IMPORTANCE: Extremely preterm infants contribute disproportionately to neonatal morbidity and mortality. OBJECTIVE: To review 20-year trends in maternal/neonatal care, complications, and mortality ...among extremely preterm infants born at Neonatal Research Network centers. DESIGN, SETTING, PARTICIPANTS: Prospective registry of 34 636 infants, 22 to 28 weeks’ gestation, birth weight of 401 to 1500 g, and born at 26 network centers between 1993 and 2012. EXPOSURES: Extremely preterm birth. MAIN OUTCOMES AND MEASURES: Maternal/neonatal care, morbidities, and survival. Major morbidities, reported for infants who survived more than 12 hours, were severe necrotizing enterocolitis, infection, bronchopulmonary dysplasia, severe intracranial hemorrhage, cystic periventricular leukomalacia, and/or severe retinopathy of prematurity. Regression models assessed yearly changes and were adjusted for study center, race/ethnicity, gestational age, birth weight for gestational age, and sex. RESULTS: Use of antenatal corticosteroids increased from 1993 to 2012 (24% 348 of 1431 infants) to 87% (1674 of 1919 infants; P < .001), as did cesarean delivery (44% 625 of 1431 births to 64% 1227 of 1921; P < .001). Delivery room intubation decreased from 80% (1144 of 1433 infants) in 1993 to 65% (1253 of 1922) in 2012 (P < .001). After increasing in the 1990s, postnatal steroid use declined to 8% (141 of 1757 infants) in 2004 (P < .001), with no significant change thereafter. Although most infants were ventilated, continuous positive airway pressure without ventilation increased from 7% (120 of 1666 infants) in 2002 to 11% (190 of 1756 infants) in 2012 (P < .001). Despite no improvement from 1993 to 2004, rates of late-onset sepsis declined between 2005 and 2012 for infants of each gestational age (median, 26 weeks 37% {109 of 296} to 27% {85 of 320}; adjusted relative risk RR, 0.93 95% CI, 0.92-0.94). Rates of other morbidities declined, but bronchopulmonary dysplasia increased between 2009 and 2012 for infants at 26 to 27 weeks’ gestation (26 weeks, 50% 130 of 258 to 55% 164 of 297; P < .001). Survival increased between 2009 and 2012 for infants at 23 weeks’ gestation (27% 41 of 152 to 33% 50 of 150; adjusted RR, 1.09 95% CI, 1.05-1.14) and 24 weeks (63% 156 of 248 to 65% 174 of 269; adjusted RR, 1.05 95% CI, 1.03-1.07), with smaller relative increases for infants at 25 and 27 weeks’ gestation, and no change for infants at 22, 26, and 28 weeks’ gestation. Survival without major morbidity increased approximately 2% per year for infants at 25 to 28 weeks’ gestation, with no change for infants at 22 to 24 weeks’ gestation. CONCLUSIONS AND RELEVANCE: Among extremely preterm infants born at US academic centers over the last 20 years, changes in maternal and infant care practices and modest reductions in several morbidities were observed, although bronchopulmonary dysplasia increased. Survival increased most markedly for infants born at 23 and 24 weeks’ gestation and survival without major morbidity increased for infants aged 25 to 28 weeks. These findings may be valuable in counseling families and developing novel interventions. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00063063.
Objective To assess the prognostic accuracy of early cumulative supplemental oxygen (CSO) exposure for prediction of bronchopulmonary dysplasia (BPD) or death, and to evaluate the independent ...association of CSO with BPD or death. Study design We performed a secondary analysis of the Trial of Late Surfactant, which enrolled 511 infants born at ≤28 weeks gestational age who were mechanically ventilated at 7-14 days of life. Our primary outcome was BPD or death at 36 weeks postmenstrual age, as determined by a physiological oxygen/flow challenge. Average daily supplemental oxygen (fraction of inspired oxygen - 0.21) was calculated. CSO was calculated as the sum of the average daily supplemental oxygen over time periods of interest up to 28 days of age. Area under the receiver operating curve (AUROC) values were generated to evaluate the accuracy of CSO for prediction of BPD or death. The independent relationship between CSO and BPD or death was assessed in multivariate modeling, while adjusting for mean airway pressure. Results In the study infants, mean gestational age at birth was 25.2 ± 1.2 weeks and mean birth weight was 700 ± 165 g. The AUROC value for CSO at 14 days was significantly better than that at earlier time points for outcome prediction (OR, 0.70; 95% CI, 0.65-0.74); it did not increase with the addition of later data. In multivariate modeling, a CSO increase of 1 at 14 days increased the odds of BPD or death (OR, 1.7; 95% CI, 1.3-2.2; P < .0001), which corresponds to a 7% higher daily supplemental oxygen value. Conclusion In high-risk extremely low gestational age newborns, the predictive accuracy of CSO plateaus at 14 days. CSO is independently associated with BPD or death. This index may identify infants who could benefit from early intervention to prevent BPD.
IMPORTANCE: Hypothermia initiated at less than 6 hours after birth reduces death or disability for infants with hypoxic-ischemic encephalopathy at 36 weeks’ or later gestation. To our knowledge, ...hypothermia trials have not been performed in infants presenting after 6 hours. OBJECTIVE: To estimate the probability that hypothermia initiated at 6 to 24 hours after birth reduces the risk of death or disability at 18 months among infants with hypoxic-ischemic encephalopathy. DESIGN, SETTING, AND PARTICIPANTS: A randomized clinical trial was conducted between April 2008 and June 2016 among infants at 36 weeks’ or later gestation with moderate or severe hypoxic-ischemic encephalopathy enrolled at 6 to 24 hours after birth. Twenty-one US Neonatal Research Network centers participated. Bayesian analyses were prespecified given the anticipated limited sample size. INTERVENTIONS: Targeted esophageal temperature was used in 168 infants. Eighty-three hypothermic infants were maintained at 33.5°C (acceptable range, 33°C-34°C) for 96 hours and then rewarmed. Eighty-five noncooled infants were maintained at 37.0°C (acceptable range, 36.5°C-37.3°C). MAIN OUTCOMES AND MEASURES: The composite of death or disability (moderate or severe) at 18 to 22 months adjusted for level of encephalopathy and age at randomization. RESULTS: Hypothermic and noncooled infants were term (mean SD, 39 2 and 39 1 weeks’ gestation, respectively), and 47 of 83 (57%) and 55 of 85 (65%) were male, respectively. Both groups were acidemic at birth, predominantly transferred to the treating center with moderate encephalopathy, and were randomized at a mean (SD) of 16 (5) and 15 (5) hours for hypothermic and noncooled groups, respectively. The primary outcome occurred in 19 of 78 hypothermic infants (24.4%) and 22 of 79 noncooled infants (27.9%) (absolute difference, 3.5%; 95% CI, −1% to 17%). Bayesian analysis using a neutral prior indicated a 76% posterior probability of reduced death or disability with hypothermia relative to the noncooled group (adjusted posterior risk ratio, 0.86; 95% credible interval, 0.58-1.29). The probability that death or disability in cooled infants was at least 1%, 2%, or 3% less than noncooled infants was 71%, 64%, and 56%, respectively. CONCLUSIONS AND RELEVANCE: Among term infants with hypoxic-ischemic encephalopathy, hypothermia initiated at 6 to 24 hours after birth compared with noncooling resulted in a 76% probability of any reduction in death or disability, and a 64% probability of at least 2% less death or disability at 18 to 22 months. Hypothermia initiated at 6 to 24 hours after birth may have benefit but there is uncertainty in its effectiveness. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00614744
To assess the usefulness of a bronchopulmonary dysplasia (BPD) outcome estimator developed by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) in ...identifying high-risk preterm infants treated with steroids.
This was a single-center retrospective study of infants born ≤30 weeks of gestational age. The NICHD BPD outcome estimator was used to retrospectively calculate BPD risk at various postnatal ages. The best combination of risk estimates for identifying steroid treatment was identified using stepwise model selection. A cut-off value with the best combination of sensitivity and specificity was identified using receiver operating characteristic analysis.
A total of 165 infants born preterm (mean gestational age 26 ± 1.6 weeks, mean birth weight 837 ± 171 g) were included. Of these, 61 were treated with steroids for BPD and 104 were not. Risk estimates for BPD or death were significantly greater in infants treated with steroids compared with controls. Both combined risk for severe BPD or death and single risk of no BPD were identified as factors with the best predictive power for identifying treatment with steroids, with accurate prediction possible as early as the second week of life. A greater than 37% risk for severe BPD or death or a less than 3% risk of no BPD on day of life 14 had 84%-92% sensitivity and 77%-80% specificity for predicting steroid treatment.
The NICHD BPD outcome estimator can be a useful objective tool for identifying infants at high risk for BPD who may benefit from postnatal steroids.
To assess the effect of pulmonary hypertension on neonatal intensive care unit mortality and hospital readmission through 1 year of corrected age in a large multicenter cohort of infants with severe ...bronchopulmonary dysplasia.
This was a multicenter, retrospective cohort study of 1677 infants born <32 weeks of gestation with severe bronchopulmonary dysplasia enrolled in the Children's Hospital Neonatal Consortium with records linked to the Pediatric Health Information System.
Pulmonary hypertension occurred in 370 out of 1677 (22%) infants. During the neonatal admission, pulmonary hypertension was associated with mortality (OR 3.15, 95% CI 2.10-4.73, P < .001), ventilator support at 36 weeks of postmenstrual age (60% vs 40%, P < .001), duration of ventilation (72 IQR 30-124 vs 41 IQR 17-74 days, P < .001), and higher respiratory severity score (3.6 IQR 0.4-7.0 vs 0.8 IQR 0.3-3.3, P < .001). At discharge, pulmonary hypertension was associated with tracheostomy (27% vs 9%, P < .001), supplemental oxygen use (84% vs 61%, P < .001), and tube feeds (80% vs 46%, P < .001). Through 1 year of corrected age, pulmonary hypertension was associated with increased frequency of readmission (incidence rate ratio IRR = 1.38, 95% CI 1.18-1.63, P < .001).
Infants with severe bronchopulmonary dysplasia-associated pulmonary hypertension have increased morbidity and mortality through 1 year of corrected age. This highlights the need for improved diagnostic practices and prospective studies evaluating treatments for this high-risk population.
Objective
To determine the association of timing of steroid therapy for bronchopulmonary dysplasia (BPD) and outcomes.
Methods
Retrospective cohort study of preterm infants treated with low‐dose ...dexamethasone for BPD. Infants treated with steroids at day of life (DOL) 14‐28 (moderately late group) were compared to infants treated at DOL 29‐42 (delayed group). Inverse probability of treatment weighting (IPTW) adjusted propensity scores were used to correct for potential confounders. The primary outcome of interest was postmenstrual age (PMA) at discharge.
Results
Fifty‐five infants (25 with moderately late treatment; 30 with delayed treatment) were identified. The mean age at treatment was 23 days in the moderately late group and 35 days in the delayed group. At time of treatment, infants treated moderately late were more likely to be on high frequency ventilation (96% vs 47%, P < 0.0001) and had higher fraction of inspired oxygen (70.7 ± 17.9% vs 56.2 ± 18.4%, P = 0.005) compared to infants treated later. Despite being the sicker group, moderately late treated infants were discharged at an earlier corrected age compared to infants with delayed treatment (PMA 42.9 ± 4.5 vs 47.5 ± 8.3 weeks, IPTW adjusted P = 0.03). Moderately late treatment was also associated with fewer days on mechanical ventilation (46.0 ± 19.0 days vs 77.4 ± 67.0 days, IPTW adjusted P = 0.02) and fewer days on supplemental oxygen (114.3 ± 40.8 days vs 149.8 ± 57.0 days, IPTW adjusted P = 0.005).
Conclusions
Among preterm infants at high risk of BPD, delaying treatment with postnatal steroids is associated with comparatively worse short‐term outcomes as compared to earlier treatment.
There are few published data on the efficacy and safety of prednisolone in preterm infants with bronchopulmonary dysplasia (BPD).
To describe the use of chronic prednisolone therapy in a population ...of infants with severe BPD, examine potential benefits on respiratory status, and document potential effects on growth.
Single-center retrospective cohort study.
Preterm infants who had received ≥30 days of prednisolone for the treatment of severe BPD.
Weekly changes in Pulmonary Severity Score (PSS), as well as weekly changes in weight, length, and head circumference during prednisolone therapy.
Forty-three infants (mean birth weight 729 g; mean gestational age 26 weeks) were identified. The average age at start of prednisolone treatment was 42.5 ± 5.9 weeks; while the median duration and median cumulative dose of prednisolone therapy were 67 (IQR 57–107) days and 61.3 (IQR 39.9–93.3) mg/kg, respectively. PSS decreased after 1 week of prednisolone therapy (mean difference, 0.19; 95% Cl, 0.01 to 0.37; p = 0.03). No further reduction in PSS was noted despite continued treatment. Length z-scores decreased after 4 weeks of continued treatment (mean difference 0.6; 95% CI 0.01 to 1.1; P = 0.04), while weight and head circumference did not change.
In one of the first reports on prednisolone therapy for severe BPD, we describe that long-term prednisolone is associated with modest short-term improvement in PSS, but impairs linear growth. Our results suggest a risk-benefit profile of prednisolone that does not favor long-term use in infants with severe BPD.
•Management of infants with severe bronchopulmonary dysplasia (BPD) is challenging.•Systemic steroids are often used in cases of severe BPD despite paucity of data.•Safety and efficacy of long-term prednisolone for BPD remain unknown.•Prednisolone was associated with modest short-term improvement in oxygenation.•Continued use, however, was associated with impairment in linear growth.
In this multicenter, randomized trial of preterm newborns with a birth weight of 1250 g or less who required ventilatory support, the initiation of inhaled nitric oxide between days 7 and 21 of life ...significantly reduced the risk of death or chronic lung disease and the duration of both hospitalization and supplemental oxygen therapy. Using a regimen of inhaled nitric oxide therapy different from that in the companion report by Kinsella et al., this group also found inhaled nitric oxide to be beneficial in preterm infants with respiratory failure.
In preterm newborns with a birth weight of 1250 g or less who required ventilatory support, the initiation of inhaled nitric oxide between days 7 and 21 of life significantly reduced the risk of death or chronic lung disease and the duration of both hospitalization and supplemental oxygen therapy.
Survival among preterm infants has improved markedly in recent decades, in large part because of the ability to enhance fetal-lung maturation with antenatal corticosteroids and manage the respiratory distress syndrome. Chronic lung disease, or bronchopulmonary dysplasia,
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is now the most important long-term pulmonary complication in these infants and is associated with prolonged hospitalization and long-term pulmonary and neurodevelopmental problems.
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Severe bronchopulmonary dysplasia is associated with inflammation,
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pulmonary hypertension,
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and increased airway resistance,
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as well as abnormalities of lung growth, including disturbed angiogenesis and alveolarization.
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Inhaled nitric oxide is an effective treatment for pulmonary hypertension . . .
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