Glycemic Observation and Metabolic Outcomes in Mothers and Offspring

Study Overview
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Brief Summary
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The overarching goal of Glycemic Observation and Metabolic Outcomes in Mothers and Offspring (GO MOMs) is to perform a comprehensive, longitudinal description of maternal glycemia over the course of pregnancy and to evaluate how glucose levels throughout pregnancy relate to traditional third trimester gestational diabetes mellitus (GDM) screening and perinatal outcomes.

Detailed Description
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GO MOMs is an observational study designed to characterize the glycemic profile of pregnancy using continuous glucose monitoring (CGM) technology in order to develop criteria using CGM measurements and/or early pregnancy oral glucose tolerance testing (OGTT) at 10w0d-14w0d gestation that are predictive, along with clinical factors, of adverse pregnancy outcomes in mothers and their newborns. GO MOMs involves multiple institutions and an anticipated 2150 participants. Participants will attend 4 research study visits: Visit 1 (10w0d-14w0d gestation), Visit 2 (16w0d-20w0d gestation), Visit 3 (24w0d-28w0d gestation), and Visit 4 (32w0d-36w0d gestation). Additional data will be collected at a Delivery Visit and via chart abstraction. Mothers will have a Remote Follow-up call after delivery to collect additional data. At Visits 1-4, a blinded CGM sensor will be placed. Participants will be instructed to wear the sensor for 10 days after which time they will follow instructions to return it to their study site. At Visit 1 (10w0d-14w0d gestation), participants will undergo a 75 g 2-hour (hr) OGTT. At Visit 3 (24w0d-28w0d gestation), participants will undergo a 100 g 3 hr OGTT. Visit 1 will include an extended maternal interview to collect social and demographic, medical history, obstetrical history, surgical history, family medical history, current health and pregnancy, and lifestyle (sleep, alcohol, tobacco use) data. Medical history, alcohol and tobacco use data will be updated at each study visit. Sleep data will be updated at Visit 3 (24w0d-28w0d gestation). Blood and urine samples will also be obtained at each visit for additional laboratory testing and some will be stored for ancillary investigations. At the Delivery Visit, newborn physical measurements including weight, length and skinfolds will be performed. Birthweight at delivery will also be obtained through chart abstraction. Primary statistical analyses will be performed to develop predictive criteria based on CGM and/or OGTT measures at Visit 1 (10w0d-14w0d gestation) along with clinical factors for primary maternal and newborn outcomes. Secondary analyses will further refine predictive models and will evaluate associations of maternal glucose with secondary outcomes and longitudinal modeling of maternal glycemia over the course of pregnancy. GO MOMs Nutrition Substudy: The GO MOMs Nutrition Study is an observational substudy nested within the GO MOMs parent study. The goal of the study is to describe self-reported dietary components in a diverse cohort of pregnant individuals and to study the relationship between maternal diet and outcomes including maternal glycemia, maternal insulin physiology, infant birth weight, and infant fat mass. Participants will complete 6 dietary recalls via the Automated Self-Administered 24-hour (ASA24) Dietary Assessment Tool during their pregnancies (Figure). Two will occur at visits and four will be unannounced, meaning they are completed on a random day without advance notice, during CGM wear. In addition, stored samples from all GO MOMs participants at visit 1 and 3 will be assayed for other nutritional markers. Primary statistical analyses will be used to identify associations between dietary carbohydrate content at <22 weeks' gestation and maternal glycemia 24-28 weeks' gestation and neonatal birthweight.

Official Title
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Glycemic Observation and Metabolic Outcomes in Mothers and Offspring / Glycemic Profile of Pregnancy Consortium

Conditions
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Gestational Diabetes, Pregnancy Related

Intervention / Treatment
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* Other: Observational


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Maternal age >=18 at consent Singleton gestation 10w0d-14w0d gestation at the time of the Visit 1 OGTT and CGM placement according to study dating criteria Conceived using own oocyte Willing and able to wear CGM as directed and adhere to CGM instructions Planning to deliver at GO MOMs-affiliated hospital (see list of accrual sites in the protocol section Key Roles and Contact Information). Exclusion Criteria: Pre-existing diabetes at enrollment Currently self-monitoring blood glucose Current use of medication with glycemic effects Fetal malformation evident at or before enrollment that is likely lethal. This includes, but is not limited to, malformations such as anencephaly, hydrops, diffuse subcutaneous edema or cystic hygroma, ectopic cordis, and encephalocele Known fetal aneuploidy based on chorionic villus sampling Participation in other research study that may modify glycemic profile or study outcomes History of bariatric surgery Extensive skin changes or diseases making CGM sensor use problematic Significant allergy to adhesive Previous participation in GO MOMs Current bulimia or anorexia nervosa Overnight shift work that alters the sleep/wake periods Hemoglobin A1c >= 6.5%, fasting glucose >= 126 mg/dL or 2 hr glucose >= 200 mg/dL noted during OGTT at 10w0d-14w0d gestation Current psychiatric illness/social situation that would limit compliance with study requirements, as determined by the site investigator

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Pregnant women less than or equal to 14w0d gestation<br> | Other: Observational<br>* Observational<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gestational diabetes (GDM) | Primary outcome in GO MOMs mothers: Number of mothers diagnosed with gestational diabetes mellitus (GDM) using a 100 g 3 hr OGTT at 24w0d-28w0d gestation according to Carpenter-Coustan criteria (at least two of the timed glucose measurements greater than or equal to the following thresholds: fasting >= 95 mg/dL, 1 hr >= 180 mg/dL, 2 hr >= 155 mg/dL, 3 hr >= 140 mg/dL). | When participants are between 24 weeks 0 days pregnant to 28 weeks 0 days pregnant | 
| Large for gestational age (LGA) | Primary outcome in GO MOMs newborns: Number of newborns who are large for gestational age (LGA), defined as birthweight >90th percentile for gestational age according to Aris et al. (2019). The first birthweight after delivery obtained from medical chart abstraction will be used for defining the primary LGA outcome. | Delivery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hypertension | Secondary outcome in GO MOMs mothers: Number of mothers with hypertensive disorders of pregnancy including preeclampsia with and without severe features, gestational hypertension, eclampsia, and Hemolysis, Elevated Liver enzymes, and Low Platelet count (HELLP) syndrome, defined by the American College of Obstetricians and Gynecologists (ACOG) criteria | Evaluated 30-90 days after delivery through chart abstraction for any events occurring during pregnancy | 
| Cesarean delivery | Secondary outcome in GO MOMs mothers: Number of mothers with cesarean delivery | Delivery | 
| Sum of skinfolds | Secondary outcome in GO MOMs newborns: Newborn sum of flank, triceps, and subscapular skinfolds, evaluated as a continuous measure and dichotomized as >90th percentile. | Within 72 hours after delivery | 
| Small for gestational age (SGA) | Secondary outcome in GO MOMs newborns: Number of newborns who are small for gestational age (SGA), defined as birthweight < 10th percentile for gestational age according to Aris et al. (2019) | Delivery | 
| Preterm birth | Secondary outcome in GO MOMs newborns: Number of newborns with preterm birth, defined as delivery prior to estimated gestational age 37 weeks 0 days. | Delivery | 
| Shoulder dystocia | Secondary outcome in GO MOMs newborns: Number of newborns with shoulder dystocia, identified through chart abstraction and defined clinically, requiring documentation that providers applied maneuvers to reduce the shoulder at delivery. | Delivery | 
| Neonatal birth injury | Secondary outcome in GO MOMs newborns: Number of newborns with neonatal birth injury, identified through chart abstraction and defined as brachial plexus palsy or clavicular, humeral, or skull fracture. | Delivery | 
| Neonatal hypoglycemia | Secondary outcome in GO MOMs newborns: Number of newborns with neonatal hypoglycemia, identified through chart abstraction and defined as treated neonatal hypoglycemia. | Within 30 days after delivery | 
| Neonatal respiratory morbidity | Secondary outcome in GO MOMs newborns: Number of newborns with neonatal respiratory morbidity, identified through chart abstraction and defined as need for respiratory support within 72 hrs after birth and consisting of one or more of the following: the use of continuous positive airway pressure (CPAP) or high-flow nasal cannula for at least 2 consecutive hrs, supplemental oxygen with a fraction of inspired oxygen of at least 0.30 for at least 4 continuous hrs, extracorporeal membrane oxygenation (ECMO), or mechanical ventilation. A high flow of air or blended air and oxygen is defined as more than 1 liter per minute | Within 30 days after delivery | 
| Neonatal hyperbilirubinemia | Secondary outcome in GO MOMs newborns: Number of newborns with neonatal hyperbilirubinemia, identified through chart abstraction and defined as treatment of hyperbilirubinemia in the first week of life with phototherapy or exchange transfusion or a diagnosis of kernicterus. | Within 30 days after delivery | 
| Nutrition Substudy: Mean CGM glucose in mothers | Outcome in mothers for Nutrition Substudy: Mean CGM glucose at 24-28 weeks' gestation in mothers | When participants are between 24 weeks 0 days pregnant to 28 weeks 0 days pregnant | 
| Nutrition Substudy: Birthweight in newborns | Outcome in newborns in Nutrition Substudy: Birthweight for gestational age percentile. The first weight after delivery from the medical record will be used for defining the primary outcome. | Delivery | 
| Nutrition Substudy: Percent time above various glycemic thresholds at 24-28 weeks | Secondary outcome in mothers for Nutrition Substudy: Percent time above various glycemic thresholds: 100 miligrams/deciliter, 105 miligrams/deciliter, 110 miligrams/deciliter, 120 miligrams/deciliter, 140 miligrams/deciliter, as measured by continuous glucose monitor at 24-28 weeks' gestation. | When participants are between 24 weeks 0 days pregnant to 28 weeks 0 days pregnant | 
| Nutrition Substudy: Mean nocturnal glucose | Secondary outcome in mothers for Nutrition Substudy: Mean nocturnal glucose (12am-6am) in miligrams/deciliter, as measured by continuous glucose monitor at 24-28 weeks' gestation. | When participants are between 24 weeks 0 days pregnant to 28 weeks 0 days pregnant | 
| Nutrition Substudy: Percent time above various glycemic thresholds at 16-36 weeks | Secondary outcome in mothers for Nutrition Substudy: Maternal continuous glucose monitor-assessed glucose defined as percent time above various glycemic thresholds: 100 miligrams/deciliter, 105 miligrams/deciliter, 110 miligrams/deciliter, 120 miligrams/deciliter, 140 miligrams/deciliter, as measured by continuous glucose monitor at 16-20, 24-28, and 32-36 weeks' gestation. | When participants are between 16 weeks 0 days pregnant to 36 weeks 0 days pregnant | 
| Nutrition Substudy: Insulin resistance | Secondary outcome in mothers for Nutrition Substudy: Insulin resistance, as estimated by the Matsuda index quantified during the oral glucose tolerance test at 24-28 weeks' gestation. The Matsuda index calculates whole body insulin resistance, with insulin resistance defined as being equal to or lower than 2.5. | When participants are between 24 weeks 0 days pregnant to 28 weeks 0 days pregnant | 
| Nutrition Substudy: Insulin secretory response | Secondary outcome in mothers for Nutrition Substudy: Insulin secretory response, as estimated by the ratio of insulin area under the curve to glucose area under the curve, during oral glucose tolerance test at 24-28 weeks' gestation. | When participants are between 24 weeks 0 days pregnant to 28 weeks 0 days pregnant | 
| Nutrition Substudy: gestational diabetes mellitus diagnosis | Secondary outcome in mothers for Nutrition Substudy: Gestational diabetes mellitus, diagnosed using Carpenter-Coustan criteria applied to an oral glucose tolerance test at 24-28 weeks' gestation. | When participants are between 24 weeks 0 days pregnant to 28 weeks 0 days pregnant | 
| Nutrition Substudy: Neonatal flank skinfold | Secondary outcome in newborns for Nutrition Substudy: Neonatal flank skin fold, measured in millimeters within 72 hours of delivery. | Within 72 hours of delivery | 
| Nutrition Substudy: Neonatal fat mass | Secondary outcome in newborns for Nutrition Substudy: Neonatal fat mass as estimated by flank skinfold, measured as percent body fat, within 72 hours of delivery. | Within 72 hours of delivery | 
| Nutrition Substudy: large for gestational age birthweight | Secondary outcome in newborns for Nutrition Substudy: Large for gestational age birth weight defined as birth weight > 90th percentile for gestational age. | Delivery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pregnancy, observational, gestational diabetes, continuous glucose monitor, oral glucose tolerance test, gestational diabetes mellitus, GDM, OGTT, CGM, glucose tolerance test, glycemic regulation, large for gestational age