Choice of growth standard and interpretation of large for gestational age outcomes: evidence from the CDC4G trial

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 foetal weight (SWE-REF), the Gestation Related Optimal Weight (GROW) and the International Foetal 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.