Low levels of maternal serum PAPP-A in early pregnancy and the risk of adverse outcomes

Objectives To determine if low maternal serum level of pregnancy associated plasma protein A (PAPP-A) measured in early pregnancy can predict adverse pregnancy outcomes and to examine the gestational age (GA) sampling interval for these outcomes. Methods This was a nested case-control study from a prospective cohort of women recruited at <20 weeks of gestation in Halifax, NS. Cases (n = 248) were defined as women who had a fetal loss or developed preeclampsia, severe pregnancy-induced hypertension (PIH), or small for gestational age infant (SGA). Controls (n = 244) were frequency matched to cases by GA at the time of serum sampling (6 to <20 weeks GA). Participant information was obtained from questionnaires and medical chart reviews. Results Women with a low PAPP-A measure [≤0.4 multiples of the median (MoM)] had an adjusted odds ratio of 2.1 [95% confidence interval (CI) 1.3-3.6] compared to others (>0.4 MoM). However, performance as a screening test was poor [sensitivity = 38.7%; specificity = 81.6%; positive likelihood ratio (LR) = 2.1; negative LR = 0.75]. In the adjusted model, the 10- to 14-week GA period was the only time period where low PAPP-A was significantly associated with adverse outcomes. Conclusions Women with a low PAPP-A early in their pregnancy have twice the risk of an adverse outcome, though PAPP-A as a one-time single marker test has limited value.