STUDIO DI NUOVI FATTORI PROGNOSTICI ECOGRAFICI FETALI NELLA GRAVIDANZA CON DIABETE PRE-GESTAZIONALE

Study of new ultrasonographic fetal prognostic factors in pregnancies with pre-gestational diabetes mellitus Objective: Firstly, to study fetal and placental biometry along with placental and fetal cardiac function at 11+0-13+6 weeks in pregnancies with pre-gestational diabetes mellitus (PGDM), by means of a series of two-dimensional (2D), three-dimensional (3D), Doppler ultrasound measurements as well as with free serum chorionic gonadotropin-β (free-βhCG), pregnancy associated plasma protein A (PAPP-A) and glycosylated hemoglobin (HbA1c) concentrations. Secondly, to evaluate differences of such measurements between normal and PGDM and eventually, to investigate their prognostic capability in the prediction of neonatal macrosomia. Materials and methods: 50 normal controls and 50 PGDM pregnant patients at 11+0-13+6 weeks were recruited in a twenty-six months period. Demographic characteristics were recorded and 2D, 3D and Doppler ultrasound assessment were performed collecting the following measurements: crown rump length (CRL), nuchal translucency (NT), nasal bone (NB), tricuspid Doppler (TR), ductus venosus Doppler (DV), left sided myocardial performance index (MPI), fetal head and trunk volume (FV), head volume (HV), placental volume (PV). The trunk volume (TV) was obtained subtracting HV from FV and the head to trunk ratio (HTR) was calculated. VOCAL technology was used to obtain 3D ultrasound measurements as previously described. DV Doppler was defined normal with positive or negative A wave and abnormal with reverse A wave. In 35 patients of both groups we also obtained maternal serum free-βhCG and PAPP-A measurements and in all PGDM cases maternal serum HbA1c was measured with High-Performance Liquid Chromatography in the periconceptional period, at 11+0-13+6 weeks and in the second trimester. All of the ultrasound measurements were performed by a single operator blind to the pregnancy outcome and according to the methodology described in separate publications-guidelines. We collected pregnancies outcomes and birthweight (BW) was transformed in centile for gestational age. Categorical variables of both groups were compared by non-parametric chi-square test. Continuous variables of both groups were compared using mean differences from expected measurements (delta values) obtained from available regression equations with non-parametric Mann Whitney U test. BW was analyzed firstly as a continuous variable by means of regression of each continuous measurements of the study and subsequently as a dichotomous variable using non parametric statistics, as previously described. Macrosomia was defined as a BW greater than the 95th centile for gestation. Statistical significance was considered with p<0.05. Results: Gestational age at delivery was significantly smaller in PGDM compared to controls (p<0.001), whereas maternal age (p<0.05), body mass index (p<0.05) and BW centile (p<0.001) were significantly greater in PGDM compared to controls. Macrosomia occurred in 13 (26%) patients with PGDM and in 2 (4%) of the normals. No significant differences between normal controls and PGDM were found for the following measurements: CRL (p=0.240), NT (p=0.521), NB (p=0.317), TR (p=0.317), free-βhCG (p=0.374), PAPP-A (p=0.725), FV (p=0.072), HV (p=0.521). Abnormal DV Doppler was more frequent in PGDM group compared to normal (LR: 6.50; p<0.001) as well as in PGDM developing neonatal macrosomia compared to those with no macrosomia (LR: 3.32; p=0.008). MPI was significantly greater in PGDM group compared to normal (p<0.001) as well as in PGDM developing macrosomia compared to those with no macrosomia (p<0.001). TV and PV were significantly smaller in PGDM compared to normal (p<0.001; p<0.001) and in PGDM with macrosomia compared to those without (p<0.001; p=0.005). HTR was significantly greater in PGDM compared to normal (p<0.001) and in PGDM with macrosomia compared to those without (p<0.001). Regression analysis showed a significant correlation between BW centile and HTR (r=0.387; p=0.006), but not with other study variables. Periconceptional HbA1c and HbA1c at 11+0-13+6 weeks were not different in PGDM with and without macrosomia (p=0.293 and p=0.187, respectively), whereas HbA1c in the second trimester was greater in PGDM developing neonatal macrosomia compared to those who did not (p=0.014). Conclusions: in our series PGDM was associated with asymmetric fetal growth restriction, reduced placental volume, abnormal ductus venosus perfusion and impaired cardiac function at 11+0-13+6 weeks of pregnancy. Fetal trunk volume, head to trunk ratio, placental volume, myocardial performance index, ductus venosus Doppler may predict neonatal macrosomia at 11+0-13+6 weeks of pregnancy and eventually may be indicators of fetal metabolic impairment in PGDM pregnancies.