Exposure to maternal diabetes is associated with altered fetal growth patterns: A hypothesis regarding metabolic allocation to growth under hyperglycemic-hypoxemic conditions

The prevalence of diabetes is rising worldwide, including women who grew poorly in early life, presenting intergenerational health problems for their offspring. It is well documented that fetuses exposed to maternal diabetes during pregnancy experience both macrosomia and poor growth outcomes in birth size. Less is known about the in utero growth patterns that precede these risk factor expressions. Fetal growth patterns and the effects of clinical class and glycemic control were investigated in 37 diabetic pregnant women and their fetuses and compared to 29 nondiabetic, nonsmoking maternal/fetal pairs who were participants in a biweekly longitudinal ultrasound study with measurements of the head, limb, and trunk dimensions. White clinical class of the diabetic women was recorded (A2-FR) and glycosylated hemoglobin levels taken at the time of measurement assessed glycemic control (median 6.9%, interquartile range 5.6-9.2%). No significant difference in fetal weight was found by exposure. The exposed sample had greater abdominal circumferences from 21 weeks (P less than or equal to 0.05) and shorter legs, but greater upper arm and thigh circumferences accompanied increasing glycemia in the second trimester. In the third trimester, exposed fetuses had a smaller slope for the occipital frontal diameter (P = 0.00) and were brachycephalic. They experienced a proximal/distal growth gradient in limb proportionality with higher humerus / femur ratios (P = 0.04) and arms relatively long by comparison with legs (P = 0.02). HbA(1)c levels above 7.5% accompanied shorter femur length for thigh circumference after 30 gestational weeks of age. Significant effects of diabetic clinical class and glycemic control were identified in growth rate timing. These growth patterns suggest that hypoxemic and hyperglycemic signals cross-talk with their target receptors in a developmentally regulated, hierarchical sequence. The increase in fetal fat often documented with diabetic pregnancy may reflect altered growth at the level of cell differentiation and proximate mechanisms controlling body composition. These data suggest that the maternal-fetal interchange circuit, designed to share and capture resources on the fetal side, may not have had a long evolutionary history of overabundance as a selective force, and modern health problems drive postnatal sequelae that become exacerbated by increasing longevity. (C) 2004 Wiley-Liss, Inc.