Transcriptomic analysis delineates preterm prelabor rupture of membranes from preterm labor in preterm fetal membranes.

BACKGROUND: Globally, preterm birth remains the leading cause of death in children younger than 5 years old. Spontaneous preterm birth is comprised of two events that may or may not occur simultaneously: preterm labor and preterm prelabor rupture of membranes (PPROM). To further explore the concept that spontaneous preterm birth can result from the initializing of two separate but overlapping pathological events, we compared fetal membrane tissue from preterm labor deliveries to fetal tissue from preterm labor with PPROM deliveries. We hypothesized that the fetal membrane tissue from preterm labor with PPROM cases will have an RNA-seq profile divergent from the fetal membrane tissue from preterm labor controls. METHODS: Chorioamnion, separated into amnion and chorion, was collected from eight gestationally age-matched cases and controls within 15 min of birth, and analyzed using RNA sequencing. Pathway enrichment analyses and functional annotations of differentially expressed genes were performed using KEGG and Gene Ontogeny Pathway enrichment analyses. RESULTS: A total of 1466 genes were differentially expressed in the amnion, and 484 genes were differentially expressed in the chorion (log2 fold change > 1, FDR < 0.05) in cases (preterm labor with PPROM), versus controls (preterm labor only). In the amnion, the most significantly enriched (FDR < 0.01) KEGG pathway among down-regulated genes was the extracellular matrix receptor interaction pathway. Seven of the most significantly enriched pathways were comprised of multiple genes from the COL family, including COL1A, COL3A1, COL4A4, and COL4A6. In the chorion, the most significantly enriched KEGG pathways in up-regulated genes were chemokine, NOD receptor, Toll-like receptor, and cytokine-cytokine receptor signaling pathways. Similarly, KEGG pathway enrichment analysis for up-regulated genes in the amnion included three inflammatory pathways: cytokine-cytokine interaction, TNF signaling and the CXCL family. Six genes were significantly up regulated in chorionic tissue discriminated between cases (preterm labor with PPROM) and controls (preterm labor only) including GBP5, CXCL9, ALPL, S100A8, CASP5 and MMP25. CONCLUSIONS: In our study, transcriptome analysis of preterm fetal membranes revealed distinct differentially expressed genes for PPROM, separate from preterm labor. This study is the first to report transcriptome data that reflects the individual pathophysiology of amnion and chorion tissue from PPROM deliveries.

Association of Maternal Versus Fetal Ehlers-Danlos Syndrome Status with Poor Pregnancy Outcomes.

The majority of research papers published on obstetrical outcomes in Ehlers-Danlos syndrome (EDS) have focused on the contribution of maternal EDS to the risk of poor pregnancy outcomes. The purpose of our study was to further clarify the fetal versus maternal contribution of EDS to poor pregnancy outcomes. A web-based, anonymous questionnaire was developed to collect pregnancy histories of families with a member with EDS. The survey was disseminated via social media through the Ehlers Danlos National Foundation. Population descriptors (age, gender, EDS diagnosis, age of diagnosis) and pregnancy descriptors (number of pregnancies, live births, and birth complications) were collected. To identify fetal and maternal contribution of EDS to poor pregnancy outcomes, three groups were compared based on maternal or infant diagnosis (EDS versus non-EDS). The rate of birth complications, treatment for preterm birth, and occurrence of preterm birth, as well as gestational age at preterm birth, were different depending on maternal/ infant EDS status, and these differences were significant when comparing infant EDS status but not when comparing maternal EDS status. The occurrence of PPROM is increased in the non-EDS mother/EDS infant group compared to both EDS mother/non-EDS infant and EDS mother/EDS infant groups (38.9%, 12.5%, 14.8%, p = 0.025). This study identifies that poor outcomes in EDS pregnancies differ depending on the maternal and the fetal EDS status. These insights into maternal and fetal association with certain poor pregnancy outcomes in pregnancies complicated by EDS can further guide physicians in educating, managing, and treating these women during pregnancy.

End-of-life care in a regional level IV neonatal intensive care unit after implementation of a palliative care initiative.

OBJECTIVE: We hypothesized that the implementation of a neonatal palliative care initiative will result in improved markers of end-of-life care. STUDY DESIGN: A retrospective and prospective chart review of neonatal intensive care unit deaths was performed for 24 months before, 16 months during and 24 months after the implementation of palliative care provider education and practice guidelines (n=106). Ancillary care, redirection of care, palliative medication usage and outcome meetings in the last 48 h of life and basic demographic data were compared between epochs. Parametric and nonparametric analysis was performed. RESULT: There was an increase in redirection of care and palliative medication usage and a decrease in variability of use of end-of-life interventions (P=0.012, 0.022 and <0.001). CONCLUSION: The implementation of a neonatal palliative care initiative was associated with increases in palliative interventions for neonates in their final 48 h of life, suggesting that such an initiative may enhance end-of-life care.