The Association Between Exercise During Pregnancy and the Risk of Preterm Birth

Introduction

The World Health Organization defined preterm birth (PTB) as less than 37 weeks gestation.¹ PTB has posed significant risks to the health of both the children and the mothers. Complications of PTB were the main cause of death in children younger than 5 years of age globally in 2016, accounting for approximately 35% of deaths among newborn babies.² China had the second-highest rate of PTB in the world in 2014,³ which suggested that we should pay attention to the health of premature children. At the same time, women with preterm babies have a higher risk of developing cardiovascular disease prematurely and experiencing related mortality in the future.⁴ Since PTB leads a huge burden of disease, it is important to focus on women’s lifestyles during pregnancy to prevent PTB.

Physical exercise was a kind of planned, organized, and repetitive exercise designed to promote a healthy body. Exercise during pregnancy referred to any physical activity during pregnancy.⁵ Some studies have shown that both sedentary behavior and high-intensity exercise during pregnancy can increase the risk of premature rupture of membranes, and moderate-intensity exercise has been found to improve adverse pregnancy outcomes.^6–8

Although there have been many studies on the effect of exercise during pregnancy on PTB, of which the conclusions have been inconsistent. Studies from different regions have not found any correlation between exercise during pregnancy and PTB.^9,10 However, a birth cohort in Japan showed that compared with mothers with moderate levels of exercise, lower levels increased the risk of preterm delivery.⁶ Since people in different regions have different exercise habits, more research needs to be done. Furthermore, few previous studies have examined each trimester separately. As the internal physiological environment of a woman is a constantly changing process during pregnancy, further research is needed to examine the relationship between exercise during each trimester and PTB.

Some countries have set standards for exercise during pregnancy. For example, the American Congress of Obstetricians and Gynecologists, the Society of Obstetricians and Gynecologists of Canada, and the Canadian Society of Exercise Physiology had some detailed recommendations for pregnant women.^11–13 It is recommended that women with no medical contraindications get at least 20 to 30 minutes of aerobic exercise and strength conditioning exercises every day during pregnancy. These areas have high economic levels and belong to developed countries. Most of them have developed exercise health guidelines for pregnant women.¹⁴ However, in developing countries, although there have been studies on exercise during pregnancy and maternal health, they still lack appropriate guidelines for their own guidance.¹⁵ The latest physical activity guidelines for Chinese do not include a part specially for pregnant woman. It is necessary to make some appropriate guidelines for women in developing countries to have scientific physical exercise during pregnancy.

Therefore, based on the data from a birth cohort in Jinan, China, we aimed to examine the association between exercise during pregnancy and PTB, which could provide a basis for the establishment of exercise standards during pregnancy in China.

Materials and Methods

Source of Population

The source population was the women who gave their babies a second dose of the vaccine a month after giving birth, which constituted the baseline population of the Jinan birth cohort. The cohort was conducted in the capital city of Shandong Province in China, from December 2018 to December 2019. Data were collected in 15 community vaccination clinics which were selected from 116 community vaccination clinics in the study area. The details of the Jinan birth cohort have been described in the previous literature.^16,17

The study was approved by the Ethics Committee of Preventive Medicine of Shandong University (Approved number: 20170315) with the informed consent of all participants.

Study Subjects

The study subjects were the mothers of the Jinan birth cohort, who received a face-to-face questionnaire survey one month after giving birth. The exclusion criteria of this study were as follows: (1) the infant was delivered with congenital disease; (2) leaving Jinan during pregnancy; (3) having mental diseases or other diseases that affect normal communication; (4) multiple births or stillbirths.

Outcome Assessment

The outcome was PTB, which was defined as a newborn born on or before the end of the last day of the 37th week after the mother’s last menstrual period.¹⁸ This is the most extensively used and accepted definition of preterm birth.¹⁹ Gestational age information was calculated from the date of last menstrual period and birth recorded in the questionnaire. The date of the last menstruation was confirmed according to the B-ultrasound diagnosis of the hospital.

Exposure Assessment

A self-designed questionnaire for basic information of infants and mothers was used for a one-to-one face-to-face questionnaire survey. The information about infants included birth outcomes, newborn birth weight, and so on, the maternal information including her general demographic characteristics, family economic conditions, last menstrual period and gestational age, physical exercise during pregnancy (including the frequency, time, and primary exercise patterns), and others included maternal tobacco exposure, and work during pregnancy.

The interview questionnaire contained items about physical exercise during pregnancy and each trimester, refers to the 1st trimester (0 to 12 weeks of gestation), the 2nd trimester (13 to 28 weeks of gestation), and the 3rd trimester (after 28 weeks of gestation). There were some questions about exercise on the questionnaire: 1) “Have you exercised during pregnancy? The exercise means any planned, organized, and repetitive physical activity”. 2) “What is your primary exercise patterns (walking, brisk walking, yoga/Pilates/maternity gymnastics, swimming, squat and others) during pregnancy?” For each trimester, take the 1st trimester as an example, 3) “How many times do you exercise per week during the 1st trimester?” 4) “How many hours do you exercise at a time?”.

Since Chinese pregnancy health guidelines do not involve exercise during pregnancy, the subjects’ activity was grouped according to the previous studies and existing guidelines.^11,12 Time spent on exercise were grouped as none and low (0–2.49h/week), moderate (2.5–7h/week), and high (>7h/week).²⁰ One study defined “moderate exercise” as that requiring 4.5 METs (Metabolic Equivalent of Energy).²⁰ So, energy expenditures were grouped as none and low (0–11.24 MET.h/week), moderate (11.25–31.5 MET.h/week), and high (>31.5 MET.h/week). The calculation of energy expenditure was based on the previous criterion.²¹

Based on the questionnaires completed, the amount of time the women spent exercising during the entire pregnancy and three trimesters was calculated, and energy expenditure at different times was assessed.

Covariates

Four types of factors were considered to be covariates. Mother-related characteristics included maternal age (less than 25, 25–30, and more than 30 years old), occupation (housewife/others), and education (less than or equal to 9, 10–12, and more than 12 years).²² Pregnancy-related characteristics consisted of parity (primiparous/multiparous), delivery mode (natural birth/cesarean), pregnancy hypertension (yes/no), delivery complications (yes/no), work during pregnancy (yes/no), and tobacco exposure during pregnancy (yes/no).^22,23 Pregnancy complications included gestational hypertension (HDP), amniotic fluid embolism, abnormal umbilical cord, and so on. Work during pregnancy (no) meant pregnant women did not work during the whole pregnancy. Both active and passive smoking were classified as maternal tobacco exposure due to the low number of active smokers, passive smoking is defined as more than 30 minutes of tobacco exposure per week. In addition, we also selected infant gender (male/female) and family income (less than 6000 yuan/more than or equal to 6000 yuan).²²

Statistical Analyses

Categorical variables were compared by using the Chi-square test. For continuous variables, normality was tested by the Kolmogorov–Smirnov test. The independent sample t-test was used for normal data, the Wilcoxon-Mann–Whitney test was used for nonnormal data.

To assess the relationship between exercise during pregnancy and the risk of PTB, multiple logistic regression was used to calculate odds ratios (ORs) and 95% of the corresponding confidence intervals (95% CIs).

Variable selection for the multiple models was guided by the directed acyclic graph (DAG). The DAG was plotted to recognize potential causality, mediation, or confounding factors.²⁴ Furthermore, women’s exercise activity during pregnancy was grouped by time spent and energy expenditure, and the none and low group was used as a reference. The effect of each trimester was observed separately. For subgroup analysis, the subjects were stratified by whether they had pregnancy complications or not.

The mediating effect was analyzed by sequential test. Sequential test can effectively reduce the required sample size and is widely used in the study of median effect.²⁵

Statistical analyses were performed using the statistical computing environment R 4.0.5. P-value of <0.05 was considered statistically significant.

Results

The Characteristics of the Study Population

The final sample size for the study was 6501 women with singleton live births, included 285 PTBs and 6216 full-term births, the preterm rate was 4.38%.

Compared to women with full-term birth, mothers who experienced PTB tended to be older, be housewife, have more than one parity, be cesarean, have pregnancy complications, and lower family income (Table 1).

Table 1 Characteristics of the Study Population by PTB Status

The Characteristics of Exercise During Each Trimester

During the 3rd trimester and throughout pregnancy, the distribution of time spent was statistically different between the preterm and full-term women (P=0.005; P=0.045). The distribution of energy expenditure was statistically different during the 3rd trimester (P=0.007). More details were provided in Supplementary Table 1. Besides, for the patterns of exercise, most subjects (90.64%) chose the option of walking.

DAG

DAG (Figure 1) was plotted according to our data analysis and previous researches.^26,27 As demonstrated, when examining the relationship between PTB and exercise during pregnancy, the potential confounding factors may include age, parity, occupation, and family income. Pregnancy complications was a potential mediator, and it was not adjusted in multivariate analysis.²⁸

Figure 1 Directed acyclic graph of the association between exercise during pregnancy and PTB.

The Effect of Exercise During Pregnancy on PTB

Among women who did not exercise during pregnancy, the PTB rate was 5.37%. Among women who exercise during pregnancy, the PTB rate was 3.97%. Exercise during pregnancy was associated with 27% (OR = 0.73, 95% CI: 0.57–0.94) lower odds of PTB. After adjusting for the covariates, exercise during pregnancy was associated with 26% (OR = 0.74, 95% CI: 0.58–0.95) lower odds of PTB. For time spent on exercise per week, the moderate group (2.5–7h/week) was less likely to have PTB, the adjusted OR (95% CI) was 0.72 (0.55–0.94). For energy expenditure per week, the moderate group (11.25–31.5 MET.h/week) was less likely to have PTB, the adjusted OR (95% CI) was 0.75 (0.58–0.96) (Table 2).

Table 2 Association Between PTB and Exercise During Pregnancy

For each trimester (Figure 2), according to the time spent on exercise, using the none and low group (0–2.4h/week) as a reference, different trimesters had different results. During the 1st trimester, the moderate group (2.5–7h/week) was less likely to have PTB, the adjusted OR (95% CI) was 0.77 (0.59–0.99). During the 2nd trimester, the moderate group was less likely to have PTB, the adjusted ORs (95% CI) were 0.74 (0.57–0.96). During the 3rd trimester, the moderate group and the high group (>7h/week) were less likely to have PTB, the adjusted ORs (95% CI) were 0.74 (0.56–0.96) and 0.65 (0.44–0.94). According to the energy expenditure (Supplementary Table 2), during the 3rd trimester, the moderate group (>7h/week) was less likely to have PTB, the adjusted ORs (95% CI) were 0.74 (0.57–0.95). More details were provided in Supplementary Tables 2 and 3.

Figure 2 Association between PTB and exercise during each trimester.

The Results of Subgroup Analysis

Among subjects with pregnancy complications, PTB rates were high regardless of whether they exercised or not, and the adjusted OR (95% CI) for the risk of PTB related to exercise during pregnancy was 0.87 (0.45–1.74), which was not significant. Among subjects without pregnancy complications, exercise during pregnancy was associated with PTB, and the adjusted OR (95% CI) was 0.72 (0.55–0.95) (Table 3). However, after interaction analysis, no statistically significant interaction terms were found.

Table 3 Association Between PTB and Exercise During Pregnancy in Subgroup Analysis

The Mediating Effect of Pregnancy Complications on the Relationship Between PTB and Exercise During Pregnancy

Pregnancy complications partially mediated the relationship between exercise and PTB, and the mediating effect accounted for 52.40% of the total effect. More details for the results of mediating analysis were provided in Supplementary Table 4.

Discussion

In our study, the PTB rates were 3.97% and 5.37% among women who did or did not exercise during pregnancy. We found that exercise during pregnancy was associated with 26% (OR = 0.74, 95% CI: 0.58–0.95) lower odds of PTB.

We further divided pregnancy into three trimesters, to observe the relationship between exercise during each trimester and PTB. The results suggested that, during the 1st and 2nd trimesters, 2.5 to 7 hours of exercise per week was associated with lower odds of PTB. During the 3rd trimester, both 2.5 to 7 hours and more than 7 hours of exercise per week were associated with lower odds of PTB. Compared to the 1st and 2nd trimesters, the 3rd trimester may require a longer period of exercise.

For the association between exercise during pregnancy and PTB, most relevant studies agree with us. One study in Denmark showed a reduced risk of PTB among the women who exercised during pregnancy (OR = 0.82, 95% CI: 0.76–0.88).²⁹ A study in Southern California reported that both moderate exercise (OR = 0.90, 95% CI: 0.84–0.96) and vigorous exercise (OR = 0.67, 95% CI: 0.46–0.98) during pregnancy were associated with lower risk of PTB.³⁰ A meta-analysis included only randomized controlled trials (RCTs) of overweight or obese pregnant women, showed that women who had an aerobic exercise for about 30–60 min three to seven times per week had a lower percentage of PTB (RR = 0.62, 95% CI: 0.41–0.95) compared with controls.³¹ And two studies in China also had similar results. Huang did analyses about the relationship between maternal exercise frequency and duration during pregnancy and PTB, and the adjusted ORs ranged from 0.43 to 0.65.³² Cai reported that women who participated in physical exercise 1–2 times, 3–4 times, and over five times per week had 20% (OR =0.80, 95% CI: 0.68–0.92), 30% (OR = 0.70, 95% CI: 0.60–0.82), and 32% (OR = 0.68, 95% CI: 0.59–0.78) lower odds of PTB, respectively.²² The reason why the third trimester requires a longer period of exercise may be that pregnant women gained more weight during the 3rd trimester than during the 1st and 2nd trimesters, and proper exercise helps pregnant women maintain a reasonable weight.³³ Obesity alters levels of related inflammatory cytokines, and elevated levels of inflammatory cytokines can stimulate increased levels of oxytocin and lead to PTB.³⁴ Also, a longer time of relaxed exercise activities in the 3rd trimester may help pregnant women relieve tension, promote blood circulation, increase pelvic floor muscle strength, which can reduce the risk of PTB.³⁵

However, there were studies with negative results. For example, a cohort study in Brazil found no link between high or moderate physical activity and PTB,⁹ which may be due to racial differences and more research is needed.

Until now, the mechanism between exercise and PTB has several hypotheses. Firstly, placental hypoplasia is one of the important causes of PTB, and there is much evidence that exercise during pregnancy promotes placenta development.^36,37 For one thing, exercise leads to a significant increase in placenta volume during the second trimester.³⁶ For another, exercise during pregnancy promotes placenta angiogenesis.³⁷ Additionally, exercise during pregnancy may confer a protective effect against PTB through IL-10 mediated pathways.³⁸

After stratifying the subjects by whether they had pregnancy complications or not, the association between PTB and exercise during pregnancy only was found among subjects without pregnancy complications. People with pregnancy complications always are considered to be at high risk for PTB,²⁶ this may account for the effect of exercise on PTB was not significant in these people. We did not adjust pregnancy complications in multivariate analysis, because it was a potential mediator in the causal pathway between exposure and outcome, the adjustment of it in the model may affect the estimation of the results based on previous studies.²⁸ And our study indicated that pregnancy complications had a partial mediating effect, which was consistent with previous studies. A meta-analysis showed that exercise during pregnancy reduces the risk of HDP,¹⁰ which is considered a risk factor for PTB.²⁶

There are some strengths of this study. Firstly, this study specifically analyzes the 1st, 2nd, and 3rd trimester exercise and PTB. Secondly, this study provides relevant evidence for the formulation of relevant standards in China. Thirdly, we firstly found a partial mediating effect of pregnancy complications on the relationship between PTB and exercise during pregnancy.

We also have some limitations. There is recall bias due to the research method being a face-to-face questionnaire. In the multivariate analysis, we did not adjust the time spent on exercise during the 1st, 2nd, and 3rd trimester for each other, because there was collinearity between the three pregnancies. And there are some confounding factors we cannot control, such as dietary differences between regions.

Conclusion

Exercise during pregnancy can reduce the risk of PTB for women without pregnancy complications. 2.5 to 7 hours of exercise (like walking) per week may be appropriate in three trimesters of pregnancy, and the time can be extended in the 3rd trimester. To provide the basis for the formulation of exercise guidelines for pregnant women in China and Asia, more researches are needed to be done.