GDM: Pharmacologic Therapy (2008)

Citation:
 
Study Design:
Class:
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Quality Rating:
Research Purpose:

The purpose of this study was to compare the management of Caucasian women with gestational diabetes (GDM) based predominately on monthly fetal growth ultrasound examinations with an approach based solely on maternal glycemia.

Inclusion Criteria:
  • GDM, diagnosed by at least 2 abnormal values in a 75- oral glucose tolerance test
  • Capillary fasting glucose (FCG) measurements < 120 mg/dl and 2-hour postprandial capillary glucose (2h-CG) measurements  200 mg/dl
  • Singleton pregnancy 16-34 completed weeks confirmed by ultrasound performed before 20 weeks
  • No maternal medical conditions known to affect fetal growth
  • No abuse of tobacco (more than 5 cigarettes/day), alcohol, or illicit drugs during pregnancy
Exclusion Criteria:

Excluded if not included above.

Description of Study Protocol:

Recruitment Subjects were recruited from women referred to 2 hospital-based diabetic prenatal care clinics from January 2000 - January 2003

Design Subjects were stratified into one of 5 blocks based on gestational age and randomized within the blocks to standard or ultrasound management. Both groups were prescribed a diet based on true body weight (30 kcal/kg/day) with caloric restriction of overweight women (25 kcal/kg/day).  Women were advised to exercise after meals and taught to self-monitor blood glucose using a reflectance meter with memory. Glucose profiles consisted of six daily measurements (three preprandial and three 2-hr postprandial) were performed twice weekly while on diet and daily on insulin.

Blinding used (if applicable)

Not applicable.

Intervention (if applicable)

In the standard group, insulin was prescribed before 36 weeks gestation if two glucose profiles had two or more elevated values (FCG > 90 mg/dl or 2h-CG >120 mg/dl) or four profiles had at least one elevated value during a 2 week period. In the ultrasound group, insulin was started whenever the AC exceeded the 75th percentile (AC >p75) before 36 completed weeks. In this group, glucose targets were not discussed with patients and glucose values were not used to guide management unless any FCG> 120 mg/dl and/or any 2h-CG >200 mg/dl was measured, at which point insulin was prescribed irrespective of AC measurement.

Ultrasound examinations were performed at entry and thereafter at 4-week intervals at 20, 24, 28, 32 and 36 weeks of gestation. Results in the standard group were not discussed with the women and were not used to guide management.  

Statistical Analysis

Differences between the groups were tested for statistical significance by t tests or ANOVA (continuous variables) or by Chi Square Analysis (categorical variables).

Data Collection Summary:

Timing of Measurements

Maternal capillary glucose levels were measured every 2 hours. Neonatal capillary blood glucose was measured at 1, 3, 6, and 12 hours postpartum. Birth weight and length were obtained immediately post delivery. Skinfold thickness was measured in triplicate at four sites (triceps, subscapular, iliac crest and thigh) at day 2 of life.

Dependent Variables

  •  Maternal characteristics
  •  Neonatal outcomes

Independent Variables

  • Insulin therapy based solely on capillary glucose measurements (fasting and 2 hour postprandial) versus insulin therapy based on capillary glucose measurements (fasting and 2 hour postprandial) and fetal AC >75th percentile.

Control Variables

  • Diet

 

Description of Actual Data Sample:

Initial N: 199 (100 to standard care)

Attrition (final N): 187 (97 standard care)

Age: Standard group  31.3 + 5.0 years, Ultrasound group 31.0 + 5.6 years

Ethnicity: Caucasian women, similar ethnic and social backgrounds

Other relevant demographics:

Anthropometrics: There were no signficant differences between the groups in regards to prepregnancy BMI, prior pregnancies with GDM or macrosomia or HBA1c upon entry. 

There were no significant differences between the number of subjects who met the criteria for insulin between the standard and ultrasound groups.

Location: Berlin, Germany

 

Summary of Results:

 

Neonatal outcome

Standard Group

Means± SE 

Ultrasound Group

Means±SE

P value

Gestational age at delivery (weeks)

39.3 ± 1.3 39.0 ± 1.9

0.2

Birth weight (g)

 3371.2±  500

 3306.1 ± 558

 0.4

SGA (%)

 13.0

 12.1

 0.5

LGA (%) 10.0 12.1 0.4
Neonatal BMI (kg/m2) 13.1±  1.2 12.8 ± 1.5 0.2
Sum of skinfolds (mm) 13.2 ± 3.2   14.1 ± 3.4 0.07

Other Findings

There were no significant differences between groups in duration of insulin therapy and maximum individual insulin doses.

 

Author Conclusion:
GDM management based on fetal growth combined with high glycemic criteria provides outcomes equivalent to management based on strict glycemia criteria alone. Inclusion of fetal growth might provide the opportunity to reduce glucose testing in low risk pregnancies.
Funding Source:
Reviewer Comments:

Well done study, looks at individualizing treatment based on fetal growth rather than glycemic control. 6 of the ultrasound group dropped out of the study because they "left care" and only 1 of the standard group dropped out for the same reason. Was there a reason the ultrasound group lost so many more subjects?

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? ???
  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? Yes
  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? Yes
  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