Clinical trial NCT03838146: Influence of Maternal Exercise on Infant Skeletal Muscle and Metabolomics
Official title: Influence of Maternal Exercise on Infant Skeletal Muscle and Metabolomics
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Exercise
Lead sponsor: East Carolina University
Sponsor class: OTHER
Collaborators: name: American Heart Association
First posted: 2019-02-12
Enrollment: 167
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: comparing 3 exercise interventions to a control (non-exercise) group
Primary purpose: PREVENTION

Brief summary: The American Heart Association suggests that heart disease prevention should target pregnancy and the first year of life; however, there is a fundamental gap in knowledge regarding the effects of prenatal exercise on the prevention of heart disease.\[1, 2\] Insulin resistance in skeletal muscle is believed to be a critical contributor to the metabolic syndrome which increases the risk for cardiovascular disease (CVD). Conversely, exercise improves insulin sensitivity and many other facets of skeletal muscle function and metabolism; however, it is unclear if this positive effect can be "imprinted" in the skeletal muscle of the fetus with maternal exercise and accordingly diminish CVD risk in offspring. Our previous studies found that exercise during pregnancy leads to improved heart measures and reduced adiposity.\[3-6\] These studies demonstrated the potential for maternal exercise to reduce risk for CVD, but the cellular mechanisms involved, however, are not clearly evident. The proposed project will fill this critical gap and assess the influence of maternal exercise intervention to "imprint" progenitor stem cells in the fetus (umbilical cord tissue) to develop into insulin sensitive skeletal muscle and also improve indices of infant morphometry and movement. Using a randomized design, 160 women will perform either exercise intervention (aerobic training, resistance training, or both) or usual care (controls). Infant cord tissue and blood will be sampled at birth while blood will be sampled at 1 month of age. Similarly, infant neuromotor and morphometric examinations will be performed at 1 month. and at 1-month of age via blood sample, neuromotor, and morphometric examinations. The rationale for the project is to elucidate the effects of maternal exercise on offspring health outcomes and determine specific metabolic targets predictive of offspring long-term disease risk. The investigators will test the central hypothesis that exercise during pregnancy alters skeletal muscle in a manner which decreases the risk of heart disease in offspring. To test this central hypothesis, the investigators will pursue two specific aims: Aim 1- Determine the ability of regular maternal exercise to imprint key myocellular metabolic (insulin sensitivity) properties of offspring mesenchymal stem cells (MSC), neuromotor function, and morphometry. Aim 2- Determine the distinct abilities of regular maternal exercise to imprint the metabolome of offspring MSC.

Detailed description: Is offspring skeletal muscle function and metabolism imprinted by regular maternal exercise? What offspring metabolome markers are altered with regular maternal exercise? The investigators will use a randomized design of 160 women to either exercise intervention (aerobic training, resistance training, or both) or usual care (controls). Infant cord tissue and blood will be sampled at birth while blood will be sampled at 1 month of age. Similarly, infant neuromotor and morphometric examinations will be performed at 1 month. and at 1-month of age via blood sample, neuromotor, and morphometric examinations. The rationale for the project is to elucidate the effects of maternal exercise on offspring health outcomes and determine specific metabolic targets predictive of offspring long-term disease risk.

Eligibility criteria: Inclusion Criteria:

* \<16 weeks gestation
* singleton pregnancy telephone/email contact

Exclusion Criteria:

* chronic conditions i.e. diabetes, hypertension, HIV, etc.
* use of medications that affect fetal development;
* use of alcohol, tobacco, or other drugs

Primary outcomes:
measure: Human Skeletal Muscles cells grown from MSCs will have insulin responsiveness measured
timeFrame: At Birth
Secondary outcomes:
measure: Global and targeted metabolomics analysis will be conducted to map out pathways and mechanisms from regular maternal exercise. Docosahexaenoic acid (DHA), Eicosapentaenoic Acid (EPA), Docosapentaenoic Acid (DPA), and Arachidonic acid (ARA).
timeFrame: At 16 weeks and 36 weeks gestation
measure: Peabody Developmental Motor Scales, 2nd edition (PDMS-2) will be performed by a pediatric physical therapist (blinded to group classification) to measure gross motor skills of infants up to 12 months of age.
timeFrame: at 1 month postnatal visit
measure: A trained (blinded) researcher will measure bicep, tricep, and subscapular skinfold measures, circumferences (abdominal, head, mid-upper arm), and lengths (body, femur, leg, humeral). All measures are recorded as mm.
timeFrame: at 1 month postnatal visit
measure: A trained (blinded) researcher will measure body weight on an infant scale
timeFrame: at 1 month postnatal visit
Other outcomes:
Locations:
city: Greenville
country: United States
facility: East Carolina University
state: North Carolina
Study officials:
References:
citation: McDonald SM, Mouro S, Wisseman B, Isler C, DeVente J, Newton E, Hildebrand J, Kuehn D, Kelley G, Chasan-Taber L, Broskey NT, May LE. Influence of prenatal exercise on the relationship between maternal overweight and obesity and select delivery outcomes. Sci Rep. 2022 Oct 15;12(1):17343. doi: 10.1038/s41598-022-22283-0.