Douglas E. Kendrick

Gender differences in neurodevelopmental outcomes among extremely preterm, extremely-low-birthweight infants.

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).

Changes in mortality and morbidities among infants born at less than 25 weeks during the post-surfactant era

Objectives: To compare mortality and death or major morbidity (DOMM) among infants <25 weeks estimated gestational age (EGA) born during two post-surfactant era time periods. Study design and patients: Comparative cohort study of very low birthweight (501–1500 g) infants <25 weeks EGA in the NICHD Neonatal Research Network born during two post-surfactant era time periods (group I, 1991–1994, n  =  1408; group II, 1995–1998, n  =  1348). Perinatal and neonatal factors were compared, and group related mortality and DOMM risk were evaluated. Results: Mortality was higher for group I (63.1% v 56.7%; p  =  0.0006). Antenatal steroids (ANS) and antenatal antibiotics (AABX), surfactant (p<0.0001), and bronchopulmonary dysplasia (p  =  0.0008) were more prevalent in group II. In a regression model that controlled for basic and delivery factors only, mortality risk was greater for group I than for group II (odds ratio (OR) 1.4, 95% confidence interval (CI) 1.2 to 1.7); the addition of AABX and surfactant, or ANS (OR 0.97, 95% CI 0.79 to 1.2) to the model appeared to account for this difference. There was no difference in DOMM (86.8% v 88.4%; p  =  0.2), but risk was lower for group I in regression models that included ANS (OR 0.70, 95% CI 0.52 to 0.94). Conclusion: Survival to discharge was more likely during the more recent period because of group differences in ANS, AABX, and surfactant. However, this treatment shift may reflect an overall more aggressive management approach. More consistent application of treatment has led to improving survival of <25 week EGA infants during the post-surfactant era, but possibly at the cost of greater risk of major in-hospital morbidities.

Outcome of Extremely Low Birth Weight Infants Who Received Delivery Room Cardiopulmonary Resuscitation

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.

Inhaled Nitric Oxide for Preterm Premature Rupture of Membranes, Oligohydramnios, and Pulmonary Hypoplasia

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.

Inhaled nitric oxide usage in preterm infants in the NICHD neonatal research network: inter-site variation and propensity evaluation

Objective:The use of inhaled nitric oxide (iNO) in preterm infants remains controversial. In October 2010, a National Institutes of Health consensus development conference cautioned against use of iNO in preterm infants. This study aims (1) to determine the prevalence and variability in use of iNO in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network (NICHD NRN) before and after the consensus conference and (2) separately, to examine associations between iNO use and severe bronchopulmonary dysplasia (BPD) or death.Study design:The NICHD NRN Generic Database collects data including iNO use on very preterm infants. A total of 13 centers contributed data across the time period 2008 to 2011. Infants exposed or not to iNO were compared using logistic regression, which included factors related to risk as well as their likelihood of being exposed to iNO.Result:A total of 4885 infants were assessed between 2008 and 2011; 128 (2.6%) received iNO before day 7, 140 (2.9%) between day 7 and 28, and 47 (1.0%) at >28 days. Center-specific iNO use during 2008 to 2010 ranged from 21.9 to 0.4%; 12 of 13 sites reduced usage and overall NRN iNO usage decreased from 4.6 to 1.6% (P<0.001) in 2011. The use of iNO started between day 7 and day 14 was more prevalent among younger infants with more severe courses in week 1 and associated with increased risk of severe BPD or death (odds ratio 2.24; 95% confidence interval 1.23 to 4.07).Conclusion:The variability and total use of iNO decreased in 2011 compared with 2008 to 2010. iNO administration started at ⩾day 7 was associated with more severe outcomes compared with infants without iNO exposure.

Characteristics of extremely low-birth-weight infant survivors with unimpaired outcomes at 30 months of age

Objective:To evaluate characteristics of unimpaired outcome in extremely low-birth-weight (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.Result:Thirty-three percent of infants had an unimpaired outcome. Seventeen percent 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 (ANS), maternal education ⩾high school and the absence of major neonatal morbidities were independent predictors of unimpaired outcome. The likelihood of an unimpaired outcome in the presence of major neonatal morbidities was higher in infants exposed to ANS.Conclusion:The majority of unimpaired ELBW survivors had cognitive scores shifted toward the lower end of the normal distribution. Exposure to ANS was associated with higher likelihood of an unimpaired outcome in infants with major neonatal morbidities.

Incidence, management, and outcomes of cardiovascular insufficiency in critically ill term and late preterm newborn infants

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.

Definitions of Cardiovascular Insufficiency and Relation to Outcomes in Critically Ill Newborn Infants

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.

Multi-Iteration Usability Testing of the U.S. Navy's Performance Management System

The U.S. Navy has undertaken the second of two iterations of usability testing for the Navys 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 personnels 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.

Prolonged respiratory support of any type impacts outcomes of extremely low birth weight infants

This 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.