UNASSIGNED: Pregnant women can choose from different prenatal genetic tests throughout their maternity journey. We aim to investigate the clinical, societal, and economic determinants influencing the selection of different options (non-invasive, invasive, or both).
UNASSIGNED: A systematic survey focusing on maternity pathways was launched by the Region of Tuscany, Italy, to collect data on pregnant women\'s experience, outcomes and satisfaction levels. Drawing from this survey, we retrospectively analyzed data on women who filled out the second-trimester questionnaire between March 2019 and February 2023 (n = 27,337), providing complete data on relevant variables. Logistic regression models were applied to identify the factors contributing to a higher likelihood of opting for non-invasive prenatal testing (NIPT) and invasive testing.
UNASSIGNED: Among the participants, 42.7 % chose only NIPT, 3.8 % opted for invasive tests exclusively, 1.3 % underwent both tests, and 52.2 % did not pursue any genetic testing. NIPT was more often chosen by older, Italian, highly educated, nulliparous women, who perceived better health, were employed (versus unemployed), had higher economic status, planned pregnancy, received hospital-based care (versus counseling center), under gynecologist supervision (versus midwife), not opted for combined testing and received pregnancy vaccinations. Conversely, invasive testing was more prevalent among older women but less common among those who were nulliparous, had Italian nationality, and had a perceived better health status. This group also tended to experience unplanned and high-risk pregnancy, did not take folate during pregnancy, received public hospital-based assistance, less frequently chose combined tests or NIPT, and had frequent delays in examinations.
UNASSIGNED: Various factors beyond clinical considerations influence the selection of a prenatal test. Therefore, NIPT pathways should include balanced, high-quality information about benefits and limitations, ensuring laboratory specialists\' active and integrated involvement in decision-making.

This EBCOG guidance reviews the current and future status of genomics within fetal and maternal medicine. This document addresses the clinical uses of genetic testing in both screening and diagnostic testing prenatally. The role of genomics within fetal and maternal medicine is described. The research and future implications of genetic testing as well as the educational, ethical and economic implications of genomics are discussed.

When an apparent de novo (new) genetic change has been identified as the cause of a serious genetic condition in a child, many couples would like to know the risk of this happening again in a future pregnancy. Current practice provides families with a population average risk of 1%-2%. However, this figure is not accurate for any specific couple, and yet, they are asked to make decisions about having another child and/or whether to have prenatal testing. The PREcision Genetic Counseling And REproduction (PREGCARE) study is a new personalized assessment strategy that refines a couple\'s recurrence risk prior to a new pregnancy, by analyzing several samples from the parent-child trio (blood, saliva, swabs, and father\'s sperm) using deep sequencing and haplotyping. Overall, this approach can reassure ~2/3 of couples who have a negligible (<0.1%) recurrence risk and focus support on those at higher risk (i.e. when mosaicism is identified in one of the parents). Here we present a qualitative interview study with UK clinical genetics professionals (n = 20), which investigate the potential implications of introducing such a strategy in genetics clinics. While thematic analysis of the interviews indicated perceived clinical utility, it also indicates a need to prepare couples for the psychosocial implications of parent-of-origin information and to support their understanding of the assessment being offered. When dealing with personalized reproductive risk, a traditional non-directive approach may not meet the needs of practitioner and client(s) and shared decision-making provides an additional framework that may relieve some patient burden. Further qualitative investigation with couples is planned.

Carrier screening has historically assessed a relatively small number of autosomal recessive and X-linked conditions selected based on frequency in a specific subpopulation and association with severe morbidity or mortality. Advances in genomic technologies enable simultaneous screening of individuals for several conditions. The American College of Medical Genetics and Genomics recently published a clinical practice resource that presents a framework when offering screening for autosomal recessive and X-linked conditions during pregnancy and preconception and recommends a tier-based approach when considering the number of conditions to screen for and their frequency within the US population in general. This laboratory technical standard aims to complement the practice resource and to put forth considerations for clinical laboratories and clinicians who offer preconception/prenatal carrier screening.

OBJECTIVE: Prenatal genetic testing is routinely offered to all pregnant patients in the United States and is variably offered to certain pregnant populations globally [1]. To achieve value-based, informed decision-making, we argue for a shift away from the predominant \"teaching\" model of genetic counseling practice that prioritizes information and counselor dominance, toward a \"counseling\" model of practice that prioritizes the patient\'s narrative, values and beliefs.
CONCLUSIONS: Since prenatal testing began, genetic counseling has aimed to facilitate informed decision-making. Many patients are not familiar with the conditions which can be screened for prenatally or the quality of life of affected children. This lack of understanding can leave expectant parents unprepared to make informed decisions about prenatal testing. As the number of prenatal genetic tests expands, genetic counselors and all healthcare providers who discuss prenatal testing face a growing amount of information that is not feasible to explain to patients in a routine appointment. Research demonstrates that the common approach to genetic counseling, including in the prenatal setting, is the provision of biomedical information. Yet, genetic counseling outcome studies suggest that attending to the relational aspects of genetic counseling are associated with more positive patient outcomes, including enhanced knowledge, informed decision-making and greater patient satisfaction [2,3]. Through case vignettes, we illustrate the application of a counseling model of practice using Accreditation Council for Genetic Counseling (ACGC) practice-based competencies in the domain of \"Interpersonal, Psychosocial and Counseling Skills\" [4]. Finally, we propose changes across the genetic counseling profession to move clinical practice toward a more relational model of care.
CONCLUSIONS: A counseling model of genetic counseling practice leads to more positive patient outcomes [2,3]. Genetic counselors and other prenatal healthcare providers can leverage existing counseling and communication skills to support clients in value-based, informed decision-making in prenatal genetic counseling practice.

Deep sequencing by NGS of targeted amplicons can identify rare genetic variants in a pool of DNA where the vast majority of genomic DNA does not contain the variant. This approach can be used to detect a previously described paternally inherited, fetal variant in cell-free DNA (cfDNA) in maternal plasma. This is useful in cases where risk for the fetus is contingent upon inheritance of a paternal variant that the woman does not have. Both pathogenic and non-pathogenic variants that the woman does not have can be detected. In cases of compound heterozygosity, presence of the paternal pathogenic variant also requires detection of the maternal variant for risk assessment, which requires a chorion villus biopsy.We have used this approach to focus on detection of fetal blood groups in cases of presence of maternal alloantibodies against blood group antigens in pregnancy, to predict whether the fetus has inherited a blood group antigen that is targeted by the alloantibodies. In cases of maternal alloantibodies against blood group antigens, the fetus is at risk of hemolytic disease of the fetus and newborn (HDFN). With a known specificity of the maternal antibodies and if the fetal blood group can be determined in the pregnancy, then it can be ascertained if the fetus is at risk of HDFN and rational pregnancy care can be instituted. A noninvasive procedure avoids risks for the fetus. We have reported a procedure based on NGS analysis of PCR amplified cfDNA from maternal plasma. Some fetuses may die as early as week 18. We use this approach to predict fetal K, k, RhC, Rhc, RhE, and ABO blood groups in cases with a risk of HDFN due to the corresponding maternally produced antibodies.The NGS-based analysis can predict the presence or absence of incompatible antigens on the fetal RBCs.In this chapter, a noninvasive method for predicting some fetal blood groups early in pregnancy is described. There is a clinical need for such assays, and they may be a useful tool for management of pregnancies complicated by these alloantibodies within the field of precision medicine.

BACKGROUND: Chromosomal microarray (CMA) is commonly utilized in the obstetrics setting. CMA is recommended when one or more fetal structural abnormalities is identified. CMA is also commonly used to determine genetic etiologies for miscarriages, fetal demise, and confirming positive prenatal cell-free DNA screening results.
METHODS: In this study, we retrospectively examined 523 prenatal and 319 products-of-conception (POC) CMA cases tested at Nationwide Children\'s Hospital from 2011 to 2020. We reviewed the referral indications, the diagnostic yield, and the reported copy number variants (CNV) findings.
RESULTS: In our cohort, the diagnostic yield of clinically significant CNV findings for prenatal testing was 7.8% (n = 41/523) compared to POC testing (16.3%, n = 52/319). Abnormal ultrasound findings were the most common indication present in 81% of prenatal samples. Intrauterine fetal demise was the common indication identified in POC samples. The most common pathogenic finding observed in all samples was isolated trisomy 21, detected in seven samples.
CONCLUSIONS: Our CMA study supports the clinical utility of prenatal CMA for clinical management and identifying genetic etiology in POC arrays. In addition, it provides insight to the spectrum of prenatal and POC CMA results as detected in an academic hospital clinical laboratory setting that serves as a reference laboratory.

UNASSIGNED: Congenital ichthyosis represents a wide spectrum of diseases. This article reviews prenatal testing for ichthyosis.
UNASSIGNED: We used pubmed.ncbi.nlm.nih.gov to search for 38 types of congenital ichthyosis combined with 17 words related to prenatal testing.
UNASSIGNED: Search resulted in 408 publications covering 13 types of ichthyoses and four types of tests.
UNASSIGNED: Biochemical testing is diagnostic in trichothiodystrophy, but nonspecific in X-linked ichthyosis and Refsum syndrome. Except in X-linked ichthyosis, biochemical testing requires invasive procedures to obtain fetal skin biopsy, amniocytes, or chorionic villus samples. It is superior to histological and cytological examination of fetal skin biopsy or amniocytes because keratinization occurs later in pregnancy and microscopy cannot differentiate between ichthyosis types. Imaging is more acceptable due to noninvasiveness and routine use, although ultrasonography is operator-dependent, nonspecific, and captures abnormalities at late stage. Molecular tests are described in at-risk pregnancies but testing of free fetal DNA was not described.

The current recommended testing algorithm for assessing the alloimmunized pregnancy utilized by many obstetricians in the United States (US) fails to consider the most recent evidence, placing fetuses, and mothers at unnecessary risk of poor outcome or death. This narrative review of the current landscape of fetal red blood cell (RBC) antigen testing evaluates the history of hemolytic disease of the fetus and newborn (HDFN) and how its discovery has continued to influence practices in the US today. We compare current US-based HDFN practice guidelines with those in Europe. We also provide transfusion medicine and hematology perspectives and recommendations addressing the limitations of US practice, particularly regarding paternal RBC antigen testing, and discuss the most valuable alternatives based on decades of data and evidence-based recommendations from Europe.

Post-Dobbs abortion restrictions impact access and choice in the context of reproductive genetic medicine, raising serious reproductive justice concerns. The consequences of these restrictions are particularly acute and far-reaching for individuals with genetic conditions and their families.