Prospective risk of stillbirth and neonatal complications for monochorionic diamniotic and dichorionic diamniotic twins after 24 weeks of gestation.

INTRODUCTION: Our study compared the prospective risks of intrauterine fetal death (IUFD), neonatal death (NND), perinatal death (PND), and neonatal morbidities in monochorionic diamniotic (MCDA) and dichorionic diamniotic (DCDA) twin pregnancies. METHODS: This retrospective cohort study included twin pregnancies who had antenatal care and delivery in a public hospital from 2011 to 2018. Exclusion criteria included monoamnionicity, one/both twin miscarriage, twin-twin transfusion syndrome, or lethal congenital abnormalities. All twins were managed in multiple pregnancy clinic with standardized protocols. Gestational age-specific IUFD, NND, PND, and neonatal morbidity rates were compared according to chorionicity. RESULTS: Three hundred seventy-eight MCDA and 1282 DCDA twins were included. MCDA twins had higher risks of PND (1.9% vs. 0.7% in DCDA twins, p = 0.05), composite neonatal morbidity (p = 0.01), preterm delivery (p < 0.01), and low birth weight (p < 0.01). The prospective risk of IUFD was 0.6% and 0.4% for MCDA and DCDA twins, respectively after 34 weeks' gestation. No NND occurred among deliveries after 30 weeks. The risk of neonatal morbidity of MCDA twins fell from 22.7% at 34 weeks to 2.7% at 37 weeks (p < 0.01). For DCDA twins, the risk of morbidity fell insignificantly from 36 to 38 weeks (4.0% vs. 3.4%, p = 0.60). Logistic regression analysis suggested that the increased risk of perinatal morbidities was related to the higher rate of preterm delivery in MCDA twins rather than chorionicity. CONCLUSION: With close fetal monitoring, the risk of late IUFD in twin pregnancies without major complications is low. Perinatal morbidity can be minimized by avoiding late preterm deliveries in twin pregnancies.

Implementation of Public Funded Genome Sequencing in Evaluation of Fetal Structural Anomalies.

With the advancements in prenatal diagnostics, genome sequencing is now incorporated into clinical use to maximize the diagnostic yield following uninformative conventional tests (karyotype and chromosomal microarray analysis). Hong Kong started publicly funded prenatal genomic sequencing as a sequential test in the investigation of fetal structural anomalies in April 2021. The objective of the study was to evaluate the clinical performance and usefulness of this new service over one year. We established a web-based multidisciplinary team to facilitate case selection among the expert members. We retrospectively analyzed the fetal phenotypes, test results, turnaround time and clinical impact in the first 15 whole exome sequencing and 14 whole genome sequencing. Overall, the molecular diagnostic rate was 37.9% (11/29). De novo autosomal dominant disorders accounted for 72.7% (8/11), inherited autosomal recessive disorders for 18.2% (2/11), and inherited X-linked disorders for 9.1% (1/11). The median turnaround time for ongoing pregnancy was 19.5 days (range, 13-31 days). Our study showed an overall clinical impact of 55.2% (16/29), which influenced reproductive decision-making in four cases, guided perinatal management in two cases and helped future family planning in ten cases. In conclusion, our findings support the important role of genome sequencing services in the prenatal diagnosis of fetal structural anomalies in a population setting. It is important to adopt a multidisciplinary team approach to support the comprehensive genetic service.

Application of Prenatal Whole Exome Sequencing for Structural Congenital Anomalies-Experience from a Local Prenatal Diagnostic Laboratory.

Fetal structural congenital abnormalities (SCAs) complicate 2-3% of all pregnancies. Whole-exome sequencing (WES) has been increasingly adopted prenatally when karyotyping and chromosomal microarray do not yield a diagnosis. This is a retrospective cohort study of 104 fetuses with SCAs identified on antenatal ultrasound in Hong Kong, where whole exome sequencing is performed. Molecular diagnosis was obtained in 25 of the 104 fetuses (24%). The highest diagnostic rate was found in fetuses with multiple SCAs (29.2%), particularly those with involvement of the cardiac and musculoskeletal systems. Variants of uncertain significance were detected in 8 out of the 104 fetuses (7.7%). Our study shows the utility of WES in the prenatal setting, and the extended use of the technology would be recommended in addition to conventional genetic workup.