Causes and timing of death in extremely premature infants from 2000 through 2011.

BACKGROUND: Understanding the causes and timing of death in extremely premature infants may guide research efforts and inform the counseling of families. METHODS: We analyzed prospectively collected data on 6075 deaths among 22,248 live births, with gestational ages of 22 0/7 to 28 6/7 weeks, among infants born in study hospitals within the National Institute of Child Health and Human Development Neonatal Research Network. We compared overall and cause-specific in-hospital mortality across three periods from 2000 through 2011, with adjustment for baseline differences. RESULTS: The number of deaths per 1000 live births was 275 (95% confidence interval [CI], 264 to 285) from 2000 through 2003 and 285 (95% CI, 275 to 295) from 2004 through 2007; the number decreased to 258 (95% CI, 248 to 268) in the 2008-2011 period (P=0.003 for the comparison across three periods). There were fewer pulmonary-related deaths attributed to the respiratory distress syndrome and bronchopulmonary dysplasia in 2008-2011 than in 2000-2003 and 2004-2007 (68 [95% CI, 63 to 74] vs. 83 [95% CI, 77 to 90] and 84 [95% CI, 78 to 90] per 1000 live births, respectively; P=0.002). Similarly, in 2008-2011, as compared with 2000-2003, there were decreases in deaths attributed to immaturity (P=0.05) and deaths complicated by infection (P=0.04) or central nervous system injury (P<0.001); however, there were increases in deaths attributed to necrotizing enterocolitis (30 [95% CI, 27 to 34] vs. 23 [95% CI, 20 to 27], P=0.03). Overall, 40.4% of deaths occurred within 12 hours after birth, and 17.3% occurred after 28 days. CONCLUSIONS: We found that from 2000 through 2011, overall mortality declined among extremely premature infants. Deaths related to pulmonary causes, immaturity, infection, and central nervous system injury decreased, while necrotizing enterocolitis-related deaths increased. (Funded by the National Institutes of Health.).

Admission Temperature and Associated Mortality and Morbidity among Moderately and Extremely Preterm Infants.

OBJECTIVE: To evaluate the temperature distribution among moderately preterm (MPT, 29-33 weeks) and extremely preterm (EPT, <29 weeks) infants upon neonatal intensive care unit (NICU) admission in 2012-2013, the change in admission temperature distribution for EPT infants between 2002-2003 and 2012-2013, and associations between admission temperature and mortality and morbidity for both MPT and EPT infants. STUDY DESIGN: Prospectively collected data from 18 centers in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network were used to examine NICU admission temperature of inborn MPT and EPT infants. Associations between admission temperature and mortality and morbidity were determined by multivariable logistic regression. EPT infants from 2002-2003 and 2012-2013 were compared. RESULTS: MPT and EPT cohorts consisted of 5818 and 3213 infants, respectively. The distribution of admission temperatures differed between the MPT vs EPT (P < .01), including the percentage <36.5°C (38.6% vs 40.9%), 36.5°C-37.5°C (57.3% vs 52.9%), and >37.5°C (4.2% vs 6.2%). For EPT infants in 2012-2013 compared with 2002-2003, the percentage of temperatures between 36.5°C and 37.5°C more than doubled and the percentage of temperatures >37.5°C more than tripled. Admission temperature was inversely associated with in-hospital mortality. CONCLUSIONS: Low and high admission temperatures are more frequent among EPT than MPT infants. Compared with a decade earlier, fewer EPT infants experience low admission temperatures but more have elevated temperatures. In spite of a change in distribution of NICU admission temperature, an inverse association between temperature and mortality risk persists.

Neonatal outcomes of moderately preterm infants compared to extremely preterm infants.

BackgroundExtremely preterm infants (EPT, <29 weeks' gestation) represent only 0.9% of births in the United States; yet these infants are the focus of most published research. Moderately preterm neonates (MPT, 29-336/7 weeks) are an understudied group of high-risk infants.MethodsTo determine the neonatal outcomes of MPT infants across the gestational age spectrum, and to compare these with EPT infants. A prospective observational cohort was formed in 18 level 3-4 neonatal intensive care units (NICUs) in the Eunice Kennedy Shriver NICHD Neonatal Research Network. Participants included all MPT infants admitted to NICUs and all EPT infants born at sites between January 2012 and November 2013. Antenatal characteristics and neonatal morbidities were abstracted from records using pre-specified definitions by trained neonatal research nurses.ResultsMPT infants experienced morbidities similar to, although at lower rates than, those of EPT infants. The main cause of mortality was congenital malformation, accounting for 43% of deaths. Central Nervous System injury occurred, including intraventricular hemorrhage. Most MPT infants required respiratory support, but sequelae such as bronchopulmonary dysplasia were rare. The primary contributors to hospitalization beyond 36 weeks' gestation were inability to achieve adequate oral intake and persistent apnea.ConclusionsMPT infants experience morbidity and prolonged hospitalization. Such morbidity deserves focused research to improve therapeutic and prevention strategies.

Late-onset Sepsis in Extremely Premature Infants: 2000-2011.

BACKGROUND: Late-onset sepsis (LOS) is an important cause of death and neurodevelopmental impairment in premature infants. The purpose of this study was to assess overall incidence of LOS, distribution of LOS-causative organisms and center variation in incidence of LOS for extremely premature infants over time. METHODS: In a retrospective analysis of infants 401-1000 g birth weight and 22-28 6/7 weeks of gestational age born at 12 National Institute of Child Health and Human Development Neonatal Research Network centers in the years 2000-2005 (era 1) or 2006-2011 (era 2) who survived >72 hours, we compared the incidence of LOS and pathogen distribution in the 2 eras using the χ test. We also examined the effect of birth year on the incidence of LOS using multivariable regression to adjust for nonmodifiable risk factors and for center. To assess whether the incidence of LOS was different among centers in era 2, we used a multivariable regression model to adjust for nonmodifiable risk factors. RESULTS: Ten-thousand one-hundred thirty-one infants were studied. LOS occurred in 2083 of 5031 (41%) infants in era 1 and 1728 of 5100 (34%) infants in era 2 (P < 0.001). Birth year was a significant predictor of LOS on adjusted analysis, with birth years 2000-2009 having a significantly higher odds of LOS than the reference year 2011. Pathogens did not differ, with the exception of decreased fungal infection (P < 0.001). In era 2, 9 centers had significantly higher odds of LOS compared with the center with the lowest incidence. CONCLUSIONS: The incidence of LOS decreased over time. Further investigation is warranted to determine which interventions have the greatest impact on infection rates.

Effects of indomethacin prophylaxis timing on intraventricular haemorrhage and patent ductus arteriosus in extremely low birth weight infants.

OBJECTIVE: Indomethacin prophylaxis (IP) reduces the risk of intraventricular haemorrhage (IVH) and patent ductus arteriosus (PDA) in preterm infants. However, the optimal time to administer IP has not been determined. We hypothesised that IP at ≤6 h is associated with a lower incidence of IVH or death than if administered at >6-24 h of age. METHODS: We performed a retrospective cohort study of extremely low birth weight infants (≤1000 g birth weight) treated in the neonatal intensive care units in the Neonatal Research Network from 2003 to 2010 and who received IP in the first 24 h of age. Infants were dichotomised based upon receipt of IP at ≤6 or >6-24 h of age. The primary outcomes were IVH alone and IVH or death. Secondary outcomes were PDA alone and PDA or death. We used multivariable analyses to determine associations between the age of IP and the study outcomes expressed as an OR and 95% CI. RESULTS: IP was given at ≤6 h to 2340 infants and at >6-24 h to 1915 infants. Infants given IP at ≤6 h had more antenatal steroid exposure, more inborn and less cardiopulmonary resuscitation (p<0.01). After multivariable analyses, age of IP receipt was not associated with IVH, and IVH or death but PDA receiving treatment/ligation or death was lower among IP at ≤6 h compared with IP at >6-24 h (OR 0.83, 95% CI 0.71 to 0.98). CONCLUSIONS: IP at ≤6 h of age is not associated with less IVH or death, but is associated with less PDA receiving treatment/ligation or death.

Cardiovascular mortality in New York City after September 11, 2001.

Major catastrophes, such as earthquakes and wars, have been associated with short-term increases in cardiac mortality. We investigated whether the terrorist attacks of September 11, 2001, were associated with increased cardiac mortality in New York City. We analyzed death certificate data in New York City for the time period around September 11, 2001. Compared with control years, there was no excess mortality from cardiac causes in the month after September 11, 2001. Also, there was no increase in death from cerebrovascular disease. In conclusion, there was no disproportionate increase in cardiovascular mortality after the terrorist attacks.

Delivery room continuous positive airway pressure/positive end-expiratory pressure in extremely low birth weight infants: a feasibility trial.

OBJECTIVE: Although earlier studies have suggested that early continuous airway positive pressure (CPAP) may be beneficial in reducing ventilator dependence and subsequent chronic lung disease in the extremely low birth weight (ELBW) infant, the time of initiation of CPAP has varied, and there are no prospective studies of infants who have received CPAP or positive end-expiratory pressure (PEEP) from initial resuscitation in the delivery room (DR). Current practice for the ELBW infant includes early intubation and the administration of prophylactic surfactant, often in the DR. The feasibility of initiating CPAP in the DR and continuing this therapy without intubation for surfactant has never been determined prospectively in a population of ELBW infants. This study was designed to determine the feasibility of randomizing ELBW infants of <28 weeks' gestation to CPAP/PEEP or no CPAP/PEEP during resuscitation immediately after delivery, avoiding routine DR intubation for surfactant administration, initiating CPAP on neonatal intensive care unit (NICU) admission, and assessing compliance with subsequent intubation criteria. METHODS: Infants who were of <28 weeks' gestation, who were born in 5 National Institute of Child Health and Human Development Neonatal Research Network NICUs from July 2002 to January 2003, and for whom a decision had been made to provide full treatment after birth were randomized to receive either CPAP/PEEP or not using a neonatal T-piece resuscitator (NeoPuff). Infants would not be intubated for the sole purpose of surfactant administration in the DR. After admission to the NICU, all nonintubated infants were placed on CPAP and were to be intubated for surfactant administration only after meeting specific criteria: a fraction of inspired oxygen of >0.3 with an oxygen saturation by pulse oximeter of <90% and/or an arterial oxygen pressure of <45 mm Hg, an arterial partial pressure of carbon dioxide of >55 mm Hg, or apnea requiring bag and mask ventilation. RESULTS: A total of 104 infants were enrolled over a 6-month period: 55 CPAP and 49 control infants. No infant was intubated in the DR for the exclusive purpose of surfactant administration. Forty-seven infants were intubated for resuscitation in the DR: 27 of 55 CPAP infants and 20 of 49 control infants. Only 4 of the 43 infants who had a birth weight of <700 g and 3 of the 37 infants of <25 weeks' gestation were resuscitated successfully without positive pressure ventilation, and no difference was observed between the treatment groups. All infants of 23 weeks' gestation required intubation in the DR, irrespective of treatment group, whereas only 3 (14%) of 21 infants of 27 weeks' required such intubation. For infants who were not intubated in the DR, 36 infants (16 CPAP infants and 20 control infants) were subsequently intubated in the NICU by day 7, in accordance with the protocol. Overall, 80% of studied infants required intubation within the first 7 days of life. The care provided for 52 (95%) of 55 CPAP infants and 43 (88%) of the 49 control infants was in compliance with the study protocol, with an overall compliance of 91%. CONCLUSIONS: This study demonstrated that infants could be randomized successfully to a DR intervention of CPAP/PEEP compared with no CPAP/PEEP, with intubation provided only for resuscitation indications, and subsequent intubation for prespecified criteria. Forty-five percent (47 of 104) of infants <28 weeks' gestation required intubation for resuscitation in the DR. CPAP/PEEP in the DR did not affect the need for intubation at birth or during the subsequent week. Overall, 20% of infants did not need intubation by 7 days of life. This experience should be helpful in facilitating the design of subsequent prospective studies of ventilatory support in ELBW infants.