96: Low pregnancy-associated plasma protein-A (PAPP-A) and elevated alpha-fetoprotein (AFP) – a bad combination?

Abstract

To evaluate the clinical significance of elevated AFP during the second trimester in those pregnancies with low first trimester PAPP-A. Retrospective cohort study of singleton gestations at a single tertiary care institution that underwent both a first trimester serum PAPP-A screen and a second trimester AFP screen between 2006 and 2008. Patients with fetal karyotype, neural tube or abdominal wall abnormalities and those that did not deliver at our institution were excluded. Two groups were identified: the study group which consisted of patients with both low PAPP-A (below the 10%ile for gestational age) and elevated maternal serum AFP (greater than 2.0 multiples of the median for gestational age) and the control group which included patients with low PAPP-A in combination with a normal AFP. Pregnancy outcomes were compared between the groups. Fisher′s exact test and Mann-Whitney U were used for comparison. 410 patients were identified. Mean maternal age was 33.3 years. 17 (4.1%) patients were found to have an elevated AFP. There were no differences between the groups with regards to maternal age, parity and use of assisted reproduction techniques. Compared to the control group, the combination of low PAPP-A and elevated AFP was associated with higher rates of small for gestational age neonates at birth (52.9% vs. 6.5%, p < 0.0001, RR 8.0) and an earlier median gestational age at delivery (34.6 weeks vs. 38.2 weeks, p= 0.04). When comparing the preterm births in each group, the study group had a higher rate of iatrogenic preterm delivery due to suspected fetal growth restriction (7/8 deliveries (87.5%) vs. 6/31 deliveries (19.3%), p = 0.0003) and fetal heart rate abnormalities (50% vs. 10.8%, p = 0.024). The combination of elevated AFP in women with low PAPP-A is associated with poor outcomes, particularly small for gestational age neonates and iatrogenic preterm birth. This combination of serum markers should prompt concern and be included in the counseling of patients with regards to the possibilities of clinical outcomes.