Simultaneous evaluation of fetal cerebrovascular Doppler ultrasound and maternal glucose homeostasis in normal pregnancy.

Abstract

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. Multivariate linear regression of the measured parameters showed that increased maternal weight at assessment, diastolic blood pressure, fetal biparietal diameter, baseline MCA velocity and head circumference were associated with an increase in neonatal weight, and increased maternal basal glycemia, systolic blood pressure, prepregnancy weight, body mass index and fetal MCA velocity 1 h after OGTT were associated with a decrease in neonatal weight. These parameters can be used to estimate birth weight with < 5% error when combined according to their coefficients obtained from multivariate linear regression analysis (Table 1). Accurate prediction of birth weight is essential as increased weight is associated with an increased risk of delivery complications, including shoulder dystocia, neonatal hypoglycemia and need for Cesarean section3. Fetal blood vessel velocimetry is a complex phenomenon influenced by maternal metabolic factors other than oximetry. We found that fetal MCA-PI was affected by maternal glycemia 1 h after glucose intake, which was associated with an increase in cord C-peptide concentration, a hypoglycemic risk for the fetus. Women with reversed flow in the fetal MCA had a significantly greater increase in blood glucose levels following glucose administration than those with normal flow. A possible explanation for this is that higher maternal insulin resistance causes greater transplacental passage of glucose, resulting in greater fetal vasoconstriction. This suggests that maternal food intake has a significant influence on fetal blood circulation even in the absence of diabetes4 and when maternal glycemic variation is within normal range. It is reasonable to hypothesize that these minor injuries to fetal brain tissue can influence cerebral circulation and, consequently, cerebral development. In conclusion, the simultaneous evaluation of OGTT and fetal Doppler ultrasound can provide more information than is obtainable from each assessment separately and can indicate the necessity for a food intake modification, even if the OGTT response is within normal range. Evaluation of fetal MCA-PI 1 h after maternal glucose intake may be a useful tool to predict the risk of complications at delivery, and measurement of the relevant parameters enables accurate estimation of birth weight. Q. C. Ianniciello1, J. Troisi1,2*, M. Niola3, C. De Rosa4, M. Rinaldi4 and M. Guida1,2 1Department of Medicine, University of Salerno, Salerno, Italy; 2Theoreo, Via degli Ulivi, 3 CAP 84090 Montecorvino Pugliano, Salerno, Italy; 3Department of Advanced Biomedical Science, University of Naples ‘Federico II’, Naples, Italy; 4San Giovani di Dio e Ruggi d'Aragona Hospital, Salerno, Italy *Correspondence. (e-mail: [email protected])