Magnetic Resonance Imaging and Thermal Imaging of Adiposity in Neonates of Women With Metabolic Diseases (MRI-TIME)

There is limited knowledge about the extent of the impact of maternal metabolic diseases (MD) and/or alterations in maternal serum lipid content upon neonatal lipid distribution and phenotypes. This observational feasibility study aims to investigate the effect of maternal MD on fat distribution, lipid content and metabolic phenotype of different neonatal tissues. We will explore whether differences in tissue fat distribution and lipid content are observed in the neonates of women with MD during pregnancy, compared to those who have a healthy, uncomplicated pregnancy and if there are changes in how the different tissues work (e.g. cardiac function). If there is evidence to show that there are alterations during pregnancy in children of women with MD, this will help inform potential interventions to ensure optimal child health.

Study Overview

• Status: Not yet recruiting
• Conditions: Diabetes Mellitus; Intrahepatic Cholestasis of Pregnancy; Metabolic Disease
• Intervention / Treatment: Diagnostic test: Thermal imaging; Diagnostic test: Echocardiogram; Diagnostic test: ECG; Diagnostic test: MRI scan; Diagnostic test: Serum blood markers

• Study Type: Observational
• Enrollment (Anticipated): 80

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 45 years (Child, Adult)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

Pregnant women with metabolic disease in pregnancy or healthy controls.

The neonates that will be studied can be of any sex/gender for inclusion in the study.

Description

Inclusion Criteria:

1. Pregnant women aged between 16 and 45 years old.
2. Women with GDM diagnosed at 26+0 to 30+6 weeks' gestation in accordance with the NICE guidelines Or
3. Pregnant women with pre-existing type 1 or type 2 diabetes mellitus Or
4. Women diagnosed with ICP at any stage of pregnancy
5. Fluent in English or presence of an interpreter or translation service (i.e. telephone translation services) at all visits.
6. Singleton pregnancy.
7. Willing and able to give written informed consent and comply with requirements of the study protocol
8. Planned antenatal, intrapartum and postpartum care at the participating centre (i.e. not planning to move before delivery)

Exclusion Criteria:

1. Known fetal congenital abnormality on ultrasound requiring fetal medicine input (excluding congenital heart disease).

1. Known fetal congenital abnormality on ultrasound requiring fetal medicine input (excluding congenital heart disease).
2. Significant pre-pregnancy co-morbidities that increase risk in pregnancy, for example renal failure, severe liver disease, transplantation, cardiac failure, psychiatric conditions requiring in-patient admission (within previous year) in the opinion of the responsible clinician or the CI.
3. Significant co-morbidity in the current pregnancy, nephropathy (estimated GFR <60ml/min), other physical or psychological conditions likely to interfere with the conduct of the study and/or interpretation of the study results in the opinion of the responsible clinician or the CI. (This does not include diabetes mellitus).
4. History of bariatric surgery.
5. Hypertension requiring treatment pre-pregnancy / in pregnancy.
6. Prescribed other medications that affect insulin sensitivity prior to OGTT for women diagnosed with GDM (oral antihyperglycemic agents, antipsychotic drugs, supraphysiological doses of steroids).
7. For the baby after birth: Not meeting the safety criteria to undergo MRI scan (e.g. metal implants, non MRI compatible devices, metal fragments in the body). [ The mother will not have an MRI scan].

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Pre-existing Type 1 Diabetes and Type 2 Diabetes; Women with type 1 diabetes and type 2 diabetes diagnosed prior to pregnancy	Diagnostic test: Thermal imaging; Use of a thermal imaging cameral to measure brown and white adipose tissue function; Diagnostic test: Echocardiogram; Echocardiographic imaging of the fetal heart to assess ventricular function; Diagnostic test: ECG; ECG of the fetus and the neonate to look at the cardiac electrical activity; Diagnostic test: MRI scan; MRI scan of the neonate to assess adipose tissue, liver architecture and cardiac structure and function; Diagnostic test: Serum blood markers; Serum sample taken from mother before birth and umbilical cord or neonatal blood spot at birth to assess glucose levels / lipid levels and lipidomics and cardiac function (using NTproBNP) as a marker
Gestational Diabetes; Women with gestational diabetes diagnosed in pregnancy by the oral glucose tolerance test	Diagnostic test: Thermal imaging; Use of a thermal imaging cameral to measure brown and white adipose tissue function; Diagnostic test: Echocardiogram; Echocardiographic imaging of the fetal heart to assess ventricular function; Diagnostic test: ECG; ECG of the fetus and the neonate to look at the cardiac electrical activity; Diagnostic test: MRI scan; MRI scan of the neonate to assess adipose tissue, liver architecture and cardiac structure and function; Diagnostic test: Serum blood markers; Serum sample taken from mother before birth and umbilical cord or neonatal blood spot at birth to assess glucose levels / lipid levels and lipidomics and cardiac function (using NTproBNP) as a marker
Intrahepatic cholestasis of pregnancy; Women with intrahepatic cholestasis of pregnancy	Diagnostic test: Thermal imaging; Use of a thermal imaging cameral to measure brown and white adipose tissue function; Diagnostic test: Echocardiogram; Echocardiographic imaging of the fetal heart to assess ventricular function; Diagnostic test: ECG; ECG of the fetus and the neonate to look at the cardiac electrical activity; Diagnostic test: MRI scan; MRI scan of the neonate to assess adipose tissue, liver architecture and cardiac structure and function; Diagnostic test: Serum blood markers; Serum sample taken from mother before birth and umbilical cord or neonatal blood spot at birth to assess glucose levels / lipid levels and lipidomics and cardiac function (using NTproBNP) as a marker
Control; Women without metabolic disease in pregnancy	Diagnostic test: Thermal imaging; Use of a thermal imaging cameral to measure brown and white adipose tissue function; Diagnostic test: Echocardiogram; Echocardiographic imaging of the fetal heart to assess ventricular function; Diagnostic test: ECG; ECG of the fetus and the neonate to look at the cardiac electrical activity; Diagnostic test: MRI scan; MRI scan of the neonate to assess adipose tissue, liver architecture and cardiac structure and function; Diagnostic test: Serum blood markers; Serum sample taken from mother before birth and umbilical cord or neonatal blood spot at birth to assess glucose levels / lipid levels and lipidomics and cardiac function (using NTproBNP) as a marker

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of the distribution of adipose tissue	To perform imaging and biochemical studies to determine whether maternal metabolic disease alters the distribution of adipose tissue (SAT, VAT, BAT) of the fetuses and neonates of women with MD during pregnancy compared to neonates of women who had a healthy pregnancy.	30 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of skeletal muscle, heart and liver	To perform imaging and biochemical studies to determine whether maternal metabolic disease alters the distribution and phenotypes of skeletal muscle, heart and liver of the fetuses and neonates of women with MD during pregnancy compared to those of women who had a healthy pregnancy.	30 months
Assessment of the function of adipose tissue	To evaluate novel MRI-based techniques to measure the function of adipose tissue (SAT, VAT, BAT) in the neonates.	30 months
Assessment of cardiac function and rhythm	To perform echocardiography and fetal/ neonatal ECG studies to understand the impact of maternal MD on the fetal heart.	30 months
Thermal assessment	To use thermal imaging to determine the temperature of regions of interest, e.g. BAT, of pregnant women with MD and their neonates.	30 months

Collaborators and Investigators

• Sponsor: Guy's and St Thomas' NHS Foundation Trust
• Collaborators: King's College London

Study record dates

Study Major Dates

• Study Start (Anticipated): June 1, 2021
• Primary Completion (Anticipated): December 1, 2023
• Study Completion (Anticipated): December 1, 2023

Study Registration Dates

• First Submitted: May 13, 2021
• First Submitted That Met QC Criteria: May 13, 2021
• First Posted (Actual): May 18, 2021

Study Record Updates

• Last Update Posted (Actual): May 18, 2021
• Last Update Submitted That Met QC Criteria: May 13, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: type 2 diabetes; gestational diabetes; type 1 diabetes; thermal imaging; ECG; liver function; cardiac function; brown adipose tissue; white adipose tissue; intrahepatic cholestasis of pregnancy; metabolic disease in pregnancy
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Biliary Tract Diseases; Bile Duct Diseases; Pregnancy Complications; Metabolic Diseases; Cholestasis; Cholestasis, Intrahepatic
• Other Study ID Numbers: 287911

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: IPD will be made available upon reasonable request and final decision from the PI.

Drug and device information, study documents

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