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

Abstract

Objectives To assess the association between maternal glucose concentrations and adverse perinatal outcomes in women without gestational or existing diabetes and 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 from two additional birth cohorts.Eligibility criteria for selecting studies Studies including pregnant women with oral glucose tolerance (OGTT) or challenge (OGCT) test results, with data on at least one adverse perinatal outcome.Appraisal and data extraction Glucose test results were extracted for OGCT (50 g) and OGTT (75 g and 100 g) at fasting and one and two hour post-load timings. Data were extracted on induction of labour; caesarean and instrumental delivery; pregnancy induced hypertension; pre-eclampsia; macrosomia; large for gestational age; preterm birth; birth injury; and neonatal hypoglycaemia. Risk of bias was assessed with a modified version of the critical appraisal skills programme and quality in prognostic studies tools.Results 25 reports from 23 published studies and two individual participant data cohorts were included, 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 with caesarean section, induction of labour, large for gestational age, macrosomia, and shoulder dystocia for all glucose exposures across the distribution of glucose concentrations. There was no clear evidence of a threshold effect. In general, associations were stronger for fasting concentration than for post-load concentration. For example, the odds ratios for large for gestational age per 1 mmol/L increase of fasting and two hour post-load glucose concentrations (after a 75 g OGTT) were 2.15 (95% confidence interval 1.60 to 2.91) and 1.20 (1.13 to 1.28), respectively. Heterogeneity was low between studies in all analyses.Conclusions This review and meta-analysis identified a large number of studies in various countries. There was a graded linear association between fasting and post-load glucose concentration across the whole glucose distribution and most adverse perinatal outcomes in women without pre-existing or gestational diabetes. The lack of a clear threshold at which risk increases means that decisions regarding thresholds for diagnosing gestational diabetes are somewhat arbitrary. Research should now investigate the clinical and cost-effectiveness of applying different glucose thresholds for diagnosis of gestational diabetes on perinatal and longer term outcomes.Systematic review registration PROSPERO CRD42013004608

Prevalence and Complications of Pregestational and Gestational Diabetes in Saudi Women: Analysis from Riyadh Mother and Baby Cohort Study (RAHMA)

“…This can be explained by the longer exposure of the fetus to more severe hyperglycemic environment than in the case of GDM. The linear relationship between the degree of hyperglycaemia and the development of certain maternal and neonatal complications was recently established by the HAPO study and similar reports [27, 28]. …”

The mediating effects of gestational diabetes on fetal growth and adiposity in women who are overweight and obese: secondary analysis of the LIMIT randomised trial

“…Gestational diabetes mellitus (GDM) is defined as carbohydrate intolerance diagnosed during pregnancy and increases in prevalence with increasing maternal BMI . GDM is associated with adverse perinatal outcomes similar to those seen among women who are overweight or obese in pregnancy, including need for induction of labour and caesarean section, and having an infant born large for gestational age or birthweight over 4 kg …”

“…7 GDM is associated with adverse perinatal outcomes similar to those seen among women who are overweight or obese in pregnancy, including need for induction of labour and caesarean section, and having an infant born large for gestational age or birthweight over 4 kg. [11][12][13] It is unclear whether the combination of maternal overweight or obesity and GDM represents an additive risk in pregnancy, and whether diagnosis and treatment of GDM among women who are overweight or obese modifies this risk. It is also unclear how much of the increased perinatal risk associated with maternal overweight and obesity is attributable to the increased prevalence of GDM.…”

Normal foetal kidney volume in offspring of women treated for gestational diabetes

“…40 Overall, evidence for the extent to which GDM affects developing human kidneys is not robust. 45 The objective of this study was to evaluate the association of treated GDM with foetal kidney size in late pregnancy. While treatment of GDM to control glucose levels can reduce the risk of some adverse perinatal and infant outcomes, 41-43 evidence of treatment benefits are often unsupported, 43,44 and there is uncertainty regarding optimal diagnostic thresholds and optimal glycemic targets.…”

“…While treatment of GDM to control glucose levels can reduce the risk of some adverse perinatal and infant outcomes, [41][42][43] evidence of treatment benefits are often unsupported, 43,44 and there is uncertainty regarding optimal diagnostic thresholds and optimal glycemic targets. 45 The objective of this study was to evaluate the association of treated GDM with foetal kidney size in late pregnancy.…”