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

Diane Farrar, Mark Simmonds, Maria Bryant, Trevor A Sheldon, Derek Tuffnell, Su Golder, Fidelma Dunne, Debbie A Lawlor, Diane Farrar, Mark Simmonds, Maria Bryant, Trevor A Sheldon, Derek Tuffnell, Su Golder, Fidelma Dunne, Debbie A Lawlor

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.

Conflict of interest statement

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.

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Figures

https://www.ncbi.nlm.nih.gov/pmc/articles/instance/5021824/bin/fard032237.f1_default.jpg
Fig 1 Flow diagram for selection of studies of hyperglycaemia and risk of adverse perinatal outcomes
https://www.ncbi.nlm.nih.gov/pmc/articles/instance/5021824/bin/fard032237.f2_default.jpg
Fig 2 Odd ratios for outcomes associated with glucose concentration (fasting combined 75 g and 100 g OGTT, one hour post-load 50 g OGCT, two hour post-load 75 g OGTT, and two hour post-load 100 g OGTT)

References

    1. Hartling L, Dryden DM, Guthrie A, Muise M, Vandermeer B, Donovan L. Benefits and harms of treating gestational diabetes mellitus: a systematic review and meta-analysis for the U.S. Preventive Services Task Force and the National Institutes of Health Office of Medical Applications of Research. Ann Intern Med 2013;159:123-9. 10.7326/0003-4819-159-2-201307160-00661 .
    1. Shah BR, Retnakaran R, Booth GL. Increased risk of cardiovascular disease in young women following gestational diabetes mellitus. Diabetes Care 2008;31:1668-9. 10.2337/dc08-0706 .
    1. Boney CM, Verma A, Tucker R, Vohr BR. Metabolic syndrome in childhood: association with birth weight, maternal obesity, and gestational diabetes mellitus. Pediatrics 2005;115:e290-6. 10.1542/peds.2004-1808 .
    1. Clausen TD, Mathiesen ER, Hansen T, et al. High prevalence of type 2 diabetes and pre-diabetes in adult offspring of women with gestational diabetes mellitus or type 1 diabetes: the role of intrauterine hyperglycemia. Diabetes Care 2008;31:340-6. 10.2337/dc07-1596 .
    1. Metzger BE, Gabbe SG, Persson B, et al. International Association of Diabetes and Pregnancy Study Groups Consensus Panel. International association of diabetes and pregnancy study groups recommendations on the diagnosis and classification of hyperglycemia in pregnancy. Diabetes Care 2010;33:676-82. 10.2337/dc10-0719 .
    1. Alwan N, Tuffnell DJ, West J. Treatments for gestational diabetes. Cochrane Database Syst Rev 2009;(3):CD003395..
    1. Horvath K, Koch K, Jeitler K, et al. Effects of treatment in women with gestational diabetes mellitus: systematic review and meta-analysis. BMJ 2010;340:c1395 10.1136/bmj.c1395 .
    1. Metzger BE, Lowe LP, Dyer AR, et al. HAPO Study Cooperative Research Group. Hyperglycemia and adverse pregnancy outcomes. N Engl J Med 2008;358:1991-2002. 10.1056/NEJMoa0707943 .
    1. World Health Organization. Diagnostic criteria and classification of hyperglycaemia first detected in pregnancy.WHO, 2013.
    1. Hod M, Kapur A, Sacks DA, et al. The International Federation of Gynecology and Obstetrics (FIGO) Initiative on gestational diabetes mellitus: A pragmatic guide for diagnosis, management, and care. Int J Gynaecol Obstet 2015;131(Suppl 3):S173-211. 10.1016/S0020-7292(15)30033-3 .
    1. National Institute for Health and Care Excellence. Diabetes in pregnancy: management from preconception to the postnatal period. NICE clinical guideline NG3. 2015.
    1. American College of Obstetricians and Gynecologists. Practice Bulletin No 137: Gestational diabetes mellitus. Obstet Gynecol 2013;122:406-16..
    1. Farrar D, Fairley L, Santorelli G, et al. Association between hyperglycaemia and adverse perinatal outcomes in south Asian and white British women: analysis of data from the Born in Bradford cohort. Lancet Diabetes Endocrinol 2015;3:795-804. 10.1016/S2213-8587(15)00255-7 .
    1. Higgins JPT, Green S, eds. Cochrane handbook for systematic reviews of interventions. Version 5.1.0. 2011. .
    1. Centre for Reviews and Dissemination. Systematic reviews: CRD’s guidance for undertaking a systematic review York: CRD.University of York, 2009.
    1. Wright J, Small N, Raynor P, Tuffnell D, Bhopal R, Cameron N. Cohort profile: The Born in Bradford multi-ethnic family cohort study. Int J Epidemiol 2013;42:978-91. 10.1093/ije/dys112 .
    1. Dunne FP, Avalos G, Durkan M, et al. ATLANTIC DIP collaborators. ATLANTIC DIP: pregnancy outcome for women with pregestational diabetes along the Irish Atlantic seaboard. Diabetes Care 2009;32:1205-6. 10.2337/dc09-1118 .
    1. O’Sullivan EP, Avalos G, O’Reilly M, Dennedy MC, Gaffney G, Dunne F. Atlantic DIP collaborators. Atlantic Diabetes in Pregnancy (DIP): the prevalence and outcomes of gestational diabetes mellitus using new diagnostic criteria. Diabetologia 2011;54:1670-5. 10.1007/s00125-011-2150-4 .
    1. World Health Organization. Definition, diagnosis and classification of diabetes mellitus and its complications. Report of a WHO consultation. Part 1: diagnosis and classification of diabetes mellitus.WHO, 1999.
    1. American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care 2006;29(Suppl 1):S43-8..
    1. Hoffman L, Nolan C, Wilson JD, Oats JJ, Simmons D. The Australasian Diabetes in Pregnancy Society. Gestational diabetes mellitus--management guidelines. Med J Aust 1998;169:93-7..
    1. National Diabetes Data Group. Classification and diagnosis of diabetes mellitus and other categories of glucose intolerance. Diabetes 1979;28:1039-57. 10.2337/diab.28.12.1039 .
    1. O’Sullivan JB, Mahan CM. Criteria for the oral glucose tolerance test in pregnancy. Diabetes 1964;13:278-85..
    1. Carpenter MW, Coustan DR. Criteria for screening tests for gestational diabetes. Am J Obstet Gynecol 1982;144:768-73. 10.1016/0002-9378(82)90349-0 .
    1. Carr DB, Newton KM, Utzschneider KM, et al. Gestational diabetes or lesser degrees of glucose intolerance and risk of preeclampsia. Hypertens Pregnancy 2011;30:153-63. 10.3109/10641950903115012 .
    1. Chandna A, Zuberi LM, Munim S. Threshold values for the glucose challenge test in pregnancy. Int J Gynaecol Obstet 2006;94:119-20. 10.1016/j.ijgo.2006.04.010 .
    1. Cheng YW, McLaughlin GB, Esakoff TF, Block-Kurbisch I, Caughey AB. Glucose challenge test: screening threshold for gestational diabetes mellitus and associated outcomes. J Matern Fetal Neonatal Med 2007;20:903-8. 10.1080/14767050701739384 .
    1. Figueroa D, Landon MB, Mele L, et al. Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Maternal-Fetal Medicine Units (MFMU) Network. Relationship between 1-hour glucose challenge test results and perinatal outcomes. Obstet Gynecol 2013;121:1241-7. 10.1097/AOG.0b013e31829277f5 .
    1. Hillier TA, Pedula KLMS, Vesco KK, et al. Excess gestational weight gain: modifying fetal macrosomia risk associated with maternal glucose. Obstet Gynecol 2008;112:1007-14. 10.1097/AOG.0b013e31818a9779 .
    1. Ong KK, Diderholm B, Salzano G, et al. Pregnancy insulin, glucose, and BMI contribute to birth outcomes in nondiabetic mothers. Diabetes Care 2008;31:2193-7. 10.2337/dc08-1111 .
    1. Scholl TO, Sowers M, Chen X, Lenders C. Maternal glucose concentration influences fetal growth, gestation, and pregnancy complications. Am J Epidemiol 2001;154:514-20. 10.1093/aje/154.6.514 .
    1. Sermer M, Naylor CD, Gare DJ, et al. Impact of increasing carbohydrate intolerance on maternal-fetal outcomes in 3637 women without gestational diabetes. The Toronto Tri-Hospital Gestational Diabetes Project. Am J Obstet Gynecol 1995;173:146-56. 10.1016/0002-9378(95)90183-3 .
    1. Witter FR, Niebyl JR. Abnormal glucose screening in pregnancy in patients with normal oral glucose tolerance tests as a screening test for fetal macrosomia. Int J Gynaecol Obstet 1988;27:181-4. 10.1016/0020-7292(88)90005-7 .
    1. Yee LM, Cheng YW, Liddell J, Block-Kurbisch I, Caughey AB. 50-Gram glucose challenge test: is it indicative of outcomes in women without gestational diabetes mellitus?J Matern Fetal Neonatal Med 2011;24:1102-6. 10.3109/14767058.2010.546450 .
    1. Aris IM, Soh SE, Tint MT, et al. Effect of maternal glycemia on neonatal adiposity in a multiethnic Asian birth cohort. J Clin Endocrinol Metab 2014;99:240-7. 10.1210/jc.2013-2738 .
    1. Yogev , Chen , Hod , et al. Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study Cooperative Research Group. Hyperglycemia and adverse pregnancy outcome (HAPO) study: preeclampsia. Am J Obstet Gynecol 2010;202:255.e1-7. 10.1016/j.ajog.2010.01.024 .
    1. Jensen DM, Damm P, Sørensen B, et al. Clinical impact of mild carbohydrate intolerance in pregnancy: a study of 2904 nondiabetic Danish women with risk factors for gestational diabetes mellitus. Am J Obstet Gynecol 2001;185:413-9. 10.1067/mob.2001.115864 .
    1. Kerényi Z, Tamás G, Kivimäki M, et al. Maternal glycemia and risk of large-for-gestational-age babies in a population-based screening. Diabetes Care 2009;32:2200-5. 10.2337/dc09-1088 .
    1. Lao TT, Ho LF. Does maternal glucose intolerance affect the length of gestation in singleton pregnancies?J Soc Gynecol Investig 2003;10:366-71. 10.1016/S1071-5576(03)00115-1 .
    1. Metzger BE, Persson B, Lowe LP, et al. HAPO Study Cooperative Research Group. Hyperglycemia and adverse pregnancy outcome study: neonatal glycemia. Pediatrics 2010;126:e1545-52. 10.1542/peds.2009-2257 .
    1. Moses RGF, Calvert D. Pregnancy outcomes in women without gestational diabetes mellitus related to the maternal glucose level. Is there a continuum of risk?Diabetes Care 1995;18:1527-33. 10.2337/diacare.18.12.1527 .
    1. Pettitt DJ, Knowler WC, Baird HR, Bennett PH. Gestational diabetes: infant and maternal complications of pregnancy in relation to third-trimester glucose tolerance in the Pima Indians. Diabetes Care 1980;3:458-64. 10.2337/diacare.3.3.458 .
    1. Savona-Ventura C, Craus J, Vella K, Grima S. Lowest threshold values for the 75g oral glucose tolerance test in pregnancy. Malta Med J 2010;22:18-20.
    1. Landon MB, Mele L, Spong CY, et al. Eunice Kennedy Shriver National Institute of Child Health, and Human Development (NICHD) Maternal–Fetal Medicine Units (MFMU) Network. The relationship between maternal glycemia and perinatal outcome. Obstet Gynecol 2011;117:218-24. 10.1097/AOG.0b013e318203ebe0 .
    1. Little RR, McKenzie EM, Shyken JM, et al. Lack of relationship between glucose tolerance and complications of pregnancy in nondiabetic women. Diabetes Care 1990;13:483-7. 10.2337/diacare.13.5.483 .
    1. Riskin-Mashiah S, Younes G, Damti A, Auslender R. First-trimester fasting hyperglycemia and adverse pregnancy outcomes. Diabetes Care 2009;32:1639-43. 10.2337/dc09-0688 .
    1. Tallarigo L, Giampietro O, Penno G, Miccoli R, Gregori G, Navalesi R. Relation of glucose tolerance to complications of pregnancy in nondiabetic women. N Engl J Med 1986;315:989-92. 10.1056/NEJM198610163151603 .
    1. Hayden JA, van der Windt DA, Cartwright JL, Côté P, Bombardier C. Assessing bias in studies of prognostic factors. Ann Intern Med 2013;158:280-6. 10.7326/0003-4819-158-4-201302190-00009 .
    1. Simmonds MC, Higgins JPT. A general framework for the use of logistic regression models in meta-analysis. Stat Methods Med Res 2014;2014:12 10.1177/0962280214534409. .
    1. HAPO Study Cooperative Research Group. Hyperglycaemia and Adverse Pregnancy Outcome (HAPO) Study: associations with maternal body mass index. BJOG 2010;117:575-84. 10.1111/j.1471-0528.2009.02486.x .
    1. Bain E, Middleton P, Crowther CA. Progressing towards standard outcomes in gestational diabetes Cochrane reviews and randomised trials.ANZJOG, 2016.
    1. Cundy T, Ackermann E, Ryan EA. Gestational diabetes: new criteria may triple the prevalence but effect on outcomes is unclear. BMJ 2014;348:g1567 10.1136/bmj.g1567 .
    1. Levitt NS. Diabetes in Africa: epidemiology, management and healthcare challenges. Heart 2008;94:1376-82. 10.1136/hrt.2008.147306 .
    1. Crampin AC, Kayuni N, Amberbir A, et al. Hypertension and diabetes in Africa: design and implementation of a large population-based study of burden and risk factors in rural and urban Malawi. Emerg Themes Epidemiol 2016;13:3 10.1186/s12982-015-0039-2 .

Source: PubMed

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