximum likelihood methods. Findings were compared to patterns in the control cohort. RESULTS: Among 1,136 TH neonates, representing 4,724 SCr observations, SCr (10th-25th-50th-75th-90th-95th) PNA centiles (day 1-10) were generated. In TH neonates, the AKI incidence was 132/1,136 (11.6%), mortality 193/1,136 (17%). AKI neonates had a higher mortality (37.2-14.3%, p < 0.001). Median SCr patterns over PNA were significantly higher in nonsurvivors (p < 0.01) or AKI neonates (p < 0.001). In TH-treated neonates, PNA and GA or birth weight explained SCr variability. Patterns over PNA were significantly higher in TH neonates to controls (801 neonates, 2,779 SCr). CONCLUSIONS: SCr patterns in TH-treated NE neonates are specific. Knowing PNA-related patterns enable clinicians to better assess kidney function and tailor pharmacotherapy, fluids, or kidney supportive therapies.

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.

Early neonatal outcomes of very-low-birth-weight infants in Turkey: A prospective multicenter study of the Turkish Neonatal Society.

OBJECTIVE: To investigate the early neonatal outcomes of very-low-birth-weight (VLBW) infants discharged home from neonatal intensive care units (NICUs) in Turkey. MATERIAL AND METHODS: A prospective cohort study was performed between April 1, 2016 and April 30, 2017. The study included VLBW infants admitted to level III NICUs. Perinatal and neonatal data of all infants born with a birth weight of ≤1500 g were collected for infants who survived. RESULTS: Data from 69 NICUs were obtained. The mean birth weight and gestational age were 1137±245 g and 29±2.4 weeks, respectively. During the study period, 78% of VLBW infants survived to discharge and 48% of survived infants had no major neonatal morbidity. VLBW infants who survived were evaluated in terms of major morbidities: bronchopulmonary dysplasia was detected in 23.7% of infants, necrotizing enterocolitis in 9.1%, blood culture proven late-onset sepsis (LOS) in 21.1%, blood culture negative LOS in 21.3%, severe intraventricular hemorrhage in 5.4% and severe retinopathy of prematurity in 11.1%. Hemodynamically significant patent ductus arteriosus was diagnosed in 24.8% of infants. Antenatal steroids were administered to 42.9% of mothers. CONCLUSION: The present investigation is the first multicenter study to include epidemiological information on VLBW infants in Turkey. Morbidity rate in VLBW infants is a serious concern and higher than those in developed countries. Implementation of oxygen therapy with appropriate monitoring, better antenatal and neonatal care and control of sepsis may reduce the prevalence of neonatal morbidities. Therefore, monitoring standards of neonatal care and implementing quality improvement projects across the country are essential for improving neonatal outcomes in Turkish NICUs.

Decreased bone ultrasound velocity in premature infants conceived with assisted reproduction.

Quantitative ultrasound (QUS) measurement of tibial speed of sound (SOS) can be used to determine bone strength. Children conceived with assisted reproduction treatments (ART) are taller than naturally conceived (NC) children, so we hypothesized that these infants would have higher SOS levels than NC infants. Thirty-seven ART (ART group) and 51 NC neonates (NC group) were included in the study. Tibial initial SOS (iSOS) was measured within 96 hours of birth using QUS. Measurements were performed weekly until the infant was discharged from the hospital. The iSOS levels of the ART group (2823.41±110.8 m/sec) were lower than those of the NC group (2917.14±145.6 m/sec) (p=0.001). A decrease in SOS levels was observed in 39 of 53 infants who had serial scans. The difference in SOS levels between the first and last scan was significant (p<0.02). In vitro manipulation during the periconceptual period can result in metabolic alterations in bone mineral content. Contrary to our null hypothesis, bone SOS of infants in the ART group was found to be lower than in the NC group. Moreover, bone SOS decreases in early postnatal life. This result emphasizes the fact that even with advances in nutritional care, the ex utero environment remains a poor substitute for in utero development.

Ponderal index of large-for-gestational age infants: comparison between infants of diabetic and non-diabetic mothers.

Ponderal index (PI) is a weight-height related parameter that is mainly used to assess the pattern of fetal growth in small-for-gestational age infants. We aimed to use PI for large-for-gestational age (LGA) infants who were born to diabetic or non-diabetic mothers, in order to predict the fetal growth pattern. One hundred sixty-six LGA infants born at the Department of Obstetrics, Hacettepe University Hospital, Ankara, Turkey were included in the study. The PI was calculated by using the following formula: PI = weight (g) x 100/(height, cm)3. Sixty-seven (40%) of these infants were born to diabetic mothers. Maternal age, maternal weight and maternal weight gain during pregnancy were similar in the diabetic and non-diabetic groups. Mean birthweight, height and head circumference were similar in both groups, but median PI of infants of diabetic mothers was significantly higher than of infants of non-diabetic mothers (3.02 and 2.89, respectively, p < 0.05). Fetal growth was different between LGA infants of diabetic and non-diabetic mothers, and PI provided useful information on the proportionality of fetal growth in LGA infants.

Inhaled beta-2 agonist salbutamol for the treatment of transient tachypnea of the newborn.

OBJECTIVE: To evaluate the efficacy of inhaled salbutamol, a beta-2 adrenergic agonist, for the treatment of transient tachypnea of the newborn (TTN) and to determine whether inhaled salbutamol is safe in newborn infants. STUDY DESIGN: Inhaled salbutamol or normal saline solution was administered to 54 infants with gestational ages ranging from 34 to 39 weeks and TTN. The response to salbutamol therapy was evaluated by determining respiratory rate, clinical score of TTN, level of respiratory support, and fraction of inspired oxygen before and at 30 minutes and 1 and 4 hours after salbutamol nebulization. RESULTS: Among the 54 infants with TTN, 32 received salbutamol and 22 received normal saline solution. After one dose, the salbutamol group showed significant improvements in respiratory rate, clinical score of TTN, fraction of inspired oxygen, and level of respiratory support (P < .05). After treatment, the mean pH, partial pressure of arterial oxygen, and partial pressure of arterial carbon dioxide values were better in the salbutamol group when compared with the placebo group (P < .05). Duration of hospitalization in the neonatal intensive care unit was also shorter for the salbutamol group (P < .05). CONCLUSION: Inhaled salbutamol treatment was effective with respect to both clinical and laboratory findings of TTN and without adverse events.

Plasminogen activator inhibitor I 4G/5G polymorphism in neonatal respiratory distress syndrome.

Fibrin monomers inhibit surfactant function. 4G/5G insertion/deletion polymorphism plays an important role in the regulation of plasminogen activator inhibitor 1 (PAI-1) gene expression. To examine the genotype distribution of PAI-1 polymorphism in 60 infants with respiratory distress syndrome (RDS) and 53 controls, an allele-specific polymerase chain reaction (PCR) was used. The proportion of 4G/4G, 4G/5G, and 5G/5G genotypes did not differ statistically between the RDS and control groups (P > .05). Having PAI-1 4G/4G genotype polymorphism appears to increase the risk of RDS (odds ratio [OR] =1.5; 95% confidence interval [CI], 0.5-4.3), although it was not statistically significant. No relation was found between the PAI-1 4G/5G polymorphisms and RDS, but there was an increased risk associated with the 4G variant of the PAI-1 gene. We believe that our findings of increased 4G allele of the PAI-1 gene in infants with RDS would also help to clarify the pathogenesis of RDS.

Fetal arterial and venous Doppler in growth restricted fetuses for the prediction of perinatal complications.

Fetal arterial and venous Doppler is a useful tool for the monitoring of growth restricted fetuses. Our aim in this study was to compare outcomes when fetuses were grouped according to the combinations of the Doppler results and also according to each vessel Doppler. Deliveries during the period 2002-2008 were reviewed retrospectively and cases with a birth weight less than the 10th percentile were selected for the study. Cases with congenital malformations or chromosomal abnormalities were excluded. Cases were then grouped according to umbilical artery (UA), middle cerebral artery (MCA) and ductus venosus (DV) Doppler results. Two hundred fifty-five cases were selected for the study. The perinatal mortality rate was 9.8% (11 prenatal and 14 neonatal). In the presence of absent or reverse flow in UA, fetal death and neonatal complication rates were higher. In the fetuses having reverse or absent "a" wave, there were findings of metabolic deterioration. Absent-reverse UA end-diastolic flow increased the odds ratios of perinatal and fetal death, bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), respiratory distress syndrome (RDS), and need for neonatal intensive care unit (NICU) (2.81, 5.94, 10.82, 5.79, 5.19, and 11.60, respectively). Absent/reverse "a" wave in DV increased the odds ratio of perinatal death, fetal death, neonatal death, RDS, and abnormal pH (19.89, 18.06, 12.50, 8.29, and 9.67, respectively). For prediction of fetal metabolic status, DV Doppler is a reliable tool. However, when perinatal complications are considered, this finding for intervention to delivery is a late point. Therefore, when reverse end-diastolic flow in the UA is observed, decision-to-delivery should be taken in order to avoid metabolic deterioration and increased postpartum death.

Maternal pertussis is hazardous for a newborn: a case report.

Pertussis, or whooping cough, a highly contagious disease caused by Bordetella pertussis, is making a comeback globally and nationally in spite of reasonable vaccination coverage. Worldwide, there have been increasing reports of Bordetella pertussis infection among adolescents and adults, but the peak incidence and highest mortality occur among infants. We report a 19-day-old female infant presenting with progressive respiratory failure. The mother was the only familial contact who complained of mild cough. However, occasional apneic episodes with cyanosis and peripheral lymphocytosis prompted us to examine the presence of Bordetella pertussis, which remains a significant cause of morbidity and mortality in unimmunized infants. Understanding the source of pertussis transmission to infants may provide new approaches to prevent pertussis in the most vulnerable infants. Various potential strategies have been reviewed or recommended in countries with the aim of better protecting infants against pertussis. Public health measures to prevent the disease could be strengthened and booster vaccinations against pertussis considered.

Early congenital syphilis with isolated bone involvement: a case report.

Congenital syphilis is the oldest recognized congenital infection and still represents a serious healthcare problem in the 21st century. It is important to be fully informed regarding the early diagnosis and treatment of congenital syphilis to prevent its devastating complications leading to death. In this manuscript, we report a newborn infant with unusual clinical findings of congenital syphilis such as a non-fluctuant mass surrounding the left calf. She did not have any additional system involvement such as hepatic or skin involvement or lymph nodes. To our best knowledge, there are only a few case reports presented with isolated bone involvement. This case demonstrates that congenital syphilis should be considered in neonates with bone fractures, lytic bone lesions and periostitis.

Mean platelet volume in neonatal respiratory distress syndrome.

The aim of this study was to investigate the differences in mean platelet volume (MPV) between neonates with and without neonatal respiratory distress syndrome (RDS). Eighty-three premature infants who were admitted to the neonatal intensive care unit were included in the study. Forty-four of these infants were diagnosed as having RDS and the other 39 infants were non-RDS patients. Infants born to mothers with pre-eclampsia, or a drug history that had negative effects on platelet count, perinatal hypoxia, sepsis and necrotizing enterocolitis were excluded. Blood collection was done on the first and third days of life. There were no demographic, gestational or platelet count differences between groups, but MPV was higher in RDS patients and this difference was statistically significant (P= 0.011). High platelet volumes in RDS patients is probably related to young platelet production and may be a result of increased platelet consumption in pulmonary damage due to RDS.

Determination of reference values for plasma cystatin C and comparison with creatinine in premature infants.

Cystatin C (CysC) is a low-molecular-mass protein (13,343 dalton, 120 amino acids) belonging to the cystatin superfamily of reversible inhibitors of cysteine proteases. CysC appears to be eliminated from the circulation almost exclusively by glomerular filtration, which makes it a promising endogenous marker of renal function. CysC has been demonstrated to reflect glomerular filtration rate better than other low-molecular-weight proteins, including creatinine (Cr). We established reference values for serum CysC and compared them with Cr in 108 preterm infants by particle-enhanced nephelometric immunoassay. On the first day, serum CysC values ranged from 1.25 to 2.84 mg/L, significantly decreasing after 3 days of life. Cr levels determined simultaneously on the first day ranged from 0.05 to 1.12 mg/dl and were also significantly different from day 3 levels. Both CysC and Cr levels were independent of gender, birth weight, hemoglobin levels, and hydration state. Cr correlated negatively with gestational age (r = -0.25, p = 0.009), but not CysC. A significant correlation was found between CysC and Cr on day 1 (r = 0.21, p = 0.031), but no correlation was found according to day 3 blood samples (r = 0.19, p = 0.053). CysC is regarded as an alternative for assessing renal function in preterm neonates, but its advantages over Cr are not yet proven.