Study design and participants

We conducted a RCT at Peking University First Hospital from December 2014 through July 2016. A flow chart of the protocol is shown in the Figure . Overweight and obesity were determined based on body mass index (BMI) recommendations of the Group of China Obesity Task Force of the Chinese Ministry of Health accounting for interracial differences: overweight BMI ≥24-<28 kg/m ² and obese BMI ≥28 kg/m ² . Singleton, nonsmoking pregnant women with a prepregnancy BMI (p-BMI) of ≥24 kg/m ² at <12 ⁺⁶ weeks’ gestation were eligible for the study. The exclusion criteria were the following: (1) age <18 years; (2) women unwilling to provide informed consent; (3) women with cervical insufficiency (historical painless cervical dilation leading to recurrent second-trimester births in the absence of other causes; dilated cervix on manual or speculum examination; transvaginal ultrasound cervical length <25 mm at <24 weeks of gestation in singleton gestations with ≥1 prior spontaneous preterm births at 14-36 weeks) ; (4) women on any medication for preexisting hypertension, diabetes, cardiac disease, renal disease, systemic lupus erythematosus, thyroid disease, or psychosis; and (5) women who were currently being treated with metformin or corticosteroids.

Trial profile

Consolidated standards of reporting trials (CONSORT) 2010 flow diagram of study participants.

Wang et al. Exercise during pregnancy reduces gestational diabetes mellitus in overweight/obese pregnant women. Am J Obstet Gynecol 2017 .

This study was reviewed and approved by the Institutional Review Board of Peking University First Hospital (reference number: 2014[726]) and registered at www.clinicaltrials.gov (NCT02304718). All participants provided written informed consent, and the ethics committee approved the consent procedure.

Randomization and masking

Eligible women were randomly allocated (ratio 1:1) into either an exercise intervention group or a control group following an allocation concealment process using an automatic computer-generated random number table. The 3 parts of the randomization process, that is, sequence generation, allocation concealment, and implementation, were conducted by 3 different individuals. Due to the nature of the intervention, all participants and research staff were aware of the allocations.

Research procedures

Eligible pregnant women were approached by research staff at a prenatal care class specifically for women in early pregnancy at the Department of Obstetrics and Gynecology, Peking University First Hospital, and provided the project details. Those who were willing to participate were asked to complete a questionnaire to assess demographic information, medical and family history, and current pregnancy information. Qualified participants were then asked to sign informed consent and randomly allocated into a group. Provided permission was granted, and demographic information was collected from women who declined participation.

Participants allocated to the control group continued with their usual daily activities and were not discouraged from participating in exercise sessions on their own. In contrast, the participants randomized to the exercise group engaged in a supervised cycling program involving at least 3 sessions per week. The intervention was initiated within 3 days of randomization and continued to the end of the third trimester (weeks 36-37). All women received standard prenatal care throughout the intervention period, and they had equal numbers of usual visits with their obstetricians during pregnancy. All women received general advice about the positive effects of physical activity during pregnancy, and no special dietary recommendation were given.

The exercise protocol was based on a previous study showing the benefits of regular stationary cycling exercise for blood glucose control in women with GDM. All the exercise sessions occurred at Peking University First Hospital under supervision. Sessions were conducted on alternate days with the supervisor maintaining detailed records regarding the participants’ physiological indexes and compliance. At the start of the intervention, each exercise session consisted of stationary cycling for 30 minutes, beginning with a 5-minute warm-up at low intensity, which was 55-65% of the age-predicted heart rate maximum (HRmax) and a rating of perceived exertion (RPE) according to Borg scale between 9-11. RPE is the perceived score of difficulty when exercising, and is frequently used to subjectively monitor the exercise intensity based on individual perception. The Borg scale is the most frequently used method to evaluate individual RPE. This scale ranges from 6-20, where exercise is perceived to be “no exertion at all” to “very very hard,” respectively. Subsequently, 5 minutes of continuous moderate-intensity cycling (65-75% of the age-predicted HRmax; RPE 12-14) ensued. Next, the participants completed a period of interval cycling consisting of 30 seconds of rapid pedaling (sprints, higher intensity efforts) at 75-85% of the age-predicted HRmax and RPE 15-16 every 2 minutes for 3-5 intervals. This sprinting was followed by 5 minutes of continuous cycling at low-to-moderate intensity (60-70% of the age-predicted HRmax; RPE 10-12) before beginning another period of interval cycling. During this interval phase, continuous moderate-intensity cycling at 65-75% of the age-predicted HRmax (RPE 12-14) was interspersed with 1-minute periods of pedaling against increased resistance (hill climb) at 75-85% of the age-predicted HRmax (RPE 13-15); these periods alternated every 2 minutes for 3 repeats. Each session ended with a 5-minute cool down of easy cycling. At the start of the intervention, the women exercised at the lower end of the calculated heart rate ranges, with progressive increases as the program continued. Additionally, the exercise duration was progressively increased to 45-60 minutes by adding 5 minutes to the intervals or the continuous moderate-intensity cycling phases according to individual ability. The inclusion of periods of interval cycling was based on a previous study showing benefits for energy expenditure and exercise enjoyment in pregnant women.

All pregnant women who receive standard prenatal care at Peking University First Hospital have 4 routine ultrasound examinations throughout pregnancy at 11-13 ⁺⁶ , 20-23 ⁺⁶ , 30-30 ⁺⁶ , and 36-36 ⁺⁶ gestational weeks. Cervical length was measured at each examination. Due to the possibility of an increased risk of preterm birth caused by cycling-induced shortening of cervical length, to ensure and evaluate the safety of exercise during pregnancy, we recorded and reviewed cervical length at each examination and excluded those women with a cervical length <25 mm at any time during the intervention because uterine cervix length is an accurate predictor of the risk of preterm birth. For consistency, we also excluded those participants in the control group with a cervical length <25 mm.

Furthermore, at study entry, we measured each participant’s height to the nearest 0.5 cm without shoes and weight accurate to 0.1 kg with light clothing. BMI was calculated as maternal weight divided by height (kg/m ² ). Additionally, blood was drawn from the antecubital vein after the participant had fasted for at least 8 hours but not >14 hours and was collected in sterile vacutainer tubes preloaded with heparin. There was at least 24 hours between the last exercise bout and the time of blood draw. Blood was centrifuged at 1800 g at 4°C for 10 minutes within 4 hours of collection; subsequently, the plasma was separated and glucose was measured immediately. The remaining plasma was stored at –80°C for later analysis of insulin and lipid parameters (triglyceride, total cholesterol, and low- and high-density lipoprotein cholesterol). Insulin was measured using radioimmunoassay commercial kits (Beifang Institute of Biochemical Technology, Beijing, China). The insulin resistance index was calculated according to the homeostasis model of assessment: fasting plasma insulin (μU/mL) × fasting glucose (mmol/L)/22.5. Fasting lipid profiles were measured using an automatic analyzer (7600; Hitachi High-Technologies Corp, Tokyo, Japan) in the Department of Clinical Laboratory, Peking University First Hospital. Maternal body weight measurement and biochemical tests were repeated at 25 and 36 gestational weeks.

To assess the participants’ physical activity levels during pregnancy, the International Physical Activity Questionnaire was used at study entry and at 25 and 36 weeks’ gestation. The questionnaire included questions about the number of days per week and the time spent sitting, walking, and doing moderate and vigorous activities, and then a score, which is expressed as metabolic equivalents of task min/wk, can be calculated using the formula 8.0 × vigorous activity + 4.0 × moderate activity + 3.3 × light activity (walking) for the different activity categories.

At 24-28 weeks’ gestation, all participants underwent a 75-g oral glucose tolerance test (OGTT) after an overnight fast to diagnose GDM. Similarly, at least 24 hours elapsed between the last exercise session and the OGTT. According to the new criteria amended in August 2014 in China, GDM was diagnosed when any 1 value was ≥5.1 mmol/L at 0 hours, ≥10.0 mmol/L at 1 hour, or ≥8.5 mmol/L at 2 hours. Values of 7.0 mmol/L at 0 hours or 11.1 mmol/L at 2 hours were diagnosed as diabetes mellitus, regardless of pregnancy stage.

Outcomes

The primary outcome was the incidence of GDM (this has been reported as a letter in Diabetes Care , but this article includes a number of other important outcomes). The secondary outcomes included physical activity levels; gestational weight gain; biochemical outcomes, including insulin resistance and lipid profiles; maternal outcomes, such as gestational hypertension (defined as blood pressure elevation [systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg] >20 weeks’ gestation in the absence of proteinuria), preeclampsia (defined as new-onset hypertension [systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg] and new-onset proteinuria [300 mg of protein in 24 hours or a urine protein/creatinine ratio of 0.3 mg/dL] >20 weeks’ gestation or, in the absence of proteinuria, new-onset hypertension with new-onset thrombocytopenia, renal insufficiency, impaired liver function, pulmonary edema, or cerebral or visual disturbances), and mode of delivery (vaginal, operative vaginal, or cesarean); and neonatal outcomes, including gestational age at delivery, preterm birth (<37 and <34 weeks), Apgar score, birthweight, macrosomia (birthweight >4000 g), large-for-gestational-age (LGA) infants (birthweight >90th percentile for gestational age), and small-for-gestational-age (SGA) infants (birthweight <10th percentile for gestational age), both LGA and SGA were defined in accordance with international standards for sex-specific newborn size for each gestational age based on data from the Newborn Cross-Sectional Study subpopulation.

Statistical analysis

We calculated that a sample size of 121 participants in each group was sufficient to detect a 50% reduction in the incidence of GDM with an α of 0.05 and a statistical power (1-β) of 0.8 based on our previous study. Assuming a dropout rate of 10-15%, the target sample size was 150 in each group.

Data were analyzed using statistical software (SPSS, 17.0, IBM Corp, Armonk, NY). Continuous variables are presented as mean ± SD, and categorical variables are presented as numbers and percentages. Differences in the means between groups were evaluated using independent sample t tests and analysis of variance. Pearson χ ² test was used for categorical variables. Analysis was by intention to treat. The level of statistical significance was set at .05.

Study design and participants

We conducted a RCT at Peking University First Hospital from December 2014 through July 2016. A flow chart of the protocol is shown in the Figure . Overweight and obesity were determined based on body mass index (BMI) recommendations of the Group of China Obesity Task Force of the Chinese Ministry of Health accounting for interracial differences: overweight BMI ≥24-<28 kg/m ² and obese BMI ≥28 kg/m ² . Singleton, nonsmoking pregnant women with a prepregnancy BMI (p-BMI) of ≥24 kg/m ² at <12 ⁺⁶ weeks’ gestation were eligible for the study. The exclusion criteria were the following: (1) age <18 years; (2) women unwilling to provide informed consent; (3) women with cervical insufficiency (historical painless cervical dilation leading to recurrent second-trimester births in the absence of other causes; dilated cervix on manual or speculum examination; transvaginal ultrasound cervical length <25 mm at <24 weeks of gestation in singleton gestations with ≥1 prior spontaneous preterm births at 14-36 weeks) ; (4) women on any medication for preexisting hypertension, diabetes, cardiac disease, renal disease, systemic lupus erythematosus, thyroid disease, or psychosis; and (5) women who were currently being treated with metformin or corticosteroids.

Trial profile

Consolidated standards of reporting trials (CONSORT) 2010 flow diagram of study participants.

Wang et al. Exercise during pregnancy reduces gestational diabetes mellitus in overweight/obese pregnant women. Am J Obstet Gynecol 2017 .

This study was reviewed and approved by the Institutional Review Board of Peking University First Hospital (reference number: 2014[726]) and registered at www.clinicaltrials.gov (NCT02304718). All participants provided written informed consent, and the ethics committee approved the consent procedure.

Randomization and masking

Eligible women were randomly allocated (ratio 1:1) into either an exercise intervention group or a control group following an allocation concealment process using an automatic computer-generated random number table. The 3 parts of the randomization process, that is, sequence generation, allocation concealment, and implementation, were conducted by 3 different individuals. Due to the nature of the intervention, all participants and research staff were aware of the allocations.

Research procedures

Eligible pregnant women were approached by research staff at a prenatal care class specifically for women in early pregnancy at the Department of Obstetrics and Gynecology, Peking University First Hospital, and provided the project details. Those who were willing to participate were asked to complete a questionnaire to assess demographic information, medical and family history, and current pregnancy information. Qualified participants were then asked to sign informed consent and randomly allocated into a group. Provided permission was granted, and demographic information was collected from women who declined participation.

Participants allocated to the control group continued with their usual daily activities and were not discouraged from participating in exercise sessions on their own. In contrast, the participants randomized to the exercise group engaged in a supervised cycling program involving at least 3 sessions per week. The intervention was initiated within 3 days of randomization and continued to the end of the third trimester (weeks 36-37). All women received standard prenatal care throughout the intervention period, and they had equal numbers of usual visits with their obstetricians during pregnancy. All women received general advice about the positive effects of physical activity during pregnancy, and no special dietary recommendation were given.

The exercise protocol was based on a previous study showing the benefits of regular stationary cycling exercise for blood glucose control in women with GDM. All the exercise sessions occurred at Peking University First Hospital under supervision. Sessions were conducted on alternate days with the supervisor maintaining detailed records regarding the participants’ physiological indexes and compliance. At the start of the intervention, each exercise session consisted of stationary cycling for 30 minutes, beginning with a 5-minute warm-up at low intensity, which was 55-65% of the age-predicted heart rate maximum (HRmax) and a rating of perceived exertion (RPE) according to Borg scale between 9-11. RPE is the perceived score of difficulty when exercising, and is frequently used to subjectively monitor the exercise intensity based on individual perception. The Borg scale is the most frequently used method to evaluate individual RPE. This scale ranges from 6-20, where exercise is perceived to be “no exertion at all” to “very very hard,” respectively. Subsequently, 5 minutes of continuous moderate-intensity cycling (65-75% of the age-predicted HRmax; RPE 12-14) ensued. Next, the participants completed a period of interval cycling consisting of 30 seconds of rapid pedaling (sprints, higher intensity efforts) at 75-85% of the age-predicted HRmax and RPE 15-16 every 2 minutes for 3-5 intervals. This sprinting was followed by 5 minutes of continuous cycling at low-to-moderate intensity (60-70% of the age-predicted HRmax; RPE 10-12) before beginning another period of interval cycling. During this interval phase, continuous moderate-intensity cycling at 65-75% of the age-predicted HRmax (RPE 12-14) was interspersed with 1-minute periods of pedaling against increased resistance (hill climb) at 75-85% of the age-predicted HRmax (RPE 13-15); these periods alternated every 2 minutes for 3 repeats. Each session ended with a 5-minute cool down of easy cycling. At the start of the intervention, the women exercised at the lower end of the calculated heart rate ranges, with progressive increases as the program continued. Additionally, the exercise duration was progressively increased to 45-60 minutes by adding 5 minutes to the intervals or the continuous moderate-intensity cycling phases according to individual ability. The inclusion of periods of interval cycling was based on a previous study showing benefits for energy expenditure and exercise enjoyment in pregnant women.

All pregnant women who receive standard prenatal care at Peking University First Hospital have 4 routine ultrasound examinations throughout pregnancy at 11-13 ⁺⁶ , 20-23 ⁺⁶ , 30-30 ⁺⁶ , and 36-36 ⁺⁶ gestational weeks. Cervical length was measured at each examination. Due to the possibility of an increased risk of preterm birth caused by cycling-induced shortening of cervical length, to ensure and evaluate the safety of exercise during pregnancy, we recorded and reviewed cervical length at each examination and excluded those women with a cervical length <25 mm at any time during the intervention because uterine cervix length is an accurate predictor of the risk of preterm birth. For consistency, we also excluded those participants in the control group with a cervical length <25 mm.

Furthermore, at study entry, we measured each participant’s height to the nearest 0.5 cm without shoes and weight accurate to 0.1 kg with light clothing. BMI was calculated as maternal weight divided by height (kg/m ² ). Additionally, blood was drawn from the antecubital vein after the participant had fasted for at least 8 hours but not >14 hours and was collected in sterile vacutainer tubes preloaded with heparin. There was at least 24 hours between the last exercise bout and the time of blood draw. Blood was centrifuged at 1800 g at 4°C for 10 minutes within 4 hours of collection; subsequently, the plasma was separated and glucose was measured immediately. The remaining plasma was stored at –80°C for later analysis of insulin and lipid parameters (triglyceride, total cholesterol, and low- and high-density lipoprotein cholesterol). Insulin was measured using radioimmunoassay commercial kits (Beifang Institute of Biochemical Technology, Beijing, China). The insulin resistance index was calculated according to the homeostasis model of assessment: fasting plasma insulin (μU/mL) × fasting glucose (mmol/L)/22.5. Fasting lipid profiles were measured using an automatic analyzer (7600; Hitachi High-Technologies Corp, Tokyo, Japan) in the Department of Clinical Laboratory, Peking University First Hospital. Maternal body weight measurement and biochemical tests were repeated at 25 and 36 gestational weeks.

To assess the participants’ physical activity levels during pregnancy, the International Physical Activity Questionnaire was used at study entry and at 25 and 36 weeks’ gestation. The questionnaire included questions about the number of days per week and the time spent sitting, walking, and doing moderate and vigorous activities, and then a score, which is expressed as metabolic equivalents of task min/wk, can be calculated using the formula 8.0 × vigorous activity + 4.0 × moderate activity + 3.3 × light activity (walking) for the different activity categories.

At 24-28 weeks’ gestation, all participants underwent a 75-g oral glucose tolerance test (OGTT) after an overnight fast to diagnose GDM. Similarly, at least 24 hours elapsed between the last exercise session and the OGTT. According to the new criteria amended in August 2014 in China, GDM was diagnosed when any 1 value was ≥5.1 mmol/L at 0 hours, ≥10.0 mmol/L at 1 hour, or ≥8.5 mmol/L at 2 hours. Values of 7.0 mmol/L at 0 hours or 11.1 mmol/L at 2 hours were diagnosed as diabetes mellitus, regardless of pregnancy stage.

Outcomes

The primary outcome was the incidence of GDM (this has been reported as a letter in Diabetes Care , but this article includes a number of other important outcomes). The secondary outcomes included physical activity levels; gestational weight gain; biochemical outcomes, including insulin resistance and lipid profiles; maternal outcomes, such as gestational hypertension (defined as blood pressure elevation [systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg] >20 weeks’ gestation in the absence of proteinuria), preeclampsia (defined as new-onset hypertension [systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg] and new-onset proteinuria [300 mg of protein in 24 hours or a urine protein/creatinine ratio of 0.3 mg/dL] >20 weeks’ gestation or, in the absence of proteinuria, new-onset hypertension with new-onset thrombocytopenia, renal insufficiency, impaired liver function, pulmonary edema, or cerebral or visual disturbances), and mode of delivery (vaginal, operative vaginal, or cesarean); and neonatal outcomes, including gestational age at delivery, preterm birth (<37 and <34 weeks), Apgar score, birthweight, macrosomia (birthweight >4000 g), large-for-gestational-age (LGA) infants (birthweight >90th percentile for gestational age), and small-for-gestational-age (SGA) infants (birthweight <10th percentile for gestational age), both LGA and SGA were defined in accordance with international standards for sex-specific newborn size for each gestational age based on data from the Newborn Cross-Sectional Study subpopulation.

Statistical analysis

We calculated that a sample size of 121 participants in each group was sufficient to detect a 50% reduction in the incidence of GDM with an α of 0.05 and a statistical power (1-β) of 0.8 based on our previous study. Assuming a dropout rate of 10-15%, the target sample size was 150 in each group.

Data were analyzed using statistical software (SPSS, 17.0, IBM Corp, Armonk, NY). Continuous variables are presented as mean ± SD, and categorical variables are presented as numbers and percentages. Differences in the means between groups were evaluated using independent sample t tests and analysis of variance. Pearson χ ² test was used for categorical variables. Analysis was by intention to treat. The level of statistical significance was set at .05.