Long-term cardiovascular follow-up after preterm birth

Cardiovascular disease is a leading cause of morbidity and mortality worldwide. A large number of studies show that the risk of cardiovascular disease is increased in people born with low birth weight. The aim of this thesis is to study the contribution of preterm birth, the most common cause of low birth weight, to later cardiovascular function and disease risk.

Clinical follow-up studies of children and adolescents born very preterm (total n=118) in the 1980’s and 1990’s were performed. Vascular endothelial function was assessed using Laser-Doppler measurements of skin perfusion responses to acetylcholine, an endothelium-dependent vasodilator (paper I-II). Dermal capillary density was studied using intra-vital video microscopy (paper II). Arterial stiffness was measured using pulse wave analysis, pulse wave velocity and ultrasound techniques (paper I and III). Arterial dimensions were studied using ultrasound and magnetic resonance imaging (paper I, III and IV).

Paper I shows that adolescent girls, born at a mean gestational age of 29 w, had narrower abdominal aorta and lower skin perfusion, as compared to controls born at term. No signs of arterial stiffening were found and the endothelial function was unaffected after preterm birth. Paper II demonstrates that in 9-year old children born very preterm, the skin capillary density was reduced, but not the endothelial function, as compared to controls. Paper III shows that the 9-year old children born very preterm had the same carotid dimensions and stiffness as controls. Paper IV reports results from magnetic resonance imaging of the aorta in 86 healthy adolescents, of whom half were born very preterm. This study confirms the findings from paper I, showing lasting aortic narrowing after preterm birth. In addition, the aortic size was also strongly and independently associated with maternal smoking in pregnancy. Papers I, II and IV also show that children and adolescents born preterm have increased blood pressure. In paper II-III, the heart rate was higher in preterm children, but the heart rate was not related to their blood pressure.

Paper V investigates the association between preterm birth and fetal growth restriction and later risk of hypertension in a cohort of 6,425 men and women born 1925-1949 in Sweden, of whom 2,931 were born preterm. At follow-up in 1987 through 2006, the risk of hypertension was increased by 53% in those born small for gestational age. Preterm birth was not associated with risk of subsequent hypertension.

In conclusion, young subjects born very preterm exhibit altered vascular development, as illustrated by a lower capillary density and aortic narrowing. They also have higher blood pressure and heart rate. No signs of premature arterial stiffening or endothelial dysfunction– early markers of atheromatous disease – were found. The significance of these findings for future cardiovascular disease risk is not yet known.

List of scientific papers

I. Bonamy AK, Bendito A, Martin H, Andolf E, Sedin G, Norman M (2005). Preterm birth contributes to increased vascular resistance and higher blood pressure in adolescent girls. Pediatr Res. 58(5): 845-9. Epub 2005 Sep 23
https://pubmed.ncbi.nlm.nih.gov/16183828

II. Bonamy AK, Martin H, Jörneskog G, Norman M (2007). Lower skin capillary density, normal endothelial function and higher blood pressure in children born preterm. J Intern Med. 262(6): 635-42. Epub 2007 Nov 7
https://pubmed.ncbi.nlm.nih.gov/17986202

III. Bonamy AK, Andolf E, Martin H, Norman M (2008). Preterm birth and carotid diameter and stiffness in childhood. Acta Paediatr. 97(4): 434-7
https://pubmed.ncbi.nlm.nih.gov/18363953

IV. Edstedt Bonamy AK, Bengtsson J, Nagy Z, De Keyser H, Norman M (2008). Preterm birth and maternal smoking in pregnancy are strong risk factors for aortic narrowing in adolescence. [Submitted]

V. Edtsedt Bonamy AK, Norman M, Kaijser M (2008). Being born too small, too early or both- does it matter for risk of hypertension in the elderly? [Submitted]