GDM: Abnormal Glucose Tolerance During Pregnancy (2008)
The objective was to study the clinical impact of mild carbohydrate intolerance in pregnant women with risk factors for gestational diabetes.
- A total of 3520 diagnostic OgTTs were performed in singleton pregnancies during the study period. All women in the study had risk factor(s) and elevated fasting glucose according to the screening procedure and criteria advocated by the Diabetic Pregnancy Study Group of the European Association for the Study of Diabetes.
- After multiple gestations in the study period were excluded, a total of 3401 women remained. Of these, 497 had GDM, and treatment with diet was indicated. Thereafter 2904 nondiabetic women referred to routine obstetric care were eligible for the analysis.
- Patients referred to the Centers from other hospitals because of a well-defined chronic disease were excluded beforehand together with patients with pregestational diabetes or multiple pregnancies.
- Patients with GDM were treated diet, insulin, or both and kept under special obstetric surveillance. These patients were excluded from the study. The nondiabetic women were referred to routine obstetric care.
Recruitment : method was not detailed.
Design : Historical cohort study of 2904 pregnant women examined for gestational diabetes on the basis of risk factors, information on the glucose tolerance results and clinical outcomes was collected from laboratory charts and medical records.
Blinding used: not applicable
Intervention
Patients with GDM were treated with diet, insulin, or both and kept under special obstetric surveillance. These patients were excluded from the study. The nondiabetic women were referred to routine obstetric care.
Statistical Analysis
- All analyses were performed with the statistical program STATA 6.0 (Stata Corporation, College Station, Texas).
- The effects of glucose levels during OGTT were analyzed by dividing the fasting and 2-hour values in quartiles and comparing the frequencies of various outcomes in these four groups by univariate logistic regression analyses. The quartiles were scored 1 to 4 and analyzed as a quantative variable.
- In the multivariate logistic regression models, the glucose values were used directly as quantitative variables. Adjustments were made for the risk factors prepregnancy body mass index, maternal age, parity, smoking, gestational age, history of macrosomia or stillbirth, ethnic background, and obstetric center.
- In all models both the fasting glucose and the 2-hour glucose values were included.
- The results are expresses as odds ratios and corresponding 95% confidence intervals and P values.
- Differences between groups were analyzed with the x2 test for categorical variables and the t test for quantative variables.
- Trends were tested with Cuzick’s nonparametric test.
- A significance level of .05 was chosen (2-sided tests).
Timing of Measurements
Dependent Variables
Diagnosis Criteria
- All women in the study had risk factor(s) and fasting blood glucose > 4.1 mmol/L (74 mg/dl) according to established screening procedures.
- For women with more than 1 pregnancy in the study period, only the first pregnancy was included.
- The project was approved by the local ethics committee of the participating centers.
- All pregnant women consulting the obstetrics departments involved were tested for GDM by the same selective screening procedure based on anamnestic risk factors, urinalysis, and measurement of fasting capillary plasma glucose or fasting capillary blood glucose.
- The urine was tested for glucose by a BM-Test Strip (Bochringer-Mannheim) on every visit throughout pregnancy.
- On the first visit to the obstetric clinics, women with certain risk factors for GDM (family history of diabetes mellitus, 20% overweight or more in the nonpregnant state, previous unexplained stillbirths, previous unexplained stillbirth, previous delivery of a baby with birth weight > 4500 g , age > 35 years, GDM in previous pregnancy) were selected for screening.
- If the fasting blood glucose level was 4.1 mmol/L (74 mg/dL) or more on two occasions (corresponding plasma glucose values of 4.7 mmol/L (85 mg/dL, a diagnostic OGTT (75g, 3 hours) was performed.
- In women without GDM the procedure with measurements of fasting glucose levels and OGTT was repeated in the third trimester (gestational weeks 30-32).
- The OGTT was considered abnormal if two or more glucose values exceeded the mean+3 SDs on a curve based on a group of Danish women , healthy, nonobese, nonpregnant women without a family history of diabetes investigated by the same procedure.
- The mean + 3 SDs for capillary blood glucose were:
|
Capililary Blood Glucose |
Minutes |
|
5.7 mmol/L(103 mg/dl) |
0 |
|
11.9 mmol/l(214 mg/dL) |
30 min |
|
12.0 mmol/L (216 mg/dL) |
60 min |
|
9.7 mmol/L (175 mg/dL) |
90 min |
|
8.9 mmol/L (160mg/dL) |
120 min |
|
8.5 mmol/L (153 mg/dL) |
150 min |
|
7.4 mmol/L(133mg/dL) |
180 min |
- Pregnancy Induced Hypertension –was diagnosed if the blood pressure met the criteria for preeclampsia without the presence of proteinuria.
- Preeclampsia-was defined as persistently elevated blood pressure (office blood pressure higher than 140/90 mm Hg on more than 1 occasion ) and proteinuria (2+ on a urine protein test strip equal to 1.0 g/L)
- Introduction of labor
- Assisted delivery-included delivery by vacuum extraction, forceps, or emergency cesarean section.
- Emergency cesarean
- Shoulder dystocia- was defined when obstetric maneuvers in addition to downward traction, episiotomy, or mild suprapubic pressure were required to deliver the shoulders. In each case the diagnosis given at delivery was reevaluated by an obstetrician.
- Macrosomia was defined by 3 different assessments: (1) birthweight> 4000g, ; (2) birth weight birthweight> 4500g; (3)LGA-defined as birth weight >90th percentile for a Danish standard population,
- Low apgar score-defined by Apgar score less than 7 after 5 minutes.
- Jaundice – the diagnosis of jaundice required treatment with phototherapy
- Neonatal-Hypoglycemia was define as the need for intravenous glucose during the first 48 hours of life
- Respiratory distress –requiring treatment with continuous positive airway pressure for at least 30 minutes.
- Fasting blood glucose (mmol/L)
- 2-Hour blood glucose (mmol/L)
Independent variables
- prepregnancy body mass index
- maternal age
- parity
- smoking
- gestational age- was estimated on the basis of early ultrasound examination if possible (90%); otherwise it was based on last menstrual period.
- history of macrosomia or stillbirth
- ethnic background
- obstetrics center
Control Variables
Initial N: 3,401
Attrition (final N): 2904 nondiabetic women referred to routine obstetric care were eligible for the analysis
Age: Mean age 30.3 years
Ethnicity: Danish women
Other relevant demographics:
Anthropometrics
Location: The University Hospitals of Copenhagen (Copenhagen County Hospital and Rigshospitalet) Aarhus, and Odense
The frequency of macrosomia and induction of labor rose significantly with increasing fasting and 2-hour glucose levels. The outcomes of hypertension, assisted delivery, emergency cesarean section, and shoulder dystocia were significantly associated with the 2-hour values (see Table 1 and table II).
Table 1 Impact of fasting glucose levels during OGTT (quartiles) on the frequency of various outcomes in 2004 women without GDM: univariate logistic regression analysis
|
|
|
|
|
|
|
|
|
- |
--------à |
Quartilies |
(mmol/L) |
ß-------- |
- |
- |
|
Outcome (%) |
<4.1 |
4.1-4.3 |
4.4-4.5 |
> 4.6 |
Odds ratio |
95% Confidence interval |
|
PIH and preeclampsia |
5.8 |
5.5 |
7.1 |
7.9 |
1.12 |
0.99-1.26 |
|
Introduction of labor* |
15.1 |
15.5 |
16.2 |
18.8 |
1.14 |
1.04-1.25 |
|
Assisted delivery |
24.9 |
24.0 |
25.5 |
27.5 |
1.04 |
0.97-1.15 |
|
Emergency caesarean |
11.7 |
12.5 |
11.9 |
14.7 |
1.08 |
0.98-1.19 |
|
Shoulder dystocia |
1.4 |
0.8 |
1.7 |
2.2 |
1.21 |
0.92-1.62 |
|
Percent delivery |
5.2 |
5.3 |
5.7 |
4.6 |
0.98 |
0.80-1.09 |
|
Birth weight > 4000g ¶ |
23.4 |
27.9 |
28.5 |
31.7 |
3.14 |
1.06-1.22 |
|
Birth weight > 4500 g£ |
4.3 |
6.3 |
6.8 |
8.1 |
1.23 |
1.08-1.40 |
|
LGA ¶ |
17.2 |
18.9 |
22.7 |
25.5 |
1.19 |
1.10-1.29 |
|
Low apgar score |
1.4 |
1.7 |
1.4 |
0.5 |
0.79 |
0.61-1.03 |
|
Jaundice |
2.8 |
3.2 |
2.8 |
2.4 |
0.95 |
0.80-1.12 |
|
Hypoglycemia |
1.5 |
3.2 |
2.8 |
2.4 |
1.11 |
0.92-1.35 |
|
Respiratory distress |
7.9 |
7.4 |
8.7 |
6.4 |
0.95 |
0.83-1.07 |
The material was divided into quartiles according to fasting glucose values. Odds ratio and 95% confidence intervals represent the relative risk for each quartile rise in blood glucose.
Cut points for quartiles in milligrams per deciliter (25%, 50 %, and 75% percentiles); 74 mg/dl, 79 mg/dl, and 83 mg/dL.
PIH. Pregnancy-Induced hypertension; LGH, large for gestational age.
*P < .05
¶ P < .001
£ P < .01
Table II Impact of 2-hour glucose during OGTT (quartiles) on the frequency of various outcomes in 2904 women without GDM: univariate logistic regression analysis
|
|
|
|
|
|
|
|
|
- |
à |
Quartilies |
(mmol/L) |
ß |
- |
- |
|
Outcome (%) |
<5.7 |
5.7-6.3 |
6.4-7.1 |
> 7.2 |
Odds ratio |
95% Confidence interval |
|
PIH and preeclampsia* |
4.8 |
5.9 |
8.4 |
7.2 |
1.15 |
1.02-1.31 |
|
Introduction of labor* |
13.9 |
15.1 |
16.2 |
18.4 |
1.11 |
1.02-1.22 |
|
Assisted delivery¶ |
21.8 |
25.4 |
27.2 |
27.8 |
1.11 |
1.03-1.20 |
|
Emergency caesarean¶ |
10.6 |
11.0 |
13.9 |
15.1 |
1.16 |
1.05-1.28 |
|
Shoulder dystocia £ |
0.4 |
1.8 |
1.8 |
2.9 |
1.78 |
1.32-2.40 |
|
Percent delivery |
4.2 |
4.4 |
5.1 |
4.9 |
1.07 |
0.92-1.25 |
|
Birth weight > 4000g € |
22.9 |
27.4 |
28.8 |
32.3 |
1.16 |
1.08-1.25 |
|
Birth weight > 4500 g* |
5.2 |
5.3 |
5.6 |
8.6 |
1.16 |
1.01-1.34 |
|
LGA £ |
16.0 |
20.7 |
21.1 |
27.2 |
1.23 |
1.134-133 |
|
Low apgar score |
1.4 |
1.0 |
1.0 |
1.5 |
1.00 |
0.78-1.37 |
|
Jaundice |
2.4 |
3.5 |
3.0 |
3.7 |
1.13 |
0.98-1.26 |
|
Hypoglycemia |
2.1 |
2.2 |
2.9 |
2.5 |
1.08 |
0.88-1.34 |
|
Respiratory distress |
5.4 |
8.7 |
8.1 |
7.2 |
1.04 |
0.92-1.17 |
The material was divided into quartiles according to fasting glucose values. Odds ratio and 95% confidence intervals represent the relative risk for each quartile rise in blood glucose.
Cut points for quartiles in milligrams per deciliter ( 25%, 50% and 75% percentiles); 74 mg/dl, 79 mg/dl, and 83 mg/dL.
PIH. Pregnancy-Induced hypertension; LGH, large for gestational age.
*P < .05
¶P < .001
£ P < .01
Table III. Characteristics of deliveries complicated by shoulder dystocia with and without severe sequela compared with other weight deliveries in women with a nondiabetic OGTT
|
|
|
|
|
|
|
|
Group A ( n=14) |
Group B (n=28) |
Group C(n=2355) |
Trend (P value) |
|
Birth weight (g) |
4223 (3822-4813) |
4170 (4025-4660) |
3500 (3286-4000) |
<.01 |
|
Fasting blood glucose * (mmol/L) |
4.8(4.7-4.9) |
4.8(3.9-4.5) |
4.4(4.1-4.6) |
.01 |
|
2-Hour blood glucose *(mmol/L) |
7.2( 6.2-7.5) |
7.0( 6.5-7.8) |
6.4(5.6-7.1) |
<.01 |
The results are presented as median with interquartile range. Group A: Shoulder dystocia with severe sequelae; group B : shoulder dystocia without severe sequela ; C: no shoulder dystocia (vaginal delivery). P values refer to Cuzick’s test for trends across ordered groups.
* 1 mmol/L= 18 mg/dL.
Other Findings
Both fasting and 2-hour glucose values were significantly associated with macrosomia, whereas only the-2-hour value was associated with assisted delivery, emergency cesarean section, and shoulder dystocia.
In a group of nondiabetic pregnant women with risk factors for gestational diabetes , there was a graded increase in the frequency in the frequency of shoulder dystocia and other maternal-fetal complications with increasing glucose levels during an oral glucose tolerance test.
Limitations:
- The results of the multivariate analysis support the contention that the adverse outcomes associated with gestational diabetes are not entirely explained by the presence of various risk factors but are to some extent attributable to the carbohydrate disorder itself.
- It remains to be seen whether there is a relationship between more severe perinatal complications and glucose levels in this range.
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.
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Quality Criteria Checklist: Primary Research
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| 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) | N/A | |
| 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.) | 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? | 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? | 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)? | 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 | |