Ruolo Del Microbiota Materno Sulla Risposta Immunitaria e Sul Metabolismo Nei Disordini Ipertensivi

Preeclampsia (PE) is one of the leading causes of maternal-fetal morbidity and mortality. It is defined as systolic blood pressure (SBP) ≥ 140 and diastolic blood pressure (DBP) ≥ 90 in two consecutive measurements taken 6 hours apart, associated with proteinuria >300 mg/24 h or 2++ detected by a urine dipstick, or the presence of organ damage or intrauterine growth restriction (IUGR). Preeclampsia complicates 3-8% of pregnancies and is responsible for over 76,000 maternal deaths each year.

Scientific evidence suggests the existence of two distinct phenotypes of the condition: placental preeclampsia and metabolic preeclampsia. The first phenotype is caused by abnormal invasion of the maternal endometrium by the trophoblast, leading to preeclampsia often associated with early presentation in pregnancy, intrauterine growth restriction, and the need for delivery at early gestational ages. Fetal growth restriction due to likely placental insufficiency is defined by the Delphi criteria: estimated fetal weight (EFW) < 3rd percentile, or at least two of the following criteria: EFW < 10th percentile, a decrease in EFW by at least 40 percentiles even if above the 10th percentile, cerebro-placental ratio (CPR) ≤ 1 (5th percentile) or umbilical artery pulsatility index (PI) ≥ 95th percentile, uterine arteries with PI ≥ 95th percentile.

Beyond the hypothesis of abnormal placentation at the beginning of pregnancy, it is now recognized that maternal metabolic risk factors may cause placental malfunction later in pregnancy. The second phenotype is rooted in a metabolic basis, representing about 4% of hypertensive disorders of pregnancy (HDP), and depends on a maternal predisposition in patients with visceral obesity and metabolic syndrome. Visceral obesity is associated with a state of chronic low-grade inflammation, which contributes to insulin resistance, altered glucose homeostasis, and cardiovascular complications.

Metabolic preeclampsia occurs in patients with a pre-existing state of low-grade inflammation related to trunk obesity and metabolic syndrome, compounded by the inflammation and insulin resistance typical of pregnancy. Scientific evidence has shown that in the placentas of these patients, there is a higher density of tertiary villi compared to physiological pregnancies, with reduced intervillous spaces, resulting in hypoperfusion and oxidative stress. Differentiation between these clinical phenotypes can be identified during pregnancy by studying fetal growth as an index of placental function, as well as maternal cardiovascular adaptation to pregnancy in terms of hemodynamic parameters and body water, and finally by studying placental histology after delivery. Hypertensive disorders of pregnancy associated with intrauterine growth restriction (HDP-IUGR) and hypertensive disorders of pregnancy with appropriate-for-gestational-age fetuses (HDP-AGA) are distinguished.

Currently, starting from the first trimester of pregnancy, maternal cardiovascular and hemodynamic function can be assessed with a non-invasive and harmless method for both mother and fetus using the USCOM (Ultra Sonic Cardiac Output Monitor) system. This provides real-time data on numerous central and peripheral hemodynamic parameters such as cardiac output and stroke volume beat-to-beat. It allows measurement of cardiac output from both the right and left heart, systolic stroke volume (SV), systemic vascular resistance, and inotropic index. Its use in pregnancy has already been validated and will significantly enhance the quality of care provided to women with high-risk or pathological pregnancies.