de Brun, Maryam, Magnuson, Anders, Montgomery, Scott, Patil, Snehal, Simmons, David, Berntorp, Kerstin, Jansson, Stefan, Wennerholm, Ulla-Britt, Wikström, Anna-Karin, Strevens, Helen, Ahlsson, Fredrik, Sengpiel, Verena, Schwarcz, Erik, Storck-Lindholm, Elisabeth, Persson, Martina, Petersson, Kerstin, Ryen, Linda, Ursing, Carina, Hildén, Karin, and Backman, Helena
Background: The World Health Organisation (WHO) 2013 diagnostic criteria for gestational diabetes mellitus (GDM) has been criticised due to the limited evidence of benefits on pregnancy outcomes in different populations when switching from previously higher glycemic thresholds to the lower WHO-2013 diagnostic criteria. The aim of this study was to determine whether the switch from previous Swedish (SWE-GDM) to the WHO-2013 GDM criteria in Sweden following risk factor-based screening improves pregnancy outcomes. Methods and findings: A stepped wedge cluster randomised trial was performed between January 1 and December 31, 2018 in 11 clusters (17 delivery units) across Sweden, including all pregnancies under care and excluding preexisting diabetes, gastric bypass surgery, or multifetal pregnancies from the analysis. After implementation of uniform clinical and laboratory guidelines, a number of clusters were randomised to intervention (switch to WHO-2013 GDM criteria) each month from February to November 2018. The primary outcome was large for gestational age (LGA, defined as birth weight >90th percentile). Other secondary and prespecified outcomes included maternal and neonatal birth complications. Primary analysis was by modified intention to treat (mITT), excluding 3 clusters that were randomised before study start but were unable to implement the intervention. Prespecified subgroup analysis was undertaken among those discordant for the definition of GDM. Multilevel mixed regression models were used to compare outcome LGA between WHO-2013 and SWE-GDM groups adjusted for clusters, time periods, and potential confounders. Multiple imputation was used for missing potential confounding variables. In the mITT analysis, 47 080 pregnancies were included with 6 882 (14.6%) oral glucose tolerance tests (OGTTs) performed. The GDM prevalence increased from 595/22 797 (2.6%) to 1 591/24 283 (6.6%) after the intervention. In the mITT population, the switch was associated with no change in primary outcome LGA (2 790/24 209 (11.5%) versus 2 584/22 707 (11.4%)) producing an adjusted risk ratio (aRR) of 0.97 (95% confidence interval 0.91 to 1.02, p = 0.26). In the subgroup, the prevalence of LGA was 273/956 (28.8%) before and 278/1 239 (22.5%) after the switch, aRR 0.87 (95% CI 0.75 to 1.01, p = 0.076). No serious events were reported. Potential limitations of this trial are mainly due to the trial design, including failure to adhere to guidelines within and between the clusters and influences of unidentified temporal variations. Conclusions: In this study, implementing the WHO-2013 criteria in Sweden with risk factor-based screening did not significantly reduce LGA prevalence defined as birth weight >90th percentile, in the total population, or in the subgroup discordant for the definition of GDM. Future studies are needed to evaluate the effects of treating different glucose thresholds during pregnancy in different populations, with different screening strategies and clinical management guidelines, to optimise women's and children's health in the short and long term. Trial registration: The trial is registered with ISRCTN (41918550). Maryam de Brun and colleagues assess whether implementation of the WHO-2013 diagnostic criteria for gestational diabetes with risk factor based screening affects pregnancy outcomes in Sweden. Author summary: Why was this study done?: The implementation of the World Health Organisation (WHO)-2013 diagnostic criteria for gestational diabetes mellitus (GDM) have been challenged due to the limited evidence of benefits on pregnancy outcomes in different populations by switching from former higher plasma glucose diagnostic cutoffs to the lower plasma glucose WHO-2013 diagnostic criteria. Screening, laboratory methods, and diagnostic criteria for GDM vary throughout the world and there is limited randomised controlled trial (RCT) evidence on the effects of switching to WHO 2013 diagnostic criteria for GDM. The Swedish National Board of Health and Welfare introduced new guidelines for GDM in 2015 and the aim was to evaluate if the switch in a real-world setting improved pregnancy outcomes. What did the researchers do and find?: A stepped wedge randomised trial was performed during 2018 which included nearly half of all pregnancies in Sweden that year (n = 47 080). Since risk factor screening was used, analysis was conducted in all pregnancies (modified intention to treat (mITT)) as well as in a subgroup affected by the switch. There was no reduction in the main outcome large for gestational age (LGA) (>90th birth weight percentile) in the mITT population or in the subgroup of women affected by the switch. What do these findings mean?: These findings indicate that the effect of treatment may differ using lower compared to higher plasma glucose diagnostic cutoffs for GDM depending on whether risk factor based screening or universal screening is used. The study findings highlight the importance of also reporting treatment effects on high absolute birth weight besides the LGA 90th percentile, since absolute high birth weight most likely results in associated adverse pregnancy outcomes. Limitations of this trial are mainly due to the trial design, including failure to adhere to guidelines within and between the clusters and influences of unidentified temporal variations. Future studies need to evaluate long-term effects on women's and children's health after diagnosing and treating lower levels of hyperglycemia during pregnancy. [ABSTRACT FROM AUTHOR]