Disparities in the acceptance of chromosomal microarray at the time of prenatal genetic diagnosis.

OBJECTIVE: Chromosomal microarray (CMA) increases the diagnostic yield of prenatal genetic diagnostic testing but is not universally performed. Our objective was to identify provider and patient characteristics associated with the acceptance of CMA at the time of prenatal genetic diagnostic testing. METHODS: Retrospective cohort study of patients undergoing prenatal genetic diagnostic testing (chorionic villus sampling or amniocentesis) at a single institution between 2014 and 2020. Primary outcome was the acceptance of CMA based on the genetic counselor ,GC who saw the patient. Secondary analyses assessed patient characteristics associated with the acceptance of CMA. RESULTS: 2372 participants were included. Fifty-eight percent of participants accepted CMA. Acceptance of CMA varied significantly by GC, ranging from 31% to 90%. Patients with public insurance and those who identified as Black or Hispanic/Latina were less likely to have CMA performed (aOR 0.24, 95% CI 0.20-0.30, and 0.68, 95% CI 0.50-0.92). Even among those with a structural anomaly present, public insurance was associated with significantly lower odds of CMA being performed (aOR 0.39, 95% CI 0.25-0.61). CONCLUSIONS: Acceptance of CMA at the time of prenatal genetic diagnostic testing varied based on the GC performing the counseling. Public insurance was associated with lower frequency of accepting CMA.

Maternal genetic disorders and fetal development.

With improvements in early diagnosis and management of genetic diseases, more women with genetic disorders are reaching reproductive age and becoming pregnant. While pregnancy can have a significant impact on a woman's health when there is an underlying genetic disorder, there can also be fetal effects, including embryopathy, fetal growth restriction, and brain injury. Some maternal genetic disorders are associated with adverse perinatal outcomes, including a high risk of perinatal loss and preterm birth. In this article, we review several maternal genetic disorders associated with fetal risk that are important for clinicians and patients to understand and manage appropriately. These include phenylalanine hydroxylase (PAH) deficiency and other inborn errors of metabolism, tuberous sclerosis complex, myotonic dystrophy, cystic fibrosis, Turner syndrome, sickle cell disease, and connective tissue disorders.

A system-based approach to the genetic etiologies of non-immune hydrops fetalis.

A wide spectrum of genetic causes may lead to nonimmune hydrops fetalis (NIHF), and a thorough phenotypic and genetic evaluation are essential to determine the underlying etiology, optimally manage these pregnancies, and inform discussions about anticipated prognosis. In this review, we outline the known genetic etiologies of NIHF by fetal organ system affected, and provide a systematic approach to the evaluation of NIHF. Some of the underlying genetic disorders are associated with characteristic phenotypic features that may be seen on prenatal ultrasound, such as hepatomegaly with lysosomal storage disorders, hyperechoic kidneys with congenital nephrosis, or pulmonary valve stenosis with RASopathies. However, this is not always the case, and the approach to evaluation must include prenatal ultrasound findings as well as genetic testing and many other factors. Genetic testing that has been utilized for NIHF ranges from standard chromosomal microarray or karyotype to gene panels and broad approaches such as whole exome sequencing. Family and obstetric history, as well as pathology examination, can yield additional clues that are helpful in establishing a diagnosis. A systematic approach to evaluation can guide a more targeted approach to genetic evaluation, diagnosis, and management of NIHF.

Investigating human placentation and pregnancy using first trimester chorionic villi.

Chorionic villus sampling (CVS), routinely used for prenatal diagnosis of cytogenetic disorders, also possesses great potential for the study of placentation. To better understand villus biology, human placentation, and how these relate to pregnancy outcomes, we examined the morphology and transcriptomes of villi obtained via CVS from 10 to 14 weeks of pregnancy and correlated these with pregnancy attributes and clinical outcomes. First, we established a morphological scoring system based on three main villus features: branching, budding and vascularization. We then tested whether morphology scores were predictive of pregnancy attributes and clinical outcomes. Finally, we used RNA sequencing to assess the transcriptional basis of villus morphology and tested the hypothesis that gene expression may predict pregnancy outcomes. We demonstrate that villus morphology varies tremendously between patients, irrespective of gestational age, and that transcriptional differences are highly predictive of villus morphology. We show that pre-eclampsia markers are associated with villi with low morphology scores. Additionally, we identify SVEP1 as a possible biomarker for defining gestational age. Overall, chorionic villi in the first trimester remain one of the few means to correlate placental function with pregnancy outcome and these samples are a valuable and increasingly rare resource.

Management of pregnancy in women with genetic disorders: Part 2: Inborn errors of metabolism, cystic fibrosis, neurofibromatosis type 1, and Turner syndrome in pregnancy.

UNLABELLED: With early diagnosis and increasingly effective medical care, more women with genetic syndromes are undergoing pregnancy, often presenting challenges for providers. Each year more women with genetic disease reach childbearing age. Advances in assisted reproductive technology have enabled pregnancy in a cohort of woman who experience impaired fertility because of their underlying diagnosis. Management of these women requires health care providers from multiple specialties to provide coordinated care to optimize outcomes. Potentially, serious medical issues specific to each diagnosis may exist in the preconception, antepartum, intrapartum, and postpartum periods, all of which must be understood to allow timely diagnosis and treatment. The fetus may also face issues, both related to risk for inheritance of the genetic disorder observed in the mother as well as risks related to her chronic disease status. In this article, the second of a 2-part series, we will review the key issues for managing women with various inborn errors of metabolism during pregnancy. Additionally, we will discuss the care of women with Turner syndrome, neurofibromatosis type 1, and cystic fibrosis. TARGET AUDIENCE: Obstetricians & Gynecologists and Family Physicians. LEARNING OBJECTIVES: After the completing the CME activity, physicians should be better able to classify the pulmonary and nutritional issues facing women with cystic fibrosis in pregnancy, assess the baseline evaluation that should take place in women with Turner syndrome, NF1 and cystic fibrosis before attempting pregnancy and evaluate the fetal risks that can be observed in women with untreated inborn errors of metabolism.