The utility of genome-wide cell-free DNA screening in the prenatal diagnosis of Pallister-Killian syndrome.

OBJECTIVE: To report genome-wide cell-free DNA (cfDNA) screening facilitating the diagnosis of Pallister-Killian syndrome (PKS). METHODS: This is a retrospective cohort analysis of positive genome-wide cfDNA screening results showing increased signal from chromosome 12 and the detection of PKS. The genome-wide cfDNA screening results and the subsequent investigations were reviewed. RESULTS: Three singleton pregnancies (3/29007) from 2016 to 2017 yielded positive results indicating large gains on the entire p-arm of chromosome 12. In two cases, multiple structural abnormalities were detected by prenatal ultrasound and the couples opted for termination of pregnancy. Chromosomal microarray performed on fetal skin tissues of the two abortuses detected mosaic tetrasomy 12p, consistent with PKS. In the third case, karyotype and chromosomal microarray performed on an amniotic fluid sample also showed mosaic tetrasomy 12p. In each of the three cases, genome-wide cfDNA screening revealed a large gain on chromosome 12p; subsequent prenatal or postnatal diagnostic testing confirmed the diagnosis of PKS. CONCLUSION: We report the ability of genome-wide cfDNA screening to provide early suspicion and facilitate the subsequent genetic diagnosis of PKS. As genome-wide cfDNA screening becomes increasingly available, incidental diagnosis of partial aneuploidies is expected to increase.

A fetus coexisting with a complete hydatidiform mole with trisomy 9 of maternal origin.

A complete hydatidiform mole (CHM) coexisting with a viable fetus is a rare finding in pregnancies. Accurate diagnosis often relies on ultrasonographic, histopathological and molecular techniques in the definite diagnosis. To the best of our knowledge, a liveborn fetus coexisting with CHM with trisomy 9 has not been described. The use of molecular genotyping and immunohistochemical laboratory investigations enabled the CHM to be fully characterized. Postzygotic diploidization of a triploid conception arising from dispermy is the proposed mechanism of its formation.

Severe Intrapartum Asphyxia from Subamniotic Hemorrhage.

Subamniotic hemorrhage results from rupture of chorionic vessels near the cord insertion. In the literature, it has never been a major cause for severe intrapartum complications. We report the first case of acute massive subamniotic hemorrhage intrapartum resulting in severe perinatal asphyxia.

Women's uptake of non-invasive DNA testing following a high-risk screening test for trisomy 21 within a publicly funded healthcare system: findings from a retrospective review.

OBJECTIVE: The objective of the study was to evaluate the uptake of non-invasive cell-free fetal DNA screening test (NIDT) after a high-risk screening result for trisomy 21 METHODS: Association between maternal and pregnancy characteristics on women's test choice was assessed after adjusting for confounding factors in Hong Kong Chinese women who had a high-risk (term risk ≥1:250) first-trimester or second-trimester screening test at three public hospitals. Main outcome measures were rate of declining further testing and obstetric and maternal factors impacting on patient's selection of testing options. RESULTS: Compared with the pre-NIDT period, the availability of NIDT resulted in a 45% (P < 0.001) reduction in the rate of refusal for further testing and a decrease from 92.2% to 66.7% in the use of invasive diagnostic test after a positive screening test. Nulliparous women with a spontaneous [adjusted odds ratio (aOR) = 2.18, 95% confidence interval (CI) 1.63-2.92] or assisted reproduction pregnancy (aOR = 3.95, 95% CI 1.6-9.32) were more likely to choose NIDT. Women with an adjusted risk of '>1:10' (aOR = 7.36, 95% CI 4.22-12.8) and '1:10 to 1:50' (aOR = 1.53, 95% CI 1.01-2.32) were more likely to opt for chorionic villi sampling or amniocentesis. CONCLUSIONS: NIDT reduced the refusal rate. Uptake of NIDT was highest in pregnancies of nulliparous women.