Role of the Maternal Microbiota on the Immune Response and Metabolism During Hypertensive Disorders

Preeclampsia Clinical Trial

— MATER  

Official title:

Role of the Maternal Microbiota on the Immune Response and Metabolism During Hypertensive Disorders

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06421493
• Other study ID #: 0004622
• Status: Recruiting
• Start date: June 6, 2020
• Est. completion date: June 6, 2025

Study information

• Verified date: May 2024
• Source: Istituto Clinico Humanitas
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Preeclampsia (PE) is a significant cause of maternal and fetal morbidity and mortality, characterized by high blood pressure and proteinuria during pregnancy. It has two main phenotypes: one linked to placental damage and the other to metabolic factors like obesity. Early identification of high-risk groups is crucial, though there's ongoing disagreement over its classification. Research suggests a potential connection between maternal gut bacteria and PE, offering avenues for improved prevention strategies. This study aims to investigate the differences in maternal gut microbiota between these two PE phenotypes.

Description:

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

Scientific evidence suggests the existence of two distinct phenotypes of the disease:

preeclampsia due to placental damage and preeclampsia on a metabolic basis. The former phenotype recognizes altered invasion of the maternal endometrium by the trophoblast as its pathogenesis, where defective trophoblast invasion leads to the development of preeclampsia often associated with early presentation in pregnancy, intrauterine growth restriction (IUGR), and the need for delivery at low gestational ages. The latter phenotype recognizes a metabolic basis, which represents about 4% of hypertensive disorders of pregnancy (HDP), and is dependent on maternal predisposition in patients with visceral obesity and metabolic syndrome.

Evidence suggests that maternal risk factors for metabolic dysfunction may lead to late placental dysfunction in pregnancy. Metabolic-based preeclampsia manifests in patients with pre-existing low-grade inflammation related to truncal obesity and metabolic syndrome, compounded by pregnancy-related inflammation and insulin resistance.

Today, starting as early as the first trimester of pregnancy, maternal cardiovascular and hemodynamic function can be assessed using a non-invasive and safe method for both the mother and fetus through the USCOM (Ultra Sonic Cardiac Output Monitor) system. This system provides real-time data on numerous central and peripheral hemodynamic parameters.

There is still disagreement among scientific societies regarding the classification of preeclampsia and its possible different clinical phenotypes, making personalized clinical approaches to this condition challenging. However, early identification of high-risk groups is becoming increasingly important for diagnostic follow-up and therapeutic strategies based on pathogenesis.

Recently, a screening method at 11-13 weeks of gestation has been developed to predict 75% of pregnancies that will develop preterm preeclampsia (<37 weeks of gestation) based on a risk calculation algorithm combining weight and height measurements, mean arterial pressure measured with automated devices, blood sampling for PLGF measurement, and Doppler ultrasound measurement of the mean pulsatility index (PI) of the uterine arteries.

However, this screening method can only predict a portion of patients who will develop preeclampsia before 37 weeks and who may benefit from aspirin intake if administered at doses >100mg and before 16 weeks. Predicting and effectively preventing preeclampsia that occurs after 37 weeks remains the subject of debate and scientific research.

Among emerging etiopathogenetic hypotheses, numerous scientific publications suggest that alterations in maternal immunity and immune tolerance are the basis of hypertensive disorders in pregnancy. Recent discoveries suggest that changes in maternal intestinal microbiota may underlie these immune alterations. Alterations in gut microbiota diversity and composition, known as "dysbiosis," can influence systemic immune responses and metabolic disturbances such as gestational diabetes and preeclampsia, posing risks of metabolic alterations in the neonate.

Based on these premises, this study aims to define the characteristics of maternal intestinal microbiota in the two different clinical phenotypes of preeclampsia: placental preeclampsia associated with growth restriction and metabolic-based preeclampsia associated with a fetus of appropriate weight for gestational age.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 300
• Est. completion date: June 6, 2025
• Est. primary completion date: June 6, 2025
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age > 18 years

• Singleton pregnancy

• Live fetus at 11-13 weeks of gestation

• Pregnancies complicated by hypertensive disorders (HDP) and fetal growth restriction (FGR) Women with pregnancies complicated by HDP and a fetus with appropriate weight for gestational age (AGAf)

• Women with pregnancies complicated solely by early fetal growth restriction (before 34 weeks)

• Women with pregnancies complicated solely by late fetal growth restriction (after 34 weeks)

• Women identified as high-risk in first-trimester screening for preeclampsia Women identified as high-risk in first-trimester screening for fetal growth restriction

• Low-risk pregnancies in first-trimester screening for preeclampsia and fetal growth restriction, with physiological follow-up visits until delivery (homogeneous control sample)

Exclusion Criteria:

• Multiple pregnancies

• Pregnancies complicated by major fetal abnormalities identified during the 11-13 week gestational assessment

• Women who are unconscious or severely ill, women with learning difficulties, and those with severe psychiatric disorders

• Age <18 years

• Women who have not provided informed consent for the study

• Women with HIV, HBV, HCV infection

• Women with a history of leukemia and lymphoma

• Women with immunodeficiency

• Women who have used corticosteroids or other immunosuppressants in the last 3 months

Related Conditions & MeSH terms

• Hypertension
• Pre-Eclampsia
• Preeclampsia

Locations

Country	Name	City	State
Italy	Humanitas University	Pieve Emanuele	Milan

Sponsors (2)

Lead Sponsor	Collaborator
Istituto Clinico Humanitas	Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Study of the Characteristics of Maternal Gut Microbiota in Women with Pregnancies Complicated by Hypertensive Disorders, with or without Fetal Growth Restriction.	Study of the characteristics of the microbiota in fecal samples from women with pregnancies complicated by hypertensive disorders, with or without fetal growth restriction.	through study completion, an average of 1 year
Primary	Study of the Characteristics of Metabolome, in Women with Pregnancies Complicated by Hypertensive Disorders, with or without Fetal Growth Restriction.	Study of the characteristics of the metabolites in fecal and blood samples from women with pregnancies complicated by hypertensive disorders, with or without fetal growth restriction.	through study completion, an average of 1 year
Primary	Study of the Characteristics of NK and B Cells in Women with Pregnancies Complicated by Hypertensive Disorders, with or without Fetal Growth Restriction.	Study of the characteristics of NK and B cells in blood samples from women with pregnancies complicated by hypertensive disorders, with or without fetal growth restriction.	through study completion, an average of 1 year
Secondary	Study of the Characteristics of Microbiota in Women with Pregnancies	Assessment of Changes in Maternal Microbiota, in High-Risk Patients in the First Trimester for Preeclampsia or Fetal Growth Restriction	through study completion, an average of 1 year
Secondary	Study of the Evolution of Metabolome in Women with Pregnancies	Assessment of Changes in Maternal Metabolites in High-Risk Patients in the First Trimester for Preeclampsia or Fetal Growth Restriction	through study completion, an average of 1 year
Secondary	Study of the Evolution of NK and B Cells in Women with Pregnancies	Assessment of Changes in B and NK Cells in High-Risk Patients in the First Trimester for Preeclampsia or Fetal Growth Restriction	through study completion, an average of 1 year
Secondary	Evaluation of a Possible Correlation Between Dietary Habits and Maternal Gut Microbiota	The diet record will be obtained through a validated questionnaire on dietary habits and lifestyle. Spearman correlation of a-diversity microbiota measures and dietary intake will be performed.	through study completion, an average of 1 year