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1.  Characteristics of extremely low birth weight infant survivors with unimpaired outcomes at 30 months of age 
To evaluate characteristics of unimpaired outcome in ELBW survivors.
Study Design
ELBW infants (n=714) with 30 months’ assessments were analyzed. Logistic regression was used to develop a model for the binary outcome of unimpaired versus impaired outcome.
Thirty-three percent of infants had an unimpaired outcome. 17% of ELBW survivors had a Bayley II Mental Developmental Index score of ≥101 and 2% had a score of ≥116. Female gender, use of antenatal steroids, maternal education ≥ high school and absence of major neonatal morbidities were independent predictors of unimpaired outcome. The likelihood of an unimpaired outcome in presence of major neonatal morbidities was higher in infants exposed to antenatal steroids.
The majority of unimpaired ELBW survivors had cognitive scores shifted towards the lower end of the normal distribution. Exposure to antenatal steroids was associated with higher likelihood of an unimpaired outcome in infants with major neonatal morbidities.
PMCID: PMC3903461  PMID: 23807719
extremely low birth weight; unimpaired outcome; outcome; antenatal steroids; cerebral palsy
2.  Outcomes of Extremely Low Birth Weight Infants with Bronchopulmonary Dysplasia: Impact of the Physiologic Definition 
Early human development  2012;88(7):509-515.
We compared neurodevelopmental outcomes of extremely low birth weight (ELBW) infants with and without bronchopulmonary dysplasia (BPD), using the physiologic definition.
Study Design
ELBW (birth weights <1000 grams) infants admitted to the Neonatal Research Network centers and hospitalized at 36 weeks postmenstrual age (n=1,189) were classified using the physiologic definition of BPD. Infants underwent Bayley III assessment at 18-22 months corrected age. Multivariable logistic regression was used to determine the association between physiologic BPD and cognitive impairment (score < 70).
BPD by the physiologic definition was diagnosed in 603 (52%) infants, 537 of whom were mechanically ventilated or on FiO2 > 30% and 66 who failed the room air challenge. Infants on room air (n=505) and those who passed the room air challenge (n=51) were classified as “no BPD” (n=556). At follow up, infants with BPD had significantly lower mean weight and head circumference. Moderate to severe cerebral palsy (7 vs. 2.1%) and spastic diplegia (7.8 vs. 4.1%) and quadriplegia (3.9 vs. 0.9%) phenotypes as well as cognitive (12.8 vs. 4.6%) and language scores < 70 (24.2 vs. 12.3%) were significantly more frequent in those with BPD compared to those without BPD. BPD was independently associated (adjusted OR 2.4; 95% CI 1.40-4.13) with cognitive impairment.
Rates of adverse neurodevelopmental outcomes in early childhood were significantly higher in those with BPD. BPD by the physiologic definition was independently associated with cognitive impairment using Bayley Scales III. These findings have implications for targeted post-discharge surveillance and early intervention.
PMCID: PMC3686277  PMID: 22236557
Outcome; preterm; bronchopulmonary dysplasia; physiologic definition
3.  Outcome of Extremely Low Birth Weight Infants Who Received Delivery Room Cardiopulmonary Resuscitation 
The Journal of Pediatrics  2011;160(2):239-244.e2.
To determine whether delivery room cardiopulmonary resuscitation (DR-CPR) independently predicts morbidities and neurodevelopmental impairment (NI) in extremely low birth weight (ELBW) infants.
Study design
Cohort study of infants born with birth weight (BW) 401-1000g and gestational age (GA) 23-30wks. DR-CPR was defined as chest compressions and/or drugs. Logistic regression was used to determine associations between DR-CPR and morbidities, mortality and NI at 18-24 months (Bayley II mental or psychomotor index < 70, cerebral palsy, blindness or deafness). Data are adjusted Odds Ratio (OR) with 95% confidence interval.
Of 8685 infants, 1333(15%) received DR-CPR. DR-CPR infants had lower BW (708±141vs 764±146g, p<0.0001) and GA (25±2 vs 26±2 wks, p<0.0001). DR-CPR infants had more pneumothoraces (OR 1.28, 1.48-2.99), Grade 3-4 intraventricular hemorrhage (OR 1.47, 1.23-1.74), bronchopulmonary dysplasia (OR 1.34, 1.13-1.59), death by 12 hours (OR 3.69, 2.98-4.57) and by 120 days after birth (OR 2.22, 1.93-2.57). NI among survivors (OR 1.23, 1.02-1.49), and death or NI (OR 1.70, 1.46-1.99) were higher for DR-CPR infants. Only 14% of DR-CPR recipients with 5-minute Apgar score<2 survived without NI.
DR-CPR is a prognostic marker for higher mortality and NI for ELBW survivors. New DR-CPR strategies are needed for this population.
PMCID: PMC3258355  PMID: 21930284
cardiac compressions; epinephrine; neurodevelopmental outcomes
4.  Early-Childhood Neurodevelopmental Outcomes Are Not Improving for Infants Born at <25 Weeks' Gestational Age 
Pediatrics  2011;127(1):62-70.
We compared neurodevelopmental outcomes at 18 to 22 months' corrected age of infants born with extremely low birth weight at an estimated gestational age of <25 weeks during 2 periods: 1999–2001 (epoch 1) and 2002–2004 (epoch 2).
We conducted a multicenter, retrospective analysis of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Perinatal and neonatal variables and outcomes were compared between epochs. Neurodevelopmental outcomes at 18 to 22 months' corrected age were evaluated with neurologic exams and Bayley Scales of Infant Development II. Logistic regression analyses determined the independent risk of epoch for adverse outcomes.
Infant survival was similar between epochs (epoch 1, 35.4%, vs epoch 2, 32.3%; P = .09). A total of 411 of 452 surviving infants in epoch 1 and 405 of 438 surviving infants in epoch 2 were evaluated at 18 to 22 months' corrected age. Cesarean delivery (P = .03), surgery for patent ductus arteriosus (P = .004), and late sepsis (P = .01) were more common in epoch 2, but postnatal steroid use was dramatically reduced (63.5% vs 32.8%; P < .0001). Adverse outcomes at 18 to 22 months' corrected age were common in both epochs. Moderate-to-severe cerebral palsy was diagnosed in 11.1% of surviving infants in epoch 1 and 14.9% in epoch 2 (adjusted odds ratio [OR]: 1.52 [95% confidence interval (CI): 0.86–2.71]; P = .15), the Mental Developmental Index was <70 in 44.9% in epoch 1 and 51% in epoch 2 (OR: 1.30 [95% CI: 0.91–1.87]; P = .15), and neurodevelopmental impairment was diagnosed in 50.1% of surviving infants in epoch 1 and 58.7% in epoch 2 (OR: 1.4 [95% CI: 0.98–2.04]; P = .07).
Early-childhood outcomes for infants born at <25 weeks' estimated gestational age were unchanged between the 2 periods.
PMCID: PMC3375467  PMID: 21187312
extremely preterm; neurodevelopmental; outcome; cerebral palsy; Bayley Scales of Infant Development II
5.  Community Supports After Surviving Extremely Low-Birth-Weight, Extremely Preterm Birth 
To determine special outpatient services (SOS) use, need, associated factors, and neurodevelopmental and functional outcomes among extremely preterm infants at 18 to 22 months’ corrected age.
Retrospective analysis.
National Institute of Child Health and Human Development (NICHD) Neonatal Research Network.
Infants younger than 28 weeks’ gestational age who had been born weighing less than 1000 g at an NICHD Neonatal Research Network center from January 1, 1997, to December 31, 2000, and who were receiving follow-up at 18 to 22 months’ corrected age.
Questionnaires were administered at the 18- to 22-month follow-up visit regarding SOS use since hospital discharge and the current need for SOS (social work, visiting nurse, medical specialty, early intervention, speech and language services, occupational therapy and physical therapy, and neurodevelopmental and behavioral services).
Main Outcome Measures
The use of and need for SOS were analyzed by gestational age. Logistic regression analysis identified factors independently associated with the use of more than 5 services and with the need for any services.
Of 2315 infants, 54.7% used more than 3 SOS by 18 to 22 months, and 19.1% used 6 to 7 SOS. The need for any SOS was reported by approximately 37%. The following variables that were commonly associated with adverse neurodevelopmental outcomes were also associated with the use of more than 5 SOS: sepsis, birth weight, postnatal corticosteroid use, bronchopulmonary dysplasia, and cystic periventricular leukomalacia or grade 3 or 4 intraventricular hemorrhage. Male sex was associated with the need for any SOS. Although high SOS use was more likely among children with adverse neurodevelopmental outcomes, a reported need for SOS was common even among those with mild developmental impairment (39.7%) and mild cerebral palsy (42.2%).
High SOS use is common, has identifiable neonatal risk factors, and is associated with neurodevelopmental impairment. Extremely preterm survivors have substantial need for community supports regardless of their impairment level. Efforts to improve comprehensive delivery of family-centered community-based services are urgently needed.
PMCID: PMC2748992  PMID: 18678807
6.  Inhaled Nitric Oxide for Preterm Premature Rupture of Membranes, Oligohydramnios, and Pulmonary Hypoplasia 
American journal of perinatology  2008;26(4):317-322.
We sought to determine if inhaled nitric oxide (iNO) administered to preterm infants with premature rupture of membranes (PPROM), oligohydramnios, and pulmonary hypoplasia improved oxygenation, survival, or other clinical outcomes. Data were analyzed from infants with suspected pulmonary hypoplasia, oligohydramnios, and PPROM enrolled in the National Institute of Child Health and Development Neonatal Research Network Preemie Inhaled Nitric Oxide (PiNO) trial, where patients were randomized to receive placebo (oxygen) or iNO at 5 to 10 ppm. Outcome variables assessed were PaO2 response, mortality, bronchopulmonary dysplasia (BPD), and severe intraventricular hemorrhage (IVH) or periventricular leukomalacia (PVL). Twelve of 449 infants in the PiNO trial met criteria. Six infants received iNO and six received placebo. The iNO group had a mean increase in PaO2 of 39±50 mm Hg versus a mean decrease of 11±15 mm Hg in the control group. Mortality was 33% versus 67%, BPD (2/5) 40% versus (2/2) 100%, and severe IVH or PVL (1/5) 20% versus (1/2) 50% in the iNO and control groups, respectively. None of these changes were statistically significant. Review of a limited number of cases from a large multicenter trial suggests that iNO use in the setting of PPROM, oligohydramnios, and suspected pulmonary hypoplasia improves oxygenation and may decrease the rate of BPD and death without increasing severe IVH or PVL. However, the small sample size precludes definitive conclusions. Further studies are required to determine if iNO is of benefit in this specific patient population.
PMCID: PMC2676224  PMID: 19067285
Nitric oxide; pulmonary hypoplasia; oligohydramnios; PPROM; bronchopulmonary dysplasia

Results 1-6 (6)