Chorionic Villous Testing Versus Amniocentesis After Abnormal Noninvasive Prenatal Testing.

In the setting of a normal first-trimester ultrasound, an amniocentesis may be a better option than chorionic villous sampling for invasive diagnostic testing after a cell-free DNA high risk for trisomy 13, given the high rates of confined placental mosaicism. In unaffected fetuses, other evaluations should be considered depending on the cell-free DNA results, including maternal karyotyping for monosomy X, uniparental disomy testing for chromosomes with imprinted genes, serial growth scans for trisomy 16, and a workup for maternal malignancy for multiple aneuploidies or autosomal monosomy.

POLR1A variants underlie phenotypic heterogeneity in craniofacial, neural, and cardiac anomalies.

Heterozygous pathogenic variants in POLR1A, which encodes the largest subunit of RNA Polymerase I, were previously identified as the cause of acrofacial dysostosis, Cincinnati-type. The predominant phenotypes observed in the cohort of 3 individuals were craniofacial anomalies reminiscent of Treacher Collins syndrome. We subsequently identified 17 additional individuals with 12 unique heterozygous variants in POLR1A and observed numerous additional phenotypes including neurodevelopmental abnormalities and structural cardiac defects, in combination with highly prevalent craniofacial anomalies and variable limb defects.

In Utero Gene Therapy for Primary Immunodeficiencies.

Primary immunodeficiencies (PIDs) have become a prime target for gene therapy given the morbidity, mortality, and the single gene etiology. Given that outcomes are better the earlier gene therapy is implemented, it is possible that fetal gene therapy may be an important future direction for the treatment of PIDs. In this chapter, the current treatments available for several PIDs will be reviewed, as well as the history and current status of gene therapy for PIDs.

Diagnostic testing after positive results on cell free DNA screening: CVS or Amnio?

Objective: The positive predictive values of cell free DNA (cfDNA) and rates of confined placental mosaicism (CPM), imprinting and other factors vary by chromosome.

Methods: We sought to review the literature for each of these features for each chromosome and provide recommendations on chorionic villus sampling (CVS) versus amniocentesis after an abnormal cfDNA result.

Results: For chromosomes with high rates of CPM (trisomy 13, monosomy X and rare autosomal trisomies [RATs]), an amniocentesis should be considered if the first trimester ultrasound is normal.

Third case of Bardet-Biedl syndrome caused by a biallelic variant predicted to affect splicing of IFT74.

Bardet-Biedl syndrome (BBS) is a rare ciliopathy characterized by rod-cone dystrophy, postaxial polydactyly, truncal obesity and renal anomalies with autosomal recessive inheritance. We describe a 6-year-old male with early onset retinal dystrophy, postaxial polydactyly, truncal obesity and motor delays. Exome sequencing revealed a homozygous variant predicted to affect splicing of the IFT74 gene, c.

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.

Utility of chromosomal microarray for diagnosis in cases of nonimmune hydrops fetalis.

Purpose: Chromosomal microarray (CMA) is recommended in the diagnostic evaluation of cases with fetal structural anomalies when invasive testing is pursued. However, the utility of CMA for nonimmune hydrops fetalis (NIHF) specifically is not well known. Our objective was to describe the overall yield of CMA in the diagnostic evaluation of NIHF, comparing isolated cases to those with concurrent structural anomalies.

X-linked duplication copy number variation in a familial overgrowth condition.

We describe an overgrowth condition associated with X-linked copy number variation. Three brothers displayed an overgrowth pattern at birth that continued postnatally. Clinical findings included macrocephaly, distinctive facial features, developmental delay and variable clubfoot.

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.

The utility of fetal fibronectin in asymptomatic singleton and twin pregnancies with a cervical length ≤ 10 mm.

To examine the utility of fetal fibronectin (fFN) for predicting spontaneous preterm birth (PTB) in asymptomatic women with a cervical length (CL) ≤10 mm compared to those with a CL 11-25 mm. Data was collected on all women with nonanomalous singleton and twin gestations who underwent transvaginal CL at a single institution between 2009 and 2012. Women with an incidental short cervix (CL ≤ 25 mm) between 22 and 32 weeks who had an fFN result within 7 days thereafter were included.

Nonimmune hydrops fetalis: identifying the underlying genetic etiology.

Purpose: Numerous etiologies may lead to nonimmune hydrops fetalis (NIHF), and the underlying cause often remains unclear. We aimed to determine the proportion of NIHF cases in which the etiology was clearly determined in a large, contemporary, and diverse cohort, as well as to describe the etiologies with a focus on genetic causes.

Methods: Retrospective review of NIHF cases between 2015 and 2017 from the five University of California Fetal-Maternal Consortium sites.

Venous Thromboembolism Prophylaxis During Antepartum Admissions and Postpartum Readmissions.

Objective: To characterize the use of venous thromboembolism prophylaxis during antepartum and postpartum hospitalizations in the United States.

Methods: A retrospective cohort study using the Perspective database was performed to analyze temporal trends of mechanical and pharmacologic venous thromboembolism prophylaxis for patients hospitalized for antepartum and postpartum indications between 2006 and 2015. Delivery hospitalizations were excluded.

Anal sphincter injury in vaginal deliveries complicated by shoulder dystocia.

Introduction And Hypothesis: Shoulder dystocia is an obstetric emergency that occurs in 0.2-3% of all cephalic vaginal deliveries. We hypothesized that because of the difficult nature of deliveries complicated by shoulder dystocia, the condition may be associated with anal sphincter injury.

A prediction model of vaginal birth after cesarean in the preterm period.

Background: A validated model exists that predicts the probability of vaginal birth after cesarean delivery in patients at term who are undergoing a trial of labor after cesarean delivery. However, a model that predicts the success of a vaginal birth after cesarean delivery in the preterm period has not been developed.

Objective: We sought to develop and validate a predictive model for vaginal birth after cesarean delivery for women undergoing a trial of labor after cesarean delivery during the preterm period.

Confined placental mosaicism and its impact on confirmation of NIPT results.

Non-invasive prenatal testing (NIPT) has been widely used to screen for common aneuploidies since 2011. While NIPT is highly sensitive and specific, false positive results can occur. One important cause of false positive results is confined placental mosaicism (CPM).