Preterm growth restriction and bronchopulmonary dysplasia: the vascular hypothesis and related physiology

KEY POINTS: Approximately 5-10% pregnancies are affected by fetal growth restriction. Preterm infants affected by fetal growth restriction have a higher incidence of bronchopulmonary dysplasia. The present study is the first to measure pulmonary artery thickness and stiffness. The findings show that impaired vasculogenesis may be a contributory factor in the higher incidence of bronchopulmonary dysplasia in preterm growth restricted infants. The study addresses the mechanistic link between fetal programming and vascular architecture and mechanics. ABSTRACT: Bronchopulmonary dysplasia is the most common respiratory sequelae of prematurity and histopathologically features fewer, dysmorphic pulmonary arteries. The present study aimed to characterize pulmonary artery mechanics and cardiac function in preterm infants with fetal growth restriction (FGR) compared to those appropriate for gestational age (AGA) in the early neonatal period. This prospective study reviewed 40 preterm infants between 28 to 32 weeks gestational age (GA). Twenty infants had a birthweight <10th centile and were compared with 20 preterm AGA infants. A single high resolution echocardiogram was performed to measure right pulmonary arterial and right ventricular (RV) indices. The GA and birthweight of FGR and AGA infants were 29.8 ± 1.3 vs. 30 ± 0.9 weeks (P = 0.78) and 923.4 g ± 168 vs. 1403 g ± 237 (P < 0.001), respectively. Assessments were made at 10.5 ± 1.3 days after birth. The FGR infants had significantly thicker right pulmonary artery inferior wall (843.5 ± 68 vs. 761 ± 40 μm, P < 0.001) with reduced pulsatility (51.6 ± 7.6 μm vs. 59.7 ± 7.5 μm, P = 0.001). The RV contractility [fractional area change (28.7 ± 3.8% vs 32.5 ± 3.1%, P = 0.001), tricuspid annular peak systolic excursion (TAPSE) (5.2 ± 0.3% vs. 5.9 ± 0.7%, P = 0.0002) and myocardial performance index (0.35 ± 0.03 vs. 0.28 ± 0.02, P < 0.001)] was significantly impaired in FGR infants. Significant correlation between RV longitudinal contractility (TAPSE) and time to peak velocity/RV ejection time (measure of RV afterload) was noted (r2  =  0.5, P < 0.001). Altered pulmonary vascular mechanics and cardiac performance reflect maladaptive changes in response to utero-placental insufficiency. Whether managing pulmonary vascular disease will alter clinical outcomes remains to be studied prospectively.