Maternal morbidity and mortality continue to rise, and pre-eclampsia is a major driver of this burden1. Yet the ability to assess underlying pathophysiology before clinical presentation to enable identification of pregnancies at risk remains elusive. Here we demonstrate the ability of plasma cell-free RNA (cfRNA) to reveal patterns of normal pregnancy progression and determine the risk of developing pre-eclampsia months before clinical presentation. Our results centre on comprehensive transcriptome data from eight independent prospectively collected cohorts comprising 1,840 racially diverse pregnancies and retrospective analysis of 2,539 banked plasma samples. The pre-eclampsia data include 524 samples (72 cases and 452 non-cases) from two diverse independent cohorts collected 14.5 weeks (s.d., 4.5 weeks) before delivery. We show that cfRNA signatures from a single blood draw can track pregnancy progression at the placental, maternal and fetal levels and can robustly predict pre-eclampsia, with a sensitivity of 75% and a positive predictive value of 32.3% (s.d., 3%), which is superior to the state-of-the-art method2. cfRNA signatures of normal pregnancy progression and pre-eclampsia are independent of clinical factors, such as maternal age, body mass index and race, which cumulatively account for less than 1% of model variance. Further, the cfRNA signature for pre-eclampsia contains gene features linked to biological processes implicated in the underlying pathophysiology of pre-eclampsia.

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Background Click-evoked auditory brainstem response (ABR) alterations are associated with autism spectrum disorder (ASD), but the specificity of these findings to the disorder are unclear. We therefore performed a meta-analysis on ABRs and attention deficit/hyperactivity disorder (ADHD), a neurodevelopmental disorder that shares some etiologic and symptom overlap with ASD. Method Seven papers compared ABR latency components (I, III, V, I–III, III–V, I–V) between participants with and without ADHD. We used random-effects regression to generate component-specific estimates (Hedges’ g ) that adjusted for study sample sizes and the number of studies contributing to each estimate. We compared these estimates to our recently published meta-analysis of ABRs and ASD. Results All ADHD studies employed cross-sectional designs. ADHD was associated with longer latencies for Waves III and V ( g =0.6, 95%CI 0.3,1.0 and g =0.6, 95%CI 0.2,0.9) and Waves I–III and I–V ( g =0.7, 95%CI 0.2, 1.3 and g =0.6, 95%CI 0.3, 1.0). Effect sizes from the ASD and ADHD meta-analyses did not differ from each other. Conclusion Similar patterns of ABR alterations are observed in ADHD and ASD. However, studies rarely screen for middle ear dysfunction or hearing loss and rely upon cross-sectional designs. Addressing these issues will inform the viability of ABRs as a prognostic and/or etiologic biomarker for these disorders.