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Hospital Variation in Mortality and Failure to Rescue after Surgery for High-Risk Neonatal Diagnoses.

A large proportion of postoperative mortality after pediatric surgery occurs among neonates with specific high-risk diagnoses. The extent to which there is hospital-level mortality variation among patients with these diagnoses and whether this variation is associated with differences in failure to rescue (FTR) is unclear. The Pediatric Health Information System® database (2012-2020) was used to identify patients who underwent surgery for eight high-risk neonatal diagnoses: gastroschisis; volvulus; necrotizing enterocolitis; intestinal atresia; meconium peritonitis; tracheoesophageal fistula; congenital diaphragmatic hernia; and perinatal intestinal perforation. Hospitals were stratified into tertiles of reliability-adjusted inpatient mortality rates (lower than average mortality - tertile 1 [T1]; higher than average mortality - tertile 3 [T3]). Multivariable hierarchical regression was used to evaluate the association between hospital-level, reliability-adjusted mortality and FTR. Overall, 20,838 infants were identified across 48 academic, pediatric hospitals. Adjusted hospital mortality rates ranged from 4.0% (95% CI, 0.0-8.2) to 16.3% (12.2-20.4). Median case volume (range, 80-1,238) and number of NICU beds (range, 24-126) were not significantly different across hospital tertiles. Compared to the hospitals with the lowest postoperative mortality (T1), the odds of FTR were significantly higher in hospitals with the highest (T3) postoperative mortality (odds ratio 1.97 [1.50-2.59]). Significant variation in neonatal hospital mortality for high-risk diagnoses does not appear to be explained by hospital structural characteristics. Rather, difference in FTR suggests quality improvement interventions targeting early recognition and management of postoperative complications could improve surgical quality and safety for high-risk neonatal care.

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Parental Experiences of Neonatal Care: A Nationwide Study on Determinants of Excellence.

Infant- and family-centered developmental care can reduce adverse outcomes in both infants and parents. Parents' experiences of the care and staff treatment remain to be evaluated. Parents of infants admitted to neonatal units in Sweden from July 2020 to May 2022 responded to a questionnaire with standardized questions about in-hospital care. Exposures were hospital, gestational age, length of hospital stay, unit level, and bed density. The proportions of parents rating aspects of neonatal care as excellent, defined as five on a Likert scale, and the determinants of excellence were described. The results were benchmarked with ratings in adult somatic care. A total of 4,475/13,108 (34%) parents responded. The ratings of excellent care varied by question from 65% to 90%. The largest variation in excellence between neonatal units (range 43-80%) was found for "participation and involvement." The proportion of excellence was significantly lower among parents of extremely preterm infants. Confidence in the staff was lower in parents of extremely preterm infants than in parents of term infants (56% vs. 83%). Longer hospital stays affected the experience of neonatal care adversely, whereas level of care and bed density were overall unrelated to the parental experience. Parents in neonatal care rated the care as excellent to a higher extent than patients cared for in adult medicine. A majority of parents rated neonatal care in Sweden as excellent. The less frequent ratings of excellence among parents of extremely preterm infants indicate that more could be done to optimize parental involvement and support.

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Neuro-Specific and Immuno-Inflammatory Biomarkers in Umbilical Cord Blood in Neonatal Hypoxic-Ischemic Encephalopathy

Objectives: The aim of the study was to evaluate neuronal injury and immuno-inflammatory biomarkers in umbilical cord blood (UCB) at birth, in cases with perinatal asphyxia with or without hypoxic-ischemic encephalopathy (HIE), compared with healthy controls and to assess their ability to predict HIE. Study Design: In this case-control study, term infants with perinatal asphyxia were recruited at birth. UCB was stored at delivery for batch analysis. HIE was diagnosed by clinical Sarnat staging at 24 h. Glial fibrillary acidic protein (GFAP), the neuronal biomarkers tau and neurofilament light protein (NFL), and a panel of cytokines were analyzed in a total of 150 term neonates: 50 with HIE, 50 with asphyxia without HIE (PA), and 50 controls. GFAP, tau, and NFL concentrations were measured using ultrasensitive single-molecule array (Simoa) assays, and a cytokine screening panel was applied to analyze the immuno-inflammatory and infectious markers. Results: GFAP, tau, NFL, and several cytokines were significantly higher in newborns with moderate and severe HIE compared to a control group and provided moderate prediction of HIE II/III (AUC: 0.681–0.827). Furthermore, the levels of GFAP, tau, interleukin-6 (IL-6), and interleukin-8 (IL-8) were higher in HIE II/III cases compared with cases with PA/HIE I. IL-6 was also higher in HIE II/III compared with HIE I cases. Conclusions: Biomarkers of brain injury and inflammation were increased in umbilical blood in cases with asphyxia. Several biomarkers were higher in HIE II/III versus those with no HIE or HIE I, suggesting that they could assist in the prediction of HIE II/III.

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Effects of Milrinone on Neonates after Patent Ductus Arteriosus Ligation: A Retrospective Nationwide Database Study

Introduction: Milrinone is administered after patent ductus arteriosus (PDA) ligation to prevent and treat postoperative hemodynamic instability (i.e., postligation cardiac syndrome). We aimed to explore the effectiveness of milrinone on in-hospital outcomes in infants who underwent PDA ligation using a nationwide inpatient database in Japan. Methods: Using the Japanese Diagnosis Procedure Combination database, we identified patients who received milrinone after PDA ligation (n = 428) in neonatal intensive care units between July 2010 and March 2021 and those who did not (n = 3,392). We conducted a 1:4 propensity score-matched analysis with adjustment for background characteristics (e.g., gestational age, birth weight, comorbidities, preoperative treatments, and hospital background) to compare morbidities (bronchopulmonary dysplasia, intraventricular hemorrhage, necrotizing enterocolitis, and retinopathy of prematurity), mortality, total hospitalization costs, and other outcomes. For sensitivity analysis, we performed an overlap propensity score-weighted analysis. Results: In-hospital morbidity, bronchopulmonary dysplasia, intraventricular hemorrhage, and necrotizing enterocolitis occurred in 58%, 48%, 9.5%, and 7.1% of patients, respectively; the in-hospital mortality was 5.4%. After 1:4 propensity score matching, no significant difference was observed regarding mortality (7.1 vs. 5.7%), in-hospital morbidity (55 vs. 50%), bronchopulmonary dysplasia (44 vs. 41%), intraventricular hemorrhage (7.8 vs. 9.1%), necrotizing enterocolitis (8.5 vs. 8.9%), retinopathy of prematurity (21 vs. 22%), or total hospitalization costs (median: approximately 86,000 vs. 82,000 US dollars) between milrinone users (n = 425) and nonusers (n = 1,698). Sensitivity analyses yielded consistent results. Conclusions: Milrinone use after PDA ligation was not associated with improved in-hospital outcomes, such as mortality and morbidity.

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Time of Delivery Contributes to Mortality and Morbidity in Preterm Infants

Introduction: Knowledge about the time of birth and its impact on premature infants is essential when planning perinatal and neonatal care and resource allocation. We studied the time of birth and its contribution to early death and morbidity in preterm infants. Methods: We explored the time and mode of birth of infants with birthweight of <1,500 g and gestational age of <32+<sup>0/7</sup> weeks. Additionally, we divided the infants into three groups stratified by their time of birth, i.e., during office hours, evening, and nighttime and assessed associations between these groups and mortality and morbidity. Results: The study comprised 1,610 infants of whom 156 (10%) died during their stay in neonatal intensive care unit. The highest number of deliveries occurred on Fridays (21%, n = 341/1,610), primarily due to high number of cesarean sections. Deliveries peaked on workdays at 10 a.m. and 2:00 p.m. Mortality was lowest among infants born on Fridays (6%, n = 21/341) and highest on Mondays (13%, n = 28/218). Intraventricular hemorrhage (IVH) (odds ratio [OR]: 1.50, 95% CI: 1.10–2.03, p = 0.010) and necrotizing enterocolitis (NEC) (OR: 2.11, 95% CI: 1.13–3.91, p = 0.019) were more common among infants born at nighttime. These associations attenuated after adjustment for covariates. Conclusion: Deliveries of premature infants peaked on Fridays. Mortality was lower among those born on Fridays, compared with Mondays. Many low-risk deliveries on Fridays may decrease, and the tendency to postpone high-risk deliveries to Mondays, increase the proportional risk of mortality. Indication of higher risk of IVH and NEC among infants born during nighttime may be due to different patient population.

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Neonatal Research at the Archiospedale Santo Spirito in Rome

Abandoning infants was a heritage of the Roman Empire. Foundling hospitals were established in Italy earlier and in greater number than in other countries; their goal was to prevent infanticides. The Foundling Hospital in Rome, established in the Santo Spirito Church in 1204, paved the way toward modern hospital care and child protection. The Order of the Holy Spirit was appointed by Pope Innocent III to care for foundlings, and set up a network of infant nurseries all over Europe. Poor unmarried pregnant women received obstetric services free of charge. Infants were admitted anonymously by the ruota, a baby hatch or turning wheel. The Order’s rule regulated infants’ admission, care, nutrition by wet nurses, and boarding out to foster families in the countryside. Chief physicians of the Santo Spirito Hospital were often Sapienza University professors and/or personal physicians to the Popes. Among them were Realdo Colombo, Andrea Caesalpino, Giovanni Lancisi, Giuseppe Flajani, Domenico Morichini, and Tommaso Prelà. They made major scientific progress in anatomy and surgery: descriptions of the pulmonary blood transit, embryonic formation, fetal circulation, malaria transmission from mosquitos, and surgery for congenital malformations such as hydrocephalus, anal atresia, and cleft lip. Per year, 800–1,000 exposed infants were admitted. Despite sufficient funding and meticulous regulation of care and nutrition, mortality in the hospital during the first month of life was around 70%; the causes were neglected surveillance, cleanliness, and artificial nutrition. The institution persisted for more than 700 years due to numerous connections with the Vatican.

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Placental Histologic Abnormalities and 2-Year Outcomes in Neonatal Hypoxic-Ischemic Encephalopathy

Objective: We aimed to examine the association between placental abnormalities and neurodevelopmental outcomes in a multicenter cohort of newborn infants with hypoxic-ischemic encephalopathy (HIE) that underwent therapeutic hypothermia. We hypothesized that subjects with acute placental abnormalities would have reduced risk of death or neurodevelopmental impairment (NDI) at 2 years of age after undergoing therapeutic hypothermia compared to subjects without acute placental changes. Study Design: Among 500 subjects born at ≥36 weeks gestation with moderate or severe HIE enrolled in the High-dose Erythropoietin for Asphyxia and Encephalopathy (HEAL) Trial, a placental pathologist blinded to clinical information reviewed clinical pathology reports to determine the presence of acute only, chronic only, or both acute and chronic histologic abnormalities. We calculated adjusted relative risks (aRRs) for associations between placental pathologic abnormalities and death or NDI at age 2 years, adjusting for HIE severity, treatment assignment, and site. Result: 321/500 subjects (64%) had available placental pathology reports. Placental abnormalities were characterized as acute only (20%), chronic only (21%), both acute and chronic (43%), and none (15%). The risk of death or NDI was not statistically different between subjects with and without an acute placental abnormality (46 vs. 53%, aRR 1.1, 95% confidence interval (CI): 0.9, 1.4). Subjects with two or more chronic lesions were more likely to have an adverse outcome than subjects with no chronic abnormalities, though this did not reach statistical significance (55 vs. 45%, aRR 1.24, 95% CI: 0.99, 1.56). Conclusion: Placental pathologic findings were not independently associated with risk of death or NDI in subjects with HIE. The relationship between multiple chronic placental lesions and HIE outcomes deserves further study.

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An Early Prediction Model for Estimating Bronchopulmonary Dysplasia in Preterm Infants

Introduction: Accurate assessment of the risk for bronchopulmonary dysplasia (BPD) is critical to determine the prognosis and identify infants who will benefit from preventive therapies. Clinical prediction models can support the identification of high-risk patients. In this study, we investigated the potential risk factors for BPD and compared machine learning models for predicting the outcome of BPD/death on days 1, 7, 14, and 28 in preterm infants. We also developed a local BPD estimator. Methods: This study involved 124 infants. We evaluated the composite outcome of BPD/death at a postmenstrual age of 36 weeks and identified risk factors that would improve BPD/death prediction. SPSS for Windows Version 11.5 and Weka 3.9 software were used for the data analysis. Results: To evaluate the combined effect of all variables, all risk factors were taken into consideration. Gestational age, birth weight, mode of respiratory support, intraventricular hemorrhage, necrotizing enterocolitis, surfactant requirement, and late-onset sepsis were risk factors on postnatal days 7, 14, and 28. In a comparison of four different time points (postnatal days 1, 7, 14, and 28), the day 7 model provided the best prediction. According to this model, when a patient was diagnosed with BPD/death, the accuracy rate was 89.5%. Conclusion: The postnatal day 7 model was the best predictor of BPD or death. Future validation studies will help identify infants who may benefit from preventive therapies and develop individualized care.

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