Infants with perinatal sentinel events in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network Hypothermia for Encephalopathy Trial had more ...basal ganglia and thalamus lesions on brain magnetic resonance imaging but similar neurodevelopmental outcomes at 18 months of age than infants without perinatal sentinel events. Outcomes correlated with the neonatal magnetic resonance imaging findings. Trial registration ClinicalTrials.gov : NCT00005772.
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).
...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.
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).
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.
Late-onset sepsis (occurring after 3 days of age) is an important problem in very low birth weight (VLBW) infants. To determine the current incidence of late-onset sepsis, risk factors for disease, ...and the impact of late-onset sepsis on subsequent hospital course, we evaluated a cohort of 6956 VLBW (401-1500 g) neonates admitted to the clinical centers of the National Institute of Child Health and Human Development Neonatal Research Network over a 2-year period (1998-2000).
The National Institute of Child Health and Human Development Neonatal Research Network maintains a prospective registry of all VLBW neonates admitted to participating centers within 14 days of birth. Expanded infection surveillance was added in 1998.
Of 6215 infants who survived beyond 3 days, 1313 (21%) had 1 or more episodes of blood culture-proven late-onset sepsis. The vast majority of infections (70%) were caused by Gram-positive organisms, with coagulase-negative staphylococci accounting for 48% of infections. Rate of infection was inversely related to birth weight and gestational age. Complications of prematurity associated with an increased rate of late-onset sepsis included patent ductus arteriosus, prolonged ventilation, prolonged intravascular access, bronchopulmonary dysplasia, and necrotizing enterocolitis. Infants who developed late-onset sepsis had a significantly prolonged hospital stay (mean length of stay: 79 vs 60 days). They were significantly more likely to die than those who were uninfected (18% vs 7%), especially if they were infected with Gram-negative organisms (36%) or fungi (32%).
Late-onset sepsis remains an important risk factor for death among VLBW preterm infants and for prolonged hospital stay among VLBW survivors. Strategies to reduce late-onset sepsis and its medical, social, and economic toll need to be addressed urgently.
Common neurologic morbidities encountered in very preterm and extremely preterm infants (intracranial hemorrhage, white matter injury and periventricular leukomalacia, and apnea of prematurity) are ...much less common in moderately preterm and late preterm infants. The frequency of germinal matrix hemorrhage-intraventricular hemorrhage and white matter injury are reported to be low, but selection bias in neuroimaging surveillance prevents ascertainment of precise frequencies. The major neurologic morbidity of moderately and late preterm infants is feeding difficulty reflecting developmental integration of suck, swallow, and breathing.
There are limited data to inform the choice between early treatment with continuous positive airway pressure (CPAP) and early surfactant treatment as the initial support for ...extremely-low-birth-weight infants.
We performed a randomized, multicenter trial, with a 2-by-2 factorial design, involving infants who were born between 24 weeks 0 days and 27 weeks 6 days of gestation. Infants were randomly assigned to intubation and surfactant treatment (within 1 hour after birth) or to CPAP treatment initiated in the delivery room, with subsequent use of a protocol-driven limited ventilation strategy. Infants were also randomly assigned to one of two target ranges of oxygen saturation. The primary outcome was death or bronchopulmonary dysplasia as defined by the requirement for supplemental oxygen at 36 weeks (with an attempt at withdrawal of supplemental oxygen in neonates who were receiving less than 30% oxygen).
A total of 1316 infants were enrolled in the study. The rates of the primary outcome did not differ significantly between the CPAP group and the surfactant group (47.8% and 51.0%, respectively; relative risk with CPAP, 0.95; 95% confidence interval CI, 0.85 to 1.05) after adjustment for gestational age, center, and familial clustering. The results were similar when bronchopulmonary dysplasia was defined according to the need for any supplemental oxygen at 36 weeks (rates of primary outcome, 48.7% and 54.1%, respectively; relative risk with CPAP, 0.91; 95% CI, 0.83 to 1.01). Infants who received CPAP treatment, as compared with infants who received surfactant treatment, less frequently required intubation or postnatal corticosteroids for bronchopulmonary dysplasia (P<0.001), required fewer days of mechanical ventilation (P=0.03), and were more likely to be alive and free from the need for mechanical ventilation by day 7 (P=0.01). The rates of other adverse neonatal outcomes did not differ significantly between the two groups.
The results of this study support consideration of CPAP as an alternative to intubation and surfactant in preterm infants. (ClinicalTrials.gov number, NCT00233324.)
To determine if antenatal variables affect the risk of spontaneous intestinal perforation (SIP) among preterm infants when prophylactic indomethacin is used.
Retrospective case-control study of ...infants <29 weeks of gestational age between January 2010 and June 2018 at one hospital. SIP was defined as acute abdominal distension and pneumoperitoneum without signs of necrotizing enterocolitis at <14 days of life. Each case (n = 57) was matched with 2 controls (n = 114) for gestational age and birth year. Maternal and infant data were abstracted until the SIP or equivalent day for controls. Univariate analyses were followed by adjusted conditional logistic regressions and reported as OR and 95% CI.
Mothers of cases were younger, more often delivering multiples (31% vs 14%, P = .007), and less abruptions (15% vs 29%, P = .045) but did not differ in intra-partum betamethasone, magnesium, or indomethacin use. Prophylactic indomethacin was given on day 1 to 99% of infants. SIP was associated with a shorter interval from last betamethasone dose to delivery (46 hours vs 96 hours, P = .01). Dopamine use (14% vs 4%, P = .02), volume expansion (23% vs 8%, P = .003), and high grade intraventricular hemorrhage (28% vs 8%, P = .0008) were related postnatal factors. The adjusted odds of SIP increased by 1% for each hour decrease between the last dose of betamethasone and delivery (OR 1.01, 95% CI 1.002-1.019) and with multiple births (OR 2.66, 95% CI 1.05-6.77).
Antenatal betamethasone given shortly before delivery is associated with an increased risk of SIP. Potential interaction with medications such as postnatal indomethacin needs study.
To evaluate the effect of a nutrition care bundle in improving growth in premature infants during neonatal hospitalization.
This study was a retrospective analysis of prospectively collected data for ...584 surviving infants with birth weight ≤1000 g and gestational age 24-29 weeks admitted to a single-center neonatal intensive care unit between July 3, 2005, and June 6, 2016. Participants were divided into 3 discrete epochs based on evolving nutrition practices during the study period: epoch 1, baseline, open-bay setting; epoch 2, improved lactation staffing, introduction of high-protein formula, single-family room setting; epoch 3, complete nutrition care bundle. Infants in each epoch were evaluated for the primary outcome of change in weight z-score between postnatal day 7 and 36 weeks postmenstrual age (PMA) or discharge if sooner. Univariate and multivariable regression analyses were conducted to evaluate the effect of clinical variables on outcome.
Significant increases in weight z-score between day of life 7 and 36 weeks PMA were observed across the 3 epochs, which accounted for 31% (P < .0001) of the variance. Variables that were positive predictors of weight z-score change included birth weight z-score, cesarean delivery, and later epochs of nutritional support. Variables that were negative predictors of weight change included gestational age, postnatal steroids, and days on parenteral nutrition.
Implementation of a nutrition care bundle was associated with improved weight gain in extremely low birth weight infants.
Hypothermia is protective against brain injury after asphyxiation in animal models. However, the safety and effectiveness of hypothermia in term infants with encephalopathy is uncertain.
We conducted ...a randomized trial of hypothermia in infants with a gestational age of at least 36 weeks who were admitted to the hospital at or before six hours of age with either severe acidosis or perinatal complications and resuscitation at birth and who had moderate or severe encephalopathy. Infants were randomly assigned to usual care (control group) or whole-body cooling to an esophageal temperature of 33.5 degrees C for 72 hours, followed by slow rewarming (hypothermia group). Neurodevelopmental outcome was assessed at 18 to 22 months of age. The primary outcome was a combined end point of death or moderate or severe disability.
Of 239 eligible infants, 102 were assigned to the hypothermia group and 106 to the control group. Adverse events were similar in the two groups during the 72 hours of cooling. Primary outcome data were available for 205 infants. Death or moderate or severe disability occurred in 45 of 102 infants (44 percent) in the hypothermia group and 64 of 103 infants (62 percent) in the control group (risk ratio, 0.72; 95 percent confidence interval, 0.54 to 0.95; P=0.01). Twenty-four infants (24 percent) in the hypothermia group and 38 (37 percent) in the control group died (risk ratio, 0.68; 95 percent confidence interval, 0.44 to 1.05; P=0.08). There was no increase in major disability among survivors; the rate of cerebral palsy was 15 of 77 (19 percent) in the hypothermia group as compared with 19 of 64 (30 percent) in the control group (risk ratio, 0.68; 95 percent confidence interval, 0.38 to 1.22; P=0.20).
Whole-body hypothermia reduces the risk of death or disability in infants with moderate or severe hypoxic-ischemic encephalopathy.
The objective of this study was to determine whether Apgar scores at 10 minutes are associated with death or disability in early childhood after perinatal hypoxic-ischemic encephalopathy.
This was a ...secondary analysis of infants who were enrolled in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network hypothermia trial. Infants who were born at >or=36 weeks' gestation and had clinical and/or biochemical abnormalities at birth and encephalopathy at <6 hours were studied. Logistic regression and classification and regression-tree analysis were used to determine associations between Apgar scores at 10 minutes and neurodevelopmental outcome, adjusting for covariates. Death or disability (moderate or severe) at 18 to 22 months of age was the measured outcome.
Twenty of 208 infants were excluded (missing data). More than 90% of the infants had Apgar scores of 0 to 2 at 1 minute, and Apgar scores at 5 and 10 minutes shifted to progressively higher values; at 10 minutes, 27% of infants had Apgar scores of 0 to 2. After adjustment, each point decrease in Apgar score at 10 minutes was associated with a 45% increase in the odds of death or disability. Death or disability occurred in 76%, 82%, and 80% of infants with 10-minute Apgar scores of 0, 1, and 2, respectively. Classification and regression-tree analysis indicated that Apgar scores at 10 minutes were discriminators of outcome.
Apgar scores at 10 minutes provide useful prognostic data before other evaluations are available for infants with hypoxic-ischemic encephalopathy. Death or moderate/severe disability is common but not uniform with Apgar scores of <3; caution is needed before adopting a specific time interval to guide duration of resuscitation.
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