GDM: Calories (2016)

Citation:
 
Study Design:
Class:
- Click here for explanation of classification scheme.
Quality Rating:
Research Purpose:
To determine the effect of moderate 30% maternal dietary energy restriction on the requirement for maternal insulin therapy and the incidence of macrosomia in gestational diabetes.
Inclusion Criteria:
  • Gestation <= 35 weeks and 6 days;
  • >110% of ideal body weight for height, or BMI of 25 (adjusted for expected pregnancy weight gain)
  • Oral glucose tolerance test with fasting plasma glucose > 5.4 mmol/L and/or 2-hr plasma glucose > 7.9 mmol/L
Exclusion Criteria:
None reported.
Description of Study Protocol:

Recruitment

Between February 1992 and June 1995 at single research hospital in Australia.

Design

Double-blinded randomized controlled trial.  Women were allocated at random by draw of opaque numbered envelopes. Stratified randomization for the following factors to ensure balance of these confounding variables between the groups:

  • maternal age (< 25 yr, 25-35 yr, > 35 yr);
  • gestational age at diagnosis (<= 28 wks or > 28 wks and one day);
  • maternal parity (nulliparous, parity of one or more);
  • degree of abnormality of oral glucose tolerance test defined by level of hyperglycemia

Blinding used (if applicable)

Both the participants and the Diabetes Service staff were blinded to the allocation to diet group. 

The decision to commence insulin therapy (based on a guideline for determined before the study) was made by medical staff who were blinded to the group allocation of each participant.

Intervention (if applicable)

 All women were seen by the research dietitian at each antenatal visit. 

  • Standard intervention (all subjects): diabetes education, control of hyperglycemia, with fetal and maternal surveillance and anticipated term delivery
  • The intervention group: instuction in a moderately energy restricted diabetic diet: 1590-1776 Kcal/day (This represents 70% of the RDI for pregnant women)
  • The control group: instruction in a diabetic diet which was not energy restricted: 2010-2200 Kcal/day

Statistical Analysis

  • Baseline data: t-test; Wilcoxon Rank Sum test or Fisher's exact test as appropriate
  • For outcome of insulin use and the incidence of macrosomia: logistic regression
  • For all other outcomes: multivariate repeated measures or linear analysis of variance

All analyses were conducted on an intention-to-treat basis.

A power calculation was performed: 60 participants per group needed.

Data Collection Summary:

Timing of Measurements

Demographic, obstetric and neonatal data were collected prospectively.

Dependent Variables

  • For mothers:

    • weight change in pregnancy: pre-pregnancy to treatment, from treatment to delivery, pre-pregnancy to delivery
    • insulin use: commence insulin therapy when fasting blood glucose > 5.5 mmol/L or 2-hr post-prandial level > 7.0 mmol/L on two or more occasions in any 72-hr period at the same pre- or post-prandial epoch
    • hyperglycemia: moderate - if the fasting plasma glucose was 5.5-5.8 mmol/L or the 2-hr level was 8.0-8.9 mmol/L; Severe abnormality - if fasting or 2-hr levels > 5.8 or 8.9 respectively, or both fasting and 2-hr level > 5.4 and 7.9 mmol/L respectively.
    • diabetes control: HbA1c, blood glucose levels (mean, fasting, post breastfast, pre lunch, post luch, pre dinner, post dinner), serum beta-hydroxybutyrate
    • urinary ketones: % of participants with non detectable
    • antenatal complications and intrapartum  
  • For babies:

    • gestation at delivery
    • anthropometic measurements: midarm circumference and four skinfold thickness measures (abdominal, triceps, suprailiac and subscapular sites) were taken at approximately 5 days of age. 
    • estimated birthweight ratio: calculated by dividing birthweight by the 50th percentile birthweight of corresponding gender, gestational age and maternal height
    • macrosomia: either as having a birthweight of or > 90th centile weight for gender, gestational age and maternal height
    • neonatal complications

Independent Variables

  • Intervention (moderately energy restricted diabetic diet) vs. control (diabetic diet which was not energy restricted)
  • To monitor diet compliance, 3-day food diaries were kept by participants at 3 time periods after recruitment. 

Control Variables

  • Stratified randomization factors (see Design)
Description of Actual Data Sample:

Initial N: 159 recruited.  125 (100% women).  67 were randomized to the intervention group; 58 to the control group.

Attrition (final N): 117

Age: Intervention group=30.2 years old, Control group=30.6 years old

Ethnicity: no data

Other relevant demographics:

Gestation at diagnosis of GDM: 28 weeks in each group (range 8-35 weeks).  BMI at diagnosis: Intervention group=37.9; control group=38.0.

Anthropometrics: 

The reported maternal medical and obstetric histories were similar in the two groups except for a significantly higher proportion of women with a history of preterm labor in the control group (13.5% in the control group and 0% in the intervention group, p=0.01).

Location: Single research hospital in Australia.

Summary of Results:

I.  Nutrient intake profile of research participants - Self-reported compliance

Actual intake*

 

Intervention Group

Value (SE)

Control group

Value (SE)

Statistical Significance of Group Difference

Energy (Kcal/day)

% of goal intake

1566

97 (2.7)

1630

77 (1.7)

NS

CHO (%energy)

% of goal intake

42 (0.7)

82 (1.3)

 41 (0.6)

88 (1.2)

NS

Fat (%energy)

% of goal intake

 31 (0.7)

125 (2.9)

 34 (0.7)

117 (2.3)

p=0.01

Protein (%energy)

% of goal intake

25 (0.3)

125 (2.9)

24 (0.3)

117 (2.3)

p=0.08

*Actual intake was based on 3-day food diaries at 3 time periods

II. Weight change in pregnancy

 

Intervention Group

Kg (SE)

Control group

Kg (SE)

Statistical Significance of Group Difference

 

 Total

Per week

 Total

Per week

 

Pre-pregnancy to treatment 11.23 (1.19) 0.37 (0.0.4)

8.84 (1.24)

0.29 (0.04) NS
From treatment to delivery 0.24 (0.36) 0.01 (0.07) 0.91 (0.40) 0.13 (0.06) NS
Pre-pregnancy to delivery 11.56 (1.32) 0.31 (0.03) 9.68 (1.45) 0.26 (0.04) NS

  •  The mean weight lost was 1.68 kg (SE 0.33, range 7.5-0.0) in the intervention group, and 1.68 kg (SE 0.32, range 5.0-0.0) in the control group (p=NS)

III. Diebetes control

  Target Intervention group Control group p value
mean fasting blood glucose levels mmol/L (SE) <=5.5 4.9 (0.1) 4.8 (0.1) NS

mean HbA1c % (SE)

< 6.0 5.3 (0.1) 5.5 (0.2) NS

Urinary ketones - % of participants with none detectable

  34.5 38.5 NS

Insulin use - 

  % requiring insulin

  Gestation commenced (weeks) median (IQR)

  Maximum daily insulin dose in units, median (IQR)

 

 

 

17.5

33 (29-35)

23 (12-62)

 

16.7

31 (30-32)

60 (34-106)

 

NS

NS

NS

IV. Neonatal outcome

All 124 infants were liveborn, of whom 11.3% (7 sets) were twins.

Value (SE) Intervention group Control gorup p value
Gestation at delivery (weeks) 37.8 (0.3) 37.6 (0.2) NS
Mean birthweight (g) 3461 (?) 3267 (96) NS
Estimated birth weight ratio 1.08 (0.02) 1.03 (0.03) NS
% of infants >= 4000 g 16.7 10.7  
% infants >= 90 percentile 28.8 24.6  

  • Of the anthropometic measurements taken the only difference was a greater average abdominal skinfold thickness among infants in the intervention group (4.2 vs. 4.0, p=0.02). The mean total skinfold measurement was similar in both groups.

Other Findings (Complications)

  • There were no differences between the groups for any of the complications of pregnancy, including anaemia, premature rupture of membranes and threatened preterm labor. There were similar rates of vaginal, assisted and Cesarean deliveries, elective and non-elective inductions, fetal distress, maternal trauma and birth trauma in each group. The 3 infants with shoulder dystocia were in the control group.
  • 90% of infants in each group were screened for hypoglycemia using a pre-second feed plasma glucose level. Of these, 37.3% (n=22) of the intervention group and 50.0% (n=25) of the control group had bolld glucose levels < 2.5 mmol/L. The difference was not significant.
  • Five infants in the control group were polycythemic (Fisher's exact test (p=0.02). The mean bilirubin level measured in the two groups was the same.
Author Conclusion:

The ability of this study to demostrate benefit for women in the energy-restricted group was reduced by the close similarity between the groups in recorded energy intake.

There was considerable slowing of maternal weight gain in both groups. Mean blood glucose levels in both groups showed excellent control.

The sample of women who participated in this research is likely to contain a higher proportion of more severe cases of gestational diabetes than that found in the general antenatal population.

We have demostrated a reduced pregnancy weight gain in this cohort without maternal or fetal compromise. This may be an advantage for women with a high risk of developing non-insulin dependent diabetes. Furthermore, it appears that compliance with a 30% energy restriction presents no problems.

This study provides evidence that a moderate energy restriction in obese women with gestational diabetes results in normoglycemia and possibly a reduction in the need for insulin therapy. This can be achieved without inducing significant ketonemia.

Funding Source:
Reviewer Comments:
This trial was government funded.
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? Yes
  5.1. In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate? Yes
  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.) Yes
  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? N/A
  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)? Yes
  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