Non-invasive fetal RHD genotyping for RhD negative women stratified into RHD gene deletion or variant groups: comparative accuracy using two blood collection tube types.

Non-invasive fetal RHD genotyping in Australia to reduce anti-D usage will need to accommodate both prolonged sample transport times and a diverse population demographic harbouring a range of RHD blood group gene variants. We compared RHD genotyping accuracy using two blood sample collection tube types for RhD negative women stratified into deleted RHD gene haplotype and RHD gene variant cohorts. Maternal blood samples were collected into EDTA and cell-free (cf)DNA stabilising (BCT) tubes from two sites, one interstate. Automated DNA extraction and polymerase chain reaction (PCR) were used to amplify RHD exons 5 and 10 and CCR5. Automated analysis flagged maternal RHD variants, which were classified by genotyping. Time between sample collection and processing ranged from 2.9 to 187.5 hours. cfDNA levels increased with time for EDTA (range 0.03-138 ng/µL) but not BCT samples (0.01-3.24 ng/µL). For the 'deleted' cohort (n=647) all fetal RHD genotyping outcomes were concordant, excepting for one unexplained false negative EDTA sample. Matched against cord RhD serology, negative predictive values using BCT and EDTA tubes were 100% and 99.6%, respectively. Positive predictive values were 99.7% for both types. Overall 37.2% of subjects carried an RhD negative baby. The 'variant' cohort (n=15) included one novel RHD and eight hybrid or African pseudogene variants. Review for fetal RHD specific signals, based on one exon, showed three EDTA samples discordant to BCT, attributed to high maternal cfDNA levels arising from prolonged transport times. For the deleted haplotype cohort, fetal RHD genotyping accuracy was comparable for samples collected in EDTA and BCT tubes despite higher cfDNA levels in the EDTA tubes. Capacity to predict fetal RHD genotype for maternal carriers of hybrid or pseudogene RHD variants requires stringent control of cfDNA levels. We conclude that fetal RHD genotyping is feasible in the Australian environment to avoid unnecessary anti-D immunoglobulin prophylaxis.

Tracheal Atresia with Segmental Esophageal Duplication: An Unusual Anatomic Arrangement.

An unusual anatomic configuration of segmental tracheal agenesis/atresia with esophageal duplication on autopsy in a fetus that demised in utero at 29 weeks is reported. The mother was scanned initially for a cardiac anomaly at 20 weeks and on follow-up scan at 27 weeks had polyhydramnios and underwent amnioreduction. The final autopsy diagnosis was vertebral, ano-rectal, cardiac, tracheoesophageal, renal, and limb malformations (VACTERL). We discuss the autopsy findings along with the embryological mechanisms and compare the configuration with Floyd's classification for tracheal agenesis. The difficulties in prenatal diagnosis are discussed.

Systematic review and metaanalysis of perinatal outcomes after radiofrequency ablation and bipolar cord occlusion in monochorionic pregnancies.

The aim of this study was to analyze perinatal outcomes after selective reduction in monochorionic pregnancies with the use of either radiofrequency ablation (RFA) or bipolar cord occlusion (BCO). This was a systematic review and metaanalysis that included all studies with ≥5 cases that described perinatal outcomes after BCO or RFA that were identified in PubMed, Embase, Web of Science, COCHRANE, CINAHL, Academic Search Premier, Science Direct, and MEDLINE that were published between 1965 and July 2014. For count data, incidence risk ratios (IRR; 95% confidence interval [CI]) were calculated with BCO as the reference standard. The analysis included 481 cases of BCO and 320 cases of RFA from 17 studies. The mean median gestations at procedure were 21.1 ± 1.2 weeks (BCO) and 18.8 ± 2.5 weeks (RFA; P = .03). The rate of cotwin death was higher in the RFA group (14.7%) vs the BCO group (10.6%; IRR, 1.38; 95% CI, 0.93-2.05; P = .11). The live birth rate was 81.3% for the RFA group and 86.7% in the BCO group (IRR, 0.93; 95% CI, 0.80-1.09; P = .41). BCO had higher neonatal death rates (8.1%) vs RFA (4.5%; IRR, 0.56; 95% CI, 0.30-1.04; P = .07). Overall survival was 76.8% for RFA and 79.1% for BCO (IRR, 0.97; 95% CI, 0.82-1.14; P = .72); however, none of these differences were statistically significant. Preterm premature rupture of membranes occurred in 17.7% of RFA cases and 28.2% of the BCO cases (IRR, 0.63; 95% CI, 0.43-0.91; P = .01). The mean median gestational age at delivery was 34.7 ± 1.7 weeks in the RFA group and 35.1 ± 1.6 weeks in the BCO group. Our data do not demonstrate clearly the superiority of 1 procedure over the other. The clinical situation and preference of the operator are important considerations. Rates of preterm delivery and preterm premature rupture of membranes remain substantial for both procedures.

An audit of first trimester ultrasound screening for chromosomal abnormalities.

BACKGROUND: Screening for Down syndrome has been funded in New Zealand since 2010 following the report 'Antenatal Down Syndrome Screening in NZ 2007' which identified that the practice of screening using maternal age and/or nuchal translucency (NT) without biochemical markers was unsafe and should not continue. AIM: This study aimed to assess the quality of the ultrasound component of first trimester screening in a metropolitan population. METHODS: Over a 5-month period, all available NT scan images for women referred to the Central Region Fetal Medicine Unit for an increased risk at first trimester screening or a fetal abnormality detected at the 20-week ultrasound scan were reviewed according to the Fetal Medicine Foundation (FMF) criteria and utilising the Herman Score. This is the standard which the National Screening Unit (NSU) and Ministry of Health (MOH) have mandated for the ultrasound component of the screening test. RESULTS: Of the 52 images, 4 (7.7%) studies were considered unacceptable and another 5 (9.6%) were considered intermediate. The mean score was 5.87 of a possible score of 9. Comparisons with Herman's data are presented and discussed. CONCLUSIONS: This review suggests that there is potential for the quality of the ultrasound component of the first trimester screening component to improve. This would in turn improve the performance of the screening program. We conclude that formal quality control of this screening program is urgently required.