GDM: Abnormal Glucose Tolerance During Pregnancy (2008)

Citation:
 
Study Design:
Class:
- Click here for explanation of classification scheme.
Quality Rating:
Research Purpose:

To determine the relationship between maternal and fetal outcomes and gestational diabetes mellitus (GDM), impaired fasting glucose (IFG) and impaired glucose tolerance (IGT).

Inclusion Criteria:
  • The study and control groups were selected from those patients who had delivered at Maternity Hospital Kuala Lumpur (MHKL) and had attended the antenatal clinics, where OGTT had been performed for the above indications
  • The inclusion criterion for the study group was abnormal OGTT, and patients in this group were divided into sub-groups according to the degree of glucose intolerance using the WHO criteria, namely GDM, IFG and IGT as defined in Table 1. 
  • The University Purta medical faculty’s research committee approved the study protocol. 
  • Medical records were retrieved from the records department of the Maternity Hospital Kuala Lumpur during the period from January to May 2002.
  • The inclusion criterion for patients in the control group was normal OGTT. These patients were selected by simple random selection based on a table of random numbers.
  • A structured pretested format was used in the study.  
Exclusion Criteria:
  • Patients with preexisting diabetes and multiple pregnancies were excluded.

 

Description of Study Protocol:

Recruitment Method was not detailed

Design Historical cohort

Blinding used:  not applicable 

Intervention:  not applicable 

Statistical Analysis

  • No estimation of prevalence of outcomes was available for the IGT and IFG groups as separate entities, as almost all studies included IFG in the IGT group, sample size was therefore difficult to determine
  • The post-hoc power determination for outcomes of this study was performed

              Post-hoc power

               Condition

          >  80%

pre-eclampsia and macrosomia in GDM and IFG

           >    50%

 induced labor and cesarean section

            >   65%

 pre-eclampsia in IGT

                 30%

 macrosomia in IGT  

 

  • The data was analyzed using SPSS (statistical Package for Social Sciences) version 11.0.
  • One-way analysis of variance (ANOVA) was applied to compare parameters amongst the different groups.
  • Normality testing was done using graphical judgment with histogram overlaid with the normal curve.
  • Homogeneity of variance was tested by using Levene’s test. Relative risk with corresponding 95% confidence interval (CI) was used to estimate the strength of association between GDM, IFG, IGT and maternal-fetal outcomes.
  • The Student’s t-test, Fisher’s exact test and the chi-square test were used, as appropriate.
  • The level of statistical significance was set at 0.05.

 

Data Collection Summary:

Timing of Measurements

Dependent Variables

Diagnostic criteria:

  • The hospital (MHKL) practiced selective screening, with the OGTT tests being performed  on patient with indications such as a family history of diabetes9 in first-degree relatives), maternal age >37 years , maternal weight > 80kg or body mass index (BMI)>27 in the current pregnancy; a past history of GDM macrosomia (>4000g), unexplained perinatal death or structural congenital abnormality, history of three or more spontaneous miscarriages, glycosuria on two or more occasions and polyhydramnios in the indexed pregnancy

Maternal Outcomes:

  • Premature rupture of membranes (PROM) - includes preterm and prelabor rupture and was diagnosed clinically by the presence of liquor on speculum examination and confirmed by the change in the color of red litmus to blue.
  • Preterm delivery
  • Polyhydramnios - defined as the maximum vertical pool measuring more than 7 cm or an amniotic fluid index greater than 25 cm on ultrasound. Clinically, it was defined as amniotic fluid that was clearly more than was appropriate for the gestational age.
  • Hypertension in pregnancy-defined as maternal diastolic blood pressure of >90mmHG (12.0 kPa) for two consecutive readings taken 4 h or longer apart, or one diastolic blood pressure reading >110 mmHG (14.7 kPa).
  • Mode of delivery

Fetal outcomes:

  • Perinatal mortality- included fresh stillbirths, macerated stillbirths and early neonatal deaths (0-6 days of life).
  • Stillbirth was defined in accordance with criteria from the UK’s Confidential Enquiry into Stillbirths and Death in Infancy.
  • Apgar score at 1 and 5 min
  • Macrosomia- defined as birth weight > 4000g.
  • Shoulder dystocia
  • Congenital abnormality

Independent Variables

  • Age
  • Ethnicity

Control Variables

 

Description of Actual Data Sample:

Initial N:A total of 149 patients with abnormal (78 patients with IGT, 57 with GDM and 14 with IFG) were included. One hundred and forty-nine patients with normal OGTT were chosen as controls.

Attrition (final N):  as above

Age: See Table 2

Ethnicity: not detailed

Other relevant demographics:

Anthropometrics

Location: Department of Human Growth and Development, Obstetric and Gynecology Division, University Putra Malaysia, Kuala Lumpur, Shool of Medical Sciences, University of Science Malaysia, and School of Human Development, Nottingham University, UK.

 

Summary of Results:

The inclusion criterion for the study group was abnormal OGTT, and patients in this group were divided into sub-groups according to the degree of glucose intolerance using the WHO criteria, namely GDM, IFG and IGT as defined in Table 1.

Table 1 World Health Organization classifications 

 

Venous Plasma>>>

>>>>>

 

Fasting

2-h post-glucose load

 

(mmol/L)

(mmol/L)

GDM

> 7.0

> 11.1

IPG

> 6.1  < 7.0

< 7.8

IGT

<7.0

> 7.8

Normoglycemia

< 6.1

-

GDM, gestational diabetes mellitus ; IPG, impaired fasting glucose ; IGT, impaired fasting glucose tolerance.

The majority of patients were Malays and most patients belonged to the 30.0-39.9 age group(Table 2).

Table 2  Age and ethnic distribution of patients with abnormal oral glucose tolerance test 

Factors of interest

Controls

(no.)

Abnormal OGTT (no.)

P-value

Age

-

-

-

< 20.0

1

0

-

20.0-29.9

59

47

-

30.0-39.9

79

89

-

40.0-49.9

10

13

P=0.341

Ethnicity

-

-

-

Malay

98

91

-

Chinese

12

12

-

Indian

21

33

-

Others

18

13

P=0.292

OGTT, oral glucose tolerance test

There were significant differences in BMI at 32 weeks POA between the GDM and IGT groups (mean difference 3.2; 95% CI, 0.26-6.15; P=0.026) and between the IFG and IGT groups (mean difference 5.50; 95% CI, 0.92-10.09; P=0.011)(Table 3).

Table 3 Comparison of mean body mass index (BMI) at 32 weeks period of amenorrhea (POA) amongst the four groups of patients  

Variable

No.

Body Mass index at 32 weeks POA mean (SD)

F statistic *

(d.f.)

P-value

GDM

57

31.96(4.65)

5.74 (3251)

0.001 ¶

IFG

14

34.26 (5.55)

-

-

AGT

78

28.76(5.46)

-

-

Controls

149

29.97 (5.40)

-

-

*One-way ANOVA applied (data were normally distributed and variances are equal, Levene’s test statistic 0.69, P=0.557). ¶ post-hoc multiple comparison (Scheffe test) applied. Two comparisons were significant at the 0.005 level: GDM versus IGT (mean difference = 3.20; 95% CI, 0.92, 10.09; P= 0.011). GDM, gestational diabetes mellitus; IFG, impaired fasting glucose; IFG, impaired fasting glucose intolerance; SD, standard deviation.

The incidence of preeclampsia was also significantly higher in the abnormal OGTT group, and the risk was three times higher in the GDM group ((RR= 3.36; 95% CI, 1.27-8.88; P=0.008) and none times higher in the IFG group (RR=2.61; 95% CI, 2.91-29.74; P=0.002)(Table 4).  

Table 4  Association of maternal and fetal factors with gestational diabetes and lesser degrees of glucose intolerance 

Outcome

Abnormal OGTT

IGT

IFG

GDM

Pre-eclampsia

-

-

-

-

P-value

0.008*

0.121

0.002*

0.039*

RR

3.36

2.36

9.31

3.34

95% CI

(1.27-8.88)

(0.75-7.45)

(2.91-29.74)

(1.07-10.42)

Polyhydramnios

-

-

-

-

P-value

0.017*

0.374

0.422

0.001*

RR

3.00

1.53

2.13

5.23

95% CI

(1.12-8.04)

(0.42-5.53)

(0.27-16.97)

(1.87-14.63)

Preterm delivery

-

-

-

-

P-value

0.088

0.068

0.367

0.355

RR

0.58

0.43

0.47

0.78

95% CI

(0.29-1.16)

(0.15-1.20)

(0.07-3.23)

(0.34-1.75)

Induction and/or augmentation

-

-

-

-

P-value

0.001*

0.016*

0.003*

0.034*

RR

2.05

1.91

3.55

1.88

95% CI

(1.28-3.28)

(1.11-3.28)

(1.84-6.84)

(1.04-3.36)

Cesarean delivery (total)

-

-

-

-

P-value

0.795

0.051

0.203

0.034*

RR

1.03

0.612

1.90

1.61

95% CI

(0.81-1.33)

(0.36-1.041)

(0.70-5.196)

(1.04-2.49)

Macrosomia

-

-

-

-

P-value

0.001*

0.277

0.015*

0.001*

RR

5.50

1.91

7.98

9.80

95% CI

(1.94-15.57)

(0.49-7.43)

1.98-32.15)

(3.40-28.29)

Apgar score at 5 min (>7)

-

-

-

-

P-value

0.751

0.656

0.914

0.478

RR

1.00

1.01

1.01

0.99

95% CI

(0.98-1.02)

(0.99-1.02)

(0.99-1.02)

(0.95-1.03)

 * P <0.05 is significant. CI, confidence interval ;GDM, gestational diabetes mellitus; IFG, impaired fasting glucose; IGT, impaired fasting glucose intolerance; OGTT, oral glucose tolerance test; RR, relative risk.

 Other Findings

The majority of patients with GDM were treated with insulin, while the majority of those with IFg and IGT were treated with diet therapy.

 

Author Conclusion:
  • There was an increased risk of preeclampsia and microsomia in both the GDM and IFG patients, but IGT was not associated with adverse fetal or maternal outcomes.
  • This is one of the first few studies in which IFG has been distinguished from IGT and the outcomes compared.  

Limitations:

  • The prepregnancy BMI was unavailable; therefore, the BMI at 32 weeks period of amenorrhea (POA) was used, as by this time the diabetogenic stress had usually manifested in patients with glucose intolerance. In addition, detection and treatment after 32 weeks POA did not improve fetal outcome.
  • Small numbers in groups

 

Funding Source:
Reviewer Comments:

In a historical cohort study, data on exposure and occurrence of disease are collected after the events have taken place—the cohorts of exposed and non-exposed subjects are assembled from existing records, or health care registries. Studies of this kind provide a better opportunity than one time cross sectional studies to examine whether certain behaviors do in fact lead to (or cause) the disease.

The limitation and critique of the study, as stated by the authors appear to be very appropriate.

 

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) N/A
  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) N/A
 
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? ???
  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) ???
  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? Yes
  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%.) N/A
  4.3. Were all enrolled subjects/patients (in the original sample) accounted for? Yes
  4.4. Were reasons for withdrawals similar across groups? N/A
  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? N/A
  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? Yes
  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? N/A
  6.1. In RCT or other intervention trial, were protocols described for all regimens studied? N/A
  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? N/A
  6.4. Was the amount of exposure and, if relevant, subject/patient compliance measured? N/A
  6.5. Were co-interventions (e.g., ancillary treatments, other therapies) described? N/A
  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? N/A
  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? ???
  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? N/A
  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? 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? 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