Cardiovascular development of the preterm infant

The numbers of preterm births and cardiovascular deaths are increasing in most countries. The causes of both developments are multiple and apparently not related to each other. However, preterm birth might provide an increasing contribution to the burden of cardiovascular morbidity and mortality, since epidemiological evidence is growing that cardiovascular disease risk factors such as hypertension, ischemic heart disease and cerebrovascular events are linked to preterm birth. Despite this, most of the underlying mechanisms remain unknown.

The overall concept of this thesis was to seek evidence for a perinatal origin of the changes seen in adults who were born preterm, regarding both vascular and cardiac function. For this purpose, we performed a longitudinal observational study, investigating diameter and intimamedia thickness of the aorta and carotid artery, and analyzing cardiac function during the first six months after preterm birth. In addition to well-established ultrasound methods, we applied innovative technology such as speckle-tracking echocardiography, since advances in myocardial imaging have facilitated the echocardiographic examination of preterm infants and even the detection of subclinical functional impairment.

In preterm born infants, we found significant alterations of the development of the vascular and cardiac systems. The arteries we examined became significantly narrower and the intima-media thickened in relation to vessel diameter when they were compared to healthy infants born at term. In addition, we found significant differences in the left ventricular systolic and diastolic function, suggesting that myocardial remodeling may occur as an adaptive process of premature exposure towards the extra-uterine circulation.

Early changes in the cardiovascular development of the preterm infant may persist and have long-term implications. In fact, adults born preterm exhibit similar alterations in cardiovascular structure and function to those found in our studies. As it is not currently possible to prevent preterm births or influence the developmental changes described in this thesis, we will meet more children and adolescents with remodeled vessels and hearts in the future. Further research on the underlying mechanisms is warranted. In addition, early and continued follow-up will be required if we are to determine the long-term and clinical significance, and to improve cardiovascular health in the growing population of individuals born preterm.

List of scientific papers

I. Aortic growth arrest after preterm birth: a lasting structural change of the vascular tree. Ulf Schubert, Matthias Müller, Anna-Karin Edstedt Bonamy, Hashim Abdul-Khaliq, Mikael Norman. Journal of Developmental Origins of Health and Disease. 2011;2(4):218-225.
https://doi.org/10.1017/S2040174411000274

II. Relative intima-media thickening after preterm birth. Ulf Schubert, Matthias Müller, Hashim Abdul-Khaliq, Mikael Norman, Anna-Karin Edstedt Bonamy. Acta Paediatrica. 2013;102:965-969.
https://doi.org/10.1111/apa.12355

III. Transition from fetal to neonatal life: Changes in cardiac function assessed by speckle-tracking echocardiography. Ulf Schubert, Matthias Müller, Mikael Norman, Hashim Abdul-Khaliq. Early Human Development. 2013;89:803-808.
https://doi.org/10.1016/j.earlhumdev.2013.06.009

IV. Preterm birth is associated with altered myocardial function in infancy. Ulf Schubert, Matthias Müller, Hashim Abdul-Khaliq, Mikael Norman. Journal of the American Society of Echocardiography. 2016;29(7):670-8.
https://doi.org/10.1016/j.echo.2016.03.011