Learning curve for fetal postmortem ultrasound.

OBJECTIVE: To determine the learning curve of fetal postmortem ultrasound (PMUS) and evaluate the evolution of its diagnostic performance over the past 8 years. METHODS: PMUS was performed by two fetal medicine specialists and two experts on 100 unselected fetuses of 12-38 weeks of gestation in a prospective, double-blind manner. 21 pre-defined internal structures were analyzed consecutively by the trainee alone and the expert, with a comparison of diagnosis and immediate feedback. The learning curves for examination duration, non-recognition of structures and final diagnoses were computed using cumulative summation analysis. Secondly, the expert PMUS diagnostic accuracy using autopsy as the gold standard was compared to the previously published data. RESULTS: The trainees reached expert level of PMUS at 28-36 cases for examination duration (12.1 ± 5.2 min), non-diagnostic rate (6.5%, 137/2100), and abnormality diagnosis. In a group of 33 fetuses ≥20 weeks who had an autopsy, the experts PMUS performance was improved after 8 years with a reduction of all organs non-diagnostic rate (6.5 %VS 11.4%, p < 0.01) and higher sensitivity for the heart (100% VS 40.9%, p < 0.01) and the abdomen (100%VS 56.5%, p < 0.05). CONCLUSION: PMUS offers a short learning curve for fetal medicine specialists and on-going improvement of diagnostic accuracy over time.

Evaluation of the new expert consensus-based definition of selective fetal growth restriction in monochorionic pregnancies.

OBJECTIVE: To compare the outcomes of a cohort of monochorionic pregnancies with selective fetal growth restriction (sFGR) diagnosed according to the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG) definition published in 2015 with a cohort considered as sFGR according to new expert consensus-based diagnostic parameters published in 2019. METHODS: This was a retrospective study, conducted between January 1st 2010 and July 30th 2019. We reviewed the medical records of all the monochorionic pregnancies followed in our center including perinatal outcomes. Pregnancies complicated by fetal anomalies, infection, twin-twin transfusion syndrome, twin anaemia-polycythemia sequence and twin reversed arterial perfusion sequence were excluded. Patients were grouped according to the 2015 ISUOG definition into: normal (Group 1), sFGR (Group 2), and monochorionic pregnancies with abnormal growth that did not fulfill the full criteria for sFGR (Group 3). After the initial classifications were made, an additional group, was created, including all pregnancies reclassified as sFGR according to the 2019 expert consensus parameters (Group 4). RESULTS: During the study period, 291 monochorionic pregnancies were followed in our center, 132 of whom were eligible for inclusion in the final analysis. The prevalence of sFGR increased from 17.4% to 26.5% after applying the expert consensus-based parameters to the study population. Compared to group 1, group 2 had higher rates of emergency cesarean, neonatal intensive care admissions, invasive and noninvasive ventilation, surfactant use, metabolic disorders and lower gestational ages at birth. In contrast, the neonatal outcomes of Groups 1 and 4 were not significantly different. CONCLUSION: When the 2019 consensus-based diagnostic parameters for sFGR were applied to our study population, the number of sFGR cases increased by over 50%, without any improvements in perinatal outcomes. Larger prospective studies are needed to examine the potential clinical implications of these new parameters for sFGR in monochorionic pregnancies.

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.

Impact of the delay between fetal death and delivery on the success of postmortem ultrasound following termination of pregnancy.

OBJECTIVE: To evaluate the impact of the delay between fetal death and delivery on the nondiagnostic rates of post-mortem ultrasound (PM-US), following the termination of pregnancy (TOP). METHODS: We reviewed 204 cases of fetal two-dimensional PM-US performed in our center as part of a post-mortem imaging research program, over the last 5 years. Informed consent was obtained from the parents for all cases. PM-US was performed and reported according to a prespecified template with operators blinded to the prenatal diagnosis. In order to calculate the precise delay between the fetal death and the delivery, we included 107 fetal TOP's ≥ 20 weeks of gestational age (GA), where feticide was performed using an injection of lidocaine 2% prior to induction of labor. Logistic regression analysis was conducted to analyze the impact of delay between fetal death and delivery (in hours), the GA at TOP (in weeks) and the method of feticide (intracardiac versus intraumbilical injection) on the PMUS nondiagnostic rates. RESULTS: The delay between fetal death and delivery increased the nondiagnostic rate of PM-US for cerebral examinations (OR: 1.04, IC 95%: 1.01-1.08, p < .05). For PM-US cardiac examination, the delay did not influence the nondiagnostic rate. However, GA (OR: 1.25, IC 95%: 1.10-1.46, p < .01) and feticide with intracardiac injection (OR: 4.29, IC 95%: 1.68-12.02, p < .01) were associated with higher nondiagnostic rates. For noncardiac thoracic and abdominal examinations, none of the studied variables influenced the nondiagnostic rate. CONCLUSION: The success rate of cerebral PM-US was influenced by the delay between fetal death and delivery, suggesting a possible advantage of performing the feticide closer to the delivery where the examination of the brain is planned. For cardiac abnormalities, feticide by intraumbilical, rather than intracardiac injection improves diagnostic rates of cardiac PM-US.

Cell-Free DNA Analysis in Maternal Blood: Differences in Estimates between Laboratories with Different Methodologies Using a Propensity Score Approach.

OBJECTIVES: To evaluate the failure rate and performance of cell-free DNA (cfDNA) testing, mainly in terms of detection rates for trisomy 21, performed by 2 laboratories using different analytical methods. METHODS: cfDNA testing was performed on 2,870 pregnancies with the HarmonyTM Prenatal Test using the targeted digital analysis of selected regions (DANSR) method, and on 2,635 pregnancies with the "Cerba test" using the genome-wide massively parallel sequencing (GW-MPS) method, with available outcomes. Propensity score analysis was used to match patients between the 2 groups. A comparison of the detection rates for trisomy 21 between the 2 laboratories was made. RESULTS: In all, 2,811 patients in the Harmony group and 2,530 patients in the Cerba group had no trisomy 21, 18, or 13. Postmatched comparisons of the patient characteristics indicated a higher no-result rate in the Harmony group (1.30%) than in the Cerba group (0.75%; p = 0.039). All 41 cases of trisomy 21 in the Harmony group and 93 cases in the Cerba group were detected. CONCLUSIONS: Both methods of cfDNA testing showed low no-result rates and a comparable performance in detecting trisomy 21; yet GW-MPS had a slightly lower no-result rate than the DANSR method.

Profile of women choosing the Harmony® Prenatal Test.

INTRODUCTION: The Harmony® Prenatal Test, a noninvasive cell-free DNA (cfDNA) method for major trisomies has been available since January 2013 at our unit, and tests were sent to the Ariosa Clinical Laboratory Improvement Amendments (CLIA) laboratory in California. From July 2017 onward, prenatal cfDNA has been reimbursed in Belgium for all pregnancies; however, since then samples are sent to a local laboratory. Little data are available on patient's profile and choices toward cfDNA and on the performance of local technology transfer centers. Areas covered: The profiles and choices of women regarding this test were evaluated. Further, the performance of cfDNA at the local laboratory was compared to the one in California. Our results showed that women from the Netherlands, as compared to Belgium, were more likely to undergo cfDNA testing for maternal request and would be less likely to undergo karyotyping if cfDNA were unavailable, therefore are better candidates for cfDNA testing, when this is used as first-line screening. Expert commentary: Our findings highlight the importance of conducting these types of studies, before decisions about clinical implementation are made by national governments and ministries of health.

Post-mortem whole-body magnetic resonance imaging of human fetuses: a comparison of 3-T vs. 1.5-T MR imaging with classical autopsy.

OBJECTIVE: To prospectively compare diagnostic accuracy of fetal post-mortem whole-body MRI at 3-T vs. 1.5-T. METHODS: Between 2012 and 2015, post-mortem MRI at 1.5-T and 3-T was performed in fetuses after miscarriage/stillbirth or termination. Clinical MRI diagnoses were assessed using a confidence diagnostic score and compared with classical autopsy to derive a diagnostic error score. The relation of diagnostic error for each organ group with gestational age was calculated and 1.5-T with 3-T was compared with accuracy analysis. RESULTS: 135 fetuses at 12-41 weeks underwent post-mortem MRI (followed by conventional autopsy in 92 fetuses). For all organ groups except the brain, and for both modalities, the diagnostic error decreased with gestation (P < 0.0001). 3-T MRI diagnostic error was significantly lower than that of 1.5-T for all anatomic structures and organ groups, except the orbits and brain. This difference was maintained for fetuses <20 weeks gestation. Moreover, 3-T was associated with fewer non-diagnostic scans and greater concordance with classical autopsy than 1.5-T MRI, especially for the thorax, heart and abdomen in fetuses <20 weeks. CONCLUSION: Post-mortem fetal 3-T MRI improves confidence scores and overall accuracy compared with 1.5-T, mainly for the thorax, heart and abdomen of fetuses <20 weeks of gestation. KEY POINTS: • In PM-MRI, diagnostic error using 3-T is lower than that with 1.5-T. • In PM-MRI, diagnostic scan rate is higher using 3-T than 1.5-T. • In PM-MRI, concordance with classical autopsy increases with 3-T. • PM-MRI using 3-T is particularly interesting for thoracic and abdominal organs. • PM-MRI using 3-T is particularly interesting for fetuses < 20 weeks' gestation.