ABSTRACT
BACKGROUND: Stillbirth impacts 1% of all pregnancies in the USA with the underlying cause often remaining unknown. The objective of this study was to identify if prenatal aneuploidy screening impacted patient agreement to stillbirth evaluation. METHODS: We performed a retrospective cohort study of patients with a singleton stillbirth after 20 weeks of gestation between October 2017 and December 2021. Demographics and stillbirth evaluation were collected for all patients. Multivariable logistic regression was performed adjusting for variables that were significant in univariate analysis. RESULTS: A total of 81 persons experienced stillbirth during the study period. Approximately 59.3% of patients had prenatal aneuploidy screening: 39.5% integrated screening, 37.5% non-invasive prenatal testing (NIPT), and 22.9% quad screen. Prenatal genetic screening did not significantly impact patient agreement to placental pathology, serum laboratory evaluation, or fetal autopsy. Patients with NIPT were less likely to have genetic testing sent at the time of stillbirth compared to those with another aneuploidy screening (aOR 0.27, 95% CI 0.07-0.99). CONCLUSIONS: Prenatal aneuploidy screening was not associated with patient acceptance of stillbirth evaluation. However, patients with NIPT were less likely to pursue further genetic testing during stillbirth evaluation, so further education regarding the benefit of karyotype and microarray should be included in patient counseling.
ABSTRACT
This study explores the hypothesis that protein hormones are nested information systems in which initial products of gene transcription, and their subsequent protein fragments, before and after secretion and initial target cell action, play additional physiological regulatory roles. The study produced four tools and key results: (1) a problem approach that proceeds, with examples and suggestions for in vivo organismal functional tests for peptide-protein interactions, from proteolytic breakdown prediction to models of hormone fragment modulation of protein-protein binding motifs in unrelated proteins; (2) a catalog of 461 known soluble human protein hormones and their predicted fragmentation patterns; (3) an analysis of the predicted proteolytic patterns of the canonical protein hormone transcripts demonstrating near-universal persistence of 9 ± 7 peptides of 8 ± 8 amino acids even after cleavage with 24 proteases from four protease classes; and (4) a coincidence analysis of the predicted proteolysis locations and the 1939 exon junctions within the transcripts that shows an excess (P < 0.001) of predicted proteolysis within 10 residues, especially at the exonal junction (P < 0.01). It appears all protein hormone transcripts generate multiple fragments the size of peptide hormones or protein-protein binding domains that may alter intracellular or extracellular functions by acting as modulators of metabolic enzymes, transduction factors, protein binding proteins, or hormone receptors. High proteolytic frequency at exonal junctions suggests proteolysis has evolved, as a complement to gene exon fusion, to extract structures or functions within single exons or protein segments to simplify the genome by discarding archaic one-exon genes.
