Risk factors of early pulmonary hypertension and its clinical outcomes in preterm infants: a systematic review and meta-analysis

The aim of this meta-analysis was to determine the incidence and risk factors of early pulmonary hypertension (PHT) in preterm infants and evaluate the association of early PHT with morbidities such as bronchopulmonary dysplasia (BPD), late PHT, and in-hospital mortality. We searched the PubMed (1980–2021), Embase (1968–2021), CINAHL (2002–2021), Cochrane library (1989–2021), and KoreaMed (1993–2021). Observational studies on the association between early PHT diagnosed within the first 2 weeks after birth and its clinical outcomes in preterm infants born before 37 weeks of gestation or with very low birth weight (< 1500 g) were included. Two authors independently extracted the data and assessed the quality of each study using a modified Newcastle–Ottawa Scale. We performed meta-analysis using Comprehensive Meta-Analysis version 3.3. A total of 1496 potentially relevant studies were found, of which 8 studies (7 cohort studies and 1 case–control study) met the inclusion criteria comprising 1435 preterm infants. The event rate of early PHT was 24% (95% confidence interval [CI] 0.174–0.310). The primary outcome of our study was moderate to severe BPD at 36 weeks postmenstrual age, and it was associated with early PHT (6 studies; odds ratio [OR] 1.682; 95% CI 1.262–2.241; P < 0.001; heterogeneity: I(2) = 0%; P = 0.492). Preterm infants with early PHT had higher OR of in-hospital mortality (6 studies; OR 2.372; 95% CI 1.595–3.528; P < 0.001; heterogeneity: I(2) = 0%; P = 0.811) and developing late PHT diagnosed after 4 weeks of life (4 studies; OR 2.877; 95% CI 1.732–4.777; P < 0.001; heterogeneity: I(2) = 0%; P = 0.648). Infants with oligohydramnios (4 studies; OR 2.134; 95% CI 1.379–3.303; P = 0.001) and those who were small-for-gestational-age (5 studies; OR 1.831; 95% CI 1.160–2.890; P = 0.009) had an elevated risk of developing early PHT. This study showed that early PHT is significantly associated with mortality and morbidities, such as BPD and late PHT. Preterm infants with a history of oligohydramnios and born small-for-gestational-age are at higher risk for developing early PHT; however, high-quality studies that control for confounders are necessary.