Antenatal Steroids, Prophylactic Indomethacin, and the Risk of Spontaneous Intestinal Perforation.

OBJECTIVE: To estimate if the odds of spontaneous intestinal perforation (SIP) are increased when antenatal steroids (ANS) given close to delivery are combined with indomethacin on day 1 after birth (Indo-D1). STUDY DESIGN: A retrospective cohort study using the Neonatal Research Network (NRN) database of inborn infants, gestational age 220-286 weeks or birth weight of 401-1000 g, born between January 1, 2016 and December 31, 2019, and surviving >12 hours. The primary outcome was SIP through 14 days. Time of last ANS dose prior to delivery was analyzed as a continuous variable (using 169 hours for durations >168 hours or no steroid exposure). Associations between ANS, Indo-D1, and SIP were obtained from a multilevel hierarchical generalized linear mixed model after covariate adjustment. This yielded aOR and 95% CI. RESULTS: Of 6851 infants, 243 had SIP (3.5%). ANS exposure occurred in 6393 infants (93.3%) and IndoD1 was given to 1863 infants (27.2%). The time (median, IQR) from last dose of ANS to delivery was 32.5 hours (6-81) vs 37.1 hours (7-110) for infants with or without SIP, respectively (P = .10). Indo-D1 was given to 51.9 vs 26.3% of infants with SIP vs no SIP, respectively (P < .0001). Adjusted analysis indicated no interaction between time of last ANS dose and Indo-D1 for SIP (P = .7). Indo-D1 but not ANS was associated with increased odds of SIP (aOR: 1.73, 1.21-2.48, P = .003). CONCLUSION: The odds of SIP were increased after receipt of Indo-D1. Exposure to ANS prior to Indo-D1 was not associated with an increase in SIP.

Markers of Successful Extubation in Extremely Preterm Infants, and Morbidity After Failed Extubation.

OBJECTIVES: To identify variables associated with successful elective extubation, and to determine neonatal morbidities associated with extubation failure in extremely preterm neonates. STUDY DESIGN: This study was a secondary analysis of the National Institute of Child Health and Human Development Neonatal Research Network's Surfactant, Positive Pressure, and Oxygenation Randomized Trial that included extremely preterm infants born at 240/7 to 276/7 weeks' gestation. Patients were randomized either to a permissive ventilatory strategy (continuous positive airway pressure group) or intubation followed by early surfactant (surfactant group). There were prespecified intubation and extubation criteria. Extubation failure was defined as reintubation within 5 days of extubation. RESULTS: Of 1316 infants in the trial, 1071 were eligible; 926 infants had data available on extubation status; 538 were successful and 388 failed extubation. The rate of successful extubation was 50% (188/374) in the continuous positive airway pressure group and 63% (350/552) in the surfactant group. Successful extubation was associated with higher 5-minute Apgar score, and pH prior to extubation, lower peak fraction of inspired oxygen within the first 24 hours of age and prior to extubation, lower partial pressure of carbon dioxide prior to extubation, and non-small for gestational age status after adjustment for the randomization group assignment. Infants who failed extubation had higher adjusted rates of mortality (OR 2.89), bronchopulmonary dysplasia (OR 3.06), and death/ bronchopulmonary dysplasia (OR 3.27). CONCLUSIONS: Higher 5-minute Apgar score, and pH prior to extubation, lower peak fraction of inspired oxygen within first 24 hours of age, lower partial pressure of carbon dioxide and fraction of inspired oxygen prior to extubation, and nonsmall for gestational age status were associated with successful extubation. Failed extubation was associated with significantly higher likelihood of mortality and morbidities. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00233324.

Perinatal asphyxia with hyperoxemia within the first hour of life is associated with moderate to severe hypoxic-ischemic encephalopathy.

OBJECTIVE: To determine whether early hyperoxemia in neonates with severe perinatal acidemia is associated with the development of hypoxic-ischemic encephalopathy (HIE). STUDY DESIGN: We identified 120 infants at ≥ 36 weeks gestational age with perinatal acidosis born at Parkland Hospital who qualified for a screening neurologic exam for cooling therapy. Based on a PaO2 measurement during the first hour of life, the cohort was divided into infants with hyperoxemia (PaO2 >100 mmHg) and those without hyperoxemia (PaO2 ≤ 100 mmHg). The rate of moderate-severe encephalopathy was compared between the groups using χ(2) analysis, as well as multiple logistic regression, taking into account baseline characteristics and confounding variables. RESULTS: Thirty-six infants (30%) had an initial PaO2 >100 mmHg. Infants with and without hyperoxemia had similar baseline maternal and infant characteristics. Infants with hyperoxemia had a higher incidence of HIE than those without hyperoxemia (58% vs 27%; P = .003). Admission hyperoxemia was associated with a higher risk of HIE (OR, 4; 95% CI, 1.4-10.5; adjusted P = .01). Among the neonates with moderate-severe HIE during the first 6 hours of life, those with hyperoxemia had a higher incidence of abnormal brain magnetic resonance imaging results, consistent with hypoxic ischemic injury, compared with those without hyperoxemia (79% vs 33%; P = .015). CONCLUSION: In neonates with perinatal acidemia, admission hyperoxemia is associated with a higher incidence of HIE. Among neonates with HIE, admission hyperoxemia is associated with abnormal brain magnetic resonance imaging findings. The judicious use of oxygen during and after resuscitation is warranted.

Perinatal acidosis and hypoxic-ischemic encephalopathy in preterm infants of 33 to 35 weeks' gestation.

OBJECTIVES: To determine the frequency of hypoxic-ischemic encephalopathy (HIE) in preterm infants of 33 to 35 weeks' gestational age on the basis of physiological screening for perinatal acidosis and neurological assessment of encephalopathy and to correlate neurodevelopmental outcomes with brain magnetic resonance imaging findings. STUDY DESIGN: This retrospective cohort study included all inborn infants of 33 to 35 weeks' gestation admitted to the neonatal intensive care unit at Parkland Memorial Hospital with perinatal acidosis from October 2005 to September 2008. Their medical records were reviewed, and pertinent data were recorded. RESULTS: Of 1305 newborns, 2.5% (n=33) had perinatal acidosis, and 27% (n=9) of these had HIE (2, mild; 4, moderate; 3, severe). Persistence of metabolic acidosis on the first arterial blood gas obtained in the first hour of age was significantly associated with HIE (P<.005). Magnetic resonance imaging results were abnormal in 3 of 4 infants with moderate HIE and in both survivors with severe HIE. Death or disability occurred in no infants with mild or moderate HIE, but in all infants with severe HIE. CONCLUSION: Screening criteria for HIE that use biochemical and neurological assessments as performed in term newborns can be applied to preterm infants of 33 to 35 weeks' gestation.