Data are limited on the impact of methicillin-resistant Staphylococcus aureus (MRSA) on morbidity and mortality among very low birth weight (VLBW) infants with S aureus (SA) bacteremia and/or ...meningitis (B/M).
Neonatal data for VLBW infants (birth weight 401-1500 g) born January 1, 2006, to December 31, 2008, who received care at centers of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network were collected prospectively. Early-onset (≤72 hours after birth) and late-onset (>72 hours) infections were defined by blood or cerebrospinal fluid cultures and antibiotic treatment of ≥5 days (or death <5 days with intent to treat). Outcomes were compared for infants with MRSA versus methicillin-susceptible S aureus (MSSA) B/M.
Of 8444 infants who survived >3 days, 316 (3.7%) had SA B/M. Eighty-eight had MRSA (1% of all infants, 28% of infants with SA); 228 had MSSA (2.7% of all infants, 72% of infants with SA). No infant had both MRSA and MSSA B/M. Ninety-nine percent of MRSA infections were late-onset. The percent of infants with MRSA varied by center (P < .001) with 9 of 20 centers reporting no cases. Need for mechanical ventilation, diagnosis of respiratory distress syndrome, necrotizing enterocolitis, and other morbidities did not differ between infants with MRSA and MSSA. Mortality was high with both MRSA (23 of 88, 26%) and MSSA (55 of 228, 24%).
Few VLBW infants had SA B/M. The 1% with MRSA had morbidity and mortality rates similar to infants with MSSA. Practices should provide equal focus on prevention and management of both MRSA and MSSA infections among VLBW infants.
The objective of this study was to determine whether Apgar scores at 10 minutes are associated with death or disability in early childhood after perinatal hypoxic-ischemic encephalopathy.
This was a ...secondary analysis of infants who were enrolled in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network hypothermia trial. Infants who were born at >or=36 weeks' gestation and had clinical and/or biochemical abnormalities at birth and encephalopathy at <6 hours were studied. Logistic regression and classification and regression-tree analysis were used to determine associations between Apgar scores at 10 minutes and neurodevelopmental outcome, adjusting for covariates. Death or disability (moderate or severe) at 18 to 22 months of age was the measured outcome.
Twenty of 208 infants were excluded (missing data). More than 90% of the infants had Apgar scores of 0 to 2 at 1 minute, and Apgar scores at 5 and 10 minutes shifted to progressively higher values; at 10 minutes, 27% of infants had Apgar scores of 0 to 2. After adjustment, each point decrease in Apgar score at 10 minutes was associated with a 45% increase in the odds of death or disability. Death or disability occurred in 76%, 82%, and 80% of infants with 10-minute Apgar scores of 0, 1, and 2, respectively. Classification and regression-tree analysis indicated that Apgar scores at 10 minutes were discriminators of outcome.
Apgar scores at 10 minutes provide useful prognostic data before other evaluations are available for infants with hypoxic-ischemic encephalopathy. Death or moderate/severe disability is common but not uniform with Apgar scores of <3; caution is needed before adopting a specific time interval to guide duration of resuscitation.
Therapeutic hypothermia (TH) is now well established as the standard of care treatment for moderate to severe neonatal encephalopathy secondary to perinatal hypoxic ischemic encephalopathy (HIE) in ...infants ≥36 weeks gestation in high income countries. The Neonatal Research Network (NRN) contributed greatly to the study of TH as a neuroprotectant with three trials now completed in infants ≥36 weeks gestation and the only large randomized-controlled trial of TH in preterm infants now in the follow-up phase. Data from the first NRN TH trial combined with data from other large trials of TH affirm the safety and neuroprotective qualities of TH and highlight the importance of providing TH to all infants who qualify. In this review we will highlight the findings of the three NRN trials of TH in the term infant population and the secondary analyses that continue to inform the care of patients with HIE.
To test the hypothesis that an Apgar score at 10 minutes is independently predictive for death or moderate or severe disability.
A secondary analysis of the Optimizing Cooling Trial (NCT01192776) ...including 347 infants with ≥36 weeks' gestational age at birth and hypoxic-ischemic encephalopathy and 18- to 22-month outcomes from 18 US centers in the National Institute of Child Health and Human Development Neonatal Research Network. The primary outcome was the composite of death or moderate/severe disability at 18 to 22 months of age. Generalized estimating equation models were used to examine the relationship between Apgar scores and outcomes, controlling for center, hypothermia treatment, and severity of hypoxic-ischemic encephalopathy (HIE). Classification and regression tree analyses were conducted to identify combinations of variables available during resuscitation that were most predictive for the composite outcome and death.
The study revealed that 50% (13 of 26) of infants with a 10-minute Apgar score of 0 survived; 46% (6 of 13) had no disability, 16% (2 of 13) had mild disability, and 38% (5 of 13) had moderate or severe disability. The 10-minute Apgar score of 0 was independently associated with death or moderate or severe disability (adjusted relative risk = 1.72, 95% confidence interval 1.11-2.68, P value = .016), but the area under the curve analysis (AUC) was low (AUC = 0.56). The predictive accuracy improved when the 10-minute Apgar score was combined with other risk variables available during resuscitation by using a classification and regression tree analysis (AUC = 0.66).
A 10-minute Apgar score of 0 alone does not predict the risk of death or moderate or severe disability well. The current study provides evidence in support of the 2020 American Heart Association/International Liaison Committee on Resuscitation recommendation for continuing resuscitative efforts for infants who need cardiopulmonary resuscitation at 10 minutes after birth.
We sought to determine if a center's approach to care of premature infants at the youngest gestational ages (22-24 weeks' gestation) is associated with clinical outcomes among infants of older ...gestational ages (25-27 weeks' gestation).
Inborn infants of 401 to 1000 g birth weight and 22 0/7 to 27 6/7 weeks' gestation at birth from 2002 to 2008 were enrolled into a prospectively collected database at 20 centers participating in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Markers of an aggressive approach to care for 22- to 24-week infants included use of antenatal corticosteroids, cesarean delivery, and resuscitation. The primary outcome was death before postnatal day 120 for infants of 25 to 27 weeks' gestation. Secondary outcomes were the combined outcomes of death or a number of morbidities associated with prematurity.
Our study included 3631 infants 22 to 24 weeks' gestation and 5227 infants 25 to 27 weeks' gestation. Among the 22- to 24-week infants, use of antenatal corticosteroids ranged from 28% to 100%, cesarean delivery from 13% to 65%, and resuscitation from 30% to 100% by center. Centers with higher rates of antenatal corticosteroid use in 22- to 24-week infants had reduced rates of death, death or retinopathy of prematurity, death or late-onset sepsis, death or necrotizing enterocolitis, and death or neurodevelopmental impairment in 25- to 27-week infants.
This study suggests that physicians' willingness to provide care to extremely low gestation infants as measured by frequency of use of antenatal corticosteroids is associated with improved outcomes for more-mature infants.
To determine the association of persistent pulmonary hypertension of the newborn (PPHN) with death or disability among infants with moderate or severe hypoxic ischemic encephalopathy (HIE) treated ...with therapeutic hypothermia.
We compared infants with and without PPHN enrolled in the hypothermia arm from three randomized controlled trials (RCTs): Induced Hypothermia trial, "usual care" arm of Optimizing Cooling trial, and Late Hypothermia trial. Primary outcome was death or disability at 18-22 months adjusted for severity of HIE, center, and RCT.
Among 280 infants, 67 (24%) were diagnosed with PPHN. Among infants with and without PPHN, death or disability was 47% vs. 29% (adjusted OR: 1.65, 0.86-3.14) and death was 26% vs. 12% (adjusted OR: 2.04, 0.92-4.53), respectively.
PPHN in infants with moderate or severe HIE was not associated with a statistically significant increase in primary outcome. These results should be interpreted with caution given the limited sample size.
Current guidelines, initially published in 1995, recommend antenatal corticosteroids for mothers with preterm labor from 24 to 34 weeks' gestational age, but not before 24 weeks due to lack of data. ...However, many infants born before 24 weeks' gestation are provided intensive care.
To determine if use of antenatal corticosteroids is associated with improvement in major outcomes for infants born at 22 and 23 weeks' gestation.
Cohort study of data collected prospectively on inborn infants with a birth weight between 401 g and 1000 g (N = 10,541) born at 22 to 25 weeks' gestation between January 1, 1993, and December 31, 2009, at 23 academic perinatal centers in the United States. Certified examiners unaware of exposure to antenatal corticosteroids performed follow-up examinations on 4924 (86.5%) of the infants born between 1993 and 2008 who survived to 18 to 22 months. Logistic regression models generated adjusted odds ratios (AORs), controlling for maternal and neonatal variables.
Mortality and neurodevelopmental impairment at 18 to 22 months' corrected age.
Death or neurodevelopmental impairment at 18 to 22 months was significantly lower for infants who had been exposed to antenatal corticosteroids and were born at 23 weeks' gestation (83.4% with exposure to antenatal corticosteroids vs 90.5% without exposure; AOR, 0.58 95% CI, 0.42-0.80), at 24 weeks' gestation (68.4% with exposure to antenatal corticosteroids vs 80.3% without exposure; AOR, 0.62 95% CI, 0.49-0.78), and at 25 weeks' gestation (52.7% with exposure to antenatal corticosteroids vs 67.9% without exposure; AOR, 0.61 95% CI, 0.50-0.74) but not in those infants born at 22 weeks' gestation (90.2% with exposure to antenatal corticosteroids vs 93.1% without exposure; AOR, 0.80 95% CI, 0.29-2.21). If the mothers had received antenatal corticosteroids, the following events occurred significantly less in infants born at 23, 24, and 25 weeks' gestation: death by 18 to 22 months; hospital death; death, intraventricular hemorrhage, or periventricular leukomalacia; and death or necrotizing enterocolitis. For infants born at 22 weeks' gestation, the only outcome that occurred significantly less was death or necrotizing enterocolitis (73.5% with exposure to antenatal corticosteroids vs 84.5% without exposure; AOR, 0.54 95% CI, 0.30-0.97).
Among infants born at 23 to 25 weeks' gestation, antenatal exposure to corticosteroids compared with nonexposure was associated with a lower rate of death or neurodevelopmental impairment at 18 to 22 months.
Little is known about the effects of antenatal corticosteroids (ANS) on extremely preterm multiples.
To examine if use of ANS is associated with improvement in major outcomes in extremely preterm ...multiples.
Infants with a gestational age between 22 and 28 weeks born at a National Institute of Child Health and Human Development Neonatal Research Network center were studied between January 1998 and December 2013. Generalized estimating equation models were used to generate adjusted relative risks (aRR) controlling for important maternal and neonatal variables.
Antenatal corticosteroids.
In-hospital mortality and the composite outcome of neurodevelopmental impairment at 18 to 22 months' corrected age or death before assessment.
A total of 6925 multiple-birth infants were studied; 5775 of 6925 (83.4%) were twins, and 4276 (61.7%) were white. Of the total study population, 6094 (88%) were born to women who received ANS. In-hospital mortality was lower among infants with exposure to ANS vs no exposure (aRR = 0.87; 95% CI, 0.78-0.96). Neurodevelopmental impairment or death was not significantly lower among those exposed to ANS vs no exposure (aRR = 0.93; 95% CI, 0.84-1.03). Other adverse outcomes that occurred less frequently among infants of women receiving ANS included severe intraventricular hemorrhage (aRR = 0.68; 95% CI, 0.58-0.78) and the combined outcomes of necrotizing enterocolitis or death and severe intraventricular hemorrhage or death. Subgroup analyses indicated that exposure to ANS was associated with a lower risk of mortality and a lower composite of neurodevelopmental impairment or mortality among nonsmall for gestational age multiples (aRR = 0.82; 95% CI, 0.74-0.92; and aRR = 0.89; 95% CI, 0.80-0.98, respectively) and a higher risk among small for gestational age multiples (aRR = 1.40; 95% CI, 1.02-1.93; and aRR = 1.62; 95% CI, 1.22-2.16, respectively). Antenatal corticosteroids were associated with higher neurodevelopmental impairment or mortality among multiple-birth infants of mothers with diabetes (aRR = 1.55; 95% CI, 1.00-2.38) but not among infants of mothers without diabetes (aRR = 0.91; 95% CI, 0.83-1.01).
Compared with no exposure, exposure to ANS was associated with a lower risk of mortality in extremely preterm multiples, with no significant differences in the composite of neurodevelopmental impairment or death. Future research should investigate the increased risks of mortality and the composite of neurodevelopmental impairment or death associated with exposure to corticosteroids among small for gestational age multiples.
Determine whether blanket temperatures during therapeutic hypothermia (TH) are associated with 18-22 month outcomes for infants with hypoxic ischemic encephalopathy (HIE).
Retrospective cohort study ...of 181 infants with HIE who received TH in two randomized trials within the Neonatal Research Network. We defined summative blanket temperature constructs and evaluated for association with a primary composite outcome of death or moderate/ severe disability at 18-22 months.
Each 0.5 °C above 33.5 °C in the mean of the highest quartile blanket temperature was associated with a 52% increase in the adjusted odds of death/ disability (aOR 1.52, 95% CI 1.09-2.11). Having >8 consecutive blanket temperatures above 33.5 °C rendered an aOR of death/disability of 5.04 in the first 24 h (95% CI 1.54-16.6) and 6.92 in the first 48 h (95% CI 2.20-21.8) of TH.
Higher blanket temperature during TH may be an early, clinically useful biomarker of HIE outcome.
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, 29-33
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.
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