The use of early pregnancy HbA1c in predicting excessive fetal growth
Research type
Research Study
Full title
The use of early pregnancy HbA1c in predicting excessive fetal growth in women at risk of glucose intolerance
IRAS ID
223162
Contact name
Una Graham
Contact email
Sponsor organisation
Belfast Health and Social Care Trust
Duration of Study in the UK
3 years, 0 months, 3 days
Research summary
Summary of Research
High blood sugars in the mother during pregnancy (gestational diabetes mellitus; GDM) are clearly associated with adverse outcomes for mother and baby. A major harmful effect is excessive fetal weight gain. This can result in complications during pregnancy, and predicts an increased future risk of diabetes and obesity in the offspring. These complications are reduced with interventions to reduce blood sugars. Traditionally, screening for GDM takes place between 24-28 weeks gestation. However, by this stage, babies of mothers with newly diagnosed GDM already have a two-fold risk of excessive abdominal weight gain due to unrecognised high blood sugars in the mother. We know that about 25% of women will develop GDM before 20 weeks; up to eight weeks before it is traditionally diagnosed. It is unknown whether screening for GDM in the first trimester would allow more timely diagnosis and more effective intervention. To examine this question we propose a prospective cohort study of 3,500 women at high risk of GDM to determine if elevated HbA1c (41-48mmol/mol) in early pregnancy (<14 weeks) identifies (1) babies at risk of excessive weight gain (as determined by ultrasound measurement) and (2) mothers who will later develop GDM (as determined by a gold standard oral glucose tolerance test; OGTT) at 28 weeks gestation. HbA1c is a low cost, non-fasting blood test used for diagnosis of diabetes in individuals outside of pregnancy. Participants will be recruited at their booking visit with blood sampling for HbA1c. They will attend for an OGTT and fetal ultrasound scanning at 28 weeks. Given the increasing prevalence of GDM (over 20% in some populations), and the association of GDM with future type 2 diabetes and childhood obesity this is an area of great clinical importance, and the results, if positive, will impact upon patient care almost immediately following study completion.
Summary of Results
186 women (19.6%) screened positive for GDM. At the time of OGTT, pregnancies complicated by GDM already demonstrated higher adjusted fetal weight percentile than non-GDM pregnancies: (50.9 ±26.6 (mean ± SD) vs 46.2 ±25.7 p=0.02). This was driven by relative increases in the fetal abdominal circumference percentile in GDM compared with non-GDM pregnancies (54.7 ±24.8 vs 46.2 ±23.0 p=<0.01).
Early pregnancy HbA1c was higher in the GDM vs non-GDM group: 35.8 ±4.7 vs 32.9
±3.8 p=<0.01. A threshold for predicting excessive fetal growth was not identified in this cohort.
Of the 122 women in the nested observational study, 26 (21.3%) developed GDM.
Women with GDM had a significantly higher VAD compared with those without GDM (4.22 ±0.97cm vs 3.12 ±1.33cm p<0.01). Using receiver operator characteristic
(ROC) curve analysis, a VAD of 3.98cm achieved a sensitivity of 73.1% and specificity of 72.2% for the later diagnosis of GDM in this cohort. Women exceeding this threshold were at seven-fold greater odds of later GDM diagnosis (Odds Ratio 7.3).
The use of this VAD threshold in this cohort increased PPV to 42.2% with a NPV of 90.9%REC name
Yorkshire & The Humber - Sheffield Research Ethics Committee
REC reference
17/YH/0207
Date of REC Opinion
22 Jun 2017
REC opinion
Favourable Opinion