Perinatal Outcomes of Fetuses and Infants Diagnosed with Trisomy 13 or Trisomy 18.

OBJECTIVES: To identify factors associated with prenatal, perinatal, and postnatal outcomes, and determine medical care use for fetuses and infants with trisomy 13 (T13) and trisomy 18 (T18). STUDY DESIGN: This population-based retrospective cohort study included all prenatal and postnatal diagnoses of T13 or T18 in the greater Cincinnati area from January 1, 2012, to December 31, 2018. Overall survival, survival to hospital discharge, medical management, and maternal, fetal, and neonatal characteristics are analyzed. RESULTS: There were 124 pregnancies (125 fetuses) that were identified, which resulted in 72 liveborn infants. Male fetal sex and hydrops were associated with a higher rate of spontaneous loss. The median length of survival was 7 and 29 days, for infants with T13 and T18, respectively. Of the 27 infants alive at 1 month of age, 13 (48%) were alive at 1 year of age. Only trisomy type (T13), goals of care (comfort care), and extremely low birthweight were associated with a shorter length of survival. A high degree of variability existed in the use of medical services, with 28% of infants undergoing at least 1 surgical procedure and some children requiring repeated (≤29) or prolonged (>1 year) hospitalizations. CONCLUSIONS: Although many infants with T13 or T18 did not survive past the first week of life, nearly 20% lived for more than 1 year with varying degrees of medical support. The length of survival for an infant cannot be easily predicted, and surviving infants have high health care use throughout their lifespans.

Experiences of reproductive genetic counselors with abortion regulations in Ohio.

Since 2010, Ohio legislators have passed more than 15 legislative changes related to abortion and abortion providers, and nine procedural abortion clinics have closed. We investigated reproductive genetic counselors' perceptions, attitudes and self-reported practices regarding Ohio's current and proposed abortion regulations. We conducted five focus groups and two telephone interviews in 2019-2020, with a total of 19 reproductive genetic counselors. Participants discussed difficulties keeping current on abortion legislation and clinics' and hospitals' policies, resulting in anticipatory anxiety and leading to additional work to discuss the laws with patients. Participants articulated that practices of reproductive genetic counseling-and patient advocacy-are impeded by the legislation. Genetic counselors perceive negative impacts on patients' autonomy, particularly reflective of healthcare disparities of marginalized groups, which may contribute to frustration and anger. Ultimately, the mental and emotional burden on genetic counselors created by abortion legislation contributes to compassion fatigue and burnout. Our findings show that Ohio's abortion regulations negatively impact reproductive genetic counselors and their relationships with their patients. Repealing existing abortion regulations and preventing future restrictive legislation may ameliorate the negative effects of regulations on reproductive genetic counselors and their patients. In the event that these laws remain, innovative communication tools and proactive professional society advocacy are potential means to mitigate the negative impact on reproductive genetic counselors.

Beyond diagnostic yield: prenatal exome sequencing results in maternal, neonatal, and familial clinical management changes.

PURPOSE: Previous studies have reported that prenatal exome sequencing (pES) can detect monogenic diseases in fetuses with congenital anomalies with diagnostic yields ranging from 6% to 81%, but there are few reports of its clinical utility. METHODS: We conducted a retrospective chart review of patients who had pES to determine whether results led to clinical management changes. RESULTS: Of 20 patients, 8 (40%) received a definitive diagnosis. Seven patients (35%) had medical management changes based on the pES results, including alterations to their delivery plan and neonatal management (such as use of targeted medications, subspecialty referrals, additional imaging and/or procedures). All patients who received a definitive diagnosis and one who received a likely pathogenic variant (n = 9; 45%) received specific counseling about recurrence risk and the medical/developmental prognosis for the baby. In five (25%) cases, the result facilitated a diagnosis in parents and/or siblings. CONCLUSION: pES results can have significant impacts on clinical management, some of which would not be possible if testing is deferred until after birth. To maximize the clinical utility, pES should be prioritized in cases where multiple care options are available and the imaging findings alone are not sufficient to guide parental decision-making, or where postnatal testing will not be feasible.

Aneuploid embryo transfer: clinical policies and provider opinions at United States fertility clinics.

OBJECTIVE: To describe institutional clinical policies and individual provider opinions regarding aneuploid embryo transfer (aET). DESIGN: A survey about clinical policies was electronically sent to Society for Assisted Reproductive Technology (SART) member laboratory directors, and a separate survey about personal opinions was electronically sent to all SART members. SETTING: Not applicable. PATIENTS: Patients pursuing preimplantation genetic testing for aneuploidy (PGT-A). INTERVENTION: Not applicable. MAIN OUTCOME MEASURES: Current clinical policies about aET were described. Individual provider opinions about aET in the context of specific aneuploidies and mosaicism were also described. RESULTS: A total of 48 laboratory directors and 212 individual providers responded to their respective surveys. Twelve (25%) clinics report that they do not have a policy regarding aET, but clinics performing PGT-A in >100 cycles per year were more likely to have a policy. Half of the individual providers agree that an embryo with trisomy 21 should be available for aET, but most disagreed with aET of embryos with other aneuploidies and most were either unsure about or unwilling to transfer embryos with mosaicism. Those who worked in primarily patient-facing roles held more agreeable opinions regarding aET. CONCLUSION: There is no consensus regarding ideal clinical policies for aET. The wide range of current clinical practices and individual provider opinions regarding under what circumstances, if any, aET should be available to patients indicates that this is a divisive issue among ART providers, and there is a clear need for specific professional guidelines to address this issue.

Making a Genetic Diagnosis in a Level IV Neonatal Intensive Care Unit Population: Who, When, How, and at What Cost?

OBJECTIVE: To investigate the prevalence of genetic disease and its economic impact in a level IV neonatal intensive care unit (NICU) by identifying and describing diseases diagnosed, genetic testing methodologies used, timing of diagnosis, length of NICU stay, and charges for NICU care. STUDY DESIGN: A retrospective chart review of patients admitted to a level IV NICU from 2013 to 2014 (n = 1327) was undertaken and data collected up to 2 years of age from the electronic medical record. RESULTS: In total, 117 patients (9%) received 120 genetic diagnoses using a variety of methodologies. A significant minority of diagnoses, 36%, were made after NICU discharge and 41% were made after 28 days of age. Patients receiving a genetic diagnosis had significantly longer mean lengths of stay (46 days vs 29.1 days; P < .01) and costlier mean charges ($598 712 vs $352 102; P < .01) for their NICU care. The NICU stay charge difference to care for a newborn with a genetic condition was on average $246 610 in excess of that for a patient without a genetic diagnosis, resulting in more than $28 000 000 in excess charges to care for all patients with genetic conditions in a single NICU over a 2-year period. CONCLUSIONS: Given the high prevalence of genetic disease in this population and the documented higher cost of care, shortening the time to diagnosis and targeting therapeutic interventions for this population could make a significant impact on neonatal care in level IV NICUs.

Pediatric Whole Exome Sequencing: an Assessment of Parents' Perceived and Actual Understanding.

Whole exome sequencing (WES) is an integral tool in the diagnosis of genetic conditions in pediatric patients, but concerns have been expressed about the complexity of the information and the possibility for secondary findings that need to be conveyed to those deciding about WES. Currently, there is no validated tool to assess parental understanding of WES. We developed and implemented a survey to assess perceived and actual understanding of WES in parents who consented to clinical WES for their child between July 2013 and May 2015. Fifty-three eligible surveys were returned (57% response rate). Areas with both low perceived and actual understanding about WES included how genes are analyzed and lack of protection against life insurance discrimination. Parents also had low actual understanding for two questions related to secondary findings - reporting of secondary findings in a parent (if tested) and whether secondary findings can be related to traits such as height and hair color. Further work to develop a validated tool to assess understanding of WES would be beneficial as WES is integrated more frequently into clinical care.