The Diagnosis of Bronchopulmonary Dysplasia in Very Preterm Infants. An Evidence-based Approach

Abstract

Rationale: Current diagnostic criteria for bronchopulmonary dysplasia rely heavily on the level and duration of oxygen therapy, do not reflect contemporary neonatal care, and do not adequately predict childhood morbidity.Objectives: To determine which of 18 prespecified, revised definitions of bronchopulmonary dysplasia that variably define disease severity according to the level of respiratory support and supplemental oxygen administered at 36 weeks' postmenstrual age best predicts death or serious respiratory morbidity through 18-26 months' corrected age.Methods: We assessed infants born at less than 32 weeks of gestation between 2011 and 2015 at 18 centers of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network.Measurements and Main Results: Of 2,677 infants, 683 (26%) died or developed serious respiratory morbidity. The diagnostic criteria that best predicted this outcome defined bronchopulmonary dysplasia according to treatment with the following support at 36 weeks' postmenstrual age, regardless of prior or current oxygen therapy: no bronchopulmonary dysplasia, no support (n = 773); grade 1, nasal cannula ≤2 L/min (n = 1,038); grade 2, nasal cannula >2 L/min or noninvasive positive airway pressure (n = 617); and grade 3, invasive mechanical ventilation (n = 249). These criteria correctly predicted death or serious respiratory morbidity in 81% of study infants. Rates of this outcome increased stepwise from 10% among infants without bronchopulmonary dysplasia to 77% among those with grade 3 disease. A similar gradient (33-79%) was observed for death or neurodevelopmental impairment.Conclusions: The definition of bronchopulmonary dysplasia that best predicted early childhood morbidity categorized disease severity according to the mode of respiratory support administered at 36 weeks' postmenstrual age, regardless of supplemental oxygen use.

Keywords: infant chronic lung disease; mechanical ventilation; supplemental oxygen.

Figure 1.

The 18 prespecified severity-graded definitions of bronchopulmonary dysplasia (BPD). Definitions 1–3 establish the initial framework. Key components of the definition evaluated in each subset are highlighted by the red boxes. All infants treated with head box oxygen are included with those receiving nasal cannula (NC) at ≤2 L/min flow. The mode of respiratory support and Fi_O2 were recorded as the highest level administered at 36 weeks’ postmenstrual age (PMA). Any temporary increases in Fi_O2 for desaturation events, apnea, bradycardia, or procedures were disregarded if the infant returned to the previous Fi_O2 within 2 hours. Supplemental oxygen administered only during feedings was not included for infants who did not receive oxygen therapy at other times during the day. nCPAP = nasal continuous positive airway pressure; NIPPV = nasal intermittent positive pressure ventilation; PPV = positive pressure ventilation.

Figure 2.

Rank order of the 18 evaluated definitions of bronchopulmonary dysplasia (BPD). The definitions are ordered from highest (top) to lowest (bottom) accuracy for predicting death between 36 weeks’ postmenstrual age (PMA) and 18- to 26-month follow-up or serious respiratory morbidity. Concordance (c) statistic values were calculated using logistic regression, adjusting for gestational age, birth weight, sex, small for gestational age, race/ethnicity, treatment with antenatal corticosteroids, treatment with antenatal magnesium, maternal level of education, insurance type, primary caregiver marital status, and study center. NC = nasal cannula; nCPAP = nasal continuous positive airway pressure; NDI = neurodevelopmental impairment; NIPPV = nasal intermittent positive pressure ventilation; PPV = positive pressure ventilation.