Molecular profiles of the great obstetrical syndromes reveal common features and dynamic changes in early pregnancy

The great obstetrical syndromes (GOS) encompass a spectrum of pregnancy-related complications that are the major determinants of maternal and neonatal mortality. Although shared placental pathology underlies these complications, knowledge of the molecular commonalities before clinical presentation remains incomplete.

In this case-control study nested within the prospective Shanghai Birth Cohort, we investigated the molecular characteristics underlying GOS conditions in the pre-symptomatic phase using serum samples from 203 nulliparas who subsequently developed GOS and 181 controls. A multi-omics approach combining protein, metabolite, and gene analysis was employed.

Here we show a shared molecular background of the spectrum of all tested GOS conditions at the co-expression module, molecule, pathway, multi-omics network and genome levels. In early pregnancy, one protein module mainly involved in the immune system and platelet function shows significant associations across the spectrum of tested GOS conditions. Different conditions share several hub proteins and enriched pathways in the innate immune system and platelet activation, signaling and aggregation. Common molecular changes could be observed before 14 weeks of gestation. Different groups of hub proteins demonstrate the potential to differentiate between normal and complicated pregnancies before and after 14 weeks of gestation.

We highlight the shared molecular signatures among different GOS conditions in the pre-symptomatic phase, suggesting the potential of a common screening and intervention strategy. Our results further support the notion that the prevention of GOS should start at 14 weeks of gestation or earlier, when the molecular signature changes have already emerged.