Exercise Capacity in Young Adults Born Small for Gestational Age

Abstract

Being born small for gestational age (SGA), approximately 10% of all births, is associated with increased risk of cardiovascular mortality in adulthood, but mechanistic pathways are unclear. Cardiac remodeling and dysfunction occur in fetuses SGA and children born SGA, but it is uncertain whether and how these changes persist into adulthood.OBJECTIVE To evaluate baseline cardiac function and structure and exercise capacity in young adults born SGA. DESIGN, SETTING, AND PARTICIPANTSThis cohort study conducted from January 2015 to January 2018 assessed a perinatal cohort born at a tertiary university hospital in Spain between 1975 and 1995. Participants included 158 randomly selected young adults aged 20 to 40 years born SGA (birth weight below the 10th centile) or with intrauterine growth within standard reference ranges (controls). Participants provided their medical history, filled out questionnaires regarding smoking and physical activity habits, and underwent incremental cardiopulmonary exercise stress testing, cardiac magnetic resonance imaging, and a physical examination, with blood pressure, glucose level, and lipid profile data collected. EXPOSURE Being born SGA. MAIN OUTCOMES AND MEASURES Cardiac structure and function assessed by cardiac magnetic resonance imaging, including biventricular end-diastolic shape analysis. Exercise capacity assessed by incremental exercise stress testing. RESULTS This cohort study included 81 adults born SGA (median age at study, 34.4 years [IQR, 30.8-36.7 years]; 43 women [53%]) and 77 control participants (median age at study, 33.7 years [interquartile range (IQR), 31.0-37.1 years]; 33 women [43%]). All participants were of White race/ethnicity and underwent imaging, whereas 127 participants (80% of the cohort; 66 control participants and 61 adults born SGA) completed the exercise test. Cardiac shape analysis showed minor changes at rest in right ventricular geometry (DeLong test z, 2.2098; P = .02) with preserved cardiac function in individuals born SGA. However, compared with controls, adults born SGA had lower exercise capacity, with decreased maximal workload (mean [SD], 180 [62] W vs 214 [60] W; P = .006) and oxygen consumption (median, 26.0 mL/min/kg [IQR, 21.5-33.5 mL/min/kg vs 29.5 mL/min/kg [IQR, 24.0-36.0 mL/min/kg]; P = .02). Exercise capacity was significantly correlated with left ventricular mass (ρ = 0.7934; P < .001).CONCLUSIONS AND RELEVANCE This cohort of young adults born SGA had markedly reduced exercise capacity. These results support further research to clarify the causes of impaired exercise capacity and the potential association with increased cardiovascular mortality among adults born SGA.

RETRACTED ARTICLE: The Effect of Preterm Birth on Maximal Aerobic Exercise Capacity and Lung Function in Healthy Adults: A Systematic Review and Meta-analysis

“…[13] reported a negative effect of prematurity on diastolic filling of the left ventricle, likely caused by an immature myocardium [14,38,39]. Similarly, data from Crispi et al [38] and McKay et al [40] indicate that the impaired early filling was accompanied by a reduced cardiac output, suggesting that the heart of prematurely born humans likely provides a reduced blood supply to working muscles during exercise, which would impair aerobic exercise capacity [41,42].…”

“…[13] reported a negative effect of prematurity on diastolic filling of the left ventricle, likely caused by an immature myocardium [14,38,39]. Similarly, data from Crispi et al [38] and McKay et al [40] indicate that the impaired early filling was accompanied by a reduced cardiac output, suggesting that the heart of prematurely born humans likely provides a reduced blood supply to working muscles during exercise, which would impair aerobic exercise capacity [41,42]. Whether the reduced stroke volume previously reported is simply an effect of the smaller left ventricle because of reduced filling [43,44] (and thus indicating more of a systemic influence of the circulating blood volume instead of impaired heart muscle function itself), or whether there is an intrinsic impairment in myocardial contraction and/or relaxation remains to be determined.…”

“…Another potential influence on the output of the heart could be blood pressure. Bennet et al [45] and Crispi et al [38] have suggested that prematurity impairs the adequate Fig. 2 Forest plot for maximal oxygen consumption (VO 2 max).…”

Overexpression of microRNAs miR-25-3p, miR-185-5p and miR-132-3p in Late Onset Fetal Growth Restriction, Validation of Results and Study of the Biochemical Pathways Involved

“…During oxygen deprivation, the heart will try to cope with this shortage by changing its shape in order to ensure oxygen availability to the principal organs. Firstly, it may develop a more spherical shape to maintain systolic volume, and if the situation persists, cardiac hypertrophy develops to increase contractility [ 56 , 57 , 58 ]. Again, not surprisingly, both miR-132-3p and miR-25-3p target the MEIS1 gene ( Figure 6 ), which is mainly involved in cardiomyocyte differentiation and cardiac muscle hypertrophy.…”

Understanding the preterm human heart: What do we know so far?

“…Additionally, children born IUGR have been shown to have smaller hearts with non‐hypertrophic spherical ventricles and impaired relaxation, all independent of body size (Sarvari et al, 2017). Although preterm‐born children with IUGR have been shown to have the greatest cardiac remodeling (Sarvari et al, 2017), alterations have also been observed by echocardiography and CMR imaging in mild IUGR cases born at term (Crispi et al, 2010, 2021) suggesting a distinct contribution of IUGR on the cardiac phenotype of prematurity.…”