Hyperglycaemia and risk of adverse perinatal outcomes: systematic review and meta-analysis
BMJ 2016; 354 doi: https://doi.org/10.1136/bmj.i4694 (Published 13 September 2016) Cite this as: BMJ 2016;354:i4694
- Diane Farrar, NIHR postdoctoral research fellow1 2,
- Mark Simmonds, research fellow3,
- Maria Bryant, NIHR career development fellow1 4,
- Trevor A Sheldon, professor of health services research and policy5,
- Derek Tuffnell, consultant obstetrician and gynaecologist6,
- Su Golder, NIHR postdoctoral research fellow2,
- Fidelma Dunne, consultant endocrinologist7,
- Debbie A Lawlor, professor of epidemiology8 9
- 1Bradford Institute for Health Research, Bradford Royal Infirmary, Bradford BD9 6RJ, UK
- 2Department of Health Sciences, University of York, York YO10 5DD, UK
- 3Centre for Reviews and Dissemination, University of York, York YO10 5DD, UK
- 4Leeds Institute of Clinical Trials Research, University of Leeds, Leeds LS2 9JT, UK
- 5Hull York Medical School, University of York, York YO10 5DD, UK
- 6Bradford Women’s and Newborn Unit, Bradford BD9 6RJ, UK
- 7Galway Diabetes Research Centre (GDRC) and School of Medicine, National University of Ireland, Republic of Ireland
- 8MRC Integrative Epidemiology Unit at the University of Bristol, Oakfield House, Bristol BS8 2BN, UK
- 9School of Social and Community Medicine, University of Bristol, Bristol BS8 2PS, UK
- Correspondence to: Diane.Farrar{at}bthft.nhs.uk
- Accepted 15 August 2016
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
Footnotes
We thank Julie Glanville and Mick Arber of the York Health Economics Consortium who carried out the searches.
Contributors: DF, DAL, and TAS designed the study and secured funding. MS wrote the statistical analysis plan with contribution from DAL and DF. MS, DF, and SG assessed study eligibility and conducted quality assessments. MS cleaned and analysed the data. DF monitored the review process. DF, MS, MB, DAL, TAS, DT, and FD interpreted the data. DF drafted the paper, and all authors contributed. DF is guarantor.
Funding: This project was funded by the National Institute for Health Research (NIHR), Health Technology Assessment (HTA) programme, project No 11/99/02. DAL’s contribution to this study is funded by grants from the US National Institute of Health (R01 DK10324) and European Research Council (ObesityDevelop 669545); she works in a unit that is supported by the University of Bristol and UK Medical Research Council ((MC_UU_12013/5) and holds a NIHR senior investigator award (NF-SI-0611-10196). The views and opinions expressed therein are those of the authors and do not necessarily reflect those of the HTA, NIHR, NIH, ERC, MRC, UK National Health Service (NHS), or the Department of Health.
Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.
Ethical approval: The Born in Bradford study was approved by the Bradford research ethics committee (07/H1302/112). All participants provided informed written consent.
Data sharing: Extracted data are available on request to the corresponding author.
Transparency: The lead author affirms that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.
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