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. Author manuscript; available in PMC: 2026 Feb 17.
Published in final edited form as: Eur J Appl Physiol. 2020 Aug 30;120(11):2547–2554. doi: 10.1007/s00421-020-04480-9

Blunted cardiac output response to exercise in adolescents born preterm

Kristin Haraldsdottir 1,2, Andrew M Watson 2, David F Pegelow 1, Mari Palta 4,7, Laura H Tetri 1, Taylor Levin 1, Melissa D Brix 1,5, Ryan M Centanni 1,5, Kara N Goss 1,3, Marlowe M Eldridge 1,5,6
PMCID: PMC12908129  NIHMSID: NIHMS2135436  PMID: 32862247

Abstract

Purpose

Premature birth is associated with lasting effects, including lower exercise capacity and pulmonary function, and is acknowledged as a risk factor for cardiovascular disease. The aim was to evaluate factors affecting exercise capacity in adolescents born preterm, including the cardiovascular and pulmonary responses to exercise, activity level and strength.

Methods

21 preterm-born and 20 term-born adolescents (age 12–14 years) underwent strength and maximal exercise testing with thoracic bioimpedance monitoring. Baseline variables were compared between groups and ANCOVA was used to compare heart rate, cardiac output (Q) and stroke volume (SV) during exercise between groups while adjusting for body surface area.

Results

Preterm-borns had lower maximal aerobic capacity than term-borns (2.0 ± 0.5 vs. 2.5 ± 0.5 L/min, p = 0.01) and lower maximal power (124 ± 26 vs. 153 ± 33 watts, p < 0.01), despite similar physical activity scores. Pulmonary function and muscular strength did not differ significantly. Although baseline Q and SV did not differ between groups, preterm adolescents had significantly lower cardiac index (Qi) at 50, 75 and 100% of maximal time to exhaustion, driven by SV volume index (SVi, 50% max time: 53.0 ± 9.0 vs. 61.6 ± 11.4; 75%: 51.7 ± 8.4 vs. 64.3 ± 11.1; 100%: 51.2 ± 9.3 vs. 64.3 ± 11.5 ml/m2, all p < 0.01), with similar heart rates.

Conclusion

Otherwise healthy and physically active adolescents born very preterm exhibit lower exercise capacity than term-born adolescents. Despite similar baseline cardiovascular values, preterm-born adolescents demonstrate significantly reduced Qi and SVi during incremental and maximal exercise.

Keywords: Preterm birth, Exercise capacity, Aerobic capacity, Stroke index, Cardiac output, Pediatric exercise physiology, Cardiovascular disease, Thoracic bioimpedance, Premature birth, Physical activity

Introduction

Ten percent of all live births worldwide are premature, and survival rates are increasing for infants requiring medical intervention (WHO 2017). However, preterm birth is now recognized as a risk factor for adult comorbidities, including hypertension (Bertagnolli et al. 2016; de Jong et al. 2012; Hovi et al. 2016), metabolic disease (Mericq et al. 2017; Parkinson et al. 2013), and cardiac disease (Lewandowski et al. 2013a, b). Regular exercise and an active lifestyle are known to reduce the risk of these diseases in healthy populations, but there is mounting evidence that exercise capacity in individuals born preterm is lower than in individuals born at term. Pretermborn individuals ranging from 8 years old through adulthood exhibit lower physical fitness, strength, and aerobic capacity, often despite similar activity levels (Tamai et al. 2019; Nixon et al. 2019; Vrijlandt et al. 2006b; Clemm et al. 2015; Duke et al. 2014). Furthermore, we previously reported both lower exercise capacity and abnormal autonomic nervous system (ANS) function in this population (Haraldsdottir et al. 2018).

Exercise capacity is influenced by several factors, including activity level, genetics, body composition and several physiological systems, including the pulmonary, autonomic nervous, and cardiovascular systems (Bassett and Howley 2000). However, preterm birth interrupts the normal development of these systems (Vrijlandt et al. 2006a; Palta et al. 2001; Vollsaeter et al. 2015, 2013; Gough et al. 2012).

We examined several mediators of exercise capacity in a healthy and physically active population of adolescent survivors of preterm birth (gestational age ≤ 32 weeks). To better evaluate causes of previously reported decreased exercise capacity, we also measured pulmonary function, strength, and the cardiovascular and ventilatory responses to exercise. We hypothesized that healthy and physically active children born preterm would have diminished exercise capacity of a multifactorial etiology, including compromised lung function, blunted cardiovascular response to exercise, and lower overall strength.

Methods

Ethical approval

The protocol was approved by the Institutional Review Board at the University of Wisconsin Madison. Each subject and legal guardian were informed of the purpose and risks associated with the study. Written consent was obtained from a legal guardian and informed assent from all subjects in accordance with the standards set by the Declaration of Helsinki.

Participants

Preterm participants were recruited from the Newborn Lung Project (Palta and Sadek-Badawi 2008; Palta et al. 2008), a cohort established in 2003–2004 and prospectively followed at the University of Wisconsin (Madison, WI). Preterm infants were born at ≤ 32 weeks gestation with very low birth weight (< 1500 g). The Newborn Lung Project also included normal birth weight term-born children whose addresses were obtained from 2003–2004 Wisconsin birth records (Palta and Sadek-Badawi 2008), from which 14 controls were recruited. The remaining control subjects were recruited from the local community using flyers. Inclusion criteria for all participants were the ability to complete a maximal exercise test, non-smoking, free of mental, physical, visual or neurological disabilities, and no diagnosed overt cardiovascular or respiratory disease. Subjects’ height was measured using a mechanical measuring rod to the nearest 0.5 cm (Seca; Hamburg, Germany), and weight was measured using a digital scale to the nearest 0.1 kg (Taylor; Oak Brook, IL) and recorded at the beginning of the study visit. Body mass index (BMI) was calculated as height in meters divided by weight in kilograms squared, and BMI-for-age reference was determined using z-scores (CDC 2009).

Pulmonary function

Subjects underwent pulmonary function testing, including forced vital capacity (FVC), forced expiratory flow at 25–75% of the pulmonary volume (FEF25–75), forced expiratory volume in 1 s (FEV1) (Desktop Diagnostics/CPFS; Medical Graphics, St. Paul, MN), and diffusing capacity of the lungs for carbon monoxide (DLCO) (MasterScreen PFT; Jaeger, Hoechberg, Germany). Values were adjusted for age, sex, and height based on Global Lung Initiative normative values (Quanjer et al. 2012; Stanojevic et al. 2017),

Baseline physical activity questionnaire

Subjects completed a physical activity questionnaire, the PAQ-C, an externally validated and widely used physical activity quantification tool for children, to determine physical activity level. Questions were based on a 7-day recall of low-intensity to high-intensity activities during school, immediately following school, and in the evening (Crocker et al. 1997).

Hand grip

Hand grip strength is positively correlated with overall body strength (Wind et al. 2010). Isometric muscle strength was assessed with a handheld dynamometer (Baseline spring hand dynamometer, White Plains, NY) in Newtons. Subjects were seated, with both feet on the floor, with the shoulder adducted and the forearm resting on a table. Subjects self-reported hand dominance, then performed maximal voluntary contractions three times with each hand, alternating hands between attempts, with 1-min rest between trials. The highest value achieved with each hand was used for analysis using the Southampton protocol (Roberts et al. 2011).

Vertical jump

Vertical jump displacement is a measure of power. Vertical jump displacement was assessed by subtracting standing reach height from maximal jump height. Participants stood perpendicular to a wall, with their dominant arm closest to the wall. Participants performed the jump from a stationary position. The test was performed three times, with 1-min rest between jumps to ensure adequate recovery. The highest displacement value (cm) achieved was used for analysis.

Exercise testing

Participants performed a maximal exercise test on an upright cycle electromagnetically controlled ergometer (Velotron; RacerMate; Seattle, WA). Participants cycled at 60–70 revolutions per minute starting at 50 watts for 2 min, and increased by 25 watts every 2 min until subjects were no longer able to maintain 55 revolutions per minute for more than 5 s, despite strong verbal encouragement. Heart rate (HR) was monitored using a three-lead ECG (Physioflow, PF-05 Lab1, Manatec Biomedical), expired gases were collected breath-by-breath (Gemini; CWE, Ardmore, PA) and ventilatory and metabolic parameters were recorded and analyzed in PowerLab (ADInstruments; Colorado Springs, CO). HR, ventilatory, and metabolic parameters were recorded and analyzed in PowerLab. Maximal oxygen consumption (VO2max) was determined from a rolling 30 s average. In order for a test to be considered a valid VO2max, the primary criteria of a plateau in VO2 was defined as a change of < 2 mL/kg/min in O2 consumption over the last 60 s of the test had to be met. In addition, one of the following secondary criteria had to be met: (1) a maximal HR (HRmax) of more than 90% age predicted HRmax (220-age), or (2) a respiratory exchange ratio (carbon dioxide production/oxygen consumption) of ≥ 1.1 (Midgley et al. 2007). Maximal power (Pmax) was determined as the highest stage maintained for more than one minute. Maximal time (Tmax) was determined as the time from the beginning of the first stage to the beginning of the recovery period. HR data were recorded and analyzed at rest, 25%, 50%, 75%, and at 100% of Tmax.

Ventilatory threshold

To account for fluctuations in breath-by-breath measurements of minute ventilation, a 30 s rolling average of minute ventilation was used to determine ventilatory threshold (VT). VT was determined as the point at which an upward deflection was noted in the slope of total ventilation over time. VT was reported as both the absolute time to VT and as the VO2 at VT (L/min and ml/kg/min).

Ventilatory equivalent

The ventilatory equivalent for oxygen (minute ventilation, VE, divided by oxygen consumption, VE/VO2) and carbon dioxide (minute ventilation divided by carbon dioxide production, VE/VCO2) was determined as the slope of the relationship between VE and VO2 or VCO2 from the beginning of each test until the VT (Sun et al. 2002).

Thoracic bioimpedance

Cardiac output (Q) was determined noninvasively at rest and throughout exercise using six-lead thoracic bioimpedance (Physioflow, PF-05 Lab1, Manatec Biomedical) (Legendre et al. 2018). Briefly, the technique uses variations in impedance (DZ) of a high-frequency (75 kHz) and low-magnitude alternating current (1.8 mA) across the thorax guided by an ECG tracing to determine the systolic phase that results in a waveform used to calculate SV. SV index is initially calculated at rest by evaluating 24 consecutive heart beats (autocalibration procedure) using measurements of the largest impedance difference during systole, the largest rate of variation of the impedance signal (contractility index), the thoracic fluid inversion time, HR, and the pulse pressure (Charloux et al. 2000). Values for Q and SV were sampled at 10 s intervals. Q and SV indexed for body surface area (Qi and SVi) for each individual was determined at rest and at 25%, 50%, 75% and 100% of Tmax using the average of three data points for each time point. Independent measures of Q and VO2 allowed for the calculation of maximal arteriovenous oxygen using the Fick principle and dividing VO2 (L/min) by Q (L/min).

Statistical analysis

Data are presented as mean ± standard deviation, unless otherwise noted. Wilcoxon Rank Sum tests were used to compare anthropometric, birth status, exercise capacity, ventilatory equivalents and thoracic bioimpedance variables between the control and preterm groups. Multiple pairwise comparisons were adjusted (Holm 1979). Analysis of covariance was used to compare SVi, HR and Qi between groups at 25, 50, 75 and 100% Tmax, while adjusting for baseline values. In a secondary analysis, linear regressions were performed to evaluate the relationship between VO2max and SV reserve (volume of blood per beat over resting values) during exercise. Statistical analyses were performed in R (Foundation for Statistical Computing, Vienna, Austria) and Graph-Pad Prism software (Version 7, GraphPad Software Inc., La Jolla, CA), and graphs generated using Prism Graphpad. All tests were two-tailed and p < 0.05 was used to define statistical significance.

Results

Characteristics of the subjects

Twenty-one preterm-born (age 13.0 ± 0.7 years, 27.9 ± 2.1 weeks gestation at birth, range: 25–32 weeks) and 20 term-born adolescents (age 13.3 ± 0.7 years, 39.7 ± 0.9 weeks gestation at birth) completed the study. Briefly, adolescents born preterm were shorter in stature with a lower body surface area (BSA), but no statistically significant differences were identified with respect to weight or BMI (Table 1). Some anthropometric results from this population have been reported (Haraldsdottir et al. 2018).

Table 1.

Anthropometric and birth status data

Term (n = 20) Preterm (n = 21) P value
Female n, % 11, 55% 13, 62%
Age (years) 13.3 ± 0.7 13.0 ± 0.7 0.09
Height (cm) 164.3 ± 8.0 158.1 ± 8.7 0.03
Weight (kg) 52.4 ± 10.5 46.6 ± 8.4 0.06
BMI (kg/m2) 19.4 ± 3.8 18.6 ± 2.6 0.42
BMI percentile (%) 47 ± 32 43 ± 29 0.68
BMI z-score −0.07 ± 1.15 −0.25 ± 0.95 0.58
BSA (m2) 1.56 ± 0.18 1.42 ± 0.17 0.01
Birthweight (grams) 3497 ± 366 1097 ± 274 < 0.001
Gestational age (weeks) 39.7 ± 0.9 27.9 ± 2.1 < 0.001
PAQ-C 1.93 ± 0.39 1.89 ± 0.45 0.76
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BMI body mass index, BSA body surface area, PAQ-C physical activity questionnaire score

Physical activity

No statistically significant differences were identified between groups with respect to general physical activity as reported on the PAQ-C (Table 1).

Pulmonary function

Lung function values were similar between term and preterm-born subjects. However, FEV1% of predicted value was lower in preterm subjects (Table 2).

Table 2.

Lung function

Term (n = 20) Preterm (n = 21) P value
FVC (L) 3.7 ± 0.9 3.2 ± 0.6 0.05
FVC % predicted 101.9 ± 13.9 96.9 ± 8.8 0.18
FEV1 (L) 3.2 ± 0.8 2.7 ± 0.5 0.02
FEV1% predicted 101.9 ± 14.6 94.4 ± 7.1 0.05
FEV1/FVC (%) 87.1 ± 4.5 85.7 ± 5.8 0.41
FEV1/FVC % predicted 98.8 ± 6.6 96.5 ± 6.4 0.43
FEF25–75 (L/s) 3.4 ± 0.9 2.9 ± 0.8 < 0.05
FEF25–75% predicted 93.2 ± 19.9 82.6 ± 17.6 0.09
DLCO (ml/min/mmHg) 21.9 ± 3.9 19.0 ± 3.6 0.02
DLCO % predicted 94.5 ± 11.7 90.7 ± 13.2 0.36
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FVC forced vital capacity, FEV1 forced expiratory volume in 1 s, FEF25–75 forced expiratory flow 25–75%, DLCO diffusion capacity of the lungs for carbon monoxide

Hand grip and vertical jump

The difference in hand grip and vertical jump scores did not reach statistical significance between groups (Table 3).

Table 3.

Exercise capacity

Term (n = 20) Preterm (n = 21) p value
VO2max (L/min) 2.5 ± 0.5 2.0 ± 0.5 0.01
VO2max (ml/kg/min) 48.3 ± 11.0 43.3 ± 6.9 0.11
Pmax (watts) 153 ± 33 124 ± 26 < 0.01
Tmax (min) 10.6 ± 2.5 8.3 ± 2.5 < 0.01
HRmax (bpm) 192 ± 9 193 ± 10 0.84
VT (min) 8.1 ± 1.9 6.2 ± 2.0 < 0.01
VT (L/min) 2.1 ± 0.6 1.6 ± 0.3 < 0.01
VT (ml/kg/min) 38.9 ± 8.4 35.8 ± 5.3 0.18
VE/VO2 slope 28.2 ± 4.0 26.1 ± 7.8 0.27
VE/VCO2 slope 30.3 ± 4.2 28.4 ± 4.8 0.21
Vertical jump (cm) 30.9 ± 5.8 27.9 ± 4.6 0.09
Handgrip dominant (N) 619 ± 134 589 ± 115 0.48
Handgrip non-dominant (N) 570 ± 115 551 ± 127 0.64
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VO2max maximal oxygen consumption, Pmax maximal power, Tmax time to exhaustion, VT ventilatory threshold, VE minute ventilation, N Newtons

Aerobic exercise capacity

VO2max was significantly lower in adolescents born preterm than controls, but the difference was no longer statistically significant when adjusted for body mass (ml/kg/min, Table 3). Preterm subjects exercised at a lower maximal workload and had a shorter time to exhaustion. VT was lower in preterm subjects when measured as time to VT and as absolute VO2 at VT. There was no difference in VT when determined as VO2 (L/min) at VT (Table 3). There was not a statistically significant difference in ventilatory equivalent, VE/VO2 or VE/VCO2 slope, during exercise between groups (Table 3).

Thoracic bioimpedance

Bioimpedance cardiography was attempted in all subjects, but due to a loss of the bioimpedance signal, complete data were only available to analyze in 19 control subjects and 16 preterm subjects (Fig. 1, Table 4). There was no difference in Q at rest or 25% Tmax between groups. Q was significantly lower in preterm subjects compared to controls at 50%, 75% and 100% of Tmax. When the components of Q were analyzed separately, there was no difference in HR at rest and throughout exercise, while SV and SVi were significantly lower in preterm subjects at 50%, 75% and 100% Tmax. There was no difference in calculated arteriovenous oxygen difference at 100% Tmax (Table 3). A positive linear relationship was found between VO2max and SV reserve, defined as the difference in SV from rest to maximal exercise (Fig. 2).

Fig. 1.

Fig. 1

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Cardiovascular response to incremental maximal exercise. a Cardiac index (Qi, L/min/m2) at rest, 25, 50, 75 and 100% Tmax. b Heart rate (HR, bpm) at rest, 25, 50, 75 and 100% Tmax. c Stroke volume index (SVi, ml/m2) at rest, 25, 50, 75 and 100% Tmax. Red squares, preterm-born adolescents; black circles, term-born adolescents

Table 4.

Thoracic bioimpedance data

Control (n = 19) Preterm (n = 16) p value
SV rest (ml) 71.5 ± 12.2 70.6 ± 11.7 0.82
SV 25%Tmax (ml) 87.6 ± 17.0* 79.5 ± 15.3* 0.17
SV 50% Tmax (ml) 95.8 ± 16.6* 73.8 ± 14.3 < 0.001
SV 75% Tmax (ml) 100.3 ± 18.8* 71.4 ± 13.3 < 0.001
SV 100% Tmax (ml) 100.5 ± 19.2* 70.4 ± 12.1 < 0.001
SVi rest (ml/m2) 46.0 ± 8.5 50.7 ± 7.5 0.1
SVi 25% Tmax (ml/m2) 56.1 ± 10.0* 56.6 ± 7.9* 0.9
SVi 50% Tmax (ml/m2) 61.6 ± 11.4* 53.0 ± 9.0 0.03
SVi 75% Tmax (ml/m2) 64.3 ± 11.1* 51.7 ± 8.4 < 0.01
SVi 100% Tmax (ml/m2) 64.3 ± 11.5* 51.2 ± 9.3 < 0.01
a-vO2diffmax (ml/100 ml) 13.3 ± 2.5 14.7 ± 4.0 0.25
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SV stroke volume, Tmax time to exhaustion, SVi SV indexed to BSA, a-vO2diffmax maximal arteriovenous oxygen difference

*

p < 0.05 vs. resting value within the same group

Fig. 2.

Fig. 2

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Relationship between SV reserve and VO2max. Linear regression between stroke volume (SV) reserve (ml, the change in SV from rest to maximal exercise value). Red circles, preterm-born adolescents; black circles, term-born adolescents

Discussion

This study assessed mediators of exercise capacity in adolescents born very-to-extremely prematurely, evaluating factors that contribute to decreased exercise tolerance including baseline physical activity, muscular strength and power, pulmonary function, ventilatory efficiency and the cardiovascular response to exercise. Our study demonstrates that: (1) otherwise healthy and physically active adolescents born preterm have lower exercise capacity than their age-matched full-term peers, as evidenced by lower absolute VO2max, Pmax, Tmax, and VT, with no difference in strength or ventilatory efficiency, (2) adolescents born preterm have lower Q throughout exercise, and (3) the lower exercise capacity in preterm adolescents is correlated with an impaired augmentation in SV in response to incremental exercise to exhaustion.

VO2max, Pmax, and Tmax are lower in adolescents born preterm (Haraldsdottir et al. 2018), a finding consistent with other literature demonstrating modest decreases in aerobic capacity in this population (Clemm et al. 2015, 2012; Smith et al. 2008). Male non-black preterm-born adolescents who received antenatal steroids have higher aerobic capacity than those who did not receive steroid treatment (Nixon et al. 2019). We hypothesized that lower exercise capacity in this population would be associated with decreased muscular strength, pulmonary function, and a lower cardiovascular response. Our finding that the SV response to exercise is blunted in adolescents born preterm provides a potential mechanism for exercise limitation in an otherwise healthy, physically fit population of children. Huckstep et al. (2018) explored the cardiac response to exercise in young adults born preterm and reported impaired Q reserve, demonstrated by a lower ejection fraction by echocardiography throughout incremental exercise. Similarly, young adults born preterm from the Newborn Lung Project exhibit a blunted SV augmentation during supine exercise, as demonstrated using the Fick method (Goss et al. 2018).

Lower physical fitness can be attributed to physical inactivity. We found that the preterm adolescents did not have significantly lower physical activity scores, but our study may have been underpowered to detect more subtle differences between groups. This differs from other reports, where aerobic capacity, muscular strength and power were lower in preterm adolescents who also had lower activity level scores than the control group (Rogers et al. 2005). Similarly, lower physical fitness can be attributed to diminished lung function, and young adults born preterm have demonstrated inefficient pulmonary gas exchange during exercise (Farrell et al. 2015). We found that percent predicted values for lung function were not statistically different between groups, with the exception of FEV1. Ventilatory efficiency, as determined by VE/VO2 and VE/VCO2 slope during exercise, was also not statistically different between groups. Taken together, these findings support that exercise capacity was not limited by pulmonary function or muscular strength and power.

A finger photo plethysmograph impedance device has been used to explore the cardiovascular response to psychosocial stress situations in adults born at extremely low birth weight, where it was found that preterm-born young adults exhibited lower Q reactivity to high stress situations than term-born adults, despite higher reported stress level (Mathewson et al. 2015a). We found that while Q did augment during exercise in both groups, it was lower at 50, 75 and 100% of intensity in preterm subjects. We found no difference in the HR response to exercise between groups at matched intensity levels. Furthermore, SV and SVi were not statistically different from resting values at 50, 75 and 100% of intensity in preterm subjects, whereas they increased significantly in controls. Similarly, we have reported a lower oxygen pulse at maximal exercise in this population, a measure often used as a surrogate for SV (Haraldsdottir et al. 2018).

There are several potential etiologies for the decreased SV reserve in the preterm population. First, there is emerging evidence that the autonomic nervous system, which plays a major role in augmenting both HR and SV in response to exercise, is altered in adolescents born preterm (Haraldsdottir et al. 2018; Mathewson et al. 2015b; Rakow et al. 2013), though HR was not significantly different between groups throughout incremental exercise. Second, a cardiac limitation to exercise tolerance could be due to smaller chamber size or overt contractile dysfunction. Among adults born premature, cardiac magnetic resonance imaging (MRI) demonstrates biventricular hypertrophy, impaired systolic and diastolic function, and reduced right ventricular ejection fraction (Lewandowski et al. 2013a, b). Preterm adolescents from the Newborn Lung Project demonstrate a smaller cardiac chamber size than controls using cardiac MRI (Goss et al. 2020), and similar findings have also been reported in 6-year-old children and adolescents born preterm using other methods (Kowalski et al. 2016; Mohlkert et al. 2018).

To gain mechanistic insight into factors contributing to lower exercise capacity in the preterm adolescent group, we explored the relationship between aerobic capacity and SV reserve. The positive correlation between VO2max and SV reserve highlights that not only did preterm adolescents have a blunted SV reserve, but also in some cases, had a decrease in SV from rest to maximal exercise (Fig. 2). A blunted SV reserve in response to exercise has been noted in patients with both diastolic (Kitzman et al. 1991) and systolic dysfunction (Dahan et al. 1995), and there is evidence of systolic dysfunction and decreased ejection fractions in young adults born preterm (Huckstep et al. 2018; Lewandowski et al. 2013a, b). Furthermore, smaller biventricular chambers size is reported in young adults born preterm (Goss et al. 2020), which could limit SV reserve capacity. While the current study was not designed to determine the mechanisms behind the lower SV reserve, the data suggest that there is an intrinsic cardiac limitation that is revealed during exercise in this population.

Taken together, the observed exercise impairment in otherwise healthy adolescents born preterm is likely not due limitations in pulmonary function, muscle strength or power, but rather a cardiac limitation during exercise. Preterm birth before 32-week gestation was reported to increase heart failure risk in adolescents and young adults by up to 17-fold (Carr et al. 2017). In a young, fit, otherwise healthy population, adolescent children with a history of premature birth have blunted SV augmentation in response to maximal exercise, an impairment that is noted in individuals with various etiologies of systolic and diastolic cardiac dysfunction.

There are a number of methodological limitations in this study. First, the thoracic bioimpedance method employed to measure SV has been validated (Legendre et al. 2017), and similar devices (Mathewson et al. 2015a) have been used in studies with subject populations similar to ours. However, we acknowledge that a direct measurement of Q and SV would be preferred. Second, the thoracic bioimpedance analysis had fewer subjects than the rest of the analysis, and may have impacted the significance of our findings. Finally, our study was not designed to gain mechanistic insight into the SV impairment during exercise.

The primary finding in this study is that despite no differences in HR during incremental to maximal exercise, Qi and SVi were lower in adolescents born preterm. These findings suggest the cause of decreased exercise capacity in individuals born preterm is a SV reserve limitation.

Funding

Project supported by funding from the National Institutes of Health: 1R01 HL086897 (M.W.E.), and UW CVRC T32-HL 07936 (KH). The authors have no financial relations relevant to this article to disclose.

Abbreviations

PAQ-C

Physical activity questionnaire

DLCO

Diffusion capacity of the lung for carbon monoxide

HRmax

Maximal heart rate

VO2max

Maximal aerobic capacity

P max

Maximal power

T max

Time to exhaustion

VE

Minute ventilation

VO2

Oxygen consumption

VCO2

Carbon dioxide production

VT

Ventilatory threshold

Q

Cardiac output

SV

Stroke volume

SVi

Stroke volume indexed to body surface area

BSA

Body surface area

BMI

Body mass index

FVC

Forced vital capacity

FEV1

Forced expiratory volume in 1 s

FEF25–75

Forced expiratory flow at 25–75% of the pulmonary volume

Footnotes

Conflict of interest The authors have no conflicts of interest relevant to this article to disclose.

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