Maternal Diabetes, Large-for-Gestational-Age Births, and First Trimester Pregnancy-Associated Plasma Protein-A

Context: Maternal pregnancy-associated plasma protein-A (PAPP-A) is measured at nuchal translucency scanning to assess the risk of fetal chromosomal disorders. Objective: The aim of this study was to examine whether PAPP-A might also be a predictor of gestational diabetes (GDM), type 2 diabetes (T2D), or large-for-gestational-age (LGA) births. Design: PAPP-A levels were measured in serum from 1664 women at their 10-14-week nuchal translucency scan at a tertiary referral hospital. Maternal diabetes was categorized as T2D, early GDM (GDM diagnosed < 22 wk), and late GDM (GDM diagnosed >= 22 wk). The relationship between PAPP-A multiples of the median (MoM), maternal diabetes, and LGA was examined with multivariate regression models. Results: PAPP-AMoM was significantly lower in women with T2D and women who developed GDM than in nondiabetic women. PAPP-AMoM was 41.3% lower in T2D, 22.6% lower in early GDM, and 8.6% lower in late GDM. Women in the lowest quartile of PAPP-AMoM were 2.7 times more likely to have early GDM(odds ratio [OR], 2.74; 95% confidence interval [CI], 1.2-6.1) compared with the highest quartile. Birth weight had a positive linear association with PAPP-A MoM. Women in the highest PAPP-AMoM quartile were twice as likely to have an LGA baby (OR, 2.2; 95% CI, 1.39-3.46; P = .0007). Conclusions: Routinely tested first-trimester PAPP-A is a novel biomarker for maternal diabetes and LGA. PAPP-A decreased with increasing severity of maternal diabetes. Although this cannot infer causality, low PAPP-A may help identify women at risk of GDM, and high PAPP-A may help identify pregnancies at risk of LGA.