Low birth weight and future cardiovascular risk – how are they connected?

13th April 2019, Dr Chee L Khoo

We know that overweight children have higher future risk of cardiovascular disease and diabetes.  Ironically, babies who are small at birth or during infancy also have increased rates of cardiovascular disease and diabetes as adults. It is thought that foetal undernutrition at different stages of gestation are somehow link to this increased risk, but the underlying mechanism is not fully understood. The key role of the endothelium, as shown by altered vasodilatation, angiogenesis, endothelial progenitor cells and microparticle number and function is flagged as a possible explanatory mechanism.

Endothelial progenitor cells are mononuclear cells that mobilise from the bone marrow into the blood stream and mature and differentiate into mature endothelial cells in response to various metabolic and hypoxic stresses.               They are involved in various reparative functions including neovascularisation especially following ischaemic injury. This process can be initiated by the upregulation of angiogenic factors including nitrous oxide (NO) and vascular endothelial growth factor (VGEF). Endothelial progenitor cells are susceptible to oxidative stress. Hill et al. (1) revealed that the number of endothelial progenitor cells was reduced in hypercholesterolemia, hypertension, and diabetes.

A recent study from Brazil explored the relationship of low birth weight with circulating endothelial progenitor cells and angiogenic factors in children aged between 7-11 years old (2). Because obesity and puberty can affect endothelial progenitor cell number, pubescent and overweight children were excluded from the study. 74 children (43 boys and 31 girls) with no clinical or laboratory signs of endocrine, renal or cardiovascular disease were studied. Apart from anthropometric measurements (weight, BMI, BP) and metabolic biochemisty profile, peripheral mononuclear cells (circulating MNCs with CD34+/CD133+/KDR+ were considered endothelial progenitor cells), NO and plasma VGEF-A were measured.

The results

Among the 58 included children (35 boys and 23 girls), the mean birth weight was 2931 g (range, 2200-3680 g), and the mean length at birth was 46.6 cm (range, 38-52 cm). Children born with very low birth weight were not included. 20% of the children had low birth weight (defined as <2.50 kg) and the prematurity rate was 5.2%. BMI, BP, glucose, lipid and insulin profile were all within the normal range in these children. In other words, we are looking at a cohort of seemingly healthy children aged between 7-11 years old with 20% of them born with low weight.

There was no relationship between birth weight and BMI, glucose, total cholesterol, HDL-C, LDL-C, insulin or HOMA. There was a small inverse relationship between birth weight and systolic BP but not diastolic BP.

A moderate positive correlation was detected between birth weight and endothelial progenitor cell number, endothelial progenitor cell colony-forming units and VEGF-A levels. It is thought that low birth weight results in low pro-angiogenic factors (NO and VGEF-A) leading to reduction of endothelial progenitor cells. This in turn, leads to impaired endothelial integrity and repair promoting vascular abnormalities in seemingly healthy children born with low birth weight.

These findings suggest that the effects of birth weight on endothelial progenitor cell number/colony-forming units and angiogenic factors are detrimental to children with a lower birth weight.

Who does this affect? I mean we don’t see low birth weight kids, do we? I can think of a few categories of pregnant women with at risk babies:

  • Women with PCOS on metformin and fail to put on enough weight during pregnancy
  • Women with hyperglycaemia at booking but may not have GDM but commenced on restricted diet
  • Women who have undergone gastric sleeve surgery and is now pregnant

Are the offsprings of these women at risk of low birth weight and thence, increased CV risk in the future?

Access the abstract here.

Further reading:

Metformin in pregnancy – first do no harm?

GDM diagnosis and management – SWS leading the way


  1. Hill JM, Zalos G, Halcox JP, Schenke WH, Waclawiw MA, Quyyumi AA, Finkel T. Circulating endothelial progenitor cells, vascular function, and cardiovascular risk. N Engl J Med. 2003;348:593–600
  2. Detrimental Impact of Low Birth Weight on Circulating Number and Functional Capacity of Endothelial Progenitor Cells in Healthy Children: Role of Angiogenic Factors Souza, Livia Victorino et al. The Journal of Pediatrics , Volume 206 , 72 – 77.e1
  3. J. Barker, P.D. Gluckman, K.M.Godfrey, J.E. Harding, J.A. Owens, J.S.RobinsonFetal nutrition and cardiovascular disease in adult life. Lancet, 341 (1993), pp. 938-941