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.

IMPORTANCE Premature birth is associated with substantially higher lifetime risk for cardiovascular disease, including arrhythmia, ischemic disease, and heart failure, although the underlying mechanisms are poorly understood.OBJECTIVE To characterize cardiac structure and function in adolescents and young adults born preterm using cardiac magnetic resonance imaging (MRI). DESIGN, SETTING, AND PARTICIPANTSThis cross-sectional cohort study at an academic medical center included adolescents and young adults born moderately to extremely premature (20 in the adolescent cohort born from 2003 to 2004 and 38 in the young adult cohort born in the 1980s and 1990s) and 52 age-matched participants who were born at term and underwent cardiac MRI. The dates of analysis were February 2016 to October 2019.EXPOSURES Premature birth (gestational age Յ32 weeks) or birth weight less than 1500 g. MAIN OUTCOMES AND MEASURESMain study outcomes included MRI measures of biventricular volume, mass, and strain. RESULTSOf 40 adolescents (24 [60%] girls), the mean (SD) age of participants in the term and preterm groups was 13.3 (0.7) years and 13.0 (0.7) years, respectively. Of 70 adults (43 [61%] women), the mean (SD) age of participants in the term and preterm groups was 25.4 (2.9) years and 26.5 (3.5) years, respectively. Participants from both age cohorts who were born prematurely had statistically significantly smaller biventricular cardiac chamber size compared with participants in the term group: the mean (SD) left ventricular end-diastolic volume index was 72 (7) vs 80 (9) and 80 (10) vs 92 (15) mL/m 2 for adolescents and adults in the preterm group compared with age-matched participants in the term group, respectively (P < .001), and the mean (SD) left ventricular end-systolic volume index was 30 (4) vs 34 (6) and 32 (7) vs 38 (8) mL/m 2 , respectively (P < .001). Stroke volume index was also reduced in adolescent vs adult participants in the preterm group vs age-matched participants in the term group, with a mean (SD) of 42 (7) vs 46 (7) and 48 (7) vs 54 (9) mL/m 2 , respectively (P < .001), although biventricular ejection fractions were preserved. Biventricular mass was statistically significantly lower in adolescents and adults born preterm: the mean (SD) left ventricular mass index was 39.6 (5.9) vs 44.4 (7.5) and 40.7 (7.3) vs 49.8 (14.0), respectively (P < .001). Cardiac strain analyses demonstrated a hypercontractile heart, primarily in the right ventricle, in adults born prematurely. CONCLUSIONS AND RELEVANCEIn this cross-sectional study, adolescents and young adults born prematurely had statistically significantly smaller biventricular cardiac chamber size and decreased cardiac mass. Although function was preserved in both age groups, these morphologic differences may be associated with elevated lifetime cardiovascular disease risk after premature birth.

Purpose: The long-term implications of premature birth on autonomic nervous system (ANS) function are unclear. Heart rate recovery (HRR) following maximal exercise is a simple tool to evaluate ANS function and is a strong predictor of cardiovascular disease. Our objective was to determine whether HRR is impaired in young adults born preterm (PYA).Methods: Individuals born between 1989 and 1991 were recruited from the Newborn Lung Project, a prospectively followed cohort of subjects born preterm weighing <1500g with an average gestational age of 28 weeks. Age-matched term-born controls were recruited from the local population. HRR was measured for two minutes following maximal exercise testing on an upright cycle ergometer in normoxia and hypoxia, and maximal aerobic capacity (VO 2max ) was measured.Results: Preterms had lower VO 2max than controls (34.88±5.24 v 46.15±10.21 ml/kg/min respectively, p<0.05), and exhibited slower HRR compared to controls after one and two minutes of recovery in normoxia (absolute drop of 20±4 v 31±10 and 41±7 v 54±11 beats per minute (bpm), respectively, p<0.01) and hypoxia (19±5 v 26±8 and 39±7 v 49±13 bpm, respectively, p<0.05). After adjusting for VO 2max , HRR remained slower in preterms at one and two minutes of recovery in normoxia (21±2 v 30±2 and 42±3 v 52±3 bpm respectively, p<0.05), but not hypoxia (19±3 v 25±2 and 40±4 v 47±3 bpm, respectively, p>0.05). Conclusions:Autonomic dysfunction as seen in this study has been associated with increased rates of cardiovascular disease in non-preterm populations, suggesting further study ofthe mechanisms of autonomic dysfunction after preterm birth.

Preterm birth temporarily disrupts autonomic nervous system (ANS) development, and the long‐term impacts of disrupted fetal development are unclear in children. Abnormal cardiac ANS function is associated with worse health outcomes, and has been identified as a risk factor for cardiovascular disease. We used heart rate variability (HRV) in the time domain (standard deviation of RR intervals, SDRR; and root means squared of successive differences, RMSSD) and frequency domain (high frequency, HF; and low frequency, LF) at rest, as well as heart rate recovery (HRR) following maximal exercise, to assess autonomic function in adolescent children born preterm. Adolescents born preterm (less than 36 weeks gestation at birth) in 2003 and 2004 and healthy age‐matched full‐term controls participated. Wilcoxon Rank Sum tests were used to compare variables between control and preterm groups. Twenty‐one adolescents born preterm and 20 term‐born controls enrolled in the study. Preterm‐born subjects had lower time‐domain HRV, including SDRR (69.1 ± 33.8 vs. 110.1 ± 33.0 msec, respectively, P = 0.008) and RMSSD (58.8 ± 38.2 vs. 101.5 ± 36.2 msec, respectively, P = 0.012), with higher LF variability in preterm subjects. HRR after maximal exercise was slower in preterm‐born subjects at 1 min (30 ± 12 vs. 39 ± 9 bpm, respectively, P = 0.013) and 2 min (52 ± 10 vs. 60 ± 10 bpm, respectively, P = 0.016). This study is the first report of autonomic dysfunction in adolescents born premature. Given prior association of impaired HRV with adult cardiovascular disease, additional investigations into the mechanisms of autonomic dysfunction in this population are warranted.

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