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.