(1195) Prior preeclampsia or chronic hypertension present distinct molecular subtypes in hypertensive disorders of pregnancy

Hypertensive disorders of pregnancy (HDP) are major causes of maternal and fetal morbidity and mortality. Previously, elevated PAPPA2 expression in cfRNA was identified as predictive of preeclampsia (PE) in a dose-dependent manner, with an exceptionally strong effect size among individuals without pre-existing high risk factors. Here we evaluate PAPPA2 expression based on HDP and gestational age (GA) at delivery in those with chronic hypertension (CHTN) or prior PE.

Study Design:
Whole blood and medical information were collected from a diverse group of 5,399 study participants collected across 11 clinical sites and direct-to-participant recruitment. Spontaneous preterm births were excluded. cfRNA was extracted and analyzed by sequencing to generate gene counts. Robust linear regression evaluated PAPPA2 dependence on delivery GA by preterm PE status.

Results:
In individuals with chronic hypertension there was no significant correlation between PAPPA2 expression level and gestational age at delivery regardless of the occurrence of either preterm PE (n=27, R2=2.8%, p=0.4, Fig1) or a pregnancy where preterm PE did not occur (n=281, R2=0%, p=0.85, Fig1). However in individuals with a history of PE, a significant correlation with PAPPA2 was observed in those who developed preterm PE (n=29, R2=16.6%, p=0.028, Fig1), but in those who did not develop preterm PE the relationship was not significant (n=249, R2=1.1%, p=0.09, Fig1). This is similar to the previously reported effect among individuals without independent high risk conditions who develop preterm PE (n=87, R2=12.2%, p< 0.001, Fig1).

Conclusion:
The molecular patterns observed for PAPPA2 in individuals without pre-existing risk is replicated in individuals with prior PE who go on to have repeated PE. The molecular pattern is different in superimposed PE where no elevation in PAPPA2 was observed. These findings support multiple etiologies of HDP and the potential for personalized treatments paths in the future.