Term-born Adults Research Articles

Impaired myocardial energetics and lower cardiac reserve in response to exercise stress in adults born preterm

Abstract Background/Introduction Preterm birth (<37 weeks’ gestation) affects 10% of live births globally and associates with an increased risk of heart failure, early cardiovascular-related mortality, and altered cardiac morphology. At rest, left ventricular (LV) ejection fraction (EF) is similar between adults born preterm and term, but right ventricular (RV) EF is lower in preterm-born adults. Exercise stress uncovers LVEF impairment in preterm-born adults but RVEF response to exercise stress has not been studied. The underlying cause of the impaired LVEF reserve and lower RVEF at rest in preterm-born adults remains uncertain and whether altered myocardial energetics contribute to this cardiac dysfunction is currently unknown. Purpose To measure resting myocardial energetics and ventricular function at rest and during exercise stress to determine whether reduced cardiac reserve in preterm-born adults may be explained by impaired myocardial energetics. Methods We conducted a cross-sectional, observational, case-control study of preterm (n=64; mean gestational age =31 weeks) and term-born (n=36) adults aged 34±5 years to compare myocardial energetics and ventricular function. Following maximal cardiopulmonary exercise testing (CPET), participants underwent 31-phosphorus magnetic resonance (MR) spectroscopy (31-P MRS) and cardiovascular MR imaging (CMR) on a 3-Tesla Siemens MR scanner. 31-P MRS was used to measure myocardial phosphocreatine to adenosine triphosphate ratio (PCr/ATP) as a measure of myocardial energetics. We obtained CMR-derived LVEF and RVEF at rest and during 40% peak wattage exercise (determined from CPET) using a MR compatible cardio-step module and steady-state free precession real-time cine imaging. Outcomes were analysed using unpaired Student’s t-tests and presented as mean±standard deviation. Results Age, body mass index, and sex did not differ between groups (p>0.05). PCr/ATP was 1.8±0.4 in preterm-born adults and 2.0±0.4 in term-born adults (p=0.01, Figure 1). Preterm-born adults had a similar LVEF versus term-born adults at rest (60.3±7.6 versus 62.1±4.5; p=0.19) though resting RVEF was lower in preterm-born adults (53.4±6.7 versus 55.9±4.5; p=0.05). LVEF increased by 6.5±5.5% in preterm-born adults and 10.9±6.0% in term-born adults from rest to 40% peak exercise (p<0.001), while RVEF increased by 9.2±6.3% in preterm-born adults versus 12.0±6.3% in term-born adults (p=0.06) (Figure 2). PCr/ATP associated with resting RVEF in preterm-born adults (R²=0.27, p=0.002), but was not associated with resting LVEF or the delta change in LVEF and RVEF with exercise stress. Conclusions Resting myocardial energetics is impaired in adults born preterm relative to term-born adults, with both the LV and RV demonstrating reduced functional reserve when challenged with low to moderate exercise stress. Metabolic modulators may help prevent progression to heart failure in preterm-born adults.Figure 1Figure 2

Improvement in cardiac function but not structure in adults born preterm following a prescribed moderate to high intensity exercise intervention: a randomized clinical trial

Abstract Background People born preterm (<37 weeks’ gestation) have a potentially adverse cardiac phenotype that progresses with blood pressure elevation and may explain their increased risk of early heart failure and cardiovascular-related mortality. It remains unknown whether lifestyle or pharmacological interventions lead to beneficial left ventricle (LV) and right ventricle (RV) structural and/or functional changes in preterm-born adults. Purpose To determine whether preterm-born adults with elevated and stage 1 hypertension exhibit similar cardiac remodelling following a 16-week aerobic exercise intervention as their term-born peers with comparable blood pressures. Methods We conducted an open, parallel, two-arm superiority randomised controlled (1:1) trial in n=203 adults aged 18-35 years old with elevated or stage 1 hypertension. Participants were randomised to a 16-week aerobic exercise intervention targeting three, 60-minute supervised sessions per week at 60-80% peak heart rate (exercise intervention) or sign-posted to educational materials (controls). In a pre-specified cardiovascular magnetic resonance imaging (CMR) sub-study in n=100 individuals, CMR was performed before and after the 16-week intervention. Group differences in outcome variables after the intervention were examined using ANCOVA adjusting for baseline outcome variables, sex, and age. Interactions between birth category and intervention effect were investigated by including an interaction term in the intervention ANCOVA analyses. Results One hundred participants completed CMR scans at baseline and after the 16-week intervention, with n=47 in the exercise intervention group (n=26 term-born; n=21 preterm-born) and n=53 controls (n=32 term-born; n=21 preterm-born). Cardiac structural measures in preterm-born adults did not change following the intervention. However, term-born adults in the exercise intervention group decreased LV mass to end-diastolic volume ratio (adjusted mean difference: -0.03, 95% CI: -0.06,-0.01, interaction term p=0.027) and increased RV stroke volume (adjusted mean difference: 5.53mL/m2, 95% CI: 2.60,8.47, interaction term p=0.076) versus controls. Preterm-born adults in the exercise intervention group increased LV basal- and mid-ventricular circumferential strain versus controls (adjusted mean difference: -1.33%, 95% CI: -2.07,-0.60, interaction term p=0.057 and adjusted mean difference: -1.54%, 95% CI: -2.46,-0.63, interaction term p=0.046, respectively), which was not observed in term-born adults. Similarly, preterm-born adults improved RV longitudinal strain versus controls (adjusted mean difference: -0.51%, 95% CI: -1.49,0.46, interaction term p=0.053), which was also not observed in term-born adults. Conclusions Aerobic exercise training improves myocardial function but not cardiac structure in preterm-born adults. Modified exercise protocols or combination with pharmacological intervention may lead to additional cardiac remodelling benefits.

Changes in social relationships from 26 to 34 years of age in adults born very preterm.

Very preterm and/or very low birthweight (VP/VLBW; <32 weeks' gestation and/or <1500 g birthweight) individuals rated their partner and peer relationships lower than term-born individuals in emerging adulthood, but their quality of relationships with parents has been rarely investigated. Moreover, it is unclear whether previously reported differences in social relationship characteristics persist or lessen from emerging to established adulthood. To investigate changes in social relationship characteristics in VP/VLBW adults compared to term-born adults from 26 to 34 years and whether the association between VP/VLBW and social relationship characteristics varies according to sex. In this prospective whole-population birth cohort study in South Bavaria, Germany, social relationship characteristics with parents, partners and peers, and overall social relationships across these domains were evaluated with a Life Course Interview at 26 and 34 years. Interview items related to these domains were extracted and scored as 0 (optimal) and 1 (non-optimal). Each score was summed into domain-specific composite scores and standardised according to the total sample. Participants included 262 VP/VLBW (52.7% males) and 230 term-born individuals (47.0% males). VP/VLBW adults had lower overall social relationship scores than term-born adults (β = -.61, 95% CI -0.85, -0.37). Specifically, partner (β = -.50, 95% CI-0.74, -0.27) and peer relationship scores (β = -.55, 95% CI-0.78, -0.32) were lower than those of term-born adults, but scores did not differ for parent relationships. On average, partner (β = .25, 95% CI 0.14, 0.35) and peer relationship scores increased (β = .16, 95% CI 0.03, 0.29), while parent relationship scores decreased (β = -.64, 95% CI-0.79, -0.49) from 26 to 34 years. These changes were similar for VP/VLBW and term-born individuals. Patterns of change for the improved partner and peer but worsening parental social relationship scores were common across VP/VLBW and term-born adults, but differences between the two groups persisted from 26 to 34 years.

The effect of very preterm birth on the Five-Factor Model of personality traits: A meta-analysis of individual participant data

There is mixed evidence on personality differences among those born very preterm or with very low birth weight (VP/VLBW). This meta-analysis of individual participant data aimed to examine differences in personality traits between VP/VLBW ( n = 568) and term-born ( n = 1,060) adults, and the role of neonatal characteristics and neurosensory impairments in childhood, which have not been previously investigated. Six studies were identified from two research consortia and a systematic search of the literature (PubMed and Scopus); studies were eligible if they included VP/VLBW and term-born adults followed from birth and assessed personality using the Five-Factor Model. Risk of bias (Newcastle-Ottawa Scale) was generally not a concern apart from the use of self-reported measures and the rate of follow-up. Using a one-stage approach, VP/VLBW scored lower on extraversion and openness and higher on neuroticism and agreeableness than term-born participants after adjusting for sex and parental education. Within the VP/VLBW group, those with bronchopulmonary dysplasia scored lower on extraversion and higher on neuroticism, with similar findings after removing participants with neurosensory impairments. Altogether, these findings suggest that a proportion of the effect of VP/VLBW birth on personality may be attributed to neonatal morbidities and altered brain development, although other confounding factors require further research.

Romantic and sexual relationships of young adults born very preterm: An individual participant data meta-analysis.

To compare romantic and sexual relationships between adults born very preterm (VP; <32 weeks of gestation) or with very low birth weight (VLBW; <1500 g) and at term, and to evaluate potential biological and environmental explanatory factors among VP/VLBW participants. This individual participant data (IPD) meta-analysis included longitudinal studies assessing romantic and sexual relationships in adults (mean sample age ≥ 18 years) born VP/VLBW compared with term-born controls. Following PRISMA-IPD guidelines, 11 of the 13 identified cohorts provided IPD from 1606 VP/VLBW adults and 1659 term-born controls. IPD meta-analyses were performed using one-stage approach. Individuals born VP/VLBW were less likely to be in a romantic relationship (OR 0.49; 95% CI 0.31-0.76), to be married/cohabiting (OR 0.70, 95% CI 0.53-0.92), or to have had sexual intercourse (OR 0.21, 95% CI 0.09-0.36) than term-born adults. If sexually active, VP/VLBW participants were more likely to experience their first sexual intercourse after the age of 18 years (OR 1.93, 95% CI 1.24-3.01) than term-born adults. Among VP/VLBW adults, males, and those with neurosensory impairment were least likely to experience romantic relationships. These findings reflect less optimal social functioning and may have implications for socioeconomic and health outcomes of adults born VP/VLBW.

Cardiac dysfunction during exercise in young adults with bronchopulmonary dysplasia.

Worldwide, 1-2% of children are born premature and at risk for developing bronchopulmonary dysplasia (BPD). Preterm-born adults are at risk for early cardiovascular disease. The role of BPD is unclear. This study aims to examine cardiorespiratory function during submaximal exercise in young adult survivors of extreme prematurity, with or without BPD. 40 preterm-born young adults, 20 with BPD (median gestational age 27 weeks, interquartile range (IQR) 26-28 weeks) and 20 without BPD (median gestational age 28 weeks, IQR 27-29 weeks) were prospectively compared to age-matched at term-born adults (median gestational age 39 weeks, IQR 38-40 weeks). Participants underwent exercise testing and cardiovascular magnetic resonance with submaximal exercise. Resting heart rate in BPD subjects was higher than in at term-born subjects (69±10 mL versus 61±7 mL, p=0.01). Peak oxygen uptake during maximal cardiopulmonary exercise testing was decreased in BPD subjects (91±18% versus 106±17% of predicted, p=0.01). In BPD subjects, cardiac stroke volume change with exercise was impaired compared to at term-born subjects (11±13% versus 25±10%; p<0.001). With exercise, left ventricular end-diastolic volume decreased more in preterm-born subjects with versus without BPD (-10±8% versus -3±8%; p=0.01) and compared to at term-born subjects (0±5%; p<0.001). Exploratory data analysis revealed that exercise stroke volume and end-diastolic volume change were inversely correlated with oxygen dependency in those born prematurely. In preterm-born young adults, particularly those with BPD, resting cardiac function, exercise performance and cardiac response to exercise is impaired compared to controls. Exercise cardiovascular magnetic resonance may reveal an important predisposition for heart disease later in life.

Impaired cerebrovascular CO2 reactivity at high altitude in prematurely born adults.

Premature birth impairs cardiac and ventilatory responses to both hypoxia and hypercapnia, but little is known about cerebrovascular responses. Both at sea level and after 2days at high altitude (3375m), 16 young preterm-born (gestational age, 29 ± 1weeks) and 15 age-matched term-born (40 ± 0weeks) adults were exposed to two consecutive 4min bouts of hyperoxic hypercapnic conditions (3% CO2 -97% O2 ; 6% CO2 -94% O2 ), followed by two periods of voluntary hyperventilation-induced hypocapnia. We measured middle cerebral artery blood velocity, end-tidal CO2 , pulmonary ventilation, beat-by-beat mean arterial pressure and arterialized capillary blood gases. Baseline middle cerebral artery blood velocity increased at high altitude compared with sea level in term-born (+24 ± 39%, P=0.036), but not in preterm-born (-4 ± 27%, P=0.278) adults. The end-tidal CO2 , pulmonary ventilation and mean arterial pressure were similar between groups at sea level and high altitude. Hypocapnic cerebrovascular reactivity was higher at high altitude compared with sea level in term-born adults (+173 ± 326%, P=0.026) but not in preterm-born adults (-21 ± 107%, P=0.572). Hypercapnic reactivity was altered at altitude only in preterm-born adults (+125 ± 144%, P<0.001). Collectively, at high altitude, term-born participants showed higher hypocapnic (P=0.012) and lower hypercapnic (P=0.020) CO2 reactivity compared with their preterm-born peers. In conclusion, exposure to high altitude revealed different cerebrovascular responses in preterm- compared with term-born adults, despite similar ventilatory responses. These findings suggest a blunted cerebrovascular response at high altitude in preterm-born adults, which might predispose these individuals to an increased risk of high-altitude illnesses. KEY POINTS: Cerebral haemodynamics and cerebrovascular reactivity in normoxia are known to be similar between term-born and prematurely born adults. In contrast, acute exposure to high altitude unveiled different cerebrovascular responses to hypoxia, hypercapnia and hypocapnia. In particular, cerebral vasodilatation was impaired in prematurely born adults, leading to an exaggerated cerebral vasoconstriction. Cardiovascular and ventilatory responses to both hypo- and hypercapnia at sea level and at high altitude were similar between control subjects and prematurely born adults. Other mechanisms might therefore underlie the observed blunted cerebral vasodilatory responses in preterm-born adults at high altitude.

Differing Impact of Preterm Birth on the Right and Left Atria in Adulthood.

Background Preterm birth affects 10% of live births and is associated with an altered left ventricular and right ventricular phenotype and increased cardiovascular disease risk in young adulthood. Because left atrial (LA) and right atrial (RA) volume and function are known independent predictors of cardiovascular outcomes, we investigated whether these were altered in preterm-born young adults. Methods and Results Preterm-born (n=200) and term-born (n=266) adults aged 18 to 39 years underwent cardiovascular magnetic resonance imaging. LA and RA maximal and minimal volumes (absolute, indexed to body surface area, and as a ratio to ventricular volumes) were obtained to study atrial morphology, while LA and RA stroke volume, strain, and strain rate were used to assess atrial function. Secondary analyses consisted of between-group comparisons based on degree of prematurity. Absolute RA volumes and RA volumes indexed to right ventricular volumes were significantly smaller in preterm-born compared with term-born adults. In addition, RA reservoir and booster strain were higher in preterm-born adults, possibly indicating functional compensation for the smaller RA volumes. LA volumes indexed to left ventricular volumes were significantly greater in preterm-born adults as compared with term-born adults, although absolute LA volumes were similar between groups. LA and RA changes were observed across gestational ages in the preterm group but were greatest in those born very-to-extremely preterm. Conclusions Preterm-born adults show changes in LA and RA structure and function, which may indicate subclinical cardiovascular disease. Further research into underlying mechanisms, opportunities for interventions, and their prognostic value is warranted.

Social Functioning in Adults Born Very Preterm: Individual Participant Meta-analysis.

There is a lack of research on individual perceptions of social experiences and social relationships among very preterm (VP) adults compared with term-born peers. To investigate self-perceived social functioning in adults born VP (<32 weeks' gestation) and/or with very low birth weight (VLBW) (<1500g) compared with term-born adults (≥37 weeks' gestation) using an individual participant data (IPD) meta-analysis. Two international consortia: Research on European Children and Adults born Preterm and Adults Born Preterm International Collaboration. Cohorts with outcomes assessed by using the Adult Self-Report Adaptive Functioning scales (friends, spouse/partner, family, job, and education) in both groups. IPD from 5 eligible cohorts were collected. Raw-sum scores for each scale were standardized as z scores by using mean and SD of controls for each cohort. Pooled effect size was measured by difference (Δ) in means between groups. One-stage analyses (1285 participants) revealed significantly lower scores for relationships with friends in VP/VLBW adults compared with controls (Δ -0.37, 95% confidence interval [CI]: -0.61 to -0.13). Differences were similar after adjusting for sex, age, and socioeconomic status (Δ -0.39, 95% CI: -0.63 to -0.15) and after excluding participants with neurosensory impairment (Δ -0.34, 95% CI: -0.61 to -0.07). No significant differences were found in other domains. Generalizability of research findings to VP survivors born in recent decades. VP/VLBW adults scored their relationship with friends lower but perceived their family and partner relationships, as well as work and educational experiences, as comparable to those of controls.

Association of Preterm Birth With Myocardial Fibrosis and Diastolic Dysfunction in Young Adulthood

BackgroundPreterm birth affects about 10% of live births worldwide and is associated with cardiac alterations. Animal models of preterm birth suggest that left ventricular functional impairment may be due to an up-regulation of myocardial fibrosis. ObjectivesThe aim of this study was to determine whether diffuse left ventricular fibrosis is evident in young adults born preterm. MethodsOne hundred one normotensive young adults born preterm (n = 47, mean gestational age 32.8 ± 3.2 weeks) and term (n = 54) were included from YACHT (Young Adult Cardiovascular Health sTudy). Left ventricular structure and function were quantified by cardiovascular magnetic resonance and echocardiography. Intravenous administration of a gadolinium-based contrast agent during cardiovascular magnetic resonance was used to quantify focal myocardial fibrosis on the basis of late gadolinium enhancement and, in combination with T1 mapping, to quantify diffuse myocardial fibrosis on the basis of assessment of myocardial extracellular volume fraction. ResultsAdults born preterm had smaller left ventricular end-diastolic and stroke volumes, with greater left ventricular mass and wall thickness (P < 0.001). In addition, longitudinal peak systolic strain and diastolic strain rate by both cardiovascular magnetic resonance and echocardiography, and E/A ratio measured by echocardiography, were lower in preterm-born compared to term-born adults (P < 0.05). Extracellular volume fraction was greater in preterm-born compared with term-born adults (27.81% ± 1.69% vs 25.48% ± 1.41%; P < 0.001) and was a significant mediator in the relationship between gestational age and both longitudinal peak diastolic strain rate and E/A ratio. ConclusionsPreterm-born young adults have greater extracellular volume fraction in the left ventricle that is inversely related with gestational age and may underlie their diastolic functional impairments.

Aberrant Claustrum Microstructure in Humans after Premature Birth.

Several observations suggest an impact of prematurity on the claustrum. First, the claustrum's development appears to depend on transient subplate neurons of intra-uterine brain development, which are affected by prematurity. Second, the claustrum is the most densely connected region of the mammalian forebrain relative to its volume; due to its effect on pre-oligodendrocytes, prematurity impacts white matter connections and thereby the development of sources and targets of such connections, potentially including the claustrum. Third, due to its high connection degree, the claustrum contributes to general cognitive functioning (e.g., selective attention and task switching/maintaining); general cognitive functioning, however, is at risk in prematurity. Thus, we hypothesized altered claustrum structure after premature birth, with these alterations being associated with impaired general cognitive performance in premature born persons. Using T1-weighted and diffusion-weighted magnetic resonance imaging in 70 very preterm/very low-birth-weight (VP/VLBW) born adults and 87 term-born adults, we found specifically increased mean diffusivity in the claustrum of VP/VLBW adults, associated both with low birth weight and at-trend with reduced IQ. This result demonstrates altered claustrum microstructure after premature birth. Data suggest aberrant claustrum development, which is potentially related with aberrant subplate neuron and forebrain connection development of prematurity.

Association of Systolic Blood Pressure Elevation With Disproportionate Left Ventricular Remodeling in Very Preterm-Born Young Adults

Preterm-born individuals have higher blood pressure with an increased risk of hypertension by young adulthood, as well as potentially adverse cardiac remodeling even when normotensive. To what extent blood pressure elevation affects left ventricular (LV) structure and function in adults born preterm is currently unknown. To investigate whether changes observed in LV structure and function in preterm-born adults make them more susceptible to cardiac remodeling in association with blood pressure elevation. This cross-sectional cohort study, conducted at the Oxford Cardiovascular Clinical Research Facility and Oxford Centre for Clinical Magnetic Resonance Research, included 468 adults aged 18 to 40 years. Of these, 200 were born preterm (<37 weeks' gestation) and 268 were born at term (≥37 weeks' gestation). Cardiac magnetic resonance imaging was used to characterize LV structure and function, with clinical blood pressure readings measured to assess hypertension status. Demographic and anthropometric data, as well as birth history and family medical history information, were collected. Data were analyzed between January 2012 and February 2021. Cardiac magnetic resonance measures of LV structure and function in response to systolic blood pressure elevation. The cohort was primarily White (>95%) with a balanced sex distribution (51.5% women and 48.5% men). Preterm-born adults with and without hypertension had higher LV mass index, reduced LV function, and smaller LV volumes compared with term-born individuals both with and without hypertension. In regression analyses of systolic blood pressure with LV mass index and LV mass to end-diastolic volume ratio, there was a leftward shift in the slopes in preterm-born compared with term-born adults. Compared with term-born adults, there was a 2.5-fold greater LV mass index per 1-mm Hg elevation in systolic blood pressure in very and extremely preterm-born adults (<32 weeks' gestation) (0.394 g/m2 vs 0.157 g/m2 per 1 mm Hg; P < .001) and a 1.6-fold greater LV mass index per 1-mm Hg elevation in systolic blood pressure in moderately preterm-born adults (32 to 36 weeks' gestation) (0.250 g/m2 vs 0.157 g/m2 per 1 mm Hg; P < .001). The LV mass to end-diastolic volume ratio per 1-mm Hg elevation in systolic blood pressure in the very and extremely preterm-born adults was 3.4-fold greater compared with those born moderately preterm (3.56 × 10-3 vs 1.04 × 10-3 g/mL per 1 mm Hg; P < .001) and 3.3-fold greater compared with those born at term (3.56 × 10-3 vs 1.08 × 10-3 g/mL per 1 mm Hg; P < .001). Preterm-born adults have a unique LV structure and function that worsens with systolic blood pressure elevation. Additional primary prevention strategies specifically targeting cardiovascular risk reduction in this population may be warranted.

Increased mitochondrial oxygen consumption in adult survivors of preterm birth.

Background:Premature birth affects roughly 10% of live births and is associated with long-term increased risk for multiple comorbidities. Though many comorbidities are associated with increased oxidative stress, the potential late impact of extreme premature birth on mitochondrial function has not previously been assessed. We hypothesized that mitochondrial function would be impaired in adult survivors of premature birth.Methods:Mitochondrial function in peripheral blood mononuclear cells from young adults born moderately to extremely preterm was measured using a Seahorse XF Analyzer at baseline and in response to acute oxidative stress, and compared to age-matched term-born adults. Adult pulmonary function was also obtained.Results:Young adults born preterm (average gestational age 29 weeks) had increased mitochondrial oxygen consumption at baseline, particularly with respect to basal and non-ATP linked respiration. Maximal and spare capacity were also higher, even in response to acute oxidative stress. Lung function was lower in adults born preterm, and the degree of airflow obstruction correlated only modestly with mitochondrial function.Conclusion:In conclusion, adults born preterm have higher basal and non-ATP linked mitochondrial respiration. Similar mitochondrial profiles have previously been documented in diabetics, and may support the increased risk for cardiometabolic disease in adults born preterm.

Birth weight and heart rate autonomic recovery following exercise in healthy term-born adults

The impact of birth weight (BW) on adult health has been studied, related to the autonomic nervous system, and implicated in cardiovascular risk. We investigated cardiorespiratory and heart rate (HR) autonomic recovery after moderate effort in healthy term-born adults with different BWs. We studied 28 healthy physically active women aged between 18 to 30 years split equally into two groups according to BW: G1 (n = 14), BW between 2500 g and 3200 g and G2 (n = 14), BW > 3200 g. The groups remained seated at rest for 15 min, followed by aerobic exercise on a treadmill (five minutes at 50–55% of maximum HR and 25 min 60–65% of maximum HR) and then remained seated for 60 min during recovery from the exercise. Cardiorespiratory parameters and HR variability (HRV) [RMSSD, HF (ms2)] were assessed before and during recovery from exercise. In G1, HR was increased from 0 to 20 min after exercise whilst in G2 HR was higher from 0 to 7 min following exercise. In G1, short-term HRV was increased from 5 to 10 min after exercise but in G2 it recovered prior to 5 min following effort. In conclusion, healthy term-born women with low normal BW present slower HR autonomic recovery after exercise.

Right ventricular morphology and function analysis in moderately preterm-born young adults

Abstract Background Previous studies have shown that prematurity leads to altered right ventricular (RV) geometry and performance with persistent impairments in RV systolic function in young adulthood. It is unknown to what extent pulmonary physiology impacts these findings. Purpose To better quantify known alterations in RV morphology and function in preterm-born young adults and to determine to what extent these changes are influenced by the pulmonary circulation. Methods A total of 101 normotensive preterm-born (n=47, mean gestational age 32.8±3.2 weeks) and term-born (n=54) young adults were recruited. Echocardiography and cardiovascular magnetic resonance (CMR) imaging were performed to characterise RV morphology, RV function, pulmonary hemodynamics and RV-pulmonary arterial vascular (PA) coupling. CMR cine images were used to create a 3D computational atlas of the RV geometry and principal component analysis was undertaken to identify the key modes of shape variation. Spirometry was performed to assess lung function. Results RV CMR revealed a higher absolute and indexed RV mass (P&amp;lt;0.05) and lower ejection fraction (54.90±5.17 versus 57.48±4.39%, P=0.008) in young adults born preterm. RV end-diastolic areas and volumes for CMR and echocardiography were lower in preterm-born compared to term-born young adults (P≤0.001). Principal component analysis of the computational atlas defined the anatomical modes of the RV geometry, with mode 1 accounting for 25.3% of the population variance. Preterm and term cohorts showed significant differences (P&amp;lt;0.001) in mode 1, which represented a smaller and shorter RV cavity in the preterm group (Figure 1). Measurements of RV function by echocardiography, including RV fractional area of change (FAC) and tricuspid annular plane systolic excursion (TAPSE), were lower in preterm-born compared to term-born adults (P&amp;lt;0.05). Despite lower pulmonary artery acceleration times (PAAT) in those born preterm (141.1±15.1 versus 159.2±21.6msec, P&amp;lt;0.001), indicating increased pulmonary vascular resistance, the RV remained coupled to its pulmonary circulation (TAPSE/PAAT: 0.13±0.02 versus 0.14±0.03m/sec, P=0.153). Reduced RV performance in preterm-born individuals remained significant when adjusting for pulmonary function parameters (P&amp;lt;0.05). Conclusions Multimodality cardiac imaging demonstrated that moderately preterm-born young adults exhibit structural and functional RV alterations, independent of lung physiology. Their RV remains hemodynamically coupled to its pulmonary circulation despite higher RV afterload, lower RV function and altered morphology. Figure 1. Statistical shape model of the RV Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): British Heart Foundation

Early Motor Trajectories Predict Motor but not Cognitive Function in Preterm- and Term-Born Adults without Pre-existing Neurological Conditions.

Very preterm (VP; <32 weeks gestation) and/or very low birth weight (VLBW; <1500 g) birth has been associated with an increased risk of adverse motor and cognitive outcomes that may persist into adulthood. The aim of this study was to determine whether motor development in the first five years of life is associated with motor and cognitive outcomes in adulthood. A prospective observational study in Germany followed 260 VP/VLBW and 229 term-born individuals from birth into adulthood. Early motor trajectories (i.e., high and low degree of motor difficulties) were determined from neurological examinations from birth to 56 months. Adult motor and cognitive outcomes were determined from information from multiple instruments and IQ tests, respectively. Associations of VP/VLBW birth and early motor difficulties on adult outcomes were assessed using regression analyses. VP/VLBW individuals had an increased risk for early motor difficulties (Relative Risk: 11.77, 95% confidence interval (CI): 4.28, 32.35). Early motor difficulties were associated with poorer motor competence in adulthood (β = 0.22, p < 0.001), independent of VP/VLBW birth. Adult IQ was predicted by VP/VLBW (β = −0.12, p < 0.05) and child IQ (β = 0.51, p < 0.001), while early motor difficulties ceased to be associated with adult IQ once participants with a neurological impairment were excluded (β = 0.02, p > 0.05). Motor problems in childhood were homotypically associated with poorer motor competence in adulthood. Similarly, early cognitive problems were homotypically associated with adult cognitive outcomes. Thus, both motor and cognitive function should be assessed in routine follow-up during childhood.

Biomarkers of ageing in New Zealand VLBW young adults and controls.

There is individual variation in physiological ageing. Former very low birthweight (VLBW; birthweight < 1500 g) young adults may have less satisfactory measurements on some physiological parameters than term controls. We hypothesized that a summation score of physiological biomarkers that change with age would show VLBW adults to have a more advanced physiologic age than controls. VLBW adults (229; 71% survivors of a national VLBW cohort) and term-born controls (100) were clinically assessed at 26-30 years. Ten measured physiological biomarkers were selected and measurements converted to z-scores using normative reference data. Between-group comparisons were tested for statistical significance for individual biomarker z-scores and a summation score. Nine of 10 biomarkers showed a mean z-score suggestive of older physiological age in the VLBW group versus controls. The observed mean difference in the summation score was highly significant (p < 0.001), representing a mean shift of 0.47 SD in the distribution of test scores for VLBW relative to controls. Utilizing a 10-biomarker score, VLBW young adults have a score indicative of poorer physiological functioning than term-born controls. Repeating these measures after an interval could provide insights into the comparative pace of ageing between VLBW and term-born adults. A summation score of 10 physiological biomarkers that are known to change with age shows that former very low birthweight adults have significantly poorer physiological functioning by the end of their third decade than term-born controls. This result adds to existing literature showing very preterm and very low birthweight young adults often have physiological and metabolic test results that are less satisfactory than those from term controls, despite mostly being in the normal range for age; for instance, higher systolic blood pressure. Although the pace of ageing in later years is yet to be established, the implications of this study are that preventative measures and lifestyle choices that impact on physiological ageing might have even greater importance for very preterm and very low birthweight graduates.

Quality of life of adults born very preterm or very low birth weight: A systematic review.

AimTo establish differences in health‐related quality of life (HRQoL) in adults born term and those born very preterm (VPT) and/or with a very low birth weight (VLBW).MethodsOur systematic review is preregistered under PROSPERO‐ID CRD42018084005. Studies were eligible for inclusion if their authors had stated the HRQoL of adults (18 years or older) born VPT (<32 weeks of gestation) or VLBW (<1500 g of birth weight) had been measured, if written in English, and if they reported a comparison with a control group or valid norms. We searched Pubmed, Scopus, Psycinfo, Web of Science, Embase and contacted experts in this field. Non‐response and other bias‐related problems were evaluated.ResultsWe included 18 studies of 15 unique cohorts from 11 countries. In 11 studies, no differences in HRQoL between VPT or VLBW and term‐born adults were found; four studies found lower HRQoL in VPT/VLB adults; and evidence from three studies was inconclusive. Disability, sex and age were associated with HRQoL.ConclusionThere is no conclusive evidence that HRQoL differs between term‐born adults and those born VPT or with a VLBW. The comparability of studies was restricted by differences between HRQoL measurements, age ranges at assessment and definition of disability.

An analysis of MRI derived cortical complexity in premature-born adults: Regional patterns, risk factors, and potential significance

Premature birth bears an increased risk for aberrant brain development concerning its structure and function. Cortical complexity (CC) expresses the fractal dimension of the brain surface and changes during neurodevelopment. We hypothesized that CC is altered after premature birth and associated with long-term cognitive development.One-hundred-and-one very premature-born adults (gestational age <32 weeks and/or birth weight <1500 ​g) and 111 term-born adults were assessed by structural MRI and cognitive testing at 26 years of age. CC was measured based on MRI by vertex-wise estimation of fractal dimension. Cognitive performance was measured based on Griffiths-Mental-Development-Scale (at 20 months) and Wechsler-Adult-Intelligence-Scales (at 26 years).In premature-born adults, CC was decreased bilaterally in large lateral temporal and medial parietal clusters. Decreased CC was associated with lower gestational age and birth weight. Furthermore, decreased CC in the medial parietal cortices was linked with reduced full-scale IQ of premature-born adults and mediated the association between cognitive development at 20 months and IQ in adulthood.Results demonstrate that CC is reduced in very premature-born adults in temporoparietal cortices, mediating the impact of prematurity on impaired cognitive development. These data indicate functionally relevant long-term alterations in the brain’s basic geometry of cortical organization in prematurity.

Preterm Birth as a Risk Factor for Metabolic Syndrome and Cardiovascular Disease in Adult Life: A Systematic Review and Meta-Analysis

To determine if preterm birth is associated with components of the metabolic syndrome in adult life. A structured literature search was performed using PubMed. All comparative studies reported metabolic and cardiovascular outcomes in adults (≥18years of age) born preterm (<37weeks of gestation) compared with adults born at term (37-42weeks of gestation) and published through March 2018 were included. The major outcomes assessed were body mass index, waist circumference, waist-to-hip ratio, fat mass, systolic blood pressure (SBP), diastolic blood pressure (DBP), 24-hour SBP, 24-hour DBP, endothelium-dependent brachial artery flow-mediated dilation, carotid intima-media thickness, pulse wave velocity, fasting glucose and insulin, Homeostasis Model Assessment-Estimated Insulin Resistance Index, and lipid profiles. Quality appraisal was performed using a modified version of the Newcastle-Ottawa scale. A meta-analysis was performed for comparable studies which reported sufficient data. Forty-three studies were included, including a combined total of 18 295 preterm and 294 063 term-born adults. Prematurity was associated with significantly higher fat mass (P=.03), SBP (P<.0001), DBP (P<.0001), 24-hour SBP (P<.001), and 24-hour DBP (P<.001). Furthermore, preterm-born adults presented higher values of fasting glucose (P=.01), insulin (P=.002), Homeostasis Model Assessment-Estimated Insulin Resistance Index (P=.05), and total cholesterol levels (P=.05) in comparison with adults born at term, in random effect models. No statistically significant difference was found between preterm and term-born adults for the other outcomes studied. Preterm birth is strongly associated with a number of components of the metabolic syndrome and cardiovascular disease in adult life.