Background: Gestational diabetes mellitus (GDM) is one of the most common metabolic conditions during pregnancy, and may lead to increased risks of morbidity for both mother and fetus. Identification of women at risk for GDM is important to facilitate timely intervention and address potential high-risk status. Pregnancy-Associated Plasma Protein-A (PAPP-A) is a glycoprotein produced by the placental syncytiotrophoblast, that is important in trophoblastic invasion and the regulation of insulin-like growth factor (IGF). Lower maternal serum PAPP-A levels, typically measured in the first trimester for aneuploidy screening, have also been associated with predicting placental dysfunction and other metabolic complications including GDM. The purpose of this study was to assess the association between first-trimester maternal serum PAPP-A levels and development of GDM.
Materials and Methods: A prospective cohort study involving 220 pregnant women between 11-13?? weeks of gestation was performed at antenatal clinics. Serum PAPP-A was determined by time-resolved immunofluorometric assay and expressed as multiples of the median (MoM). All participants underwent the standard 75-g oral glucose tolerance test (OGTT) and were seen at 24-28 weeks of gestation. GDM was diagnosed using the criteria proposed by the International Association of Diabetes and Pregnancy Study Groups (IADPSG). Participants were divided into two groups: those who developed GDM (n = 58) and those who did not (n = 162). Statistical analyses included an independent t-test, chi-square test, Pearson correlation, and receiver operating characteristic (ROC) curve to investigate the predictive value of PAPP-A for GDM.
Results: The average PAPP-A level in the first trimester was significantly lower in women who developed gestational diabetes than in women who did not (0.58 ± 0.14 MoM vs. 0.91 ± 0.23 MoM; p < 0.001). There was a significant negative correlation between PAPP-A levels and fasting plasma glucose (r = -0.42; p < 0.01). ROC analysis indicated that a cutoff PAPP-A value of ?0.65 MoM predicted gestational diabetes with a sensitivity of 80% and specificity of 78% (AUC = 0.86, p < 0.001). Logistic regression suggested that low PAPP-A is an independent risk factor for gestational diabetes (adjusted OR = 3.94; 95% CI: 2.12-7.32; p < 0.001), after adjustment for maternal age, BMI and parity.
Conclusion: Low serum PAPP-A levels in the first trimester are significantly correlated with a higher risk of developing gestational diabetes mellitus (GDM). Thus, the PAPP-A measurement during conventional aneuploidy screening may provide an early risk biomarker for GDM and give time for risk-based screening and prevention efforts in the antenatal period. Incorporating biochemical markers such as PAPP-A with clinical risk factors may improve predictive models in early GDM risk prediction.
International Journal of Clinical Obstetrics and Gynaecology
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