(334) Is there clinical utility of PAPP-A in the age of cell free DNA?

SMFM recommends against performing first trimester screen(FTS) with cell free DNA(cfDNA). However PAPP-A<0.4 multiples of the mean(MoM) has been associated with adverse perinatal outcomes. We aimed to prove there was additional clinical utility of analytes, specifically PAPP-A, in FTS. We hypothesized that FTS+cfDNA, compared to NT+cfDNA, would increase sensitivity to detect adverse outcomes, guide aspirin initiation, and thus decrease rates of adverse maternal outcomes such as preeclampsia and placental abruption.

Study Design:

This was a prospective observational cohort study comparing patients at 2 hospitals from 2021-2022. Site 1 received NT+cfDNA, while site 2 received FTS+cfDNA or NT+cfDNA. Those with PAPP-A<0.4 were recommended aspirin and fetal surveillance. Demographics, aspirin use, and outcomes were reviewed. The McNemar test was performed on FTS+cfDNA group to determine additional sensitivity that PAPP-A<0.4 had to detect adverse outcomes, while adjusting for treatment.

Results:

FTS+cfDNA was sent on 688 and NT+cfDNA on 701 patients. In the FTS+cfDNA group patients were older, lower BMI, predominantly White, more in vitro fertilization(IVF), less hypertension, more nulliparous, and less publicly insured compared to NT+cfDNA group (p< 0.01). After adjusting for hypothetical proportions of prevented outcomes with the McNemar test in FTS+cfDNA group, PAPP-A added additional sensitivity to detect adverse maternal outcomes compared to only NT+cfDNA(Table 1). 78% PAPP-A<0.4 took aspirin compared to 33% of those recommended aspirin for ACOG risk factors. Adverse maternal outcomes were similar between FTS +cfDNA group and NT+cfDNA group (10.6% vs 11.8%, p=0.46).

Conclusion:

Our data suggests PAPP-A has additional sensitivity to detect adverse maternal outcomes and increases aspirin compliance. Though we anticipated decreased adverse outcomes in the FTS+cfDNA group, it is possible that differing group demographics lead to similar rates of adverse maternal outcomes. As preeclampsia causes maternal and fetal morbidity, all known noninvasive interventions to increase detection should be considered.