(117) Large-Scale Proteomics in Early Pregnancy and Timing of Diagnosis of Hypertensive Disorders of Pregnancy

Hypertensive disorders of pregnancy (HDP) may first develop antepartum, during labor, or postpartum, and whether these presentations represent a similar disease process remains uncertain. We utilized untargeted large-scale proteomics to identify pathways associated with HDP based on their timing of onset.

Study Design:

We used data and first-trimester plasma samples from the NuMoM2b-Heart Health Study, a multi-site prospective cohort that followed nulliparous pregnant individuals from the first trimester through pregnancy. We compared differential protein expression based on timing of onset of HDP (categorized as antepartum, intrapartum, postpartum) versus controls (referent) in a nested case-control design using SomaScan 7K platform. Associations of individual proteins with timing of onset of HDP, adjusted for co-variates (age, self-reported race as a social construct, insurance, body mass index, diabetes, fetal sex), were assessed using logistic regression q value-based false discovery rates. Pathway enrichment and differential expression analysis was conducted using Ingenuity Pathway Analysis.

Results:

Of 1628 individuals included, 678 had a HDP, of which 67.3% initially manifested antepartum (AP), 29.5% intrapartum (IP), and 1.4% postpartum (PP). After adjusting for co-variates, compared to controls, 698 proteins, 39 proteins, and 144 proteins were differentially expressed in those with HDP according to AP, IP, PP onset, respectively. There was little overlap in individual protein expression based on timing of HDP onset, with pathway enrichment analysis suggesting distinct processes. Ingenuity graphical summary noted downregulation of angiogenesis in AP HDP, downregulation of insulin-like growth factor regulation in IP HDP, and upregulation of fibroblast proliferation in PP HDP.

Conclusion:

There are differences in protein expression in early pregnancy compared to controls based on whether HDP first manifests in the AP, IP or PP period. This raises the possibility that there may be distinct mechanistic phenotypes that could uniquely inform diagnostic and therapeutic targets for HDP.