Junctional Epidermolysis Bullosa Linked to Homozygous Mutation in LAMC2 Gene: A Case Report With Eosinophil-Rich Inflammatory Infiltrate.

ABSTRACT: Junctional epidermolysis bullosa (JEB) is a rare, incurable, devastating, and mostly fatal congenital genetic disorder characterized by painful blistering of the skin and mucous membranes in response to minor trauma or pressure. JEB is classified roughly into 2 subtypes: JEB-Herlitz is caused by mutations on genes encoding laminin-332. The authors present a patient consulted with a suspicion of primary immunodeficiency due to skin sores that started at the age of 1 month and a history of 3 siblings who died with similar sores, who was diagnosed with JEB-Herlitz after detecting a homozygous LAMC2 gene mutation in WES analysis. Microscopic evaluation of hematoxylin and eosin-stained sections showed vesicle formation with subepidermal separation, which is accompanied by striking neutrophil and eosinophil leukocyte infiltration both in the vesicle and papillary dermis (eosinophil-rich inflammatory infiltrate). Such a histopathological finding has been rarely reported in this condition.

Should the sex of the fetus be considered when administering antenatal corticosteroids to preterm fetuses?

AIM: We aimed to determine whether the effect of antenatal corticosteroids (ANS) differs in male and female fetuses without anomalies born before 32 weeks in terms of mortality and short-term morbidity. METHODS: This single-center retrospective study included infants born before 32 weeks' gestation and admitted to the neonatal intensive care unit between January 1, 2018, and December 31, 2020. RESULTS: The study included 210 infants with a median gestational age of 28.6 weeks (24-31.6), a birth weight of 1065 g (445-2165), and an ANS use rate of 80%. Compared to female fetuses exposed to ANS, male fetuses exposed to ANS had a lower mortality rate (23% and 11%, respectively, p = 0.038), but there were no differences in intraventricular hemorrhage, retinopathy of prematurity, necrotizing enterocolitis, respiratory distress syndrome, and APGAR scores of 1st and 5th but an increased rate of bronchopulmonary dysplasia (moderate/severe) (p = 0.008). In addition, the mortality rate was similar in exposed and unexposed female fetuses (p = 0.850). Enzyme activities and steroid levels in the placenta might be different in male and female fetuses, which could explain the results of ANS administration. CONCLUSIONS: In our study, we have shown that ANS has no effect on mortality in female fetuses younger than 32 weeks. Future studies may focus on adjusting the administration of ANS based on fetal sex, altering the dose or taking fetal sex into account when performing ANS.

Effect of Antenatal Magnesium Sulfate Exposure on Patent Ductus Arteriosus in Premature Infants.

OBJECTIVE: Magnesium sulfate (MgSO4) provides effective fetal neuroprotection. However, there is conflicting evidence regarding the association between antenatal MgSO4 exposure and patent ductus arteriosus (PDA). Thus, herein, we aimed to evaluate the association between antenatal MgSO4 exposure and PDA. STUDY DESIGN: Preterm infants born between 240/7 and 316/7 weeks of gestation were included in this retrospective study. Infants who died within the first 72 hours of life and those with significant congenital anomalies were excluded from the study. Echocardiographic and clinical assessment parameters were used to define PDA and hemodynamically significant PDA (hsPDA). Treatments were planned according to the standard protocols of the unit. The following data were collected from hospital medical records: perinatal characteristics, neonatal outcomes, detailed PDA follow-up findings, and maternal characteristics including MgSO4 exposure and doses. RESULTS: Of the 300 included infants, 98 (32.6%) were exposed to antenatal MgSO4. hsPDA rates were similar in the infants exposed and not exposed to antenatal MgSO4, when adjusted for antenatal steroid administration, gestational age, and birth weight (OR: 1.6, 95% CI: 0.849-3.118, p = 0.146). The rates of PDA ligation and open PDA at discharge were similar between the groups. A cumulative MgSO4 dose of >20 g was associated with an increased risk of hsPDA (crude OR: 2.476, 95% CI: 0.893-6.864, p = 0.076; adjusted OR: 3.829, 95% CI: 1.068-13.728, p = 0.039). However, the cumulative dose had no effect on the rates of PDA ligation or open PDA at discharge. Rates of prematurity-related morbidities and mortality were similar between the groups. CONCLUSION: Although antenatal MgSO4 exposure may increase the incidence of hsPDA, it may not affect the rates of PDA ligation or open PDA at discharge. Further studies are required to better evaluate the dose-dependent outcomes and identify the MgSO4 dose that not only provides neuroprotection but also has the lowest risk of adverse effects. KEY POINTS: · Antenatal exposure of MgSO4 may cause PDA.. · Antenatal MgSO4 exposure may not increase the rates of PDA ligation or open PDA at discharge.. · Further studies are required to better evaluate the dose-dependent outcomes and optimal MgSO4 dose..

Incidence of medical device-related pressure injuries and identification of risk factors in the neonatal unit.

AIM: This study was conducted to investigate the incidence of medical device-related pressure injuries (MDRPIs) and the risk factors influencing their occurrence in the neonatal intensive care unit (NICU). METHOD: This study is a prospective, descriptive study. The research was conducted with 116 newborns between June 1, 2022, and June 1, 2023. Newborns who stayed in the neonatal intensive care unit for at least 24 h were observed daily for medical device-related pressure injuries under and around each medical device throughout their stay in the intensive care unit. The "Case Report Form," "MDRPIs Monitoring Form," "Braden Q scale for children," National Pressure Injury Advisory Panel (NPIAP) Pressure Grading, and Glasgow Coma Scale were used in the research. RESULTS: The incidence of medical device-related pressure injuries is 35.3 % (41/116). It was found that 38.1 % (16/42) of medical device-related pressure injuries developed due to Near-Infrared Spectroscopy (NIRS) probes, and 33.5 % (14/42) developed due to medical devices related to the respiratory system. In terms of anatomical location, 38.1 % occurred on the forehead, and 23.8 % on the arm/leg. The difference between birth weight, gestational age, development of MDRPIs in newborns receiving sedation and inotropes was found to be statistically significant. Regression analysis identified gestational age (p = 0.040, OR = 0.795, 95%CI = [0.632-1.000]) as an independent risk factor for the occurrence of medical device-related pressure injuries. CONCLUSIONS: The incidence of medical device-related pressure injuries in newborns was relatively high in this study, with gestational age being the most significant risk factor for MDRPIs formation. It is crucial for neonatal intensive care nurses to consider associated risk factors while providing newborn care and implement appropriate preventive measures to reduce the incidence of MDRPIs.

Evaluation of the "Neonatal Sequential Organ Failure Assessment" to Predict Mortality in Late-Onset Sepsis in Very Preterm Infants.

INTRODUCTION: We aimed to evaluate the use of "Neonatal Sequential Organ Failure Assessment" (nSOFA) scoring in predicting mortality, to compare the accuracy of nSOFA scores at different time points in very preterm infants with late-onset sepsis (LOS), and to investigate other possible parameters that would improve the prediction. METHODS: This single-center, retrospective study included preterm infants born atS<32 weeks' gestation with culture-proven LOS. The nSOFA scores of non-fatal and fatal episodes were compared at nine time points. RESULTS: Of 120 culture-proven LOS episodes in 106 infants, 90 (75%) episodes were non-fatal and 30 (25%) episodes were fatal. The mean birth weight (BW) of the infants who died was lower than that of survivors (p=0.038). In the fatal LOS episodes, median nSOFA scores were higher at all time points measured before sepsis evaluation, at the time of evaluation, and at all time points measured after the evaluation (p<0.001). nSOFA scores before death and at 48 hours were higher in the fatal episodes (p<0.001). At the time of sepsis assessment, nSOFA score>4 was associated with a 7- to 16-fold increased risk of mortality. Adjustment for BW, lymphocyte and monocyte counts increased the risk to 9- to 18-fold. CONCLUSION: This study demonstrated that the use of nSOFA to predict mortality and morbidity in extremely preterm infants seems feasible. The scoring system could be improved by evaluating the other parameters.

Evaluation of the efficacy and associated complications of regional citrate anticoagulation in neonates: experience from a fourth level neonatal intensive care unit.

Continuous kidney replacement therapy (CKRT) use has increased in recent years, but anticoagulation is a challenge for neonates. Regional citrate anticoagulation (RCA) is rarely preferred in neonates because of citrate accumulation (CA) and metabolic complications. We aimed to demonstrate the efficacy and safety of RCA in neonates. We retrospectively analyzed the medical records of 11 neonates treated with RCA-CKRT between 2018 and 2023. The initial dose of RCA was 2.1-3 mmol/l, and then, its dose was increased according to the level of ionized calcium (iCa+2) in the circuit and patients. The total/iCa+2 ratio after-treatment > 2.5 was indicated as CA. We evaluated to citrate dose, CA, circuit lifespan, and dialysis effectivity. The median gestational age was 39 (36.4-41.5) weeks, the median body weight (BW) was 3200 (2400-4000) grams, and the mean postnatal age was 4 (2-24) days. The most common indication for CKRT was hyperammonemia (73%). All neonates had metabolic acidosis and hypocalcemia during CKRT. Other common metabolic complications were hypophosphatemia (90%), hypokalemia (81%), and hypomagnesemia (63%). High dialysate rates with a median of 5765 ml/h/1.73 m2 allowed for a rapid decrease in ammonia levels to normal. Four patients (36.3%) had CA, and seven (63.7%) did not (non-citrate accumulation, NCA). Mean BW, median postnatal age, biochemical parameters, coagulation tests, and ammonia levels were similar between the CA and NCA groups. Low pH, low HCO3, high lactate, and SNAPPE-II scores could be associated with a higher T/iCa ratio. CONCLUSION:  RCA was an efficient and safe anticoagulation for neonates requiring CKRT. Metabolic complications may occur, but they could be managed with adequate supplementation. WHAT IS KNOWN: • Continuous kidney replacement therapy (CKRT) has become popular in recent years due to its successful treatment of fluid overload, electrolyte imbalance, metabolic acidosis, multi-organ failure, and hyperleucinemia/hyperammonemia associated with inborn errors of metabolism. • The need for anticoagulation is the major difficulty in neonatal CKRT. In adult and pediatric patients, regional citrate anticoagulation has been shown to be effective. WHAT IS NEW: • RCA is an effective and safe anticoagulation method for neonates who require CKRT. • Electrolyte imbalances and metabolic acidosis could be managed with adequate supplementation and appropriate treatment parameters such as citrate dose, blood flow rate, and dialysate flow rate.

Comparison of Definitions for Bronchopulmonary Dysplasia: A Cohort Study.

We aimed to compare the definitions of National Institute of Child Health and Human Development (NICHD) for bronchopulmonary dysplasia (BPD) for determining the incidences, and predicting late death and respiratory outcome. This retrospective cohort study included infants born at<32 weeks' gestation who survived up to 36 weeks' postmenstrual age (PMA). Infants were classified as having BPD or no BPD per thedefinitions of NICHD 2001 and 2018. The incidences of BPD were 49 and 32% according to the 2001 and 2018 NICHD definitions. Gestational age, birth weight and intubation after birth were associated with BPD by both definitions. The NICHD 2018 definition displayed similar sensitivity (100%) and negative predictive value (100%), and higher specificity (70 vs. 52%) for predicting death after 36 weeks' PMA; a higher specificity (72 vs. 53%), comparable negative predictive value (77 vs.76%), but lower sensitivity for predicting adverse respiratory outcome within 12 months corrected age compared with the NICHD 2001 definition. The NICHD 2018 definition is as powerful as the 2001 definition for predicting late death and seems to be a better indicator for long-term respiratory outcome. The use of supplemental oxygen or oxygen plus respiratory support should be considered while predicting both late death and long-term respiratory outcome.

Acute Abdomen in an Extremely Low-Birth-Weight Preterm Neonate: A Case of Appendicitis.

INTRODUCTION: Neonatal appendicitis is a very rare surgical entity. Non-specific symptoms such as feeding intolerance, abdominal distension, vomiting, increased gastric residue, lethargy, and fever may be present. The majority of reported cases could not be identified early. In this report, we present an extremely low-birth-weight preterm neonate who has been diagnosed with appendicitis. CASE PRESENTATION: A 980-gram preterm baby girl was born at 31 1/7 weeks of gestation. The physical examination was normal at birth. Her initial clinical course was uneventful. On the 7th day of life, she developed abdominal distention and tenderness. She had an episode of bloody stools and bilious vomiting. An abdominal X-ray suggested localized perforation in the cecum with an air-fluid level in the right lower quadrant. The clinical findings suggested necrotizing enterocolitis and perforation, and a diagnostic laparotomy was performed. The bowel was found to be normal with a necrotic appendix. The appendectomy was performed. She was discharged from the neonatal intensive care unit with no complications. CONCLUSION: Appendicitis is extremely rare in the neonatal period. It is quite challenging to evaluate the presentation accurately, which causes a delay in diagnosis. However, if an atypical NEC or peritonitis is present, appendicitis should be considered. Early diagnosis and timely surgical intervention improve the prognosis of neonatal appendicitis.

Clinical characteristics and outcomes of continuous renal replacement therapy performed on younger children weighing up to 10 kg.

BACKGROUND: This study aimed to investigate the clinical features, modality, complications, and effecting factors on the survival of children weighing up to 10 kg who received continuous renal replacement therapy (CRRT). METHODS: This study was a retrospective observational study conducted in five pediatric intensive care units in tertiary hospitals in Turkey between January 2015 and December 2019. RESULTS: One hundred and forty-one children who underwent CRRT were enrolled in the study. The median age was 6 (range, 2-12)months, and 74 (52.5%) were male. The median weight of the patients was 6 (range, 4-8.35) kg and 52 (36.9%) weighed less than 5 kg. The most common indication for CRRT was fluid overload in 75 (53.2%) patients, and sepsis together with multiorgan failure in 62 (44%). The overall mortality was 48.2%. DISCUSSION: Despite its complexity, CRRT in children weighing less than 10 kg is a beneficial, lifesaving extracorporeal treatment modality.

Epidemiologic and clinical characteristics of neonates with late-onset COVID-19: 1-year data of Turkish Neonatal Society.

The literature on neonates with SARS-CoV-2 is mainly concerned with perinatal cases, and scanty data are available about environmentally infected neonates. To fill knowledge gaps on the course and prognosis of neonatal cases, we analyzed 1-year data from the Turkish Neonatal Society in this prospective cohort study of neonates with postnatal transmission. Data from 44 neonatal intensive care units (NICUs), of neonates with positive RT-PCR results at days 5-28 of life, were extracted from the online registry system and analyzed. Of 176 cases, most were term infants with normal birth weight. Fever was the most common symptom (64.2%), followed by feeding intolerance (25.6%), and cough (21.6%). The median length of hospitalization was 9 days, with approximately one quarter of infants receiving some type of ventilatory support. Myocarditis (5.7%) was the most common complication during follow-up. Among the clinical findings, cough (odds ratio [OR]: 9.52, 95% confidence interval [CI]: 4.17-21.71), tachypnea (OR: 26.5, 95% CI: 9.59-73.19), and chest retractions (OR: 27.5, 95% CI: 5.96-126.96) were associated with more severe clinical disease. Also, there were significant differences in the C-reactive protein level, prothrombin time (PT), partial thromboplastin time, international normalized ratio, and days in the NICU (p = 0.002, p = 0.012, p = 0.034, p = 0.008, and p < 0.001, respectively) between patients with mild-moderate and severe-critical presentations. A PT above 14 s was a significant predictor of severe/critical cases, with a sensitivity of 64% and specificity of 73%. CONCLUSIONS: Our data showed that late-onset COVID-19 infection in neonates who need hospitalization can be severe, showing associations with high rates of ventilatory support and myocarditis. Cough, tachypnea, and retractions on admission suggest a severe disease course. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04401540. WHAT IS KNOWN: • Neonatal cases of COVID-19 infection are mainly reported as perinatal COVID-19 cases. • Neonates with perinatal transmission have a mild course and favorable prognosis. WHAT IS NEW: • Among symptomatic neonates with late-onset COVID-19 infection, fever was the most common symptom, and almost one quarter of hospitalized cases needed some type of respiratory support. Myocarditis was the most common complication. • The presence of cough, tachypnea, retractions, and a PT above 14 s were associated with an increased risk of severe COVID-19.

Inherited metabolic disorders in the neonatal intensive care unit: Red flags to look out for.

BACKGROUND: We aimed to assess symptoms, laboratory findings, and radiological abnormalities in patients diagnosed with inherited metabolic disorders (IMDs) in the neonatal intensive care unit. METHODS: A total of 6,150 newborns treated in a third-level neonatal intensive care unit between 2012 and 2020 in Turkey were screened, of which 195 consulted with a suspicion of metabolic disease based on their clinical, laboratory, or radiological findings were included in the present study. RESULTS: The prevalence of IMDs in the patients was 1:94.6. Those consulted in the department of pediatric metabolism were divided into two groups, with the 65 diagnosed with IMDs assigned as Group I, and the 130 patients who were not diagnosed with IMDs as Group II. The most common IMDs were organic acidemias (29.23%) and urea cycle disorders (UCDs) (26.15%). The rates of consanguinity marriage (75.3% vs 37.6%, P < 0.001), siblings diagnosed with an IMD (27.6% vs 3.8%, P < 0.001), and sibling death (56.9% vs 14.6%, P < 0.001) were higher in Group I than in Group II. Hyperammonemia (61.5% vs 18.4%, P < 0.001) was the most common laboratory finding in Group I, and anemia (Group I 60.0% vs 43.0% P = 0.033), metabolic acidosis (53.8% vs 36.9%, P = 0.028) and respiratory alkalosis (16.9% vs 1.5%, P < 0.001) were all higher in Group I. CONCLUSIONS: This retrospective study found that the results of clinical findings and basic laboratory tests could be strong indicators of IMDs, although extensive newborn screening tests and advanced biochemical and genetic tests should be carried out for the diagnosis of IMDs in newborns.

Prolonged Tracheal Intubation and the Association Between Patent Ductus Arteriosus and Bronchopulmonary Dysplasia: A Secondary Analysis of the PDA-TOLERATE trial.

In the PDA-TOLERATE trial, persistent (even for several weeks) moderate to large patent ductus arteriosus (PDA) was not associated with an increased risk of BPD when the infant required <10 days of intubation. However, in infants requiring intubation for ≥10 days, prolonged PDA exposure (≥11 days) was associated with an increased risk of moderate/severe BPD.

A multicenter study on epidemiological and clinical characteristics of 125 newborns born to women infected with COVID-19 by Turkish Neonatal Society.

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: NCT04401540 What 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.

Risk Factors for Respiratory Syncytial Virus Infections in Moderate/Late Premature Infants in Turkey: A Prospective Multicenter Epidemiological Study.

OBJECTIVE: Respiratory syncytial virus (RSV) is one of the most prevalent causes of lower respiratory tract infection (LRTI). The primary objective of this study is to provide the risk modelling of confirmed RSV infection in children who were born preterm at 29 to 35 weeks of gestational age and presented with LRTI. STUDY DESIGN: This prospective, multicenter study was performed between October 2015 and March 2017. Premature infants born with gestational age between 29 and 35 weeks that were ≤2 years of age at the beginning of the RSV season and admitted to the hospital with clinical findings of LRTI during the season were included. RSV-positive and -negative infants were compared in terms of demographic features, risk factors, and requirement of hospitalization. RESULTS: RSV positive group was lower than RSV negative group and ratio of ≤3 months age at admission was significant higher in RSV (+) group. RSV-positive infants were found to be significantly born during or 3 months prior to RSV season. The rate and duration of hospitalization and need for mechanical ventilation were significantly higher in RSV positive infants. The rate and duration of hospitalization in RSV positive patients was related to the chronological age. CONCLUSION: This study showed that preterm infants with RSV-associated LRTI significantly needed more hospitalization, intensive care admission, and mechanical ventilation. In addition need of hospitalization and duration of hospitalization were significant higher in ≤3 months of age. Therefore, we suggest the importance of palivizumab prophylaxis in infants ≤ 3 months chronological age, especially during the RSV season.

Continuous venovenous hemodiafiltration in the treatment of newborns with an inborn metabolic disease: a single center experience

Background/aim: Most inborn metabolic diseases are diagnosed during the neonatal period. The accumulation of toxic metabolites may cause acute metabolic crisis with long-term neurological dysfunction and death. Renal replacement therapy (RRT) modalities allow the efficient removal of toxic metabolites. In this study, we reviewed our experience with continuous venovenous hemodiafiltration (CVVHDF) as RRT for newborns with an inborn metabolic disease. Materials and methods: Patients diagnosed with an inborn metabolic disease and who received CVVHDF treatment at our neonatal intensive care unit between January 2014 and December 2017 were included in this study. Their demographic and clinical data were collected, and the efficacy and safety of CVVHDF was evaluated. Results: A total of nine continuous RRT (CRRT) sessions as CVVHDF were performed in eight newborns with a diagnosis of urea cycle defect (n = 5), maple syrup urine disease (n = 2), or methylmalonic acidemia (n = 1). The mean age at admission was 10 ± 8.6 days (range: 3­28 days). The mean plasma levels of ammonium were 1120 ± 512.6 mg/dL and 227.5 ± 141.6 mg/dL before and at the end of the treatment, respectively. Plasma levels of leucine were 2053.5 ± 1282 µmol/L and 473.5 ± 7.8 µmol/L before and at the end of the treatment, respectively. The CVVHDF duration was 32.3 ± 11.1 h (median: 37 h; range: 16­44 h), and the mean length of hospitalization was 14.6 ± 12.9 days. The mean duration of CVVHDF was 32.3 ± 11.1 h (range: 16­44 h). Circuit clotting was the most common observed complication (37.5%) and the survival rate was 50%. Among surviving patients, two developed severe and two developed mild mental and motor retardation. Conclusion: CVVHDF is a CRRT modality that can be used to treat newborns with an inborn metabolic disease. Early diagnosis, commencement of specific medical therapy, diet, and extracorporeal support, if needed, are likely to result in improved short and long- term outcomes.

PDA-TOLERATE Trial: An Exploratory Randomized Controlled Trial of Treatment of Moderate-to-Large Patent Ductus Arteriosus at 1 Week of Age.

OBJECTIVE: To compare early routine pharmacologic treatment of moderate-to-large patent ductus arteriosus (PDA) at the end of week 1 with a conservative approach that requires prespecified respiratory and hemodynamic criteria before treatment can be given. STUDY DESIGN: A total of 202 neonates of <28 weeks of gestation age (mean, 25.8 ± 1.1 weeks) with moderate-to-large PDA shunts were enrolled between age 6 and 14 days (mean, 8.1 ± 2.2 days) into an exploratory randomized controlled trial. RESULTS: At enrollment, 49% of the patients were intubated and 48% required nasal ventilation or continuous positive airway pressure. There were no differences between the groups in either our primary outcome of ligation or presence of a PDA at discharge (early routine treatment [ERT], 32%; conservative treatment [CT], 39%) or any of our prespecified secondary outcomes of necrotizing enterocolitis (ERT, 16%; CT, 19%), bronchopulmonary dysplasia (BPD) (ERT, 49%; CT, 53%), BPD/death (ERT, 58%; CT, 57%), death (ERT,19%; CT, 10%), and weekly need for respiratory support. Fewer infants in the ERT group met the rescue criteria (ERT, 31%; CT, 62%). In secondary exploratory analyses, infants receiving ERT had significantly less need for inotropic support (ERT, 13%; CT, 25%). However, among infants who were ≥26 weeks gestational age, those receiving ERT took significantly longer to achieve enteral feeding of 120 mL/kg/day (median: ERT, 14 days [range, 4.5-19 days]; CT, 6 days [range, 3-14 days]), and had significantly higher incidences of late-onset non-coagulase-negative Staphylococcus bacteremia (ERT, 24%; CT,6%) and death (ERT, 16%; CT, 2%). CONCLUSIONS: In preterm infants age <28 weeks with moderate-to-large PDAs who were receiving respiratory support after the first week, ERT did not reduce PDA ligations or the presence of a PDA at discharge and did not improve any of the prespecified secondary outcomes, but delayed full feeding and was associated with higher rates of late-onset sepsis and death in infants born at ≥26 weeks of gestation. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01958320.

N-terminal B-type natriuretic peptide urinary concentrations and retinopathy of prematurity.

BackgroundTo validate the findings of a single-center pilot study showing elevated urinary N-terminal B-type natriuretic peptide (NTproBNP) concentrations in preterm infants subsequently developing severe retinopathy of prematurity (ROP) in a multicenter setting across eight European and Middle East countries.MethodsProspective observational study in 967 preterm infants <30 weeks' gestational age assessing the capacity of urinary NTproBNP on days of life (DOLs) 14 and 28 to predict ROP requiring treatment.ResultsUrinary NTproBNP concentrations were markedly elevated in infants who developed ROP requiring treatment (n=94) compared with survivors without ROP treatment (n=837), at both time points (median (interquartile range) DOL14: 8,950 (1,925-23,783) vs. 3,083 (1,193-17,393) vs. 816 (290-3,078) pg/ml, P<0.001) and DOL28 (2,203 (611-4,063) vs. 1,671 (254-11,340) vs. 408 (162-1,126) pg/ml, P<0.001). C-statistic of NTproBNP for treated ROP or death was 0.731 (95% confidence interval 0.654-0.774) for DOL14 and 0.683 (0.622-0.745) for DOL28 (P<0.001). Threshold scores were calculated, potentially enabling around 20% of infants with low NTproBNP scores never to be screened with ophthalmoscopy.ConclusionThere is a strong association between early urinary NTproBNP and subsequent ROP development, which can be used to further refine subgroups of patients with high or low risk of severe ROP.

Neurodevelopmental Outcomes of Preterm Infants Treated with Oral Paracetamol Versus Ibuprofen for Patent Ductus Arteriosus.

Objective This study aims to determine the effects of paracetamol versus ibuprofen treatment given to preterm infants for the pharmacological closure of patent ductus arteriosus (PDA) on neurodevelopmental outcomes at 18 to 24 months' corrected age. Method A follow-up study was conducted to evaluate the neurodevelopmental outcomes of preterm infants (gestational age ≤ 30 weeks) enrolled in a randomized controlled trial comparing oral paracetamol versus oral ibuprofen for the closure of PDA. The developmental assessment was done by using "Bayley Scales of Infant Development, Second Edition" at 18 to 24 months' corrected age. Results A total of 80 infants completed the trial protocol. Of the 75 infants eligible for follow-up, 61 infants (30 in the paracetamol group and 31 in the ibuprofen group) were evaluated. There was no significant difference in neurodevelopmental outcomes between the two groups. Conclusion The neurodevelopmental outcomes did not differ among the preterm infants who receive either paracetamol or ibuprofen at 18 to 24 months' corrected age.

Does ibuprofen treatment in patent ductus arteriosus alter oxygen free radicals in premature infants?

Introduction Ibuprofen is used widely to close patent ductus arteriosus in preterm infants. The anti-inflammatory activity of ibuprofen may also be partly due to its ability to scavenge reactive oxygen species and reactive nitrogen species. We evaluated the interaction between oxidative status and the medical treatment of patent ductus arteriosus with two forms of ibuprofen. Materials and methods This study enrolled newborns of gestational age ⩽32 weeks, birth weight ⩽1500 g, and postnatal age 48-96 hours, who received either intravenous or oral ibuprofen to treat patent ductus arteriosus. Venous blood was sampled before ibuprofen treatment from each patient to determine antioxidant and oxidant concentrations. Secondary samples were collected 24 hours after the end of the treatment. Total oxidant status and total antioxidant capacity were measured using Erel's method. RESULTS: This prospective randomised study enrolled 102 preterm infants with patent ductus arteriosus. The patent ductus arteriosus closure rate was significantly higher in the oral ibuprofen group (84.6 versus 62%) after the first course of treatment (p=0.011). No significant difference was found between the pre- and post-treatment total oxidant status and total antioxidant capacity in the groups. Discussion Ibuprofen treatment does not change the total oxidant status or total antioxidant capacity. We believe that the effect of ibuprofen treatment in inducing ischaemia overcomes the scavenging effect of ibuprofen.