Early Pulmonary Vascular Disease in Young Adults Born Preterm

Abstract

Rationale: Premature birth affects 10% of live births in the United States and is associated with alveolar simplification and altered pulmonary microvascular development. However, little is known about the long-term impact prematurity has on the pulmonary vasculature.Objectives: Determine the long-term effects of prematurity on right ventricular and pulmonary vascular hemodynamics.Methods: Preterm subjects (n = 11) were recruited from the Newborn Lung Project, a prospectively followed cohort at the University of Wisconsin-Madison, born preterm with very low birth weight (≤1,500 g; average gestational age, 28 wk) between 1988 and 1991. Control subjects (n = 10) from the same birth years were recruited from the general population. All subjects had no known adult cardiopulmonary disease. Right heart catheterization was performed to assess right ventricular and pulmonary vascular hemodynamics at rest and during hypoxic and exercise stress.Measurements and Main Results: Preterm subjects had higher mean pulmonary arterial pressures (mPAPs), with 27% (3 of 11) meeting criteria for borderline pulmonary hypertension (mPAP, 19-24 mm Hg) and 18% (2 of 11) meeting criteria for overt pulmonary hypertension (mPAP ≥ 25 mm Hg). Pulmonary vascular resistance and elastance were higher at rest and during exercise, suggesting a stiffer vascular bed. Preterm subjects were significantly less able to augment cardiac index or right ventricular stroke work during exercise. Among neonatal characteristics, total ventilatory support days was the strongest predictor of adult pulmonary pressure.Conclusions: Young adults born preterm demonstrate early pulmonary vascular disease, characterized by elevated pulmonary pressures, a stiffer pulmonary vascular bed, and right ventricular dysfunction, consistent with an increased risk of developing pulmonary hypertension.

Keywords: bronchopulmonary dysplasia; exercise; prematurity; pulmonary hypertension; right ventricular function.

Figures

Figure 1.

Distribution of resting hemodynamic data in term and preterm subjects in reference to clinical thresholds. For mean pulmonary artery pressure (mPAP) and cardiac index (CI), the solid red line represents accepted clinical thresholds for pulmonary hypertension and cardiac dysfunction, respectively. The dashed red line represents cut-point for borderline pulmonary hypertension. The solid black line represents 2 SDs above published and internal normative values for total pulmonary vascular resistance (TPVR) and elastance (Ea), respectively; the dashed black line represents 1 SD above published normative values. Error bars are SD.

Figure 2.

Cardiac response to exercise in term and preterm subjects. Preterm subjects demonstrate a significantly blunted cardiac response to exercise, demonstrated by lower augmentation of cardiac index (CI). This difference is driven primarily by stroke volume. Solid lines represent group response, and lighter dashed lines represent individual responses. HR = heart rate; SVI = stroke volume index.

Figure 3.

Correlation of hemodynamic parameters at rest and during exercise in term and preterm subjects. Left: Cardiac output (CO) versus mean pulmonary artery pressure (mPAP) demonstrates a greater pulmonary vascular resistance (slope) for a given volume of pulmonary flow among preterm subjects. Right: Systolic right ventricular pressure (sRVP) versus stroke volume (SV) demonstrates a lower volume ejected for any RV pressure among preterm subjects. Individual data points are missing for four term and two preterm subjects because of failure to meet prespecified quality measures.

Figure 4.

Correlation of neonatal characteristics with mean pulmonary artery pressure (mPAP). Subjects diagnosed with bronchopulmonary dysplasia (BPD), defined by use of supplemental oxygen at 36 weeks postmenstrual age, are denoted by open circles (males) or open triangles (females).