The aim of the present study will be to evaluate whether fetal cardiac remodeling is already present at the moment of the diagnosis of gestational diabetes (GD) in comparison with fetuses of healthy pregnant women.

We will recruited patients at the time of 75-g oral glucose tolerance test (OGTT); GDM will be diagnosed at 24-28.6 weeks when one or more of the venous plasma glucose measurements met or exceeded the following thresholds: fasting blood glucose ≥ 92 mg/dL; 1 h plasma glucose level ≥ 180 mg/dL; or 2 h plasma glucose level ≥ 153 mg/dL, as recommended by the International Association of the Diabetes and Pregnancy Study Groups. Consecutive women with singleton pregnancies with negative OGTT findings wil be also recruited during this period.

Maternal Characteristics The baseline variables, including maternal age, height, weight (1st ans 2nd trimester), parity will be collected at the time of the ultrasound examination. Additionally, fasting blood glucose, 1 h plasma glucose level and 2 h plasma glucose level in 75-g OGTT and glycated hemoglobin A1 (HbA1c) will be recorded. Body mass index of all mothers will be calculated.

Ultrasonographic examination using Voluson E6 (GE Medical Systems, Milwaukee, MI, USA) with 2-8 MHz linear curved-array probes, including estimated fetal weight, anomaly scan, and fetal echocardiography. The images will be recorded as clips and anonymized, and all the measurements will be performed offline.

Fetal biometric measurements will be obtained following ISUOG recommendations and fetal weight with Hadlock 4 formula.

Comprehensive two-dimensional, M-mode, and Doppler echocardiographic examination will be performed to rule out cardiac defects, and to evaluate cardiac morphometry and function following standard protocols. Cardiac, thoracic, and ventricular areas and diameters will be measured on 2-dimensional images from an apical or basal four-chamber (4 ChV) view at end diastole. Ventricular sphericity indices calculated by dividing the longitudinal by basal-transverse ventricular diameters. Atrial areas measured at maximum distension at end of systole. Atria and ventricle to-heart ratios will be calculated. Myocardial wall thicknesses measured on M-mode images from a transverse 4 ChV. Ventricular ejection fractions will be obtained from M-mode transverse 4 ChV using the Teichholz's formula. MAPSE/TAPSE will be assessed by M-mode from an apical or basal 4 ChV. Mitral and tricuspid early and late ventricular filling will be obtained by Doppler, and E/A ratios calculated. The left and right myocardial performance indices obtained from Doppler spectrum in a cross-sectional image of the thorax.

Inclusion Criteria:

• All pregnant women who will undergo 75g OGTT between 24 and 28.6 weeks of gestation will be invited to participate. Before being recruited, the objective of the research will be explained, the confidential nature of the information and informed consent will be requested. Inclusion criteria: singleton spontaneously conceived pregnancy, first trimester ultrasound screening to establish gestational age and first trimester serum glycemia < 92 mg/dL.

Exclusion Criteria:

• Those women with conditions or comorbidities that could induce cardiac remodeling and suboptimal function or could modify fetal growth will be excluded: fetus conceived by ssisted reproductive technology, pregestational diabetes, systemic lupus erythematosus, antiphospholipid antibody syndrome and other thrombophilias, heart disease, chronic pulmonary or renal disease, and thyroid disease. In addition, any hypertensive disease in pregnancy or derived complications (chronic arterial hypertension, gestational hypertension, pre-eclampsia, eclampsia). Patients with exposure to substances that could affect fetal weight will be excluded: teratogens (cyclophosphamide, valproic acid, antithrombotic drugs), tobacco, alcohol, cocaine or coffee consumption of more than 1 cup/day. Finally, women with a history of intrauterine growth restriction (IUGR) and/or preeclampsia in previous pregnancies, high risk of IUGR and/or preeclampsia in the current pregnancy estimated at first trimester screening, mean uterine artery greater than the 95th percentile for gestational age at 24-28.6 weeks, fetal structural defects or markers of aneuploidy on first or second trimester ultrasonography will be also excluded.

Pregnant women

The study population will consist of patients with singleton spontaneously conceived pregnancies who will undergo 75g OGTT at 24-28.6 weeks, with regular medical checkups throughout their entire pregnancy, delivered after 24-week gestation and fulfilled inclusion criteria. This study will be performed according to the standards of the Helsinki Declaration and approval will be obtained from the ethics and educational issues coordinating committee of our University Hospital.