Special Issue "Clinical Research into the Cardiovascular Health of People Born Preterm"

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Cardiology".

Deadline for manuscript submissions: closed (30 September 2021).

Special Issue Editor

Dr. Adam J. Lewandowski
E-Mail Website
Guest Editor
Oxford Cardiovascular Clinical Research Facility, Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK
Interests: developmental biology; pregnancy complications; cardiovascular prevention; systems physiology; medical imaging

Special Issue Information

Dear Colleagues,

Preterm birth affects around 10% of births worldwide, with overall neonatal survival rates >90% due to advances in perinatal clinical care over recent decades. As a result, a new generation of preterm-born survivors is now reaching adulthood, including those born at less than 25 weeks’ gestation. In addition to numerous acute complications, epidemiological studies have identified preterm birth as an independent risk factor for cardiovascular diseases across gestational age categories, including hypertension, early heart failure, and ischaemic heart disease. Clinical research studies have revealed that preterm birth associates with changes in the vasculature, pulmonary system, and morphology and function of the heart, which may put them at increased risk of long-term cardiovascular disease development. Many of these alterations are observed as early as infancy and continue to be seen into adulthood. While the underlying pathophysiological mechanisms remain unclear, there are a number of factors to consider, including altered angiogenesis, disruptions to the renin­–angiotensin system, and reduced cardiac and vascular endowment.

In this Special Issue of the Journal of Clinical Medicine, the aim is to bring together some of the latest cardiovascular research in the field, building on previous findings in people born preterm. Submitted articles can investigate either the short-term (neonates and infants) or the long-term (children, adolescents and adults) cardiovascular health of preterm-born individuals, or both if applicable.

I look forward to receiving your submission.

Dr. Adam J. Lewandowski
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Clinical Medicine is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2400 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • preterm birth
  • prematurity
  • cardiovascular disease
  • cardiovascular risk
  • hypertension
  • vascular stiffness
  • pulmonary hypertension

Published Papers (12 papers)

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Research

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Article
Right Ventricular Structure and Function in Young Adults Born Preterm at Very Low Birth Weight
J. Clin. Med. 2021, 10(21), 4864; https://doi.org/10.3390/jcm10214864 - 22 Oct 2021
Viewed by 345
Abstract
Being born preterm (PT, <37 weeks gestation) or at very low birth weight (VLBW, <1500 g) is associated with increased rates of cardiopulmonary disorders in childhood. As survivors age, late cardiac effects, including right ventricular (RV) remodelling and occult pulmonary hypertension are emerging. [...] Read more.
Being born preterm (PT, <37 weeks gestation) or at very low birth weight (VLBW, <1500 g) is associated with increased rates of cardiopulmonary disorders in childhood. As survivors age, late cardiac effects, including right ventricular (RV) remodelling and occult pulmonary hypertension are emerging. In this population-based study, we aimed to investigate right heart structure and function in young adults born PT at VLBW compared to normal-weight term-born controls. The New Zealand VLBW Study has followed all infants born in 1986 with birth weight <1500 g. All were born preterm from 24 to 37 weeks. A total of 229 (71% of survivors) had echocardiograms aged 26–30 years which were compared to age-matched, term-born, normal-weight controls (n = 100). Young adults born preterm at very low birth weight exhibited smaller RV dimensions compared to term-born peers. Standard echocardiographic measures of RV function did not differ, but mildly reduced function was detected by RV longitudinal strain. This difference was related to birth weight and gestational age but not lung function or left ventricular function. Echocardiographic strain imaging may be an important tool to detect differences in RV function preterm and VLBW. Full article
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Article
Safety, Feasibility, and Impact of Enalapril on Cardiorespiratory Physiology and Health in Preterm Infants with Systemic Hypertension and Left Ventricular Diastolic Dysfunction
J. Clin. Med. 2021, 10(19), 4519; https://doi.org/10.3390/jcm10194519 - 29 Sep 2021
Viewed by 478
Abstract
Neonatal hypertension has been increasingly recognized in premature infants with bronchopulmonary dysplasia (BPD); of note, a sub-population of these infants may have impaired left ventricular (LV) diastolic function, warranting timely treatment to minimize long term repercussions. In this case series, enalapril, an angiotensin-converting [...] Read more.
Neonatal hypertension has been increasingly recognized in premature infants with bronchopulmonary dysplasia (BPD); of note, a sub-population of these infants may have impaired left ventricular (LV) diastolic function, warranting timely treatment to minimize long term repercussions. In this case series, enalapril, an angiotensin-converting enzyme (ACE) inhibitor, was started in neonates with systemic hypertension and echocardiography signs of LV diastolic dysfunction. A total of 11 patients were included with birth weight of 785 ± 239 grams and gestational age of 25.3 (24, 26.1) weeks. Blood pressure improvement was noticed within 2 weeks of treatment. Improvement in LV diastolic function indices were observed with a reduction in Isovolumic Relaxation Time (IVRT) from 63.1 ± 7.2 to 50.9 ± 7.4 msec and improvement in the left atrium size indexed to aorta (LA:Ao) from1.73 (1.43, 1.88) to 1.23 (1.07, 1.29). Neonatal systemic hypertension is often underappreciated in ex-preterm infants and may be associated with important maladaptive cardiac changes with long term implications. It is biologically plausible that identifying and treating LV diastolic dysfunction in neonates with systemic hypertension may have a positive modulator effect on cardiovascular health in childhood and beyond. Full article
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Article
Discriminant Analysis of Main Prognostic Factors Associated with Hemodynamically Significant PDA: Apgar Score, Silverman–Anderson Score, and NT-Pro-BNP Level
J. Clin. Med. 2021, 10(16), 3729; https://doi.org/10.3390/jcm10163729 - 22 Aug 2021
Viewed by 831
Abstract
Hemodynamically significant patent ductus arteriosus (hsPDA) in premature newborns is associated with a risk of PDA-related morbidities. Classification into risk groups may have a clinical utility in cases of suspected hsPDA to decrease the need for echocardiograms and unnecessary treatment. This prospective observational [...] Read more.
Hemodynamically significant patent ductus arteriosus (hsPDA) in premature newborns is associated with a risk of PDA-related morbidities. Classification into risk groups may have a clinical utility in cases of suspected hsPDA to decrease the need for echocardiograms and unnecessary treatment. This prospective observational study included 99 premature newborns with extremely low body weight, who had an echocardiogram performed within the first three days of life. Discriminant analysis was utilized to find the best combination of prognostic factors for evaluation of hsPDA. We used binary logistic regression analysis to predict the relationship between parameters and hsPDA. The cohort’s mean and standard deviation gestational age was 27.6 ± 2.55 weeks, the mean birth weight was 1015 ± 274 g. Forty-six (46.4%) infants had a PDA with a mean diameter of 2.78 mm. Median NT-pro-BNP levels were 17,600 pg/mL for infants with a PDA and 2773 pg/mL in the non-hsPDA group. The combination of prognostic factors of hsPDA in newborns of extremely low body weight on the third day of life was determined: NT-pro-BNP, Apgar score, Silverman–Anderson score (Se = 82%, Sp = 88%). A cut-off value of NT-pro-BNP of more than 8500 pg/mL can predict hsPDA (Se = 84%, Sp = 86%). Full article
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Article
Association between Neonatal Intakes and Hyperglycemia, and Left Heart and Aortic Dimensions at 6.5 Years of Age in Children Born Extremely Preterm
J. Clin. Med. 2021, 10(12), 2554; https://doi.org/10.3390/jcm10122554 - 09 Jun 2021
Viewed by 793
Abstract
Survivors of extremely preterm birth (gestational age < 27 weeks) have been reported to exhibit an altered cardiovascular phenotype in childhood. The mechanisms are unknown. We investigated associations between postnatal nutritional intakes and hyperglycemia, and left heart and aortic dimensions in children born [...] Read more.
Survivors of extremely preterm birth (gestational age < 27 weeks) have been reported to exhibit an altered cardiovascular phenotype in childhood. The mechanisms are unknown. We investigated associations between postnatal nutritional intakes and hyperglycemia, and left heart and aortic dimensions in children born extremely preterm. Postnatal nutritional data and echocardiographic dimensions at 6.5 years of age were extracted from a sub-cohort of the Extremely Preterm Infants in Sweden Study (EXPRESS; children born extremely preterm between 2004–2007, n = 171, mean (SD) birth weight = 784 (165) grams). Associations between macronutrient intakes or number of days with hyperglycemia (blood glucose > 8 mmol/L) in the neonatal period (exposure) and left heart and aortic dimensions at follow-up (outcome) were investigated. Neonatal protein intake was not associated with the outcomes, whereas higher lipid intake was significantly associated with larger aortic root diameter (B = 0.040, p = 0.009). Higher neonatal carbohydrate intake was associated with smaller aorta annulus diameter (B = −0.016, p = 0.008). Longer exposure to neonatal hyperglycemia was associated with increased thickness of the left ventricular posterior wall (B = 0.004, p = 0.008) and interventricular septum (B = 0.004, p = 0.010). The findings in this study indicate that postnatal nutrition and hyperglycemia may play a role in some but not all long-lasting developmental adaptations of the cardiovascular system in children born extremely preterm. Full article
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Article
Left Ventricle Phenotyping Utilizing Tissue Doppler Imaging in Premature Infants with Varying Severity of Bronchopulmonary Dysplasia
J. Clin. Med. 2021, 10(10), 2211; https://doi.org/10.3390/jcm10102211 - 20 May 2021
Viewed by 757
Abstract
Bronchopulmonary dysplasia (BPD) is characterized by alveolar-capillary simplification and is associated with pulmonary hypertension (PH) in preterm infants. The contribution of left ventricle (LV) disease towards this severe BPD-PH phenotype is not well established. We aimed to describe the longitudinal trajectory of the [...] Read more.
Bronchopulmonary dysplasia (BPD) is characterized by alveolar-capillary simplification and is associated with pulmonary hypertension (PH) in preterm infants. The contribution of left ventricle (LV) disease towards this severe BPD-PH phenotype is not well established. We aimed to describe the longitudinal trajectory of the LV function as measured by tissue Doppler imaging (TDI) and its association with BPD-PH. We retrospectively assessed prospectively acquired clinical and echocardiographic data from 77 preterm infants born between 2011 and 2013. We characterized the LV function by measuring systolic and diastolic myocardial velocities (s’, e’, a’), isovolumetric relaxation time (IVRT), and myocardial performance index with TDI at three time periods from 32 and 36 weeks, postmenstrual age through one year of age. We also measured post systolic motion (PSM), a marker of myocardial dysfunction that results from asynchronous movement of the ventricular walls, and not previously described in preterm infants. Patients were stratified into groups according to BPD severity and the presence of PH and compared over time. Conventional TDI measures of the LV function were similar between groups, but the septal PSM was significantly prolonged over the first year of age in patients with BPD-PH. PSM provides a novel objective way to assess the hemodynamic impact of lung and pulmonary vascular disease severity on LV function in preterm infants with BPD and PH. Full article
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Article
Left Ventricle Structure and Function in Young Adults Born Very Preterm and Association with Neonatal Characteristics
J. Clin. Med. 2021, 10(8), 1760; https://doi.org/10.3390/jcm10081760 - 18 Apr 2021
Cited by 4 | Viewed by 813
Abstract
Preterm birth increases risk of cardiovascular disease and early death. A body of evidence suggests left ventricle (LV) echocardiographic alterations in children and adults born preterm. We aimed to determine if neonatal characteristics were associated with alterations in LV structure and function in [...] Read more.
Preterm birth increases risk of cardiovascular disease and early death. A body of evidence suggests left ventricle (LV) echocardiographic alterations in children and adults born preterm. We aimed to determine if neonatal characteristics were associated with alterations in LV structure and function in preterm adults. We evaluated a cohort of 86 young adults born preterm below 30 weeks of gestation, and 85 full-term controls. We determined LV dimensions and function using tissue Doppler imaging, conventional and speckle tracking echocardiography (STE). Adults born preterm had smaller LV dimensions, but these differences did not remain after adjustment for body surface area (BSA), which was smaller in the preterm group. Stroke volume and cardiac output were reduced even after adjustment for BSA. We found a smaller e’ wave in the preterm group, but other markers of systolic and diastolic function did not differ. Use of antenatal steroids may be associated with a further reduced cardiac output in those born preterm. Adults born preterm show alterations in markers of LV dimensions and function. Identification of these markers may represent opportunities for early prevention of cardiovascular events in this at-risk population. Full article
Article
Dynamic FDG PET Imaging to Probe for Cardiac Metabolic Remodeling in Adults Born Premature
J. Clin. Med. 2021, 10(6), 1301; https://doi.org/10.3390/jcm10061301 - 22 Mar 2021
Viewed by 716
Abstract
Individuals born very premature have an increased cardiometabolic and heart failure risk. While the structural differences of the preterm heart are now well-described, metabolic insights into the physiologic mechanisms underpinning this risk are needed. Here, we used dynamic fluorodeoxyglucose (FDG) positron emission tomography/magnetic [...] Read more.
Individuals born very premature have an increased cardiometabolic and heart failure risk. While the structural differences of the preterm heart are now well-described, metabolic insights into the physiologic mechanisms underpinning this risk are needed. Here, we used dynamic fluorodeoxyglucose (FDG) positron emission tomography/magnetic resonance imaging (PET-MRI) in young adults born term and preterm during normoxic (N = 28 preterm; 18 term) and hypoxic exposure (12% O2; N = 26 preterm; 17 term) to measure the myocardial metabolic rate of glucose (MMRglc) in young adults born term (N = 18) and preterm (N = 32), hypothesizing that young adults born preterm would have higher rates of MMRglc under normoxic conditions and a reduced ability to augment glucose metabolism under hypoxic conditions. MMRglc was calculated from the myocardial and blood pool time-activity curves by fitting the measured activities to the 3-compartment model of FDG kinetics. MMRglc was similar at rest between term and preterm subjects, and decreased during hypoxia exposure in both groups (p = 0.02 for MMRglc hypoxia effect). There were no differences observed between groups in the metabolic response to hypoxia, either globally (serum glucose and lactate measures) or within the myocardium. Thus, we did not find evidence of altered myocardial metabolism in the otherwise healthy preterm-born adult. However, whether subtle changes in myocardial metabolism may preceed or predict heart failure in this population remains to be determined. Full article
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Article
The Preterm Heart-Brain Axis in Young Adulthood: The Impact of Birth History and Modifiable Risk Factors
J. Clin. Med. 2021, 10(6), 1285; https://doi.org/10.3390/jcm10061285 - 19 Mar 2021
Viewed by 934
Abstract
People born preterm are at risk of developing both cardiac and brain abnormalities. We aimed to investigate whether cardiovascular physiology may directly affect brain structure in young adulthood and whether cardiac changes are associated with modifiable biomarkers. Forty-eight people born preterm, followed since [...] Read more.
People born preterm are at risk of developing both cardiac and brain abnormalities. We aimed to investigate whether cardiovascular physiology may directly affect brain structure in young adulthood and whether cardiac changes are associated with modifiable biomarkers. Forty-eight people born preterm, followed since birth, underwent cardiac MRI at age 25.1 ± 1.4 years and brain MRI at age 33.4 ± 1.0 years. Term born controls were recruited at both time points for comparison. Cardiac left and right ventricular stroke volume, left and right ventricular end diastolic volume and right ventricular ejection fraction were significantly different between preterm and term born controls and associated with subcortical brain volumes and fractional anisotropy in the corpus callosum in the preterm group. This suggests that cardiovascular abnormalities in young adults born preterm are associated with potentially adverse future brain health. Associations between left ventricular stroke volume indexed to body surface area and right putamen volumes, as well as left ventricular end diastolic length and left thalamus volumes, remained significant when adjusting for early life factors related to prematurity. Although no significant associations were found between modifiable biomarkers and cardiac physiology, this highlights that cardiovascular health interventions may also be important for brain health in preterm born adults. Full article
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Article
Exaggerated Cardiac Contractile Response to Hypoxia in Adults Born Preterm
J. Clin. Med. 2021, 10(6), 1166; https://doi.org/10.3390/jcm10061166 - 10 Mar 2021
Cited by 1 | Viewed by 752
Abstract
Individuals born prematurely have smaller hearts, cardiac limitations to exercise, and increased overall cardiometabolic risk. The cardiac effects of acute hypoxia exposure as another physiologic stressor remain under explored. The purpose of this study was to determine the effects of hypoxia on ventricular [...] Read more.
Individuals born prematurely have smaller hearts, cardiac limitations to exercise, and increased overall cardiometabolic risk. The cardiac effects of acute hypoxia exposure as another physiologic stressor remain under explored. The purpose of this study was to determine the effects of hypoxia on ventricular function in adults born preterm. Adults born moderately to extremely preterm (≤32 weeks gestation or <1500 g, N = 32) and born at term (N = 18) underwent cardiac magnetic resonance imaging under normoxic (21% O2) and hypoxic (12% O2) conditions to assess cardiovascular function. In normoxia, cardiac function parameters were similar between groups. During hypoxia, the right ventricular (RV) contractile response was significantly greater in participants born premature, demonstrated by greater increases in RV ejection fraction (EF) (p = 0.002), ventricular-vascular coupling (VVC) (p = 0.004), and strain (p < 0.0001) measures compared to term-born participants, respectively. Left ventricular contractile reserve was similar to term-born participants. Adults born preterm exhibit an exaggerated contractile response to acute hypoxia, particularly in the RV. This suggests that adults born preterm may have contractile reserve, despite the lack of volume reserve identified in previous exercise studies. However, this exaggerated and hyper-adapted response may also increase their risk for late RV failure. Full article
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Article
Right Heart Structure, Geometry and Function Assessed by Echocardiography in 6-Year-Old Children Born Extremely Preterm—A Population-Based Cohort Study
J. Clin. Med. 2021, 10(1), 122; https://doi.org/10.3390/jcm10010122 - 31 Dec 2020
Cited by 2 | Viewed by 777
Abstract
Preterm birth has been associated with altered cardiac phenotype in adults. Our aim was to test the hypothesis that children surviving extremely preterm birth have important structural or functional changes of the right heart or pulmonary circulation. We also examined relations between birth [...] Read more.
Preterm birth has been associated with altered cardiac phenotype in adults. Our aim was to test the hypothesis that children surviving extremely preterm birth have important structural or functional changes of the right heart or pulmonary circulation. We also examined relations between birth size, gestational age, neonatal diagnoses of bronchopulmonary dysplasia (BPD) and patent ductus arteriosus (PDA) with cardiac outcomes. We assessed a population-based cohort of children born in Sweden before 27 weeks of gestation with echocardiography at 6.5 years of age (n = 176). Each preterm child was matched to a healthy control child born at term. Children born preterm had significantly smaller right atria, right ventricles with smaller widths, higher relative wall thickness and higher estimated pulmonary vascular resistance (PVR) than controls. In preterm children, PVR and right ventricular myocardial performance index (RVmpi’) were significantly higher in those with a PDA as neonates than in those without PDA, but no such associations were found with BPD. In conclusion, children born extremely preterm exhibit higher estimated PVR, altered right heart structure and function compared with children born at term. Full article
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Article
Physical Activity in 6.5-Year-Old Children Born Extremely Preterm
J. Clin. Med. 2020, 9(10), 3206; https://doi.org/10.3390/jcm9103206 - 04 Oct 2020
Cited by 3 | Viewed by 1578
Abstract
Physical activity (PA) can prevent cardiovascular diseases. Because of increased risks of impairments affecting motor activity, PA in children born preterm may differ from that in children born at term. In this prospective cohort study, we compared objectively measured PA in 71 children [...] Read more.
Physical activity (PA) can prevent cardiovascular diseases. Because of increased risks of impairments affecting motor activity, PA in children born preterm may differ from that in children born at term. In this prospective cohort study, we compared objectively measured PA in 71 children born extremely preterm (<27 weeks gestational age), to their 87 peers born at term, at 6.5 years of age. PA measured with accelerometer on the non-dominant wrist for 7 consecutive days was compared between index and control children and analyzed for associations to prenatal growth, major neonatal brain injury, bronchopulmonary dysplasia and neonatal septicemia, using ANOVA. Boys born extremely preterm spent on average 22 min less time per day in moderate to vigorous physical activity (MVPA) than control boys (95% CI: −8, −37). There was no difference in girls. Amongst children born extremely preterm, major neonatal brain injury was associated with 56 min less time in MVPA per day (95%CI: −88, −26). Subgroups of children born extremely preterm exhibit lower levels of physical activity which may be a contributory factor in the development of cardiovascular diseases as adults. Full article
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Review

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Review
Effect of Preterm Birth on Cardiac and Cardiomyocyte Growth and the Consequences of Antenatal and Postnatal Glucocorticoid Treatment
J. Clin. Med. 2021, 10(17), 3896; https://doi.org/10.3390/jcm10173896 - 30 Aug 2021
Viewed by 526
Abstract
Preterm birth coincides with a key developmental window of cardiac growth and maturation, and thus has the potential to influence long-term cardiac function. Individuals born preterm have structural cardiac remodelling and altered cardiac growth and function by early adulthood. The evidence linking preterm [...] Read more.
Preterm birth coincides with a key developmental window of cardiac growth and maturation, and thus has the potential to influence long-term cardiac function. Individuals born preterm have structural cardiac remodelling and altered cardiac growth and function by early adulthood. The evidence linking preterm birth and cardiovascular disease in later life is mounting. Advances in the perinatal care of preterm infants, such as glucocorticoid therapy, have improved survival rates, but at what cost? This review highlights the short-term and long-term impact of preterm birth on the structure and function of the heart and focuses on the impact of antenatal and postnatal glucocorticoid treatment on the immature preterm heart. Full article
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