EAL

GDM: Abnormal Glucose Tolerance During Pregnancy (2008)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

The purpose of this study was to determine maternal parameters with the strongest influence on fetal growth in different periods of pregnancies complicated by an abnormal glucose tolerance test (GTT).

Inclusion Criteria:

Pregnant women with glucose intolerance who attended the diabetes clinic of the Vivantes Medical Center Neukoelln, Berlin Germany between 1994 and 1998.
Documented presence of glucose intolerance first diagnosed in pregnancy
Accurate gestational age (GA), confirmed by an ultrasound examination before 20 weeks of gestation
Singleton pregnancy
Complete fetal biometry determined by ultrasound at entry to diabetic therapy and a concurrent glucose profile measured within 3 days of the ultrasound examination
Absence of identified fetal anomalies
Absence of maternal vascular disease including preexisting hypertension

Exclusion Criteria:

Excluded if not included above.

Description of Study Protocol:

Recruitment

Subjects were selected from the population of pregnant women with glucose intolerance who attended the diabetes clinic of the Vivantes Medical Center Neukoelln in Berlin, Germany, between 1994 and 1998.

Design

Women with either GDM or IGT were divided into categories according to gestational age (GA) at the time of entry visit. The categories were: <24 weeks, 24 weeks, 28 weeks, 32 weeks and 36 weeks GA. Abdominal circumference (AC) was classified as either AC <90th %ile or > 90 percentile. Subjects were followed to birth.

Blinding used (if applicable)

Standards for GDM and AC measurement were utilized.

Intervention (if applicable)

Monthly ultrasound for fetal AC was done.

Statistical Analysis

Difference between pregnancies with and without fetal macrosomia or LGA at birth and differences between women with GDM and IGT were tested for statistical signficance by t tests or ANOVA (continuous variables) or by Chi Squared analysis (categorical variables). Univariate logistic regression analysis was performed to determine parameters with signficant correlation to the fetal macrosomia status at entry and at each GA category.

Data Collection Summary:

Timing of Measurements

Fetal AC measurements were done at the study entry and montly.
Glucose measurements were done 6 times day twice weekly
HbA1c measurements were done at time of diagnosis
Neonatal and maternal outcomes were done upon birth

Dependent Variables

Maternal outcomes
Neonatal outcomes

Independent Variables

Fetal AC
Maternal GDM or IGT

Control Variables

Description of Actual Data Sample:

Initial N: 406

Attrition (final N): 368 (280 with GDM), 88 with IGT

Age: See chart below

Ethnicity: not stated

Other relevant demographics:

Anthropometrics:

Women with GDM compared to women with IGT had significantly higher OGTT values (p <0.05) and entry HbA1c levels (p= 0.04) and more frequently required insulin therapy (p=0.006) however, third semester glycemic control was not different after initiation of therapy. No other maternal entry parameters were signficantly different between subjects with GDM and IGT. Therefore, women with GDM and IGT were analyzed.

Location: Berlin, Germany

Summary of Results:

	AC <90th percentile	AC > 90th %ile	p value
n	300	68
Maternal age (years)	30.2 5.4	31.5 5.4	0.08
Parity	1.9 1.2	2.4 2.0	0.013
Prepregnancy wt (kg)	71.5 15.9	80.4 20.0	0.0001
Prepregnancy BMI (kg/m2)	26.8 5.9	29.8 5.1	0.03
Prepregnancy BMI >30 (%)	25.7	44.1	0.002
Prior LGA (%)	8.0	25.0	<0.0001

Neonatal LGA: AC <90 th percentile (12.6%), AC > 90th percentile (43.1 %), p<0.0001

Other Findings

	at entry	<24 GA	24 GA	28 GA	32 GA	36 GA	at birth
AC > 90th %ile N/total ultrasounds (%)	68/368 (18.5)	21/138 (15.2)	20/121 (16.5)	32/212 (15.0)	52/255 (20.4)	25/143 (17.5)	69/368 (17.6)
Historical	LGA		LGA	LGA
	BMI*		BMI	BMI	BMI	BMI	BMI
	OBesity		Obesity	Obesity	Obesity	Obesity	Obesity
	GDM
	Parity		Parity

Glycemic parameter		OGTT-FCG§	OGTT-FCG
					Profile-FCG€	Profile FCG	Profile-FCG

Significant univariate predictors for fetal AC > at entry to diabetic care, at different gestational ages, and for LGA at birth

* BMI > 30 kg/m2

§ FCG - Fasting Capillary Glucose of the OGTT

€ Profile- FCG: Fasting capillary glucose of the profile at 32-35 weeks.

Author Conclusion:

In the late second and early third trimester, maternal BMI and LGA in a previous pregnancy appear to have the strongest influence on fetal growth, while later in the third trimester coincident with the period of maximum growth described in diabetic pregnancies, maternal glycemia predominates.

Funding Source:

University/Hospital:

Humbolt University, Vivantes Medical Center, University of Southern California

Reviewer Comments:

Authors note limitations of bias in selection of the different cohorts, as well as a high rate of obese women (29%) compared with the average German population (10%) which could account for the stronger influence of obesity compared with the possible influence of maternal glycemia on fetal growth.

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?		???
	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?		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.)	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?	N/A
	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%.)	Yes
	4.3.	Were all enrolled subjects/patients (in the original sample) accounted for?	Yes
	4.4.	Were reasons for withdrawals similar across groups?	Yes
	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?	Yes
	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?		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?	N/A
	6.3.	Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect?	Yes
	6.4.	Was the amount of exposure and, if relevant, subject/patient compliance measured?	Yes
	6.5.	Were co-interventions (e.g., ancillary treatments, other therapies) described?	Yes
	6.6.	Were extra or unplanned treatments described?	???
	6.7.	Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups?	Yes
	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