Evidence Synthesis Number 204 Screening for Gestational Diabetes Mellitus: A Systematic Review to Update the 2014 U.S. Preventive Services Task Force Recommendation Prepared for: Agency for Healthcare Research and Quality U.S. Department of Health and Human Services 5600 Fishers Lane Rockville, MD 20857 www.ahrq.gov Contract No. HHSA-290-2015-00009-I Prepared by: Pacific Northwest Evidence-Based Practice Center Oregon Health & Science University Mail Code: BICC 3181 SW Sam Jackson Park Road Portland, OR 97239 www.ohsu.edu/epc University of Alberta Evidence-Based Practice Center 4-474 Edmonton Clinic Health Academy 11405 – 87 Avenue Edmonton, Alberta, Canada T6G 1C9 Investigators: Jennifer Pillay, MSc Lois Donovan, MD Samantha Guitard, MSc Bernadette Zakher, MD Christina Korownyk, MD Michelle Gates, PhD Allison Gates, PhD Ben Vandermeer, MSc Christina Bougatsos, MPH Roger Chou, MD Lisa Hartling, PhD AHRQ Publication No. 21-05273-EF-1 February 2021 This report is based on research conducted by the Pacific Northwest Evidence-based Practice Center (EPC) and the University of Alberta EPC under contract to the Agency for Healthcare Research and Quality (AHRQ), Rockville, MD (Contract No. HHSA-290-2015-00009-I). The findings and conclusions in this document are those of the authors, who are responsible for its contents, and do not necessarily represent the views of AHRQ. Therefore, no statement in this report should be construed as an official position of AHRQ or of the U.S. Department of Health and Human Services. The information in this report is intended to help health care decisionmakers—patients and clinicians, health system leaders, and policymakers, among others—make well-informed decisions and thereby improve the quality of health care services. This report is not intended to be a substitute for the application of clinical judgment. Anyone who makes decisions concerning the provision of clinical care should consider this report in the same way as any medical reference and in conjunction with all other pertinent information (i.e., in the context of available resources and circumstances presented by individual patients). The final report may be used, in whole or in part, as the basis for 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. None of the investigators have any affiliations or financial involvement that conflicts with the material presented in this report. Acknowledgements The authors acknowledge the following individuals: AHRQ Medical Officers Justin Mills, MD, MPH, and Brandy Peaker, MD, MPH; and current members of the U.S. Preventive Services Task Force. The authors thank Diana Keto Lambert, MLIS, at the University of Alberta EPC, for updating the searches for key questions, and their previous librarian, Robin Featherstone, MLIS, for searching for systematic reviews to inform topic refinement and the contextual questions. Screening for Gestational Diabetes Mellitus ii Pacific Northwest and Alberta EPCs Structured Abstract Background: Gestational diabetes mellitus (GDM) is largely asymptomatic; screening for GDM during pregnancy could identify women who could benefit from treatments to reduce adverse consequences of GDM. Purpose: To systematically update the 2012 evidence review used to inform United States Preventive Services Task Force (USPSTF) recommendations on benefits and harms of screening for GDM. Data Sources: MEDLINE, Embase, and CINAHL (2010 to May 2020), ClinicalTrials.gov, reference lists of primary studies and systematic reviews; with surveillance through December 2020. All previously reviewed studies were re-assessed for eligibility. Study Selection: Two investigators independently reviewed abstracts and full-text articles against a set of a priori inclusion criteria. Disagreements were resolved through discussion. We included English-language controlled trials for effectiveness of screening and treatment; observational studies on screening effectiveness, harms, and association between GDM and outcomes; and prospective studies on diagnostic accuracy of screening tests. Data Extraction: One investigator abstracted data and a second investigator checked data abstraction for completeness and accuracy. Two investigators independently rated quality of the included studies using design-specific criteria. Data Synthesis (Results): Eighteen trials (different screening strategies [N=2,483]; treatment benefits and harms [N=4,235]) and 87 observational studies (screening benefits [N=4,336] and harms [N=166,082]; diagnostic accuracy [N=91,260]; outcome associations [N=105,492]) were included. Four observational studies (N=4,336) of screening versus no screening suggested that screening may be associated with reduced risk of some pregnancy and neonatal outcomes, but findings for each outcome were based on single studies with methodological limitations. Undergoing screening or receiving a false positive result may not be associated with anxiety; GDM may be associated with unnecessary cesarean delivery. Three small trials (N=1,059) found screening using a 1-step International Association of Diabetes and Pregnancy Study Group (IADPSG), versus 2-step Carpenter-Coustan (CC), strategy associated with decreased risk of primary cesarean deliveries (RR, 0.73 [95% CI, 0.55 to 0.97; absolute risk reduction [ARD], 6.3%), large-for-gestational age [LGA] infants (RR, 0.46 [95% CI, 0.25 to 0.83]; ARD, 3.2%), NICU admissions (RR, 0.49 [95% CI, 0.29 to 0.84]; ARD, 3.7%) and neonatal hypoglycemia (RR, 0.52 [95% CI, 0.28 to 0.95]; ARD, 2.7%), with no differences or limited data for other pregnancy and neonatal outcomes. Inconsistency was present in analyses, there were study quality concerns, and two additional large trials are pending. One trial (N=922) suggested that early versus usual timing of 2-step CC screening may not improve outcomes in obese women. Screening for Gestational Diabetes Mellitus iii Pacific Northwest and Alberta EPCs Forty-five studies (N=91,260) evaluated diagnostic accuracy. At 24 to 28 weeks’ gestation, the oral glucose challenge test using 135 or 140 mg/dL thresholds, against CC and National Diabetes Data Group (NDDG) criteria, and a fasting plasma glucose of 85 mg/dL or 90 mg/dL against CC GDM, had reasonable accuracy (sensitivities ≥81% and specificities ≥73%). Fasting glucose at or below 80 mg/dL appears useful for ruling out CC or IADPSG GDM. Screening with the glucose challenge test against IADPSG criteria had low sensitivity. Being diagnosed with GDM based on more (e.g., 1-step IADPSG) versus less (e.g., 2-step CC) inclusive criteria, but not treated, associated with increased risk of preeclampsia, cesarean deliveries, preterm deliveries, macrosomia, LGA, neonatal hypoglycemia, and hyperbilirubinemia. No association was found for NICU admissions. From nine trials (N=3,982), treatment for mild GDM at or after 24 weeks’ gestation associated with decreased risk of primary cesarean deliveries (RR, 0.70 [95% CI, 0.54 to 0.91]; ARD, 5.3%), preterm deliveries (RR, 0.75 [95% CI, 0.56 to 1.01]; ARD 2.3%), preeclampsia (RR, 0.60 [95% CI, 0.35 to 1.01]; ARD, 1%; after excluding one outlier trial), shoulder dystocia (RR, 0.42 [95% CI, 0.23 to 0.77]; ARD, 1.3%), macrosomia by 8.9% (RR, 0.53 [95% CI, 0.41 to 0.68]; ARD, 8.9%), LGA (RR, 0.56 [95% CI, 0.47 to 0.66]; ARD, 8.4%), birth injuries (e.g., fracture or nerve palsies) (OR, 0.33 [95% CI, 0.11 to 0.99]; ARD, 0.2%) and NICU admissions (RR, 0.73 [95% CI, 0.53 to 0.99; ARD, 2.0%). There was no association with risk of neonatal hypoglycemia or total cesarean deliveries, or for the potential harm of small-for-gestational age. There was limited evidence on long-term health outcomes. Limitations: Evidence on screening versus no screening was observational; very limited evidence on early treatment; restricted to English language studies; unable to formally assess for publication bias; limited evidence for some comparisons and outcomes, and most subgroups; heterogeneity present in some analyses. Conclusions: While direct evidence on outcomes of screening remains very limited, screening tests can identify with gestational diabetes at or after 24 weeks’ gestation and treatment is associated with improvement in various maternal and neonatal outcomes without serious harms. More research is needed to determine the impacts of screening and treatment earlier or based on more inclusive criteria. Screening for Gestational Diabetes Mellitus iv Pacific Northwest and Alberta EPCs Table of Contents Chapter 1. Introduction and Background .................................................................... 1 Purpose ..........................................................................................................................................1 Condition Background Condition Definition ..................................................................................................................1 Prevalence and Burden of Disease/Illness .................................................................................1 Etiology and Natural History .....................................................................................................2 Risk Factors ...............................................................................................................................3 Rationale for Screening/Screening Strategies ............................................................................3