Noninvasive Evaluation of Fetal Hyperinsulinemia With Ultrasound Radiomics

The goal of this observational study is to compare fetal liver ultrasound radiomics between pregnancies complicated by type 1 diabetes and healthy controls.

The main questions it aims to answer are:

• Are fetal liver ultrasound radiomic features reproducible?
• Does fetal liver ultrasound radiomics differ between pregnancies complicated by type 1 diabetes and healthy controls?

Participants will undergo ultrasound examination to collect ultrasound data for the analyses.

Study Overview

• Status: Not yet recruiting
• Conditions: Diabetes Mellitus, Type 1; Pregnancy in Diabetic

Detailed Description

Gestational diabetes is a growing health concern posing the neonate in the risk of adverse outcomes, such as macrosomia, cesarean delivery, hypoglycemia, respiratory morbidity, and need for neonatal intensive care. Most of these outcomes are either closely or causally related to fetal hyperinsulinemia, which is induced by maternal hyperglycemia. However, the accurate and non-invasive means of estimating fetal hyperinsulinemia are currently lacking.

Given that maternal diabetes and fetal hyperinsulinemia are associated with profound changes in fetal liver blood supply, biometry, metabolism, and lipid content, it was hypothesized that fetal hyperinsulinemia would be detectable by ultrasound using modern computer-aided technologies, i.e., radiomics and machine learning. In this prospective pilot study, the aim is to recruit 20 pregnant women with type I diabetes and compare them to 40 healthy controls. Patients with type 1 diabetes were chosen because their pregnancies are known to be associated with fetal hyperinsulinemia. Study subjects will be recruited at Turku University Hospital and the City of Turku maternity welfare clinics. It is assumed that radiomics analysis of fetal liver ultrasound pictures will indicate fetal hyperinsulinemia in pregnancies complicated by type 1 diabetes at 34 gestational weeks. Simultaneously, the inter- and intraobserver variability for fetal liver ultrasound radiomic features will be characterized.

In the future, non-invasive evaluation of fetal hyperinsulinemia could provide a useful tool in managing pregnancies complicated by maternal diabetes - either pre-gestational or gestational.

• Study Type: Observational
• Enrollment (Estimated): 60

Contacts and Locations

• Study Contact: Name: Mikael Huhtala, M.D., Ph.D.; Phone Number: +35823130000; Email: misahu@utu.fi

Study Locations

• Finland
  • Turku, Finland
    • Turku University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Pregnant women will be recruited at Turku University Hospital and Turku maternity welfare clinics during their routine pregnancy follow-up.

Description

Inclusion Criteria:

• Age between 18-45 years
• Capable to give an informed consent
• Singleton pregnancy
• Planning to deliver in Turku University Hospital
• Maternal BMI < 40
• Gestational age should be confirmed by first trimester ultrasound
• Normal oral glucose tolerance test (OGTT) at 24-28 gestational weeks in controls

Exclusion Criteria:

• Major fetal chromosomal, genetic, or structural anomaly
• Fetal growth restriction, or birth weight < 10th centile
• Birth weight > 90th centile or polyhydramnios in the controls
• Non-reassuring fetal status requiring immediate treatment, or intrauterine fetal demise
• Verified fetal infection (e.g. cytomegalovirus, toxoplasma, hepatitis B and C), excluding bacterial infection due to intrapartum chorioamnionitis
• Placenta accreta spectrum disorder
• Major maternal medical condition requiring systemic pharmacological treatment, other than non-severe hypertension, hypothyroidism, asthma, mild psychiatric disorders, etc.
• Alcohol or tobacco use, or substance abuse in pregnancy

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Type 1 diabetes; Pregnant woman with type 1 diabetes.
Healthy controls; Pregnant women with uncomplicated pregnancy and normal oral glucose tolerance test (OGTT).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fetal liver ultrasound texture	Fetal liver ultrasound texture is the collection of radiomic features that are extracted from the fetal liver ultrasound picture. The ultrasound pictures are acquired using transabdominal ultrasound. The radiomic features are extracted using conventional radiomics libraries e.g. pyradiomics.	34+0 - 34+6 weeks of gestation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Birth weight in grams	Birth weight in grams as routinely measured after birth.	After delivery, up to 24 hours
Birth weight centile	Birth weight adjusted for gestational age, fetal sex, and maternal parity.	After delivery, up to 24 hours
Large for gestational age (LGA)	Birth weight above 90th centile	After delivery, up to 24 hours
Interventricular septum (IVS) width	Fetal cardiac interventricular septum (IVS) width, measured at 34 gestational weeks	34+0 - 34+6 weeks of gestation
Number of pregnancies with neonatal hypoglycemia	Neonatal plasma glucose < 2.6 mmol/L	During initial hospitalization, up to one week of age
Rate of neonatal hypoglycemia treated with oral dextrose gel	Neonatal plasma glucose < 2.6 mmol/L and treatment with oral dextrose gel	During initial hospitalization, up to three weeks of age
Rate of neonatal hypoglycemia treated with intravenous (IV) glucose	Neonatal plasma glucose < 2.6 mmol/L and treatment with IV glucose	During initial hospitalization, up to three weeks of age
Length of treatment for neonatal hypoglycemia	Length of dextrose gel or IV glucose treatment (days)	During initial hospitalization, up to three weeks of age
Number of neonates admitted to neonatal intensive care unit (NICU)	Neonatal admission to NICU	During initial hospitalization, up to one week of age
Length of NICU admission	Length of NICU admission (days)	During initial hospitalization, up to the age of three months
Number of pregnancies with neonatal respiratory complications related to maternal diabetes	Diagnosis of respiratory distress syndrome and/or transient tachypnea of the newborn	During initial hospitalization, up to one week of age
Number of pregnancies with neonatal hyperbilirubinemia	Neonatal hyperbilirubinemia requiring phototherapy	During initial hospitalization, up to two weeks of age
Maternal HbA1c concentration	Maternal HbA1c (mmol/mol)	Close to 12, 21 and 32 weeks of gestation
Glucose management indicator (GMI)	HbA1c estimation based on continuous glucose monitoring (CGM) or flash glucose monitoring data	Close to 12, 21 and 32 weeks of gestation
Time in glycemic range (TIR)	Time in glycemic range (TIR), if using CGM or flash monitoring	Close to 12, 21 and 32 weeks of gestation
Time above glucose range	Time above glucose range, if using CGM or flash monitoring	Close to 12, 21 and 32 weeks of gestation
Time below glucose range	Time below glucose range, if using CGM or flash monitoring	Close to 12, 21 and 32 weeks of gestation

Collaborators and Investigators

• Sponsor: Turku University Hospital
• Investigators: Principal Investigator: Mikael Huhtala, M.D., Ph.D., Turku University Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2024
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): May 1, 2026

Study Registration Dates

• First Submitted: March 25, 2024
• First Submitted That Met QC Criteria: April 2, 2024
• First Posted (Actual): April 3, 2024

Study Record Updates

• Last Update Posted (Actual): April 3, 2024
• Last Update Submitted That Met QC Criteria: April 2, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: pregnancy; liver; ultrasonography; radiomics; fetus; hyperinsulinemia
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Diabetes Mellitus, Type 1; Hyperinsulinism; Pregnancy in Diabetics
• Other Study ID Numbers: 0843

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: To ensure study subject anonymity the study data will not be published.

Drug and device information, study documents

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