Implementation of fetal clinical exome sequencing: Comparing prospective and retrospective cohorts.

PURPOSE: We compared the diagnostic yield of fetal clinical exome sequencing (fCES) in prospective and retrospective cohorts of pregnancies presenting with anomalies detected using ultrasound. We evaluated factors that led to a higher diagnostic efficiency, such as phenotypic category, clinical characterization, and variant analysis strategy. METHODS: fCES was performed for 303 fetuses (183 ongoing and 120 ended pregnancies, in which chromosomal abnormalities had been excluded) using a trio/duo-based approach and a multistep variant analysis strategy. RESULTS: fCES identified the underlying genetic cause in 13% (24/183) of prospective and 29% (35/120) of retrospective cases. In both cohorts, recessive heterozygous compound genotypes were not rare, and trio and simplex variant analysis strategies were complementary to achieve the highest possible diagnostic rate. Limited prenatal phenotypic information led to interpretation challenges. In 2 prospective cases, in-depth analysis allowed expansion of the spectrum of prenatal presentations for genetic syndromes associated with the SLC17A5 and CHAMP1 genes. CONCLUSION: fCES is diagnostically efficient in fetuses presenting with cerebral, skeletal, urinary, or multiple anomalies. The comparison between the 2 cohorts highlights the importance of providing detailed phenotypic information for better interpretation and prenatal reporting of genetic variants.

Antenatal management and neonatal outcomes of monochorionic twin pregnancies in a tertiary teaching hospital: a 10-year review.

Monochorionic (MC) pregnancy is a high risk pregnancy with well-defined specific complications, such as twin-to-twin transfusion syndrome (TTTS) and twin anaemia-polycythaemia sequence (TAPS). Laser photocoagulation (LPC) is an effective treatment for both complications. In the current retrospective study, we determined the incidence of MC pregnancy complications in a tertiary care centre during a 10-year period. Single foetal death (FD) beyond 14 weeks' gestation was significantly higher when complicated by either TTTS, TAPS or selective foetal growth restriction (21.4%, 16.7% and 9.1% versus 1.6%, p<.001, p=.02 and p=.04, respectively). We also demonstrated that twins' weight discordance >20% is an independent risk factor for single or double FD after LPC. Consequently, prior to LPC, patients should be counselled that early diagnosis of TTTS, advanced Quintero stages and weight discordances >20% are potential risk factors for FD. Further studies are needed to identify additional risk factors for TTTS and TAPS outcome after LPC.Impact StatementWhat is already known on this subject? Monochorionic (MC) pregnancy is a high risk pregnancy with well-defined specific complications, such as twin-twin transfusion syndrome (TTTS) and twin anaemia-polycythaemia sequence (TAPS). Laser photocoagulation (LPC) is an effective treatment for both complications.What the results of this study add? The results of the current study determined the incidence of MC pregnancy complications in a tertiary care centre in Brussels, and identified that twins' weight discordance >20% is an independent risk factor for single or double foetal death after LPC.What the implications are of these findings for clinical practice and/or further research? Prior to laser coagulation, patients should be counselled that early diagnosis of TTTS, Quintero stages 3 or 4 and weight discordances >20% are potential risk factors for foetal demise. Further studies are needed to identify additional risk factors for TTTS and TAPS outcome after LPC.

Agenesis of olfactory bulbs: A forgotten diagnostic indicator of acampomelic campomelic dysplasia.

Campomelic dysplasia (CD) and its variant acampomelic campomelic dysplasia (ACD) are caused by SOX9 haploinsufficiency. This gene encodes a transcription factor crucial for embryogenesis and primarily expressed in the olfactory bulbs. The detection of agenesis of olfactory bulbs could help establish a prenatal diagnosis of CD or ACD, although prevalence of this sign remains unknown.

Analysis of terminal events in 109 successive deaths in a Belgian intensive care unit.

OBJECTIVE: To determine the incidence of end-of-life decisions in intensive care unit (ICU) patients. DESIGN AND SETTING: Prospective data collection and questionnaire in a 31-bed medicosurgical ICU in a university hospital. PATIENTS AND PARTICIPANTS: All 109 ICU patients who died during a 3-month period (April-June 2001). Members of the ICU team were also invited to complete a questionnaire regarding the circumstances of each patient's death. Cardiopulmonary resuscitation was performed in 21 of the patients; other mechanisms leading to death were brain death (n=19), refractory shock (n=17), and refractory hypoxemia (n=2). The decision was taken in the remaining 50 patients to withdraw (n=43) or withhold (n=7) therapy. Questionnaires were completed for 68 patients, by physician and nurse in 40 cases, physician only in 20 cases, and nurse only in 8 cases. Questionnaires were obtained for 34 of 50 patients for whom a decision was made to limit therapy. RESULTS: Respondents generally felt that the decision was timely (n=28, 82%), 5 (15%) felt the decision was too late, and one (3%) that the decision was made too soon, before the family could be informed. CONCLUSIONS: Therapeutic limitations are frequent in patients dying in the ICU, with withdrawing more common than withholding life support. Generally members of the ICU staff were satisfied with the end-of-life decisions made.