GDM: Abnormal Glucose Tolerance During Pregnancy (2008)

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

To examine the relationship between the World Health Organization category of impaired glucose tolerance (IGT) (two-hour value of the 75-g oral glucose tolerance test at 8-10.9 mmol/L) and outcome in large-for-gestational age (LGA) infants to determine whether IGT affects perinatal morbidity in addition to affecting infant size.

 

Inclusion Criteria:

In this study, the 4,146 cases of singleton pregnancies with a nonanomalous LGA infant of more than 36 completed weeks of gestation delivered within a 12-month period were reviewed. Only those IGT cases with diet treatment (study group) and cases without GDM (control group) in order to eliminate the influence of insulin treatment and interventions for severe GDM on pregnancy outcome. Large for gestational infants (LGA) defined as those whose birth weight was > 90th percentile based on the local birth weight percentile chart.

Exclusion Criteria:
Exclusion criteria was not delineated.
Description of Study Protocol:

Recruitment method not detailed

Design Historical cohort

Blinding used (if applicable):  not applicable

Intervention

  • Women diagnosed as having IGT or DM were placed on dietary control (30 kcal/kg) initially
  • They were then assessed with a two-hour postprandial blood sugar profile.  
  • Insulin therapy was started for inadequate control (postprandial glucose >7 mmol/L) if dietary adjustments failed to normalize the blood glucose profile
  • Routine multivitamin and iron supplements (with 29 mg of elemental iron in a proprietary preparation) were given to all women.  
  • Every woman received electronic fetal monitoring during labor.
  • Pediatricians attended the delivery for resuscitation in all cases of suspected fetal distress, preterm delivery and other potential neonatal complications.
  • Within 30 minutes after birth, heel prick was performed for blood glucose estimation with hemoglucostix and was repeated every two hours for three times, then every six hours for one more day.
  • If hypoglycemia was detected (<2.5 mmol/L), a blood sample is sent to the laboratory for repeat glucose measurement.
  • If the newborn exhibited such signs as jitteriness, blood calcium and magnesium levels are estimated.
  • Feeding with breast milk or formula was done within two hours of birth.

Statistical Analysis 

  • Statistical analysis was performed with Student’s t test and the Mann-Whitney U test on continuous variables depending on the distribution of the results.
  • x2 or Fisher’s exact test on categorical variables
  • multiple logistic regression analysis, using a commercial statistical package (SPSS/PC, Chicago, Illinois).  
Data Collection Summary:

Timing of Measurements:  as below

Dependent Variables

  • 75-g OGTT was arranged for all antenatal patients with risk factors for the development of GDM, including maternal age >35 years, relevant past obstetric and family history, obesity, and recurrent and /or significant glycosuria.
  • In addition, all low –risk women and those with previously normal OGTT undergo random blood glucose testing at 28-30 weeks to screen for glucose intolerance.
  • Those with raised spot glucose (>5.8 mmol/L for <2 hours postprandial and >5.0 mmol/L for > 2 hours postprandial) also undergo the 75-g OGTT.
  • The diagnosis of IGT (two-hour value > 8.0mmol/L) or DM (two-hour value> 11.0 mmol/L) was based on the original WHO criteria which had been used at the hospital for more than a decade.
  • Pregnancy outcomes: delivery (breech, spontaneous, instrumental, cesarean),      gestational age (wk), birth weight (g), macrosomia, crown-heel length (cm), BMI (kg/m2), Apgar score (1 min [< 7 min] ; 5 min [<7 min] ), Male infant
  • Perinatal complications: cephalohematoma, fractured clavicle (with radiologic confirmation), shoulder dystocia (difficulty encountered at delivery of the shoulders and requiring manipulations such as McRoberts’s maneuver to overcome the obstruction), Erb’s palsy, hypocalcemia (serum ionized calcium<1.0 mmol/L), hypomagnesium (serum total magnesium <0.65 mmol/L), hypoglycemia (blood glucose <2.5 mmol/L), jaundice requiring phototherapy (serum bilirubin > µ mol/L), sepsis (cultural positivity or laboratory evidence of infection requiring antibiotic treatment, Meconium-stained fluid together with compatible radiologic features in the absence of a positive bacteriologic culture.

Independent Variables

Maternal characteristics:

  • age (yr)
  • multiparas
  • height (cm)
  • weight (kg) - prepregnancy, predelivery, total gain, % gain
  • BMI (kg/m2) –prepregnancy, predelivery
  • complications: placenta previa, antepartum hemorrhage, premature rupture of membrane, anemia, preeclampsia

Control Variables

 

Description of Actual Data Sample:

Initial N: 461 Large for Gestational Age newborns

Attrition (final N):  461

Age: Newborns

Ethnicity: not detailed

Other relevant demographics:

Anthropometrics

Location: Department of Obstetrics and Gynaecology and of Pediatrics, Tsan Yuk Hospital, University of Hong Kong, Hong Kong, PRC

 

Summary of Results:

The IGT group was significantly older and had more multiparas and higher prepregnancy weight, and prepregnancy and predelivery BMI (Table I).

Table 1 Maternal Demographics and Complications in relation to Glycemic status in Pregnancies with Large-for –Gestational- Age Infants 

Factor

IGT Group (n=79)

Non-IGT group (n=382)

P

Maternal age(yr)

32.1 + 4.6

29.9   +   4.6

<.0001

Multiparas

53 (67.1)

221(57.9)

.008

Height(cm)

156.5 + 5.0

157.3 + 5.7

NS

Weight (kg)

-

-

-

Prepregnancy

57.7 +  9.0

54.5+ 7.7

.004

Predelivery

72.3 + 9.7

70.4 + 8.2

NS

Total gain

13.9 + 5.2

16.0 + 4.8

.002

% Gain

25.0 +10.2

30.0 + 10.1

.000

BMI(kg/m2 )

-

-

-

Prepregnancy

23.5 + 3.6

21.9 2.9

.001

Predelivery

29.5 + 3.7

28.5 +  3.1

.024

Complications

-

-

-

Placenta previa

1(1.3)

3 (0.8)

NS

Antepartum hemorrhage

2 (2.5)

11(2.9)

NS

Premature rupture of membranes

12 (15.2)

55 (14.4)

NS

Anemia

4 (5.1)

25(6.5)

NS

Preeclampsia

3( 3.8)

13 (3.4)

NS

Results are given as mean + SD or number (%)

There was no difference in mode of delivery, gestational age, infant birth weight, Apgar scores or incidence of male infants. However, overall perinatal complications was more common in the IGT group (44.3% vs. 24.9%, OR 2, 40, 95% CI 1.46-3.97(Table II).

Table  II  Pregnancy Outcome in Relation to Maternal Glycemic Status in Pregnancies with Large-for-Gestational-Age Infants  

Outcome

IGT group (n=79)

Non-IGT group

P

Delivery

-

-

-

Breech

0

1( 0.3)

-

Spontaneous

35 (44.3)

198 (51.8)

NS

Instrumental

17 (21.5)

89 (23.3)

-

Cesarean

27 (34.2)

94 (24.6)

-

Gestational age (wk)

39.3+ 1.1

39.5+ 1.4

NS

Birth weight (g)

3970 + 259

3911+ 263

NS

Macrosomia

23(29.1)

116 + (30.4)

NS

Crown-heel length (cm)

52.6 + 2.0

52.8+ 2.1

NS

BMI (kg/m2)

14.4+ 1.2

14.1 + 1.2

NS

Apgar score

-

-

-

1 min

8.1 + 1.6

8.4 + 1.4

NS

<7

8(10.1)

31(8.1)

NS

5 min

9.5 + 0.8

9.7 + 0.8

NS

<7

1(1.3)

2 (0.5)

NS

Male infant

41 (51.9)

236 (61.8)

NS

Results are given as mean + SD or number (%)

Significant differences were found with Erb’s palsy (OR 3.87, 95% CI 1.06-14.08), meconium aspiration syndrome (OR 3.87, 95% CI 1.06-14.08), neonatal jaundice requiring photo therapy (OR 1.83, 95% CI 1.04-3.22) and neonatal sepsis requiring treatment (OR 2.42, 95% CI 1.22-4.78)(Table III).

Table III     Perinatal Complications in Relation to Maternal Glycemic Status in Pregnancies with Large-for-Gestational-Age Infants 

Complication

IGT group (n=79) (n, %)

Non-IGT Group  (n=79) (n, %)

P

Complications overall

35 (44.3)

95(24.9)

.001

Cephalhematoma

6 (7.6)

23(6.)

NS

Shoulder dystocia

3(3.8)

5(1.3)

NS

Clavicle fracture

3(3.8)

5 (1.3)

NS

Erb’s palsy

4(5.1)

5(1.3)

0.51

Hypocalcemia

2(2.5)

2(0.5)

NS

Hypomagnesia

3(3.8)

8(2.1)

NS

Hypoglycemia

1(1.3)

1(0.3)

NS

All metabolic complications

5(6.3)

11(2.9)

NS

Phototherapy

14(17.7)

37(9.7)

.038

Sepsis

11(13.9)

22(5.8)

.010

Meconium –stained  fluid

15(19.0)

47(12.3)

NS

Meconium aspiration syndrome

4(5.1)

5(1.3)

.051

Other Findings

 

Author Conclusion:

Despite dietary treatment, maternal IGT was associated with increased perinatal morbidity independent of its effect on fetal size.

Limitation

  • Although IGT was found in this study to be a significant risk factor for neonatal sepsis, the cause was not apparent, as there was no difference in the incidence of prelabor rupture of the membranes or mode of delivery. Further studies are necessary to elucidate the mechanism of this complication.
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? N/A
  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? 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? 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? 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