PAPP-A and HbA1c in first trimester and Gestational Diabetes

• Research type

  Research Study

• Full title

  Prediction of Gestational Diabetes by measuring serum pregnancy associated protein-A (PAPP-A) and HbA1c in the first trimester of pregnancy

• IRAS ID

  332778

• Contact name

  Emily Leach

• Contact email

  emily.leach@nnuh.nhs.uk

• Sponsor organisation

  Norfolk and Norwich University Hospital

• Duration of Study in the UK

  0 years, 5 months, 3 days

• Research summary

  Research Summary:
  Glossary of terms
  Gestation - the time between conception and birth.
  Glycosuria - glucose (sugar) in urine.
  PAPP-A - Pregnancy associated plasma protein-A.
  

  This is a retrospective cohort study. First trimester and 24-28-week data related to pregnant women will be retrieved from the Laboratory Information Management System (LIMS) and Lifecycle database at the Norfolk and Norwich University Hospital (NNUH). A logistic model will be used to analyse the association between first trimester PAPP-A and HbA1c and subsequent glucose tolerance test results or Glucose and HbA1c performed between 24-28 weeks’ gestation.

  Only pregnant women with the following risk factors were offered first trimester HbA1c and follow up oral glucose tolerance test (OGTT) at between 24 and 28 weeks’ gestation:
  • Susceptible ethnic group
  • An episode of glycosuria
  • A previous baby weighing over 4.5kg
  • A body mass index (BMI) of over 30 (clinically obese)
  • A family history of diabetes

  Only pregnant women with one or more of the above risk factors, within the ‘at risk of GDM’ group, will be included in this study. Pregnant women with pre-existing diabetes type 1 or type 2 will be excluded from the data analysed.
  The patients will be split into two groups, those with low PAPP-A (less than 0.4 MoM) will be defined as the ‘exposure group’ and those with ‘normal’ PAPP-As will be defined as the ‘non-exposure group. HbA1c and OGTT results will be compared in the two groups to determine if patients with low PAPP-A have increased HbA1c at booking and if they have increased risk of GDM.

  The objectives of the project are as follows:

  Primary objectives

  • To determine if pregnant patients with low PAPP-A between 11-14 weeks’ gestation have an increased risk of developing GDM.

  • To determine if there is a correlation between first trimester PAPP-A results and first trimester HbA1c results.

  Lay summary of study results:
  Study Title: Prediction of Gestational Diabetes by measuring serum pregnancy associated protein-A (PAPP-A) and HbA1c in the first trimester of pregnancy

  Objective
  This study aimed to investigate the association between maternal first trimester PAPP-A and HbA1c measurements and subsequent gestational diabetes mellitus (GDM) development in high-risk pregnant women.

  Method
  This retrospective cohort study assessed the patient data on 120 pregnant women who attended routine prenatal care from January to November 2023. All pregnant women included in the study were defined as high risk for gestational diabetes (GDM) based on the following criteria: body mass index (BMI) above 30 kg/m2, previous macrosomic baby weighing 4.5 kg or more, previous gestational diabetes, family history of diabetes or an ethnicity with a high prevalence of diabetes. Pregnancy associated plasma protein-A (PAPP-A) was measured as part of the first trimester aneuploidy screening and was converted to multiples-of-median (MoM) values. It is standard practice to express PAPP-A values as MoM, which gives a measure of how far a result deviates from the median, where 1.0 is the median. HbA1c was also measured in the first trimester between 11+2 and 14+1 weeks of pregnancy. In the second trimester, between 24 and 28 weeks of pregnancy, study participants underwent a 2-hour 75g oral glucose tolerance test (OGTT). OGTT is a testing procedure used to diagnose GDM and is the standard method of diagnosis according to NICE guidelines. Pregnant women were divided into two groups, based on the serum concentration on PAPP-A. The normal group had PAPP-A > 0.5 MoM and the low PAPP-A group had PAPP-A < 0.4 MoM. PAPP-A, HbA1c and OGTT data were collected and analysed with appropriate statistical tests.
  Results
  Of the 120 pregnant women, 16 (13.4%) developed GDM. There was no significant difference in PAPP-A measurement in GDM pregnancies and non-GDM pregnancies. However, the calculated odds ratio indicated that women in the low PAPP-A group had 2.9 times the odds of developing GDM than the women in the normal PAPP-A group, though this was found not to be statistically significant. Sensitivity of low PAPP-A (<0.4) was calculated to have 63% sensitivity, 52% specificity, 17% PPV and 90% NPV. Positive likelihood ratio was 1.30 and negative likelihood ratio was 0.72. ROC analysis revealed that PAPP-A measurement in this study was unable to distinguish between GDM and non-GDM pregnancies. Spearman’s rank correlation showed that there was no correlation between first trimester HbA1c and first trimester PAPP-A. Finally, there was no significant difference in first trimester HbA1c measurement in GDM and non-GDM pregnancies. ROC curve analysis revealed HbA1c to be a poor predictor of GDM in this study.

  Conclusion
  In this study low maternal PAPP-A in first trimester did not significantly increase risk of GDM. There was no significant correlation between first trimester PAPP-A and HbA1c. Finally, there was no significant association found between raised HbA1c in first trimester and GDM. Based on the findings of this study, neither PAPP-A nor HbA1c alone are reliable predictors of GDM. Further work needs to be done to determine if used in conjunction with existing risk prediction methods, both PAPP-A and HbA1c may have a role in predicting risk within risk prediction models.

• REC name

  London - West London & GTAC Research Ethics Committee

• REC reference

  23/PR/1218

• Date of REC Opinion

  26 Oct 2023

• REC opinion

  Favourable Opinion