Rebecca Bara

Brain injury following trial of hypothermia for neonatal hypoxic-ischaemic encephalopathy

Objective The objective of our study was to examine the relationship between brain injury and outcome following neonatal hypoxic–ischaemic encephalopathy treated with hypothermia. Design and patients Neonatal MRI scans were evaluated in the National Institute of Child Health and Human Development (NICHD) randomised controlled trial of whole-body hypothermia and each infant was categorised based upon the pattern of brain injury on the MRI findings. Brain injury patterns were assessed as a marker of death or disability at 18–22 months of age. Results Scans were obtained on 136 of 208 trial participants (65%); 73 in the hypothermia and 63 in the control group. Normal scans were noted in 38 of 73 infants (52%) in the hypothermia group and 22 of 63 infants (35%) in the control group. Infants in the hypothermia group had fewer areas of infarction (12%) compared to infants in the control group (22%). Fifty-one of the 136 infants died or had moderate or severe disability at 18 months. The brain injury pattern correlated with outcome of death or disability and with disability among survivors. Each point increase in the severity of the pattern of brain injury was independently associated with a twofold increase in the odds of death or disability. Conclusions Fewer areas of infarction and a trend towards more normal scans were noted in brain MRI following whole-body hypothermia. Presence of the NICHD pattern of brain injury is a marker of death or moderate or severe disability at 18–22 months following hypothermia for neonatal encephalopathy.

Hypocarbia and Adverse Outcome in Neonatal Hypoxic-Ischemic Encephalopathy

OBJECTIVE To evaluate the association between early hypocarbia and 18- to 22-month outcome among neonates with hypoxic-ischemic encephalopathy. STUDY DESIGN Data from the National Institute of Child Health and Human Development Neonatal Research Network randomized, controlled trial of whole-body hypothermia for neonatal hypoxic-ischemic encephalopathy were used for this secondary observational study. Infants (n = 204) had multiple blood gases recorded from birth to 12 hours of study intervention (hypothermia versus intensive care alone). The relationship between hypocarbia and outcome (death/disability at 18 to 22 months) was evaluated by unadjusted and adjusted analyses examining minimum PCO(2) and cumulative exposure to PCO(2) <35 mm Hg. The relationship between cumulative PCO(2) <35 mm Hg (calculated as the difference between 35 mm Hg and the sampled PCO(2) multiplied by the duration of time spent <35 mm Hg) and outcome was evaluated by level of exposure (none-high) using a multiple logistic regression analysis with adjustments for pH, level of encephalopathy, treatment group (± hypothermia), and time to spontaneous respiration and ventilator days; results were expressed as odds ratios and 95% confidence intervals. Alternative models of CO(2) concentration were explored to account for fluctuations in CO(2). RESULTS Both minimum PCO(2) and cumulative PCO(2) <35 mm Hg were associated with poor outcome (P < .05). Moreover, death/disability increased with greater cumulative exposure to PCO(2) <35 mm Hg. CONCLUSIONS Hypocarbia is associated with poor outcome after hypoxic-ischemic encephalopathy.

Predictive Value of an Early Amplitude Integrated Electroencephalogram and Neurologic Examination

OBJECTIVE: To examine the predictive validity of the amplitude integrated electroencephalogram (aEEG) and stage of encephalopathy among infants with hypoxic-ischemic encephalopathy (HIE) eligible for therapeutic whole-body hypothermia. DESIGN: Neonates were eligible for this prospective study if moderate or severe HIE occurred at <6 hours and an aEEG was obtained at <9 hours of age. The primary outcome was death or moderate/severe disability at 18 months. RESULTS: There were 108 infants (71 with moderate HIE and 37 with severe HIE) enrolled in the study. aEEG findings were categorized as normal, with continuous normal voltage (n = 12) or discontinuous normal voltage (n = 12), or abnormal, with burst suppression (n = 22), continuous low voltage (n = 26), or flat tracing (n = 36). At 18 months, 53 infants (49%) experienced death or disability. Severe HIE and an abnormal aEEG were related to the primary outcome with univariate analysis, whereas severe HIE alone was predictive of outcome with multivariate analysis. Addition of aEEG pattern to HIE stage did not add to the predictive value of the model; the area under the curve changed from 0.72 to 0.75 (P = .19). CONCLUSIONS: The aEEG background pattern did not significantly enhance the value of the stage of encephalopathy at study entry in predicting death and disability among infants with HIE.

Evolution of Encephalopathy during Whole Body Hypothermia for Neonatal Hypoxic-Ischemic Encephalopathy

OBJECTIVE To examine the predictive ability of stage of hypoxic-ischemic encephalopathy (HIE) for death or moderate/severe disability at 18 months among neonates undergoing hypothermia. STUDY DESIGN Stage of encephalopathy was evaluated at <6 hours of age, during study intervention, and at discharge among 204 participants in the National Institute of Child Health and Human Development Neonatal Research Network Trial of whole body hypothermia for HIE. HIE was examined as a predictor of outcome by regression models. RESULTS Moderate and severe HIE occurred at <6 hours of age among 68% and 32% of 101 hypothermia group infants and 60% and 40% of 103 control group infants, respectively. At 24 and 48 hours of study intervention, infants in the hypothermia group had less severe HIE than infants in the control group. Persistence of severe HIE at 72 hours increased the risk of death or disability after controlling for treatment group. The discharge exam improved the predictive value of stage of HIE at <6 hours for death/disability. CONCLUSIONS On serial neurologic examinations, improvement in stage of HIE was associated with cooling. Persistence of severe HIE at 72 hours and an abnormal neurologic exam at discharge were associated with a greater risk of death or disability.

Outcomes of small for gestational age infants born at <27 weeks' gestation

OBJECTIVE To determine whether small for gestational age (SGA) infants born at <27 weeks gestational age (GA) are at increased risk for mortality, morbidity, and growth and neurodevelopmental impairment at 18-22 months corrected age. STUDY DESIGN This was a retrospective cohort study from National Institute of Child Health and Human Development Neonatal Research Networks Generic Database and Follow-Up Studies. Infants born at <27 weeks GA between January 2006 and July 2008 were included. SGA was defined as birth weight <10th percentile for GA based on Olsen growth curves. Infants with birth weight ≥ 10th percentile for GA were classified as non-SGA. Maternal and infant characteristics, neonatal outcomes, and neurodevelopmental data were compared in SGA and non-SGA infants. Neurodevelopmental impairment was defined as any of the following: cognitive score <70 on the Bayley Scales of Infant Development III, moderate or severe cerebral palsy, bilateral hearing loss (with and without amplification), or blindness (bilateral vision <20/200). Logistic regression analysis was applied to evaluate the associations between SGA status and death or neurodevelopmental impairment. RESULTS The SGA group comprised 385 infants; the non-SGA group, 2586 infants. Compared with mothers of non-SGA infants, mothers of SGA infants were more likely to have a high school education, prenatal care, cesarean delivery, pregnancy-induced hypertension, and antenatal corticosteroid exposure. Compared with non-SGA infants, SGA infants had higher mortality and were more likely to have postnatal growth failure, prolonged mechanical ventilation, and postnatal steroid use. SGA status was associated with increased risk of death or neurodevelopmental impairment (OR, 3.91; 95% CI, 2.91-5.25; P < .001). CONCLUSION SGA status in infants born at <27 weeks GA is associated with an increased likelihood of postnatal steroid use, mortality, growth failure, and neurodevelopmental impairment at 18-22 months corrected age.

Outcomes of Small for Gestational Age Infants Born at

OBJECTIVE To determine whether small for gestational age (SGA) infants born at <27 weeks gestational age (GA) are at increased risk for mortality, morbidity, and growth and neurodevelopmental impairment at 18-22 months corrected age. STUDY DESIGN This was a retrospective cohort study from National Institute of Child Health and Human Development Neonatal Research Networks Generic Database and Follow-Up Studies. Infants born at <27 weeks GA between January 2006 and July 2008 were included. SGA was defined as birth weight <10th percentile for GA based on Olsen growth curves. Infants with birth weight ≥ 10th percentile for GA were classified as non-SGA. Maternal and infant characteristics, neonatal outcomes, and neurodevelopmental data were compared in SGA and non-SGA infants. Neurodevelopmental impairment was defined as any of the following: cognitive score <70 on the Bayley Scales of Infant Development III, moderate or severe cerebral palsy, bilateral hearing loss (with and without amplification), or blindness (bilateral vision <20/200). Logistic regression analysis was applied to evaluate the associations between SGA status and death or neurodevelopmental impairment. RESULTS The SGA group comprised 385 infants; the non-SGA group, 2586 infants. Compared with mothers of non-SGA infants, mothers of SGA infants were more likely to have a high school education, prenatal care, cesarean delivery, pregnancy-induced hypertension, and antenatal corticosteroid exposure. Compared with non-SGA infants, SGA infants had higher mortality and were more likely to have postnatal growth failure, prolonged mechanical ventilation, and postnatal steroid use. SGA status was associated with increased risk of death or neurodevelopmental impairment (OR, 3.91; 95% CI, 2.91-5.25; P < .001). CONCLUSION SGA status in infants born at <27 weeks GA is associated with an increased likelihood of postnatal steroid use, mortality, growth failure, and neurodevelopmental impairment at 18-22 months corrected age.

Cognitive Outcomes After Neonatal Encephalopathy

OBJECTIVES: To describe the spectrum of cognitive outcomes of children with and without cerebral palsy (CP) after neonatal encephalopathy, evaluate the prognostic value of early developmental testing and report on school services and additional therapies. METHODS: The participants of this study are the school-aged survivors of the National Institute of Child Health and Human Development Neonatal Research Network randomized controlled trial of whole-body hypothermia. Children underwent neurologic examinations and neurodevelopmental and cognitive testing with the Bayley Scales of Infant Development–II at 18 to 22 months and the Wechsler intelligence scales and the Neuropsychological Assessment–Developmental Neuropsychological Assessment at 6 to 7 years. Parents were interviewed about functional status and receipt of school and support services. We explored predictors of cognitive outcome by using multiple regression models. RESULTS: Subnormal IQ scores were identified in more than a quarter of the children: 96% of survivors with CP had an IQ <70, 9% of children without CP had an IQ <70, and 31% had an IQ of 70 to 84. Children with a mental developmental index <70 at 18 months had, on average, an adjusted IQ at 6 to 7 years that was 42 points lower than that of those with a mental developmental index >84 (95% confidence interval, −49.3 to −35.0; P < .001). Twenty percent of children with normal IQ and 28% of those with IQ scores of 70 to 84 received special educational support services or were held back ≥1 grade level. CONCLUSIONS: Cognitive impairment remains an important concern for all children with neonatal encephalopathy.

Temperature profile and outcomes of neonates undergoing whole body hypothermia for neonatal hypoxic-ischemic encephalopathy

Background: Decreases below the target temperature were noted among neonates undergoing cooling in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network Trial of whole body hypothermia for neonatal hypoxic-ischemic encephalopathy. Objective: To examine the temperature profile and impact on outcome among ≥36 wk gestation neonates randomized at ⩽6 hrs of age targeting an esophageal temperature of 33.5°C for 72 hrs. Design, Setting, Patients: Infants with intermittent temperatures recorded of <32.0°C during induction and maintenance of cooling were compared to all other cooled infants, and the relationship with outcome at 18 months was evaluated. Interventions: None. Measurements and Main Results: There were no differences in the stage of encephalopathy, acidosis, or 10 min Apgar scores between infants with temperatures of <32.0°C during induction (n = 33) or maintenance (n = 10) and all other infants who were cooled (n = 58); however, birth weight was lower and the need for blood pressure support higher among infants with temperatures of <32.0°C compared to all other cooled infants. No increase in acute adverse events was noted among infants with temperatures of <32.0°C, and hours spent at <32°C was not associated with the primary outcome of death or moderate/severe disability or the Bayley II Mental Developmental Index at 18 months. Conclusions: Term infants with a lower birth weight are at risk for decreasing temperatures of <32.0°C while undergoing body cooling using a servo-controlled system. This information suggests extra caution during the application of hypothermia as these lower birth weight infants are at risk for overcooling. Our findings may assist in planning additional trials of lower target temperature for neonatal hypoxic-ischemic encephalopathy.

Mortality and Morbidity of VLBW Infants With Trisomy 13 or Trisomy 18

OBJECTIVE: Little is known about how very low birth weight (VLBW) affects survival and morbidities among infants with trisomy 13 (T13) or trisomy 18 (T18). We examined the care plans for VLBW infants with T13 or T18 and compared their risks of mortality and neonatal morbidities with VLBW infants with trisomy 21 and VLBW infants without birth defects. METHODS: Infants with birth weight 401 to 1500 g born or cared for at a participating center of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network during the period 1994–2009 were studied. Poisson regression models were used to examine risk of death and neonatal morbidities among infants with T13 or T18. RESULTS: Of 52 262 VLBW infants, 38 (0.07%) had T13 and 128 (0.24%) had T18. Intensity of care in the delivery room varied depending on whether the trisomy was diagnosed before or after birth. The plan for subsequent care for the majority of the infants was to withdraw care or to provide comfort care. Eleven percent of infants with T13 and 9% of infants with T18 survived to hospital discharge. Survivors with T13 or T18 had significantly increased risk of patent ductus arteriosus and respiratory distress syndrome compared with infants without birth defects. No infant with T13 or T18 developed necrotizing enterocolitis. CONCLUSIONS: In this cohort of liveborn VLBW infants with T13 or T18, the timing of trisomy diagnosis affected the plan for care, survival was poor, and death usually occurred early.

Neurodevelopmental outcome of extremely premature infants exposed to incomplete, no or complete antenatal steroids

Abstract Objective: To compare the neurodevelopmental outcomes at 18–22 months’ corrected age of extremely premature infants exposed to a complete course, an incomplete course or no dose of antenatal steroids (ANS). Methods: Retrospective chart review of extremely premature (<28 weeks gestational age) neonates over a 3-year period. Neurodevelopmental assessment at 18–22 months’ corrected age included a standardized neurologic examination and the Bayley Scales of Infant and Toddler development II or III. Intact survival was defined as survival without cerebral palsy (CP), blindness or deafness and mental developmental index (MDI)/cognitive score ≥85. Neurodevelopmental impairment (NDI) was defined as any of the following: moderate or severe CP, MDI/cognitive score <70, deafness or blindness. Patients were categorized into three groups: (A) no ANS; (B) incomplete course and (C) complete course of ANS. Results: Outcome data were available for 134 (88%) patients of our cohort (n = 153). Severe intraventricular hemorrhage (IVH) was significantly lower and intact survival was higher in the complete ANS group (p < 0.01). On logistic regression, with gestational age, gender, maternal insurance and ANS exposure as covariates, an incomplete (versus complete) course of ANS (p = 0.006) and gestational age were significantly associated with lower intact survival at 18–22 months. Conclusions: A complete course of ANS was associated with an increased likelihood of intact survival at a corrected age of 18–22 months among extremely premature infants, compared with an incomplete course. Follow-up studies should account for the differential benefit of complete versus incomplete course of ANS administration.