Fanconi Anemia Type C: Results of Population Carrier Testing [2A]

INTRODUCTION:Fanconi Anemia Type C (FAC) is an autosomal recessive disorder characterized by skeletal malformations, bone marrow failure, increased risk of malignancy, and severe aplastic anemia. Currently, carrier testing for FAC is recommended for the Ashkenazi Jewish (AJ) population. A joint ACOG/ACMG statement highlighted the increasingly multi-ethnic society as consideration for pan-ethnic carrier testing, and recent ACOG committee opinion states that pan-ethnic testing is a reasonable strategy. Our current study assesses how many non-AJ individuals screened positive for FAC when pan-ethnic carrier testing was implemented. METHODS:Retrospective database analysis of individuals that received expanded carrier testing utilizing a genotyping panel for three pathologic variants of FAC (c.322delG, IVS4 c.456(+4)A>T, p.R548X) was performed. Expected number of positive carriers in AJ and non-AJ groups were calculated and compared to observed rates. Chi-square analysis was performed to assess for statistical significance (p < 0.01). RESULTS:A total of 71,235 individuals were tested for FAC. A higher than expected number of non-AJ individuals tested positive for FAC (56 observed vs 8.89 expected, p<0.001). The number of AJ individuals that screened positive was consistent with expected values (10 observed vs 11.11 expected, p<0.73). CONCLUSION:Non-AJ carriers of FAC were more common than expected in this cohort. Pan-ethnic expanded carrier testing will increase the detection of carriers for FAC compared with current ethnicity based screening recommendations. Importantly, carriers of FAC who would be missed by ethnicity based testing convention, will be identified allowing for more complete genetic counseling and family planning options for those who choose testing

Tay-Sachs: An Ashkenazi Jewish Disease or Not? [26E]

INTRODUCTION:Tay-Sachs disease (TSD) is an autosomal recessive disorder characterized by progressive neurodegeneration leading to total incapacitation and death by age four. Currently, carrier testing for TSD is recommended for the Ashkenazi Jewish (AJ) population. A joint ACOG/ACMG statement highlighted the increasingly multi-ethnic society as consideration for pan-ethnic carrier testing, and recent ACOG committee opinion states that pan-ethnic carrier testing is a reasonable strategy. This study assesses how many non-AJ Caucasian individuals screened positive for TSD when pan-ethnic carrier screening was implemented. METHODS:Retrospective database analysis of individuals that received expanded carrier testing utilizing a genotyping panel for nine pathologic variants of TSD (1278+TATC, IVS12+1G>C, IVS7+1G>A, IVS9+1G>A, p.G269S, p.R178H, p.R247W, P.R249W, del7.6kb). Expected number of positive carriers for TSD in AJ and Caucasian groups were calculated and compared to observed rates. Chi-square analysis was performed to assess for statistical significance (p < 0.01). RESULTS:A total of 71,829 individuals were tested for TSD. A higher than expected number of Caucasian individuals screened positive for TSD (110 observed vs 58.48 expected, p<0.001). The number of AJ individuals that screened positive was consistent with expected values (33 observed vs 31.14 expected, p<0.88). CONCLUSION:Caucasian carriers of TSD were more common than expected in this cohort. Pan-ethnic expanded carrier testing will increase the detection of carriers for TSD compared with current ethnicity based screening recommendations. Importantly, carriers of TSD, who would be missed by ethnicity based testing convention, will be identified allowing for more complete genetic counseling and family planning options for those who choose testing

Familial Dysautonomia: Rare Disease or More Common than You Think? [20D]

INTRODUCTION:Familial Dysautonomia (FD) is an autosomal recessive disorder affecting the sensory and autonomic nervous systems causing life threatening autonomic crises, hypotonia, and progressive neuronal degeneration. Currently, carrier testing for FD is recommended for the Ashkenazi Jewish (AJ) population. A joint ACOG/ACMG statement highlighted the increasingly multi-ethnic society as consideration for pan-ethnic carrier testing, and recent ACOG committee opinion states that pan-ethnic carrier testing is a reasonable strategy. This study assesses how many non-AJ individuals screened positive for FD when pan-ethnic carrier screening was implemented. METHODS:Retrospective database analysis of individuals that received expanded carrier testing utilizing a genotyping panel for two pathologic variants of FD (c.2204+6T>C, R696P) was performed. Expected number of positive carriers for FD in AJ and non-AJ groups were calculated and compared to observed rates. Chi-square analysis was performed to assess for statistical significance (p < 0.01). RESULTS:A total of 71,243 individuals were tested for FD. A higher than expected number of non-AJ individuals screened positive for FD (38 observed vs 14.05 expected, p<0.001). The number of AJ individuals that screened positive was consistent with expected values (33 observed vs 32.08 expected, p<0.86). CONCLUSION:Non-AJ carriers of FD were more common than expected in this cohort. Pan-ethnic expanded carrier testing will increase the detection of carriers for FD compared with current ethnicity based screening recommendations. Importantly, carriers of FD, who would be missed by ethnicity based testing convention, will be identified allowing for more complete genetic counseling and family planning options for those who choose testing

Immunological Role of the Maternal Uterine Microbiome in Pregnancy: Pregnancies Pathologies and Alterated Microbiota

Understanding what happens at the time of embryo implantation has been the subject of significant research. Investigators from many differing fields including maternal fetal medicine, microbiology, genetics, reproductive endocrinology and immunology have all been studying the moment the embryo interacts with the maternal endometrium. A perfect relationship between the uterus and the embryo, mediated by a tightly controlled interaction between the embryo and the endometrium, is required for successful implantation. Any factors affecting this communication, such as altered microbiome may lead to poor reproductive outcomes. Current theories suggest that altered microbiota may trigger an inflammatory response in the endometrium that affects the success of embryo implantation, as inflammatory mediators are tightly regulated during the adhesion of the blastocyst to the epithelial endometrial wall. In this review, we will highlight the various microbiome found during the periconceptual period, the microbiomes interaction with immunological responses surrounding the time of implantation, its effect on implantation, placentation and ultimately maternal and neonatal outcomes

Association Between Senior Obstetrician Supervision of Resident Deliveries and Mode of Delivery

OBJECTIVE: In December 2012, the Mount Sinai Hospital implemented a program to have senior obstetricians (more than 20 years of experience) supervise residents on labor and delivery during the daytime. The objective of this study was to estimate the association of resident supervision by senior obstetricians with mode of delivery. METHODS: This was a retrospective cohort study of all resident deliveries at Mount Sinai from July 2011 to June 2015. We included all patients with live, term, singleton, vertex fetuses. We compared delivery outcomes between patients delivered before December 2012 and patients delivered December 2012 and later using logistic regression analysis to control for age, body mass index, parity, induction, and prior cesarean delivery. During the study period there were no other specific departmental initiatives to increase forceps deliveries aside from having six obstetricians with significant experience in operative deliveries supervise and teach residents on labor and delivery. RESULTS: There were 5,201 live, term, singleton, vertex deliveries under the care of residents, 1,919 (36.9%) before December 2012 and 3,282 (63.1%) December 2012 or later. The rate of forceps deliveries significantly increased from 0.6% to 2.6% (adjusted odds ratio [OR] 8.44, 95% confidence interval [CI] 3.1-23.1), and the rate of cesarean deliveries significantly decreased from 27.3% to 24.5% (adjusted OR 0.68, 95% CI 0.55-0.83). There were no statistically significant differences in the rates of third-or fourth-degree lacerations or 5-minute Apgar scores less than 7. Among nulliparous women, the forceps rate increased from 1.0% to 3.4% (adjusted OR 4.87, 95% CI 1.74-13.63) and the cesarean delivery rate decreased from 25.6% to 22.7% (adjusted OR 0.69, 95% CI 0.53-0.89). The increase in forceps deliveries and the decrease in cesarean deliveries were seen only in daytime hours (7 AM to 7 PM), that is, the shift that was covered by senior obstetricians. CONCLUSION: Having senior obstetricians supervise resident deliveries is significantly associated with an increased rate of forceps deliveries and a decreased rate of cesarean deliveries

The Association between Solo versus Group Obstetrical Practice Model and Delivery Outcomes

Objective To determine if women under the care of obstetricians in solo practice have different delivery outcomes from women in a group practice. Study Design This is a retrospective cohort of live, term, singleton, vertex (LTSV) deliveries at one hospital from 2011 to 2015. We compared outcomes between women whose obstetrician was in solo practice with women in a group practice model. Results There were 18,214 LTSV deliveries by private obstetricians. Solo obstetricians were more likely to deliver at night (41.0 vs. 37.5%, p = 0.002) and less likely to induce labor (22.6 vs. 30.6%, p < 0.001). Solo obstetricians had a significantly higher rate of cesarean delivery (35.7 vs. 27.2%, adjusted odds ratio, aOR: 1.53, 95% confidence interval, CI [1.32, 1.78]), but also had a significantly lower rate of shoulder dystocia (0.4 vs. 1.4, aOR: 0.42, 95% CI [0.19, 0.89]), third or fourth degree lacerations (1.6 vs. 2.4%, aOR: 0.56, 95% CI [0.35, 0.914]), and neonatal intensive care unit admission rates (3.2 vs. 6.2%, aOR: 0.57, 95% CI [0.42, 0.77]). Conclusion In a large, tertiary care hospital, solo obstetricians have similar neonatal outcomes as group obstetricians. Their higher cesarean delivery rate is balanced by fewer shoulder dystocias and third/fourth degree lacerations, indicating a more conservative approach to labor management. Patient outcomes should not be a reason to discourage a solo practice model