GDM: Monitoring (2008)

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

The purpose of the study was to summarize the relationship between the metabolic status of pregnant women, as reflected by the presence of hypoglycemia and measurements of urinary acetone, hemoglobin A1C, and fasting plasma glucose, B-hydroxybutyrate, and free fatty acids, during the second and third trimesters of pregnancy and the intellectual growth of their offspring in early childhood as assessed by the mental-development index of the Bayley Scales of Infant Development at the age of two years and their average score on the Stanford-Binet Intelligence Scale at the ages of three, four and five years.

Inclusion Criteria:
  • Women with pregestational diabetes followed through out metropolitan Chicago
  • Women with gestational diabetes (those women screened relatively early in gestation because of classic risk factors and women from the general prenatal clincs at Northwestern Memorial Hospital who were screened for glucose intolerance at 24-28 weeks gestation)
  • Pregnant Women with normal glucose metabolism as documented by oral glucose tolerance defined by the criteria of O'Sullivan and Mahan.
Exclusion Criteria:
  • Requiring medication on a long-term basis for treatment of medical or psychiatric problems.
  • Failure to adhere to study protocol
  • Twin pregnancy
  • IUGR
  • Prematurity
Description of Study Protocol:

Recruitment:

Wmen with singleton pregnancy followed by the Center for Endocrinology, Northwestern U of Medicine, Chicago  

Design:

Cohort Study.

Blinding Used (if applicable):

Not applicable.

Intervention (if applicable):

Women with diabetes were given care consistent with prevailing practice including multiple insulin injections daily.  Infants had APGAR, Bayley Scales of Infant Development and Stanford-Binet Intelligence Scale testing.

Statistical Analysis:

Statistical analyses included partial-correlation, one-way analysis of variance, and multivariate analyses of variance.

 

Data Collection Summary:

Timing of Measurements

Biweekly clinic visits before 30 wk and weekly visits thereafter.  A single composite index of socioeconomic status was computed to reflect variables such as the IQ of the mother, her level of education, father's level of education and family income which are correlated to the child's IQ.

Dependent Variables

Women

  • Overnight fasting blood drawn for plasma glucose, B-hydroxybuterate, and free fatty acids
  • Glycoslyated hemoglobin was measured initially as hemoglobin AIC by column chromatogrophy with macrocolums and the last 2 years of the study as total glycoslyated hemoglobin by gel electrophoresis.
  • Hypoglycemia as defined by percentage of days on which an insulin reaction occurrred
  • Urine tests for acetonuria four times daily as outpatients and on each voided specimen during hospitalization

Infants

  • Mental Development Index Score at 2 years of age
  • Stanford-Binet Score at 3, 4 and 5 years of age
  • Mean gestational age at delivery
  • Birthweight
  • Macrosomia
  • Intrauterine growth retardation
  • Neonatal hypoglycemia
  • Newborn infants were immediately transferred to radiant bed warmers and Apgar scores were recorded at one and five minutes.

Independent Variables

  • Metabolic status of mother

Control Variables

Description of Actual Data Sample:

Initial N:  223 women with singleton pregnancy followed by the Center for Endocrinology, Northwestern University of Medicine, Chicago

Attrition (Final N):  223 pregnant women were enrolled.  89 had pregestational diabetes (enrolled at 11.9+7.5 wk of gestation), 99 had gestational diabetes (enrolled at 24.0+9.0 wk gestation), and 35 were normal controls (enrolled at 18.5+3.3 wk gestation).

Age:  Not mentioned 

Ethnicity:  Not mentioned

Other relevant demographics:

Anthropometry:

Location:  Chicago

Summary of Results:

Other Findings

The mean gestational age at delivery was signficantly lower in infants of mothers with diabetes(pregestational 38.1 1.7, gestational 38.7 + 2.0 ) than in the infants of the nondiabetic mothers 39.6 + 2.0 (P <0.05).

Birth wt was significantly higher­ in infants born of mothers with pregestational diabetes (P<0.05), 3771 +755 kg compared to 3512+711 g in mothers with gestational diabetes and 3333+479 g in controls.

The incidence of macrosomia was signficantly higher  in infants of pregestational diabetics (40%) compared with gestational (23%) and controls (11%) (P<0.01).

% of newborns with 5-minute Apgar scores < 7 were significantly higher in the pregestational diabetic women (8) compared to the gestational (0) (P<0.001) and non-diabetic women (0) (P<0.10).

After correction for socioeconomic status, race or ethnic origin, and patient group, the children’s mental-development-index scores at the age of 2 yr correlated inversely with the mothers’ 3rd trimester plasma b-hydroxybutyrate (r=-0.21, P<0.01) and the average Standford-Binet scores correlated inversely with 3rd trimester plasma b-hydroxybutyrate (r=-0.20, P<0.02) and free fatty acids (r=-0.27, P<0.002)

Author Conclusion:

Maternal diabetes during pregnancy may affect behavioral and intellectual development in the offspring. The associations between gestational ketonemia in the mother and lower IQ in the child warrant continued efforts to avoid ketoacidosis and accelerated starvation in all pregnant women.

Funding Source:
Government: NIH
Reviewer Comments:

This study suggests that ketonuria during pregnancy is associated with subsequent mental development of the fetus.  Well thought out and designed study, large sample size.

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? No
  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.) 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%.) ???
  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? 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.) 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? 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? 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? ???
  6.6. Were extra or unplanned treatments described? Yes
  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? ???
  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)? ???
  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