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Exercise, Inflammation and Preterm Labor
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Exercise, Inflammation, and Spontaneous Preterm Labor



Objective: Current research suggests that maternal systemic inflammation leads to the induction of preterm labor (PTL). Many environmental factors influence the activity of the innate and adaptive immune systems and thus, the amount of systemic inflammation that an individual experiences. Although the relationship between exercise patterns and systemic inflammation has been studied effectively in the general population, exercise studies in the context of pregnancy have been inconclusive and limited by poor study design. These few studies have failed to consider a variety of pro- and anti-inflammatory cytokines as markers of inflammation, and have not considered the intensity of exercise in relation to cytokine expression. Categorization of exercise intensity in general population studies has demonstrated that exercise cannot be treated as one all-encompassing variable because the physiological effects of exercise at different intensities are inherently distinct. Thus, our study aimed to effectively investigate antenatal exercise patterns in relationship to systemic inflammation and PTL by considering exercise intensity in relation to a variety of pro- and anti-inflammatory cytokines.

Methods: All data used for this study was collected through the Ontario Birth Study (OBS): a platform for research on pregnancy complications, and maternal and infant health. Out of 1375 pregnant participants, 40 experienced SPTB (delivery at <37 weeks) and 28 of these subjects completed the questionnaires containing exercise information and gave blood samples during the relevant periods (gestational age (GA) 16.2 and 27.1 weeks). Utilizing a case-control study design, this group was compared to 52 healthy pregnant controls that delivered at term (>37 weeks) and also provided blood samples at 16.2 and 27.1 weeks. Subjects were matched on age (<3 years difference) and parity (via dichotomization as nulliparous or multiparous). Luminex bead-based assays were used to simultaneously measure the concentration of 19 cytokines in maternal blood samples. Physical activity was assessed using the validated International Physical Activity Questionnaire (IPAQ).

Results: We found that PTL women tended to do less walking at 16.1 weeks GA than those who gave birth at term (p=0.055). Based on preliminary analyses, there is no significant relationship between cytokine concentration at 16.2 or 27.1 weeks GA and PTL or patterns of physical activity.

Conclusion: These results suggest that the contribution of physical activity, assessed cumulatively or based on intensity, is insignificant to total systemic inflammation. These results also suggest that systemic inflammation during pregnancy is not a reliable predictor of PTL.



•Preterm birth (<37 weeks gestation) occurs in 8-11% of pregnancies and is the leading cause of perinatal morbidity and mortalityi
•60% of preterm labors are spontaneous (sPTL), and 40% are associated with inflammation and infection at the maternal-fetal interfaceii
•The role of systemic inflammation in the onset of sPTL is less established, but literature suggests that high concentrations of pro-inflammatory cytokines throughout pregnancy may be predictive of sPTLiii
•Exercise immunology studies in the general population have shown that physical activity induces immune responses that differ with the intensity of exercise:
•High-intensity exercise tends to promote a predominantly pro-inflammatory response
•Low-intensity exercise tends to promote an acute pro-inflammatory response, followed by a sustained anti-inflammatory responseiv
•The literature surrounding exercise immunology and pregnancy is limited

1. Systemic inflammatory profiles of asymptomatic pregnant women could be predictive of spontaneous preterm birth.

2. Low intensity physical activity protects pregnant women from spontaneous preterm birth by inducing anti-inflammatory immune responses.

•To determine whether systemic inflammatory profiles of women who gave birth preterm (28-36 weeks of gestation) are different from women who delivered at term (≥37 weeks of gestation), and if so, whether these differences are gestational age-dependent



•To examine whether physical activity (in the form of walking, moderate- or high-intensity exercise) is associated with incidence of preterm birth
•To study systemic cytokine profiles in peripheral maternal plasma of asymptomatic pregnant women at 16 and 27 weeks of gestational age, and evaluate immune response to physical activity

The Ontario Birth Study began at Mount Sinai Hospital in 2013 and is an open, longitudinal cohort study designed to serve as a platform for research on maternal and infant health.

•Blood samples were collected from January 2013 - November 2015
•The International Physical Activity Questionnaire (IPAQ) was used to assess walking, moderate-intensity, and vigorous physical activity:
•Continuously: via computation to metabolic equivalents (MET-minutes) per week
•Categorically: via classification as “Inactive” or “Sufficiently Active”
•Luminex assays (BioRad) were used to quantify the concentration of 19 cytokines in maternal plasma samples collected at 16 and 27 weeks gestational age
•All data analyses were completed using SPSS and GraphPad Prism
•Categorical data was analyzed by Pearson’s chi-square tests, with Yates’ and Fisher’s corrections as required
•Numerical data was analyzed using independent t-tests

Figure 1) Assessment of exercise intensities in asymptomatic pregnant women at 16 and 27 weeks of gestation. Total MET-minutes of walking (A), moderate-intensity (B), and vigorous (C) physical activity, as well as cumulative (D) physical activity per week are shown. Women who delivered spontaneously preterm reported less walking at 16 and 27 weeks GA than women who subsequently delivered at term (p<0.01). Combination of all three categories of physical activity at 27 weeks GA showed that cumulatively, sPTL women exercised less than TL controls (p<0.01). Data presented as mean ± SEM. 

Figure 2) Categorization of activity levels indicating whether women are inactive or sufficiently active. The activity levels of sPTL and TL women were not different at either time point. Data presented as percentage of participants in each group (sPTL/TL). 

Figure 3) Categorization of physical activity level in relation to peripheral blood sample cytokine concentration. At 27 weeks GA, women who were sufficiently active had significantly higher concentrations of IL-17 (A), IFNγ(B), and IL-4 (C) than those who were inactive (p<0.05). Data presented as mean ± SEM. 



•There was no relationship between concentration of any of the 19 measured cytokines (IL-4, IL-10, IL-13, IL-1β, IL-2, IL-5, IL-6, IL-7, IL-12 (p70), IL-16, IL-17, TNFα, IFNγ, G-CSF, GM-CSF, IL-8, MIP-1β, MCP-1 and MCP-3) and incidence of spontaneous preterm delivery at 16 or 27 weeks GA
•Women who spontaneously gave birth preterm reported less walking at 16 and 27 weeks of gestation, and less cumulative exercise at 27 weeks of gestation
•Sufficiently active women had higher peripheral blood concentrations of IFNγ, IL-4, and IL-17 than women who were inactive
•Cytokines in peripheral blood plasma of asymptomatic pregnant women at 16 or 27 weeks of gestation are not predictive of spontaneous preterm birth
•Low-intensity exercise may be protective against sPTL
•Exercise modulates immune function in pregnant women by changing the concentration of pro- and anti-inflammatory cytokines
The authors would like to acknowledge funding from the Canadian Institute of Health Research (CIHR) for completion of this project. A special thank you to the Ontario Birth Study research nurses, research assistants, study participants, Biospecimen Repository staff, and staff of Mount Sinai’s Mother and Baby Unit and Labour and Delivery Unit for their contributions to the collection of data used in this study.
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