Hyperglycaemia and risk of adverse perinatal outcomes:A systematic review and meta-analysis

Objectives: Assess the association between maternal l glucose levels and adverse perinatal outcomes in women without gestational or existing diabetes, to determine whether clear thresholds for identifying women at risk of perinatal outcomes can be identified. Design: Systematic review and meta-analysis of prospective cohort studies and control arms of randomised trials Data sources: Databases including MEDLINE and Embase were searched up to October 2014 and combined with individual participant data (IPD) from two additional birth cohorts. Eligibility criteria for selecting studies: Studies including pregnant women with oral glucose tolerance (OGTT) or challenge test (OGCT) results, with data on at least one adverse perinatal outcome. Appraisal and Data extraction: Glucose test results were extracted for OGCT (50g) and OGTT (75g and 100g) at fasting, one and two-hour post-load timings. Data were extracted on: induction of labour (IOL); Caesarean and instrumental delivery; pregnancy-induced hypertension; pre-eclampsia; macrosomia ; large for gestational age (LGA); preterm birth; birth injury and neonatal hypoglycaemia. Risk of bias was assessed using a modified version of the critical appraisal skills programme and quality in prognostic studies tools. Results: We included 25 reports from 23 published studies and two IPD cohorts, with up to 207,172 women (numbers varied by the test and outcome analysed in the meta-analyses). Overall most studies were judged as having a low risk of bias. There were positive linear associations for all glucose exposures with Caesarean-section, IOL, LGA, macrosomia and shoulder dystocia, across the distribution of glucose. There was no clear evidence of a threshold effect. In general, associations were stronger for fasting compared with post-load glucose. For example, the odds ratios for LGA per 1mmol/L of fasting and two-hour post-load glucose (following a 75g OGTT) were 2.15 (95% CI 1.60 to 2.91,), and 1.20 (95% CI 1.13 to 1.28), respectively. Heterogeneity was very low between studies in all analyses. Conclusions: This review and meta-analysis identified a large number of studies, in a variety of countries. We have demonstrated a graded linear association between fasting and post-load glucose, across the whole glucose distribution, and the majority of adverse perinatal outcomes in women without pre-existing or gestational diabetes. The lack of a clear glucose threshold at which risk increases means that decisions regarding thresholds for diagnosing gestational diabetes are somewhat arbitrary. We suggest that research should now investigate the clinical and cost-effectiveness of applying different glucose thresholds for gestational diabetes diagnosis on perinatal and longer-term outcomes.