BACKGROUND: First trimester maternal serum PAPP-A is used to assess the risk of fetal chromosomal abnormalities. More recently, lower PAPP-A has been linked to the development of gestational diabetes (GDM). In other studies, higher PAPP-A is associated with increased birthweight. The exact relationship between maternal diabetes, PAPP-A and birthweight is unknown. AIMS: To examine the relationship between PAPP-A and GDM or pregestational diabetes, and between PAPP-A and birthweight. METHODS: We prospectively measured serum PAPP-A in 1382 women presenting for their nuchal translucency scan from July 2009-July 2011 at our institution. Pregnancy outcomes were obtained through the statewide Obstetrix database. Another 305 women with pregestational or gestational diabetes who attended the diabetes clinic in the same antenatal service between August 2007 and December 2012 were added to the database. RESULTS: There were 1282 women without diabetes, 364 with GDM, 23 with T1D and 18 with T2D. Lower PAPP-A was independently associated with GDM and T2D. GDM was associated with an 8.5% (CI 15.4, 1.6%) (p=0.016) decrease and T2D with a 36.8% (CI 63.6, 10.0%) (p=0.007) decrease in PAPP-A MoM. Conversely, higher PAPP-A was associated with a higher birthweight. In a multivariate model, women with the highest PAPP-A quartile had an OR of 2.1 (CI 1.3-2.3) for a LGA baby (p=0.001), with babies that were 129g (CI 74, 185g) (p<0.001) heavier than the lowest quartile. PAPP-A and pregestational diabetes were independent predictors of birthweight. CONCLUSION: Maternal PAPP-A at the time of nuchal translucency screening is independently associated with diabetes status and baby size. This may reflect placental function as well as the underlying metabolic milieu. Further evaluation should determine if PAPP-A can help identify pregnancies at risk of either GDM or LGA.