Innovations in Placental Metabolism and Association With Antioxidants and Nutrients in Diabetes and Gestational Obesity (IMPACTING)

This research project aims to investigate, in an innovative way, the molecular pathophysiology of gestational complications induced by maternal obesity and gestational diabetes mellitus (GDM). These complications have an immediate impact on obstetric outcomes - such as pre-eclampsia and intrauterine growth restriction - as well as long-term consequences for the health of the mother and child. This proposal aims to advance the understanding of the relationship between subclinical maternal and placental inflammation with dietary components through a prospective cohort of pregnant women. To this end, a prospective cohort of pregnant women will be conducted with four follow-up waves: 13th-20th (baseline), 24th-28th, 32nd-36th gestational weeks and at the time of delivery. Retrospective data referring to the first trimester of pregnancy will be obtained from the medical records. Pregnant women will be invited to participate in the study by registering at the prenatal service. Women who start prenatal care with less than 13 weeks of gestation will be registered, for capture in the 2nd consultation. The initial sample calculation is 120 volunteers. Maternal blood samples will be collected at 2 times: 2nd trimester appointment and 3rd trimester appointment. Placental and umbilical cord blood samples will be collected immediately after delivery. Dietary consumption during pregnancy will be assessed by 2 24-hour recalls at each visit (1 in person and 1 by telephone). The identification of functional biomarkers in maternal blood and placenta will serve for prognostic purposes of gestational complications such as Gestational Diabetes Mellitus. The identification of dietary factors associated with obesity and gestational diabetes mellitus and associated complications will provide information that will serve as a basis for nutritional guidelines for pregnant women.

Study Overview

• Status: Suspended
• Conditions: Pregnancy Complications; Obesity, Maternal; Diabetes Mel Gestational - in Pregnancy

• Study Type: Observational
• Enrollment (Estimated): 120

Contacts and Locations

Study Locations

• Brazil
  • Rio de Janeiro, Brazil
    • Maternidade Escola da UFRJ

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

The study population consists of pregnant women with a single fetus, aged between 18-45 years who attended prenatal care at the Maternity School at Federal University of Rio de Janeiro. The study group includes healthy pregnant women, pregnant women with obesity and gestational diabetes mellitus associated or not with obesity.

Description

Inclusion Criteria:

• Age between 18 and 45 years;
• Free from chronic non-communicable diseases such as high blood pressure and type 2 diabetes mellitus, except obesity;
• Free from infectious diseases;
• Carrying a single fetus;
• Intention to deliver at Maternity School-Federal University of Rio de Janeiro

Exclusion Criteria:

• Smokers;
• With low weight in early pregnancy (BMI < 18.5 kg/m²). They will be verified by interview, before the signing the informed consent form.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maternal redox homeostasis	Redox homeostasis will be assessed in maternal blood using a biological assay to measure the capacity of the sample to prevent the oxidation of a known fluorescence probe, in the presence of an oxidant. The unit of measure is concentration of plasma expressed as equivalent to a know antioxidant (after performing a calibration curve).	between 24th and 28th gestational week
Maternal redox homeostasis [change]	Redox homeostasis will be assessed in maternal blood using a biological assay to measure the capacity of the sample to prevent the oxidation of a known fluorescence probe, in the presence of an oxidant. The unit of measure is concentration of plasma expressed as equivalent to a know antioxidant (after performing a calibration curve).	between 34th and 35th gestational week
Fetal (cord blood) redox homeostasis	Redox homeostasis will be assessed in maternal blood using a biological assay to measure the capacity of the sample to prevent the oxidation of a known fluorescence probe, in the presence of an oxidant. The unit of measure is concentration of plasma expressed as equivalent to a know antioxidant (after performing a calibration curve).	At delivery
Placental redox homeostasis	Redox homeostasis will be assessed in maternal blood using a biological assay to measure the capacity of the sample to prevent the oxidation of a known fluorescence probe, in the presence of an oxidant. The unit of measure is concentration of plasma expressed as equivalent to a know antioxidant (after performing a calibration curve).	At delivery
Maternal inflammatory profile	Inflammatory profile will be assessed in maternal blood using a commercial kit to measure cytokines using ELISA assay, expressed as concentration per volume of sample.	between 24th and 28th gestational week
Maternal inflammatory profile [change]	Inflammatory profile will be assessed in maternal blood using a commercial kit to measure cytokines using ELISA assay, expressed as concentration per volume of sample.	between 34th and 35th gestational week
Fetal (cord blood) inflammatory profile	Inflammatory profile will be assessed in maternal blood using a commercial kit to measure cytokines using ELISA assay, expressed as concentration per volume of sample.	At delivery
Placental inflammatory profile	Inflammatory profile will be assessed in maternal blood using a commercial kit to measure cytokines using ELISA assay, expressed as concentration per volume of sample.	At delivery
Maternal metabolic profile	Metabolic profile will be assesses in maternal blood using Nuclear Magnetic Resonance metabolomics which measure small molecules (<1,500 Da) in the biological sample. The unit is intensity of the peak measured in a known volume/mass of sample obtained from the nuclear magnetic resonance spectra	between 24th and 28th gestational week
Maternal metabolic profile [change]	Metabolic profile will be assesses in maternal blood using Nuclear Magnetic Resonance metabolomics which measure small molecules (<1,500 Da) in the biological sample. The unit is intensity of the peak measured in a known volume/mass of sample obtained from the nuclear magnetic resonance spectra	between 34th and 35th gestational week
Fetal (cord blood) metabolic profile	Metabolic profile will be assesses in maternal blood using Nuclear Magnetic Resonance metabolomics which measure small molecules (<1,500 Da) in the biological sample. The unit is intensity of the peak measured in a known volume/mass of sample obtained from the nuclear magnetic resonance spectra	At delivery
Placental metabolic profile	Metabolic profile will be assesses in maternal blood using Nuclear Magnetic Resonance metabolomics which measure small molecules (<1,500 Da) in the biological sample. The unit is intensity of the peak measured in a known volume/mass of sample obtained from the nuclear magnetic resonance spectra	At delivery
Placental mitochondrial function at delivery	Mitochondrial function will be assessed using an electrode sensitive to oxygen which measures the decrease in oxygen tension in the chamber after addition of substrates and modulators of mitochondrial oxidative phosphorylation. This will be assessed in placental tissue and the units is concentration of oxygen per mass per time.	At delivery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Placental lipid metabolism	To investigate the alterations in lipid metabolism as a function of pre-gestational maternal obesity and gestational diabetes mellitus. Lipid metabolism will be assessed by lipid analysis using mass spectrometry to identify the major categories and lipid species in maternal, fetal and placental tissue. The unit is relative abundance per mass of tissue and volume of plasma.	At delivery

Collaborators and Investigators

• Sponsor: Rio de Janeiro State University
• Collaborators: Coordenação de Aperfeiçoamento de Pessoal de Nível Superior.; Conselho Nacional de Desenvolvimento Científico e Tecnológico; University of Cambridge; Université Montpellier; Rio de Janeiro State Research Supporting Foundation (FAPERJ); Universidade Federal do Rio de Janeiro; Maternidade Escola da UFRJ
• Investigators: Principal Investigator: Tatiana El-Bacha, DSc, UFRJ; Study Chair: Carolina S Ferreira, DSc, UFRJ; Study Chair: Deborah AB Guimarães, DSc, UFRJ; Study Chair: Gabriela DA Pinto, DSc, UFRJ; Study Chair: Vanessa A Goes, DSc, UFRJ

Study record dates

Study Major Dates

• Study Start (Actual): July 20, 2017
• Primary Completion (Actual): January 25, 2019
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: November 4, 2021
• First Submitted That Met QC Criteria: December 13, 2021
• First Posted (Actual): January 3, 2022

Study Record Updates

• Last Update Posted (Actual): May 14, 2024
• Last Update Submitted That Met QC Criteria: May 13, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: pregnancy; gestational diabetes mellitus; pre-gestational maternal obesity
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Overnutrition; Nutrition Disorders; Overweight; Body Weight; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Diabetes Mellitus; Obesity; Pregnancy Complications; Obesity, Maternal
• Other Study ID Numbers: 66949217.0.0000.5275

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: It might be available if there is enough funding to perform RNA sequencing and DNA methylation in placental samples. The data to be shared will involved differential expressed genes and methylation sites in the placenta in order to help the investigation of the placental role in the origins of chronic diseases.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No