Routine Prenatal cfDNA Screening for Autosomal Dominant Single-Gene Conditions.

Background: Genetic screening has advanced from prenatal cell-free DNA (cfDNA) screening for aneuploidies (cfDNA-ANP) to single-gene disorders (cfDNA-SGD). Clinical validation studies have been promising in pregnancies with anomalies but are limited in the general population.

Methods: Chart review and laboratory data identified pregnancies with cfDNA-SGD screening for 25 autosomal dominant conditions at our academic center.

Technical Success and Serious Adverse Events for Fetal Aortic Valvuloplasty in a Large 20-Year Cohort.

Background: FAV is offered to fetuses with severe aortic valve stenosis and evolving hypoplastic left heart syndrome. An inferential analysis of TS and SAE in a large series has not been reported.

Objectives: The purpose of this study was to determine factors associated with fetal aortic valvuloplasty (FAV) technical success (TS) and serious adverse events (SAEs).

The patient experience of a postpartum readmission for hypertension: a qualitative study.

Background: Hypertensive disorders of pregnancy (HDP) are the most common cause of postpartum readmission. Prior research led to clinical guidelines for postpartum management; however, the patient experience is often missing from this work. The objective of this study is to understand the perspective of patients readmitted for postpartum hypertension.

Unique Challenges of NIPT for Sex Chromosome Aneuploidy.

Noninvasive prenatal testing (NIPT) for the sex chromosome aneuploidies (45,X, 47,XXY, 47,XXX, and 47,XYY) differs significantly from that for the autosomal aneuploidies (trisomy 13, 18, and 21). As a group, sex chromosome aneuploidies occur more commonly (1/400) than any one isolated autosomal aneuploidy, the phenotypic variation is greater, the role of mosaicism more challenging, and the positive predictive value of a high-risk NIPT result is substantially lower. These considerations should be identified during pretest counseling, the inclusion of sex chromosome testing offered separately, and the differences from autosomal aneuploidy NIPT clearly delineated.

Postnatal genetic testing on cord blood for prenatally identified high-probability cases.

Objective: To evaluate the utility of postnatal genetic testing on umbilical cord blood (CB) for prenatally identified high-probability fetuses.

Method: CB for genetic testing was offered to individuals who met one of the following criteria: (i) fetal anomaly, (ii) positive non-invasive prenatal screening by cfDNA or biochemical analysis, or (iii) family history. Individuals with diagnostic testing, but not microarray, were also included when recommended by society guidelines.

Single gene non-invasive prenatal screening for autosomal dominant conditions in a high-risk cohort.

Purpose: To determine the utility of single gene non-invasive prenatal screening (NIPS-SGD) in a high-risk reproductive genetics clinic.

Methods: A clinical pilot for NIPS-SGD was conducted from March 2020 to November 2021. A NIPS-SGD panel assessing pathogenic variants in 30 genes was offered to pregnant individuals for the following indications: (1) advanced sperm age ≥40 years, (2) nuchal translucency (NT) ≥ 3.

Redesigning Care for the Management of Postpartum Hypertension: How Can Ob-Gyns and Primary Care Physicians Partner in Caring for Patients after a Hypertensive Pregnancy?

The standard care model in the postpartum period is ripe for disruption and attention. Hypertensive disorders of pregnancy (HDPs) can continue to be a challenge for the postpartum person in the immediate postpartum period and is a harbinger of future health risks. The current care approach is inadequate to address the needs of these women.

Overcoming roadblocks in clinical innovation via high fidelity simulation: use of a phantom simulator to achieve FDA and IRB approval of a clinical trial of fetal embolization of vein of Galen malformations.

Background: Vein of Galen malformation (VOGM) is a rare, life-threatening vascular malformation in neonates and is treated with embolization. However, even at the most experienced centers, patients face high mortality and morbidity. In utero treatment options have been limited by lack of animal models or simulations.

The hypergonadotropic hypogonadism conundrum of classic galactosemia.

Background: Hypergonadotropic hypogonadism is a burdensome complication of classic galactosemia (CG), an inborn error of galactose metabolism that invariably affects female patients. Since its recognition in 1979, data have become available regarding the clinical spectrum, and the impact on fertility. Many women have been counseled for infertility and the majority never try to conceive, yet spontaneous pregnancies can occur.

Prenatal diagnosis of sex chromosome aneuploidy-What do we tell the prospective parents?

Sex chromosome aneuploidy (SCA) can be detected on prenatal diagnostic testing and cell free DNA screening (cfDNA). High risk cfDNA results should be confirmed with diagnostic testing. This summary article serves as an update for prenatal providers and assimilates data from neurodevelopmental, epidemiologic, and registry studies on the most common SCA.

Hemodynamic and anatomic changes after fetal aortic valvuloplasty are associated with procedural success and postnatal biventricular circulation.

Background: There are minimal data characterizing the trajectory of left heart growth and hemodynamics following fetal aortic valvuloplasty (FAV).

Methods: This retrospective study included patients who underwent FAV between 2000 and 2019, with echocardiograms performed pre-FAV, immediately post-FAV, and in late gestation.

Results: Of 118 fetuses undergoing FAV, 106 (90%) underwent technically successful FAV, of which 55 (52%) had biventricular circulation.

Percutaneous transuterine fetal cerebral embolisation to treat vein of Galen malformations at risk of urgent neonatal decompensation: study protocol for a clinical trial of safety and feasibility.

Introduction: Although endovascular techniques have improved outcomes in vein of Galen malformations (VOGM), there is still a high rate of morbidity and mortality, particularly among cases with decompensation in the neonatal period. The dimension of the draining venous sinus on fetal imaging correlates with the risk of neonatal decompensation. In fetuses within this high-risk group who do not have end-organ injury, there is a theoretical therapeutic opportunity to reduce the arteriovenous shunt before the normal physiological changes of birth precipitate decompensation.

International Society for Prenatal Diagnosis Updated Position Statement on the use of genome-wide sequencing for prenatal diagnosis.

The research and clinical use of genome-wide sequencing for prenatal diagnosis of fetuses at risk for genetic disorders have rapidly increased in recent years. Current data indicate that the diagnostic rate is comparable and for certain indications higher than that of standard testing by karyotype and chromosomal microarray. Responsible clinical implementation and diagnostic use of prenatal sequencing depends on standardized laboratory practices and detailed pre-test and post-test counseling.

ISPD 2021 debate - All in vitro fertilization cycles should involve pre-implantation genetic testing to improve fetal health and pregnancy outcomes.

For 3 decades, couples at increased risk for a genetic disorder have been offered preimplantation genetic testing (PGT). Simultaneously, PGT for aneuploidy (PGT-A) to improve in vitro fertilization (IVF) outcomes was introduced, but evidence of value-added remains inconsistent. Recently, lower genetic testing costs and shorter turnaround time have reinvigorated PGT-A.

Counseling for personal health implications identified during reproductive genetic carrier screening.

Objective: Preconception and prenatal carrier screening is designed to provide reproductive risk information, but carriers for some autosomal recessive or X-linked conditions also have personal health risks. This study investigated the prevalence of and inclusion of personal health implications in pre- and post-test counseling.

Methods: Twelve genetic conditions with personal health risks for carriers included on carrier screening panels but not otherwise screened routinely were identified (e.

Problems with Using Polygenic Scores to Select Embryos.

Companies have recently begun to sell a new service to patients considering in vitro fertilization: embryo selection based on polygenic scores (ESPS). These scores represent individualized predictions of health and other outcomes derived from genomewide association studies in adults to partially predict these outcomes. This article includes a discussion of many factors that lower the predictive power of polygenic scores in the context of embryo selection and quantifies these effects for a variety of clinical and nonclinical traits.

General practitioners' knowledge about pregnancy complications associated with long-term cardiovascular risk.

Introduction: Cardiovascular disease (CVD) is the leading cause of mortality in women; preeclampsia (PE) and gestational diabetes mellitus (GDM) are associated with an increased risk of CVD.

Objective: To evaluate general practitioners (GP) knowledge about complicated pregnancies and their association with CVD.

Methods: An anonymous case-based electronic questionnaire designed to assess the level of understanding on the influence of a history of pregnancy complications on long-term cardiovascular risk and general knowledge about CVD risk was sent to GPs.

Late gestation predictors of a postnatal biventricular circulation after fetal aortic valvuloplasty.

Objectives: Fetal aortic valvuloplasty (FAV) for severe aortic stenosis (AS) has shown promise in averting progression to hypoplastic left heart syndrome. After FAV, predicting which fetuses will achieve a biventricular (BiV) circulation after birth remains challenging. Identifying predictors of postnatal circulation on late gestation echocardiography will improve parental counseling.