Improving the Diagnosis of Gestational Diabetes Mellitus
Researchers at the UCD Centre for Human Reproduction at the Coombe Women and Infants University Hospital have demonstrated the impact of implementing strict preanalytical sample handling procedures on the diagnosis of gestational diabetes mellitus (GDM) in pregnant women. The prospective observational study of women being screened with an Oral Glucose Tolerance Test (OGTT) was published recently in the Journal of Clinical Chemistry Laboratory Methods. It found that the prevalence of GDM was 2.7 times higher if standards for preanalytic prevention of glycolysis in the maternal samples were strictly implemented compared with the customary hospital conditions.
These findings by Dr Niamh Daly and her colleagues at the UCD Centre for Human Reproduction raise the possibility that suboptimal implementation of measures to prevent glycolysis is causing GDM to be under-diagnosed across the country, with potentially serious clinical consequences. Gestational diabetes mellitus (GDM) is associated with adverse pregnancy outcomes, but risk is reduced with identification and early treatment. Variations in pre-analytical standards may also contribute to the wide variations reported in the prevalence of GDM and the poor reproducibility of OGTTs.
Improving Detection of Gestational Diabetes Mellitus
While there is little international consensus in the criteria for the diagnosis of gestational diabetes mellitus (GDM), many countries and the World Health Organization have adopted the International Association of the Diabetes and Pregnancy Study Groups (IADPSG) recommendations. In addition, stricter recommendations have also been produced and endorsed by the National Academy of Clinical Biochemistry (NACB) for laboratory standards in the analysis of maternal glucose measurements. These laboratory standards have assumed greater importance for the diagnosis of GDM now that the diagnostic fasting cut-off point has been lowered, and that the diagnosis can be made on the basis of one increased value with the IADPSG criteria, and not two as previously.
Optimising Pre-Analytical Inhibition of Glycolysis
The importance of pre-ananalytical inhibition of glycolysis in the diagnosis of GDM has been shown by the UCD centre for Human Reproduction Research group in two recent studies of women being screened using a one-step 75 g oral glucose tolerance test (OGTT) using the latest IADPSG diagnostic criteria. In 24 obese women, the incidence of GDM was 54% when the NACB recommendations for the OGTT were implemented compared to 17% when they were not. In a larger study of all women screened selectively with an OGTT (n = 155), the incidence was 38% when the NACB recommendations were implemented compared with 14% when they were not (p < 0.001).
Maternity services in Ireland are highly centralised with all 19 units around the country delivering over 1,000 women annually. Wide variations in the incidence of GDM have been recently reported across these maternity units. Of the 19, 18 have a biochemistry laboratory on site within walking distance of the maternity outpatients department. In one unit, the samples have to be transferred a short distance by car from the maternity hospital to the laboratory in an acute general hospital.
The UCD Centre for Human Reproduction conducted a cross-sectional study of the pre-ananalytical handling of glucose samples in all 19 units in the Republic of Ireland. Significant variation was noted in the fasting duration, the use of a one-step test, the nature and quantity of glucose challenge, the number and timing of blood samples taken, the timing of the challenge, the precautions taken to inhibit glycolysis and the time until analysis was conducted. The phlebotomy-analysis interval, for example, varied nationally from 2.25–24 hours compared with the recommended 30 minutes.
Significance for Clinical Care in Ireland
A previous study of the implementation of guidelines for gestational diabetes reported three-fold differences in GDM between units from 2.2%–7.4%, which raised the strong possibility that GDM is being under-diagnosed. The reported studies suggest that there is poor awareness of the importance of preventing glycolysis in maternal glucose samples. These wide variations in preananalytical standards nationally are potentially serious clinically and legally because if GDM is underdiagnosed, maternal hyperglycaemia may potentially lead to complications such as fetal macrosomia, shoulder dystocia and a brachial plexus injury.
Hence the UCD Centre for Human Reproduction group recommend that laboratory standards for maternal glucose analysis and preanalytical handling are implemented strictly in all settings. Particular care needs to be taken with the fasting plasma glucose for diagnostic purposes and the group proposes that future clinical studies of GDM should state their preanalytical as well as their analytical standards in the methods section of their reports.
Professor Michael Turner is UCD Professor of Obstetrics & Gynaecology and director at the UCD Centre for Human Reproduction and leads the HSE National Clinical Programme in Obstetrics & Gynaecology. Dr Niamh Daly is the UCD Special Lecturer in Obstetrics & Gynaecology and a clinical researcher within the UCD Centre for Human Reproduction, and this work forms part of her PhD studies. Dr Maria Farren and Dr Aoife McKeating are clinical researchers at the UCD Centre. Dr Ciara Carroll is currently an intern in gynaecology and along with Dr Iseult Flynn, currently working as a foundation year doctor in trauma and orthopaedics in Southampton general hospital, contributed to the research as medical students as part of the UCD Student Summer Research initiative. Dr Carroll won first prize (out of 120 submissions) for a recent presentation of the work at the National Junior Obstetrics and Gynaecology Society.
A national survey of preanalytical handling of oral glucose tolerance tests in pregnancy
Niamh Daly*, Iseult Flynn, Ciara Carroll, Maria Farren, Aofie McKeating, Michael J Turner. Clin Chem Lab Med. 2016 Jan 7. pii: /j/cclm.ahead-of-print/cclm-2015-1083/cclm-2015-1083.xml. doi: 10.1515/cclm-2015-1083. [Epub ahead of print]