Background:
Pulmonary hypertension is one of the most common co-morbidities in infants with
bronchopulmonary dysplasia (BPD), but its risk factors are unclear. The onset of
pulmonary hypertension in BPD has been associated with poor morbidity- and mortality-related outcomes in infants. Two review and meta-analysis studies have evaluated the risk factors and outcomes associated with
pulmonary hypertension in infants with BPD. However, the limitations in those studies and the publication of recent cohort studies warrant our up-to-date study. We designed a systematic review and meta-analysis to evaluate the risk factors and outcomes of
pulmonary hypertension in infants with BPD. Objective: To systematically evaluate the risk factors and outcomes associated with
pulmonary hypertension in infants with BPD. Methods: We systematically searched the academic literature according to the
PRISMA guidelines across five databases (Web of Science, EMBASE, CENTRAL, Scopus, and MEDLINE). We conducted random-effects meta-analyses to evaluate the
pulmonary hypertension risk factors in infants with BPD. We also evaluated the overall morbidity- and mortality-related outcomes in infants with BPD and
pulmonary hypertension. Results: We found 15 eligible studies (from the initial 963 of the search result) representing data from 2,156 infants with BPD (mean age, 25.8 ± 0.71 weeks). The overall methodological quality of the included studies was high. Our meta-analysis in infants with severe BPD revealed increased risks of
pulmonary hypertension [Odds ratio (OR) 11.2],
sepsis (OR, 2.05),
pre-eclampsia (OR, 1.62), and
oligohydramnios (OR, 1.38) of being small for gestational age (3.31). Moreover, a comparative analysis found medium-to-large effects of
pulmonary hypertension on the total duration of
hospital stay (Hedge's g, 0.50), the total duration of
oxygen received (g, 0.93), the cognitive score (g, -1.5), and the overall mortality (g, 0.83) in infants with BPD. Conclusion: We identified several possible risk factors (i.e., severe BPD,
sepsis, small for gestational age,
pre-eclampsia) which promoted the onset of
pulmonary hypertension in infants with BPD. Moreover, our review sheds light on the morbidity- and mortality-related outcomes associated with
pulmonary hypertension in these infants. Our present findings are in line with the existing literature. The findings from this research will be useful in development of efficient risk-based screening system that determine the outcomes associated with
pulmonary hypertension in infants with BPD.