ORP: Structured Programs and Interventions (2014)

Citation:

Hopkins SA, Baldi JC, Cutfield WS, McCowan L, Hoffman PL. Excercise training in pregnancy reduces offspring size without changes in maternal insulin sensitivity. J Clin Endocrinol Metab.  2010 May; 95(5): 2,080-2,088.

PubMed ID: 20335449
 
Study Design:
Randomized Controlled Trial
Class:
A - Click here for explanation of classification scheme.
Quality Rating:
Positive POSITIVE: See Quality Criteria Checklist below.
Research Purpose:

To determine the effects of aerobic exercise training during pregnancy on maternal insulin sensitivity and neonatal outcomes (including auxology, body composition and cord blood concentrations of growth-associated peptides).  

Inclusion Criteria:
  • Healthy women
  • Age 20 to 40 years
  • Singleton pregnancy of less than 20 week gestation
  • Written consent obtained.
Exclusion Criteria:
  • Multi-parous pregnancy
  • Gestation greater than 20 weeks 
  • Alcohol consumption
  • Tobacco use
  • Personal or family history of type 2 diabetes
  • Development of any medical condition for which participation in an exercise program was contraindicated by the American College of Obstetricians and Gynecologists.
Description of Study Protocol:

Recruitment

Volunteers recruited using advertisements and the assistance of maternity provides in Auckland.

Design

  • Randomized controlled trial
  • Participants were randomly assigned to exercise or control group
  • Control group was asked to continue their normal daily activities for the duration of the pregnancy.

Intervention 

  • Home-based aerobic exercise program using stationary cycling
  • Individually prescribed to a maximum of five sessions of 40-minute aerobic exercise per week 
  • Aiming for 65% of predicted aerobic capacity
  • Regular exercise was recommended until at least 36 week gestation
  • After 36 weeks, participants were encouraged to maintain as close their prescribed exercise program as possible
  • Fortnightly supervised exercise session were conducted and exercise prescription was updated to maintain the prescribed exercise intensity
  • Compliance measured by self-reported exercise diaries and downloadable heart rate monitors.

Statistical Analysis

  • Sample size calculations were planned to detect differences in the two main outcomes of offspring birth weight and maternal insulin sensitivity
  • Based on previous pregnancy data, a sample size of 50 per group had 80% power at the 0.05 level of significance to detect a 20% difference between groups in insulin sensitivity
  • All variables were checked for normality and transformed where necessary
  • Simple group comparisons were conducted using independent samples T-test or ?2 test for categorical data
  • Within comparison blocks, the Bonferroni method was used to adjust for multiple comparisons
  • Intention to treat analyses were performed using repeated measures ANOVA to investigate differences in insulin sensitivity, aerobic fitness and maternal size between groups from baseline to late pregnancy
  • Data analyzed using SPSS version 15.

 

Data Collection Summary:

Timing of Measurements

  • Recruitment occurred between December 2004 and May 2007
  • Baseline assessments were completed at approximately 19 weeks gestation
  • Heart rate and blood pressure were measured during fortnightly supervised exercise session 
  • Maternal insulin sensitivity was assessed at 19 and 34 to 36 week gestation
  • Infants were assessed within 48 hours of birth and DXA was completed at 17 days of age.

Dependent Variables

  • Maternal insulin sensitivity: After overnight fast, participants underwent a 180-minute intravenous glucose tolerance test for minimal model analysis of parameters of insulin sensitivity
  • Neonatal outcomes:
    • Auxological measures obtained by a study investigator within 48 hours of birth
    • Birth weight: Measured using electronic infant scales
    • Birth crown-heel length: Measured using a neonatometer
    • Head and chest circumference.
  • Maternal Biochemical assays:
    • Plasma glucose
    • Plasma insulin concentrations
    • Serum IGF-I, IGF-II, IGFBP-1 and IGFBP-3.

Independent Variables

  • Exercise program:
    • Individually prescribed to a maximum of five sessions of 40-minute aerobic exercise per week 
    • Aiming for 65% of predicted aerobic capacity.

Control Variables

  • Maternal heart rate:
    • Obtained during fortnightly supervised exercise sessions
    • Downloadable monitors for home use.
  • Blood pressure: Obtained during fortnightly supervised exercise sessions
  • Exercise intensity:
    • Metabolic equivalents 
    • Averaged for each phase of the exercise program:
      • Familiarization (20 to 27 week)
      • Maintenance (28 to 35 week)
      • Subject to capacity (36 to 40 week).
  • Compliance: Percentage of prescribed weekly exercise duration completed
  • Aerobic fitness: Submaximal graded exercise test in mid and late pregnancy on a stationary cycle to 150 beats per minute
  • Maternal height: Taken with a fixed wall-stadiometer
  • Maternal body weight: Measured using calibrated electronic scales
  • Dietary intake: Assessed by two seven-day food records at 20 and 33 weeks gestation.

 

 

 

Description of Actual Data Sample:
  • Initial N: 98 women recruited
  • Attrition (final N): 84 women (47 exercise, 37 control).

Age

  • Control: 29±4 years
  • Exercise: 31±3 years

Ethnicity

93% European.

Anthropometrics

  • Body weight:
    • Control: 84.0kg±10.2kg
    • Exercise: 86.9kg±12.4kg.
  • Body mass index:
    • Control: 25.5kg±2.9 kg/m2
    • Exercise: 26.7kg±3.3 kg/m2.

Location

Auckland, New Zealand.

 

Summary of Results:

 Key Findings

  • Exercise training had no impact on changes in maternal body weight and BMI during late pregnancy 
  • Exercise training resulted in an increase in total test time and VO2 at submaximal peak exercise in the training group (P<0.05)
  • Exercise training had no impact on any parameter of glucose regulation (time*group interaction):
    • Insulin sensitivity index (tg=0.29)
    • Acute insulin response (tg=0.42)
    • Disposition index (tg=0.56)
    • Glucose effectiveness (tg=0.53)
    • Glucose disappearance (tg=0.69).
  • Offspring effects: Infants of exercisers:
    • No differences in other cord blood concentrations of IGFBP-1, IGFBP-3, leptin, plasma glucose or insulin
    • Cord serum concentrations of IGF-I and IFG-II were lower in exercise than control:
      • IFG-I (ng per ml): control 45 (36 to 55) and exercise 32 (26 to 40), P<0.05
      • IGF-II (ng per ml): control 421 (386 to 458) and exercise 372 (343 to 403), P<0.05.
    • Smaller body size persisted at the time of the 17 day postnatal DXA scan. DXA scan indicated that body composition was unaffected by exercise with similar percentage of body fat (8.17%±2.2%, 7.86%±2.6%)
    • When birthweight was adjusted for gender and gestational age, there was a significant reduction in exercise offspring body weight compared with controls (0.22±0.8, -0.19±0.9; P<0.05)
    • Lower BMI (13.7±1.0, 13.2±1.1; P<0.05)
    • On average, 143kg±94kg lighter than controls.

Other Findings

  • Compliance
    • Overall for the full intervention period: 75±17%
    • Exercise duration was similar between the groups during the familiarization period (20 to 27 weeks), significant difference between exercise and control for the overall duration of the program (P<0.001)
    • Exercise intensity was higher in the exercise group at all time periods, with a significant difference overall difference (P<0.001).
  • Maternal characteristics and changes in size, energy intake and aerobic fitness during pregnancy.
  Control (N=37) Exercise (N=47)  
  Baseline Late Gestation Baseline Late Gestation P values (Time, Group, Interaction)
Body weight (kg) 71.6±10.7 79.6±9.8 70.3±13.1 78.5±13.6 t<0.01, g=0.76, tg=0.35
BMI (kg/m2) 25.4±2.9 28.3±2.6 25.5±4.3 28.4±4.3 t<0.01, g=0.94, tg=0.40
Energy intake (kcal per day) 2046±352 2113±425 1929±305 1979±288 t=0.21, g=0.11, tg=0.64
PWC150time (seconds) 518±150 536±137 485±112 580±133 t<0.01, g=0.85, tg<0.01
Peak VO2(ml per kg per minute) 20.3±4.0 18.7±3.3 19.2±3.7 20.0±3.5 t=0.08, g=0.85, tg<0.01

Values are expressed as mean±SD. Repeated measures ANOVA were used to assess changes with pregnancy and differences between groups during pregnancy. Energy intake was assessed using seven-day diet records. Aerobic fitness was assessed using a submaximal exercise test to a heart rate of 150 beats per minute (PWC150).  

PWC=peak work capacity, t=time effect, g=group effect, tg=time*group interaction.

Author Conclusion:

Regular moderate-intensity, non-weight-bearing exercise training during the second half of pregnancy was associated with reduced concentrations of fetal IGFs and lower offspring birth weight but had no measurable effect on aspects of maternal glucose metabolism. Exercise resulted in a modest shift in the birthweight distribution within the normal range when compared with the control group. Our observations suggest that during a healthy pregnancy, maternal insulin sensitivity is persistently regulated to achieve optimal fetal growth and is not sensitive to modest increases in energy expenditure through exercise.

Funding Source:
Government: National Research Centre for Growth and Development
Industry:
Novo Nordisk
Other:
Reviewer Comments:

 The study was under-powered to detect differential effects of exercise training on maternal insulin sensitivity.

Quality Criteria Checklist: Primary Research
Relevance Questions
  1. Would implementing the studied intervention or procedure (if found successful) result in improved outcomes for the patients/clients/population group? (Not Applicable for some epidemiological studies) Yes
  2. Did the authors study an outcome (dependent variable) or topic that the patients/clients/population group would care about? Yes
  3. Is the focus of the intervention or procedure (independent variable) or topic of study a common issue of concern to dieteticspractice? Yes
  4. Is the intervention or procedure feasible? (NA for some epidemiological studies) Yes
 
Validity Questions
1. Was the research question clearly stated? Yes
  1.1. Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified? Yes
  1.2. Was (were) the outcome(s) [dependent variable(s)] clearly indicated? Yes
  1.3. Were the target population and setting specified? Yes
2. Was the selection of study subjects/patients free from bias? Yes
  2.1. Were inclusion/exclusion criteria specified (e.g., risk, point in disease progression, diagnostic or prognosis criteria), and with sufficient detail and without omitting criteria critical to the study? Yes
  2.2. Were criteria applied equally to all study groups? Yes
  2.3. Were health, demographics, and other characteristics of subjects described? Yes
  2.4. Were the subjects/patients a representative sample of the relevant population? Yes
3. Were study groups comparable? Yes
  3.1. Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT) Yes
  3.2. Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline? Yes
  3.3. Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.) Yes
  3.4. If cohort study or cross-sectional study, were groups comparable on important confounding factors and/or were preexisting differences accounted for by using appropriate adjustments in statistical analysis? N/A
  3.5. If case control study, were potential confounding factors comparable for cases and controls? (If case series or trial with subjects serving as own control, this criterion is not applicable.) N/A
  3.6. If diagnostic test, was there an independent blind comparison with an appropriate reference standard (e.g., "gold standard")? N/A
4. Was method of handling withdrawals described? Yes
  4.1. Were follow-up methods described and the same for all groups? Yes
  4.2. Was the number, characteristics of withdrawals (i.e., dropouts, lost to follow up, attrition rate) and/or response rate (cross-sectional studies) described for each group? (Follow up goal for a strong study is 80%.) Yes
  4.3. Were all enrolled subjects/patients (in the original sample) accounted for? Yes
  4.4. Were reasons for withdrawals similar across groups? Yes
  4.5. If diagnostic test, was decision to perform reference test not dependent on results of test under study? N/A
5. Was blinding used to prevent introduction of bias? No
  5.1. In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate? No
  5.2. Were data collectors blinded for outcomes assessment? (If outcome is measured using an objective test, such as a lab value, this criterion is assumed to be met.) No
  5.3. In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded? N/A
  5.4. In case control study, was case definition explicit and case ascertainment not influenced by exposure status? N/A
  5.5. In diagnostic study, were test results blinded to patient history and other test results? N/A
6. Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were interveningfactors described? Yes
  6.1. In RCT or other intervention trial, were protocols described for all regimens studied? Yes
  6.2. In observational study, were interventions, study settings, and clinicians/provider described? N/A
  6.3. Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect? Yes
  6.4. Was the amount of exposure and, if relevant, subject/patient compliance measured? Yes
  6.5. Were co-interventions (e.g., ancillary treatments, other therapies) described? Yes
  6.6. Were extra or unplanned treatments described? ???
  6.7. Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups? Yes
  6.8. In diagnostic study, were details of test administration and replication sufficient? N/A
7. Were outcomes clearly defined and the measurements valid and reliable? Yes
  7.1. Were primary and secondary endpoints described and relevant to the question? Yes
  7.2. Were nutrition measures appropriate to question and outcomes of concern? Yes
  7.3. Was the period of follow-up long enough for important outcome(s) to occur? Yes
  7.4. Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures? Yes
  7.5. Was the measurement of effect at an appropriate level of precision? Yes
  7.6. Were other factors accounted for (measured) that could affect outcomes? Yes
  7.7. Were the measurements conducted consistently across groups? Yes
8. Was the statistical analysis appropriate for the study design and type of outcome indicators? Yes
  8.1. Were statistical analyses adequately described and the results reported appropriately? Yes
  8.2. Were correct statistical tests used and assumptions of test not violated? Yes
  8.3. Were statistics reported with levels of significance and/or confidence intervals? Yes
  8.4. Was "intent to treat" analysis of outcomes done (and as appropriate, was there an analysis of outcomes for those maximally exposed or a dose-response analysis)? N/A
  8.5. Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)? Yes
  8.6. Was clinical significance as well as statistical significance reported? Yes
  8.7. If negative findings, was a power calculation reported to address type 2 error? Yes
9. Are conclusions supported by results with biases and limitations taken into consideration? Yes
  9.1. Is there a discussion of findings? Yes
  9.2. Are biases and study limitations identified and discussed? Yes
10. Is bias due to study's funding or sponsorship unlikely? Yes
  10.1. Were sources of funding and investigators' affiliations described? Yes
  10.2. Was the study free from apparent conflict of interest? Yes