Physical exercise protects low-birth-weight children from cardiovascular disease in adulthood

Groundbreaking study shows that regular exercise in prepubertal childhood improves the functioning of cells essential to vascular health. Babies weighing less than 2.5 kg at birth are more likely to develop cardiovascular diseases in adulthood.

By Chloé Pinheiro  |  Agência FAPESP – Babies born at term (after 37-41 weeks of gestation) and weighing less than 2.5 kg face an increased risk of developing cardiovascular disease in adulthood, but regular physical exercise during childhood can mitigate this risk by improving the functioning of the cells involved in vascular health.

This is shown by a study published in the journal Nutrition, Metabolism & Cardiovascular Diseases. The last author is Maria do Carmo Pinho Franco, a professor at Escola Paulista de Medicina (EPM), the medical school of the Federal University of São Paulo (UNIFESP) in Brazil. Franco was the principal investigator for the corresponding project supported by FAPESP. 

Her coauthors are Livia Victorino de Souza, Franciele de Meneck, Edilamar Menezes de Oliveira and Tiago Fernandes.

The study sample comprising 35 children aged 6-11 was divided into a low-birth-weight group (weighing less than 2.5 kg at birth) and a normal-birth-weight group (3 kg or higher). All the children were submitted to a ten-week training program with four sessions per week, each lasting 60 minutes. The program prioritized exercises for coordination, flexibility, strength and stamina, such as skipping, racing and playing ball games. Baseline assessments were performed before and after the program, covering cardiorespiratory fitness, anthropometrics (weight, height and waist), blood pressure, and plasma analysis. 

At the end of the intervention, waist circumference and cardiorespiratory fitness were found to have improved significantly in all subjects. Blood pressure also improved in the low-birth-weight group, as well as the number of circulating endothelial progenitor cells and the functionality of these cells.

“Endothelial progenitor cells are produced by the bone marrow and are involved in several vascular processes, including repair of blood vessels and formation of new ones, so they’re important to maintain cardiovascular health,” Franco told Agência FAPESP.

Fetal programming

A correlation between low birth weight and a propensity for cardiovascular disease was proposed in the late 1980s, when British epidemiologist David Barker (1938-2013) formulated what became known as the fetal programming hypothesis, according to which reduced fetal growth is strongly associated with a number of chronic conditions in later life. Scientific research has elucidated the link over the years.

Fetal programming is now known to include adverse responses to environmental factors such as a poor maternal diet, placental insufficiency and stress during pregnancy. It can be construed as an attempt by the fetus to adapt to restricted intrauterine nutrition, guaranteeing its survival at the cost of permanent modifications to its structures and vital organs. 

Franco has focused on exploring the consequences of low birth weight since her master’s research, starting with animal models and extending in recent years to studies of children for a postdoctoral project and a Young Investigator Grant. 

The vascular endothelium – the thin inner layer of cells lining arteries and veins – is the focus for this latest line of research.

“Even before puberty, it’s possible to see a decrease in the dilation of certain arteries and alterations in blood pressure, particularly an increase in systolic pressure [maximum arterial pressure during contraction of the heart muscle while pumping blood],” Franco said. “These alterations are minor but serve as markers of increased cardiovascular risk in the future if nothing is done to repair them.”

Effects of exercise

The main aim of the group’s latest study was to find out how physical exercise affected the functioning of endothelial progenitor cells in children aged 6-11 who frequented a youth center in São Paulo City.

“Previous research has shown that the capacity of endothelial progenitor cells to travel from the bone marrow to the bloodstream and their capacity to transform into mature endothelial cells can be changed by different types of stimuli. In this context, we observed that physical exercise plays an important beneficial role in mobilizing these cells,” Franco said.

The results of the study showed that the positive effects of the training program were most evident in the group of low-birth-weight children. The levels of endothelial progenitor cells in the bloodstream rose, as did the levels of nitric oxide (NO) and of vascular endothelial growth factor-A (VEGF-A).

“These two molecules [NO and VEGF-A] are involved in the mobilization and recruitment of endothelial progenitor cells,” Franco explained.

Vascular reprogramming

Data from the scientific literature suggest that fetal programming is associated with epigenetic factors – biochemical changes that occur in cells, generally in response to environmental conditions, and modulate gene expression without altering genetic sequences.

Franco and her team suspect that regular physical exercise in childhood can produce epigenetic changes of this kind, potentially reversing the harmful pattern of gene expression induced by adverse conditions during pregnancy.

In Franco’s opinion, the results of the study indicate that a simple, affordable intervention can have a decisive effect on the adult lives of low-birth-weight children.

“Parents should be counseled to encourage their children to engage in regular physical activities as early as possible. Pediatricians should treat these children differently, performing regular tests to measure their lipid profile, blood pressure and other cardiovascular markers,” she said.

The article “Physical activity intervention improved the number and functionality of endothelial progenitor cells in low-birth-weight children” can be read at www.nmcd-journal.com/article/S0939-4753(19)30328-X/fulltext.