Proteomic signatures during pregnancy: an exploratory cohort study of long-term health indicators

Abstract

Summary Background Pregnancies complicated by fetal growth restriction (FGR) and preeclampsia are associated with increased long-term chronic disease risk. A blood test could possibly identify those at risk, opening the door to early interventions soon after delivery. Prior work in non-pregnant people have identified protein signatures associated with 18 different health parameters, called SomaSignal Tests. Methods This study applied SomaSignal tests to plasma samples collected in pregnancy from two independent cohorts to assess the 18 health parameters in those who later developed FGR and preeclampsia. SomaScan Assay measured ∼7000 modified aptamers in plasma from two independent cohorts. Plasma samples (Melbourne, Australia) were collected at 36 weeks' gestation from women who later delivered an FGR infant (<3rd birthweight centile, n = 118), preeclampsia at term (n = 92) or did not develop either condition (n = 177). The second cohort (Cambridge, UK) were plasma samples collected at 36 weeks’ gestation from women who later delivered an FGR infant (n = 80), and those who did not (n = 172). Findings In the Australian cohort, women who later delivered growth-restricted infants had composite protein signatures associated with reduced cardiac function (p = 0.001), increased cardiovascular events (p = 7.6 × 10−6), mid-life dementia (p = 1.5 × 10−9), and higher visceral fat (p = 4.06 × 10−6), compared to pregnancies without complications. Findings were largely consistent in both Australian and UK sample sets. Those who developed preeclampsia had protein signatures signifying cardiovascular (p = 5.54 × 10−6), hepatic (p = 0.001), and renal (p = 0.0007) disease risks, compared to pregnancies without complications. Interpretation Since signatures were more pronounced in pregnancies that were later diagnosed with FGR and preeclampsia, underlying physiological changes may have been present before diagnosis. These changes result in protein signatures concordant with those associated with poor long-term health outcomes in non-pregnant populations. These associations require validation in large, longitudinal cohorts investigating pregnancy, with long-term maternal follow-up. Funding Stillbirth CRE, Mercy Hospital Foundation and National Health and Medical Research Council, Royal Australian and New Zealand College of Obstetricians and Gynaecologists, Taylor Hammond Scholarship, National Health and Medical Research Council Fellowships and Australian Research Council Future Fellowships.