Fetal growth is influenced by maternal in utero environment and genetic factors inherited from both parents. The combined influence of environment and genes can be seen through the dual effects of insulin on glucose metabolism and fetal growth. Whereas maternal diabetes and hyperglycemia lead to excess fetal insulin secretion and increased fetal growth, a fetus that inherits risk alleles for type 2 diabetes may have reduced insulin secretion or insulin resistance that lead to fetal growth restriction: the fetal insulin hypothesis.
The role of maternally inherited risk alleles for type 2 diabetes on fetal growth is difficult to assess owing to the confounding effect of maternal hyperglycemia on in utero environment. Support for the fetal insulin hypothesis has come from epidemiological studies that showed men who develop diabetes in later life were more likely to have fathered low-birth weight offspring. These fathers are also at increased risk of cardiovascular disease. Whether this latter observation is secondary to paternal diabetes or other risks shared by parents of low-birth weight offspring, such as smoking, is uncertain. Men who father small-for-gestational-age infants are more likely to be obese, have larger waist circumferences and elements of the insulin resistance syndrome, including hyper-insulinemia, hyperglycemia, endothelial dysfunction, dyslipidemia and hypertension.
Other paternal genetic and epigenetic influences on fetal growth-restriction and over-growth syndromes will be presented.