GDM: Abnormal Glucose Tolerance During Pregnancy (2008)

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

This study determined whether maternal glucose tolerance had a progressive effect on the length of gestation in singleton pregnancies and whether there was an increasing tendency towards spontaneous preterm birth with increasing glucose intolerance.

 

 

Inclusion Criteria:
  • In this study, we first obtained from the registry the serial numbers and names of women who had the antenatal OGTT over a 24-month period (1996-1997) and who delivered at our hospital.
  • The study was confined to women who did not require insulin in order to avoid any possible effect or side effect of insulin treatments, such as hypoglycemia, on the initiation of labor.
Exclusion Criteria:
  • All women with significant medical complications and those who were taking medications such as corticosteroids were managed in the High-Risk Clinic of another hospital under the same department and were not included in this study.

 

Description of Study Protocol:

Recruitment method was not detailed

Design: Historical Cohort

Blinding used:  not applicable 

Intervention 

  • Women with GDM were referred to a dietitian and put on diet control (30 kcal/kg of ideal weight) and then assessed with pre- and 2-hour postprandial blood glucose profiles.
  • Insulin therapy was started for inadequate control (fasting plasma glucose >5.9 mmol/L or postprandial glucose >7mmol/L) if dietary readjustment failed to normalize the blood glucose profile.
  • Obstetrical intervention was based on clear-cut-clinical indications only, and labor induction or elective cesarean section is not performed for suspected large for gestational age (LGA) fetuses in pregnancies complicated by GDM unless other complications, such as malpresentations, were also present.

Statistical Analysis  

  • One-way analysis of variance to determine differences in continuous variables  among the six groups
  • Duncan’s multiple range test (set at 5% level) was used to identify the groups that were different from the others
  • X2 test with Spearman’s correlation coefficient (p) for categorical variables
  • Multiple regression, using a commercially available statistical package (statistical package for the Social Sciences 10.0; SPSS Inc, Chicago, IL ).  
Data Collection Summary:

Timing of Measurements

The OGTT was performed in the morning after an overnight fast (8-12 hours), and all were instructed to continue with their usual diet before the OGTT.

Dependent Variables

Diagnostic criteria

  • All women referred for antenatal care undergo a routine ultrasound scanning at 18-20 weeks’ gestation for both dating and exclusion of fetal anomalies, irrespective of whether there were was prior ultrasound confirmation of their dates.
  • At the time of the first antenatal visit, women identified to have risk factors for the development of GDM , such as advanced maternal age(>35 years), relevant past obstetric and family history, obesity, and recurrent or significant glycosuria , undergo the 75-g OGTT.
  • The results of the OGTT was interpreted by the original World Health Organization (WHO) criteria - women who have impaired glucose tolerance (IGTT) (OGTT 2-hour value > 8.0 mmol/L) or diabetes mellitus (2-hour value > 11.0 mmol/L) were both categorized as having GDM.
  • All low-risk women have random blood glucose testing at the beginning of the third trimester(28-30 weeks) to screen for glucose intolerance. Those with abnormal spot glucose(>5.8 mmol/L if less than 2 hours postprandial and > 5.0 mmol/L if more than 2 hours postprandial) also undergo the 75-g OGTT.
  • Each woman was classified into one of 6 groups according to the 2-hour glucose value of the OGTT (in mmol/L) as follows: 

 

Classification based on original W.H.O. criteria

 

Group 1

Non-diabetic

5.9 or less

Group 2

Non-diabetic

6.0-6.9

Group 3

Non-diabetic

7.0-7.9

Group 4

IGT

8.0-8.9

Group 5

IGT

9.0-10.9

Group 6

Diabetes mellitus

11.0 or greater

 

  • For the women who had a repeat OGTT in the third trimester, only the result of the last test was used for classification.
  • The women considered non-diabetic were analyzed as three groups to determine whether there were any differences among them
  • The women diagnosed with IGT were classified as two groups for analysis, with 9.0 mmol/L as the cutoff value, because 9.0 mmol/L has also been proposed as the definition of GDM.
  • The women diagnosed with diabetes mellitus were analyzed as one group

Neonatal Outcome:

  • Caesarean delivery
  • Incidence of total preterm delivery (< 37 weeks; < 32 weeks)
  • Macrosomia
  • Large for Gestational Age (LGA, birthweight >90th percentile for the local population)
  • Small for gestational age (SGA, birth weight< 400 g )   

Independent Variables

Maternal anthropometric parameters

  • age (y) 
  • weight (kg)
  • height (cm)
  • BMI (kg/m2)

Infant

  • gestation (wk)
  • birth weight (g)
  • BMI (kg/m2)

Control Variables

 

Description of Actual Data Sample:

Initial N: 2,168 included women delivering in the hospital and had complete records, including 1169 women with GDM treated with diet restriction only.

Attrition (final N):  as above

Age: See Table I

Ethnicity: ethnic Chinese

Other relevant demographics:

Anthropometrics

Location: Department of Obstetrics and Gynecology, The University of Hong Kong and Department of Obstetrics and Gynecology, Queen Mary Hospital, Hong Kong People's Republic of China.

Summary of Results:

Of the 2,168 women in the final study cohort, 1169 (53.9%) had GDM, and the distribution of these subjects according to the OGTT 2-hour glucose values is shown in Table 1. For the mothers, there were significant differences in the age, weight, height, and body mass index (BMI).

Table 1. Maternal and Infant Characteristics in Relation to the OGTT 2-Hour Glucose Values for the Entire Cohort 

 

>

OGTT

2-h <Value>>

(mmol/L)

    <

 

-

Group1 (<6.0)

Group 2

(6.0-6.9)

Group 3

(7.0-7.9)

Group 4

(8.0-8.9)

Group 5

(9.0-10.9)

Group 6

(> 11.0)

n

304

386

304

665

436

54

Maternal

-

-

-

-

-

-

Age(y)*

28.6 + 4.6

29.6+4.6¶

30.8 + 4.4 ||

32.0+ 4.8♦ 

32.5+4.4♦ 

33.3+4.5 £ 

Weight

(kg)*

51.9 + 6.7

 

52.7 + 6.7

52.3+ 7.1

55.0 + 9.2♦ 

54.8+8.7♦ 

57.8+10.8§

Height (cm)#

155.4+ 5.5

155.9+ 5.2

155.0 + 5.4

154.8+ 5.3

154.7+5.3§

154.0+6.1 ||

BMI (kg/m2)*

21.5+2.6

21.7 + 2.7

21.8+ 2.8

23.0+3.7♦ 

22.9+3.5♦ 

24.5 + 4.2 §

Gestation at OGTT (wk)

30.7+ 3.6

30.8 + 3.1

30.9 + 3.1

27.2 +7.2♦ 

26.9+7.4 ♦

27.0+8.0♦ 

Infant

-

-

-

-

-

-

Gestation

(wk)*

39.0 + 1.6

39.0 + 1.5

38.9 + 2.0

38.7+2.5

38.6+2.2

37.9 + 1.6§

Birth weight(g)

3147+ 454

3225 + 424

3225 + 424

3208+467

3165 +533

3235 +545

BMI( kg/m2)

12.7 + 1.3

12.8 +1.6

12.8 + 1.6

12.7+1.4

12.6+1.5

12.8 +1.4

Results are mean + standard deviation

*  P<.0001 by one-way analysis of variance

¶   P<.05 vs. group 1 by Duncan test.

|| P<.05 by vs. groups 1 and 2 by Duncan test.                      

♦  P<.05 vs. groups 1-3 by Duncan test.

£  P<.05 vs. groups 1-4 by Duncan test.

§  P<.05 vs. group 2 by Duncan test.

#  P<.005 by one-way analysis of variance

When pregnancy outcome was analyzed, the incidence of cesarean delivery was significantly different among the six groups and was positively associated with the OGTT 2-hour glucose values (Table 2).

Table 2. Pregnancy Outcome in Relation to the OGTT 2-Hour Glucose Values for the Entire Cohort 

 

>

OGTT

2-h Value

(mmol/L)

    <

 

-

Group1 (<6.0)

Group 2

(6.0-6.9)

Group 3

(7.0-7.9)

Group 4

(8.0-8.9)

Group 5

(9.0-10.9)

Group 6

(> 11.0)

n

304

386

304

665

436

54

Cesarean delivery*

12.1

12.7

16.8

14.9

18.2

31.5

Delivery <37 wk ||

5.3

4.1

4.3

6.1

7.8

9.3

Delivery <32 wk

0.3

0.3

1.3

0.9

1.8

1.9

Macrosomia

3.3

2.6

3.6

2.6

5.3

7.4

LGA

15.8

14.8

16.2

18.8

18.9

27.8

SGA

7.9

5.4

7.3

4.6

6.0

3.7

 

Results are expressed as percentage

* x2test P=.002

¶ P=.002 by Spearman correlation

 || P =.017 by Spearman correlation

♦ P = .009 by Spearman correlation

 

The incidence of spontaneous labor was examined, there were significant differences (P<0.0001) among the six groups. These resulting percentage figures were inversely correlated with the OGTT 2-hour glucose values (P<0.0001)(Table 3).

Table 3. Maternal and Infant Characteristics in Relation to the OGTT 2-Hour Glucose Values for the Cohort With Spontaneous Labor 

 

>

OGTT

2-h Value

(mmol/L

    <

 

-

Group1 (<6.0)

Group 2

(6.0-6.9)

Group 3

(7.0-7.9)

Group 4

(8.0-8.9)

Group 5

(9.0-10.9)

Group 6

(> 11.0)

n

255

305

241

509

315

29

Maternal

-

-

-

-

-

-

Age(y)*

28.4 + 4.8

29.4 + 4.8

30.2+ 4.4¶

31.9+ 4.8 ||

32.2+4.4||

32.2+4.0 ||

Weight (kg)*

51.9 +  7.0

53.0 +6.8

52.9 + 7.4

54.6 + 9.1¶

54.4+ 8.6¶

56.2+ 7.4 ♦

Height (cm)£ 

155.5 + 5.7

156.4 + 5.2

155.5 + 5.3

155.0 + 5.3

155.1+5.5

154.4 + 7.4 §

BMI (kg/m2)*

21.5 + 2.7

21.7 + 2.9

21.9 + 2.9

22.7 +3.6#

22.6+3.5#

23.8 + 2.8 ♦

Infant

-

-

-

-

-

-

Gestation (wk)*

39.0 + 1.6

39.0 + 1.4

38.9 +1.6

38.9+ 1.6

38.6+ 2.2

37.4 + 2.1 ♦

Birthweight (g)**

3128 + 448

326 + 423

3215 + 469

3217 + 432

3150 + 502

3176 + 620

BMI (kg/m2)

12.5 + 1.2

12.7 +1.3

12.8 + 1.5

12.6 + 1.3

12.5+1.4

12.9 + 1.5

Results are mean + standard deviation

* P<.0001 by one-way analysis of variance

¶ P<.05 vs. group 1 by Duncan test.                    

|| P<.05 vs. groups 1-3 by Duncan test.

 ♦ P<.05 vs. groups 1-5 by Duncan test.

 £ P<.02 by one-way analysis of variance

 § P<.05 vs. group 2 by Duncan test.

#  P < .05 vs. group 1 and 2 by Duncan test.

** P<.01 by one-way analysis of variance

When the incidences of cesarean and spontaneous delivery before 37 and 32 weeks were analyzed, significant differences were found among the 6 groups (Table 4).

Table 4. Pregnancy Outcome in Relation to OGTT 2-Hour Glucose values for the Cohort With Spontaneous Labor 

 

>

OGTT

2-h Value

(mmol/L

    <

 

-

Group1 (<6.0)

Group 2

(6.0-6.9)

Group 3

(7.0-7.9)

Group 4

(8.0-8.9)

Group 5

(9.0-10.9)

Group 6

(> 11.0)

n

255

305

241

509

315

29

Cesarean delivery*

7.4

5.6

10.7

6.7

6.6

24.1

Delivery < 37 wk ¶ ||

5.5

2.6

3.7

4.9

8.5

10.3

Delivery < 32 wk ♦ £

0.4

0.3

0.8

0.4

2.2

3.4

Macrosomia

2.7

2.6

2.9

2.0

3.8

6.9

LGA

15.7

15.7

14.1

17.7

14.3

27.6

SGA

7.8

4.9

7.5

4.1

6.7

0

 Results are expressed as percentage

*P= .003 by x2 test.

¶ P= .015 by x2 test.

|| P=.009 by Spearman correlation

♦ P = .018 by x2 test.

 £ P= .005 Spearman correlation

Other Findings

To determine whether maternal parity had any effect on the incidence of spontaneous birth, the analysis of the spontaneous labor cohort was stratified for parity (nulliparous or multiparous) and confined to delivery before 37 weeks because of the few deliveries before 32 weeks. The incidence of preterm delivery was still significantly different for both the nulliparous and multiparous subjects. 

Author Conclusion:

Gestational glucose intolerance affected gestational length and incidence of preterm births, which should be considered a confounding factor in the analysis of the neonatal outcome of GDM pregnancies.

Limitation

There was no information on the incidence of previous preterm birth in the database and thus there was no examination of the contribution of this factor to the outcome of the index pregnancy.

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 limitations 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) 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? 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? N/A
  4.1. Were follow-up methods described and the same for all groups? N/A
  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? N/A
  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? N/A
  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.) N/A
  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? N/A
  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? 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? 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? 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