Gestational Diabetes Mellitus: An Exploration of Temporal Trends in Maternal and Neonatal Outcomes in Ontario and a Systematic Review of Benefits of Induction

Abstract

Background Gestational diabetes mellitus (GDM) is a common pregnancy complication that has increased substantially worldwide over the past decades. However, there are few data on recent trends in GDM and the associated impact on adverse pregnancy outcomes in the Canadian population. Induction of labour is recommended to improve perinatal outcomes for GDM pregnancies reaching term gestation, however, epidemiological studies have yielded inconsistent results. The three primary objectives of this thesis were to (1) describe recent trends in GDM and their associations with common risk factors; (2) assess temporal trends in the rates of GDM-associated adverse maternal and neonatal outcomes and compare risks of these outcomes by delivery period; (3) assess the impact of induction of labour at term gestation on adverse outcomes among pregnancies with GDM. Methods A population-based retrospective cohort study of all pregnant individuals who had a singleton hospital birth (live birth and stillbirth) between April 1, 2012 and March 31, 2020 in Ontario, Canada, was used to address thesis objectives (1) and (2). Decomposition and multivariable regression analyses with generalized estimation equations were used to evaluate temporal trends and associations with changing trends in GDM. A systematic review and meta-analysis of experimental and observational comparative studies was undertaken to address thesis objective (3). Results Objective (1) Among 1 044 258 pregnant individuals, the annual rate of GDM increased significantly between 2012/13 and 2019/20, from 6.1 to 10.4 per 100 deliveries, in Ontario, Canada (adjusted relative risk:1.53, 95% CI [1.50, 1.56]). The increase was greater in those who did not receive pharmaceutical treatments than those who received pharmaceutical treatments, especially in more recent years. Twenty seven percent of the temporal increase in GDM can be attributed to the distributional changes of three risk factors: the increasing prevalence of advanced maternal age at delivery, pre-pregnancy obesity, and Asian race/ethnicity. Objective (2) Among adverse maternal outcomes, despite temporally increasing rates of induction in both GDM and non-GDM pregnancies, the magnitude of the association between GDM and induction was similar between 2012/13-2015/16 and 2016/17-2019/20 (1.62, 95% CI [1.60, 1.64] vs 1.60, 95% CI [1.59, 1.62]). The adjusted relative risk of pregnancy-induced hypertension for GDM compared to non-GDM attenuated from 1.45 (95% CI 1.41, 1.49) in 2012/13-2015/16 to 1.29 (95% CI 2.25, 2.32) in 2016/17-2019/20. The association between GDM and CS (1.10, 95% CI [1.08, 1.12] vs 1.07, 95% CI [1.05, 1.08]), and assisted vaginal delivery (0.96, 95% CI [0.92, 1.00] vs 0.94, 95% CI [0.90, 0.98]) remained similar between the two time periods. For overall maternal morbidity and mortality, the adjusted relative risk was close to 1 and not statistically significant in either time period (0.93, 95% CI [0.78, 1.08] vs 1.09, 95% CI [0.97, 1.20]). Among adverse neonatal outcomes, although the rate of overall severe neonatal morbidity and mortality (SNM) increased over time among both pregnancies with and without GDM, the positive association between GDM and SNM was stable between the time periods (1.50, 95% CI [1.48, 1.52] vs 1.54, 95% CI [1.52, 1.56]). The magnitude of the association of GDM with LGA and macrosomia was lower in 2016/17-2019/20 than 2012/13-2015/16 (1.42, 95% CI [1.39, 1.45] vs 1.31, 95% CI [1.28, 1.34] for LGA; 0.98, 95% CI [0.95, 1.02] vs 0.86, 95% CI [0.83, 0.90] for macrosomia). There were no significant changes in the associations of GDM with other neonatal outcomes. Objective (3) The systematic review identified 11 experimental and observational comparative studies. Random-effects meta-analysis demonstrated that compared to expectant management, induction at term gestation was associated with a lower pooled odds of macrosomia (randomized controlled trials: 0.49, 95% CI [0.30, 0.81]; I2=0%; observational studies: 0.64, 95% CI [0.54, 0.77]; I2=0%); and severe perineal lacerations (observational studies: 0.59, 95% CI [0.39, 0.88]; I2=0%) among GDM pregnancies. There were no significant differences in odds of CS or other adverse perinatal outcomes between the two groups. Conclusion There has been a substantial increase in the GDM rates in Ontario from 2012/13 to 2019/20, with twenty seven percent of this increase attributed to the higher prevalence of advanced maternal age at delivery, pre-pregnancy obesity, and Asian ethnicity. On the other hand, despite the increasing rate of GDM, no significant increase in the risk of GDM-associated adverse maternal and neonatal outcomes was observed, except for postpartum hemorrhage with interventions. For pregnant individuals with GDM, induction at term gestation could lower the risk of macrosomia and severe perineal lacerations compared to expectant management. Future well-designed clinical trials with large sample sizes are needed for better screening, diagnosis, and management of GDM.