Pulmonary hypertension in preterm neonates with bronchopulmonary dysplasia: a meta-analysis

CONTEXT: Knowledge gaps exist on the incidence and risk factors for developing pulmonary hypertension (PH) in preterm infants with bronchopulmonary dysplasia (BPD) and its impact on outcomes. OBJECTIVE: To systematically review and meta-analyse the incidence, risk factors and short- and long-term outcomes of BPD-PH in preterm infants. DESIGN: PubMed, Embase, Cochrane CENTRAL and CINAHL were searched for studies including infants<37 weeks gestational age (GA) or birth weight<2500 g with BPD-PH versus BPD-no PH from inception until 5 April 2023. MAIN OUTCOME MEASURES: Incidence, risk factors and short- and long-term outcomes. RESULTS: 44 observational studies evaluating 7677 preterm infants were included. The incidence of PH in mild, moderate and severe BPD was 5%, 18% and 41%, respectively. Small for GA (25 studies; N=5814; OR 1.8; 95% CI 1.3, 2.5), necrotising enterocolitis (22 studies; N=3387; OR 1.6; 95% CI 1.3, 2.2), early PH (four studies; N=820 OR 2.2; 95% CI 1.5, 3.3) and severe BPD (20 studies; N=2587; OR 5.4; 95% CI 3.2, 9.1) were significant risk factors for BPD-PH. Compared with BPD-no PH, the BPD-PH group had significantly higher mortality (22 studies; N=4882; OR 6.4; 95% CI 4.7, 8.6), longer duration of mechanical ventilation, oxygen supplementation, length of hospital stay, need for home oxygen and tracheostomy requirement. The BPD-PH infants also had a significantly higher risk of neurodevelopmental impairment in the motor domain. CONCLUSIONS: PH increases across the severity of BPD and is associated with higher odds of mortality and adverse short-term and neurodevelopmental outcomes. PROSPERO REGISTRATION NUMBER: CRD42023413119.