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The 'stem cell burden' hypothesis represents a plausible explanation for the association between birth-weight and the risk of breast cancer in adulthood. The size of the overall stem cell pool would be expected to affect organ size and consequently birth-weight, making birth-weight a proxy for the overall number of fetal stem cells. As stem cells are self-renewing, the greater their number is at birth, the higher will be the chance that one of them will undergo carcinogenesis over the years. To investigate the correlation between birth-weight and stem cell burden, we examined the cord blood hematopoietic CD34+ stem cell population as an indicator of the overall fetal stem cell number. We measured both the CD34+ level (by flow cytometry) and the CD34+ proliferative potential (by the GM-CFU culture), in a sample of 1037 healthy newborn cord blood donors. We found that heavier babies had a significantly greater CD34+ stem cell concentration (p<0.001) and a higher GM-CFU number than lighter babies (p<0.001). Thus, a high birth-weight was positively associated with a high concentration of CD34+ stem cells and also with a qualitatively higher "stemness" of this pool. Therefore, our data support the theory that birth-weight reflects the number of fetal stem cells., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Birth weight is known to be a direct indicator of perinatal mortality and a clear predictor of adult pathologies too. It has been correlated with several causes of mortality in adulthood: low birth weight with diabetes, nephropathy and cardiovascular diseases and high birth weight with autoimmune diseases and cancer. In genome-wide studies, an extended human leucocyte antigen (HLA) region has been linked to birth weight variation. We focused our attention on the HLA haplotypes marked by HLA-A, HLA-B and HLA-DRB1 polymorphisms in 1206 healthy Caucasian newborns belonging to the Cord Blood Bank of Pavia (Italy) and their mothers, aiming to investigate the association between this restricted HLA region and birth weight variation. In our study, the HLA-B*38;DRB1*13 haplotype showed an ascending trend among centiles addressing to the high foetal weight. The HLA-A*02;B*15 haplotype showed a descending trend among centiles addressing to the low foetal weight. Besides the acknowledged correlation between the HLA-A*02 and HLA-B*15 alleles (as well as low birth weight) and type I diabetes and between the HLA-B*38 and HLA-DRB1*13 alleles (as well as high birth weight) and several autoimmune diseases, we cannot predict if our babies, healthy at birth, will suffer from these pathologies during life. Nevertheless, our data point to the HLA telomeric end for markers linked to the low birth weight and to the HLA centromeric end for markers linked to the high birth weight, thus limiting the region involved in birth weight variation, which still represents a useful predictor of disease risk in adulthood.