Assessment of Corticosteroid Therapy and Death or Disability According to Pretreatment Risk of Death or Bronchopulmonary Dysplasia in Extremely Preterm Infants.

2023

e2312277

05/2023

2574-3805

IMPORTANCE: Meta-analyses suggest that corticosteroids may be associated with increased survival without cerebral palsy in infants at high risk of bronchopulmonary dysplasia (BPD) but are associated with adverse neurologic outcomes in low-risk infants. Whether this association exists in contemporary practice is uncertain because most randomized clinical trials administered corticosteroids earlier and at higher doses than currently recommended.

OBJECTIVE: To evaluate whether the pretreatment risk of death or grade 2 or 3 BPD at 36 weeks' postmenstrual age modified the association between postnatal corticosteroid therapy and death or disability at 2 years' corrected age in extremely preterm infants.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study analyzed data on 482 matched pairs of infants from 45 participating US hospitals in the National Institute of Child Health and Human Development Neonatal Research Network Generic Database (GDB). Infants were included in the cohort if they were born at less than 27 weeks' gestation between April 1, 2011, and March 31, 2017; survived the first 7 postnatal days; and had 2-year death or developmental follow-up data collected between January 2013 and December 2019. Corticosteroid-treated infants were propensity score matched with untreated controls. Data were analyzed from September 1, 2019, to November 30, 2022.

EXPOSURE: Systemic corticosteroid therapy to prevent BPD that was initiated between day 8 and day 42 after birth.

MAIN OUTCOMES AND MEASURES: The primary outcome was death or moderate to severe neurodevelopmental impairment at 2 years' corrected age. The secondary outcome was death or moderate to severe cerebral palsy at 2 years' corrected age.

RESULTS: A total of 482 matched pairs of infants (mean [SD] gestational age, 24.1 [1.1] weeks]; 270 males [56.0%]) were included from 656 corticosteroid-treated infants and 2796 potential controls. Most treated infants (363 [75.3%]) received dexamethasone. The risk of death or disability associated with corticosteroid therapy was inversely associated with the estimated pretreatment probability of death or grade 2 or 3 BPD. The risk difference for death or neurodevelopmental impairment associated with corticosteroids decreased by 2.7% (95% CI, 1.9%-3.5%) for each 10% increase in the pretreatment risk of death or grade 2 or 3 BPD. This risk transitioned from estimated net harm to benefit when the pretreatment risk of death or grade 2 or 3 BPD exceeded 53% (95% CI, 44%-61%). For death or cerebral palsy, the risk difference decreased by 3.6% (95% CI, 2.9%-4.4%) for each 10% increase in the risk of death or grade 2 or 3 BPD and transitioned from estimated net harm to benefit at a pretreatment risk of 40% (95% CI, 33%-46%).

CONCLUSIONS AND RELEVANCE: Results of this study suggested that corticosteroids were associated with a reduced risk of death or disability in infants at moderate to high pretreatment risk of death or grade 2 or 3 BPD but with possible harm in infants at lower risk.

10.1001/jamanetworkopen.2023.12277

JAMA Netw Open

37155165

Assessment of Corticosteroid Therapy and Death or Disability According to Pretreatment Risk of Death or Bronchopulmonary Dysplasia in Extremely Preterm Infants.

2023

e2312277

05/2023

2574-3805

IMPORTANCE: Meta-analyses suggest that corticosteroids may be associated with increased survival without cerebral palsy in infants at high risk of bronchopulmonary dysplasia (BPD) but are associated with adverse neurologic outcomes in low-risk infants. Whether this association exists in contemporary practice is uncertain because most randomized clinical trials administered corticosteroids earlier and at higher doses than currently recommended.

OBJECTIVE: To evaluate whether the pretreatment risk of death or grade 2 or 3 BPD at 36 weeks' postmenstrual age modified the association between postnatal corticosteroid therapy and death or disability at 2 years' corrected age in extremely preterm infants.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study analyzed data on 482 matched pairs of infants from 45 participating US hospitals in the National Institute of Child Health and Human Development Neonatal Research Network Generic Database (GDB). Infants were included in the cohort if they were born at less than 27 weeks' gestation between April 1, 2011, and March 31, 2017; survived the first 7 postnatal days; and had 2-year death or developmental follow-up data collected between January 2013 and December 2019. Corticosteroid-treated infants were propensity score matched with untreated controls. Data were analyzed from September 1, 2019, to November 30, 2022.

EXPOSURE: Systemic corticosteroid therapy to prevent BPD that was initiated between day 8 and day 42 after birth.

MAIN OUTCOMES AND MEASURES: The primary outcome was death or moderate to severe neurodevelopmental impairment at 2 years' corrected age. The secondary outcome was death or moderate to severe cerebral palsy at 2 years' corrected age.

RESULTS: A total of 482 matched pairs of infants (mean [SD] gestational age, 24.1 [1.1] weeks]; 270 males [56.0%]) were included from 656 corticosteroid-treated infants and 2796 potential controls. Most treated infants (363 [75.3%]) received dexamethasone. The risk of death or disability associated with corticosteroid therapy was inversely associated with the estimated pretreatment probability of death or grade 2 or 3 BPD. The risk difference for death or neurodevelopmental impairment associated with corticosteroids decreased by 2.7% (95% CI, 1.9%-3.5%) for each 10% increase in the pretreatment risk of death or grade 2 or 3 BPD. This risk transitioned from estimated net harm to benefit when the pretreatment risk of death or grade 2 or 3 BPD exceeded 53% (95% CI, 44%-61%). For death or cerebral palsy, the risk difference decreased by 3.6% (95% CI, 2.9%-4.4%) for each 10% increase in the risk of death or grade 2 or 3 BPD and transitioned from estimated net harm to benefit at a pretreatment risk of 40% (95% CI, 33%-46%).

CONCLUSIONS AND RELEVANCE: Results of this study suggested that corticosteroids were associated with a reduced risk of death or disability in infants at moderate to high pretreatment risk of death or grade 2 or 3 BPD but with possible harm in infants at lower risk.

10.1001/jamanetworkopen.2023.12277

JAMA Netw Open

37155165

Assessment of Corticosteroid Therapy and Death or Disability According to Pretreatment Risk of Death or Bronchopulmonary Dysplasia in Extremely Preterm Infants.

2023

e2312277

05/2023

2574-3805

IMPORTANCE: Meta-analyses suggest that corticosteroids may be associated with increased survival without cerebral palsy in infants at high risk of bronchopulmonary dysplasia (BPD) but are associated with adverse neurologic outcomes in low-risk infants. Whether this association exists in contemporary practice is uncertain because most randomized clinical trials administered corticosteroids earlier and at higher doses than currently recommended.

OBJECTIVE: To evaluate whether the pretreatment risk of death or grade 2 or 3 BPD at 36 weeks' postmenstrual age modified the association between postnatal corticosteroid therapy and death or disability at 2 years' corrected age in extremely preterm infants.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study analyzed data on 482 matched pairs of infants from 45 participating US hospitals in the National Institute of Child Health and Human Development Neonatal Research Network Generic Database (GDB). Infants were included in the cohort if they were born at less than 27 weeks' gestation between April 1, 2011, and March 31, 2017; survived the first 7 postnatal days; and had 2-year death or developmental follow-up data collected between January 2013 and December 2019. Corticosteroid-treated infants were propensity score matched with untreated controls. Data were analyzed from September 1, 2019, to November 30, 2022.

EXPOSURE: Systemic corticosteroid therapy to prevent BPD that was initiated between day 8 and day 42 after birth.

MAIN OUTCOMES AND MEASURES: The primary outcome was death or moderate to severe neurodevelopmental impairment at 2 years' corrected age. The secondary outcome was death or moderate to severe cerebral palsy at 2 years' corrected age.

RESULTS: A total of 482 matched pairs of infants (mean [SD] gestational age, 24.1 [1.1] weeks]; 270 males [56.0%]) were included from 656 corticosteroid-treated infants and 2796 potential controls. Most treated infants (363 [75.3%]) received dexamethasone. The risk of death or disability associated with corticosteroid therapy was inversely associated with the estimated pretreatment probability of death or grade 2 or 3 BPD. The risk difference for death or neurodevelopmental impairment associated with corticosteroids decreased by 2.7% (95% CI, 1.9%-3.5%) for each 10% increase in the pretreatment risk of death or grade 2 or 3 BPD. This risk transitioned from estimated net harm to benefit when the pretreatment risk of death or grade 2 or 3 BPD exceeded 53% (95% CI, 44%-61%). For death or cerebral palsy, the risk difference decreased by 3.6% (95% CI, 2.9%-4.4%) for each 10% increase in the risk of death or grade 2 or 3 BPD and transitioned from estimated net harm to benefit at a pretreatment risk of 40% (95% CI, 33%-46%).

CONCLUSIONS AND RELEVANCE: Results of this study suggested that corticosteroids were associated with a reduced risk of death or disability in infants at moderate to high pretreatment risk of death or grade 2 or 3 BPD but with possible harm in infants at lower risk.

10.1001/jamanetworkopen.2023.12277

JAMA Netw Open

37155165

Comparison of tracheal aspirate and bronchoalveolar lavage samples in the microbiological diagnosis of lower respiratory tract infection in pediatric patients.

2022

2405-2410

05/2022

1099-0496

BACKGROUND: Bacterial cultures from tracheal aspirates (TA) and bronchoalveolar lavage (BAL) specimens can be used to assess patients with artificial airways for lower respiratory tract infections (LRTI). TA collection may be advantageous in situations of limited resources or critical illness. Literature comparing these diagnostic modalities in pediatric populations is scarce.

METHODS: Single-center, retrospective analysis of 52 pediatric patients with an artificial airway undergoing evaluation for LRTI. All patients had a TA specimen collected for semiquantitative Gram stain and culture followed by BAL within 48 h. Microbiologic diagnosis of LRTI was defined as a BAL sample with >25% neutrophils and growth of >10 colony-forming units/ml of one or more bacterial species. The test characteristics of TA were compared with these BAL results as the reference standard. Concordance in microorganism identification was also assessed.

RESULTS: Overall, 24 patients (47%) met criteria for LRTI using BAL as the diagnostic standard. TA samples positive for an isolated organism had poor sensitivity for acute LRTI when compared with BAL, regardless of semiquantitative white blood cell (WBC) count by Gram stain. Using a TA diagnostic threshold of organism growth and at least "moderate" WBC yielded a specificity of 93%. Positive predictive value was highest when an organism was identified by TA. Negative predictive value was >70% for TA samples with no WBC by semiquantitative analysis, with or without growth of an organism. Complete concordance of cultured species was 58% for all patients, with a higher rate seen among those with endotracheal tubes.

CONCLUSIONS: The role of cultures obtained by TA remains limited for the diagnosis of acute LRTI as demonstrated by the poor correlation to BAL results within our cohort. Optimal strategies for diagnosing LRTI across patient populations and airway types remain elusive.

10.1002/ppul.26049

Pediatr Pulmonol

35781810

Chronic lung disease-related mortality in the US from 1999-2017: trends and racial disparities.

2022

1244-1245

07/2022

1476-5543

10.1038/s41372-022-01468-5

J Perinatol

35906284

Accuracy of Brain Natriuretic Peptide for Diagnosing Pulmonary Hypertension in Severe Bronchopulmonary Dysplasia.

2019

147-153

2019

1661-7819

<p><strong>BACKGROUND: </strong>Premature infants with severe bronchopulmonary dysplasia (sBPD) are at risk of pulmonary hypertension (PH). Serum brain natriuretic peptide (BNP) is used to predict disease severity in adult PH. Its diagnostic utility in sBPD-associated PH is unknown.</p>

<p><strong>OBJECTIVE: </strong>The aim of this paper was to determine the accuracy of BNP, against echocardiogram (echo), to diagnose PH in infants born &lt;32 weeks' gestation with sBPD.</p>

<p><strong>METHODS: </strong>We conducted a retrospective cohort study of all infants with sBPD with an echo and BNP within a 24-h period, at ≥36 weeks postmenstrual age. PH was defined as: right ventricular pressure &gt;½ systemic blood pressure estimated from tricuspid regurgitant jet or patent ductus arteriosus (PDA) velocity, bidirectional or right-to left-PDA, and/or flat/bowing ventricular septum at end-systole. Receiver-operating characteristic (ROC) curves were constructed to test the diagnostic accuracy of BNP.</p>

<p><strong>RESULTS: </strong>Of 128 infants, 68 (53%) had echo evidence of PH. BNP was higher among the infants with PH (median [interquartile range]: 127 pg/mL [39-290] vs. 35 [20-76], p &lt; 0.001). The area under the ROC curve for diagnosing PH using BNP was 0.74 (95% CI 0.66-0.83). At an optimal cutpoint of 130 pg/mL, BNP correctly classified the presence or absence of PH in 70% of the infants (specificity: 92, sensitivity: 50%).</p>

<p><strong>CONCLUSIONS: </strong>BNP, relative to concurrent echo, demonstrated moderate accuracy for diagnosing PH in this cohort of preterm infants with sBPD. BNP may help rule in PH in this population but has low utility to rule out the disease.</p>

10.1159/000499082

Neonatology

31096210

Early motor development in infants with moderate or severe bronchopulmonary dysplasia.

2021

2021 Oct 12

1878-4429

<p><strong>BACKGROUND: </strong>Timely development of early motor skills is essential for later skill development in multiple domains. Infants with severe bronchopulmonary dysplasia (BPD) have significant risk for developmental delays. Early motor skill development in this population has not been described. The aim of the present study was to characterize motor skill acquisition at 3 and 6 months corrected age (CA) and assess trajectories of skill development over this time period in infants with severe BPD.</p>

<p><strong>METHODS: </strong>We performed a single-center, retrospective descriptive study. Motor skills were categorized as present and normal, present but atypical, or absent at 3 and 6 months CA. Logistic regression was used to identify clinical characteristics associated with negative trajectories of skill acquisition.</p>

<p><strong>RESULTS: </strong>Data were available for 232 infants and 187 infants at 3 and 6 months CA, respectively. Ten motor skills were present and normal in 5-44%(range) of subjects at 3 months. Nineteen motor skills were present and normal in 1-63%(range) of subjects at 6 months. Significant postural asymmetry was noted throughout the study period. Loss of skills and worsening asymmetries over time were common. Exposure to sedating medications was significantly associated with poor development.</p>

<p><strong>CONCLUSION: </strong>We report delays in motor skill acquisition and postural asymmetries in infants with severe BPD at both 3 and 6 months CA. The association between sedating medications and poor development suggests that efforts to limit these exposures may lead to improved development. Targeted interventions to facilitate early motor development may improve outcomes of this high-risk population.</p>

10.3233/NPM-210750

J Neonatal Perinatal Med

34657851

The association between diuretic class exposures and enteral electrolyte use in infants developing grade 2 or 3 bronchopulmonary dysplasia in United States children's hospitals.

2021

2021 Jan 28

1476-5543

<p><strong>OBJECTIVE: </strong>To evaluate the association between chronic diuretic exposures and enteral electrolyte use in infants developing severe bronchopulmonary dysplasia (sBPD).</p>

<p><strong>STUDY DESIGN: </strong>Retrospective longitudinal cohort study in infants admitted to United States children's hospitals. We identified diuretic exposures and measured enteral NaCl and KCl use during pre-defined exposure risk-interval days. We used mixed-effects logistic regression to model the association between diuretic exposures and electrolyte use.</p>

<p><strong>RESULTS: </strong>We identified 442,341 subject-days in 3252 infants. All common diuretic classes and class combinations were associated with increased NaCl and KCl use. Thiazide monotherapy was associated with greater electrolyte use than loop monotherapy. The addition of potassium-sparing diuretics was associated with a limited reduction in KCl use compared to thiazide monotherapy.</p>

<p><strong>CONCLUSIONS: </strong>Chronic diuretic exposures are associated with increased NaCl and KCl use. Presumptions about the relative impact of different diuretic classes on electrolyte derangements may be inaccurate and require further study.</p>

10.1038/s41372-021-00924-y

J Perinatol

33510422

Poor postnatal weight growth is a late finding after sepsis in very preterm infants.

2020

2020 Nov 04

1468-2052

<p><strong>OBJECTIVE: </strong>To characterise the association between sepsis and postnatal weight growth when accounting for the degree of growth restriction present at birth.</p>

<p><strong>DESIGN: </strong>Retrospective matched cohort study using data from the Postnatal Growth and Retinopathy of Prematurity study. Participants were born with birth weights of &lt;1500 g or gestational ages of &lt;32 weeks between 2006 and 2011 at 29 neonatal centres in the USA and Canada. Sepsis was defined as a culture-confirmed bacterial or fungal infection of the blood or cerebrospinal fluid before 36 weeks' postmenstrual age (PMA). Growth was assessed as the change in weight z-score between birth and 36 weeks' PMA.</p>

<p><strong>RESULTS: </strong>Of 4785 eligible infants, 813 (17%) developed sepsis and 693 (85%) were matched 1:1 to controls. Sepsis was associated with a greater decline in weight z-score (mean difference -0.09, 95% CI -0.14 to -0.03). Postnatal weight growth failure (decline in weight z- score&gt;1) was present in 237 (34%) infants with sepsis and 179 (26%) controls (adjusted OR 1.49, 95% CI 1.12 to 1.97). Longitudinal growth trajectories showed similar initial changes in weight z-scores between infants with and without sepsis. By 3 weeks after sepsis onset, there was a greater decline in weight z-scores relative to birth values in those with sepsis than without sepsis (delta z-score -0.89 vs -0.77; mean difference -0.12, 95% CI -0.18 to -0.05). This significant difference persisted until 36 weeks or discharge.</p>

<p><strong>CONCLUSION: </strong>Infants with sepsis had similar early weight growth trajectories as infants without sepsis but developed significant deficits in weight that were not apparent until several weeks after the onset of sepsis.</p>

10.1136/archdischild-2020-320221

Arch Dis Child Fetal Neonatal Ed

33148685

Loop Diuretics in Severe Bronchopulmonary Dysplasia: Cumulative Use and Associations with Mortality and Age at Discharge.

2020

2020 Nov 02

1097-6833

<p><strong>OBJECTIVES: </strong>To measure between-center variation in loop diuretic use for infants developing severe bronchopulmonary dysplasia (BPD) in United States children's hospitals, and to compare mortality and age at discharge among infants from low versus high use centers.</p>

<p><strong>STUDY DESIGN: </strong>We performed a retrospective cohort study of preterm infants &lt;32 weeks gestational age developing severe BPD. The primary outcome was cumulative loop diuretic use, defined as the proportion of days with exposure between admission and discharge. Infant characteristics associated with loop diuretic use at P &lt; .10 were included in multivariable models to adjust for center differences in case-mix. Hospitals were ranked from lowest to highest in adjusted use, and dichotomized into low or high use centers. We then compared mortality and postmenstrual age at discharge between groups through multivariable analyses.</p>

<p><strong>RESULTS: </strong>We identified 3252 subjects from 43 centers. Significant variation between centers remained despite adjustment for infant characteristics, with use present in an adjusted mean range of 7.3% to 49.4% of days, p &lt; 0.0001. Mortality (adjusted odds ratio 0.98 [95% CI 0.62, 1.53], p = 0.92) and postmenstrual age at discharge (marginal mean [95% CI]: 47.3 [46.8 , 47.9] versus 47.4 [46.9, 47.9] weeks, p = 0.96) were similar in low and high use groups, respectively.</p>

<p><strong>CONCLUSIONS: </strong>Marked variation in loop diuretic use for infants developing severe BPD exists between US children's hospital, without an observed difference on mortality or discharge age. Research to provide evidence-based guidance for this common exposure is needed.</p>

10.1016/j.jpeds.2020.10.073

J Pediatr

33152371