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

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DateAccepted/In press - 15 Aug 2016
DatePublished (current) - 13 Sep 2016
Number of pages11
Pages (from-to)1-11
Original languageEnglish


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.

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© 2016, The Author(s).

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