Antiseizure medication at discharge in infants with hypoxic-ischaemic encephalopathy: an observational study.

OBJECTIVES: To assess variability in continuation of antiseizure medication (ASM) at discharge and to evaluate if continuation of ASM at discharge is associated with death or disability among infants with hypoxic-ischaemic encephalopathy (HIE) and seizures. DESIGN: Retrospective study of infants enrolled in three National Institute of Child Health and Human Development Neonatal Research Network Trials of therapeutic hypothermia. SETTING: 22 US centres. PATIENTS: Infants with HIE who survived to discharge and had clinical or electrographic seizures treated with ASM. EXPOSURES: ASM continued or discontinued at discharge. OUTCOMES: Death or moderate-to-severe disability at 18-22 months, using trial definitions. Multivariable logistic regression evaluated the association between continuation of ASM at discharge and the primary outcome, adjusting for severity of HIE, hypothermia trial treatment arm, use of electroencephalogram, discharge on gavage feeds, Apgar Score at 5 min, birth year and centre. RESULTS: Of 302 infants included, 61% were continued on ASMs at discharge (range 13%-100% among 22 centres). Electroencephalogram use occurred in 92% of the cohort. Infants with severe HIE comprised 24% and 22% of those discharged with and without ASM, respectively. The risk of death or moderate-to-severe disability was greater for infants continued on ASM at discharge, compared with those infants discharged without ASM (44% vs 28%, adjusted OR 2.14; 95% CI 1.13 to 4.05). CONCLUSIONS: In infants with HIE and seizures, continuation of ASM at discharge varies substantially among centres and may be associated with a higher risk of death or disability at 18-22 months of age.

Achieved oxygen saturations and retinopathy of prematurity in extreme preterms.

OBJECTIVE: To identify achieved oxygen saturations (SpO2) associated with increased risk of severe retinopathy of prematurity (ROP). DESIGN: This is a secondary analysis of the Surfactant Positive Airway Pressure and Pulse Oximetry Trial (SUPPORT)randomised controlled trial. SpO2 was recorded up to 36 weeks' postmenstrual age. Saturations through 9 postnatal weeks were explored graphically, and logistic regression models were created to predict severe ROP. SETTING: 20 centres of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. PATIENTS: 984 surviving infants of 24-27 weeks' gestational age born in 2005-2009. INTERVENTIONS: SUPPORT targeted SpO2 to a lower (85%-89%) or higher (91%-95%) range through 36 weeks' postmenstrual age or off respiratory support. MAIN OUTCOME MEASURES: Severe ROP defined as threshold ROP, ophthalmological surgery or bevacizumab treatment. RESULTS: There were statistically significant interactions between duration of oxygen supplementation and percentage of time in certain achieved saturation ranges. Specifically, for infants who spent at least 2 weeks on oxygen in postnatal weeks 1-5, a higher percentage of time at 91%-96% SpO2 was associated with increased odds of severe ROP. For infants who spent at least 3 weeks on oxygen in postnatal weeks 6-9, a higher percentage of time at 97%-100% SpO2 was associated with increased odds of severe ROP. Other significant risk factors were lower gestational age and birth weight, non-Hispanic white versus black race, prospectively defined severe illness, late-onset sepsis or meningitis, and clinical centre. CONCLUSIONS: Among extremely preterm survivors to discharge, the association between SpO2 and severe ROP depended on the timing and duration of oxygen supplementation.

Chorioamnionitis and early childhood outcomes among extremely low-gestational-age neonates.

IMPORTANCE: Chorioamnionitis is strongly linked to preterm birth and neonatal infection. The association between histological and clinical chorioamnionitis and cognitive, behavioral, and neurodevelopmental outcomes among extremely preterm neonates is less clear. We evaluated the impact of chorioamnionitis on 18- to 22-month neurodevelopmental outcomes in a contemporary cohort of extremely preterm neonates. OBJECTIVE: To compare the neonatal and neurodevelopmental outcomes of 3 groups of extremely low-gestational-age infants with increasing exposure to perinatal inflammation: no chorioamnionitis, histological chorioamnionitis alone, or histological plus clinical chorioamnionitis. DESIGN, SETTING, AND PARTICIPANTS: Longitudinal observational study at 16 centers of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Two thousand three hundred ninety extremely preterm infants born at less than 27 weeks' gestational age (GA) between January 1, 2006, and December 31, 2008, with placental histopathology and 18 to 22 months' corrected age follow-up data were eligible. MAIN EXPOSURE: Chorioamnionitis. MAIN OUTCOMES AND MEASURES: Outcomes included cerebral palsy, gross motor functional limitation, behavioral scores (according to the Brief Infant-Toddler Social and Emotional Assessment), cognitive and language scores (according to the Bayley Scales of Infant and Toddler Development, Third Edition), and composite measures of death/neurodevelopmental impairment. Multivariable logistic and linear regression models were developed to assess the association between chorioamnionitis and outcomes while controlling for important variables known at birth. RESULTS: Neonates exposed to chorioamnionitis had a lower GA and higher rates of early-onset sepsis and severe periventricular-intraventricular hemorrhage as compared with unexposed neonates. In multivariable models evaluating death and neurodevelopmental outcomes, inclusion of GA in the model diminished the association between chorioamnionitis and adverse outcomes. Still, histological plus clinical chorioamnionitis was associated with increased risk of cognitive impairment as compared with no chorioamnionitis (adjusted odds ratio [OR], 2.38 [95% CI, 1.32 to 4.28] without GA; adjusted OR, 2.00 [95% CI, 1.10 to 3.64] with GA as a covariate). Histological chorioamnionitis alone was associated with lower odds of death/neurodevelopmental impairment as compared with histological plus clinical chorioamnionitis (adjusted OR, 0.68 [95% CI, 0.52 to 0.89] without GA; adjusted OR, 0.66 [95% CI, 0.49 to 0.89] with GA as a covariate). Risk of behavioral problems did not differ statistically between groups. CONCLUSIONS AND RELEVANCE: Antenatal exposure to chorioamnionitis is associated with altered odds of cognitive impairment and death/neurodevelopmental impairment in extremely preterm infants.

Spontaneous intestinal perforation in extremely low birth weight infants: association with indometacin therapy and effects on neurodevelopmental outcomes at 18-22 months corrected age.

BACKGROUND: Spontaneous intestinal perforation (SIP) is associated with the use of postnatal glucocorticoids and indometacin in extremely low birth weight (ELBW) infants. The authors hypothesised: 1) an association of SIP with the use of antenatal steroids (ANS) and indometacin either as prophylaxis for intraventricular hemorrhage (IVH) (P Indo) or for treatment of PDA (Indo/PDA) and 2) an increased risk of death or abnormal neurodevelopmental outcomes in infants with SIP at 18-22 months corrected age. DESIGN/METHODS: The authors retrospectively identified ELBW infants with SIP in the Neonatal Research Network's generic database. Unadjusted analysis identified the differences in maternal, neonatal and clinical variables between infants with and without SIP. Logistic regression analysis identified the adjusted OR for SIP with reference to ANS, P Indo and Indo/PDA. Neurodevelopmental outcomes were assessed among survivors at 18-22 months corrected age. RESULTS: Indo/PDA was associated with an increased risk of SIP (adjusted OR 1.61; 95% CI 1.25 to 2.08), while P Indo and ANS were not. SIP was independently associated with an increased risk of death or neurodevelopmental impairment (NDI) (adjusted OR 1.85; 95% CI 1.32 to 2.60) and NDI among survivors (adjusted OR 1.75, 95% CI 1.20 to 2.55). CONCLUSION: Indometacin used for IVH prophylaxis and ANS were not associated with the occurrence of SIP in ELBW infants. Indometacin used for treatment of symptomatic PDA was however associated with an increased risk of SIP. ELBW infants with SIP have an increased risk of poor neurodevelopmental outcomes.

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.

Outcomes of safety and effectiveness in a multicenter randomized, controlled trial of whole-body hypothermia for neonatal hypoxic-ischemic encephalopathy.

BACKGROUND: Whole-body hypothermia reduced the frequency of death or moderate/severe disabilities in neonates with hypoxic-ischemic encephalopathy in a randomized, controlled multicenter trial. OBJECTIVE: Our goal was to evaluate outcomes of safety and effectiveness of hypothermia in infants up to 18 to 22 months of age. DESIGN/METHODS: A priori outcomes were evaluated between hypothermia (n = 102) and control (n = 106) groups. RESULTS: Encephalopathy attributable to causes other than hypoxia-ischemia at birth was not noted. Inotropic support (hypothermia, 59% of infants; control, 56% of infants) was similar during the 72-hour study intervention period in both groups. Need for blood transfusions (hypothermia, 24%; control, 24%), platelet transfusions (hypothermia, 20%; control, 12%), and volume expanders (hypothermia, 54%; control, 49%) was similar in the 2 groups. Among infants with persistent pulmonary hypertension (hypothermia, 25%; control, 22%), nitric-oxide use (hypothermia, 68%; control, 57%) and placement on extracorporeal membrane oxygenation (hypothermia, 4%; control, 9%) was similar between the 2 groups. Non-central nervous system organ dysfunctions occurred with similar frequency in the hypothermia (74%) and control (73%) groups. Rehospitalization occurred among 27% of the infants in the hypothermia group and 42% of infants in the control group. At 18 months, the hypothermia group had 24 deaths, 19 severe disabilities, and 2 moderate disabilities, whereas the control group had 38 deaths, 25 severe disabilities, and 1 moderate disability. Growth parameters were similar between survivors. No adverse outcomes were noted among infants receiving hypothermia with transient reduction of temperature below a target of 33.5 degrees C at initiation of cooling. There was a trend in reduction of frequency of all outcomes in the hypothermia group compared with the control group in both moderate and severe encephalopathy categories. CONCLUSIONS: Although not powered to test these secondary outcomes, whole-body hypothermia in infants with encephalopathy was safe and was associated with a consistent trend for decreasing frequency of each of the components of disability.

A cluster-randomized trial of benchmarking and multimodal quality improvement to improve rates of survival free of bronchopulmonary dysplasia for infants with birth weights of less than 1250 grams.

OBJECTIVE: We tested whether NICU teams trained in benchmarking and quality improvement would change practices and improve rates of survival without bronchopulmonary dysplasia in inborn neonates with birth weights of <1250 g. METHODS: A cluster-randomized trial enrolled 4093 inborn neonates with birth weights of <1250 g at 17 centers of the National Institute of Child Health and Human Development Neonatal Research Network. Three centers were selected as best performers, and the remaining 14 centers were randomized to intervention or control. Changes in rates of survival free of bronchopulmonary dysplasia were compared between study year 1 and year 3. RESULTS: Intervention centers implemented potentially better practices successfully; changes included reduced oxygen saturation targets and reduced exposure to mechanical ventilation. Five of 7 intervention centers and 2 of 7 control centers implemented use of high-saturation alarms to reduce oxygen exposure. Lower oxygen saturation targets reduced oxygen levels in the first week of life. Despite these changes, rates of survival free of bronchopulmonary dysplasia were all similar between intervention and control groups and remained significantly less than the rate achieved in the best-performing centers (73.3%). CONCLUSIONS: In this cluster-randomized trial, benchmarking and multimodal quality improvement changed practices but did not reduce bronchopulmonary dysplasia rates.