Exercise During Pregnancy: Effects on the Maternal-Fetal Unit (PREGFIT)

Benefits of Exercise for the Maternal-Fetal Unit During Pregnancy

Metabolic alterations during pregnancy have been associated with adverse maternal-fetal outcomes, including low birth weight and pregnancy complications. Maternal endothelial dysfunction, oxidative stress, insulin resistance, and placental mitochondrial dysfunction are thought to contribute to fetal metabolic disturbances. Lifestyle changes, such as structured exercise during pregnancy, may modulate maternal and placental factors.

This randomized controlled trial will evaluate the effects of a multicomponent exercise program during the second and third trimester on maternal functional capacity, vascular health, anthropometry, metabolic biomarkers, placental function, and newborn health outcomes.

Study Overview

• Status: Enrolling by invitation
• Conditions: Pregnancy
• Intervention / Treatment: Behavioral: Intervention

Detailed Description

To investigate the effects of a multicomponent supervised exercise program during pregnancy on the maternal-fetal unit.

• Study Type: Interventional
• Enrollment (Estimated): 64
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Spain
  • Navarre
    • Pamplona, Navarre, Spain, 31010
      • Navarrabiomed, Hospital Universitario de Navarra (HUN) and Universidad Pública de Navarra (UPNA)

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Primigravid women
• Gestational age 16-20 weeks
• No severe malformations on ultrasound
• Regular prenatal care and medical clearance from obstetrician
• Being healthy and able to exercise following American College of Obstetricians and Gynecologists (ACOG) guidelines

Exclusion Criteria:

• Medical or obstetric complication excluding exercise ( ACOG guideline) Major surgery or trauma in past year
• Cancer diagnosis
• Cervical incompetence
• History of ≥2 spontaneous abortions
• Multiple pregnancy
• Vaginal bleeding, placenta previa, or threatened abortion
• COPD, asthma, or chronic bronchitis
• Renal, musculoskeletal, cardiovascular, or systemic infections limiting exercise
• Polyhydramnios or oligohydramnios
• Not availability to attend to the physical exercise program

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Exercise training; Participants will perform a supervised aerobic exercise program at 70% of maximum heart rate (HRmax), for 45 minutes per session, 3 times per week, during 12 weeks. Each session will follow a standardized protocol: 10 minutes of warm-up, 30 minutes of aerobic exercise, 5 minutes of cool-down and stretching. In addition, strength training sessions will be included 1-2 times per week. All exercise sessions will be delivered by qualified professionals, including exercise specialists, nutritionists, and physiotherapists with >3 years of experience and a master's-level education in the field. The intervention will be conducted at the Exercise Physiology Unit (E-FIT Group Laboratory), Navarrabiomed Research Center, Pamplona, Spain.	Behavioral: Intervention; Exercise
No Intervention: Control; Usual care as provided by the health services in Spain. The investigators will not advice the women to be inactive.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cardiorespiratory fitness (Vo2max)	The modified cycle protocol will be performed to estimate maximal oxygen uptake (VO2max), and will be used as measure of cardiorespiratory fitness.	at the 16th and 34-36th week of gestation
Maternal weight gain (kg)	Maternal weight gain will be defined as the weight change from baseline measurement to the last measurement	34-36th week of gestation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Systolic and diastolic blood pressure (mmHg)	Systolic and diastolic blood pressure (mmHg) will be measured after 5 minutes of rest, on 2 separate occasions (with 2 minutes between trials), with the person seated (Omron Health Care Europe B.V. Hoolddorp). The lowest value of the two trials will be selected for the analysis.	at the 16th and 34-36th week of gestation
Resting heart rate (bpm)	Resting heart rate (bpm), will be measured after 5 minutes of rest, on 2 separate occasions (with 2 minutes between trials), with the person seated (Omron Health Care Europe B.V. Hoolddorp). The lowest value of the two trials will be selected for the analysis.	at the 16th and 34-36th week of gestation
Muscle strength (kg)	The handgrip strength and leg press test will be used as measure of strength (upper and lower limbs)	at the 16th and 34-36th week of gestation
Whole bone mineral density (g/cm2)	Dual-energy X-ray absorptiometry (DXA) body composition measure	at the 16th to 34-36th week of gestation
Fat free mass	Dual-energy X-ray absorptiometry (DXA) body composition measure	at the 16th to 34-36th week of gestation
Lean mass/fat mass ratio	Dual-energy X-ray absorptiometry (DXA) body composition measure	at the 16th to 34-36th week of gestation
Fat mass (kg)	Dual-energy X-ray absorptiometry (DXA) body composition measure	at the 16th to 34-36th week of gestation
Fat mass index (kg/m2)	Dual-energy X-ray absorptiometry (DXA) body composition measure	at the 16th to 34-36th week of gestation
Appendicular lean mass index (kg/m2)	Dual-energy X-ray absorptiometry (DXA) body composition measure	at the 16th to 34-36th week of gestation
Lean mass index (kg/m2)	Dual-energy X-ray absorptiometry (DXA) body composition measure	at the 16th to 34-36th week of gestation
Lean mass (kg)	Dual-energy X-ray absorptiometry (DXA) body composition measure	at the 16th to 34-36th week of gestation
Physical activity and sedentary behaviour (in minutes)	Accelerometry will be used to objectively assess physical activity and sedentary time. Women will be asked to wear a tri-axial accelerometer (ActiSleep+, Pensacola, Florida, United States) for 5-7 consecutive days, starting the same day they receive the monitor (e.g. participants who receive the accelerometer on Monday, will carry the device until Tuesday of the next week).	at the 16th and 34-36th week of gestation
Pittsburgh Sleep Quality Index	Accelerometry will be used to objectively assess physical activity and sedentary time. Women will be asked to wear a tri-axial accelerometer (ActiSleep+, Pensacola, Florida, United States) for 5-7 consecutive days, starting the same day they receive the monitor (e.g. participants who receive the accelerometer on Monday, will carry the device until Tuesday of the next week).	at the 16th and 34-36th week of gestation
Quality of life (EQ-5D-5L)	We will use the EQ-5D-5L survey, for assessing health-related quality of life, ranging from 0 ("worst imaginable health state") to 100 ("best imaginable health state"), with higher scores representing better perceived health.	at the 16th and 34-36th week of gestation
Epidemiological Studies-Depression Scale questionnaire	The pregnant antenatal depression levels will be assessed by the Center for Epidemiological Studies-Depression Scale questionnaire, which is validated and widely employed in pregnancy. The total score ranges from 0 to 60, with higher scores indicating more severe depressive symptoms.	at the 16th and 34-36th week of gestation
Oswestry Disability Index score	Low-back pain will be assessed with the Spanish version of the Oswestry Disability Index (ODI) score. The final ODI score ranges from 0 to 100, where 0 represents no disability and 100 represents maximum disability.	at the 16th and 34-36th week of gestation
Physical Activity index	Physical Activity will be assessed with the Spanish adaptation and validation of the Pregnancy Physical Activity Questionnaire (PPAQ). The scale ranges from 0 to 400+ MET·h/week, with higher scores indicating greater energy expenditure and physical activity levels.	at the 16th and 34-36th week of gestation
Pain Visual Analogue Scale	General or specific pain intensity will also be assessed using the Pain Visual Analogue Scale (VAS), a validated self-reported measure of perceived pain intensity. The VAS consists of a 10-centimeter horizontal line anchored by "no pain" (0) and "worst imaginable pain" (10) at each end. Participants will indicate their current pain level by marking a point along the line, with higher scores representing greater pain intensity.	at the 16th and 34-36th week of gestation
Cognitive Function	Global cognitive function will be assessed using the Montreal Cognitive Assessment (MoCA), a validated screening tool that evaluates multiple cognitive domains, including executive function, memory, attention, language, and visuospatial abilities. The total score ranges from 0 to 30, with higher scores indicating better cognitive performance.	at the 16th and 34-36th week of gestation
Adherence to the Mediterranean Diet	Adherence to the Mediterranean dietary pattern will be assessed using the Mediterranean Diet Adherence Screener (MEDAS), a validated 14-item questionnaire designed to evaluate compliance with key components of the Mediterranean diet. Each item is scored 0 or 1, depending on whether the dietary criterion is met, yielding a total score ranging from 0 to 14, where higher scores indicate greater adherence to the Mediterranean diet.	at the 16th and 34-36th week of gestation
Psychological Distress	The Kessler Psychological Distress Scale (K10) will be used to assess nonspecific psychological distress, including symptoms of anxiety and depression, experienced over the past four weeks. The K10 consists of 10 items, each rated on a 5-point Likert scale ranging from 1 (none of the time) to 5 (all of the time), resulting in a total score between 10 and 50. Higher scores indicate greater psychological distress.	at the 16th and 34-36th week of gestation
Erythrocytes	Erythrocyte count (×10⁶ cells/µL), will be measured using an automated Coulter haematology analyser (Brand, City, Country).	at 34th week of gestation and at delivery
Lipid profile (in mother and cord blood)	Plasma total, high-density lipoprotein and low-density lipoprotein cholesterol and triglycerides (all in mg/dL) will be assessed using an autoanalyzer.	at 34th week of gestation and at delivery
Plasma glucose (in mother and cord blood)	Plasma glucose concentrations will be determined using the glucose oxidase enzymatic colorimetric method.	at 34th week of gestation and at delivery
Total plasma antioxidant capacity (in mother and cord blood)	Total plasma antioxidant capacity (in maternal and cord blood) will be measured using a commercial colorimetric assay kit based on spectrophotometry, following the manufacturer's instructions. Results will be expressed in Trolox equivalents (mmol Trolox/L), where higher values indicate greater antioxidant capacity.	at 34th week of gestation and at delivery
Antioxidant enzymes activity (in mother and cord blood)	Erythrocyte membrane catalase, glutathione peroxidase, and superoxide dismutase enzyme activities will be measured by spectrophotometry using standard biochemical assays. Results will be expressed in units per milligram of hemoglobin (U/mg Hb), where higher values indicate greater enzymatic antioxidant activity.	at 34th week of gestation and at delivery
Pro- and anti-inflammatory signal (in mother and cord blood)	Some maternal and umbilical cord plasma pro-inflammatory and anti-inflammatory cytokines (IL-1β, IL-2, IL-6, IL-8, IL-10, IFN-γ and TNF-α, IL-1ra and TNF Srii α), some adipokines (adiponectin, adipsin, resistin, PAI-active, insulin and leptin) and myokines (irisin) will be measured by the employment of Luminex xMAP technology. Other relevant biomarkers related to bone metabolism (ACTH, DKK-1, FGF-23, Osteocalcin, OPN-Osteopontin, Osteoprotegerin, PTH and SOST) will be measured with Luminex xMAP technology. Each outcome will be reported separately, with concentrations expressed in pg/mL or ng/mL, as appropriate for the specific analyte.	at 34th week of gestation and at delivery
Birth weight	Birth weight will be recorded in grams (g).	At delivery
Delivery complications	Mode of delivery (vaginal or caesarean section) and any maternal or neonatal complications occurring during delivery will be obtained from hospital medical records and classified according to the attending obstetrician's report.	At delivery
Apgar score	Apgar score will be evaluated at 1 and 5 minutes after delivery by trained obstetric or neonatal staff, following standard clinical procedures. Scores range from 0 to 10, with higher values indicating better neonatal condition.	At delivery
Polypharmacy	Polypharmacy will be defined as the concurrent use of five or more medications.	At delivery and 6 and 12 months postpartum
Resting energy expenditure	Resting energy expenditure is measured in the fasting and fed state by indirect calorimetry	at the 16th and 34-36th week of gestation
Haematocrit	Haemoglobin concentration (g/dL) will be measured using an automated Coulter haematology analyser (Brand, City, Country).	at 34th week of gestation and at delivery
Platelet count and leukocyte	Platelet count (×10³ cells/µL) and leukocyte count (×10³ cells/µL) will be measured using an automated Coulter haematology analyser (Brand, City, Country).	at 34th week of gestation and at delivery
Mean corpuscular volume	Mean corpuscular volume (fL) will be measured using an automated Coulter haematology analyser (Brand, City, Country).	at 34th week of gestation and at delivery
Insulin levels (in mother and cord blood)	Plasma insulin levels will be quantified by enzyme-linked immunosorbent assay (ELISA).	at 34th week of gestation and at delivery
Glycosylated haemoglobin levels (in mother and cord blood)	Glycosylated haemoglobin (HbA1c) will be determined using the enzymatic colorimetric method.	at 34th week of gestation and at delivery
Body length and head circumference	Length in centimeters (cm), and head circumference in centimeters (cm).	At delivery
Hospitalization days	Hospitalization will be recorded as the number and duration of inpatient stays.	At delivery
Cost-effectiveness analyses	Cost-effectiveness analyses will be conducted based on health service utilization and associated costs extracted from the hospital database. Each outcome will be reported separately, with appropriate units (e.g., number of admissions, days hospitalized, number of medications, EQ-5D-5L index score, euros): Count (episodes, days, or medications), EQ-5D-5L index (score), and euros (€).	At delivery and 6 and 12 months postpartum

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Placental mitochondrial leak respiration	Mitochondrial oxygen (O₂) flux will be measured in placental tissue using high-resolution respirometry (Oroboros O₂k, Oroboros Instruments, Innsbruck, Austria). Tissue samples will be analyzed in fresh homogenates under controlled substrate-uncoupler-inhibitor titration (SUIT) protocols to evaluate basal, leak, and maximal respiratory states. Oxygen flux will be expressed as picomoles of O₂ consumed per second per milligram of tissue (pmol O₂·s-¹·mg-¹).	At delivery
Changes to maternal, placenta and umbilical cord proteome	Changes in proteome will be analyzed using the Olink® proximity extension assay (PEA) technology, following the manufacturer's standardized protocol (Olink Proteomics, Uppsala, Sweden). Protein abundance will be expressed as normalized protein expression (NPX) units, where higher NPX values indicate greater relative protein concentration.	At delivery

Collaborators and Investigators

• Sponsor: Universidad Pública de Navarra
• Collaborators: Complejo Hospitalario de Navarra; NavarraBiomed Biomedical Research Center; Instituto de Investigación Sanitaria de Navarra (IdiSNA)

Publications and helpful links

General Publications

• Ramirez-Velez R, Aguilar de Plata AC, Escudero MM, Echeverry I, Ortega JG, Salazar B, Rey JJ, Hormiga C, Lopez-Jaramillo P. Influence of regular aerobic exercise on endothelium-dependent vasodilation and cardiorespiratory fitness in pregnant women. J Obstet Gynaecol Res. 2011 Nov;37(11):1601-8. doi: 10.1111/j.1447-0756.2011.01582.x. Epub 2011 Jul 6.
• Ramirez-Velez R, Lobelo F, Aguilar-de Plata AC, Izquierdo M, Garcia-Hermoso A. Exercise during pregnancy on maternal lipids: a secondary analysis of randomized controlled trial. BMC Pregnancy Childbirth. 2017 Nov 28;17(1):396. doi: 10.1186/s12884-017-1571-6.
• Pinzon DC, Zamora K, Martinez JH, Florez-Lopez ME, de Plata AC, Mosquera M, Ramirez-Velez R. Type of delivery and gestational age is not affected by pregnant Latin-American women engaging in vigorous exercise: a secondary analysis of data from a controlled randomized trial. Rev Salud Publica (Bogota). 2012 Oct;14(5):731-43.

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2025
• Primary Completion (Estimated): December 15, 2027
• Study Completion (Estimated): December 20, 2027

Study Registration Dates

• First Submitted: September 23, 2025
• First Submitted That Met QC Criteria: December 1, 2025
• First Posted (Estimated): December 4, 2025

Study Record Updates

• Last Update Posted (Estimated): December 4, 2025
• Last Update Submitted That Met QC Criteria: December 1, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Exercise; Motor Activity
• Additional Relevant MeSH Terms: Behavior; Motor Activity; Investigative Techniques; Methods
• Other Study ID Numbers: PI_2024/148

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: This section provides details of the study plan, including how the study is designed and what the study is measuring.

Drug and device information, study documents

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