Early pulmonary vascular disease in preterm infants at risk for bronchopulmonary dysplasia

Abstract

Rationale: Pulmonary hypertension (PH) is associated with poor outcomes among preterm infants with bronchopulmonary dysplasia (BPD), but whether early signs of pulmonary vascular disease are associated with the subsequent development of BPD or PH at 36 weeks post-menstrual age (PMA) is unknown.

Objectives: To prospectively evaluate the relationship of early echocardiogram signs of pulmonary vascular disease in preterm infants to the subsequent development of BPD and late PH (at 36 wk PMA).

Methods: Prospectively enrolled preterm infants with birthweights 500-1,250 g underwent echocardiogram evaluations at 7 days of age (early) and 36 weeks PMA (late). Clinical and echocardiographic data were analyzed to identify early risk factors for BPD and late PH.

Measurements and main results: A total of 277 preterm infants completed echocardiogram and BPD assessments at 36 weeks PMA. The median gestational age at birth and birthweight of the infants were 27 weeks and 909 g, respectively. Early PH was identified in 42% of infants, and 14% were diagnosed with late PH. Early PH was a risk factor for increased BPD severity (relative risk, 1.12; 95% confidence interval, 1.03-1.23) and late PH (relative risk, 2.85; 95% confidence interval, 1.28-6.33). Infants with late PH had greater duration of oxygen therapy and increased mortality in the first year of life (P < 0.05).

Conclusions: Early pulmonary vascular disease is associated with the development of BPD and with late PH in preterm infants. Echocardiograms at 7 days of age may be a useful tool to identify infants at high risk for BPD and PH.

Keywords: bronchopulmonary dysplasia; echocardiography; prematurity; pulmonary hypertension; pulmonary vascular disease.

Figures

Figure 1.

Enrollment and follow-up of study participants. BPD = bronchopulmonary dysplasia; ECHO = echocardiogram; PH = pulmonary hypertension.

Figure 2.

The proportion of subjects with pulmonary hypertension (PH) according to the primary criteria (detailed in the text) at 7 days of age displayed by bronchopulmonary dysplasia (BPD) status (A), and at 36 weeks post-menstrual age (PMA) (B). There was a significantly higher proportion of infants with PH in the severe BPD group at 36 weeks PMA compared with the other BPD status groups (P < 0.001).

Figure 3.

Adjusted relative risk for the development of bronchopulmonary dysplasia (BPD) (A) after adjusting for maternal, birth, and early infant factors (see Methods). Gestational age at birth, birthweight z score, ventricular septal flattening, multiple gestation, and center were significantly associated with BPD. (B) Echocardiographic risk factors at postnatal day 7 (septal wall flattening and right ventricular dilation) were significantly associated with pulmonary hypertension (PH) at 36 weeks post-menstrual age.

Figure 4.

Infants with late pulmonary hypertension (PH) were treated with oxygen longer (from birth) than infants without late PH after adjusting for gestational age at birth, center, and bronchopulmonary dysplasia (BPD) status.