E. Scibetta

Clinical accuracy of abnormal cell‐free fetal DNA results for the sex chromosomes

To investigate factors associated with abnormal cell‐free DNA (cfDNA) results for sex chromosomes (SCs).

OP23.10: Prenatal genetic screening and neonatal outcomes in fetuses with echogenic intra-abdominal structures: Short oral presentation abstracts

and their subunits implicated in chromatin remodelling, leading to clinical complications such as neurological development impairment, cancers or high risk of recurrent infections that appear during childhood. We report a case of prenatal diagnosis of CSS. The mother (Gravida 3, Para 2) had no prior medical history. The first ultrasound showed no abnormality. At 18 weeks’ gestation, the ultrasound showed hydrocephalus and macrocephaly, corpus callosum agenesis, a left diaphragmatic hernia, severe IUGR (2nd percentile) and a ventricular septal defect. She requested a medical termination which was accepted according to French law. The autopsy showed an aplasia of the distal phalanx (5th finger), a coarse facies and malformations were confirmed. Sequencing analysis found a de novo ARID1A mutation which is responsible for CSS. Our case highlights signs that could lead to evoking the diagnosis. IUGR is the most frequent sign described prenatally. Ventriculomegaly however had never been described in CSS. Cardiac malformations or cleft palate have been reported in infants with CSS. Their prenatal description remains extremely rare. In one recent case report, ultrasound showed left diaphragm hernia with IUGR, aortic arch hypoplasia, small left sided cardiac structures and a ventricular septal defect. The karyotype was normal, and the diagnosis of CSS was based on clinical findings and whole genome sequencing after birth (ARID1B mutation). To our knowledge, our case and this one are the most severe cases described so far. However, the possibility of prenatal diagnosis appears limited in the absence of an index case. The typical features cannot be seen by sonography, and the malformations reported are variable and non-specific.

P19.09: Regional differences in the management of monochorionic diamniotic (MCDA) twins complicated by Twin-twin transfusion syndrome (TTTS): Poster discussion hub abstracts

Objectives: To elucidate regional differences in management of MCDA pregnancies complicated by TTTS from Facebook (FB) group members. Methods: This was a cross-sectional survey of members of a Facebook (FB) group called ‘‘MoDi Twins’’. REDCAP survey was posted for five days with daily reminders. Participants were collected through ‘‘snowballing,’’ whereby individuals shared the survey to assist with recruiting. Data was analysed using Stata to explore provider type, frequencies of ultrasound screening, treatments and pregnancy outcomes. Categorical variables were analysed using Chi-squared using a p-value of < 0.05. Results: The survey was completed by 2,169 (63% of clicks) subjects, of which 486 (22.4%) were complicated by TTTS. Eighty (16.5%) were diagnosed <16 weeks, 259 (53.5%) between 17-26 weeks and 140 (28.9%) >27 weeks or during labour. Biweekly surveillance resulted in more diagnoses of TTTS at the extremes of GA, when compared to monthly surveillance: at <16 weeks (18.1% versus 8.3%, p<0.001) and > 27 weeks (31.2% versus 18.7%, p<0.001). Regarding treatment of TTTS, 206 (42.5%) had laser ablation, 33 (6.8%) had amnioreduction, and 120 (24.7%) were delivered upon diagnosis. Treatment was performed in stage 1, 2, 3, 4 and 5 in 31.4%, 21.6%, 30.0%, 11.2% and 5.8%, of cases, respectively. Method of treatment had no effect on take home baby rate (p=0.268). MFM involvement in care was associated with a higher take-home baby rate of 73.1% for both and 95.8% of at least one infant, compared to 66.6% and 81.1% with CNM or OB care (p=0.001). Conclusions: The management of TTTS in MCDA gestations varies widely by region and provider type. Guideline recommended biweekly screening increased diagnosis of TTTS at extremes of gestational age, but did not change rate of diagnoses between 17-26 weeks. MFM involvement in care was associated with the highest take-home baby rate in MCDA pregnancies complicated by TTTS.

OC07.08: Variations in antenatal surveillance and patient education in monochorionic-diamniotic (MCDA) twins

Methods: 298 patients with DTT via IVF-ET from January 2012 to December 2016 were retrospectively analysed. These cases were divided into group A (reduced to MS, n = 84), group B (reduced to MDT, n = 149) and group C (without MFPR, n = 65). Group A and B received MFPRs at the 11-13+6 gestational weeks. Fetuses of group C were alive during this time. Results: The live birth rate was higher in group A than B and C (90.50% vs 87.20% vs 86.20%), but with no significance (P > 0.05). Compared with group B, group A had significantly lower rates of premature delivery (11.90% vs 51.70%, P < 0.001), perinatal mortality (5.00% vs 13.40%, P = 0.037), Caesarean section (CS, 66.30% vs 82.10%, P = 0.007) and low birthweight (LBW, 9.20% vs 59.00%, P < 0.001); the gestational age (GA) at delivery (37.9 ± 3.8 vs 35.0 ± 4.2 weeks, P < 0.001) and the live birthweight (3167.8 ± 557.1 vs 2350.8 ± 483.5 g, P < 0.001) were significantly higher in group A. Compared with group C, group A had significantly lower rates of premature delivery (11.90% vs 89.20%, P < 0.001), perinatal mortality (5.00% vs 15.80%, P = 0.015), CS (66.30% vs 83.60%, P = 0.020) and LBW (9.20% vs 92.90%, P < 0.001); the GA at delivery (37.9 ± 3.8 vs 32.8 ± 3.7 weeks, P < 0.001) and the live birthweight (3167.8 ± 557.1 vs 1863.4 ± 409.8 g, P < 0.001) were significantly higher in group A. The rates of preterm delivery (51.70% vs 89.20%, P < 0.001) and LBW (59.00% vs 92.90%, P < 0.001) in group B were significantly lower compared with group C. Conclusions: Both MFPR of DTT to MS and to MDT could obtain better pregnancy outcomes than DTT without reduction. The perinatal pregnancy of MS was better than MDT.

Identification of novel PIEZO1 variants using prenatal exome sequencing and correlation to ultrasound and autopsy findings of recurrent hydrops fetalis

Nonimmune hydrops fetalis (NIHF) is a rare disorder with a high perinatal mortality of at least 50%. One cause of NIHF is generalized lymphatic dysplasia (GLD), a rare form of primary lymphedema of the extremities and systemic involvement including chylothoraces and pericardial effusions. An autosomal recessive form of GLD has been described, caused by variants in the PIEZO1 gene. It has been reported clinically to cause NIHF and childhood onset of facial and limb lymphedema, most of which were diagnosed postnatally. We present a case of a woman with recurrent pregnancies affected by NIHF because of novel compound heterozygous variants in the PIEZO1 gene diagnosed prenatally using exome sequencing (ES). Two variants in PIEZO1 (c.3206G>A and c.6208A>C) were identified that were inherited from the father and mother, and are predicted to cause a nonsense and missense change, respectively, in the PIEZO1 subunits. Ultrasound demonstrated severe bilateral pleural effusions, whole body edema and polyhydramnios. Histopathology revealed an increased number of lymphatic channels, many of which showed failure of luminal canalization. Sanger sequencing confirmed the same variants in a prior fetal demise. We provide phenotypic correlation with ultrasound and autopsy finding, review PIEZO1 variants as a cause of GLD and discuss the uses of prenatal ES to date.