Final Research Plan

Gestational Diabetes: Screening

June 06, 2019

Recommendations made by the USPSTF are independent of the U.S. government. They should not be construed as an official position of the Agency for Healthcare Research and Quality or the U.S. Department of Health and Human Services.

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The final Research Plan is used to guide a systematic review of the evidence by researchers at an Evidence-based Practice Center. The resulting Evidence Review will form the basis of the USPSTF Recommendation Statement on this topic.

The draft Research Plan was available for comment from February 28 until March 27, 2019 at 8:00 p.m., ET.

The analytic framework depicts the key questions (KQs) that will guide the evidence review. The far left of the framework describes the target population as asymptomatic, pregnant women without known pre-existing diabetes mellitus. To the right is an arrow that represents GDM screening, which diverges to lines pointing to either a positive or negative GDM diagnosis. Above this line there is indication of the questions on accuracy of screening tests (KQ 4). An arrow below this line indicates assessment of harms of screening or a GDM diagnosis (KQ 2). Two arrows to the right of the population diagnosed with GDM represent treatment (KQ 6) and no treatment. Another arrow is directed up from the treatment arrow to indicate harms of treatment (KQ 7). Between the two arrows from the GDM diagnosis population (that is not treated) and the no GDM diagnosis population is KQ 5, representing outcomes for women diagnosed with more vs. less inclusive criteria for GDM. All three arrows leading from the GDM and no GDM populations go to an oval box identifying intermediate outcomes and then further towards a box identifying health outcomes. Intermediate outcomes include pregnancy (excessive weight gain in pregnancy) and long-term outcomes (maternal and childhood development of metabolic impairment and obesity). Health outcomes include pregnancy outcomes (preeclampsia/hypertension, cesarean delivery, and induction of labor); fetal/neonatal outcomes (mortality, birth injury, fetal overgrowth, shoulder dystocia, and acute morbidity); and long-term outcomes (development of type 2 diabetes and cardiovascular outcomes for the mother and child, mortality or morbidity from type 2 diabetes or cardiovascular disease for the mother, and long-term neurocognitive outcomes for the child). An overarching arrow from the screened population to the intermediate and health outcomes symbolizes KQ 1, about the direct benefits of screening, and KQ 3, the comparative effectiveness of different screening strategies based on diagnostic criteria or timing during pregnancy.

* No assumptions will be made about whether hyperglycemia first discovered early in pregnancy (e.g., in the first trimester) is GDM or some other form of diabetes; the term GDM will be used to include all women with hyperglycemia but not meeting criteria for overt diabetes at any time point during pregnancy.
† Screening using two-step (screening first and, when indicated, diagnostic tests second) or one-step (diagnostic tests only) strategies, each based on various criteria and thresholds, and offering treatment to patients diagnosed with GDM.

Abbreviations: GDM=gestational diabetes mellitus; IGT=impaired glucose tolerance; KQ=key question; T2DM=type 2 diabetes mellitus.

1 a. Does screening for gestational diabetes mellitus (GDM) reduce poor health outcomes?
    b. Does screening for GDM reduce poor intermediate outcomes?
    c. Does the effectiveness of screening for GDM vary according to maternal subgroup characteristics, including timing during pregnancy, previous GDM diagnosis, family history of type 2 diabetes mellitus, body mass index, age, or race/ethnicity?
2. What are the harms of screening for and diagnosis of GDM to the mother, fetus, or neonate?
3  a. What is the comparative effectiveness of different screening strategies for GDM on health outcomes?
    b. What is the comparative effectiveness of different screening strategies for GDM on intermediate outcomes?
    c. Does the comparative effectiveness of different screening strategies vary according to maternal subgroup characteristics, including timing during pregnancy, previous GDM diagnosis, family history of type 2 diabetes mellitus, body mass index, age, or race/ethnicity?
4  a. What is the diagnostic accuracy of commonly used screening tests for GDM?
    b. Does the accuracy of commonly used screening tests for GDM vary according to maternal subgroup characteristics, including timing during pregnancy, body mass index, age, race/ethnicity, or prevalence of GDM?
5. What is the association between diagnosis of GDM and outcomes in women meeting more inclusive but not less inclusive diagnostic criteria for GDM?
6  a. Does treatment of GDM during pregnancy reduce poor health outcomes?
    b. Does treatment of GDM during pregnancy reduce poor intermediate outcomes?
    c. Does the effectiveness of treatment of GDM vary according to maternal subgroup characteristics, including timing and criteria used for diagnosis during pregnancy, severity of hyperglycemia, body mass index, age, or race/ethnicity?
7. What are the harms of treatment of GDM, including severe maternal and fetal/neonatal hypoglycemia, delivery of neonates who are small for gestational age, and poor long-term growth and development outcomes in the child?

Contextual questions will not be systematically reviewed and are not shown in the Analytic Framework.

  1. What is the association between measures of serum glucose (e.g., fasting and postload glucose concentrations, percent hemoglobin A1c) and outcomes, and does it differ based on timing of diagnosis?
  2. What is the association between GDM diagnosed before 24 weeks of gestation and outcomes, and does it differ based on screening strategy, timing of diagnosis, and severity of risk factors?
  3. What are the long-term health consequences of diagnosis of GDM for mothers and their children, including neonatal hypoglycemia, shoulder dystocia, and fetal overgrowth?
  4. Are postpartum interventions effective for reducing incidence of long-term health outcomes in women previously diagnosed with GDM or their children?

The Research Approach identifies the study characteristics and criteria that the Evidence-based Practice Center will use to search for publications and to determine whether identified studies should be included or excluded from the Evidence Review. Criteria are overarching as well as specific to each of the key questions (KQs).

  Include Exclude
Population KQs 1–5: Pregnant women with no known history of pre-existing diabetes mellitus

KQs 6, 7: Pregnant women with GDM or hyperglycemia

KQs 1c, 3c, 6c: Pre-pregnancy body mass index (i.e., <25 vs. ≥25 kg/m2, <30 vs. ≥30 kg/m2); age (e.g., <25 vs. ≥25 years, <35 vs. ≥35 years); timing during pregnancy (e.g., <24 vs ≥24 weeks); race/ethnicity (i.e., non-Hispanic white, American Indian or Alaskan Native, African American, Asian, Hispanic, or Pacific Islander); family history of type 2 diabetes mellitus, history of GDM, identified as “high-risk” by study authors (KQs 1 and 3 only), and severity of hyperglycemia (KQ 6 only)		  
Interventions/ Exposure KQs 1–3: Screening using one- or two-step strategies,* followed by intention-to-treat patients with a diagnosis of GDM:
  • In two-step screening, the screening test must be FPG, 50-g OGCT, risk factor–based method (clinical or historical using ≥1 factors), or hemoglobin A1c; in both one- and two-step screening, the diagnostic tool must be FPG or OGTT (using any GDM criteria)
  • Screening strategies may vary the timing of screening based on patient characteristics (e.g., early screening for patients with risk factors vs. later screening for those without)

KQ 4: Screening tests (i.e., FPG, 50-g OGCT, risk factor-based method, or hemoglobin A1c)

KQ 5: Diagnosis of GDM using one of the below criteria, but no treatment of GDM or meeting two-step Carpenter-Coustan or NDDG criteria:

  • IADPSG (also known as HAPO 1.75 criteria, new World Health Organization GDM criteria, or the Diabetes Canada alternative strategy)
  • One-step Carpenter-Coustan, NDDG, or HAPO 2.0 criteria
  • Two-step Carpenter-Coustan or NDDG criteria (both using only one abnormal glucose value) or HAPO 2.0 criteria (also known as the Diabetes Canada preferred criteria)
KQs 6, 7: Any treatment of GDM offered during pregnancy, including but not limited to dietary advice, physical activity, blood glucose monitoring, insulin therapy (all preparations), or glucose-lowering medications		 KQs 1–5: Alternative methods to delivering glucose (e.g., candy bars)
Comparators KQs 1, 2: No screening; for KQ2, may be no intervention comparison if study authors measure outcomes before and after screening in each participant

KQ 3: Another screening strategy, such as one- vs. two-step screening, different diagnostic criteria or cut-offs, different timing in pregnancy (may be due to risk factors), or selective/risk-based vs. universal screening

KQ 4: Any FPG or OGTT used for diagnosis

KQ 5: No GDM by any criteria applied in the study study (e.g., OCGT negative, OCGT positive but no GDM [false-positive result], both OGCT negative and false-positive results)

KQs 6, 7: No treatment (i.e., no additional management or minimally active intervention, such as printed materials)		 KQs 1–5: Alternative methods to deliver glucose (e.g., candy bars, glucose loads) with same diagnostic criteria

KQs 6, 7: All active interventions
Outcomes KQs 1, 3, 5, 6:

Intermediate

  • Pregnancy: Excessive gestational weight gain (as per guidance from the Institute of Medicine, or defined by study author)
  • Long-term: Maternal and childhood development of metabolic impairment (impaired glucose tolerance) or obesity

Health

  • Pregnancy: Pre-eclampsia/maternal hypertension, cesarean delivery, and induction of labor
  • Fetal/neonatal: Mortality (miscarriage, stillbirth, neonatal death), birth injury (fracture, permanent nerve injury), acute morbidity (e.g., hypoglycemia, hyperbilirubinemia, NICU admission, respiratory distress syndrome), fetal overgrowth (large for gestational age or macrosomia), and shoulder dystocia
  • Long-term maternal: Development of type 2 diabetes mellitus; mortality or major morbidity from type 2 diabetes mellitus (e.g., retinopathy, neuropathy), cardiovascular disease, or both; and quality of life
  • Long-term childhood: Development of type 2 diabetes mellitus, cardiovascular outcomes, and neurocognitive outcomes

KQ 2: Adverse effects from screening tests (e.g., vomiting, anxiety or depression for the mother), from a GDM diagnosis (i.e., consequences from the label of GDM to the woman, fetus or neonate, such as unnecessary delivery interventions, additional interventions with formula, separation of infant and mother, breastfeeding challenges/failure), or both

KQ 4: Sensitivity, specificity, positive or negative predictive values, accuracy, and yield (i.e., prevalence)

KQ 7: Severe maternal or neonatal hypoglycemia, delivery of neonate who is small for gestational age, and long-term growth and development of the child

 KQs 1, 3–6: Other outcomes
Outcome assessment timing Any duration of followup  
Setting KQs 1–3, 5–7: Settings applicable to primary care; countries not categorized as “Very High” on the Human Development Index (as defined by the United Nations Development Programme) will be subject to sensitivity analysis

KQ 4: Any setting

  
Study designs KQs 1, 2: RCTs, CCTs, and controlled observational studies

KQ 2: Studies in which all participants are screened but harms are assessed before (i.e., earlier in pregnancy) and after screening

KQ 3: RCTs and CCTs

KQ 4: Prospective cohort studies, single arms of trials

KQ 5: Observational studies and single-arm trials (i.e., trial arms not receiving treatment)

KQs 6, 7: RCTs, CCTs; controlled observational studies, if no trials exist		 Systematic reviews†, abstracts, and conference proceedings
Publication language English  

*Two-step screening involves a screening test (e.g., 50-g OGCT, risk factor–based method) followed by a diagnostic test (i.e., OGTT), whereas one-step screening involves one test used for diagnosis in everyone.
†Systematic reviews, identified from a preliminary search for reviews on GDM and from searches for primary studies, will be scanned for potentially relevant studies but will not be included as the unit of analysis. 

Abbreviations: CCT=controlled clinical trial; FPG=fasting plasma glucose; GDM=gestational diabetes mellitus; HAPO=Hyperglycemia and Adverse Pregnancy Outcome Study; IADPSG=International Association of Diabetes and Pregnancy Study Group; KQ=key question; NDDG=National Diabetes Data Group; NICU=neonatal intensive care unit; OGCT=oral glucose challenge test; OGTT=oral glucose tolerance test; RCT=randomized, controlled trial.

The draft Research Plan was posted for public comment on the USPSTF Web site from February 28 to March 27, 2019. Based on the comments it received, the USPSTF recategorized some intermediate outcomes as health outcomes; moved KQ 5 on the analytic framework to a more precise location; added subgroups of persons with previous GDM diagnosis and family history of type 2 diabetes mellitus to KQs 1 and 3 and severity of hyperglycemia to KQ 6; and clarified the language and inclusion criteria for KQ 5. The USPSTF revised Contextual Questions 3 and 4 to focus on specific outcomes of interest. In addition, the USPSTF clarified that KQ 2 requires no comparator, clarified that the interventions for KQs 6 and 7 would be offered during pregnancy and that physical activity would also be included, and expanded upon the race/ethnicity subgroups. The USPSTF also decided to no longer exclude studies of populations with more than 20% pre-existing diabetes mellitus, recognizing that screening studies for GDM will ultimately include some women with unrecognized diabetes mellitus.