GDM: Pharmacologic Therapy (2008)

Citation:
 
Study Design:
Class:
- Click here for explanation of classification scheme.
Quality Rating:
Research Purpose:
The purpose of this study was to compare management based on maternal glycemic criteria and fetal abdominal circumference (AC) measurements in order to select patients for insulin treatment of gestational diabetes mellitus (GDM) with fasting hyperglycemia.
Inclusion Criteria:
  • Women with GDM
  • Fasting plasma glucose concentrations >105 and < 120 mg/dl
  • Gestational age >14 and <34 weeks at time of study entry
  • Singleton pregnancy
  • No medical complications e.g., hypertension or vascular disease except GDM known to affect fetal growth or neonatal morbidity
  • Reliable estimation of gestational age
  • No use of tobacco, alcohol or illicit drugs during pregnancy
  • Literacy
Exclusion Criteria:
Excluded if not included above.
Description of Study Protocol:

Recruitment

Subjects were recruited from prenatal clinics at either Los Angeles County and University of Southern Californa Medical Center and at the Good Samaritan Hospital in Los Angeles, California from Oct 1995- Nov 1997.

Design:  Randomized Controlled Trial

Women were stratified into 1 of 5 blocks according to their gestational age (< 20 weeks + 6 days, 21-23 weeks + 6 days, 24-26 weeks + 6 days, 27-29 weeks + 6 days or 29-33 weeks + 6 days) and then randomized within the blocks into 1 of 2 study groups:

  • standard management (insulin therapy) or
  • experimental management (monthly fetal ultrasound and fasting plasma glucose levels every 1-2 weeks).

Those in the experimental management group were prescribed insulin therapy only if the fetal AC > 70th %ile for gestational age.

Blinding used (if applicable)

Assessment of the neonates was done by neonatologists blinded to the study group.

Intervention (if applicable)

The use of monthly fetal ultrasound measurements to determine abdominal circumferance and the decision to prescribe insulin versus diet therapy only based on the fetal AC.

Statistical Analysis

Continuous variables were compared using Student's test or analysis of variance. Categorical variables were compared using Pearson's Chi Squared or Fisher's exact tests.

 

Data Collection Summary:

Timing of Measurements

Women self-monitored blood glucose values 4- 7 times daily.

Fetal AC measurements were done at baseline, and at weeks 20, 24, 29, 32 and 36 gestation.

Neonatal capillary blood glucose levels were measured immediately after birth, and then at 1, 2 and 4 hours of life. Physical exams and other lab values were done on the first day of life.

Dependent Variables

  • Maternal outcomes
  • Neonatal characteristics 

Independent Variables

  • Standard therapy for gestational diabetes (insulin + diet)
  • Experimental therapy for GDM (insulin only if fetal AC >70th %ile and/or fasting plasma glucose > 120 mg/dl

Control Variables

None

 

Description of Actual Data Sample:

Initial N: 98 subjects (49 in each group)

Attrition (final N): 96 (48 in each group)

Age: See table below

Ethnicity: Not stated

Other relevant demographics:

Anthropometrics (e.g., were groups same or different on important measures)

 

 

 Standard group

 Experimental group  pvalue
 Maternal age years (SD)  31.9 (4.9)  30.9 (7.3)  NS
 Prior GDM  26.5 %  20.4 %  NS
BMI at entry- (SD) 33.8 (6.5) 31.2 (4.6) 0.03
Gestational age at diagnosis of GDM weeks (SD) 0.7 (7.5) 20.6 (7.4) NS

Location:

Los Angeles California

 

Summary of Results:

 

Variables

Standard Group

Experimental group

 

Experimental subgroups

Diet only

Experimental subgroups

Diet plus insulin

P value
No of subjects 48

48

10

30 NS

Gestational weeks at delivery

 38.2 (0.9)

 38.3 (1.2)

 38.1 (1.0)

38.3 (0.9) NS
Birthweight > 4000 gm 2.0 (4.2%) 3.03 (6.3%) 0 3.0 (10%)  NS

Birthweight  grams (SD)

 3271 (458)

 3369 (461)

 3180 (425)

3482 (451) < 0.05 between subgroups
Circumference  cm (SD)          
Head 34.2 (1.6) 34.6 (1.3) 34.1 (1.5) 34.9 (1.1)  < 0.05 between subgroups
Chest 33.1 (1.8) 33.6 (1.8) 32.7 (1.5) 34.2 (1.7)  < 0.01 between subgroups
Arm 10.5 (0.9) 10.7 (1.0)  10.3 (0.8)  11.0 (1.0)  < 0.05 between subgroups
Thigh  14.9 (1.6)  15.1 (1.7)  14.6 (1.3)  15.3 (1.8)  NS

Other Findings:

Women in the standard group had significantly lower mean venous FPG (84.9 + 15.5 versus 88.1 + 15.4 mg/dl, p = 0.003 and capillary blood glucose levels (97.0+ 13.6 vs. 99.0 + 13.2 mg/dl, p = 0.049) than the experimental group.

The standard group had a signficantly lower rate of abdominal delivery compared to the the experimental group (14.6 versus 33.3 %, p = 0.03).

In the experimental subgroups, the diet only group had lower prepregnancy BMI (27.8 + 3.2 versus 31.1 + 4.6 kg/m2, p = 0.01) and significantly lower borderline HbA1C levels (6.07+ 0.65 vs. 6.55+ 0.89 % of HB, p = 0.05 compared to the diet plus insulin group.

 

Author Conclusion:
In women with GDM and fasting hyperglycemia, glucose plus fetal AC measurements identified pregnancies at low risk for macrosomia and resulted in the avoidance of insulin therapy of in 38% of patients without increasing rates of neonatal morbidity.
Funding Source:
Reviewer Comments:
Ethnicity of subjects not stated. Question that the difference in gestational age at diagnosis of GDM weeks between 2 groups is not signficant - typographical error?  Groups not similar in terms of BMI.
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? ???
3. Were study groups comparable? ???
  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? ???
  3.3. Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.) N/A
  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? 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? Yes
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? ???
  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? ???
  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? N/A
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