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You are here: HomeRecommendations for Primary Care PracticePublished RecommendationsRecommendation SummaryOther Supporting Document : Treatment: Evidence Summary

Treatment: Evidence Summary

Other Supporting Document for Gestational Diabetes Mellitus, Screening

Preface

A Systematic Review and Meta-Analysis for the U.S. Preventive Services Task Force and the National Institutes of Health Office of Medical Applications of Research

Release Date: May 28, 2013


By: Lisa Hartling, PhD; Donna M. Dryden, PhD; Alyssa Guthrie, MSSc; Melanie Muise, MA; Ben Vandermeer, MSc; and Lois Donovan, MD


The information in this report is intended to help clinicians, employers, policymakers, and others make informed decisions about the provision of health care services. This report is intended as a reference and not as a substitute for clinical judgment.

This report may be used, in whole or in part, as the basis for the development of clinical practice guidelines and other quality enhancement tools, or as a basis for reimbursement and coverage policies. AHRQ or U.S. Department of Health and Human Services endorsement of such derivative products may not be stated or implied.

This report was first published in the Annals of Internal Medicine on May 28, 2013 (Ann Intern Med 2013; http://www.annals.org). Select for copyright and source information.

Abstract

Background: Outcomes of treating gestational diabetes mellitus (GDM) are not well-established.

Purpose: To summarize evidence about the maternal and neonatal benefits and harms of treating GDM.

Data Sources: 15 electronic databases from 1995 to May 2012, gray literature, Web sites of relevant organizations, trial registries, and reference lists.

Study Selection: English-language randomized, controlled trials (n = 5) and cohort studies (n = 6) of women without known preexisting diabetes.

Data Extraction: One reviewer extracted data, and a second reviewer verified them. Two reviewers independently assessed methodological quality and evaluated strength of evidence for primary outcomes by using a Grading of Recommendations Assessment, Development and Evaluation approach.

Data Synthesis: All studies compared diet modification, glucose monitoring, and insulin as needed with no treatment. Women who were treated had more prenatal visits than those in control groups. Moderate evidence showed fewer cases of preeclampsia, shoulder dystocia, and macrosomia in the treated group. Evidence was insufficient for maternal weight gain and birth injury. Low evidence showed no difference between groups for neonatal hypoglycemia. Evidence was insufficient for long-term metabolic outcomes among offspring. No difference was found for cesarean delivery (low evidence), induction of labor (insufficient evidence), small-for-gestational-age neonates (moderate evidence), or admission to a neonatal intensive care unit (low evidence).

Limitations: Evidence is low or insufficient for many outcomes of greatest clinical importance. The strongest evidence supports reductions in intermediate outcomes; however, other factors (for example, maternal weight and gestational weight gain) may impart greater risk than GDM, particularly when glucose levels are modestly elevated.

Conclusion: Treating GDM results in less preeclampsia, shoulder dystocia, and macrosomia; however, current evidence does not show an effect on neonatal hypoglycemia or future poor metabolic outcomes. There is little evidence of short-term harm of treating GDM other than an increased demand for services.

Primary Funding Source: Agency for Healthcare Research and Quality.

Introdcution

Gestational diabetes mellitus (GDM) is defined as glucose intolerance first discovered in pregnancy. It predicts risk for overt diabetes in women. The more immediate risk for adverse outcomes of GDM in the mother and child is less well-established.

The prevalence of GDM ranges from 1.1% to 25.5% of pregnancies in the United States 1-3 and is influenced by diagnostic criteria and population characteristics, such as ethnicity. The incidence of this condition has increased over the past decades in parallel with the increase in rates of obesity and type 2 diabetes mellitus, and this trend is expected to continue.

Initial treatment of GDM involves diet modification, glucose monitoring, and moderate exercise. When dietary management does not achieve desired glucose control, insulin or oral antidiabetic medications may be used 4. Increased prenatal surveillance and changes in delivery management may also occur.

A report commissioned by the U.S. Preventive Services Task Force in 2008 found that treatment of women with mild GDM diagnosed after 24 weeks' gestation improved maternal and neonatal health outcomes 5. Specifically, on the basis of 1 study, they found a reduction in “any serious perinatal complication,” which included death, shoulder dystocia, bone fracture, and nerve palsy 6. The number of events for many of the individual outcomes was extremely small, which did not provide adequate evidence to make conclusions for individual outcomes. The same study also found less depression and a trend to better quality of life 3 months after parturition and reduced maternal hypertension in the treated group 6.

Potential harms of GDM treatment may include small-for-gestational-age neonates; maternal stress; and additional costs, including those associated with laboratory testing as well as patient and clinician time 7. Anxiety of health care providers over the diagnosis could result in unnecessary or overly aggressive fetal and neonatal surveillance and delivery management. The purpose of this review is to evaluate whether treatment of GDM modifies outcomes of mothers and their offspring and whether it is associated with any harms.

Methods

An a priori protocol was followed. Questions were developed by the Office of Medical Applications of Research and the U.S. Preventive Services Task Force. A technical expert panel that included representatives from both organizations provided content and methodological expertise. The full technical report is available at http://effectivehealthcare.ahrq.gov/index.cfm/search-for-guides-reviews-and-reports/?productid=1295&pageaction=displayproduct.

Data Sources and Searches

We searched for trials and cohort studies published in English from 1995 to May 2012 in MEDLINE (Ovid interface) (Appendix Table 1), Ovid MEDLINE In-Process & Other Non-Indexed Citations, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, Global Health, EMBASE, Pascal CINAHL Plus with Full Text (EBSCOhost), BIOSIS Previews (Web of Knowledge), Science Citation Index Expanded and Conference Proceedings Citation Index (both via Web of Science), PubMed, Latin American and Caribbean Health Science Literature, National Library of Medicine Gateway, and OCLC ProceedingsFirst and PapersFirst. We also searched trial registries and the Web sites of relevant professional associations and research groups for conference abstracts and proceedings between 2010 and 2012. We evaluated the reference lists of relevant reviews and included studies.

Study Selection

Two reviewers independently screened titles, keywords, and abstracts. We retrieved the full text for any study that was considered potentially relevant by at least 1 reviewer. Two reviewers independently assessed each full-text article by using a detailed form. We resolved disagreements through discussion. We included studies if they were randomized, controlled trials (RCTs) or non-RCTs or cohort studies; involved pregnant women with no known preexisting diabetes; compared any treatment of GDM with no treatment; and reported short- and long-term maternal, fetal, neonatal, and child outcomes that the technical panel deemed important.

Data Extraction and Quality Assessment

One reviewer extracted data by using a structured, electronic form, and a second reviewer checked the data for accuracy and completeness. Discrepancies were resolved through consensus. We extracted information on study characteristics, populations, interventions, outcomes, and results.

Two reviewers independently assessed the methodological quality of included studies and resolved disagreements through discussion. We used the Cochrane risk-of-bias tool to assess RCTs 8 and the Newcastle-Ottawa Scale to assess cohort studies 9.

Data Synthesis and Analysis

Two independent reviewers graded the strength of evidence by using the Evidence-based Practice Center Grading of Recommendations Assessment, Development and Evaluation approach 10. We resolved discrepancies by discussion. We assessed 4 major domains (risk of bias, consistency, directness, and precision) and summarized the overall strength of evidence for each outcome as high, moderate, or low. When no studies were available for an outcome or the evidence did not permit estimation of an effect, we rated strength of evidence as insufficient.

We described the results of studies qualitatively and in evidence tables. We performed meta-analyses when studies were sufficiently similar in terms of statistical homogeneity (that is, I2 ≤ 75%). We used the Mantel–Haenszel method for relative risks and the inverse variance method for pooling mean differences.

We combined results by using the random-effects model 11. For dichotomous outcomes, we computed relative risk to estimate between-group differences. If no event was reported in 1 treatment group, a correction factor of 0.5 was added to each cell of the 2 × 2 table to obtain estimates of the relative risk.

For continuous variables, we calculated mean differences for individual studies. We reported all results with 95% CIs and used Review Manager Version 5.0 (The Cochrane Collaboration, Copenhagen, Denmark) to perform meta-analyses.

Role of the Funding Source

The Agency for Healthcare Research and Quality (AHRQ) approved copyright assertion for this manuscript but did not participate in the literature search, data analysis, or interpretation of the results.

Results

Of 14,428 citations, 5 RCTs 6, 12-15 and 6 retrospective cohort studies 16-21 met inclusion criteria (Appendix Figure 1). All studies compared diet modification, glucose monitoring, and insulin as needed with standard care. Two studies had 2 associated publications reporting initial 6, 15 and longer-term 22, 23 outcomes. Diagnostic testing in all studies occurred at or after 24 weeks' gestation (when reported).

Numerous glucose inclusion criteria were used, varying from screening positive on the 50-g glucose challenge with nondiagnostic oral glucose tolerance tests to meeting National Diabetes Data Group criteria for a diagnosis of GDM. The 2 largest RCTs used different glucose thresholds for entry in their trials: World Health Organization 6 and Carpenter–Coustan criteria with a fasting glucose level less than 5.3 mmol/L (95 mg/dL) 12; however, the mean glucose levels of women at study entry were similar between these 2 studies. Risk of bias was low for 1 trial 6, unclear for 3 trials 12-14, and high for 1 trial 15. All cohort studies were considered high quality, with overall scores of 7 to 9 on a 9-point scale.

Benefits of Treating GDM

The Table and Appendix Table 2 show results for maternal outcomes. Moderate evidence from 3 RCTs showed less preeclampsia with treatment (Appendix Figure 2). In 2 of these trials, there was no difference between groups in gestational age at delivery. The strength of evidence for maternal weight gain was insufficient because of inconsistency across studies and imprecise effect estimates (Appendix Figure 3). Two RCTs showed no difference 13, 15, whereas 2 large RCTs showed less weight gain with treatment 6, 12. Given the high body mass index (BMI) of the women studied, less gestational weight gain in the treatment group would be beneficial.

One RCT reported on BMI at delivery and showed lower BMI with treatment; however, this evidence was considered insufficient. There was no evidence from the included studies for long-term maternal outcomes, such as type 2 diabetes mellitus, obesity, and hypertension.

The Table and Appendix Table 3 show the findings for fetal, neonatal, or child outcomes. Evidence was insufficient for birth injury due to imprecision (low number of events and participants across studies) and inconsistency (2 RCTs showed no difference 12, 15, and 1 cohort study showed fewer cases with treatment 18. Moderate evidence showed fewer cases of shoulder dystocia with treatment (Figure 1). For other injury outcomes (that is, brachial plexus injury and clavicular fractures), results were inconsistent across study designs, with the RCTs showing no differences and the cohort study showing fewer cases with treatment.

For outcomes related to birthweight (including birthweight >4000 g, actual birthweight, and large-for-gestational-age neonates), lower weights or fewer cases were observed with treatment. The strength of evidence was moderate for birthweight >4000 g (Figure 1). There was no difference in hyperbilirubinemia for RCTs (low strength of evidence), whereas the cohort study showed significantly less hyperbilirubinemia in the treated group.

There were no differences in perinatal death, although the number of events was extremely low (<0.5%). Randomized, controlled trials showed no difference between groups for the respiratory distress syndrome, whereas 1 cohort study found fewer “respiratory complications” 17 in the treated group; overall respiratory distress syndrome was rare (4.3% across all studies). Several studies assessed Apgar scores; although differences were found for the Apgar score at 1 minute, no differences were observed at 5 minutes.

One RCT followed a subset of the offspring for 7 to 11 years and found no differences for impaired glucose tolerance or type 2 diabetes mellitus (insufficient strength of evidence). No differences were observed in single studies that assessed offspring with BMIs greater than the 95th percentile (7- to 11-year follow-up) and greater than the 85th percentile (4- to 5-year follow-up). Overall, pooled results showed no difference in BMI (low strength of evidence).

Harms of Treating GDM

One RCT assessed maternal depression and anxiety at 6 weeks after study entry and 3 months after parturition 6. There was no difference between groups in anxiety at either time point. Depression rates were lower in the treatment group 3 months after parturition (Appendix Table 2).

Moderate evidence from 4 RCTs showed no difference in small-for-gestational-age neonates. Pooled results from 4 RCTs showed no difference between groups in neonatal hypoglycemia and no statistical heterogeneity (Figure 1). Two cohort studies showed inconsistent results, which may be partly due to different definitions of hypoglycemia used across the studies and different protocols for screening neonates for hypoglycemia. Overall, the strength of evidence was low, suggesting that further study may change the results of our findings (Table).

Low evidence showed no difference overall in admission to the neonatal intensive care unit (Appendix Figure 4). One trial was an outlier, with significantly more neonatal intensive care unit admissions in the treated group. Two RCTs reported on the number of prenatal visits and found more visits among the treatment groups. The strength of evidence for induction of labor was insufficient because of lack of precision and inconsistency across studies, with no difference found for the RCTs overall. There was low evidence of no differences between groups for cesarean delivery (Figure 2) or unplanned cesarean delivery.

Discussion

Moderate evidence showed that treatment of GDM reduced preeclampsia, shoulder dystocia, and macrosomia (birthweight >4000 g). These outcomes, specified a priori to be of interest to our stakeholders, may be intermediate to outcomes of greater clinical importance, such as prematurity or brachial plexus injury. Evidence showing differences between groups for other benefits to mother or infant was lacking or weak.

In terms of harms, there was no evidence for some of the outcomes stipulated in the protocol, including costs and resource allocation, although there were more prenatal visits in the treatment groups. No difference was found in small-for-gestational-age neonates, which may be due to inadequate power to detect differences because of the small number of events. No differences were found for admission to the neonatal intensive care unit or rate of induction of labor. However, there was heterogeneity in these outcomes that may be attributable to different site-specific policies and procedures, study protocols, and practice patterns. Low evidence showed no difference in rates of cesarean delivery.

Our results are consistent with other recent systematic reviews showing some evidence of benefit of treating GDM for select maternal and infant outcomes yet little evidence of an effect on patient-important outcomes (for example, perinatal or neonatal mortality). This is probably due to the infrequent occurrence of these events and a resulting lack of power across the studies to adequately assess for differences 24, 25.

Several caveats related to this body of evidence should be considered when interpreting and applying the results of this review. First, although we found differences in preeclampsia, macrosomia, and shoulder dystocia, most such events occur in pregnant women without GDM 26. Such factors as maternal weight and gestational weight gain have been shown to impart greater risk for these outcomes, particularly in women diagnosed with GDM at lower glucose thresholds 27, 28. For example, analyses adjusting for these variables show that glycemia accounted for only 1.7% of the risk for large-for-gestational-age neonates 27. Second, where reported, definitions of preeclampsia varied (for example, a blood pressure of 140/90 mm Hg on 2 occasions 4 hours apart, these criteria with laboratory measures indicative of preeclampsia, or an increase in blood pressure medications). Preeclampsia events in our pooled analysis may have included women with the much-less-serious condition of gestational hypertension; however, a study that used the more rigorous definition showed a treatment benefit 12. Preeclampsia occurs in 3% to 5% of pregnancies 29, and the risk for this condition attributable to GDM is probably small 30. Third, this review assessed the risks and benefits of treating GDM but not those of screening for this condition. Of note, our larger technical report, which addressed screening, found no randomized trials examining the effect of screening on health outcomes (http://effectivehealthcare.ahrq.gov/index.cfm/search-for-guides-reviews-and-reports/?productid=1295&pageaction=displayproduct).

Evidence was very limited for 2 outcomes of particular interest to stakeholders. The first was patient anxiety associated with a diagnosis of GDM. A single study assessed depression and anxiety in a subgroup of a larger RCT. It found no difference between groups in anxiety at 6 weeks after study entry and 3 months after parturition, although the treatment group had lower rates of depression at 3 months after parturition. Research has shown that women with GDM had a higher level of anxiety at the time of the first GDM assessment than glucose-tolerant women; however, these differences in anxiety scores did not persist before delivery 31. Further, a survey of women 3 to 5 years after diagnosis of GDM showed more concern about their own health and rated their children's health poorer than matched control participants 32. The second outcome was metabolic changes in the children born to mothers with GDM. Follow-up of offspring from participants in 2 RCTs 6, 16 did not show any treatment effect of GDM on metabolic outcomes of the children.

Further study of the long-term metabolic effect on offspring whose mothers have been treated for GDM is warranted. Well-conducted prospective cohort studies of the real-world effect of GDM treatment on health care utilization are needed. Research is also needed to help determine the glucose thresholds and treatment targets at which GDM treatment benefits outweigh the risks of treatment and no treatment.

The IDEAL (Investigation of Dietary Advice and Lifestyle for Women With Borderline Gestational Diabetes) study, an RCT to assess the effect of treating women with very mild glucose impairment in pregnancy, is under way. Randomized, controlled trials investigating the care of women diagnosed with GDM, including fetal surveillance protocols, are needed to guide obstetric investigations and management of GDM. Such work may help avoid unnecessary interventions that are driven by the apprehension of health care providers.

The review process had several limitations. We limited the search dates from 1995 onward on the basis of advice from our technical expert panel. Our results are consistent with other systematic reviews on this topic that included studies before 1995 24, 25. We included only studies published in English. Most studies were conducted in North America or Australia. Most of the North American studies included mixed racial populations and are probably applicable to the general U.S. population. We included cohort studies because an earlier review 5 found few RCTs; results from cohort studies should be interpreted cautiously, particularly when they differ from those of the RCTs.

In summary, evidence supports benefits of treating mild GDM. Specifically, treatment of GDM results in lower incidence of preeclampsia, macrosomia, large-for-gestational-age infants, and shoulder dystocia; however, the risk for these outcomes attributable to GDM is low, particularly when glucose levels are modestly elevated. Current research does not show a treatment effect of GDM on clinical neonatal hypoglycemia or future poor metabolic outcomes of the offspring. Randomized, controlled trials of GDM treatment show limited harm related to treating GDM, other than an increased demand for services.

Copyright and Source Information

Source: This article was first published in Annals of Internal Medicine (Ann Intern Med 2013;159:28 May).

Disclaimer: The findings and conclusions in this document are those of the authors, who are responsible for its content, and do not necessarily represent the views of AHRQ. No statement in this report should be construed as an official position of AHRQ or the U.S. Department of Health and Human Services.

Acknowledgment: The authors thank Tamara Durec (searching), Andrea Milne (searching, technical support), Walie Atkary (screening, data extraction), Dion Pasichnyk (data extraction), Jennifer Seida (screening, project coordination), Teodora Radisic (article retrieval), Jocelyn Shulhan (screening), Annabritt Chisholm (research support, reference management), and Dr. Alun Edwards for providing clinical input throughout the project.

Financial Support: By AHRQ (contract no. 290-2007-10021-I).

Potential Conflicts of Interest: Ms. Guthrie: Grant (money to institution); support for travel to meetings for the study or other purposes (money to institution); fees for participation in review activities such as data monitoring boards, statistical analysis, end point committees, and the like (money to institution); payment for writing or reviewing the manuscript (money to institution): AHRQ. Ms. Muise: Grant (money to institution): AHRQ. Mr. Vandermeer: Grant (money to institution): AHRQ. Dr. Donovan: Other: Dr. Donovan reports grants from Bridges Grant (International Diabetes Federation and Eli Lilly) outside the submitted work. All other authors have no disclosures. Disclosures can also be viewed at http://www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M13>www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M13-0190.

Requests for Single Reprints: Lisa Hartling, PhD, ECHA 4-472, 11405-87 Avenue, Edmonton, AB T6G 1C9, Canada; e-mail, hartling@ualberta.ca.

Table. Strength of Evidence for Benefits and Harms of Treating GDM

Table. Strength of Evidence for Benefits and Harms of Treating GDM
Outcome Source Risk of Bias Consistency Directness Precision Overall Strength of Evidence Summary
Preeclampsia 3 RCTs
1 cohort study
Low
High
Consistent
Unknown
Direct
Direct
Imprecise
Imprecise
Moderate (favors treatment)
Insufficient
Difference in favor of treatment for RCTs (RR, 0.62 [95% CI, 0.43 to 0.89]); no difference observed for cohort study
Maternal weight gain 4 RCTs
2 cohort studies
Medium
High
Inconsistent
Consistent
Direct
Direct
Imprecise
Imprecise
Insufficient
Insufficient
Results not pooled for RCTs because of substantial heterogeneity; no difference for cohort studies (MD, −1.04 [CI, −2.89 to 0.81])
Birth injury 2 RCTs
1 cohort study
Medium
High
Consistent
Unknown
Direct
Direct
Imprecise
Imprecise
Low
Insufficient (favors treatment)
No difference for RCTs (RR, 0.48 [CI, 0.12 to 1.90]); difference favoring treatment for cohort study (RR, 0.02 [CI, 0.00 to 0.22])
Shoulder dystocia 3 RCTs
4 cohort studies
Medium
High
Consistent
Consistent
Direct
Direct
Precise
Precise
Moderate (favors treatment)
Low (favors treatment)
No difference for RCTs (RR, 0.48 [CI, 0.12 to 1.90]); difference favoring treatment for cohort study (RR, 0.02 [CI, 0.00 to 0.22])
Neonatal hypoglycemia 4 RCTs
2 cohort studies
Medium
High
Consistent
Indirect
Direct
Direct
Imprecise
Imprecise
Low (no difference)
Insufficient
No difference for RCTs (RR, 1.18 [CI, 0.92 to 1.52]) or cohort studies (RR, 0.55 [CI, 0.10 to 2.97])
Macrosomia (birthweight >4000 g) 5 RCTs
6 cohort studies
Medium
High
Consistent
Inconsistent
Direct
Direct
Precise
Precise
Moderate (favors treatment)
Low (favors treatment)
No difference for RCTs (RR, 1.18 [CI, 0.92 to 1.52]) or cohort studies (RR, 0.55 [CI, 0.10 to 2.97])
Long-term metabolic outcomes: impaired glucose tolerance 1 RCT Medium Unknown Direct
Imprecise Insufficient No difference between groups (RR, 5.63 [CI, 0.31 to 101.32])
Long-term metabolic outcomes: type 2 DM 1 RCT Medium Unknown Direct
Imprecise Insufficient No difference between groups (RR, 1.88 [CI, 0.08 to 44.76])
Long-term metabolic outcomes: BMI (assessed as >85th and>95th percentile) 2 RCTs Medium Consistent Direct
Imprecise Low (no difference) No difference between groups (RR, 1.26 [CI, 0.86 to 1.84])

BMI = body mass index; DM = diabetes mellitus; GDM = gestational diabetes mellitus; MD = mean difference; RCT = randomized, controlled trial; RR = risk ratio.

Appendix Table 1. Medline Search Strategy*

Ovid MEDLINE (1948 to week 4 of September 2011)
Search date: 9 October 2011
Results: 8234

  1. Diabetes, Gestational/
  2. Fetal Macrosomia/
  3. Pregnancy Complications/
  4. GDM.tw.
  5. (gestation$ adj2 (diabet$ or DM or glucose intoleran$ or insulin resistan$)).mp.
  6. (pregnan$ adj3 (diabet$ or DM or glucose intoleran$ or insulin resistan$)).mp.
  7. (maternal adj2 (diabet$ or DM or glyc?emia or hyperglyc?emia)).tw.
  8. (hyperglyc?emia adj2 pregnan$).tw.
  9. macrosomia.tw.
  10. or/1-9
  11. mass screening/
  12. prenatal diagnosis/
  13. screen$.tw.
  14. ((prenatal or early) adj2 diagnosis).tw.
  15. Glucose Tolerance Test/
  16. Glucose Intolerance/
  17. Blood Glucose/
  18. Risk Factors/
  19. (glucose adj (tolerance or intolerance or challenge)).tw.
  20. OGTT.tw.
  21. GCT.tw.
  22. (fasting adj2 glucose).tw.
  23. or/11-22
  24. “Sensitivity and Specificity”/
  25. “Predictive Value of Tests”/
  26. ROC Curve/
  27. specific$.tw.
  28. sensitiv$.tw.
  29. predictive value.tw.
  30. accurac$.tw.
  31. diagnostic errors/
  32. diagnostic error?.tw.
  33. false negative reactions/
  34. false positive reactions/
  35. (false adj (negative or positive)).tw.
  36. “reproducibility of results”/
  37. reference values/
  38. reference standards/
  39. or/24-38
  40. and/10,23,39
  41. intervention?.mp.
  42. (treating or treatment? or therapy or therapies).mp.
  43. manage$.mp.
  44. monitor$.mp.
  45. exp sulfonylurea compounds/
  46. Gliclazide/
  47. Glyburide/
  48. Tolbutamide/
  49. sulfonylurea?.tw.
  50. gliclazid$.tw.
  51. glimepirid$.tw.
  52. glipizid$.tw.
  53. glyburid$.tw.
  54. tolbutamid$.tw.
  55. (antidiabet$ or anti-diabet$).tw.
  56. insulin?.mp.
  57. glibenclamid$.mp.
  58. acarbos$.mp.
  59. exp Diet Therapy/
  60. (diet adj2 (therap$ or restrict$ or advice)).tw.
  61. medical nutrition$ therapy.tw.
  62. MNT.tw.
  63. exp Life Style/
  64. (lifestyle$ or life-style$).mp.
  65. Blood Glucose Self-Monitoring/
  66. (blood glucose adj (self monitor$ or self-monitor$)).tw.
  67. ((self monitor$ or self-monitor$) adj blood glucose).tw.
  68. SMBG.tw.
  69. Counseling/
  70. counsel$.tw.
  71. Labor, Induced/
  72. (induc$ adj2 labo?r).tw.
  73. exp Cesarean Section/
  74. c?esarean.tw.
  75. exp Pregnancy Outcome/
  76. pregnanc$ outcome?.tw.
  77. or/41-76
  78. and/10,77
  79. or/40,78
  80. clinical trial.pt.
  81. randomized controlled trial.pt.
  82. randomi?ed.ti,ab.
  83. placebo.ti,ab.
  84. dt.fs.
  85. randomly.ti,ab.
  86. trial.ti,ab.
  87. groups.ti,ab.
  88. or/80-87
  89. animals/
  90. humans/
  91. 89 not (89 and 90)
  92. 88 not 91
  93. cohort studies/
  94. follow-up studies/
  95. longitudinal studies/
  96. prospective studies/
  97. retrospective studies/
  98. ((cohort? or follow-up or followup or longitud$ or prospectiv$ or retrospectiv$) adj (study or studies or trial?)).tw.
  99. or/93-98
  100. 99 not 91
  101. exp Guideline/
  102. Health Planning Guidelines/
  103. (clinical adj2 guideline?).tw.
  104. CPG?.tw.
  105. ((practice or consensus or position) adj2 (guideline? or recommendation? or statement?)).tw.
  106. standard?.tw.
  107. protocol?.tw.
  108. or/101-107
  109. meta analysis.mp,pt.
  110. review.pt.
  111. search:.tw.
  112. or/109-111 [Reviews balanced - HIRU]
  113. and/79,92 [Clinical trials & RCTs]
  114. and/79,100 [Observational studies]
  115. and/79,108 [Guidelines]
  116. and/79,112 [SRs MAs]
  117. or/113-116
  118. limit 117 to (english language and yr=“2000 -Current”)
  119. limit 117 to (english language and yr=“2000 -2005”)
  120. limit 117 to (english language and yr=“2006 -Current”)
  121. remove duplicates from 119
  122. remove duplicates from 120
  123. or/121-122
  124. 113 or 114 or 115
  125. 113 or 114 or 115
  126. limit 125 to (english language and yr=“2000 -Current”)
  127. limit 125 to (english language and yr=“2000 -2005”)
  128. remove duplicates from 127
  129. limit 125 to (english language and yr=“2006 -Current”)
  130. remove duplicates from 129
  131. 128 or 130
  132. 113 or 114
  133. limit 132 to (english language and yr=“2000 -Current”)
  134. limit 132 to (english language and yr=“2000 -2005”)
  135. remove duplicates from 134
  136. limit 132 to (english language and yr=“2006 -Current”)
  137. remove duplicates from 136
  138. 135 or 137

Appendix Table 2. Evidence Summary for Benefits and Harms of Treating GDM: Maternal Outcomes

Appendix Table 2. Evidence Summary for Benefits and Harms of Treating GDM: Maternal Outcomes
Outcome Studies, n Participants, n Effect Estimate Risk Ratio
(95% CI)*
I2, %
Benefits
Preeclampsia
RCT 3 2014 0.62 (0.43 to 0.89) 16
Cohort 1 258 0.97 (0.43 to 2.15) NA
Preeclampsia or gestational hypertension
RCT 1 931 0.63 (0.44 to 0.92) NA
Cohort 1 874 0.30 (0.15 to 0.62) NA
Weight gain (kg)
RCT 4 2530 Pooled estimate not reported because of heterogeneity 88
Cohort 2 515 −1.04 (−2.89 to 0.81) 8
Maternal birth trauma
Cohort 1 874 0.95 (0.21 to 4.28) NA
BMI at delivery
RCT 1 931 −1.00 (−1.67 to −0.33) NA
Harms
Cesarean delivery
RCT 5 2613 0.90 (0.79 to 1.01) 0
Cohort 6 3110 1.09 (0.90 to 1.31) 23
Unplanned cesarean delivery
RCT 1 1000 0.81 (0.62 to 1.05) NA
Cohort 1 126 0.83 (0.33 to 2.06) NA
Induction of labor
RCT 2 1931 1.16 (0.91 to 1.49) 69
Cohort 1 1665 0.63 (0.55 to 0.72)§ NA
Anxiety (6 wk after study entry)
RCT 1 682 −0.30 (−0.88 to 0.28) NA
Anxiety (3 mo after parturition)
RCT 1 573 −0.20 (−0.83 to 0.43) NA
Depression (3 mo after parturition)
RCT 1 568 0.50 (0.31 to 0.79) NA

BMI = body mass index; GDM = gestational diabetes mellitus; NA = not applicable; RCT = randomized, controlled trial.
* Risk ratios unless otherwise specified.
Statistically significant with better results for the treated group.
Mean difference.
§ This result was statistically significant; however, all untreated women in this cohort presented at or after 37 wks' gestation, and institutional policy required that such women be delivered within 1 wk of presentation

Appendix Table 3. Evidence Summary for Benefits and Harms of Treating GDM: Infant Outcomes

Appendix Table 3. Evidence Summary for Benefits and Harms of Treating GDM: Infant Outcomes
Outcome Studies, n Participants, n Effect Estimate Risk Ratio
(95% CI)*
I2, %
Benefits
Birthweight >4000 g
RCT 5 2643 0.50 (0.35 to 0.71) 50
Cohort 6 3426 Results not pooled because of substantial heterogeneity 86
Birthweight >4500 g
RCT 1 299 1.01 (0.33 to 3.05) NA
Cohort 2 647 0.29 (0.07 to 1.25) 69
Birthweight (actual)
RCT 5 2670 −120.81 (−163.40 to −78.23) 2
Cohort 2 515 Results not pooled because of substantial heterogeneity 77
Large-for-gestational-age neonate
RCT 3 2261 0.56 (0.45 to 0.69) 0
Cohort 4 2294 0.43 (0.27 to 0.70) 58
Shoulder dystocia
RCT 3 2044 0.42 (0.23 to 0.77) 0
Cohort 4 3054 0.38 (0.19 to 0.78) 20
Brachial plexus injury
RCT 1 1000 0.15 (0.01 to 2.87) NA
Cohort 1 389 0.04 (0.00 to 0.66) NA
Clavicular fracture
RCT 1 1030 0.35 (0.01 to 8.45) NA
Cohort 1 389 0.02 (0.00 to 0.22) NA
Birth trauma
RCT 2 1230 0.48 (0.12 to 1.90) NA
Cohort 1 389 0.02 (0.00 to 0.11) NA
Hyperbilirubinemia
RCT 3 1467 0.79 (0.56 to 1.10) 0
Cohort 1 1665 0.26 (0.18 to 0.37) NA
Perinatal deaths
RCT 3 2287 0.00 (−0.01 to 0.01)§ 66
Cohort 3 2928 0.00 (−0.01 to 0.01)§ 0
Respiratory complications
RCT (RDS) 2 1962 1.05 (0.48 to 2.28) 58
Cohort (complications) 1 1665 0.16 (0.10 to 0.26) NA
Apgar score at 1 min
RCT 1 83 −0.30 (−0.56 to −0.04) NA
Cohort 1 126 −1.00 (−1.54 to −0.46) NA
Apgar score at 5 min
RCT 2 383 Results not pooled because of substantial heterogeneity 77
Cohort 1 126 0.00 (−0.27 to 0.27) NA
Type 2 DM (long-term)
RCT 1 89 1.88 (0.08 to 44.76) NA
Impaired glucose tolerance
RCT 1 89 5.63 (0.31 to 101.32) 44
BMI (long-term)
>95th percentile 1 85 1.58 (0.66 to 3.79) NA
>85th percentile 1 199 1.19 (0.78 to 1.82) NA
Any BMI (2 studies above combined) 2 284 1.26 (0.86 to 1.84) 0
Harms
Small-for-gestational-age neonate
RCT 4 2345 1.10 (0.81 to 1.48) 0
Hypoglycemia
RCT 4 2367 1.18 (0.92 to 1.52) 0
Cohort 2 2054 0.55 (0.10 to 2.97) 49
Admission to NICU
RCT 3 2262 0.96 (0.67 to 1.37) 61
Cohort 1 126 0.66 (0.19 to 2.35) NA

BMI = body mass index; DM = diabetes mellitus; GDM = gestational diabetes mellitus; NA = not applicable; NICU = neonatal intensive care unit; RCT = randomized, controlled trial; RDS = respiratory distress syndrome.
* Risk ratios unless otherwise specified.
Results statistically significant with better results for the treated group.
Mean difference.
§ Risk difference.

Figure 1. Effect of treatment for shoulder dystocia, neonatal hypoglycemia, and macrosomia (birthweight >4000 g) based on data from randomized, controlled trials.

Text Description is below the image.

MH = Mantel–Haenszel.

[D]. Select for Text Description.

Figure 1 is a metagraph depicting the effect of treatment compared with no treatment on the outcome of shoulder dystocia, neonatal hypoglycemia, and macrosomia (>4,000 g) in infants born to women with gestational diabetes. Three randomized, controlled trials contributed data on shoulder dystocia; pooled results significantly favored the treatment group (RR, 0.42 [95% CI, 0.23 to 0.77]; I2=0%). Four randomized, controlled trials contributed data on neonatal hypoglycemia; pooled results showed no significant difference between groups (RR, 1.18 [95% CI, 0.92 to 1.52]; I2=0%). Five randomized, controlled trials contributed data on fetal macrosomia; pooled results significantly favored the treatment group (RR, 0.50 [95% CI, 0.35 to 0.71]; I2=50%).

 

Figure 2. Effect of treatment on outcomes of women with GDM who have cesarean delivery.

Text Description is below the image.

GDM = gestational diabetes mellitus; MH = Mantel–Haenszel; RCT = randomized, controlled trial.

[D]. Select for Text Description.

Figure 2 is a metagraph comparing cesarean delivery rates between women treated for GDM and those left untreated. Five randomized, controlled trials contributed data; pooled results showed no significant difference between groups (RR, 0.90 [95% CI, 0.79 to 1.01]; I2=0%). Additionally, six cohort studies contributed data; pooled results demonstrated no significant difference between groups (RR, 1.09 [95% CI, 0.90 to 1.31]; I2=23%).

Appendix Figure 1. Summary of evidence search and selection.

Text Description is below the image.

KQ = key question.
* This systematic review was part of a larger technical report. The search was done to identify relevant studies for all objectives of the full report, which is available at http://effectivehealthcare.ahrq.gov/index.cfm/search-for-guides-reviews-and-reports/?productid=1295&pageaction=displayproduct.

[D]. Select for Text Description.

Appendix Figure 1 is a flow diagram that outlines the study retrieval and selection process. The search strategy identified 14,398 citations from electronic databases. Screening based on titles and abstracts identified 598 potentially relevant studies. 30 additional studies were found by hand searching the reference lists from included studies. Using the detailed selection criteria, 151 studies met the inclusion criteria and 469 were excluded. Of the 151 studies, 26 were identified as companion publications and 125 were unique studies. Of the 125 unique studies, 28 were further excluded during data extraction due to a lack of comparison or outcome of interest, leaving the total number of included studies at 97. The most frequent reasons for exclusion were: ineligible comparator; ineligible publication type; ineligible study design; study did not report prespecified outcomes of interest; duplicate publication; intervention not of interest; and population not of interest.

 

Appendix Figure 2. Effect of treatment on outcomes of women with GDM: preeclampsia.

Text Description is below the image.

Text Description is below the image.

[D]. Select for Text Description.

Appendix Figure 2 is a metagraph comparing rates of preeclampsia between women treated for GDM and those who were not. Three randomized, controlled trials contributed data. Pooled results favored treatment (RR, 0.62 [95% CI, 0.43 to 0.89]; I2=16%). In addition, one cohort study contributed data, demonstrating no significant difference between groups (RR, 0.97 [95% CI, 0.43 to 2.15]).

 

Appendix Figure 3. Effect of treatment on outcomes of women with GDM: maternal weight gain.

Text Description is below the image.

GDM = gestational diabetes mellitus; IV = inverse variance; MH = Mantel–Haenszel; RCT = randomized, controlled trial.

[D]. Select for Text Description.

Appendix Figure 3 is a metagraph comparing weight gain (continuous) in women treated for GDM versus those who were not. Four randomized, controlled trials contributed data, results were not pooled due to substantial heterogeneity (I2=88%). Two cohort studies contributed data. The pooled results are reported in the text and showed no significant difference between groups (mean difference, −1.04 [95% CI, −2.89 to 0.81]; I2=8%).

 

Appendix Figure 4. Effect of treatment on outcomes of women with GDM: admission to the NICU.

Text Description is below the image.

GDM = gestational diabetes mellitus; MH = Mantel–Haenszel; NICU = neonatal intensive care unit; RCT = randomized, controlled trial.

[D]. Select for Text Description.

Appendix Figure 4 compares the number of NICU admissions between mothers treated for GDM and those untreated. Three randomized, controlled trials contributed data; pooled results showed no significant difference between groups (RR, 0.96 [95% CI, 0.67 to 1.37]; I22=61%). One cohort study contributed data and showed no significant difference between groups (RR, 0.66 [95% CI, 0.19 to 2.35]).

 

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Current as of: May 2013

Internet Citation: Treatment: Evidence Summary: Gestational Diabetes Mellitus, Screening. U.S. Preventive Services Task Force. May 2013.
https://www.uspreventiveservicestaskforce.org/Page/Document/treatment-evidence-summary/gestational-diabetes-mellitus-screening

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