ObjectivesThis study tested the hypothesis that longer duration of any type of respiratory support is associated with an increased rate of death or neurodevelopmental impairment (NDI) at 18-22 months. MethodsRetrospective cohort study using the Generic Database of NICHD Neonatal Research Network from 2006 to 2010. Infants were born at <27 weeks gestational age with birth weights of 401-1000g. Respiratory support received during initial hospitalization from birth was characterized as follows: no support, only invasive support, only non-invasive support or mixed invasive, and non-invasive support. The primary outcome was death after 24h of life or NDI at 18-22 months corrected age. ResultsIn a cohort of 3651 infants, 1494 (40.9%) died or had NDI. Cumulative respiratory support of any type beyond 60 days was associated with the likelihood of death or NDI. Infants who only received invasive support had the highest rate (89.1%), followed by those received mixed support (26.1%). Infants who received only non-invasive support had the lowest rate (7.7%). When compared to the only non-invasive support group, both invasive [OR 62.7 (95%CI 25.7, 152.6)] and mixed [OR 6.1 (95%CI 2.6, 14.4)] support groups were significantly more likely to die or have NDI. ConclusionProlonged respiratory support, whether invasive or non-invasive, is associated with increased odds of a poor outcome. The proportion of infants with a poor outcome increased in a dose dependent manner by two factors: the cumulative duration of respiratory support beyond 60 days, and the extent to which invasive support is provided.

Background We previously reported on the overall incidence, management, and outcomes in infants with cardiovascular insufficiency (CVI). However, there are limited data on the relationship of the specific different definitions of CVI to short-term outcomes in term and late preterm newborn infants. Objective This study aims to evaluate how four definitions of CVI relate to short-term outcomes and death. Study Design The previously reported study was a multicenter, prospective cohort study of 647 infants ≥ 34 weeks gestation admitted to a Neonatal Research Network (NRN) newborn intensive care unit (NICU) and mechanically ventilated (MV) during their first 72 hours. The relationship of five short-term outcomes at discharge and four different definitions of CVI were further analyzed. Results All the four definitions were associated with greater number of days on MV and days on O2. The definition using a threshold blood pressure (BP) measurement alone was not associated with days of full feeding, days in the NICU or death. The definition based on the treatment of CVI was associated with all the outcomes including death. Conclusions The definition using a threshold BP alone was not consistently associated with adverse short-term outcomes. Using only a threshold BP to determine therapy may not improve outcomes.

OBJECTIVE: Antenatal magnesium (anteMg) is used for various obstetric indications including fetal neuroprotection. Infants exposed to anteMg may be at risk for respiratory depression and delivery room (DR) resuscitation. The study objective was to compare the risk of acute cardiorespiratory events among preterm infants who were and were not exposed to anteMg.STUDY DESIGN: This was a retrospective analysis of prospective data collected in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network's Generic Database from April 1, 2011, through March 31, 2012. The primary outcome was DR intubation or respiratory support at birth or on day 1 of life. Secondary outcomes were invasive mechanical ventilation, hypotension treatment, neonatal morbidities, and mortality. Logistic regression analysis evaluated the risk of primary outcome after adjustment for covariates.RESULTS: We evaluated 1544 infants < 29 weeks' gestational age (1091 in anteMg group and 453 in nonexposed group). Mothers in the anteMg group were more likely to have higher education, pregnancy-induced hypertension, and antenatal corticosteroids, while their infants were younger in gestation and weighed less (P < .05). The primary outcome (odds ratio [OR], 1.2; 95% confidence interval [CI], 0.88-1.65) was similar between groups. Hypotension treatment (OR, 0.70; 95% CI, 0.51-0.97) and invasive mechanical ventilation (OR, 0.54; 95% CI, 0.41-0.72) were significantly less in the anteMg group.CONCLUSION: Among preterm infants age < 29 weeks' gestation, anteMg exposure was not associated with an increase in cardiorespiratory events in the early newborn period. The safety of anteMg as measured by the need for DR intubation or respiratory support on day 1 of life was comparable between groups.

Objective The objective of this study was to characterize the incidence, management, and short-term outcomes of cardiovascular insufficiency (CVI) in mechanically ventilated newborns, evaluating four separate prespecified definitions. Study Design Multicenter, prospective cohort study of infants ≥34 weeks gestational age (GA) and on mechanical ventilation during the first 72 hours. CVI was prospectively defined as either (1) mean arterial pressure (MAP) < GA; (2) MAP < GA + signs of inadequate perfusion; (3) any therapy for CVI; or (4) inotropic therapy. Short-term outcomes included death, days on ventilation, oxygen, and to full feedings and discharge. Results Of 647 who met inclusion criteria, 419 (65%) met ≥1 definition of CVI. Of these, 98% received fluid boluses, 36% inotropes, and 17% corticosteroids. Of treated infants, 46% did not have CVI as defined by a MAP < GA ± signs of inadequate perfusion. Inotropic therapy was associated with increased mortality (11.1 vs. 1.3%; p < 0.05). Conclusion More than half of the infants met at least one definition of CVI. However, almost half of the treated infants met none of the definitions. Inotropic therapy was associated with increased mortality. These findings can help guide the design of future studies of CVI in newborns.

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.

Aims: 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 g) infants admitted to the Neonatal Research Network centers and hospitalized at 36 weeks postmenstrual age (n=1189) 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).Results: BPD by the physiologic definition was diagnosed in 603 (52%) infants, 537 of whom were mechanically ventilated or on FiO(2)>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 (242 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.Conclusions: 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. (C) 2012 Elsevier Ireland Ltd. All rights reserved.

Objective To determine whether delivery room cardiopulmonary resuscitation (DR-CPR) independently predicts morbidities and neurodevelopmental impairment (NDI) in extremely low birth weight infants.Study design We conducted a cohort study of infants born with birth weight of 401 to 1000 g and gestational age of 23 to 30 weeks. DR-CPR was defined as chest compressions, medications, or both. Logistic regression was used to determine associations among DR-CPR and morbidities, mortality, and NDI at 18 to 24 months of age (Bayley II mental or psychomotor index <70, cerebral palsy, blindness, or deafness). Data are adjusted ORs with 95% CIs.Results Of 8685 infants, 1333 (15%) received DR-CPR. Infants who received DR-CPR had lower birth weight (708 +/- 141 g versus 764 +/- 146g, P < .0001) and gestational age (25 +/- 2 weeks versus 26 +/- 2 weeks, P < .0001). Infants who received DR-CPR had more pneumothoraces (OR, 1.28; 95% CI, 1.48-2.99), grade 3 to 4 intraventricular hemorrhage (OR, 1.47; 95% CI, 1.23-1.74), bronchopulmonary dysplasia (OR, 1.34; 95% CI, 1.13-1.59), death by 12 hours (OR, 3.69; 95% CI, 2.98-4.57), and death by 120 days after birth (OR, 2.22; 95% CI, 1.93-2.57). Rates of NDI in survivors (OR, 1.23; 95% CI, 1.02-1.49) and death or NDI (OR, 1.70; 95% CI, 1.46-1.99) were higher for DR-CPR infants. Only 14% of DR-CPR recipients with 5-minute Apgar score <2 survived without NDI.Conclusions DR-CPR is a prognostic marker for higher rates of mortality and NDI for extremely low birth weight infants. New DR-CPR strategies are needed for this population. (J Pediatr 2012;160:239-44).

Objective The study goal was to evaluate maternal and neonatal risk factors associated with post-neonatal intensive care unit (NICU) discharge mortality among extremely low birth weight (ELBW) infants.Study design This is a retrospective analysis of ELBW (<1000 g) and <27 weeks' gestational age infants born in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network sites between January 2000 and June 2007. Infants were tracked until death or 18 to 22 months' corrected age. Infants who died between NICU discharge and the 18- to 22-month follow-up visit were classified as post-NICU discharge mortality (P-NDM). Association of maternal and infant risk factors with P-NDM was determined using logistic regression analysis. A prediction model with 6 significant predictors was developed and validated.Results There were 5364 infants who survived to NICU discharge; 557 (10%) infants were lost to follow-up, and 107 infants died following NICU discharge. P-NDM rate was 22.3 per 1000 ELBW infants. In the prediction model, African American race, unknown maternal health insurance, and hospital stay >= 120 days significantly increased risk, and maternal exposure to intrapartum antibiotics was associated with decreased risk of P-NDM.Conclusion We identified African American race, unknown medical insurance, and prolonged NICU stay as risk factors associated with P-NDM among ELBW infants. (J Pediatr 2012;square:square-square).

OBJECTIVE: 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). PATIENTS AND METHODS: 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. RESULTS: 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). CONCLUSIONS: Early-childhood outcomes for infants born at <25 weeks' estimated gestational age were unchanged between the 2 periods.

OBJECTIVE. The purpose of this work was to evaluate therapy for patent ductus arteriosus as a risk factor for death or neurodevelopmental impairment at 18 to 22 months, bronchopulmonary dysplasia, or necrotizing enterocolitis in extremely low birth weight infants. METHODS. We studied infants in the National Institute of Child Health and Human Development Neonatal Research Network Generic Data Base born between 2000 and 2004 at 23 to 28 weeks' gestation and at <1000-g birth weight with patent ductus arteriosus. Patent ductus arteriosus therapy was evaluated as a risk factor for outcomes in bivariable and multivariable analyses. RESULTS. Treatment for subjects with patent ductus arteriosus (n = 2838) included 403 receiving supportive treatment only, 1525 treated with indomethacin only, 775 with indomethacin followed by secondary surgical closure, and 135 treated with primary surgery. Patients who received supportive therapy for patent ductus arteriosus did not differ from subjects treated with indomethacin only for any of the outcomes of interest. Compared with indomethacin treatment only, patients undergoing primary or secondary surgery were smaller and more premature. When compared with indomethacin alone, primary surgery was associated with increased adjusted odds for neurodevelopmental impairment and bronchopulmonary dysplasia in multivariable logistic regression. Secondary surgical closure was associated with increased odds for neurodevelopmental impairment and increased adjusted odds for bronchopulmonary dysplasia but decreased adjusted odds for death. Risk of necrotizing enterocolitis did not differ among treatments. Indomethacin prophylaxis did not significantly modify these results. CONCLUSIONS. Our results suggest that infants treated with primary or secondary surgery for patent ductus arteriosus may be at increased risk for poor short- and long-term outcomes compared with those treated with indomethacin. Prophylaxis with indomethacin in the first 24 hours of life did not modify the subsequent outcomes of patent ductus arteriosus therapy.

The U. S. Navy has undertaken the second of two iterations of usability testing for the Navy's Human Performance Feedback and Development (HPFD) and ePerformance system. This second of two iterations included 34 officer and enlisted supervisors and nonsupervisors in usability testing conducted at three Navy locations-Naval Meteorology and Oceanographic Center (NAVMETOCCEN) Norfolk in Norfolk, Virginia; USS HOWARD (DDG 83) in San Diego, California; and the Bureau of Naval Personnel (BUPERS) in Arlington, Virginia. Each participant completed a usability test scenario in addition to pretest and posttest surveys designed to obtain Navy personnel's subjective impressions of the HPFD and ePerformance systems. Results from analyses comparing data from Iteration 1 (reported in Schwerin, Dean, Robbins, Bourne, & Reed, 2006) and Iteration 2 (reported in Dean, Aspinwall, Schwerin,& Kendrick, 2006) show an overall reduction in user burden (e. g., fewer errors and less time to complete usability tasks) and increased user satisfaction (e. g., more satisfied with the professionalism, efficiency, and overall effectiveness). These findings indicate that the Navy HPFD and ePerformance systems are easier to use but, more generally, results support the value and effectiveness of usability in human systems integration (HSI) and usability testing. Recommendations for system refinement, policy development, and implementation planning are discussed.

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 PaO (2) 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 PaO (2) 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.

Objective: 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.Design: Retrospective analysis. Setting: National Institute of Child Health and Human Development (NICHD) Neonatal Research Network.Participants: 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.Interventions: 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.Results: 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%).Conclusions: 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.

Aim: To determine whether gender-specific responses to perinatal and neonatal events and exposures explain the male disadvantage in early childhood outcomes. Methods: Infants were in the National Institute of Child Health and Human Development ( NICHD) Neonatal Research Network, born 1/1/1997 - 12/31/2000, < 28 wk, with neurodevelopmental follow-up at 18 - 22 mo corrected age. We evaluated and compared univariate and multivariate associations of risk factors with neurodevelopmental outcomes for girls and boys. Neurodevelopmental impairment ( NDI) was one or more of the following: moderate - severe cerebral palsy ( CP), Bayley Mental ( MDI) or Psychomotor ( PDI) Development Indices < 70, deafness or blindness. Results : Boys ( n = 1216) were more likely than girls ( n = 1337) to have adverse outcomes ( moderate - severe CP: 10.7% vs 7.3%; MDI < 70: 41.9% vs 27.1%; NDI: 48.1% vs 34.1%). Major risk factors were also more common in boys. Independent multivariate associations of risk factors with outcome differed by gender, but not consistently in favor of girls. In multivariate models including both girls and boys, male gender remained an independent risk factor for MDI < 70 ( 2.0, 95% CI 1.6 - 2.5) and NDI ( 1.8, 95% CI 1.5 - 2.2).Conclusion: Perinatal, neonatal and early childhood factors confer similar incremental risk or protection to boys and girls, but boys appear to have inherently greater baseline risk. Unmeasured biological variables likely contribute to the preterm male neurodevelopmental outcome disadvantage.

Aim: To determine whether gender-specific responses to perinatal and neonatal events and exposures explain the male disadvantage in early childhood outcomes. Methods: Infants were in the National Institute of Child Health and Human Development (NICHD) Neonatal Research Network, born 1/1/1997–12/31/2000, <28 wk, with neurodevelopmental follow-up at 18–22 mo corrected age. We evaluated and compared univariate and multivariate associations of risk factors with neurodevelopmental outcomes for girls and boys. Neurodevelopmental impairment (NDI) was one or more of the following: moderate–severe cerebral palsy (CP), Bayley Mental (MDI) or Psychomotor (PDI) Development Indices <70, deafness or blindness. Results: Boys ( n =1216) were more likely than girls ( n =1337) to have adverse outcomes (moderate–severe CP: 10.7% vs 7.3%; MDI<70: 41.9% vs 27.1%; NDI: 48.1% vs 34.1%). Major risk factors were also more common in boys. Independent multivariate associations of risk factors with outcome differed by gender, but not consistently in favor of girls. In multivariate models including both girls and boys, male gender remained an independent risk factor for MDI<70 (2.0, 95% CI 1.6–2.5) and NDI (1.8, 95% CI 1.5–2.2). Conclusion: Perinatal, neonatal and early childhood factors confer similar incremental risk or protection to boys and girls, but boys appear to have inherently greater baseline risk. Unmeasured biological variables likely contribute to the preterm male neurodevelopmental outcome disadvantage.

: The Navy Human Performance Center (HPC) and Navy Personnel Command (NPC) have reached the final phase of development for the Navy's Human Performance Feedback and Development (HPFD) and ePerformance system. This second and final iteration of usability testing was designed to verify the functionality of system revisions made as a result of recommendations offered in Schwerin et al. (2004) and gather user perceptions of system usability and cultural issues that may affect HPFD and ePerformance system implementation. This report documents the results of usability test and user survey data collection. Usability timing and errors analyses suggest that system enhancements as a result of the first usability study improved the overall usability of the HPFD and ePerformance system, but users still have significant difficulty finding, opening and creating HPFD and ePerformance documents.