A set of 21 early maternal serum samples (19 first-trimester and two at 14 weeks) from pregnancies resulting in a child with Down syndrome was matched for gestation and length of storage with 63 samples from unaffected pregnancies. The concentrations of alpha-fetoprotein (AFP), unconjugated oestriol (uE3), human chorionic gonadotrophin (hCG), pregnancy-specific beta 1-glycoprotein (SP1), and placental alkaline phosphatase (PALP) were measured. The ratios of the medians for Down syndrome pregnancies compared with the medians for controls were AFP 0.71, uE3 0.67, hCG 1.43, SP1 0.79, and PALP 0.92. Although the differences between the medians for affected and unaffected pregnancies were not significant, the trends for AFP, uE3, and hCG confirm earlier findings on first-trimester samples.

BackgroundTesting for human papillomavirus (HPV) is being incorporated into the cervical screening programme, with the probable future introduction of HPV as a primary test and a possibility of HPV self‐sampling. In anticipation of this development, we sought to inform future policy and practice by identifying potential barriers to HPV self‐sampling.MethodsA cross‐sectional survey of 194 women aged 20‐64 years was conducted. Logistic regression analysis was used to identify determinants of self‐sampling intentions. A purposive subsample of 19 women who reported low self‐sampling intentions were interviewed. Interviews were framework‐analysed.ResultsMost survey participants (N=133, 69.3%) intended to HPV self‐sample. Lower intention was associated with lower self‐efficacy (OR=24.96, P≤.001), lower education (OR=6.06, P≤.05) and lower perceived importance of HPV as a cause of cervical cancer (OR=2.33, P≤.05). Interviews revealed personal and system‐related barriers. Personal barriers included a lack of knowledge about HPV self‐sampling, women's low confidence in their ability to self‐sample correctly and low confidence in the subsequent results. System‐related factors included a lack of confidence in the rationale for modifying the current cervical screening programme, and concerns about sample contamination and identity theft.ConclusionsInsights gained from this research can be used to guide further enquiry into the possibility of HPV self‐sampling and to help inform future policy and practice. Personal and system‐related barriers including low confidence in the reasons for changing current cervical screening provision need to be addressed, should HPV self‐sampling be incorporated into the cervical screening programme.

BACKGROUND The currently recommended technologies of HPLC and isoelectric focusing for newborn blood spot screening for sickle cell disease (SCD) identify both the disease and carrier states, resulting in large numbers of infants being followed up unnecessarily. Analysis of blood spot tryptic peptides performed by using tandem mass spectrometry (MS/MS) is an alternative technology to detect hemoglobin (Hb) variant disorders. METHODS We analyzed 2154 residual newborn blood spots and 675 newborn blood spots from infants with Hb variants by using MS/MS after trypsin digestion. Screening cutoffs were developed by using the ratio between the variant peptide–to–wild-type peptide abundance for HbS, C, DPunjab, OArab, Lepore, and E peptides. A postanalytical data analysis protocol was developed using these cutoffs to detect only the disease states of SCD and not to identify carrier states. A parallel study of 13 249 newborn blood spots from a high-prevalence SCD area were analyzed by both MS/MS and HPLC. RESULTS Screening cutoffs developed distinguished the infants with the disease states of SCD, infants who were carriers of SCD, and infants with normal Hb. In the parallel study no false-negative results were identified, and all clinically relevant cases were correctly identified using the MS/MS protocol. Unblinding the data revealed a total of 328 carrier infants that were successfully excluded by the protocol. CONCLUSIONS The screening protocol developed correctly identified infants with the disease states of SCD. Furthermore, large numbers of sickle cell carrier infants were successfully not identified, thereby avoiding unnecessary follow-up testing and referral for genetic counseling.

The distribution of blood spot TSH data from neonates in Wales has revealed no evidence to support the hypothesis that the population is iodine deficient. However, given that mild iodine deficiency has been reported in a cohort that will be childbearing in the next decade, we recommend that the distribution of neonatal blood spot TSH concentrations is monitored by the UK newborn screening programmes to identify any emerging trends in iodine status. Further studies to correlate maternal urinary iodine and newborn blood spot TSH are required to clarify the TSH cut-off points associated with mild iodine deficiency relevant to the time of blood spot sampling in the UK.

Background Most post-colonoscopy interval colorectal cancers are proximal; serrated polyps are often precursors to these cancers and are considered difficult to detect. We assessed the safety, feasibility, and economic effect of chromocolonoscopy on detection of proximal serrated neoplasia. Methods We did an open-label, multicentre, randomised, controlled non-inferiority trial including patients from Bowel Screening Wales centres. Participants who tested positive for faecal occult blood and who were eligible for and considered fit to have colonoscopy (patients with known cases of polyposis syndromes, Lynch syndrome, and chronic inflammatory disease were excluded) were randomly assigned (1:1; with the use of minimisation, stratified by centre with an 80:20 random element) to either standard white light colonoscopy (standard group) or chromocolonoscopy (indigo carmine dye [0•2%]; chromocolonoscopy group) using a secure, internet-based, computerised, randomisation system that used centralised, dynamic allocation. Participants were followed up for 1 year and data from index colonoscopies and associated clearance procedures were analysed. All proximal polyps were reviewed by an expert pathologist panel. The main outcome on which power was based was time taken to perform the colonoscopy procedure, defined as from the time when the scope was inserted to withdrawal from the anus, assessed in the per-protocol population. The non-inferiority margin was 15 min. This trial is complete and is registered with ClinicalTrials.gov, number NCT01972451.

Background Tandem mass spectrometry (MS/MS) has recently become an alternative method for the newborn screening of sickle cell disorders (SCD), as it is able to detect haemoglobin (Hb) peptides following digestion of bloodspots with trypsin. Using the SpOtOn Diagnostics Reagent Kit, we previously developed a screening protocol to detect only the disease states of SCD, using action values based on the ratio between the variant Hb peptide to wild-type peptide abundances for the HbS, C, D, O, E and Lepore peptides. Methods Action values using the ratios between the wild type HbA (ßT1-3) peptides and the foetal Hb (γT2) peptide were developed to identify bloodspot samples from premature and transfused infants. An evaluation was undertaken to assess the transferability of the action values onto an additional MS/MS instrument. We report here our experience using this MS/MS protocol. Results During a three-year period, we screened 100,456 babies and identified 10 SCD cases (1 HbS/HPFH, 5 HbS/S and 4 HbS/C) and a case of HbE/ß-thalassaemia that was identified as a by-product. The Hb variant to wild-type peptide ratio action values were transferable to a second MS/MS instrument. Our protocol prevented the identification of an estimated 810 carrier infants. Gestational age-related action values for HbA to HbF peptide ratios were required to minimize the number of samples referred for second-line testing to exclude ß-thalassaemia. Conclusion MS/MS is a robust alternative screening technology for SCD; in addition, it also optimizes the use of equipment and expertise that currently exist in newborn screening laboratories.

Objective To evaluate the implementation of non‐invasive prenatal testing (NIPT) on pregnant women's choices in a national NHS antenatal screening programme for Down's syndrome, Edwards' syndrome and Patau's syndrome. Method An observational study of all pregnant women with a singleton pregnancy and higher chance (≤1:150) combined or quadruple screening result from 30 April 2018 to 25 September 2020 in Wales, UK. Pregnant women's journey through the pathway was determined including uptake of NIPT, performance of NIPT in a non‐research setting and invasive procedures performed. Results Of the 1273 women with a higher chance initial screening, 1073 (84%) chose NIPT contingent test, 174 (14%) no further testing and 26 (2%) invasive procedure. There were 1001 (93%) low chance NIPT results; 11 (1%) failed results and 61 (6%) high chance results. Average annual incidence of 27 invasive procedures undertaken compared to 229 pre‐NIPT implementation, a nearly ninefold reduction. Down's syndrome annual live birth rate remained unchanged across the implementation period. Discussion This study demonstrates that NIPT contingent screening was highly acceptable to women with a resulting reduction in invasive procedures performed. Conclusion The high uptake of NIPT in NHS antenatal screening pathway conditions should inform planning for other national screening programmes.

Background Response to the early stages of the COVID-19 pandemic resulted in the temporary disruption of cancer screening in the UK, and strong public messaging to stay safe and to protect NHS capacity. Following reintroduction in services, we explored the impact on inequalities in uptake of the Bowel Screening Wales (BSW) programme to identify groups who may benefit from tailored interventions. Methods Records within the BSW were linked to electronic health records (EHR) and administrative data within the Secured Anonymised Information Linkage (SAIL) Databank. Ethnic group was obtained from a linked data method available within SAIL. We examined uptake for the first 3 months of invitations (August to October) following the reintroduction of BSW programme in 2020, compared to the same period in the preceding 3 years. Uptake was measured across a 6 month follow-up period. Logistic models were conducted to analyse variations in uptake by sex, age group, income deprivation quintile, urban/rural location, ethnic group, and clinically extremely vulnerable (CEV) status in each period; and to compare uptake within sociodemographic groups between different periods. Results Uptake during August to October 2020 (period 2020/21; 60.4%) declined compared to the same period in 2019/20 (62.7%) but remained above the 60% Welsh standard. Variation by sex, age, income deprivation, and ethnic groups was observed in all periods studied. Compared to the pre-pandemic period in 2019/20, uptake declined for most demographic groups, except for older individuals (70–74 years) and those in the most income deprived group. Uptake continues to be lower in males, younger individuals, people living in the most income deprived areas and those of Asian and unknown ethnic backgrounds. Conclusion Our findings are encouraging with overall uptake achieving the 60% Welsh standard during the first three months after the programme restarted in 2020 despite the disruption. Inequalities did not worsen after the programme resumed activities but variations in CRC screening in Wales associated with sex, age, deprivation and ethnic group remain. This needs to be considered in targeting strategies to improve uptake and informed choice in CRC screening to avoid exacerbating disparities in CRC outcomes as screening services recover from the pandemic.