Previous Article in Journal
Association Mapping for Biomass and Kernel Traits in Doubled-Haploid Population Derived from Texas Wheat Cultivars
 
 
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Review

Physical Activity During Pregnancy and Gestational Weight Gain: Implications for Maternal–Fetal Epigenetic Programming and Long-Term Health

by
Nektaria Zagorianakou
1,
Stylianos Makrydimas
2,
Efthalia Moustakli
1,
Ioannis Mitrogiannis
3,
Ermanno Vitale
4 and
George Makrydimas
5,*
1
Department of Nursing, School of Health Sciences University of Ioannina, 4th Kilometer National Highway Str. Ioannina-Athens, 45500 Ioannina, Greece
2
Medical School, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece
3
Harris Birthright Research Centre for Fetal Medicine, King’s College London, London SE5 8BB, UK
4
Department of Medicine and Surgery, University of Enna “Kore”, 94100 Enna, Italy
5
Department of Obstetrics & Gynecology, University Hospital of Ioannina, 45500 Ioannina, Greece
*
Author to whom correspondence should be addressed.
Genes 2025, 16(10), 1173; https://doi.org/10.3390/genes16101173
Submission received: 26 August 2025 / Revised: 19 September 2025 / Accepted: 2 October 2025 / Published: 6 October 2025
(This article belongs to the Section Epigenomics)

Abstract

Background/Objectives: Gestational weight gain (GWG) is a crucial factor influencing mother and fetal health, as high GWG is associated with adverse pregnancy outcomes and an increased long-term risk of obesity and metabolic issues in the children. In addition to controlling weight, maternal physical activity (PA) during pregnancy may influence fetal development through potential epigenetic mechanisms, including histone modifications, DNA methylation, and the production of non-coding RNA. Methods: This narrative review synthesizes evidence from randomized controlled trials (RCTs; n = 11, 3654 participants) investigating the impact of aerobic PA on GWG, while also highlighting emerging, primarily indirect findings on maternal–fetal epigenetic programming. Results: The majority of RCTs found that supervised PA interventions, especially when paired with nutritional counseling, decreased both the incidence of excessive GWG and total GWG. Enhancements in lipid metabolism, adipokine profiles, and maternal insulin sensitivity point to likely biochemical mechanisms that connect PA to epigenetic modification of fetal metabolic genes (e.g., IGF2, PGC-1α, LEP). Animal and observational studies suggest that maternal activity may influence offspring epigenetic pathways related to obesity and cardiometabolic conditions, although direct human evidence is limited. Conclusions: In addition to potentially changing gene–environment interactions throughout generations, prenatal PA is a low-cost, safe method of improving maternal and newborn health. Future RCTs ought to incorporate molecular endpoints to elucidate the epigenetic processes by which maternal exercise may provide long-term health benefits.

1. Introduction

Pregnancy is a complex physiological state requiring comprehensive clinical monitoring to ensure optimal maternal and fetal outcome. Standard prenatal care includes screening for chromosomal aneuploidies [1], assessment of fetal anatomy and growth [2], and evaluation of maternal risk for complications such as gestational diabetes mellitus (GDM) and preeclampsia [3]. Gestational weight gain (GWG) is an important clinical parameter, as deviations from established recommendations are associated with increased maternal and neonatal morbidity [4,5]. Accordingly, at each routine prenatal visit, healthcare providers should assess maternal weight and provide individualized, evidence-based guidance to support gestational weight gain within the ACOG-recommended ranges, which are approximately 12.5–18 kg for underweight, 11.5–16 kg for normal weight, 7–11.5 kg for overweight, and 5–9 kg for obese women [6].
Excessive GWG (EGWG) is a significant public health concern, associated with preterm birth, cesarean delivery, fetal macrosomia, infant mortality, GDM, and hypertensive disorders of pregnancy [7,8]. Additionally, EGWG has been implicated in adverse long-term outcomes for offspring through mechanisms of metabolic programming, increasing susceptibility to obesity, insulin resistance, and type 2 diabetes [9,10]. Both low and high birthweights independently heightened risks for obesity and cardiovascular disease in later life, underscoring the intergenerational impact of maternal weight management [11,12,13]. Globally, clinicians advocate for personalized lifestyle interventions to support appropriate GWG.
Physical activity (PA) during pregnancy has been consistently associated with improvements in physical and mental health [14,15], and a growing body of evidence suggests its potential in reducing risks of adverse outcomes including preterm birth and delivery complications [16,17,18,19,20,21,22]. Adherence to international guidelines, such as those from the World Health Organization, facilitates the safe integration of PA into prenatal care [23]. By improving placental perfusion, enhancing insulin sensitivity, and modulating inflammatory cytokines, maternal PA optimizes the intrauterine environment. Experimental and observational research also indicates that exercise may influence epigenetic modifications, such as DNA methylation and histone changes in genes that control growth and energy metabolism (e.g., IGF2, LEP, PGC-1α), which could reduce the risk of metabolic disease in offspring. However, direct evidence from human randomized controlledtrials (RCTs) remains limited, and results are heterogeneous depending on PA type, intensity, and adherence.
The framework for comprehending how maternal environment and behaviors, like exercise, may leave molecular “signatures” that endure across generations has been made possible by recent developments in epigenetics [24]. This notion is in line with the Developmental Origins of Health and illness (DOHaD) hypothesis, which holds that exposure to certain environmental factors during crucial developmental windows can influence a person’s chance of developing an illness in later life [25]. Maternal PA, for instance, has been linked to modifications in the methylation patterns of growth-related and metabolic genes (such as IGF2, LEP, and PGC-1α), indicating that lifestyle modifications may impact the regulation of fetal genes [26,27]. These results demonstrate PA’s potential as a gene-environment interaction modulator of intergenerational health in addition to its use as a GWG management method [28].
Many high-income nations estimate that 40–60% of people have EGWG, and rates are said to be rising worldwide. This rising trend highlights the pressing need for efficient preventative measures and coincides with rising rates of maternal obesity [29]. Significant gaps still exist despite the evidence supporting PA, including the optimal type, level, and timing of exercise during pregnancy, as well as the application of molecular results from animal models to humans. It is imperative to fill these gaps to improve maternal–fetal health outcomes globally and inform clinical recommendations [30].
This narrative review synthesizes current evidence from randomized controlled trials on the relationship between aerobic PA and GWG. It further explores potential molecular and epigenetic mechanisms, emphasizing that most human evidence is indirect. The aim is to provide obstetricians, gynecologists, and researchers with a comprehensive, evidence-based understanding of PA in pregnancy management and its possible implications for intergenerational health.

2. Methods

2.1. Literature Search and Study Selection

A narrative review of the literature was conducted to explore the association between PA, particularly aerobic exercise, and GWG in pregnant women. PubMed and Scopus databases were searched for articles published in English from January 2000 to June 2024. Search terms included combinations of “gestational weight gain” AND “pregnancy,” “excessive gestational weight gain” AND “physical activity,” and “excessive gestational weight gain” AND “exercise”. We acknowledge that alternative terminology such as “maternal exercise,” “prenatal physical activity,” or “weight control in pregnancy” may have identified additional studies.
The search initially identified 117 articles. After title and abstract screening, studies were excluded for irrelevance, duplicate publication, or failure to meet eligibility criteria. Screening and data extraction were performed independently by two authors, and discrepancies were resolved by discussion. Full-text review was then performed, and 11 articles were retained for final synthesis. The detailed selection process is presented in Figure 1.

2.2. Inclusion Criteria

Studies were included if they met the following criteria: (1) GWG was reported as a primary or secondary outcome; (2) the population consisted of pregnant women, including those who conceived via in vitro fertilization (IVF); and (3) the intervention involved aerobic exercise exclusively. Studies were considered regardless of whether the reported association between PA and GWG was positive, negative, or neutral.

2.3. Exclusion Criteria

Studies were excluded if they met any of the following conditions: (1) study design was a case report, case series, meta-analysis, systematic review, umbrella review, or study protocol; (2) the population involved non-human species, non-pregnant or postpartum individuals; (3) the focus was on genes, proteomics, or epigenetic changes rather than PA and GWG; (4) the study was retracted or not published in English; or (5) the primary topic was unrelated, such as COVID-19. Systematic reviews and meta-analyses were intentionally excluded to avoid duplication of data and maintain the focus on primary RCT evidence. A quality assessment was performed for all included studies using Cochrane Risk of Bias Tool (RoB 2.0). The risk of bias was evaluated in each study according to the following criteria: low risk, moderate concerns, or high risk. These criteria included the randomization method, variations from intended interventions, missing outcome data, measurement of outcomes, and selection of the reported results. The majority of studies demonstrated a low risk of bias for outcome reporting and randomization; however, certain issues with missing outcome data and blinding of outcome assessment were noted in a few trials.

3. Results

Following the application of the inclusion and exclusion criteria, the final review contained 11 RCTs with a total of 3654 participants. These studies assessed how GWG and associated maternal and newborn outcomes were affected by supervised aerobic exercise regimens, either with or without dietary advice.
The majority of RCTs demonstrated that PA treatments improved overall GWG, especially when combined with dietary counseling and when adherence was high. Several studies reported significant reductions in total GWG, incidence of excessive GWG, or improved metabolic parameters such as insulin sensitivity and neonatal adiposity. A detailed summary of the included studies is presented in Table 1.

3.1. Effects of Physical Activity on Gestational Weight Gain

Among the RCTs reviewed, several studies reported favorable effects of PA interventions on GWG. Ruchat et al. [40] found that women assigned to an exercise and diet regimen had over a 70% likelihood of remaining within the Institute of Medicine (IOM) recommendations (χ2 = 4.72, p = 0.32, not significant). Wang et al. [35] observed significant differences in GWG between intervention and control groups both at mid-pregnancy (4.08 ± 3.02 vs. 5.92 ± 2.58 kg; p < 0.001) and at term (8.38 ± 3.65 vs. 10.47 ± 3.33 kg; p < 0.001). Similarly, Nobles et al. [36] reported a 30% reduction in the odds of exceeding GWG guidelines (OR = 0.69, p = 0.30, not significant), though the 1 kg difference between groups was not statistically significant.
Other studies also demonstrated benefits of exercise programs. Barakat et al. (2018) [32] reported lower total GWG (12.19 vs. 13.33 kg; p = 0.005) and reduced incidence of EGWG (30.2% vs. 20.5%; OR = 0.597; p = 0.018) in the exercise group. Pelaez et al. [31] observed that participants with BMI ≥ 25 kg/m2 were less likely to exceed GWG recommendations (22.0% vs. 34.3%; p = 0.03). Barakat et al. (2014) [38] similarly found EGWG significantly less common among women engaging in exercise programs (21.2% vs. 35.6%; p = 0.02). The BHIP study suggested a trend toward meeting IOM criteria when combining diet and PA, although differences did not reach statistical significance [42].
In contrast, several trials reported no significant differences in GWG. McDonald et al. [41] observed slightly higher GWG in the intervention group (29.0 vs. 25.0 kg; p = 0.22). Nitert et al. [39] found no differences among obese participants (7.87 ± 4.00 vs. 8.28 ± 6.10 kg; p = 0.81), attributing this to low adherence. da Silva et al. [34], the PAMELA study [33], and Brik et al. [33] also reported non-significant GWG differences, although Brik et al. noted improvements in fetal cardiac function and postpartum weight recovery.
Most RCTs indicated that PA, particularly when combined with dietary advice and implemented with sufficient rigor and adherence, can help control gestational weight gain, although results are somewhat mixed and epigenetic effects have not been directly assessed [43,44].

3.2. Maternal Metabolic and Physical Health Outcomes

Beyond GWG, PA interventions demonstrated benefits for maternal metabolic health. Wang et al. [35] reported improvements in insulin sensitivity and reductions in neonatal birth weight among participants engaging in structured aerobic exercise. The DALI study by Simmons et al. [37] showed that combining healthy eating with PA reduced GWG in obese women, although metabolic outcomes were only modestly improved. Pelaez et al. [31] additionally noted enhanced maternal self-perception and physical fitness, highlighting the multidimensional benefits of prenatal exercise.

3.3. Fetal and Neonatal Outcomes

Potential benefits for the fetus were noted in several trials. Exercise groups exhibited improved fetal cardiac function, improved birth weight distribution, and decreased neonatal adiposity, indicating that maternal PA may have a favorable effect on the intrauterine environment. These metabolic and developmental advantages suggest that PA may have independent health benefits for offspring, even in cases where GWG was not considerably changed.

3.4. Epigenetic and Molecular Mechanisms

Maternal PA may alter development and metabolism-related molecular pathways, according to observational and animal research, even though none of the RCTs specifically evaluated epigenetic effects. Among the possible processes are changes in DNA methylation, histone modifications, and the expression of non-coding RNA in the placenta and cord blood, namely in genes like IGF2, LEP, and PGC-1α [45,46]. These molecular changes may partly explain how prenatal exercise contributes to long-term offspring health and support the concept of intergenerational benefits of maternal PA [47] (Figure 2).

4. Discussion

4.1. Impact of PA on GWG and Maternal Outcomes

This narrative review highlights the complex yet promising role of PA during pregnancy in regulating GWG and promoting maternal–fetal health. The majority of reviewed studies support the beneficial impact of structured exercise programs in helping women remain within the IOM guidelines for GWG, particularly when PA is combined with dietary counseling and sustained adherence [31,32,36,40,43].
Several trials reported significant reductions in total GWG and the incidence of EGWG. Notably, Barakat et al. and Wang et al. demonstrated potential improvements in maternal weight control and metabolic parameters, including enhanced insulin sensitivity and reduced neonatal birth weight [32,35]. These findings are clinically important as they suggest that PA may mitigate complications such as gestational diabetes mellitus (GDM), hypertensive disorders, and cesarean delivery while supporting normal birth outcomes and faster postpartum recovery [30,33].

4.2. Variability Among Studies and Role of Adherence

Not all studies observed consistent effects. McDonald et al. and Nitert et al. found no significant differences in GWG between intervention and control groups [39,41]. Such discrepancies may be attributed to variations in study design, participant characteristics (e.g., baseline BMI), type and intensity of PA interventions, and adherence rates. In particular, trials involving obese women often reported low compliance with exercise protocols, emphasizing that adherence is a critical determinant of intervention success [39,40]. A recurrent problem was low adherence, especially among obese women, indicating that compliance is a critical factor in determining the effectiveness of interventions. To increase participation and adherence, future research could use tactics like behavioral support, supervised sessions, or digital engagement tools.

4.3. Broader Maternal and Fetal Benefits

Beyond weight management, PA during pregnancy offers additional maternal benefits, including improved mood, reduced postpartum depression risk, better cardiovascular health, and reduced postpartum weight retention [31,36,40]. Enhanced maternal self-perception and physical fitness have also been reported [31,36,39,43]. From a fetal perspective, regular maternal exercise appears safe and may even confer advantages such as improved cardiac function and a reduced risk of macrosomia, a factor often associated with delivery complications [33].

4.4. Practical Recommendations for Clinicians

Clinicians should encourage pregnant women without contraindications to participate in at least 150 min of moderate-intensity aerobic exercise per week, preferably in 30- to 60-min sessions three to five times a week, according to current research and international guidelines [14,23]. The probability of reaching the recommended GWG is increased when PA is combined with customized nutritional counseling. To guarantee safety, exercise routines should be tailored to the woman’s fitness level and trimester, avoiding contact sports and supine positions after mid-pregnancy.

4.5. Barriers and Equity Considerations

Participation in PA may be restricted by cultural or financial barriers, lack of time, pregnancy-related exhaustion, and access to safe exercise facilities. Reducing disparities and enhancing adherence may be achieved by addressing these barriers through group classes, home-based programs, culturally specific education, and integration into regular prenatal visits. Many studies differ in intervention protocols, participant demographics, and outcome measures, limiting the generalizability of results [48], and few trials have explored the potential molecular or epigenetic mechanisms underlying the observed effects [49].

4.6. Epigenetic and Intergenerational Implications

Emerging evidence, primarily from animal models and observational studies, suggests that maternal PA may influence fetal epigenetic programming by modulating DNA methylation and histone modifications in metabolic pathways, potentially impacting offspring health in the long term. However, this remains an underexplored area requiring rigorous investigation [50].
From the standpoint of genes and environments, PA might act as a molecular regulator of intrauterine development. The metabolic environment resulting from exercise-induced improvements in maternal glucose regulation, adipokine secretion, and inflammatory balance can alter epigenetic markers in fetal tissues placenta [51]. Intergenerational programming effects are plausible, as evidenced by research conducted outside of the RCT paradigm that have connected maternal PA with altered DNA methylation in genes associated with growth and metabolism, including IGF2, LEP, and PGC-1α [50]. Similarly, non-coding RNA regulation and histone modifications might act as additional epigenetic control layers that enable maternal behavior to influence the phenotypes of her offspring [52].

4.7. Future Research and Directions

In addition to objectively tracking adherence, future RCTs should develop standardized exercise regimens tailored to diverse maternal demographics. To clarify underlying mechanisms, studies should include molecular endpoints such as placental omics analyses, longitudinal evaluations of cord blood DNA methylation, histone modifications, and non-coding RNA profiles. Understanding how maternal activity affects the health trajectories of subsequent generations would be advanced by integrating these methods with clinical outcomes like prenatal weight gain and child metabolic health.

4.8. Novelty and Contribution

To the best of our knowledge, this review is the first attempt to combine mechanistic theories about the epigenetic and intergenerational impacts of maternal physical activity with data from RCTs on GWG. This work offers a distinctive viewpoint that connects clinical outcomes and possible underlying biological pathways by fusing solid clinical trial data with new molecular discoveries. Emphasizing this integration highlights the manuscript’s value addition for clinicians and researchers interested in maternal–fetal health, and it may help guide the planning of further translational studies.

5. Conclusions

Optimizing GWG and reducing the risk of excessive weight gain during pregnancy can be achieved safely and effectively through PA. Evidence from randomized controlled trials supports its role in enhancing maternal metabolic health, decreasing pregnancy complications, and promoting positive neonatal outcomes. PA therapies are most effective when combined with nutritional counseling and consistent adherence. Incorporating structured exercise programs into routine prenatal care can help mothers and their unborn children experience healthier pregnancies and improved long-term health.

Author Contributions

Conceptualization, N.Z. and S.M.; methodology, E.M. and I.M.; validation, E.M., E.V. and G.M.; writing—original draft preparation, N.Z. and E.M.; writing—review and editing, S.M., I.M., E.V., and G.M.; visualization, N.Z. and E.M.; supervision, G.M.; project administration, G.M. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

No new data were created or analyzed in this study.

Conflicts of Interest

The authors declare no conflicts of interest.

Abbreviations

The following abbreviations are used in this manuscript:
GWGGestational Weight Gain
PAPhysical Activity
RCTsRandomized Control Trials
EGWGExcessive Gestational Weight Gain
DOHaDDevelopmental Origins of Health and Illness

References

  1. American College of Obstetricians and Gynecologists’ Committee on Practice Bulletins—Obstetrics, Committee on Genetics, Society for Maternal-Fetal Medicine. Screening for Fetal Chromosomal Abnormalities: ACOG Practice Bulletin, Number 226. Obstet. Gynecol. 2020, 136, e48–e69. [Google Scholar] [CrossRef]
  2. Salomon, L.J.; Alfirevic, Z.; Da Silva Costa, F.; Deter, R.L.; Figueras, F.; Ghi, T.; Glanc, P.; Khalil, A.; Lee, W.; Napolitano, R.; et al. ISUOG Practice Guidelines: Ultrasound assessment of fetal biometry and growth. Ultrasound Obstet. Gynecol. 2019, 53, 715–723. [Google Scholar] [CrossRef] [PubMed]
  3. ACOG Practice Bulletin, No. 190: Gestational Diabetes Mellitus. Obstet. Gynecol. 2018, 131, e49–e64. [Google Scholar] [PubMed]
  4. Goldstein, R.F.; Abell, S.K.; Ranasinha, S.; Misso, M.; Boyle, J.A.; Black, M.H.; Li, N.; Hu, G.; Corrado, F.; Rode, L.; et al. Association of Gestational Weight Gain with Maternal and Infant Outcomes: A Systematic Review and Meta-analysis. JAMA 2017, 317, 2207. [Google Scholar] [CrossRef] [PubMed]
  5. LifeCycle Project-Maternal Obesity and Childhood Outcomes Study Group; Voerman, E.; Santos, S.; Inskip, H.; Amiano, P.; Barros, H.; Charles, M.A.; Chatzi, L.; Chrousos, G.P.; Corpeleijn, E.; et al. Association of Gestational Weight Gain with Adverse Maternal and Infant Outcomes. JAMA 2019, 321, 1702. [Google Scholar] [CrossRef]
  6. Obesity in Pregnancy: ACOG Practice Bulletin, Number 230. Obstet. Gynecol. 2021, 137, e128–e144. [CrossRef] [PubMed]
  7. Goławski, K.; Giermaziak, W.; Ciebiera, M.; Wojtyła, C. Excessive Gestational Weight Gain and Pregnancy Outcomes. J. Clin. Med. 2023, 12, 3211. [Google Scholar] [CrossRef]
  8. Lackovic, M.; Jankovic, M.; Mihajlovic, S.; Milovanovic, Z.; Rovcanin, M.; Mitic, N.; Nikolic, D. Gestational Weight Gain, Pregnancy Related Complications and the Short-Term Risks for the Offspring. J. Clin. Med. 2024, 13, 445. [Google Scholar] [CrossRef]
  9. Godfrey, K.M.; Reynolds, R.M.; Prescott, S.L.; Nyirenda, M.; Jaddoe, V.W.; Eriksson, J.G.; Broekman, B.F. Influence of maternal obesity on the long-term health of offspring. Lancet Diabetes Endocrinol. 2017, 5, 53–64. [Google Scholar] [CrossRef]
  10. Poston, L.; Caleyachetty, R.; Cnattingius, S.; Corvalán, C.; Uauy, R.; Herring, S.; Gillman, M.W. Preconceptional and maternal obesity: Epidemiology and health consequences. Lancet Diabetes Endocrinol. 2016, 4, 1025–1036. [Google Scholar] [CrossRef]
  11. Barker, D.J.P. The developmental origins of adult disease. J. Am. Coll. Nutr. 2004, 23 (Suppl 6), 588S–595S. [Google Scholar] [CrossRef]
  12. Eriksson, J.; Forsén, T.; Osmond, C.; Barker, D. Obesity from cradle to grave. Int. J. Obes. Relat. Metab. Disord. J. Int. Assoc. Study Obes. 2003, 27, 722–727. [Google Scholar] [CrossRef]
  13. Boney, C.M.; Verma, A.; Tucker, R.; Vohr, B.R. Metabolic syndrome in childhood: Association with birth weight, maternal obesity, and gestational diabetes mellitus. Pediatrics 2005, 115, e290–e296. [Google Scholar] [CrossRef]
  14. Physical Activity and Exercise During Pregnancy and the Postpartum Period: ACOG Committee Opinion, Number 804. Obstet. Gynecol. 2020, 135, e178–e188. [CrossRef] [PubMed]
  15. Mottola, M.F.; Davenport, M.H.; Ruchat, S.M.; Davies, G.A.; Poitras, V.J.; Gray, C.E.; Jaramillo Garcia, A.; Barrowman, N.; Adamo, K.B.; Duggan, M.; et al. 2019 Canadian guideline for physical activity throughout pregnancy. Br. J. Sports Med. 2018, 52, 1339–1346. [Google Scholar] [CrossRef] [PubMed]
  16. Dumith, S.C.; Domingues, M.R.; Mendoza-Sassi, R.A.; Cesar, J.A. Atividade física durante a gestação e associação com indicadores de saúde materno-infantil. Rev. Saúde. Pública. 2012, 46, 327–333. [Google Scholar] [CrossRef] [PubMed]
  17. Davenport, M.H.; Ruchat, S.M.; Poitras, V.J.; Jaramillo Garcia, A.; Gray, C.E.; Barrowman, N.; Skow, R.J.; Meah, V.L.; Riske, L.; Sobierajski, F.; et al. Prenatal exercise for the prevention of gestational diabetes mellitus and hypertensive disorders of pregnancy: A systematic review and meta-analysis. Br. J. Sports Med. 2018, 52, 1367–1375. [Google Scholar] [CrossRef] [PubMed]
  18. Barakat, R.; Pelaez, M.; Cordero, Y.; Perales, M.; Lopez, C.; Coteron, J.; Mottola, M.F. Exercise during pregnancy protects against hypertension and macrosomia: Randomized clinical trial. Am. J. Obstet. Gynecol. 2016, 214, 649.e1-8. [Google Scholar] [CrossRef]
  19. Stuebe, A.M.; Oken, E.; Gillman, M.W. Associations of diet and physical activity during pregnancy with risk for excessive gestational weight gain. Am. J. Obstet. Gynecol. 2009, 201, 58.e1-8. [Google Scholar] [CrossRef]
  20. Domingues, M.R.; Barros, A.J.; Matijasevich, A. Leisure time physical activity during pregnancy and preterm birth in Brazil. Int. J. Gynaecol. Obstet. Off. Organ. Int. Fed. Gynaecol. Obstet. 2008, 103, 9–15. [Google Scholar] [CrossRef]
  21. Hamann, V.; Deruelle, P.; Enaux, C.; Deguen, S.; Kihal-Talantikite, W. Physical activity and gestational weight gain: A systematic review of observational studies. BMC Public Health 2022, 22, 1951. [Google Scholar] [CrossRef] [PubMed]
  22. Tobias, D.K.; Zhang, C.; van Dam, R.M.; Bowers, K.; Hu, F.B. Physical activity before and during pregnancy and risk of gestational diabetes mellitus: A meta-analysis. Diabetes Care. 2011, 34, 223–229. [Google Scholar] [CrossRef] [PubMed]
  23. Bull, F.C.; Al-Ansari, S.S.; Biddle, S.; Borodulin, K.; Buman, M.P.; Cardon, G.; Carty, C.; Chaput, J.P.; Chastin, S.; Chou, R.; et al. World Health Organization 2020 guidelines on physical activity and sedentary behaviour. Br. J. Sports Med. 2020, 54, 1451–1462. [Google Scholar] [CrossRef] [PubMed]
  24. Keating, D.P. Transformative Role of Epigenetics in Child Development Research: Commentary on the Special Section. Child Dev. 2016, 87, 135–142. [Google Scholar] [CrossRef]
  25. Lacagnina, S. The Developmental Origins of Health and Disease (DOHaD). Am. J. Lifestyle Med. 2020, 14, 47–50. [Google Scholar] [CrossRef]
  26. Faienza, M.F.; Urbano, F.; Anaclerio, F.; Moscogiuri, L.A.; Konstantinidou, F.; Stuppia, L.; Gatta, V. Exploring Maternal Diet-Epigenetic-Gut Microbiome Crosstalk as an Intervention Strategy to Counter Early Obesity Programming. Curr. Issues Mol. Biol. 2024, 46, 4358–4378. [Google Scholar] [CrossRef]
  27. Saftić Martinović, L.; Mladenić, T.; Lovrić, D.; Ostojić, S.; Dević Pavlić, S. Decoding the Epigenetics of Infertility: Mechanisms, Environmental Influences, and Therapeutic Strategies. Epigenomes 2024, 8, 34. [Google Scholar] [CrossRef]
  28. Virolainen, S.J.; VonHandorf, A.; Viel, K.C.M.F.; Weirauch, M.T.; Kottyan, L.C. Gene-environment interactions and their impact on human health. Genes Immun. 2023, 24, 1–11. [Google Scholar] [CrossRef]
  29. Langley-Evans, S.C.; Pearce, J.; Ellis, S. Overweight, obesity and excessive weight gain in pregnancy as risk factors for adverse pregnancy outcomes: A narrative review. J. Hum. Nutr. Diet. Off. J. Br. Diet. Assoc. 2022, 35, 250–264. [Google Scholar] [CrossRef]
  30. Corson, A.E.; MacDonald, M.; Tzaneva, V.; Edwards, C.M.; Adamo, K.B. Breaking boundaries: A chronology with future directions of women in exercise physiology research, centred on pregnancy. Adv. Exerc. Health Sci. 2024, 1, 67–75. [Google Scholar] [CrossRef]
  31. Pelaez, M.; Gonzalez-Cerron, S.; Montejo, R.; Barakat, R. Protective Effect of Exercise in Pregnant Women Including Those Who Exceed Weight Gain Recommendations: A Randomized Controlled Trial. Mayo. Clin. Proc. 2019, 94, 1951–1959. [Google Scholar] [CrossRef] [PubMed]
  32. Barakat, R.; Refoyo, I.; Coteron, J.; Franco, E. Exercise during pregnancy has a preventative effect on excessive maternal weight gain and gestational diabetes. A randomized controlled trial. Braz. J. Phys. Ther. 2019, 23, 148–155. [Google Scholar] [CrossRef] [PubMed]
  33. Brik, M.; Fernández--Buhigas, I.; Martin--Arias, A.; Vargas--Terrones, M.; Barakat, R.; Santacruz, B. Does exercise during pregnancy impact on maternal weight gain and fetal cardiac function? A randomized controlled trial. Ultrasound Obstet. Gynecol. 2019, 53, 583–589. [Google Scholar] [CrossRef] [PubMed]
  34. da Silva, S.G.; Hallal, P.C.; Domingues, M.R.; Bertoldi, A.D.; Silveira, M.F.D.; Bassani, D.; da Silva, I.C.M.; da Silva, B.G.C.; Coll, C.V.N.; Evenson, K. A randomized controlled trial of exercise during pregnancy on maternal and neonatal outcomes: Results from the PAMELA study. Int. J. Behav. Nutr. Phys. Act. 2017, 14, 175. [Google Scholar] [CrossRef]
  35. Wang, C.; Wei, Y.; Zhang, X.; Zhang, Y.; Xu, Q.; Sun, Y.; Su, S.; Zhang, L.; Liu, C.; Feng, Y.; et al. A randomized clinical trial of exercise during pregnancy to prevent gestational diabetes mellitus and improve pregnancy outcome in overweight and obese pregnant women. Am. J. Obstet. Gynecol. 2017, 216, 340–351. [Google Scholar] [CrossRef]
  36. Nobles, C.; Marcus, B.H.; Stanek, E.J., 3rd; Braun, B.; Whitcomb, B.W.; Manson, J.E.; Markenson, G.; Chasan-Taber, L. The Effect of an Exercise Intervention on Gestational Weight Gain: The Behaviors Affecting Baby and You (B.A.B.Y.) Study: A Randomized Controlled Trial. Am. J. Health Promot. AJHP. 2018, 32, 736–744. [Google Scholar] [CrossRef]
  37. Simmons, D.; Devlieger, R.; van Assche, A.; Jans, G.; Galjaard, S.; Corcoy, R.; Adelantado, J.M.; Dunne, F.; Desoye, G.; Harreiter, J.; et al. Effect of physical activity and/or healthy eating on GDM risk: The DALI Lifestyle Study. J. Clin. Endocrinol. Metab. 2016, 102, 903–913. [Google Scholar] [CrossRef]
  38. Barakat, R.; Cordero, Y.; Coteron, J.; Luaces, M.; Montejo, R. Exercise during pregnancy improves maternal glucose screen at 24-28 weeks: A randomised controlled trial. Br. J. Sports Med. 2012, 46, 656–661. [Google Scholar] [CrossRef]
  39. Dekker Nitert, M.; Barrett, H.L.; Denny, K.J.; McIntyre, H.D.; Callaway, L.K.; the BAMBINO group. Exercise in pregnancy does not alter gestational weight gain, MCP --1 or leptin in obese women. Aust. N Z J Obstet. Gynaecol. 2015, 55, 27–33. [Google Scholar] [CrossRef]
  40. Ruchat, S.M.; Davenport, M.H.; Giroux, I.; Hillier, M.; Batada, A.; Sopper, M.M.; Hammond, J.M.; Mottola, M.F. Nutrition and exercise reduce excessive weight gain in normal-weight pregnant women. Med. Sc.i Sports Exerc. 2012, 44, 1419–1426. [Google Scholar] [CrossRef]
  41. McDonald, S.M.; Isler, C.; Haven, K.; Newton, E.; Kuehn, D.; Kelley, G.; Chasan-Taber, L.; May, L.E. Moderate intensity aerobic exercise during pregnancy and 1-month infant Morphometry. Birth. Defects Res. 2021, 113, 238–247. [Google Scholar] [CrossRef]
  42. Atkinson, S.A.; Maran, A.; Dempsey, K.; Perreault, M.; Vanniyasingam, T.; Phillips, S.M.; Hutton, E.K.; Mottola, M.F.; Wahoush, O.; Xie, F.; et al. Be Healthy in Pregnancy (BHIP): A Randomized Controlled Trial of Nutrition and Exercise Intervention from Early Pregnancy to Achieve Recommended Gestational Weight Gain. Nutrients 2022, 14, 810. [Google Scholar] [CrossRef] [PubMed]
  43. da Silva, S.G.; Ricardo, L.I.; Evenson, K.R.; Hallal, P.C. Leisure-Time Physical Activity in Pregnancy and Maternal-Child Health: A Systematic Review and Meta-Analysis of Randomized Controlled Trials and Cohort Studies. Sports Med. Auckl. NZ 2017, 47, 295–317. [Google Scholar] [CrossRef] [PubMed]
  44. Hébert, J.R.; Frongillo, E.A.; Adams, S.A.; Turner-McGrievy, G.M.; Hurley, T.G.; Miller, D.R.; Ockene, I.S. Perspective: Randomized Controlled Trials Are Not a Panacea for Diet-Related Research. Adv. Nutr. Bethesda. Md. 2016, 7, 423–432. [Google Scholar] [CrossRef] [PubMed]
  45. Rojas-Rodriguez, R.; Price, L.L.; Somogie, J.; Hauguel-de Mouzon, S.; Kalhan, S.C.; Catalano, P.M. Maternal Lipid Metabolism Is Associated with Neonatal Adiposity: A Longitudinal Study. J. Clin. Endocrinol. Metab. 2022, 107, e3759–e3768. [Google Scholar] [CrossRef]
  46. Gómez-Vilarrubla, A.; Mas-Parés, B.; Carreras-Badosa, G.; Bonmatí-Santané, A.; Martínez-Calcerrada, J.-M.; Niubó-Pallàs, M.; de Zegher, F.; Ibáñez, L.; López-Bermejo, A.; Bassols, J. DNA Methylation Signatures in Paired Placenta and Umbilical Cord Samples: Relationship with Maternal Pregestational Body Mass Index and Offspring Metabolic Outcomes. Biomedicines 2024, 12, 301. [Google Scholar] [CrossRef]
  47. Lu, S.; Wang, J.; Kakongoma, N.; Hua, W.; Xu, J.; Wang, Y.; He, S.; Gu, H.; Shi, J.; Hu, W. DNA methylation and expression profiles of placenta and umbilical cord blood reveal the characteristics of gestational diabetes mellitus patients and offspring. Clin. Epigenetics 2022, 14, 69. [Google Scholar] [CrossRef]
  48. Deaton, A.; Cartwright, N. Understanding and misunderstanding randomized controlled trials. Soc. Sci. Med. 2018, 210, 2–21. [Google Scholar] [CrossRef]
  49. Mahmoud, A.M. An Overview of Epigenetics in Obesity: The Role of Lifestyle and Therapeutic Interventions. Int. J. Mol. Sci. 2022, 23, 1341. [Google Scholar] [CrossRef]
  50. Banik, A.; Kandilya, D.; Ramya, S.; Stünkel, W.; Chong, Y.S.; Dheen, S.T. Maternal Factors that Induce Epigenetic Changes Contribute to Neurological Disorders in Offspring. Genes 2017, 8, 150. [Google Scholar] [CrossRef]
  51. Mittal, R.; Prasad, K.; Lemos, J.R.N.; Arevalo, G.; Hirani, K. Unveiling Gestational Diabetes: An Overview of Pathophysiology and Management. Int. J. Mol. Sci. 2025, 26, 2320. [Google Scholar] [CrossRef]
  52. Cai, S.; Quan, S.; Yang, G.; Chen, M.; Ye, Q.; Wang, G.; Yu, H.; Wang, Y.; Qiao, S.; Zeng, X. Nutritional Status Impacts Epigenetic Regulation in Early Embryo Development: A Scoping Review. Adv. Nutr. 2021, 12, 1877–1892. [Google Scholar] [CrossRef]
Figure 1. PRISMA flow diagram illustrating the study selection process. Abbreviations: RCT = Randomized Control Trial; GWG = gestational weight gain; PA = physical activity. Note: NS indicates results that were not statistically significant.
Figure 1. PRISMA flow diagram illustrating the study selection process. Abbreviations: RCT = Randomized Control Trial; GWG = gestational weight gain; PA = physical activity. Note: NS indicates results that were not statistically significant.
Genes 16 01173 g001
Figure 2. Pathway from exercise to maternal physiology, then epigenetic changes, and finally to intergenerational health benefits. These steps are based on limited and indirect human data and should not be interpreted as established causal effects. ↓ = low; ↑ = high.
Figure 2. Pathway from exercise to maternal physiology, then epigenetic changes, and finally to intergenerational health benefits. These steps are based on limited and indirect human data and should not be interpreted as established causal effects. ↓ = low; ↑ = high.
Genes 16 01173 g002
Table 1. Summary of included RCTs on aerobic PA during pregnancy outcomes related to GWG.
Table 1. Summary of included RCTs on aerobic PA during pregnancy outcomes related to GWG.
First Author (Year)CountrySample SizeIntervention (Frequency/Timing)Population CharacteristicsPrimary/Secondary OutcomesKey Findings
Pelaez et al. (2019) [31]Spain345Moderate–vigorous exercise 3×/week from 12–38 weeksBMI stratified; avg age ~30GWG, adherence, GDM↓EGWG (esp. BMI ≥ 25), improved fitness
Barakat et al. (2019) [32]Spain594Moderate exercise 3×/week 8–39 weeksHealthy singleton pregnanciesGWG, GDM incidence↓Total GWG, ↓GDM
Brik et al. (2019) [33]Spain12060-min sessions 3×/weekLow-risk pregnanciesGWG, fetal cardiac functionNo GWG reduction, improved fetal cardiac parameters
da Silva et al. (2017) [34]Brazil639Exercise 3×/week 16–36 weeksMixed-risk populationGWG, preterm birth, GDMNS
Wang et al. (2017) [35]China300Cycling 3×/week < 13–37 weeksOverweight/obese womenGWG, GDM, insulin resistance↓GWG, ↓GDM, ↓birth weight
Nobles et al. (2018) [36]USA24112-week structured programEthnically diverseGWG (primary), adherence30% ↓odds EGWG (NS)
Simmons et al. (2016) [37]Europe436HE, PA, HE + PA interventionsObese womenGDM risk, GWGHE + PA ↓GWG; metabolic outcomes NS
Barakat et al. (2012) [38]Spain200Moderate exercise entire pregnancyHealthy nulliparasGWG, maternal/fetal outcomes↓EGWG, safe intervention
Dekker Nitert et al. (2015) [39]Australia35Individualized planObese womenGWG, metabolic markersNS
Ruchat et al. (2012) [40]Canada94Walking + nutrition controlNormal BMI womenGWG, postpartum weight↑IOM compliance, ↓postpartum weight
McDonald et al. (2021) [41]USA128Moderate exercise < 16 wks–deliveryHealthy pregnanciesNeonatal morphometry, GWG↓neonatal adiposity; GWG slightly ↑ (NS)
Abbreviations: GWG = gestational weight gain; EGWG = excessive gestational weight gain; GDM = gestational diabetes mellitus; HE = healthy eating; NS = not significant; PA = physical activity; IOM = Institute of Medicine. Note: NS indicates results that were not statistically significant. ↓ = low; ↑ = high.
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.

Share and Cite

MDPI and ACS Style

Zagorianakou, N.; Makrydimas, S.; Moustakli, E.; Mitrogiannis, I.; Vitale, E.; Makrydimas, G. Physical Activity During Pregnancy and Gestational Weight Gain: Implications for Maternal–Fetal Epigenetic Programming and Long-Term Health. Genes 2025, 16, 1173. https://doi.org/10.3390/genes16101173

AMA Style

Zagorianakou N, Makrydimas S, Moustakli E, Mitrogiannis I, Vitale E, Makrydimas G. Physical Activity During Pregnancy and Gestational Weight Gain: Implications for Maternal–Fetal Epigenetic Programming and Long-Term Health. Genes. 2025; 16(10):1173. https://doi.org/10.3390/genes16101173

Chicago/Turabian Style

Zagorianakou, Nektaria, Stylianos Makrydimas, Efthalia Moustakli, Ioannis Mitrogiannis, Ermanno Vitale, and George Makrydimas. 2025. "Physical Activity During Pregnancy and Gestational Weight Gain: Implications for Maternal–Fetal Epigenetic Programming and Long-Term Health" Genes 16, no. 10: 1173. https://doi.org/10.3390/genes16101173

APA Style

Zagorianakou, N., Makrydimas, S., Moustakli, E., Mitrogiannis, I., Vitale, E., & Makrydimas, G. (2025). Physical Activity During Pregnancy and Gestational Weight Gain: Implications for Maternal–Fetal Epigenetic Programming and Long-Term Health. Genes, 16(10), 1173. https://doi.org/10.3390/genes16101173

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop