Jane E. Brumbaugh

Between-Hospital Variation in Treatment and Outcomes in Extremely Preterm Infants

BACKGROUND Between-hospital variation in outcomes among extremely preterm infants is largely unexplained and may reflect differences in hospital practices regarding the initiation of active lifesaving treatment as compared with comfort care after birth. METHODS We studied infants born between April 2006 and March 2011 at 24 hospitals included in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Data were collected for 4987 infants born before 27 weeks of gestation without congenital anomalies. Active treatment was defined as any potentially lifesaving intervention administered after birth. Survival and neurodevelopmental impairment at 18 to 22 months of corrected age were assessed in 4704 children (94.3%). RESULTS Overall rates of active treatment ranged from 22.1% (interquartile range [IQR], 7.7 to 100) among infants born at 22 weeks of gestation to 99.8% (IQR, 100 to 100) among those born at 26 weeks of gestation. Overall rates of survival and survival without severe impairment ranged from 5.1% (IQR, 0 to 10.6) and 3.4% (IQR, 0 to 6.9), respectively, among children born at 22 weeks of gestation to 81.4% (IQR, 78.2 to 84.0) and 75.6% (IQR, 69.5 to 80.0), respectively, among those born at 26 weeks of gestation. Hospital rates of active treatment accounted for 78% and 75% of the between-hospital variation in survival and survival without severe impairment, respectively, among children born at 22 or 23 weeks of gestation, and accounted for 22% and 16%, respectively, among those born at 24 weeks of gestation, but the rates did not account for any of the variation in outcomes among those born at 25 or 26 weeks of gestation. CONCLUSIONS Differences in hospital practices regarding the initiation of active treatment in infants born at 22, 23, or 24 weeks of gestation explain some of the between-hospital variation in survival and survival without impairment among such patients. (Funded by the National Institutes of Health.).

Altered Brain Function, Structure, and Developmental Trajectory in Children Born Late Preterm

Background:Late preterm birth (34–36 wk gestation) is a common occurrence with potential for altered brain development.Methods:This observational cohort study compared children at age 6–13 y based on the presence or absence of the historical risk factor of late preterm birth. Children completed a battery of cognitive assessments and underwent magnetic resonance imaging of the brain.Results:Late preterm children (n = 52) demonstrated slower processing speed (P = 0.035) and scored more poorly in visual-spatial perception (P = 0.032) and memory (P = 0.007) than full-term children (n = 74). Parents of late preterm children reported more behavioral difficulty (P = 0.004). There were no group differences in cognitive ability or academic achievement. Imaging revealed similar intracranial volumes but less total tissue and more cerebrospinal fluid (P = 0.004) for late preterm children compared to full-term children. The tissue difference was driven by differences in the cerebrum (P = 0.028) and distributed across cortical (P = 0.051) and subcortical tissue (P = 0.047). Late preterm children had a relatively smaller thalamus (P = 0.012) than full-term children. Only full-term children demonstrated significant decreases in cortical tissue volume (P < 0.001) and thickness (P < 0.001) with age.Conclusion:Late preterm birth may affect cognition, behavior, and brain structure well beyond infancy.

Neonatal survival after prolonged preterm premature rupture of membranes before 24 weeks of gestation.

OBJECTIVE: To evaluate neonatal survival after prolonged preterm premature rupture of membranes (PROM) in the era of antenatal corticosteroids, surfactant, and inhaled nitric oxide. METHODS: A single-center retrospective cohort study of neonates born from 2002–2011 after prolonged (1 week or more) preterm (less than 24 weeks of gestation) rupture of membranes was performed. The primary outcome was survival to discharge. Neonates whose membranes ruptured less than 24 hours before delivery (n=116) were matched (2:1) on gestational age at birth, sex, and antenatal corticosteroid exposure with neonates whose membranes ruptured 1 week or more before delivery (n=58). Analysis used conditional logistic regression for categorical data and Wilcoxon signed rank test for continuous data. RESULTS: The prolonged preterm PROM exposed and unexposed cohorts had survival rates of 90% and 95%, respectively, although underpowered to assess the statistical significance (P=.313). Exposed neonates were more likely have pulmonary hypoplasia (26/58 exposed, 1/114 unexposed, P<.001), pulmonary hypertension (21/56 exposed, 10/112 unexposed, P<.001), and pulmonary air leak (21/58 exposed, 14/114 unexposed, P<.001). Gestational age at rupture (20.4 weeks exposed, 22.3 weeks unexposed, P=.189), length of rupture (3.7 weeks exposed, 6.4 weeks unexposed, P=.717), and lowest maximal vertical pocket before 24 weeks of gestation (0 cm exposed, 1.4 cm unexposed, P=.114) did not discriminate between survivors and nonsurvivors after exposure to prolonged preterm PROM. CONCLUSION: With antenatal steroid exposure and aggressive pulmonary management, survival to discharge after prolonged preterm PROM was 90%. Pulmonary morbidities were common. Of note, the data were limited to women who remained pregnant 1 week or longer after rupture of membranes. LEVEL OF EVIDENCE: II

Effect of Therapeutic Hypothermia Initiated After 6 Hours of Age on Death or Disability Among Newborns With Hypoxic-Ischemic Encephalopathy: A Randomized Clinical Trial

Importance Hypothermia initiated at less than 6 hours after birth reduces death or disability for infants with hypoxic-ischemic encephalopathy at 36 weeks’ or later gestation. To our knowledge, hypothermia trials have not been performed in infants presenting after 6 hours. Objective To estimate the probability that hypothermia initiated at 6 to 24 hours after birth reduces the risk of death or disability at 18 months among infants with hypoxic-ischemic encephalopathy. Design, Setting, and Participants A randomized clinical trial was conducted between April 2008 and June 2016 among infants at 36 weeks’ or later gestation with moderate or severe hypoxic-ischemic encephalopathy enrolled at 6 to 24 hours after birth. Twenty-one US Neonatal Research Network centers participated. Bayesian analyses were prespecified given the anticipated limited sample size. Interventions Targeted esophageal temperature was used in 168 infants. Eighty-three hypothermic infants were maintained at 33.5°C (acceptable range, 33°C-34°C) for 96 hours and then rewarmed. Eighty-five noncooled infants were maintained at 37.0°C (acceptable range, 36.5°C-37.3°C). Main Outcomes and Measures The composite of death or disability (moderate or severe) at 18 to 22 months adjusted for level of encephalopathy and age at randomization. Results Hypothermic and noncooled infants were term (mean [SD], 39 [2] and 39 [1] weeks’ gestation, respectively), and 47 of 83 (57%) and 55 of 85 (65%) were male, respectively. Both groups were acidemic at birth, predominantly transferred to the treating center with moderate encephalopathy, and were randomized at a mean (SD) of 16 (5) and 15 (5) hours for hypothermic and noncooled groups, respectively. The primary outcome occurred in 19 of 78 hypothermic infants (24.4%) and 22 of 79 noncooled infants (27.9%) (absolute difference, 3.5%; 95% CI, −1% to 17%). Bayesian analysis using a neutral prior indicated a 76% posterior probability of reduced death or disability with hypothermia relative to the noncooled group (adjusted posterior risk ratio, 0.86; 95% credible interval, 0.58-1.29). The probability that death or disability in cooled infants was at least 1%, 2%, or 3% less than noncooled infants was 71%, 64%, and 56%, respectively. Conclusions and Relevance Among term infants with hypoxic-ischemic encephalopathy, hypothermia initiated at 6 to 24 hours after birth compared with noncooling resulted in a 76% probability of any reduction in death or disability, and a 64% probability of at least 2% less death or disability at 18 to 22 months. Hypothermia initiated at 6 to 24 hours after birth may have benefit but there is uncertainty in its effectiveness. Trial Registration clinicaltrials.gov Identifier: NCT00614744

Hot executive function following moderate-to-late preterm birth: altered delay discounting at 4 years of age.

Interest in monitoring long-term neurodevelopmental outcomes of children born moderate-to-late preterm (32-36 weeks gestation) is increasing. Moderate-to-late preterm birth has a negative impact on academic achievement, which may relate to differential development of executive function (EF). Prior studies reporting deficits in EF in preterm children have almost exclusively assessed EF in affectively neutral contexts in high-risk preterm children (< 32 weeks gestation). Disrupted function in motivational or emotionally charged contexts (hot EF) following preterm birth remains uninvestigated, despite evidence that preterm children show differential development of neural circuitry subserving hot EF, including reduced orbitofrontal cortex volume. The present study is the first to examine whether low-risk, healthy children born moderate-to-late preterm exhibit impairments in the development of hot EF. Preterm children at age 4.5 years were less likely to choose larger, delayed rewards across all levels of reward magnitude on a delay discounting task using tangible rewards, but performed more similarly to their full-term peers on a delay aversion task involving abstract rewards and on measures of cool EF. The relationship between gestational age at birth and selection of delayed rewards extended across the entire gestational age range of the sample (32-42 weeks), and remained significant after controlling for intelligence and processing speed. Results imply that there is not a finite cut-off point at which children are spared from potential long-term neurodevelopmental effects of PT birth. Further investigation of reward processing and hot EF in individuals with a history of PT birth is warranted given the susceptibility of prefrontal cortex development to early environmental variations.

The Relationship Between Brain Structure and Cognition in Transfused Preterm Children at School Age

Examine the relationship between brain structure and cognition in preterm children randomly assigned to a liberal red blood cell (RBC) transfusion strategy as neonates. Intelligence, achievement, and neuropsychological measures were assessed and structural imaging was obtained (n = 26; 38% male). Global brain volumes were related to cognitive outcome. Additionally, females performed lower on verbal fluency; lower performance was related to temporal white matter volume. Findings provide possible evidence of the adverse effect of a liberal RBC transfusion strategy in which females had decreased temporal lobe white matter directly related to poor verbal fluency.

Outcomes of Extremely Preterm Infants Born to Insulin-Dependent Diabetic Mothers

BACKGROUND AND OBJECTIVE: Little is known about in-hospital morbidities and neurodevelopmental outcomes among extremely preterm infants born to women with insulin-dependent diabetes mellitus (IDDM). We examined risks of mortality, in-hospital morbidities, and neurodevelopmental outcomes at 18 to 22 months’ corrected age between extremely preterm infants of women with insulin use before pregnancy (IBP), with insulin use started during pregnancy (IDP), and without IDDM. METHODS: Infants 22 to 28 weeks’ gestation born or cared for at a Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network center (2006–2011) were studied. Regression models compared the association between maternal IDDM and timing of insulin use and the outcomes of the 3 groups. RESULTS: Of 10 781 infants, 536 (5%) were born to women with IDDM; 58% had IBP, and 36% had IDP. Infants of mothers with IBP had higher risks of necrotizing enterocolitis (adjusted relative risk [RR] = 1.55 [95% confidence interval (CI) 1.17–2.05]) and late-onset sepsis (adjusted RR = 1.26 [95% CI 1.07–1.48]) than infants of mothers without IDDM. There was some indication of higher in-hospital mortality risk among infants of mothers with IBP compared with those with IDP (adjusted RR = 1.33 [95% CI 1.00–1.79]). Among survivors evaluated at 18 to 22 months’ corrected age, average head circumference z score was lower for infants of mothers with IBP compared with those without IDDM, but there were no differences in risk of neurodevelopmental impairment. CONCLUSIONS: In this cohort of extremely preterm infants, infants of mothers with IBP had higher risks of necrotizing enterocolitis, sepsis, and small head circumference.

The changing relationship between bronchopulmonary dysplasia and cognition in very preterm infants

To characterise the relationship between bronchopulmonary dysplasia (BPD) severity and cognition in the post‐surfactant era.

Body temperatures of very low birth weight infants on admission to a neonatal intensive care unit

Abstract Objective: Hypothermia occurs frequently in the first minutes after birth in preterm infants. Hyperthermia also occurs, often as a consequence of efforts to provide thermal support. Both hypothermia and hyperthermia are potentially harmful. Our objective was to examine the distribution of admission temperatures of very low birth weight (VLBW) infants, the effect of gestational age on admission temperatures, and the time required for correction of low temperatures. Methods: Admission axillary temperatures were retrieved from the medical records for all VLBW infants born in our hospital during a 5-year period. The temperatures were classified as severe (<35.0 °C), moderate (35.0–35.9 °C), or mild (36.0–36.4 °C) hypothermia, normothermia (36.5–37.4 °C), or hyperthermia (≥37.5 °C). The relationship between gestational age and admission temperature was examined. In addition, we analyzed the time required for normalization of low temperatures. Results: Overall, 12% of infants were severely hypothermic, 40% moderately hypothermic, 27% mildly hypothermic, 19% normothermic, and 2% hyperthermic. Gestational age was inversely related to hypothermia risk and to the time required for recovery to normothermia. Conclusion: Admission hypothermia is common among VLBW infants and is affected by gestational age.