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.

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.

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.

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

OBJECTIVES: 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. METHODS: Retrospective 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 401-1000 g. 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 24 h of life or NDI at 18-22 months corrected age. RESULTS: In 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. CONCLUSION: Prolonged 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.

Stryker SMARTLock Hybrid Maxillomandibular Fixation System: Clinical Application, Complications, and Radiographic Findings.

BACKGROUND: The SMARTLock Hybrid MMF System from Stryker is a newer approach for maxillomandibular fixation. This study was performed to determine the clinical application, complications, radiographic findings, and cost effectiveness of the SMARTLock system. METHODS: A retrospective cohort study was performed with the SMARTLock system over 6 months. Demographics, history, fracture location, placement/removal time, and complications were obtained, along with cost analysis. RESULTS: The authors identified 35 patients with the SMARTLock system. Twenty-four patients remained after exclusion criteria. There were 19 male patients (79 percent) and five female patients (21 percent), with a mean age of 30.7 years. The mean application time of the SMARTLock system was 14.4 minutes, and the mean removal time was 10.5 minutes. Three hundred nineteen total screws were placed. The number and percentage of patients with complications associated with the SMARTLock system were as follows: mucosal overgrowth [n = 9 (38 percent)], screw loosening [n = 4 (17 percent)], lip irritation [n = 4 (17 percent)], malocclusion [n = 3 (13 percent)], nonunion [n = 1 (4 percent)], wound dehiscence [n = 1 (4 percent)], screw loss [n = 1 (4 percent)], tooth devitalization [n = 1 (4 percent)], loose plate [n = 1 (4 percent)], and plate fracture [n = 1 (4 percent)]. There were no instances of sharps exposure, tooth loss, or infection. One tooth required endodontic therapy. The number of screws that damaged teeth on cone-beam computed tomographic imaging was 24 (7.5 percent). The cost analysis showed similar cost between Erich arch bars and the SMARTLock system. CONCLUSIONS: This study suggests that the SMARTLock Hybrid MMF System is safe and easy to use, and with a cost similar to that of Erich arch bars. Appropriate treatment planning and previous surgical experience should be used to determine appropriate case selection, as this system is not ideal in all situations. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

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.

Outcomes of extremely low birth weight infants with bronchopulmonary dysplasia: impact of the physiologic definition.

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 (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. 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.

Early-childhood neurodevelopmental outcomes are not improving for infants born at <25 weeks' gestational age.

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.

Community supports after surviving extremely low-birth-weight, extremely preterm birth: special outpatient services in early childhood.

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.

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). 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.

Changes in neurodevelopmental outcomes at 18 to 22 months' corrected age among infants of less than 25 weeks' gestational age born in 1993-1999.

BACKGROUND: Increased survival rates for extremely preterm, extremely low birth weight infants during the postsurfactant era have been reported, but data on changes in neurosensory and developmental impairments are sparse. OBJECTIVE: To compare neuromotor and neurodevelopmental outcomes at 18 to 22 months' corrected age for infants of <25 weeks' estimated gestational age (EGA) who were born in the 1990s. METHODS: This was a multicenter, retrospective, comparative analysis of infants of <25 weeks' EGA, with birth weights of 501 to 1000 g, born between January 1993 and June 1996 (epoch I) or between July 1996 and December 1999 (epoch II), in the National Institute of Child Health and Human Development Neonatal Research Network. Neurodevelopmental assessments were performed at 18 to 22 months' corrected age. Logistic-regression models were constructed to evaluate the independent risk of cerebral palsy, Mental Development Index of <70, Psychomotor Development Index of <70, and neurodevelopmental impairment. RESULTS: A total of 366 patients in epoch I and 473 patients in epoch II were evaluated. Prenatal steroid use, cesarean section, surfactant treatment, bronchopulmonary dysplasia, and severe retinopathy of prematurity were more likely in epoch II, whereas Apgar scores of <5 at 5 minutes, patent ductus arteriosus, and severe intraventricular hemorrhage were more likely in epoch I. The prevalences of cerebral palsy, Psychomotor Development Index of <70, and neurodevelopmental impairment were similar between epochs. The prevalences of Mental Development Index of <70 were 40% for epoch I and 47% for epoch II. Regression analysis revealed that epoch II was an independent risk factor for Mental Developmental Index of <70 (epoch I versus II: odds ratio: 0.63; 95% confidence interval: 0.45-0.87) but not for other outcomes. CONCLUSIONS: Early childhood neurodevelopmental outcomes among infants of <25 weeks' EGA are not improving in the postsurfactant era, despite more aggressive perinatal and neonatal treatment. Later childhood follow-up assessment is needed to delineate trends in severe cognitive impairment in this extremely high-risk group.

Neurodevelopmental and growth outcomes of extremely low birth weight infants after necrotizing enterocolitis.

OBJECTIVES: Necrotizing enterocolitis (NEC) is a significant complication for the premature infant. However, subsequent neurodevelopmental and growth outcomes of extremely low birth weight (ELBW) infants with NEC have not been well described. We hypothesized that ELBW infants with surgically managed (SurgNEC) are at greater risk for poor neurodevelopmental and growth outcomes than infants with medically managed NEC (MedNEC) compared with infants without a history of NEC (NoNEC). The objective of this study was to compare growth, neurologic, and cognitive outcomes among ELBW survivors of SurgNEC and MedNEC with NoNEC at 18 to 22 months' corrected age. METHODS: Multicenter, retrospective analysis was conducted of infants who were born between January 1, 1995, and December 31, 1998, and had a birth weight <1000 g in the National Institute of Child Health and Human Development Neonatal Research Network Registry. Neurodevelopment and growth were assessed at 18 to 22 months' postmenstrual age. chi2, t test, and logistic regression analyses were used. RESULTS: A total of 2948 infants were evaluated at 18 to 22 months, 124 of whom were SurgNEC and 121 of whom were MedNEC. Compared with NoNEC, both SurgNEC and MedNEC infants were of lower birth weight and had a greater incidence of late sepsis; SurgNEC but not MedNEC infants were more likely to have received a diagnosis of cystic periventricular leukomalacia and bronchopulmonary dysplasia and been treated with postnatal steroids. Weight, length, and head circumference <10 percentile at 18 to 22 months were significantly more likely among SurgNEC but not MedNEC compared with NoNEC infants. After correction for anthropometric measures at birth and adjusted age at follow-up, all growth parameters at 18 to 22 months for SurgNEC but not MedNEC infants were significantly less than for NoNEC infants. SurgNEC but not MedNEC was a significant independent risk factor for Mental Developmental Index <70 (odds ratio [OR]: 1.61; 95% confidence interval [CI]: 1.05-2.50), Psychomotor Developmental Index <70 (OR: 1.95; 95% CI: 1.25-3.04), and neurodevelopmental impairment (OR: 1.78; 95% CI: 1.17-2.73) compared with NoNEC. CONCLUSIONS: Among ELBW infants, SurgNEC is associated with significant growth delay and adverse neurodevelopmental outcomes at 18 to 22 months' corrected age compared with NoNEC. MedNEC does not seem to confer additional risk. SurgNEC is likely to be associated with greater severity of disease.