Italian1 and American2 guidelines for management of normal pregnancy recommend screening for gestational diabetes mellitus (GDM), by means of the oral glucose tolerance test (OGTT), in the second trimester. These guidelines also suggest fetal Doppler ultrasound evaluation at the same stage in gestation to assess for fetal development and wellbeing. When considered separately, these clinical assessments provide information on different aspects of pregnancy; however, when performed simultaneously, the information obtained may be more extensive than when the two examinations are considered separately. To test this hypothesis, 21 healthy nulliparous women aged ≥ 18 years with a spontaneously conceived pregnancy were enrolled in the second trimester of pregnancy. At 30 weeks’ gestation, a complete clinical and obstetric examination was performed, including evaluation of maternal basal blood glucose after an 8-h fast and measurement of fetal middle cerebral artery (MCA) pulsatility index (PI) and velocity on Doppler ultrasound. In the same visit, an OGTT (75 g glucose in 300 mL water) was performed. Fetal MCA-PI and maternal blood glucose levels were re-evaluated at 1 h and 2 h after glucose intake. Neonatal biochemical parameters, such as umbilical cord glycemia, C-peptide concentration and bilirubinemia, were measured at delivery. The study was approved by the ethics committee and all subjects gave informed consent. We found that maternal hyperglycemia induced by OGTT caused vasoconstriction in the fetal MCA, which was stronger in the lenticostriatal branches than in the lateral branches. In six cases, we observed reversed end-diastolic flow in the fetal MCA after glucose intake. This finding suggests that vasoconstriction was so strong that it could not be overcome by the systolic pressure and the afterload allowed the direction of flow to change. This condition may represent an ultrasound sign of fetal compromise.