Non‐immune hydrops fetalis (NIHF) has multiple genetic etiologies diagnosable by exome sequencing (ES). We evaluated the yield of prenatal ES for NIHF, and the contribution of additional clinical findings and history. Systematic review was performed with PROSPERO tag 232951 using CINAHL, PubMed, and Ovid MEDLINE from January 1, 2000 through December 1, 2021. Selected studies performed ES to augment standard prenatal diagnostic approaches. Cases meeting a strict NIHF phenotype were tabulated with structured data imputed from papers or requested from authors. Genetic variants and diagnostic outcomes were harmonized across studies using current ACMG and ClinGen variant classification guidelines. Thirty‐one studies reporting 445 NIHF cases had a 37% (95% CI: 32%–41%) diagnostic rate. There was no significant difference between isolated NIHF and NIHF with fetal malformations or between recurrent and simplex cases. Diagnostic rate was higher for consanguineous than non‐consanguineous cases. Disease categories included RASopathies (24%), neuromuscular (21%), metabolic (17%), lymphatic (13%), other syndromes (9%), cardiovascular (5%), hematologic (2%), skeletal (2%), and other categories (7%). Inheritance patterns included recessive (55%), dominant (41%), and X‐linked (4%). ES should be considered in the diagnostic workup of NIHF with and without associated ultrasound findings regardless of history of recurrence or consanguinity.

Background Expanded carrier screening (ECS) utilizes high‐throughput next‐generation sequencing to evaluate an individual's carrier status for multiple conditions. Combined malonic and methylmalonic aciduria (CMAMMA) due to ACSF3 deficiency is a rare inherited disease included in such screening panels. Some cases have been reported with metabolic symptoms in childhood yet other cases describe a benign clinical course, suggesting the clinical phenotype is not well defined. Methods/Case Report Clinical and laboratory findings during the prenatal period were obtained retrospectively from medical records. Results A 37‐year‐old nulliparous woman and her partner were each identified as carriers of ACSF3 variants and presented at 9 weeks gestation for prenatal genetic consultation. The couple received extensive genetic counseling and proceeded with chorionic villus sampling at 11 weeks gestation. Subsequent analysis confirmed that the fetus inherited both parental ACSF variants. The couple was devastated by the results and after reviewing options of pregnancy continuation and termination, they decided to terminate the pregnancy. Following this decision, the patient was diagnosed with acute stress disorder. Conclusion This case highlights how expanded carrier screening adds complexity to reproductive decision‐making. Stronger guidelines and additional research are needed to direct and evaluate the timing, composition, and implementation of ECS panels.

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Monochorionic pregnancies with abnormal distribution of inter-twin anastomoses may be complicated by twin-anemia polycythemia sequence (TAPS) and/or twin-twin transfusion syndrome (TTTS). Unlike TTTS, the optimal management of TAPS is less well understood. The objective of this study was to compare the surgical and obstetric outcomes in patients with TAPS, TTTS + TAPS and TTTS alone who underwent fetoscopic laser surgery (FLS) in pregnancy. STUDY DESIGN: Prospective cohort study of 482 patients with MCDA twins who underwent FLS at a single fetal center during the years 2011-2019. Exclusion criteria were any patients who terminated pregnancy (n ¼ 10), patients for whom no delivery or neonatal outcomes were available (n ¼ 49), and for whom middle cerebral artery Doppler could not be obtained at time of initial evaluation (n ¼ 34). Delivery and pediatric outcomes were obtained from records at patients' delivery hospital. TAPS was diagnosed when the MCA PSV was > 1.5 MoM and < 1.0 MoM in the twin pair. Patients with an initial diagnosis of TAPS, TTTS+TAPS and TTTS alone were compared. RESULTS: 389 patients met inclusion criteria, of which 11 (2.8%) had TAPS, 29 (7.5%) had TTTS+TAPS and 348 (89.7%) had TTTS alone. Patients with TAPS were more likely to have a higher donor MVP and lower recipient MVP. Delta MCA was also higher in patients with TAPS or TAPS +TTTS and there were fewer male fetuses and fewer anastomoses in pregnancies complicated by TAPS or TAPS + TTTS compared to isolated TTTS. Lastly, operative laser time and total energy required to perform FLS was significantly lower in the patients with TAPS. There was no difference in the gestational age at delivery, incidence of PPROM or the distribution of neonatal survivors between the groups. CONCLUSION: FLS is a safe management strategy for pregnancies complicated by TAPS with outcomes similar to patients with TTTS.