Primary Subject area Neonatal-Perinatal Medicine Background Pulmonary Hypertension (PH) is estimated to occur in 1 in 4 infants with Bronchopulmonary Dysplasia (BPD). The impact of PH in infants with BPD on their neurodevelopmental (ND) outcomes is uncertain. Objectives This systematic review aims to evaluate whether PH in infants with BPD is associated with ND delay. Design/Methods A systematic literature search was performed to identify studies that reported ND outcomes of infants with BPD (based on NIH definition) and PH (based on echocardiographic findings of PH at 36 weeks PMA). The primary outcome was ND delay in infants with pulmonary hypertension associated with BPD compared with BPD alone. Standardized developmental tests evaluated ND outcomes at 18-24 months corrected age (CA) and three years of age. Quality assessment of the studies was done using the Newcastle-Ottawa Quality Assessment for Cohort studies. Results Three retrospective cohort studies met the inclusion criteria. Two studies reported ND outcomes based on Bayley Scales of Infant and Toddler Development-III Edition in cognitive, language, and motor domains at 18-24 months CA (Table 1 and Figure 1). One study reported outcomes at 3 years, including overall developmental delay (Kyoto Scale of Psychological Development [KSPD] scores < 70) and cerebral palsy. The quality of all 3 studies was rated between good, fair, and poor. Pooled data from the 2 studies reporting outcomes at 18-24 months showed no difference between the 2 infant groups for Bayley cognitive score < 85 (Odds ratio [OR]: 3.78; 95% CI 0.87-16.52), Bayley language score < 85 (OR: 1.19; 95% CI0.57-2.49), and Bayley motor score < 85 (OR: 2.04; 95% CI 0.89-4.67). At 3 years of age, children in the BPD-PH group had an increased risk of developmental delay (DQ < 70 in all areas) compared with the BPD group (OR: 4.37; 95% CI 1.16-16.46), but no difference in the risk of cerebral palsy (OR: 0.57; 95%0.03-12.39). Conclusion PH in BPD is not associated with a developmental delay compared to BPD alone at 18-24 months CA. However, a single study showed infants in BPD-PH had delayed development at 3 years of age. A large prospective cohort study with longer multidisciplinary follow-up is required to confirm this.

Background More than 1 in 4 preterm infants with bronchopulmonary dysplasia (BPD) develop BPD-associated pulmonary hypertension (BPD-PH) that is associated with significant morbidity. Data regarding neurodevelopmental outcomes with BPD-PH in preterm infants are lacking. Objectives To determine neurodevelopmental outcomes of preterm infants born < 29 weeks gestational age (GA) with BPD associated pulmonary hypertension at 18 to 24 months corrected gestational age (CGA). Design/Methods In this retrospective cohort study, preterm infants born < 29 weeks GA between January 2016 and December 2019 at level 3 Neonatal Intensive Care Units at Foothills Hospital in Calgary and the University of Texas Medical Branch (UTMB) in Galveston, who were evaluated at 18-24 months CGA in the neonatal follow-up clinics were included. We compared demographic factors, neurodevelopmental status including Bayley-III scores and sensory impairments between the two groups based on the presence of PH at 36 weeks CGA: Group I: BPD with PH and Group II: BPD without PH, using univariate and multivariable regression models. The primary outcome was a composite of death or neurodevelopmental impairments (NDI). NDI was defined as any cerebral palsy (GMFCS≥1), Bayley-III score < 85 on one or more of the cognitive, motor, or language composite scores, sensorineural or mixed hearing impairment or unilateral or bilateral visual impairment. Results Of 372 eligible infants, 118 (Group I [BPD-PH] =7, Group II [BPD with no PH] =111) were lost to follow up. Of the remaining 254 infants, 52 in Group I and 202 in Group II were followed at 18-24 months CGA. Group I and Group II had median (IQR) birth weight of 710g (323) and 815g (314) [p=0.004] and median gestational ages (IQR) were 25 weeks (2) and 26 weeks (2) [p=0.020], respectively . Rates of associated impairments are shown in Figure 1. Infants in BPD-PH group (Group I) were more likely to have mortality or NDI (adjusted Odds Ratio [aOR] 3.82; 95% CI: 1.17-12.41) (Table 1). Conclusion BPD-PH in preterm infants born < 29 weeks GA is associated with increased odds of the composite outcome of death or neurodevelopmental impairment and language delay at 18-24 months CGA.

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