In-hospital outcomes of premature infants with severe bronchopulmonary dysplasia.
ABSTRACT: OBJECTIVE:To characterize in-hospital outcomes of premature infants diagnosed with severe bronchopulmonary dysplasia (BPD). STUDY DESIGN:Retrospective cohort study including premature infants with severe BPD discharged from 348 Pediatrix Medical Group neonatal intensive care units from 1997 to 2015. RESULTS:There were 10?752 infants with severe BPD, and 549/10?752 (5%) died before discharge. Infants who died were more likely to be male, small for gestational age, have received more medical interventions and more frequently diagnosed with surgical necrotizing enterocolitis, culture-proven sepsis and pulmonary hypertension following 36 weeks of postmenstrual age compared with survivors. Approximately 70% of infants with severe BPD were discharged by 44 weeks of postmenstrual age, and 86% were discharged by 48 weeks of postmenstrual age. CONCLUSIONS:A majority of infants diagnosed with severe BPD were discharged home by 44 weeks of postmenstrual age. These results may inform discussions with families regarding the expected hospital course of infants diagnosed with severe BPD.
Project description:To assess the contribution of the severity of bronchopulmonary dysplasia (BPD) and the time point of its diagnosis to the prediction of neurodevelopmental impairment (NDI) at corrected age of 2 years in preterm infants.Retrospective cohort study.Level-III perinatal centre.Infants born in 2000-2013 with gestational age <30 weeks. BPD was defined as FiO2 >21% for ?28 days and its severity classified as mild, FiO2=21%; moderate, FiO2 <30% and severe, FiO2 ?30%?and/or positive pressure support. We applied these criteria at two time points: 36 and 40 weeks' postmenstrual age (PMA). Multivariable regression models were used to estimate the association (OR (95%?CI)) between BPD characteristics and NDI defined as cognitive or motor development score?<2 SD; severe cerebral palsy; deafness and blindness.Of 610 (81% of cohort) children assessed at 2 years, 357 (58%) had BPD and 98 (16%) had NDI. Neither FiO2 >21% for ?28 days nor mild or moderate BPD at either 36 or 40 weeks' PMA was associated with NDI, but severe BPD was (at 36 weeks' PMA 5.6 (2.0 to 16.0) and at 40 weeks' PMA 16.6 (4.6 to 59.9)). Infants with severe BPD at both 36 and 40 weeks' PMA had lower mental (mean difference -11.4 (-18.5 to -4.3), -25.7(-35.9 to -15.5), respectively) and motor (-7.8 (-14.9 to -0.6), -20.1(-30.7 to -9.5), respectively), developmental scores than infants without BPD.In this cohort, severe BPD was a better independent predictor of NDI at 2 years than mild or moderate BPD. BPD diagnosed at 40 weeks' PMA might allow better identification of infants at highest risk for NDI.
Project description:Importance:Patent ductus arteriosus (PDA) is associated with increased mortality and worsened respiratory outcomes, including bronchopulmonary dysplasia (BPD), in preterm infants. Nonsteroidal anti-inflammatory drugs (NSAIDs) are efficacious in closing PDA, but the effectiveness of NSAID-mediated PDA closure in improving mortality and preventing BPD is unclear. Objective:To determine the effectiveness of NSAID treatment for PDA in reducing mortality and moderate/severe BPD at 36 weeks postmenstrual age. Design, Setting, and Participants:This cohort study included 12 018 infants born at 28 gestational weeks or younger discharged between January 2006 and December 2013 from neonatal intensive care units in 25 US children's hospitals included in the Pediatric Health Information System. We performed an instrumental variable analysis that incorporated clinician preference-based, institutional variation in NSAID treatment frequency to determine the effect of NSAID treatment for PDA on mortality and BPD. Exposures:Proportion of NSAID-treated infants born at each infant's institution within ±6 months of that infant's birth. Main Outcomes and Measures:The primary composite outcome was death, moderate, or severe BPD at 36 weeks postmenstrual age. Results:Of the 6370 male and 5648 female infants in this study, 4995 (42%) were white, 3176 (26%) were African American, 1823 (15%) were Hispanic, and 1555 (13%) were other races/ethnicities. The proportion of NSAID-treated infants at each infant's hospital within ±6 months of that infant's birth was associated with NSAID treatment and not associated with gestation, race/ethnicity, or sex. An infant's chances of receiving NSAID treatment increased by 0.84% (95% CI, 0.8-0.9; P < .001) for every 1% increase in the annual NSAID treatment percentage at a given hospital. An instrumental variable analysis demonstrated no association between NSAID treatment and the odds of mortality or BPD (odds ratio, 0.94; 95% CI, 0.70-1.25; P = .69), mortality (odds ratio, 0.73; 95% CI, 0.43-1.13; P = .18), or BPD (odds ratio, 1.01; 95% CI, 0.73-1.45; P = .94) in survivors. Conclusions and Relevance:When we incorporated clinician preference-based practice variation as an instrument to minimize the effect of unmeasured confounding, we detected no changes in the odds of mortality or moderate/severe BPD among similar preterm infants born at 28 weeks or younger following NSAID treatment for PDA initiated 2 to 28 days postnatally. Our findings agree with available randomized clinical trial evidence and support a conservative approach to PDA management.
Project description:OBJECTIVES:To compare medical and developmental outcomes over the first 2 years of life in extremely preterm infants with bronchopulmonary dysplasia (BPD) who were discharged on supplemental oxygen via nasal cannula with outcomes of infants with a similar severity of respiratory illness who were discharged breathing in room air. METHODS:We performed a propensity score-matched cohort study. Eligible infants were born at <27 weeks' gestation, were receiving supplemental oxygen or respiratory support at 36 weeks' postmenstrual age, and were assessed at 18 to 26 months' corrected age. Study outcomes included growth, resource use, and neurodevelopment between discharge and follow-up. Outcomes were compared by using multivariable models adjusted for center and age at follow-up. RESULTS:A total of 1039 infants discharged on supplemental oxygen were propensity score matched 1:1 to infants discharged breathing in room air. Infants on oxygen had a marginal improvement in weight z score (adjusted mean difference 0.11; 95% confidence interval [CI] 0.00 to 0.22), with a significantly improved weight-for-length z score (adjusted mean difference 0.13; 95% CI 0.06 to 0.20) at 22 to 26 months' corrected age. Infants on oxygen were more likely to be rehospitalized for respiratory illness (adjusted relative risk 1.33; 95% CI 1.16 to 1.53) and more likely to use respiratory medications and equipment. Rates of neurodevelopmental impairment were similar between the groups. CONCLUSIONS:In this matched cohort of infants with BPD, postdischarge oxygen was associated with marginally improved growth and increased resource use but no difference in neurodevelopmental outcomes. Ongoing and future trials are critical to assess the efficacy and safety of postdischarge supplemental oxygen for infants with BPD.
Project description:OBJECTIVES:The objectives describe the frequency that inadequate oral feeding (IOF) is the reason why moderately preterm (MPT) infants remain hospitalized and its association with neonatal morbidities. STUDY DESIGN:Prospective study using the NICHD Neonatal Research Network MPT Registry. Multivariable logistic regression was used to describe associations between IOF and continued hospitalization at 36 weeks postmenstrual age (PMA). RESULT:A total of 6017 MPT infants from 18 centers were included. Three-thousand three-seventy-six (56%) remained hospitalized at 36 weeks PMA, of whom 1262 (37%) remained hospitalized due to IOF. IOF was associated with RDS (OR 2.02, 1.66-2.46), PDA (OR 1.86, 1.37-2.52), sepsis (OR 2.36, 95% 1.48-3.78), NEC (OR 16.14, 7.27-35.90), and BPD (OR 3.65, 2.56-5.21) compared to infants discharged and was associated with medical NEC (OR 2.06, 1.19-3.56) and BPD (OR 0.46, 0.34-0.61) compared to infants remaining hospitalized for an alternative reason. CONCLUSION:IOF is the most common barrier to discharge in MPT infants, especially among those with neonatal morbidities.
Project description:Infants may benefit from early nutritional intervention to decrease hospital stay. To evaluate the effects of adding a human milk (HM)-derived cream (Cream) product to a standard feeding regimen in preterm infants.In a prospective multicenter randomized study, infants with birth weights 750-1,250?g were assigned to a Control or Cream group. The Control group received a standard feeding regimen consisting of mother's own milk or donor HM with donor HM-derived fortifier. The Cream group received the standard feeding regimen along with an additional HM-derived cream supplement when the HM they received was <20 kcal/oz. Primary outcomes of this secondary analysis included comorbidities, length of stay (LOS), and postmenstrual age (PMA) at discharge.We enrolled 75 infants (Control n?=?37, Cream n?=?38) with gestational age 27.7?±?1.8 weeks and birth weight 973?±?145?g (mean ± SD). After adjusting for gestational age, birth weight, and presence of bronchopulmonary dysplasia (BPD), the Cream group had a decreased PMA at discharge (39.9?±?4.8 versus 38.2?±?2.7 weeks, p?=?0.03) and LOS (86?±?39 versus 74?±?22 days, p?=?0.05). For 21 infants with BPD, these values trended toward significance for PMA at discharge (44.2?±?6.1 versus 41.3?±?2.7 weeks, p?=?0.08) and LOS (121?±?49 versus 104?±?23 days, p?=?0.08).Very preterm infants who received an HM-derived cream supplement were discharged earlier. Infants with BPD may have benefited the most.
Project description:Twin studies suggest that heritability of moderate-severe bronchopulmonary dysplasia (BPD) is 53% to 79%, we conducted a genome-wide association study (GWAS) to identify genetic variants associated with the risk for BPD.The discovery GWAS was completed on 1726 very low birth weight infants (gestational age = 25(0)-29(6/7) weeks) who had a minimum of 3 days of intermittent positive pressure ventilation and were in the hospital at 36 weeks' postmenstrual age. At 36 weeks' postmenstrual age, moderate-severe BPD cases (n = 899) were defined as requiring continuous supplemental oxygen, whereas controls (n = 827) inhaled room air. An additional 795 comparable infants (371 cases, 424 controls) were a replication population. Genomic DNA from case and control newborn screening bloodspots was used for the GWAS. The replication study interrogated single-nucleotide polymorphisms (SNPs) identified in the discovery GWAS and those within the HumanExome beadchip.Genotyping using genomic DNA was successful. We did not identify SNPs associated with BPD at the genome-wide significance level (5 × 10(-8)) and no SNP identified in previous studies reached statistical significance (Bonferroni-corrected P value threshold .0018). Pathway analyses were not informative.We did not identify genomic loci or pathways that account for the previously described heritability for BPD. Potential explanations include causal mutations that are genetic variants and were not assayed or are mapped to many distributed loci, inadequate sample size, race ethnicity of our study population, or case-control differences investigated are not attributable to underlying common genetic variation.
Project description:Importance:Preterm infants must establish regular respirations at delivery. Sustained inflations may establish lung volume faster than short inflations. Objective:To determine whether a ventilation strategy including sustained inflations, compared with standard intermittent positive pressure ventilation, reduces bronchopulmonary dysplasia (BPD) or death at 36 weeks' postmenstrual age without harm in extremely preterm infants. Design, Setting, and Participants:Unmasked, randomized clinical trial (August 2014 to September 2017, with follow-up to February 15, 2018) conducted in 18 neonatal intensive care units in 9 countries. Preterm infants 23 to 26 weeks' gestational age requiring resuscitation with inadequate respiratory effort or bradycardia were enrolled. Planned enrollment was 600 infants. The trial was stopped after enrolling 426 infants, following a prespecified review of adverse outcomes. Interventions:The experimental intervention was up to 2 sustained inflations at maximal peak pressure of 25 cm H2O for 15 seconds using a T-piece and mask (n?=?215); standard resuscitation was intermittent positive pressure ventilation (n?=?211). Main Outcome and Measures:The primary outcome was the rate of BPD or death at 36 weeks' postmenstrual age. There were 27 prespecified secondary efficacy outcomes and 7 safety outcomes, including death at less than 48 hours. Results:Among 460 infants randomized (mean [SD] gestational age, 25.30 [0.97] weeks; 50.2% female), 426 infants (92.6%) completed the trial. In the sustained inflation group, 137 infants (63.7%) died or survived with BPD vs 125 infants (59.2%) in the standard resuscitation group (adjusted risk difference [aRD], 4.7% [95% CI, -3.8% to 13.1%]; P?=?.29). Death at less than 48 hours of age occurred in 16 infants (7.4%) in the sustained inflation group vs 3 infants (1.4%) in the standard resuscitation group (aRD, 5.6% [95% CI, 2.1% to 9.1%]; P?=?.002). Blinded adjudication detected an imbalance of rates of early death possibly attributable to resuscitation (sustained inflation: 11/16; standard resuscitation: 1/3). Of 27 secondary efficacy outcomes assessed by 36 weeks' postmenstrual age, 26 showed no significant difference between groups. Conclusions and Relevance:Among extremely preterm infants requiring resuscitation at birth, a ventilation strategy involving 2 sustained inflations, compared with standard intermittent positive pressure ventilation, did not reduce the risk of BPD or death at 36 weeks' postmenstrual age. These findings do not support the use of ventilation with sustained inflations among extremely preterm infants, although early termination of the trial limits definitive conclusions. Trial Registration:clinicaltrials.gov Identifier: NCT02139800.
Project description:Importance:Dexamethasone initiated after the first week of life reduces the rate of death or bronchopulmonary dysplasia (BPD) but may cause long-term adverse effects in very preterm infants. Hydrocortisone is increasingly used as an alternative, but evidence supporting its efficacy and safety is lacking. Objective:To assess the effect of hydrocortisone initiated between 7 and 14 days after birth on death or BPD in very preterm infants. Design, Setting, and Participants:Double-blind, placebo-controlled randomized trial conducted in 19 neonatal intensive care units in the Netherlands and Belgium from November 15, 2011, to December 23, 2016, among preterm infants with a gestational age of less than 30 weeks and/or birth weight of less than 1250 g who were ventilator dependent between 7 and 14 days of life, with follow-up to hospital discharge ending December 12, 2017. Interventions:Infants were randomly assigned to receive a 22-day course of systemic hydrocortisone (cumulative dose, 72.5 mg/kg) (n?=?182) or placebo (n?=?190). Main Outcomes and Measures:The primary outcome was a composite of death or BPD assessed at 36 weeks' postmenstrual age. Twenty-nine secondary outcomes were analyzed up to hospital discharge, including death and BPD at 36 weeks' postmenstrual age. Results:Among 372 patients randomized (mean gestational age, 26 weeks; 55% male), 371 completed the trial; parents withdrew consent for 1 child treated with hydrocortisone. Death or BPD occurred in 128 of 181 infants (70.7%) randomized to hydrocortisone and in 140 of 190 infants (73.7%) randomized to placebo (adjusted risk difference, -3.6% [95% CI, -12.7% to 5.4%]; adjusted odds ratio, 0.87 [95% CI, 0.54-1.38]; P?=?.54). Of 29 secondary outcomes, 8 showed significant differences, including death at 36 weeks' postmenstrual age (15.5% with hydrocortisone vs 23.7% with placebo; risk difference, -8.2% [95% CI, -16.2% to -0.1%]; odds ratio, 0.59 [95% CI, 0.35-0.995]; P?=?.048). Twenty-one outcomes showed nonsignificant differences, including BPD (55.2% with hydrocortisone vs 50.0% with placebo; risk difference, 5.2% [95% CI, -4.9% to 15.2%]; odds ratio, 1.24 [95% CI, 0.82-1.86]; P?=?.31). Hyperglycemia requiring insulin therapy was the only adverse effect reported more often in the hydrocortisone group (18.2%) than in the placebo group (7.9%). Conclusions and Relevance:Among mechanically ventilated very preterm infants, administration of hydrocortisone between 7 and 14 days after birth, compared with placebo, did not improve the composite outcome of death or BPD at 36 weeks' postmenstrual age. These findings do not support the use of hydrocortisone for this indication. Trial Registration:Netherlands National Trial Register Identifier: NTR2768.
Project description:BACKGROUND:In this study, we aimed to analyze differences in plasma protein abundances between infants with and without bronchopulmonary dysplasia (BPD), to add new insights into a better understanding of the pathogenesis of this disease. METHODS:Cord and peripheral blood of neonates (? 30?weeks gestational age) was drawn at birth and at the 36th postmenstrual week (36 PMA), respectively. Blood samples were retrospectively subdivided into BPD(+) and BPD(-) groups, according to the development of BPD. RESULTS:Children with BPD were characterized by decreased afamin, gelsolin and carboxypeptidase N subunit 2 levels in cord blood, and decreased galectin-3 binding protein and hemoglobin subunit gamma-1 levels, as well as an increased serotransferrin abundance in plasma at the 36 PMA. CONCLUSIONS:BPD development is associated with the plasma proteome changes in preterm infants, adding further evidence for the possible involvement of disturbances in vitamin E availability and impaired immunological processes in the progression of prematurity pulmonary complications. Moreover, it also points to the differences in proteins related to infection resistance and maintaining an adequate level of hematocrit in infants diagnosed with BPD.
Project description:OBJECTIVE:To use a large current prospective cohort of infants <29 weeks to compare bronchopulmonary dysplasia (BPD) rates in black and white infants. STUDY DESIGN:The Prematurity and Respiratory Outcome Program (PROP) enrolled 835 infants born in 2011-2013 at <29 weeks of gestation; 728 black or white infants survived to 36 weeks postmenstrual age (PMA). Logistic regression was used to compare BPD outcomes (defined as supplemental oxygen requirement at 36 weeks PMA) between the races, adjusted for gestational age (GA), antenatal steroid use, intubation at birth, and surfactant use at birth. RESULTS:Of 707 black or white infants with available BPD outcomes, BPD was lower in black infants (38% vs 45%), even though they were of significantly lower GA. At every GA, BPD was more common in white infants. The aOR for BPD was 0.60 (95% CI, 0.42-0.85; P?=?.004) for black infants compared with white infants after adjusting for GA. Despite the lower rate of BPD, black infants had a higher rate of first-year post-prematurity respiratory disease (black, 79%; white, 63%). CONCLUSIONS:In this large cohort of recently born preterm infants at <29 weeks GA, compared with white infants, black infants had a lower risk of BPD but an increased risk of persistent respiratory morbidity.