Feature Article Exposure to Maternal Diabetes is Associated With Altered Fetal Growth Patterns: A Hypothesis Regarding Metabolic Allocation to Growth Under Hyperglycemic-Hypoxemic Conditions MICHELLE LAMPL 1 * AND PHILIPPE JEANTY 2 1 Department of Anthropology, Emory University, Atlanta, Georgia 30324 2 Women’s Health Alliance, Nashville, Tennessee 37202-2131 ABSTRACT 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 documen- ted 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  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 ¼ 0.00) and were brachycephalic. They experienced a proximal/distal growth gradient in limb proportionality with higher humerus / femur ratios (P ¼ 0.04) and arms relatively long by comparison with legs (P ¼ 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 be- come exacerbated by increasing longevity. Am. J. Hum. Biol. 16:237–263, 2004. # 2004 Wiley-Liss, Inc. The importance of fetal growth and devel- opment for adult health has been an intensely investigated topic for the past decade, focus- ing on negative outcomes in adulthood that are predicted by small size at birth (Barker et al., 1993; Phenekos, 2001). Discussions re- garding associations between the intrauterine environment and adult chronic diseases often look to an increased incidence of insulin dys- regulation as a potential mechanism, and relationships between insulin resistance and insulin growth factor (IGF) levels have been projected to be critical in putative fetal pro- gramming (Desai et al., 1995). A number of developmental IGF models have been explored for insights into potential sequelae of fetal growth restriction. These include investiga- tions of IGF levels in children related to their size at birth (Fall et al., 1995; Cance- Rouzaud et al., 1998) and subsequent stature (Arends et al., 2002), as well as studies look- ing for the presence of insulin resistance in children and adults who were born either small for gestational age (Woods et al., 2002) ß 2004 Wiley-Liss, Inc. *Correspondence to: M. Lampl, Department of Anthro- pology, 1557 Dickey Drive, Emory University, Atlanta, GA 30324. E-mail: mlampl@emory.edu Received 8 September 2003; Revision received 1 January 2004; Accepted 12 January 2004 Published online in Wiley InterScience (www.interscience. wiley.com). DOI: 10.1002/ajhb.20015 AMERICAN JOURNAL OF HUMAN BIOLOGY 16:237–263 (2004)