GDM: Abnormal Glucose Tolerance During Pregnancy (2008)

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

The aim of this study was to evaluate the prevalence of the metabolic syndrome and its effect on neonatal outcomes in pregnancies with different degrees of hyperglycemia.

 

Inclusion Criteria:

700 Caucasian women were identified and enrolled in one of 4 groups - Normal (controls) and thereby increasing severity of glucose tolerance

1.      OGTT negative (normal) n = 100

2.      OGTT positive, OGTT negative n = 350

3.      OGTT only one abnormal value n = 100

4.      GDM positive n = 150

All women gave informed consent to enrollment in the study and all procedures were according to the Helsinki Declaration of 1975.

Exclusion Criteria:

Pregnant women known to have diabetes mellitus or a disease affecting glucose metabolism.

Description of Study Protocol:

Recruitment : Subject selection was based on a sequential screening from April 1999-February 2001. All pregnant women attending the Unit were routinely screened with a 50-g oral glucose test at 24-28 weeks of gestational age.

Design : Cohort

Blinding used: Data on children’s birth weight and health status were obtained from the clinical records by a trained physician and blinded to the results of the OGTT

Intervention

1. OGTT negative (normal) n = 100

2. OGTT positive, OGTT negative n = 350, received no diet counseling or treatment

3. OGTT only one abnormal value n = 100 & 4. GDM positive n = 150, both received a diet plan, and about 10% of GDM patients placed on insulin

Statistical Analysis

  • Analysis of variance (ANOVA) and the chi-square test were used to compare means for continuous variables or frequencies of discrete variables.
  • Analysis of covariance (ANCOVA) was performed to compare different parameters, using gestational age and BMI as covariates.
  • Multiple logistic regression analyzes were performed to evaluate the independent association of classes of glucose tolerance, the metabolic syndrome and its components with neonatal macrosomia, morbidity and icterus, after adjustment for multiple variables.
  • As insulin, triglyceride and birth weight values were not normally distributed, they were log transformed.
  • Data were presented as mean + standard deviation or percentages, with P<0.05 as the significant cutoff.
Data Collection Summary:

Timing of Measurements  

  • Height/weight-measured at the time of screening
  • Waist circumference (at the point of minimal abdominal girth) was measured in all women, as it is minimally influenced by uterine growth between 24 and 28 weeks of gestational age.
  • Serum insulin and plasma triglycerides and HDL-cholesterol were measured after an overnight fast at the time of the screening test.

Dependent Variables

  • Data on children’s birth weight and health status were obtained from the clinical records by a trained physician and blinded to the results of the OGTT.
  • Data were available in each class of glucose tolerance for 90% of the women(all carrying singleton pregnancies).
  • Large for gestational age-birth weight exceeded the 90th percentile &
  • Small for gestational age-birth weight below the 10th percentile , both were determined  by considering sex and gestational age neonatal anthropometric standards for a population of Northern Italy.
  • Preterm births- if maternal gestational age at delivery was <37 weeks.
  • Neonatal morbidity was diagnosed in the presence of any pathological conditions described in the clinical records , which required a specific treatment or a prolonged in-hospital stay, i.e. malformations, respiratory diseases, infections, icterus, neurological , gastrointestinal or hematological diseases, etc.

Independent Variables

  • Height/weight-measured at the time of screening
  • Pre-pregnancy weight was recorded form patients’ recall
  • Body Mass Index(BMI) was calculated as pre-pregnancy weight in kilograms divided by the square of their height in meters.
  • Waist circumference (at the point of minimal abdominal girth) was measured in all women, as it is minimally influenced by uterine growth between 24 and 28 weeks of gestational age.
  • Information concerning medically diagnosed diabetes in living or dead parents and education levels ( primary, secondary or tertiary schools ) were collected.
  • Serum insulin and plasma triglycerides and HDL-cholesterol were measured after an overnight fast at the time of the screening test.
  • Serum glucose was measured by the glucose oxidase method( Glucose-Analyzer II Beckman, Fullerton CA, USA ) and  insulin by radioimmunoassay (Corning Kit, Modfield, Massachusetts, USA); the variable coefficients were 3.4-5.1%.
  • Plasma triglycerides were measured by enzymatic colorimetric assay ( Poli , Clinical Chemistry CL7000 , Shimadzu , Kyoto , Japan ) ; high density lipoprotein (HDL)- cholesterol by enzymatic colorimetric assay  after precipitation  of low density lipoprotein (LDL) and very low density lipoprotein (VLDL) fractions using heparin-MnClsolution and centrifugation at 4 o C.
  • Metabolic syndrome - There is no definition for metabolic syndrome in pregnancy. The researchers decided the following:  any one of 3 primary criteria [one abnormal value of GDM or hyperinsulinemia ( >2 SD above the mean for  the 100 women with negative OGTTs, used as controls)], plus at least 2 of the following secondary criteria: arterial blood pressure > 140/90; plasma triglycerides > 2 SD above the mean of the controls and/or low HDL-cholesterol (<1.0 mmol/l); BMI > 30kg/m 2  or waist > 2 SD above the means of the controls, in accordance with recent consensus. 

Control Variables

 

 

Description of Actual Data Sample:

Initial N:

700 Caucasian women were identified and enrolled in one of 4 groups: Normal (controls) and there by increasing severity of glucose tolerance

  • OGTT negative (normal) n = 100
  • OGTT positive, OGTT negative n = 350
  • OGTT only one abnormal value n = 100
  • GDM positive n = 150

Attrition (final N):  as above

Age: See Table I

Ethnicity: Caucasian women

Other relevant demographics:

Anthropometrics

Location:  Department of Internal Medicine and Obstetrician and Gynecology, University of Turin, Turin, Italy.

 

Summary of Results:

 

Class 2 women were older and showed larger waist, higher systolic and diastolic blood pressures, insulin levels and lower HDL-cholesterol and education levels than controls (Table I).  

Table I. Clinical characteristics of the subjects studied

 

Class 1

Class 2

Class 3

Class 4

p

Number

100

350

100

150

-

Age (years)

30.8±4.2*

31.8±4.3§

32.9±4.7♦

32.6±4.9 €

0.002

Parental diabetes(%)

32.0

27.4 ¶

33.0

39.3

NS

Nulliparous(%)

58.0

61.7

57.0

57.3

NS

Smoking (%)

11.0

12.9

15.0

18.0

NS

Primary school(%)

38.0

32.9¶

36.0

46.7

0.03

*p<0.05 class 1 versus class 2.

♦p<0.01 class 1 versus class 3

 € p<0.01 class 1 versus class 4

§ p<0.05 class 2 versus class 3

¶ p<0.01 class 2 versus class 4

The prevalence of the metabolic syndrome significantly increased from the class 1 women to those with GDM and was significantly higher in class 2 patients versus class 1 (p=0.025)(Table II).

Table II. Anthropometric and laboratory characteristics in the subjects studied 

 

Class 1

Class 2

Class 3

Class 4

p

Number

100

350

100

150

-

Prepregnancy weight(kg)

60.9±12.0

62.8±13.8**€€ 

67.0±14.5

66.4±15.3§

0.001

Height(m)

1.63±0.05

1.63±0.06 €€ 

1.62±0.06

1.62±0.06

NS

Prepregnancy BMI (kg/m2)

23.1±4.6

23.5±4.8**€€

25.6±5.4 €

25.3±5.4§

0.00001

BMI at screening(kg/m2)

25.8±4.4

26.2±4.5**€€ 

29.0±5.0€

28.9±5.6§

<0.00001

Waist (cm)

85.2±9.2♦

96.5±10.4**€€ 

100.4±10.5€

98.7±12.4§

<0.00001

Systolic pressure(mmHg)

102.4±11.6♦

112.7±14.1¶€€ 

116.2±14.3€

117.5±16.6§

<0.00001

Diastolic pressure(mmHg)

62.7±8.5♦

72.5±10.9€€ 

75.0±11.8€

75.1±10.4§

<0.00001

Triglycerides(mmol/L)

1.76±0.67

1.82±0.68**€€ 

2.09±0.78€

2.06±0.75§

0.00008

HDL-cholesterol(mmol/L)

2.10±0.38♦

1.94±0.38

1.88±0.39€

1.88±0.39§

0.00003

Fasting insulin(pmol/L)

47.9±44.9♦

64.4±59.1**€€ 

119.8±191.0€

130.6±211.5§

<0.00001

Metabolic syndrone(%)

0*

4.9**€€ 

20€

18§

<0.00001

*p<0.05 class 1 versus class 2.

♦ p<0.01 class 1 versus class 2

p<0.01 class 1 versus class 3

§ p<0.01 class 1 versus class 4

 ¶ p<0.05 class 2 versus class 3

 * * p<0.01 class 2 versus class 3

♦ ♦ p<0.05 class 2 versus class 4

€€ p<0.01 class 2 versus class 4

Birth weight of offspring, prevalence of LGA babies and prevalence of icetrus or any neonatal disease were significantly higher in women with OGCT + (both classes 2, 3, 4).

Table III. Pregnancy outcomes in the different classes of glucose tolerance

 

Class 1

Class 2

Class 3

Class 4

p

Number

91

315

90

135

-

Cesarean section (%)

30.8

32.7

43.3

40.7

NS

Weeks of delivery

38.8±2.2

39.0±1.8

38.8±2.2

38.9±1.8

NS

Premature births (%)

7.7

6.7

10.0

8.1

NS

Birth weight(g)

3.174±0.51 ♦ 

3.345±0.48 ♦  ♦ 

3.226±0.59

3.319±0.48 ¶

0.01

LGA (%)

8.8*

19.0

18.9

20.7

NS

SGA (%)

 2.2

 4.8

 4.4

 6.7

 NS

Apgar score

 8.7±0.8

 8.6±1.0

 8.3±1.6 €

 8.6±1.0

 NS

Icterus (%)

 4.4*

 13.3

 15.5 €

 17.0**

 0.04

Respiratory distress

 2.2

 4.4

 4.4

 4.4

 NS

Malformations(%)

 0

 2.2

 3.3

 2.2

 NS

Death (%)

 2.2

 1.3

 0

 0

 NS

Neonatal diseases(any,%)

 9.9 ♦ 

 26.3

 30.0 §

 25.2**

 0.008

 * p<0.05 class 1 versus class 2.

  ♦  p<0.01 class 1 versus class 2

  € p<0.05 class 1 versus class 3

  § p<0.01 class 1 versus class 3

  ¶ p<0.05 class 1 versus class 4

   ♦ ♦ p<0.01 class 1 versus class 4

   €€ p<0.05 class 2 versus class 3

Other Findings

 

 

Author Conclusion:

Authors’ conclusion: 

  • Metabolic syndrome in mid-pregnancy was an independent predictor of macrosomia in women with any degree of gestational hyperglycemia
  • The oral glucose challenge test identified pregnancies with metabolic abnormalities and adverse neonatal outcomes also in the presence of a normal oral glucose tolerance test.     

Limitations:

  • Considering the potential limit of the weight circumference measurements during pregnancy, the prevalence of the metabolic syndrome was assessed without considering waist values.
  • As no definition of the metabolic syndrome in pregnancy exists, the researchers noted that their definition was arbitrary, though based on recent consensus.
  • If studies on larger sample sizes provide support for these presumptions, the follow-up of all women with OGTT+ and the research of the components of the metabolic syndrome, to identify higher risk subjects for adverse neonatal outcomes, might be warranted.
Funding Source:
Reviewer Comments:

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

Analytical longitudinal surveys refer to what epidemiologists term prospective or cohort studies. A Cohort Study is a study in which patients who presently have a certain condition and/or receive a particular treatment are followed over time and compared with another group who are not affected by the condition under investigation. 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.

 

                 

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? 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.) N/A
  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? 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)? N/A
  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