Genetic and behavioral modification of hemoglobin and iron status among first-time and high-intensity blood donors.

BACKGROUND: Some people rapidly develop iron deficiency anemia following blood donation, while others can repeatedly donate without becoming anemic. METHODS: Two cohorts of blood donors were studied. Participants (775) selected from a 2-year longitudinal study were classified into six analysis groups based on sex, donation intensity, and low hemoglobin deferral. Associations with iron supplement use, cigarette smoking, and four genetic variants of iron metabolism were examined at enrollment and with longitudinal regression models. An unbiased assessment of genetic variability and ability to repeatedly donate blood without experiencing low hemoglobin deferral was conducted on participants (13,403) in a cross-sectional study who were examined by genome wide association (GWA). RESULTS: Behaviors and genetic variants were associated with differences in hemoglobin and ferritin change following repeated donation. At least weekly iron supplement use was associated with improved status in first-time donors, while daily use was associated with improved status in high-intensity donors. Cigarette smoking was associated with 0.5 g/dL increased hemoglobin in high-intensity donors. A736V in TMPRSS6 was associated with a rapid drop in hemoglobin and ferritin in first-time females following repeated donation. Conversely, the protective TMPRSS6 genotype was not enriched among high-intensity donors. H63D in HFE was associated with increased hemoglobin in female high-intensity donors. However, no differences in genotype between first-time and high-intensity donors were found in GWA analyses. CONCLUSION: Behavioral and genetic modifiers contributed to first-time donor hemoglobin and iron status, while iron supplement use was more important than underlying genetics in high-intensity donors.

Outcomes of Preterm Infants following Discussions about Withdrawal or Withholding of Life Support.

OBJECTIVES: To describe the frequency of postnatal discussions about withdrawal or withholding of life-sustaining therapy (WWLST), ensuing WWLST, and outcomes of infants surviving such discussions. We hypothesized that such survivors have poor outcomes. STUDY DESIGN: This retrospective review included registry data from 18 centers of the National Institute of Child Health and Human Development Neonatal Research Network. Infants born at 22-28 weeks of gestation who survived >12 hours during 2011-2013 were included. Regression analysis identified maternal and infant factors associated with WWLST discussions and factors predicting ensuing WWLST. In-hospital and 18- to 26-month outcomes were evaluated. RESULTS: WWLST discussions occurred in 529 (15.4%) of 3434 infants. These were more frequent at 22-24 weeks (27.0%) compared with 27-28 weeks of gestation (5.6%). Factors associated with WWLST discussion were male sex, gestational age (GA) of ≤24 weeks, birth weight small for GA, congenital malformations or syndromes, early onset sepsis, severe brain injury, and necrotizing enterocolitis. Rates of WWLST discussion varied by center (6.4%-29.9%) as did WWLST (5.2%-20.7%). Ensuing WWLST occurred in 406 patients; of these, 5 survived to discharge. Of the 123 infants for whom intensive care was continued, 58 (47%) survived to discharge. Survival after WWLST discussion was associated with higher rates of neonatal morbidities and neurodevelopmental impairment compared with babies for whom WWLST discussions did not occur. Significant predictors of ensuing WWLST were maternal age >25 years, necrotizing enterocolitis, and days on a ventilator. CONCLUSIONS: Wide center variations in WWLST discussions occur, especially at ≤24 weeks GA. Outcomes of infants surviving after WWLST discussions are poor. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00063063.

Prediction of bronchopulmonary dysplasia by postnatal age in extremely premature infants.

RATIONALE: Benefits of identifying risk factors for bronchopulmonary dysplasia in extremely premature infants include providing prognostic information, identifying infants likely to benefit from preventive strategies, and stratifying infants for clinical trial enrollment. OBJECTIVES: To identify risk factors for bronchopulmonary dysplasia, and the competing outcome of death, by postnatal day; to identify which risk factors improve prediction; and to develop a Web-based estimator using readily available clinical information to predict risk of bronchopulmonary dysplasia or death. METHODS: We assessed infants of 23-30 weeks' gestation born in 17 centers of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network and enrolled in the Neonatal Research Network Benchmarking Trial from 2000-2004. MEASUREMENTS AND MAIN RESULTS: Bronchopulmonary dysplasia was defined as a categorical variable (none, mild, moderate, or severe). We developed and validated models for bronchopulmonary dysplasia risk at six postnatal ages using gestational age, birth weight, race and ethnicity, sex, respiratory support, and Fi(O(2)), and examined the models using a C statistic (area under the curve). A total of 3,636 infants were eligible for this study. Prediction improved with advancing postnatal age, increasing from a C statistic of 0.793 on Day 1 to a maximum of 0.854 on Day 28. On Postnatal Days 1 and 3, gestational age best improved outcome prediction; on Postnatal Days 7, 14, 21, and 28, type of respiratory support did so. A Web-based model providing predicted estimates for bronchopulmonary dysplasia by postnatal day is available at https://neonatal.rti.org. CONCLUSIONS: The probability of bronchopulmonary dysplasia in extremely premature infants can be determined accurately using a limited amount of readily available clinical information.

Hypocarbia and adverse outcome in neonatal hypoxic-ischemic encephalopathy.

OBJECTIVE: To evaluate the association between early hypocarbia and 18- to 22-month outcome among neonates with hypoxic-ischemic encephalopathy. STUDY DESIGN: Data from the National Institute of Child Health and Human Development Neonatal Research Network randomized, controlled trial of whole-body hypothermia for neonatal hypoxic-ischemic encephalopathy were used for this secondary observational study. Infants (n = 204) had multiple blood gases recorded from birth to 12 hours of study intervention (hypothermia versus intensive care alone). The relationship between hypocarbia and outcome (death/disability at 18 to 22 months) was evaluated by unadjusted and adjusted analyses examining minimum PCO(2) and cumulative exposure to PCO(2) <35 mm Hg. The relationship between cumulative PCO(2) <35 mm Hg (calculated as the difference between 35 mm Hg and the sampled PCO(2) multiplied by the duration of time spent <35 mm Hg) and outcome was evaluated by level of exposure (none-high) using a multiple logistic regression analysis with adjustments for pH, level of encephalopathy, treatment group (± hypothermia), and time to spontaneous respiration and ventilator days; results were expressed as odds ratios and 95% confidence intervals. Alternative models of CO(2) concentration were explored to account for fluctuations in CO(2). RESULTS: Both minimum PCO(2) and cumulative PCO(2) <35 mm Hg were associated with poor outcome (P < .05). Moreover, death/disability increased with greater cumulative exposure to PCO(2) <35 mm Hg. CONCLUSIONS: Hypocarbia is associated with poor outcome after hypoxic-ischemic encephalopathy.

Acute neonatal effects of cocaine exposure during pregnancy.

OBJECTIVE: To identify associations between cocaine exposure during pregnancy and medical conditions in newborn infants from birth through hospital discharge. DESIGN: Multisite, prospective, randomized study. SETTING: Brown University, University of Miami, University of Tennessee (Memphis), and Wayne State University. Subjects A total of 717 cocaine-exposed infants and 7442 nonexposed infants. MAIN OUTCOME MEASURES: Results of physical examination and conditions observed during hospitalization. RESULTS: Cocaine-exposed infants were about 1.2 weeks younger, weighed 536 g less, measured 2.6 cm shorter, and had head circumference 1.5 cm smaller than nonexposed infants (all P<.001). Results did not confirm previously reported abnormalities. Central and autonomic nervous system symptoms were more frequent in the exposed group: jittery/tremors (adjusted odds ratio, 2.17; 99% confidence interval, 1.44-3.29), high-pitched cry (2.44; 1.06-5.66), irritability (1.81; 1.18-2.80), excessive suck (3.58; 1.63-7.88), hyperalertness (7.78; 1.72-35.06), and autonomic instability (2.64; 1.17-5.95). No differences were detected in organ systems by ultrasound examination. Exposed infants had more infections (3.09; 1.76-5.45), including hepatitis (13.46; 7.46-24.29), syphilis (8.84; 3.74-20.88), and human immunodeficiency virus exposure (12.37; 2.20-69.51); were less often breastfed (0.26; 0.15-0.44); had more child protective services referrals (48.92; 28.77-83.20); and were more often not living with their biological mother (18.70; 10.53-33.20). CONCLUSIONS: Central and autonomic nervous system symptoms were more frequent in the exposed cohort and persisted in an adjusted analysis. They were usually transient and may be a true cocaine effect. Abnormal anatomic outcomes previously reported were not confirmed. Increased infections, particularly sexually transmitted diseases, pose a serious public health challenge. Exposure increased involvement of child protective services and out-of-home placement.

Outcome trajectories in extremely preterm infants.

OBJECTIVE: Methods are required to predict prognosis with changes in clinical course. Death or neurodevelopmental impairment in extremely premature neonates can be predicted at birth/admission to the ICU by considering gender, antenatal steroids, multiple birth, birth weight, and gestational age. Predictions may be improved by using additional information available later during the clinical course. Our objective was to develop serial predictions of outcome by using prognostic factors available over the course of NICU hospitalization. METHODS: Data on infants with birth weight ≤ 1.0 kg admitted to 18 large academic tertiary NICUs during 1998-2005 were used to develop multivariable regression models following stepwise variable selection. Models were developed by using all survivors at specific times during hospitalization (in delivery room [n = 8713], 7-day [n = 6996], 28-day [n = 6241], and 36-week postmenstrual age [n = 5118]) to predict death or death/neurodevelopmental impairment at 18 to 22 months. RESULTS: Prediction of death or neurodevelopmental impairment in extremely premature infants is improved by using information available later during the clinical course. The importance of birth weight declines, whereas the importance of respiratory illness severity increases with advancing postnatal age. The c-statistic in validation models ranged from 0.74 to 0.80 with misclassification rates ranging from 0.28 to 0.30. CONCLUSIONS: Dynamic models of the changing probability of individual outcome can improve outcome predictions in preterm infants. Various current and future scenarios can be modeled by input of different clinical possibilities to develop individual "outcome trajectories" and evaluate impact of possible morbidities on outcome.

Impact of postnatal corticosteroid use on neurodevelopment at 18 to 22 months' adjusted age: effects of dose, timing, and risk of bronchopulmonary dysplasia in extremely low birth weight infants.

OBJECTIVE: Postnatal steroid use decreases lung inflammation but increases impairment. We hypothesized that increased dose is associated with increased neurodevelopmental impairment, lower postmenstrual age at exposure increases impairment, and risk of bronchopulmonary dysplasia modifies the effect of postnatal corticosteroid. METHODS: Steroid dose and timing of exposure beyond 7 days was assessed among 2358 extremely low birth weight infants nested in a prospective trial, with 1667 (84%) survivors examined at 18 to 22 months' postmenstrual age. Logistic regression tested the relationship between impairment (Bayley Mental Developmental Index/Psychomotor Developmental Index of <70, disabling cerebral palsy, or sensory impairment), total dose (tertiles: <0.9, 0.9-1.9, and >/=1.9 mg/kg), and postmenstrual age at first dose. Separate logistic regression tested effect modification according to bronchopulmonary dysplasia severity (Romagnoli risk > 0.5 as high risk, n = 2336 (99%) for days of life 4-7). RESULTS: Three hundred sixty-six (16%) neonates were steroid-treated (94% dexamethasone). Treated neonates were smaller and less mature; 72% of those treated were at high risk for bronchopulmonary dysplasia. Exposure was associated with neurodevelopmental impairment/death. Impairment increased with higher dose; 71% dead or impaired at highest dose tertile. Each 1 mg/kg dose was associated with a 2.0-point reduction on the Mental Developmental Index and a 40% risk increase for disabling cerebral palsy. Older age did not mitigate the harm. Treatment after 33 weeks' postmenstrual age was associated with greatest harm despite not receiving the highest dose. The relationship between steroid exposure and impairment was modified by the bronchopulmonary dysplasia risk, with those at highest risk experiencing less harm. CONCLUSIONS: Higher steroid dose was associated with increased neurodevelopmental impairment. There is no "safe" window for steroid use in extremely low birth weight infants. Neonates with low bronchopulmonary dysplasia risk should not be exposed. A randomized trial of steroid use in infants at highest risk is warranted.

Persistent beneficial effects of breast milk ingested in the neonatal intensive care unit on outcomes of extremely low birth weight infants at 30 months of age.

BACKGROUND: We previously reported beneficial effects of breast milk ingestion by infants with extremely low birth weight in the NICU on developmental outcomes at 18 months' corrected age. The objective of this study was to determine whether these effects of breast milk in infants with extremely low birth weight persisted at 30 months' corrected age. METHODS: Nutrition data, including enteral and parenteral feeds, were prospectively collected, and 30 months' corrected age follow-up assessments were completed on 773 infants with extremely low birth weight who participated in the National Institute of Child Health and Human Development Neonatal Research Network Glutamine Trial. A total of 593 ingested some breast milk during the neonatal hospitalization, and 180 ingested none. Neonatal feeding characteristics and morbidities and 30-month interim history, neurodevelopmental outcomes, and growth parameters were analyzed. Children were divided into quintiles of breast milk volume to evaluate the effects of volume of human milk ingested during the NICU hospitalization. RESULTS: At 30 months, increased ingestion of breast milk was associated with higher Bayley Mental Developmental Index scores, higher Bayley behavior score percentiles for emotional regulation, and fewer rehospitalizations between discharge and 30 months. There were no differences in growth parameters or cerebral palsy. For every 10 mL/kg per day increase in breast milk, the Mental Developmental Index increased by 0.59 points, the Psychomotor Developmental Index by 0.56 points, and the total behavior percentile score by 0.99 points, and the risk of rehospitalization between discharge and 30 months decreased by 5%. CONCLUSIONS: Beneficial effects of ingestion of breast milk in the NICU persist at 30 months' corrected age in this vulnerable extremely low birth weight population. Continued efforts must be made to offer breast milk to all extremely low birth weight infants both in the NICU and after discharge.

Early provision of parenteral amino acids in extremely low birth weight infants: relation to growth and neurodevelopmental outcome.

OBJECTIVE: To determine if postnatal growth failure exerts an adverse effect on subsequent growth and neurodevelopment. STUDY DESIGN: A secondary analysis of 1018 infants who were enrolled in a randomized, clinical trial of glutamine supplementation was performed to determine whether early provision of parenteral amino acids (AA) is associated with better growth and neurodevelopmental outcomes. Infants were stratified by whether they were provided > or =3 g/kg per day of AA at < or =5 days of life (early; n = 182) or not (late; n = 836). RESULTS: At 36 weeks' postmenstrual age, significant differences were found in weight, length, and head circumference in favor of the infants who received early AA; the odds of having weight less than the 10(th) percentile for age was 4-fold higher for infants in the late group. At 18 months' CA, there were no differences in weight, length, or measures of neurodevelopment between the groups; however, male infants in the late group were twice as likely to have head circumference less than the 10(th) percentile. CONCLUSIONS: Early AA were associated with significantly better growth outcomes at 36 weeks' postmenstrual age, and fewer infants who received early AA were found to have suboptimal head growth at 18 months' CA.

Cumulative index of exposure to hypocarbia and hyperoxia as risk factors for periventricular leukomalacia in low birth weight infants.

BACKGROUND: Hypocarbia and hyperoxia are risk factors for periventricular leukomalacia in low birth weight infants. The association of a cumulative index of exposure to hypocarbia and hyperoxia and periventricular leukomalacia has not been evaluated. OBJECTIVE: Our goal was to examine the relationship between cumulative index of exposure to hypocarbia and hyperoxia and periventricular leukomalacia during the first 7 days of life in low birth weight infants. METHODS: Blood gas results were recorded in 6-hour intervals among low birth weight infants in a prospective data registry. Cumulative index of exposure to hypocarbia was calculated as the difference between arterial carbon dioxide level and 35 mmHg multiplied by the time interval in hours for each 6-hour block in a 24-hour day for the first 7 days of life. Cumulative index of exposure to hyperoxia was calculated in the same manner for arterial oxygen level >80 mm Hg. The relationship between exposure to hypocarbia, hyperoxia, and periventricular leukomalacia was examined in 778 infants with blood gas and cranial sonography data. RESULTS: Twenty-one infants had periventricular leukomalacia. Hypocarbia occurred in 489 infants and hyperoxia in 502 infants. Infants with periventricular leukomalacia were more likely to have a lower gestational age and to require delivery room resuscitation than those without periventricular leukomalacia. More infants in the highest quartile of exposure to hypocarbia had periventricular leukomalacia compared to those with no hypocarbia. Risk of periventricular leukomalacia was increased in infants with the highest quartile of exposure to hypocarbia after adjusting for maternal and neonatal variables, none to be associated with periventricular leukomalacia. Cumulative index exposure to hyperoxia was not related to periventricular leukomalacia. CONCLUSIONS: Cumulative exposure to hypocarbia and not hyperoxia was independently related to risk of periventricular leukomalacia in low birth weight infants.

Beneficial effects of breast milk in the neonatal intensive care unit on the developmental outcome of extremely low birth weight infants at 18 months of age.

OBJECTIVE: Beneficial effects of breast milk on cognitive skills and behavior ratings have been demonstrated previously in term and very low birth weight infants. Extremely low birth weight infants are known to be at increased risk for developmental and behavior morbidities. The benefits of breast milk that is ingested in the NICU by extremely low birth weight infants on development and behavior have not been evaluated previously. METHODS: Nutrition data including enteral and parenteral feeds were collected prospectively, and follow-up assessments of 1035 extremely low birth weight infants at 18 months' corrected age were completed at 15 sites that were participants in the National Institute of Child Health and Human Development Neonatal Research Network Glutamine Trial between October 14, 1999, and June 25, 2001. Total volume of breast milk feeds (mL/kg per day) during hospitalization was calculated. Neonatal characteristics and morbidities, interim history, and neurodevelopmental and growth outcomes at 18 to 22 months' corrected age were assessed. RESULTS: There were 775 (74.9%) infants in the breast milk and 260 (25.1%) infants in the no breast milk group. Infants in the breast milk group were similar to those in the no breast milk group in every neonatal characteristic and morbidity, including number of days of hospitalization. Mean age of first day of breast milk for the breast milk infants was 9.3 +/- 9 days. Infants in the breast milk group began to ingest non-breast milk formula later (22.8 vs 7.3 days) compared with the non-breast milk group. Age at achieving full enteral feeds was similar between the breast milk and non-breast milk groups (29.0 +/- 18 vs 27.4 +/- 15). Energy intakes of 107.5 kg/day and 105.9 kg/day during the hospitalization did not differ between the breast milk and non-breast milk groups, respectively. At discharge, 30.6% of infants in the breast milk group still were receiving breast milk. Mothers in the breast milk group were significantly more likely to be white (42% vs 27%), be married (50% vs 30%), have a college degree (22% vs 6%), and have private health insurance (34% vs 18%) compared with the no breast milk group. Mothers who were black, had a low household income (< or = dollar 20000), or had higher parity were less likely to provide breast milk feeds. The analysis of outcomes between the any human milk and no human milk groups were adjusted for maternal age, maternal education, marital status, race/ethnicity, and the other standard covariates. Children in the breast milk group were more likely to have a Bayley Mental Development Index > or = 85, higher mean Bayley Psychomotor Development Index, and higher Bayley Behavior Rating Scale percentile scores for orientation/engagement, motor regulation, and total score. There were no differences in the rates of moderate to severe cerebral palsy or blindness or hearing impairment between the 2 study groups. There were no differences in the mean weight (10.4 kg vs 10.4 kg), length (80.5 cm vs 80.5 cm), or head circumference (46.8 cm vs 46.6 cm) for the breast milk and no breast milk groups, respectively, at 18 months. Multivariate analyses, adjusting for confounders, confirmed a significant independent association of breast milk on all 4 primary outcomes: the mean Bayley (Mental Development Index, Psychomotor Development Index, Behavior Rating Scale, and incidence of rehospitalization). For every 10-mL/kg per day increase in breast milk ingestion, the Mental Development Index increased by 0.53 points, the Psychomotor Development Index increased by 0.63 points, the Behavior Rating Scale percentile score increased by 0.82 points, and the likelihood of rehospitalization decreased by 6%. In an effort to identify a threshold effect of breast milk on Bayley Mental Development Index and Psychomotor Development Index scores and Behavior Rating Scale percentile scores, the mean volume of breast milk per kilogram per day during the hospitalization was calculated, and infants in the breast milk group were divided into quintiles of breast milk ingestion adjusted for confounders. Overall, the differences across the feeding quintiles of Mental Development Index and Psychomotor Development Index were significant. There was a 14.0% difference in Behavior Rating Scale scores between the lowest and highest quintiles. For the outcomes (Mental Development Index, Psychomotor Development Index, Behavior Rating Scale, and Rehospitalization <1 year), only the values for the >80th percentile quintile of breast milk feeding were significantly different from the no breast milk values. In our adjusted regression analyses, every 10 mL/kg per day breast milk contributed 0.53 points to the Bayley Mental Development Index; therefore, the impact of breast milk ingestion during the hospitalization for infants in the highest quintile (110 mL/kg per day) on the Bayley Mental Development Index would be 10 x 0.53, or 5.3 points. CONCLUSIONS: An increase of 5 points potentially would optimize outcomes and decrease costs by decreasing the number of very low birth weight children who require special education services. The societal implications of a 5-point potential difference (one third of an SD) in IQ are substantial. The potential long-term benefit of receiving breast milk in the NICU for extremely low birth weight infants may be to optimize cognitive potential and reduce the need for early intervention and special education services.

Outcome of extremely-low-birth-weight infants at highest risk: gestational age < or =24 weeks, birth weight < or =750 g, and 1-minute Apgar < or =3.

OBJECTIVE: The purpose of this study was to evaluate neurodevelopmental outcome in extremely-low-birth-weight (ELBW) infants, all of whom had 3 characteristics: gestational age (GA) < or =24 weeks, birth weight < or =750 g, and 1-minute Apgar score < or =3. STUDY DESIGN: Surviving infants were evaluated at 18 to 22 months' corrected age with a neurologic examination and the Bayley II Mental and Psychomotor Developmental Index (MDI and PDI). RESULTS: Between 1993 and 1999, 1016 infants had GA < or =24 weeks, birth weight < or =750 g, and 1-minute Apgar score < or =3. Of 246 survivors, 30% had cerebral palsy (CP), 5% had hearing impairment, and 2% were blind. MDI was > or =85 in 33% and < 70 in 46% of infants, while PDI was > or =85 in 41% and < 70 in 36% infants. Predictors of MDI < 70 were grade III-IV ICH, cystic periventricular leukomalacia (PVL), male gender, black race, and Medicaid insurance. Two-parent household was associated with an MDI >70. Predictors of PDI < 70 were grade III-IV ICH, PVL, steroids for bronchopulmonary dysplasia (BPD), and Medicaid insurance. CP was associated with grade III-IV ICH and PVL. CONCLUSION: Perinatologists and neonatologists should be aware of the risk of morbidity and mortality in this high-risk ELBW group.

The maternal lifestyle study: cognitive, motor, and behavioral outcomes of cocaine-exposed and opiate-exposed infants through three years of age.

OBJECTIVE: To evaluate the direct effects of prenatal cocaine exposure and prenatal opiate exposure on infant mental, motor, and behavioral outcomes longitudinally between 1 and 3 years old. METHODS: As part of a prospective, longitudinal, multisite study, the Bayley Scales of Infant Development II were administered to 1227 infants who were exposed to cocaine (n = 474), opiates (n = 50), cocaine and opiates (n = 48), and neither substance (n = 655) at 1, 2, and 3 years of corrected age by certified, masked examiners. Hierarchic linear modeling of the 1-, 2-, and 3-year scores was conducted using cocaine and opiate exposure as predictors with and without controlling for covariates. RESULTS: Overall retention was 88.4% and did not differ by cocaine or opiate exposure. Overall (at 1, 2, and 3 years), cocaine-exposed infants scored 1.6 Mental Development Index points below infants who were not exposed to cocaine. Opiate-exposed infants scored 3.8 Psychomotor Development Index points below infants who were not exposed to opiates. Neither the cocaine nor the opiate effect remained significant after controlling for covariates. Neither cocaine nor opiate exposure was associated with the Behavioral Record Score during the examination. Low birth weight and indices of nonoptimal caregiving were associated with lower Mental Development Index, Psychomotor Development Index, and Behavioral Record Score scores for all groups of infants. CONCLUSIONS: In the largest at-risk sample observed longitudinally to date, infant prenatal exposure to cocaine and to opiates was not associated with mental, motor, or behavioral deficits after controlling for birth weight and environmental risks.

Risk factors for early death among extremely low-birth-weight infants.

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.