Maryam de Brun

Background: The lack of a standardised definition of large for gestational age (LGA) complicates clinical assessments and the interpretation of research. Objective: The objective of this study is to assess how different definitions of LGA affect the interpretation of outcomes in a stepped wedge cluster randomised controlled trial (SW‐CRT). Methods: Secondary analysis of the Changing Diagnostic Criteria for Gestational Diabetes (CDC4G, ISRCTN41918550) study population ( n = 47,080 pregnancies), including eight delivery units in Sweden during 2018. The outcome measures were the prevalence of LGA and severe LGA before and after switching from the previous Swedish diagnostic criteria for gestational diabetes (SWE‐GDM) to the World Health Organisation (WHO‐2013) criteria. LGA and severe LGA were defined as birthweight > 90th and > 97th percentile, respectively, using the following reference growth charts: The new Swedish reference ranges for fetal weight (SWE‐REF), the Gestation Related Optimal Weight (GROW) and the International Fetal and Newborn Growth Consortium for the 21st Century (Intergrowth‐21st). Analyses were performed on a modified intention‐to‐treat (mITT) population and on the subgroup discordant for GDM diagnosis between new and former criteria, i.e., glucose levels between the WHO‐2013 and SWE‐GDM diagnostic thresholds. Results: In the mITT population, the prevalence of LGA decreased from 19.4% to 13.1% after the switch to the WHO‐2013 GDM criteria, as defined by SWE‐REF (adjusted relative risk [RR], 0.92; 95% confidence interval [CI] 0.86, 0.98). There was no change in severe LGA using any of the reference charts. In the subgroup, LGA defined by SWE‐REF (RR 0.68, 95% CI 0.50, 0.91) and GROW (RR 0.78, 95% CI 0.63, 0.95) was reduced, but not when defined by Intergrowth‐21st (RR 0.88, 95% CI 0.74, 1.06). Severe LGA was reduced only when defined by Intergrowth‐21st (RR 0.73, 95% CI 0.62, 0.85). Conclusions: The choice of LGA definition affected the interpretation of the results in the CDC4G trial.

Objective: To estimate the effect on healthcare resource use after introducing the World Health Organization diagnostic criteria (WHO‐2013) for gestational diabetes mellitus (GDM) compared to former criteria in Sweden (SWE‐GDM).Design: A cost‐analysis alongside the Changing Diagnostic Criteria for Gestational Diabetes (CDC4G) randomised controlled trial.Setting: Sweden, with risk‐factor based screening for GDM.Population: 47 080 pregnant women and their infants.Methods: A register‐based cost‐analysis from a healthcare perspective alongside a stepped‐wedge cluster RCT of switching from SWE‐GDM to WHO‐2013 criteria in 2018. Analyses were made on the population level and repeated in the subgroup affected by the intervention, that is, those with plasma glucose values between SWE‐GDM and WHO‐2013 criteria. Sensitivity analysis by bootstrapping was performed.Main Outcome Measures: Estimated costs for obstetric surveillance (including GDM‐management), delivery and neonatal healthcare until 28 days postpartum.Results: On a population level, the WHO‐2013 criteria were associated with increased costs of obstetric surveillance (adjusted mean [bootstrap confidence interval]) €94.0 [24.5–169.1], delivery care €20.4 [−33.5 to 75.4] and neonatal care €331.0 [75.1–589.0] per pregnancy, and in the affected subgroup €606.9 [377.7–872.4], €348.5 [126.0–542.0] and €129.3 [−559.0 to 980.9] respectively.Conclusions: Implementation of the WHO‐2013 criteria in Sweden was associated with increased costs for obstetric surveillance and delivery on a population level, driven by the affected subgroup. The increased costs for neonatal care were associated with large uncertainty. A detailed understanding of the changes in resource use can guide decisions to mitigate cost increases.

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).

Background: The screening strategy in Sweden for GDM is mainly based on random plasma glucose measurements combined with presence of risk factors (previous GDM or LGA (large for gestational age) /macrosomia, obesity, heredity, accelerated growth or polyhydramnios) . The association of risk factors with mean levels of glucose in the diagnostic OGTT in different populations is unclear. Method/Material: Data from Changing Diagnostic Criteria for GDM in Sweden (CDC4G) - a stepped wedge randomised RCT (ISRCTN41918550) where centers during 2018 were randomized to switch to new IADPSG criteria for GDM every month. All pregnant women underwent a venous OGTT during 2018. Mean glucose values by risk factor are presented with 95% CI, significant p value <0. (marked bold in the table) . Results: Of 53 124 pregnancies 69 (13.0%) underwent venous OGTT. Either metformin or Insulin was used in 11% before the diagnostic criteria switch and 18.8% after the switch. Metformin only was used in 9.7% before and in 16.4% after randomization to new criteria. Conclusions: BMI≥35 or Previous LGA/macrosomia were associated with a higher fasting glucose value in OGTT, but previous GDM, accelerated growth and high random blood glucose were statistically significantly associated with higher glucose values in all measurements in the diagnostic OGTT. Women with previous GDM had the highest proportion treated with either insulin and/or metformin Disclosure: H.E.Fadl: None. H.Strevens: None. U.Wennerholm: None. M.Persson: None. M.De brun: None. S.Montgomery: None. D.Simmons: Other Relationship; Elsevier, Research Support; Abbott, Hitachi, Ltd., Novo Nordisk, Speaker's Bureau; Sanofi. S.Patil: None. A.Wikström: None. S.P.Jansson: None. V.Sengpiel: None. K.Berntorp: None. L.Ryen: None. F.Ahlsson: None. E.S.Lindholm: None. Funding: Swedish Research Council (2018-00470)

The Swedish National Board of Health and Welfare (SNBHW) recommended the new diagnostic criteria for GDM based upon Hyperglycaemia and Adverse Pregnancy Outcomes (HAPO) study thresholds. Due to limited knowledge base, no recommendations were made on GDM screening. The aim of this study is to evaluate test characteristics of risk factors and fasting blood glucose as screening tests for diagnosing GDM using diagnostic thresholds based upon HAPO study 1.75/2.0 (model I/II respectively) odds ratio for adverse pregnancy outcomes. This cross-sectional, population-based study included all pregnant women who attended maternal health care in Örebro County, Sweden between the years 1994–96. A 75 g OGTT with capillary fasting and 2-h blood glucose was offered to all pregnant women at week 28–32. Risk factors and repeated random glucose samples were collected. Sensitivity, specificity and predictive values of blood glucose were calculated. Prevalence of GDM was 11.7% with model I and 7.2% with the model II criteria. Risk factors showed 28%, (95% CI 24–32) and 31%, (95% CI 25–37) sensitivity for model I and II respectively. A fasting cut off ≥4.8 mmol/l occurred in 24% of women with 91%, (95% CI 88–94) sensitivity and 85%, (95% CI 83–86) specificity using model I while a fasting cut off ≥5.0 mmol/l occurred in 14% with 91%, (95% CI 87–94) sensitivity and 92%, (95% CI 91–93) specificity using model II. Risk factor screening for GDM was found to be poorly predictive of GDM but fasting glucose of 4.8–5.0 mmol/l showed good test characteristics irrespective of diagnostic model and results in a low rate of OGTTs.