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


METHODS
Systematic review and meta-analysis of prospective cohort studies and control arms of randomised trials.


METHODS
Databases including Medline and Embase were searched up to October 2014 and combined with individual participant data from two additional birth cohorts.


METHODS
Studies including pregnant women with oral glucose tolerance (OGTT) or challenge (OGCT) test results, with data on at least one adverse perinatal outcome.
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.


BACKGROUND
PROSPERO CRD42013004608.
Bradford Institute for Health Research, Bradford Royal Infirmary, Bradford BD9 6RJ, UK Department of Health Sciences, University of York, York YO10 5DD, UK Diane.Farrar@bthft.nhs.uk.
Diane
D
Farrar
Centre for Reviews and Dissemination, University of York, York YO10 5DD, UK.
Mark
M
Simmonds
Bradford Institute for Health Research, Bradford Royal Infirmary, Bradford BD9 6RJ, UK Leeds Institute of Clinical Trials Research, University of Leeds, Leeds LS2 9JT, UK.
Maria
M
Bryant
Hull York Medical School, University of York, York YO10 5DD, UK.
Trevor A
TA
Sheldon
Bradford Women's and Newborn Unit, Bradford BD9 6RJ, UK.
Derek
D
Tuffnell
Department of Health Sciences, University of York, York YO10 5DD, UK.
Su
S
Golder
Galway Diabetes Research Centre (GDRC) and School of Medicine, National University of Ireland, Republic of Ireland.
Fidelma
F
Dunne
MRC Integrative Epidemiology Unit at the University of Bristol, Oakfield House, Bristol BS8 2BN, UK School of Social and Community Medicine, University of Bristol, Bristol BS8 2PS, UK.
Debbie A
DA
Lawlor
D001724:Birth Weight; D016640:Diabetes, Gestational / Q000175:diagnosis / Q000517:prevention & control*; D004420:Dystocia / Q000209:etiology; D019317:Evidence-Based Medicine; D005260:Female; D005320:Fetal Macrosomia / Q000209:etiology / Q000517:prevention & control*; D005951:Glucose Tolerance Test / Q000379:methods; D006801:Humans; D006943:Hyperglycemia / Q000097:blood / Q000150:complications* / Q000175:diagnosis / Q000517:prevention & control*; D007231:Infant, Newborn; D011247:Pregnancy; D011256:Pregnancy Outcome; D047928:Premature Birth / Q000209:etiology*; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors