Ultrasound methods in conjunction with microbubbles have been used for brain drug delivery, treatment of stroke, and imaging of cerebral blood flow. Despite advances in these areas, questions remain regarding the range of ultrasound parameters that disrupt the blood-brain barrier (BBB). In this study, several conditions were investigated to either enhance or reduce the likelihood of BBB disruption. Pulsed focused ultrasound (frequency: 1.5 MHz, pressure: 0.46 MPa, pulse repetition frequency (PRF): 0.1 to 25 Hz, pulse length (PL): 0.03 to 30 milliseconds) was noninvasively and locally administered to a predetermined region in the left hemisphere in the presence of circulating preformed microbubbles (Definity, Lantheus Medical Imaging, N. Billerica, MA, USA; 0.01, 0.05, 0.25 μL/g). Trans-BBB delivery of 3-kDa dextran was observed at PRFs as low as 1 Hz, whereas consistent delivery was observed at 5 Hz and above. Delivery was demonstrated at a PL as low as 33 microseconds. Although the delivered dextran concentration increased with the PL, this also increased the heterogeneity of the resulting distribution. In conclusion, key parameters that disrupt the BBB were identified out of a wide range of conditions. Reducing the total number of emitted acoustic cycles by shortening the PL, or decreasing the PRF, was also found to facilitate a more spatially uniform distribution of delivered dextran.

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.

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nonobese women (Table) and occurred in 50% of patients with CL <20mm in both groups. CL performed equally well as a predictor for sPTB <34 weeks in obese and nonobese women (Figure). The sensitivity and specificity of CL <20mm for sPTB <34 weeks did not differ between groups. CONCLUSION: Obese women are at higher risk for sPTB prior to 34, 28, and 24 weeks. This risk appears to be independent of midtrimester CL, suggesting that the etiology of PTB in obese patients may not be cervical insufficiency.

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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.

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