Cardiovascular function in 6-year-old children born extremely preterm

In western countries, approximately 6 to 12 per cent of all pregnancies end preterm, i.e., before 37 weeks of gestation. After the introduction of antenatal corticosteroids, surfactant therapy and neonatal intensive care, survival rates after preterm birth have increased markedly worldwide. While this progress is very welcome, concerns have been raised that preterm birth may carry increased risk for adult morbidity and shortened life-span due to conditions associated with aging, such as stroke and cardiovascular disease. This may be particularly important in populations with increasing overweight and sedentary.

This thesis aims at providing new knowledge on blood pressure, growth and dynamics of the arterial tree as well as cardiac structure and function in children born extremely preterm. Addressing these issues may help our current understanding of cardiovascular development after preterm birth, if and when cardiovascular follow-up is needed in childhood, and provide important clues on how lasting cardiovascular health after preterm birth may be promoted.

We studied a population based cohort EXPRESS (Extremely Preterm Infants in Sweden Study) consisting of children born between 2004 and 2007 at 22-26 weeks of gestation, and age and sex-matched controls born at term. At the age of 6½ years, we measured blood pressure and performed a comprehensive evaluation of cardiovascular structure and function using echocardiography. In addition, we measured lung function using spirometry.

The conduit and coronary arteries were of similar or smaller size in children born extremely preterm than in controls born at term, also after adjusting for body size. Reassuringly, the arterial tree had no signs of accelerated intima media thickening or premature arterial stiffening – two early markers of a predisposition for atheroma formation. Casual blood pressures were normal but higher in children born extremely than in their peers born at term. This finding could not be explained by fetal growth restriction, antenatal corticosteroid exposure or neonatal morbidity. Children born extremely preterm also exhibited a unique cardiac phenotype characterized by smaller left ventricles with altered systolic and diastolic functions than same-aged children born at term. Finally, reduced lung function or airway obstruction in children born extremely preterm at age of 6 ½ years did not predict right ventricular hypertrophy or pulmonary hypertension.

In conclusion, children born extremely preterm exhibit a cardiovascular phenotype that differ from same-aged peers born a term. The long term significance for cardiovascular health of these findings remains to be established.

List of scientific papers

I. Mohlkert LA, Hallberg J, Broberg O, Hellström M, Pegelow Halvorsen C, Sjöberg G, Edstedt Bonamy AK, Liuba P, Fellman V, Domellöf M and Norman M. Preterm Arteries in Childhood: Dimensions, Intima-Media Thickness and Elasticity of The Aorta, Coronaries, Carotids in 6-Year-Old Children Born Extremely Preterm. Pediatr Res. 2017 Feb;81(2):299-306.
https://doi.org/10.1038/pr.2016.212

II. Edstedt Bonamy AK, Mohlkert LA, Hallberg J, Liuba P, Fellman V, Domellöf M, Norman M. Blood Pressure in 6-Year-Old Children Born Extremely Preterm. J Am Heart Assoc. 2017 Aug 1;6(8). pii: e005858.
https://doi.org/10.1161/JAHA.117.005858

III. Mohlkert LA, Hallberg J, Broberg O, Rydberg A, Pegelow Halvorsen C, Liuba P, Fellman V, Domellöf M, Sjöberg G, Norman M. The Preterm Heart in Childhood: Left Ventricular Structure, Geometry and Function Assessed by Echocardiography in 6-Year-Old Survivors of Periviable Births. J Am Heart Assoc. 2018 Jan 20;7(2).
https://doi.org/10.1161/JAHA.117.007742

IV. Mohlkert LA, Sjöberg G, Rydberg A, Pegelow Halvorsen C, Thuvfesson E, Hallberg J, Domellöf M, Norman M. Lung Function and Pulmonary Circulation in 6-Year-Old Survivors of Extremely Preterm Birth. [Submitted]