423: Functional genomic analysis of TTTS recipient amniotic fluid supernatant reveals major alterations in nervous and cardiovascular system gene expression

Abstract

amniotic fluid supernatant reveals major alterations in nervous and cardiovascular system gene expression LISA HUI, Heather Wick, Kenneth Moise, Anthony Johnson, Michael Belfort, Kirby Johnson, Diana Bianchi Tufts Medical Center, Mother Infant Research Institute, Boston, MA, Tufts University, Computer Science, Medford, MA, Baylor College of Medicine, Obstetrics and Gynecology, Houston, TX OBJECTIVE: To understand the molecular mechanisms underlying the recipient’s response to twin-twin transfusion syndrome (TTTS) and develop fetal biomarkers by performing functional genomic analysis of amniotic fluid supernatant (AFS). STUDY DESIGN: We have previously shown that AFS contains RNA from multiple fetal organs, including brain. This was a prospective study analyzing cell-free RNA transcripts in recipient AFS from women undergoing clinically-indicated laser surgery. Normal AFS was obtained from singleton fetuses undergoing genetic amniocentesis. The independent t test with the Benjamini-Hochberg correction was used to evaluate up-regulated genes in TTTS vs normal controls, and Quintero Stage III vs stage II cases. Functional analyses of the significantly up-regulated genes were performed with Ingenuity software. RESULTS: AFS samples from 8 recipient twins (4 Stage II and 4 Stage III, EGA 17-21 w) and 4 euploid controls (EGA 17-22 w) were included. Compared with controls, 811 genes were significantly upregulated in TTTS cases. The most statistically significant biological process that differed between cases and controls was nervous system development and function. There were 19 up-regulated nervous system genes in TTTS cases including microtubule-associated protein tau, a biomarker of adult neurodegeneration. Other important upregulated transcripts in TTTS were vascular endothelial growth factor 1 and angiotensin II receptor type 2. The most statistically significant up-regulated biological process in Stage III vs Stage II fetuses was cardiovascular disease. Among the 58 cardiovascular disease genes up-regulated in Stage III recipients were some specifically associated with hypertension and left ventricular dysfunction (TRPC4) and congenital pulmonary stenosis (NTRK3). CONCLUSION: Our study provides novel molecular evidence of the impact of TTTS on the developing nervous system. We also identified the cardiovascular genes specifically associated with Stage III vs Stage II disease. These results further our understanding of the pathophysiology of TTTS and provide potential prognostic fetal biomarkers. 424 Gender equality in fetal reduction (FR) patient decision preferences: major cultural change in the USA Mara Rosner, Stephanie Andriole, Avishai Alkalay, Rachel Greenbaum, Juliana Gebb, Mark Evans Montefiore Medical Center/Albert Einstein College of Medicine, Obstetrics & Gynecology and Women’s Health, Bronx, NY, Comprehensive Genetics, Genetic Counseling, New York, NY, Albert Einstein College of Medicine/ Montefiore Medical Center, Obstetrics and Gynecology & Women’s Health, Bronx, NY, Comprehensive Genetics, Ultrasound, New York, NY, Comprehensive Genetics & Mt. Sinai School of Medicine, Obstetrics & Gynecology, New York, NY OBJECTIVE: 20 years ago, a disproportionate % of gender preference requests for prenatal diagnosis, terminations, and reductions were from patients of ethnic groups that valued boys over girls. We refused to participate. As patient interest expanded to all ethnic groups and gender preference seemed to equalize, our bioethicist had us re-evaluate and incorporate patient preference. STUDY DESIGN: We prioritize FR decisions by: 1. documented major (M) anomaly; 2. suspicious or minor (m) findings; 3. if neither, we consider gender preference. We retrospectively reviewed patient choices in our last 400 CVS/FR cases starting with triplets or twins. Patients were categorized based on type of reduction (3i2, 3i1, or 2i1), presence or absence of M or m findings, and whether all fetuses were the same gender (SG) or a gender choice was possible. Higher order and non-CVS pregnancies were excluded. RESULTS: 178/321 (56%) had either M/m or SG. Of 3i2 with option, 71/79 reduced to M/F of which about 1/3rd had no preference. 1 chose MM and 7 chose FF. Most 3i1 included MZ twins for whom we reduced MZ in 33/35 cases. Of 20 3i1 with option, 10 chose M and 10 chose F. Of 44 2i1 with option, 20 chose M & 24 chose F. CONCLUSION: There has been a major shift in culture from a generation ago. Male preponderance has ended in the USA. The vast majority of our patients who reduced to 2 preferred one of each or had no preference. When reducing to 1, a non-significant trend towards female preference was found. In addition to identifying abnormalities, CVS prior to FR expands patient autonomy. Poster Session III Doppler Assessment, Fetus, Prematurity www.AJOG.org