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Importance: The Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network (NRN) extremely preterm birth outcome model is widely used for prognostication by practitioners caring for families expecting extremely preterm birth. The model provides information on mean outcomes from 1998 to 2003 and does not account for substantial variation in outcomes among US hospitals., Objective: To update and validate the NRN extremely preterm birth outcome model for most extremely preterm infants in the United States., Design, Setting, and Participants: This prognostic study included 3 observational cohorts from January 1, 2006, to December 31, 2016, at 19 US centers in the NRN (derivation cohort) and 637 US centers in Vermont Oxford Network (VON) (validation cohorts). Actively treated infants born at 22 weeks' 0 days' to 25 weeks' 6 days' gestation and weighing 401 to 1000 g, including 4176 in the NRN for 2006 to 2012, 45 179 in VON for 2006 to 2012, and 25 969 in VON for 2013 to 2016, were studied. VON cohorts comprised more than 85% of eligible US births. Data analysis was performed from May 1, 2017, to March 31, 2019., Exposures: Predictive variables used in the original model, including infant sex, birth weight, plurality, gestational age at birth, and exposure to antenatal corticosteroids., Main Outcomes and Measures: The main outcome was death before discharge. Secondary outcomes included neurodevelopmental impairment at 18 to 26 months' corrected age and measures of hospital resource use (days of hospitalization and ventilator use)., Results: Among 4176 actively treated infants in the NRN cohort (48% female; mean [SD] gestational age, 24.2 [0.8] weeks), survival was 63% vs 62% among 3702 infants in the era of the original model (47% female; mean [SD] gestational age, 24.2 [0.8] weeks). In the concurrent (2006-2012) VON cohort, survival was 66% among 45 179 actively treated infants (47% female; mean [SD] gestational age, 24.1 [0.8] weeks) and 70% among 25 969 infants from 2013 to 2016 (48% female; mean [SD] gestational age, 24.1 [0.8] weeks). Model C statistics were 0.74 in the 2006-2012 validation cohort and 0.73 in the 2013-2016 validation cohort. With the use of decision curve analysis to compare the model with a gestational age-only approach to prognostication, the updated model showed a predictive advantage. The birth hospital contributed equally as much to prediction of survival as gestational age (20%) but less than the other factors combined (60%)., Conclusions and Relevance: An updated model using well-known factors to predict survival for extremely preterm infants performed moderately well when applied to large US cohorts. Because survival rates change over time, the model requires periodic updating. The hospital of birth contributed substantially to outcome prediction.

Periviable births are those occurring from 20 0/7 through 25 6/7 weeks of gestation. Among and within developed nations, significant variation exists in the approach to obstetric and neonatal care for periviable birth. Understanding gestational age-specific survival, including factors that may influence survival estimates and how these estimates have changed over time, may guide approaches to the care of periviable births and inform conversations with families and caregivers. This review provides a historical perspective on survival following periviable birth, summarizes recent and new data on gestational age-specific survival rates, and addresses factors that have a significant impact on survival., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Between-hospital variation in outcomes among extremely preterm infants is largely unexplained and may reflect differences in hospital practices regarding the initiation of active lifesaving treatment as compared with comfort care after birth., Methods: We studied infants born between April 2006 and March 2011 at 24 hospitals included in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Data were collected for 4987 infants born before 27 weeks of gestation without congenital anomalies. Active treatment was defined as any potentially lifesaving intervention administered after birth. Survival and neurodevelopmental impairment at 18 to 22 months of corrected age were assessed in 4704 children (94.3%)., Results: Overall rates of active treatment ranged from 22.1% (interquartile range [IQR], 7.7 to 100) among infants born at 22 weeks of gestation to 99.8% (IQR, 100 to 100) among those born at 26 weeks of gestation. Overall rates of survival and survival without severe impairment ranged from 5.1% (IQR, 0 to 10.6) and 3.4% (IQR, 0 to 6.9), respectively, among children born at 22 weeks of gestation to 81.4% (IQR, 78.2 to 84.0) and 75.6% (IQR, 69.5 to 80.0), respectively, among those born at 26 weeks of gestation. Hospital rates of active treatment accounted for 78% and 75% of the between-hospital variation in survival and survival without severe impairment, respectively, among children born at 22 or 23 weeks of gestation, and accounted for 22% and 16%, respectively, among those born at 24 weeks of gestation, but the rates did not account for any of the variation in outcomes among those born at 25 or 26 weeks of gestation., Conclusions: Differences in hospital practices regarding the initiation of active treatment in infants born at 22, 23, or 24 weeks of gestation explain some of the between-hospital variation in survival and survival without impairment among such patients. (Funded by the National Institutes of Health.).

Objectives: To assess the influence of clinical status on the association between total plasma bilirubin and unbound bilirubin on death or adverse neurodevelopmental outcomes at 18-22 months corrected age in extremely low birth weight infants., Method: Total plasma bilirubin and unbound bilirubin were measured in 1101 extremely low birth weight infants at 5 +/- 1 days of age. Clinical criteria were used to classify infants as clinically stable or unstable. Survivors were examined at 18-22 months corrected age by certified examiners. Outcome variables were death or neurodevelopmental impairment, death or cerebral palsy, death or hearing loss, and death prior to follow-up. For all outcomes, the interaction between bilirubin variables and clinical status was assessed in logistic regression analyses adjusted for multiple risk factors., Results: Regardless of clinical status, an increasing level of unbound bilirubin was associated with higher rates of death or neurodevelopmental impairment, death or cerebral palsy, death or hearing loss and death before follow-up. Total plasma bilirubin values were directly associated with death or neurodevelopmental impairment, death or cerebral palsy, death or hearing loss, and death before follow-up in unstable infants, but not in stable infants. An inverse association between total plasma bilirubin and death or cerebral palsy was found in stable infants., Conclusions: In extremely low birth weight infants, clinical status at 5 days of age affects the association between total plasma bilirubin and death or adverse neurodevelopmental outcomes at 18-22 months of corrected age. An increasing level of UB is associated a higher risk of death or adverse neurodevelopmental outcomes regardless of clinical status. Increasing levels of total plasma bilirubin are directly associated with increasing risk of death or adverse neurodevelopmental outcomes in unstable, but not in stable infants.

Objectives: To compare the rates of adverse neurodevelopmental outcome or death at 18 to 22 months among extremely low birth weight (ELBW) infants born to mothers >or=4 0 years to the corresponding rates among infants of younger mothers., Study Design: Prospective evaluation of ELBW infants to quantify the relative risks of maternal age and multiple birth for death or adverse neurodevelopmental outcome., Results: The sample consisted of 14 671 live ELBW births divided into maternal age groups: <20, 20 to 29, 30 to 39, and >or= 40 years. Of infants born to mothers >or= 40 years, 20% were multiples. Mothers >or= 40 years had high rates of obstetric interventions and medical morbidities compared with mothers <40 years. ELBW live births of mothers >or= 40 years were 22% more likely to survive and had a 13% decreased risk of neurodevelopmental impairment or death compared with mothers <20. Multiple birth, however, was associated with a 10% greater risk of neurodevelopmental impairment or death., Conclusion: Although mothers >or= 40 years had high pregnancy-related morbidities, we found no overall increased risk of the composite outcome of death or NDI. Multiple birth, however, was a predictor of all adverse outcomes examined, regardless of maternal age.

Objective: To document the mortality and morbidity of infants weighing 501-1500 g at birth according to gestational age, birthweight, and sex., Study Design: Prospective collection of perinatal events and neonatal course to 120 days of life, discharge, or death from January 1990 through December 2002 for infants born at 16 participating centers of the National Institute of Child Health & Human Development Neonatal Research Network., Results: Compared with 1995-1996, for 1997-2002 the survival of infants with birthweight of 501-1500 g increased by 1 percentage point (from 84% to 85%). Survival without major neonatal morbidity remained static, at 70%; this includes bronchopulmonary dysplasia (BPD), intraventricular hemorrhage (IVH), and necrotizing enterocolitis (NEC). Survival increased for multiple births (26%, up from 22%), antenatal corticosteroid use (79%, up from 71%), and maternal antibiotics (70%, up from 62%) (P < .05). From 1997 to 2002, birthweight-specific survival was 55% for infants weighing 501-750 g, 88% for 751-1000 g, 94% for 1001-1250 g, and 96% for 1251-1500 g. More females survived. The incidence of NEC (7%), severe IVH (12%), and late-onset septicemia (22%) remained essentially unchanged, but BPD decreased slightly, from 23% to 22%. The use of postnatal corticosteroids declined from 20% in 1997-2000 to 12% in 2001-2002. Growth failure (weight <10th percentile) at 36 weeks' postmenstrual age decreased from 97% in 1995-1996 to 91% in 1997-2002., Conclusion: There have been no significant increases in survival without neonatal and long-term morbidity among VLBW infants between 1997 and 2002. We speculate that to improve survival without morbidity requires determining, disseminating, and applying best practices using therapies currently available, and also identifying new strategies and interventions.

Objective: Previous multicenter studies have shown significant center differences in neonatal characteristics and morbidities. This study evaluated center differences in outcome at 18 to 22 months among extremely low birth weight (ELBW; 401-1000 g) infants after adjusting for demographics and antenatal interventions, and it identified neonatal interventions associated with outcome differences., Methods: We assessed the outcome of 2478 liveborn infants who were admitted in 1993 and 1994 to the 12 centers of the Neonatal Research Network of the National Institute of Child Health and Human Development; 1483 (60%) infants survived to 18 to 22 months, and 1151 (78%) had comprehensive evaluations. Logistic regression analyses were performed to identify center differences and the association of 4 neonatal interventions--active resuscitation, postnatal steroids, ventilator treatment for < or =27 days, and full enteral feedings < or =24 days--with adverse outcomes (cerebral palsy, low Bayley scores, and neurodevelopmental impairment [NDI]), after adjusting for demographics and antenatal interventions., Results: Using bivariate analyses, significant center differences were identified for mortality, antenatal and postnatal interventions, social and environmental variables, neonatal morbidities, and neurodevelopmental outcomes for the 12 centers. After adjustment for maternal and infant demographics and antenatal interventions, the percentage of ELBW infants who had died or had NDI at 18 to 22 months ranged from 52% to 85%. Active resuscitation and postnatal steroids were associated with increases of NDI of 11.8% and 19.3%, whereas shorter ventilation support and shorter time to achieve full enteral feeds were associated with decreases in NDI of 20.7% and 17.3%, respectively., Conclusion: There are large and disturbing differences among centers in outcomes at 18 to 22 months after adjusting for demographic and antenatal interventions. Center differences in postnatal interventions associated with differences in outcome can provide hypotheses for testing in clinical trials to improve outcome.

Objective: The purposes of this study were to compare the clinical characteristics of extremely low birth-weight infants (501-1000 g birth weight) who die early (<12 hours of age) with those of infants who die >12 hours after birth and infants who survive to neonatal intensive care unit discharge and to develop a model of risk for early death., Study Design: Perinatal data were prospectively collected on 5986 infants in the 12 participating centers of the National Institute of Child Health and Human Development Neonatal Research Network from March 1993 through December 1997. Maternal and neonatal characteristics of infants who died early were compared with infants who survived and infants who died beyond 12 hours of age. A model for risk for early death was developed by logistic regression analysis, with results expressed as odds ratio with 95% CI., Results: Mothers of infants who died early were more likely to be delivered in an inborn setting and experience labor and were less likely to have hypertension or preeclampsia, to receive antenatal corticosteroids, or to be delivered by cesarean birth than mothers of infants who died >12 hours after birth or infants who survived. Infants who died early were more likely to have lower Apgar scores and lower gestational age/birth weight and were less likely to be intubated at birth and to receive mechanical ventilation and surfactant therapy than infants who died >12 hours after birth or infants who survived. Greater risk for early death versus survival to neonatal intensive care unit discharge was associated with the lack of surfactant administration (odds ratio, 8.6; 95% CI, 6.3-11.9), lack of delivery room intubation (odds ratio, 5.3; 95% CI, 3.5-8.1), lack of antenatal corticosteroid use (odds ratio, 2.3; 95% CI, 1.6-3.2), lower 1-minute Apgar score (odds ratio, 2.0; 95% CI, 1.8-2.2), male sex (odds ratio, 1.7; 95% CI, 1.3-2.3), multiple gestation (odds ratio, 1.7; 95% CI, 1.2-2.5), no tocolytics (odds ratio, 1.7; 95% CI, 1.2-2.3), lower gestational age per week (odds ratio, 1.4; 95% CI, 1.3-1.6), and lower birth weight per 50 g (95% CI, 1.2-1.4)., Conclusion: Early death (<12 hours of age) among extremely low-birth-weight infants may reflect an assessment of non-viability by obstetricians and neonatologists.

Objectives: To determine the mortality and morbidity for infants weighing 401 to 1500 g (very low birth weight [VLBW]) at birth by gestational age, birth weight, and gender., Study Design: Perinatal data were collected prospectively on an inborn cohort from January 1995 through December 1996 by 14 participating centers of the National Institute of Child Health and Human Development Neonatal Research Network and were compared with the corresponding data from previous reports. Sociodemographic factors, perinatal events, and the neonatal course to 120 days of life, discharge, or death were evaluated., Results: Eighty four percent of 4438 infants weighing 501 to 1500 g at birth survived until discharge to home or to a long-term care facility (compared with 80% in 1991 and 74% in 1988). Survival to discharge was 54% for infants 501 to 750 g at birth, 86% for those 751 to 1000 g, 94% for those 1001 to 1250 g, and 97% for those 1251 to 1500g. The incidence of chronic lung disease (CLD; defined as receiving supplemental oxygen at 36 weeks' postmenstrual age; 23%), proven necrotizing enterocolitis (NEC; 7%), and severe intracranial hemorrhage (ICH; grade III or IV; 11%) remained unchanged between 1991 and 1996. Furthermore, 97% of all VLBW infants and 99% of infants weighing <1000 g at birth had weights less than the 10th percentile at 36 weeks' postmenstrual age. Mortality for 195 infants weighing 401 to 500 g was 89%, with nearly all survivors developing CLD. Mortality in infants weighing 501 to 600 g was 71%; among survivors, 62% had CLD, 35% had severe ICH, and 15% had proven NEC., Conclusions: Survival for infants between 501 and 1500 g at birth continued to improve, particularly for infants weighing <1000 g at birth. This improvement in survival was not associated with an increase in major morbidities, because the incidence of CLD, proven NEC, and severe ICH did not change. However, poor postnatal growth remains a major concern, occurring in 99% of infants weighing <1000 g at birth. Mortality and major morbidity (CLD, severe ICH, and NEC) remain high for the smallest infants, particularly those weighing <600 g at birth.

Objective: To determine the differences in short term outcome of very low birthweight infants attributable to sex., Methods: Boys and girls weighing 501-1500 g admitted to the 12 centres of the National Institute of Child Health and Human Development Neonatal Research Network were compared. Maternal information and perinatal data were collected from hospital records. Infant outcome was recorded at discharge, at 120 days of age if the infant was still in hospital, or at death. Best obstetric estimate based on the last menstrual period, standard obstetric factors, and ultrasound were used to assign gestational age in completed weeks. Data were collected on a cohort that included 3356 boys and 3382 girls, representing all inborn births from 1 May 1991 to 31 December 1993., Results: Mortality for boys was 22% and that for girls 15%. The prenatal and perinatal data indicate few differences between the sex groups, except that boys were less likely to have been exposed to antenatal steroids (odds ratio (OR) = 0.80) and were less stable after birth, as reflected in a higher percentage with lower Apgar scores at one and five minutes and the need for physical and pharmacological assistance. In particular, boys were more likely to have been intubated (OR = 1.16) and to have received resuscitation medication (OR = 1.40). Boys had a higher risk (OR > 1.00) for most adverse neonatal outcomes. Although pulmonary morbidity predominated, intracranial haemorrhage and urinary tract infection were also more common., Conclusions: Relative differences in short term morbidity and mortality persist between the sexes.

Objectives: Our purpose was to determine the mortality and morbidity rates for infants weighing 501 to 1500 g according to gestational age, birth weight, and gender., Study Design: Perinatal data were collected prospectively on an inborn cohort from January 1993 through December 1994 by 12 participating centers of the National Institute of Child Health and Human Development Neonatal Research Network and were compared with the corresponding data from previous reports. Sociodemographic factors, perinatal events, and the neonatal course to 120 days of life, discharge, or death were evaluated., Results: Eighty-three percent of infants survived until discharge to home or to a long- term care facility (compared with 74% in 1988). Survival to discharge was 49% for infants weighing 501 to 750 g at birth, 85% for those 751 to 1000 g, 93% for those 1001 to 1250 g, and 96% for those 1251 to 1500 g. The majority of deaths occurred within the first 3 days of life. Mortality rates were greater for male than for female infants. Respiratory distress syndrome was the most frequent pulmonary disease (52%). Chronic lung disease (defined as an oxygen requirement at 36 weeks after conception) developed in 19%. Thirty-two percent of infants had evidence of intracranial hemorrhage. Periventricular leukomalacia was noted in 6% of infants who had ultrasonography after 2 weeks. The average duration of hospitalization for survivors was 68 days (122 days for surviving infants weighing 501 to 750 g, compared with an average of 43 days for surviving infants 1251 to 1500 g). Among infants who died, the average length of stay was 19 days., Conclusions: The mortality rate for infants weighing between 501 and 1500 g at birth continues to decline. This increase in survival is not accompanied by an increase in medical morbidity. There are interactions between birth weight, gestational age, sex, and survival rates.

Objectives: To assess risk factors affecting viability and analyze the effects of mechanical ventilation (MV) on neonatal outcome and resource use among extremely premature infants., Design: Inception cohort study., Setting: Neonatal intensive care units of the 12-center National Institute of Child Health and Human Development Neonatal Research Network., Participants: A total of 1126 infants with a birth weight of 501 to 800 g born in network centers between January 1, 1994, and December 31, 1995., Main Outcome Measures: Observed survival; maximum estimated survival (assuming the same survival among infants who died without MV as among infants in the same risk category who received MV); observed and maximum estimated survival without severe brain injury (either interventricular echodensity with ventricular dilation or parenchymal echodensity); hospital stay; resource investment., Results: Overall mortality was 43%; mortality in infants without MV was 93%. A total of 15% of all the infants died without MV. Females, small-for-gestational-age infants, and infants whose mothers received antenatal steroids had an advantage in survival with MV equivalent to an increase in birth weight of 90 g, 57 g, and 67 g, respectively. The corresponding advantage of these infants in survival without severe brain injury was 107 g, 97 g, and 64 g, respectively. Females in the lowest birth-weight group were more likely to die without MV than were larger males with a similar estimated likelihood of survival with MV. Mean hospital stay was 115 days for the survivors, values much greater than the 17.9-day standard for 501- to 800-g survivors under the diagnosis related group system. Resource investment was considerable (127 hospital days per survivor and 148 days per survivor without severe brain injury), but, like outcome, varied markedly between risk categories. Had MV been used for all infants who died, we estimate a substantial increase in resource use and a maximum of 8 additional survivors (no more than 6 without severe brain injury per 100 infants with a birth weight of 501 to 800 g., Conclusions: Although recommendations to initiate or forgo MV for extremely premature infants have often focused on 1 factor (birth weight or gestational age), multiple factors should be considered. Other factors being equal, our analyses support use of MV for females at a minimum birth weight approximately 100 g lower than that for males. The current diagnosis related group reimbursement system can be expected to compromise resources for 501- to 800-g infants who would benefit from MV. Such care entails considerable resource use, although the cost per life-year gained is likely to be considerably less than that for many adults given intensive care. Our findings can be used to facilitate more appropriate treatment decisions, determine adequate resources, and better inform the debate about the benefits and burdens of intensive care for extremely premature newborns.

Objective: Our purpose was to describe the neonatal outcomes of 1804 very-low-birth-weight (< or = 1500 gm) infants delivered between November 1989 and October 1990 in the participating centers of the National Institute of Child Health and Human Development Neonatal Research Network., Study Design: In an observational study sociodemographic, pregnancy, and delivery data were collected soon after birth, and neonatal and outcome data at discharge, at 120 days, or at death., Results: Maternal and birth weight characteristics included 64% black, 29% white; 71% single mothers; 18% no prenatal care; 17% antenatal steroids; and 12% multiple gestations. Birth weight distributions included 18% weighing 501 to 750 gm, 23% 751 to 1000 gm, 28% 1001 to 1250 gm, and 31% 1251 to 1500 gm. Survival was 39% at < 751 gm birth weight, 77% at 751 to 1000 gm, 90% at 1001 to 1250 gm, and 93% at 1251 to 1500 gm. Survival was 15% to 18% at < or = 23 weeks' gestation, 54% at 24 weeks, 59% at 25 weeks, and 71% at 26 weeks. Surfactant was administered to 45% of the 56% of infants with respiratory distress syndrome. Morbidity, including intraventricular hemorrhage (40%), septicemia (24%), symptomatic patent ductus arteriosus (22%), and necrotizing entercolitis (8%), increased with decreasing birth weight. Oxygen was administered for > or = 28 days to 82% of < 751 gm infants, 49% of 751 to 1000 gm infants, and 10% of > 1001 gm infants. Steroids were administered to 28% of infants who required oxygen for > or = 28 days. Mean hospital stay was 62 days for survivors and 18 days for infants who died. There were large intercenter variations in mortality and morbidity., Conclusion: Mortality and morbidity in very-low-birth-weight infants improved in 1989 to 1990 without an increase in morbidity or length of hospital stay. The threshold of the improved survival was > or = 24 weeks and 601 to 700 gm. Although such data are reassuring, the rate of major morbidity in < 1001 gm birth weight infants continues to be high.

This report describes the neonatal outcomes of 1765 very low birth weight (less than 1500 g) infants delivered from November 1987 through October 1988 at the seven participating centers of the National Institute of Child Health and Human Development Neonatal Intensive Care Network. Survival was 34% at less than 751 g birth weight (range between centers 20% to 55%), 66% at 751 through 1000 g (range 42% to 75%), 87% at 1001 through 1250 g (range 84% to 91%), and 93% at 1251 through 1500 g (range 89% to 98%). By obstetric measures of gestation, survival was 23% at 23 weeks (range 0% to 33%), 34% at 24 weeks (range 10% to 57%), and 54% at 25 weeks (range 30% to 72%). Neonatal morbidity included respiratory distress (67%), symptomatic patent ductus arteriosus (25%), necrotizing enterocolitis (6%), septicemia (17%), meningitis (2%), urinary tract infection (4%), and intraventricular hemorrhage (45%, 18% grade III and IV). Morbidity increased with decreasing birth weight. Oxygen was administered for greater than or equal to 28 days to 79% of less than 751-g birth weight infants (range between centers 67% to 100%), 45% of 751- through 1000-g infants (range 20% to 68%), and 13% of 1001- through 1500-g infants (range 5% to 23%). Ventilator support for greater than or equal to 28 days was given to 68% of infants at less than 751 g, 29% at 751 through 1000 g, and 4% at greater than 1000 g. Hospital stay was 59 days for survivors vs 15 days for infants who died. Sixty-nine percent of survivors had subnormal (less than 10th percentile) weight at discharge. The data demonstrate important intercenter variation of current neonatal outcomes, as well as differences in philosophy of care and definition and prevalence of morbidity.