Is fetal macrosomia in adequately controlled diabetic women the result of a placental defect? – a hypothesis G. Desoye 1 , E. T. Korgun 2,3 , N. Ghaffari-Tabrizi 1,2 and T. Hahn 2 1 Clinic of Obstetrics and Gynecology, Karl-Franzens University, Graz, Austria 2 Institute of Histology and Embryology, Karl-Franzens University, Graz, Austria 3 Institute of Histology and Embryology, Akdeniz University, Antalya, Turkey Fetal macrosomia may occur even in adequately controlled diabetic mothers. This may reflect the problem of using maternal glycemia as an indicator of fetal glycemia, because the placenta inter- posed between both compartments has its own glucose metabolism. Here, we propose a model by which the placenta protects the fetus at moderate levels of maternal hyperglycemia. One characteristic feature of the human placenta in diabetes is the increased deposition of glyco- gen. Neither hyperglycemia nor hyperinsulinemia increase the glycogen content in the trophoblast. Since the glycogen increments in diabetes are predominantly located around fetoplacental vessels, it is tempting to assume a fetal origin of glucose making up the glycogen deposits. In fact, glucose can be transported back from the fetus into the placenta and this reflux is increased in diabetes. Therefore, in conditions of fetal glucose levels exceeding the demand for sustaining fetal growth and metabolism, glucose can be stored in the liver and other fetal tissues. Once these stores are saturated, glucose is extracted from the fetal circulation by the glucose transporters GLUT1 and GLUT3 on cells surrounding the fetoplacental vasculature and stored therein, again in the form of glycogen. These processes might be under the control of fetal insulin, because insulin injected into the fetal circulation increases placental glycogen stores. Fetal macrosomia would then occur only when fetal hyperglycemia exceeds the placental capacity to store excess fetal glucose. Thus, the placental failure to protect the fetus would cause the ‘unexplained’ phenotypic changes occasionally found in fetuses born to well-controlled diabetic women. Key words: MACROSOMIA; PLACENTA; DIABETES; GLYCOGEN; GLUT1; GLUT3 INTRODUCTION Despite considerable efforts and success in improving the treatment of diabetic women in pregnancy, fetal macrosomia is still a problem that occurs with higher inci- dence in diabetic than in non-diabetic pregnancies. ‘Un- explained fetal macrosomia’ refers to macrosomia in a pregnancy characterized by an excellent quality of glycemic control of the mother. However, because fetal macrosomia is the result of inadequate treatment of the fetus, treatment strategies have been developed that depend on the assess- ment of the metabolic status of the fetus 1–3 . These take into account the findings that maternal glycemic control readings do not necessarily reflect fetal glycemic control, because the placenta is interposed between both compartments. The placenta has its own metabolism that sustains continuous growth of itself and provides the energy for fulfilling a broad range of functions, with the ultimate goal of ensuring adequate fetal growth 4,5 . Any assessment of fetal metabolic status by measuring maternal hemoglobin A 1c or any other parameter related to glucose levels largely ignores the glucose-consuming and -metabolizing activity of the placenta. We have developed a model that takes into account the glucose-metabolizing function of the placenta and that may help to explain the occurrence of ‘unexplained fetal macrosomia’. The Journal of Maternal–Fetal and Neonatal Medicine 2002;11:258–261 Correspondence: Dr G. Desoye, Clinic of Obstetrics and Gynecology, Auenbruggerplatz 14, A-8036 Graz, Austria ORIGINAL ARTICLE 258 Received 02–10–01 Revised 10–01–02 Accepted 31–01–02