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.

Mesenchymal stromal cell (MSC) derived exosomes mediate tissue protection and regeneration in many injuries and diseases by modulating cell protein production, protecting from apoptosis, inhibiting inflammation, and increasing angiogenesis. In the present study, daily intraperitoneal injection of MSC-derived exosomes protected alveolarization and angiogenesis in a newborn rat model of bronchopulmonary dysplasia (BPD) induced by 14 days of neonatal hyperoxia exposure (85% O). Exosome treatment during hyperoxia prevented disruption of alveolar growth, increased small blood vessel number, and inhibited right heart hypertrophy at P14, P21, and P56. In vitro, exosomes significantly increased tube-like network formation by HUVEC, in part through a VEGF mediated mechanism. In summary, daily intraperitoneal injection of exosomes increased blood vessel number and size in the lung through pro-angiogenic mechanisms. MSC-derived exosomes therefore have both anti-inflammatory and pro-angiogenic mechanism to protect the lung from hyperoxia induced lung and heart disease associated with BPD.

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.

PurposeTo evaluate the influence of sport characteristics and face mask use on COVID-19 incidence among high school athletes.MethodsSurveys were distributed to high school athletic directors throughout the United States regarding sport re-initiation, COVID-19 cases, and risk reduction procedures in fall 2020.Separate mixed effects Poisson regression models were developed to evaluate the associations between reported COVID-19 incidence and 1) sport characteristics (contact/non-contact, individual/team, indoor/outdoor) and 2) face mask use while playing (yes/no).Results991 schools had restarted fall sports, representing 152,484 athletes on 5,854 teams. 2,565 cases of COVID-19 were reported, representing a case rate of 1,682 cases per 100,000 athletes and an incidence rate of 24.6 cases per 100,000 player-days. COVID-19 incidence was lower among outdoor versus indoor sports (incidence rate ratio [IRR]=0.54, 95% CI=0.49-0.60, p<0.001) and non-contact versus contact sports (IRR=0.78 [0.70-0.87], p<0.001), but not team versus individual sports (IRR=0.96 [0.84-1.1], p=0.49). Face mask use was associated with a decreased incidence in girls’ volleyball (IRR=0.53 [0.37-0.73], p<0.001), boys’ basketball (IRR=0.53 [0.33-0.83], p=0.008) and girls’ basketball (IRR=0.36 [0.19-0.63], p<0.001), and approached statistical significance in football (IRR=0.79 [0.59-1.04], p=0.10) and cheer/dance (IRR=0.75 [0.53-1.03], p=0.081).ConclusionsIn this nationwide survey of US high school athletic directors representing 152,484 athletes, lower COVID-19 incidence was independently associated with participation in outdoor versus indoor and non-contact versus contact sports, but not team versus individual sports. Face mask use was associated with decreased COVID-19 incidence among indoor sports, and may be protective among outdoor sports with prolonged close contact between participants.

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Context: As sports reinitiate around the country, the incidence of COVID-19 among youth soccer athletes remains unknown. Objective: To determine the incidence of COVID-19 among youth soccer athletes and the risk mitigation practices utilized by youth soccer organizations. Design: Retrospective cohort. Participants: Youth soccer club directors throughout the United States. Main Outcome Measures: Surveys were completed in late August 2020 regarding phase of return to soccer (individual only, group non-contact, group contact), date of reinitiation, number of players, cases of COVID-19, and risk reduction procedures being implemented. Case and incidence rates were compared to national pediatric data and county data from the prior 10 weeks. A negative binomial regression model was developed to predict club COVID-19 cases with local incidence rate and phase of return as covariates and the log of club player-days as an offset. Results: 124 respondents had reinitiated soccer, representing 91,007 players with a median duration of 73 days (IQR: 53-83 days) since restarting. Of the 119 that had progressed to group activities, 218 cases of COVID-19 were reported among 85,861 players. Youth soccer players had a lower case rate and incidence rate than children in the US (254 v. 477 cases per 100,000; incidence rate ratio [IRR]=0.511, 95% CI = [0.40-0.57], p&lt;0.001) and the general population from the counties where data was available (268 v. 864 cases per 100,000; IRR=0.202 [0.19–0.21], p&lt;0.001). After adjusting for local COVID-19 incidence, there was no relationship between club COVID-19 incidence and phase of return (non-contact: b=0.35±0.67, p=0.61; contact: b=0.18±0.67, p=0.79). Soccer clubs reported utilizing a median of 8 (IQR: 6-10) risk reduction procedures. Conclusions: The incidence of COVID-19 among youth soccer athletes is relatively low when compared to the background incidence among children in the United States in summer of 2020. No relationship was identified between club COVID-19 incidence and phase of return to soccer.