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Cell-free fetal DNA (cffDNA) can be detected in the maternal circulation from 4 weeks gestation, and is present with cell-free maternal DNA at a level of between 5 % and 20 %. Cell-free DNA (cfDNA) can be extracted from a maternal blood sample and, although it is not possible to separate the fetal from the maternal cfDNA, it has enabled non-invasive prenatal diagnosis (NIPD) without the associated miscarriage risk that accompanies invasive testing. NIPD for monogenic diseases was first reported in 2000 and since then there have been many proof of principle studies showing how analysis of cfDNA can provide a definitive diagnosis early in pregnancy for a wide range of single gene diseases. Testing for a number of these diseases has been available in the UK National Health Service (NHS) since 2012. This review highlights the main techniques that are being used for NIPD and discusses the technical limitations of the methods, as well as the advances that are being made to overcome some of the issues. NIPD is technologically challenging for a number of reasons. Firstly, because it requires the detection of low level fetal variants in a high maternal background. For de novo and paternally-inherited variants this has been achieved through the use of techniques such as next-generation sequencing (NGS) and digital PCR to detect variants in the cffDNA that are not present in the maternal cfDNA. However, for maternally-inherited variants this is much more challenging and relies on dosage-based techniques to detect small differences in the levels of mutant and wild-type alleles. Alongside the technical advances that are making NIPD more widely available in both the public healthcare and commercial settings, it is crucial that we continue to monitor the social and ethical impact to ensure that patients are being offered safe and accurate testing. [ABSTRACT FROM AUTHOR]

Aim: To estimate the rate of unexpected brain abnormalities detected by in utero magnetic resonance imaging (iuMRI) in fetuses without abnormalities at ultrasonography (USS).Materials and Methods: A prospective cohort study of pregnant women whose fetus had no structural brain (or body) abnormalities recognised on antenatal ultrasonography. Women were recruited from 12 centres across the UK and underwent iuMRI at 18 gestational weeks or more in the [blinded for review]. The imaging studies were reviewed by an experienced neuroradiologist. The positive and negative predictive values of both USS and iuMRI have been calculated by combining the results of this study with the results from the main [blinded for review] study.Results: One hundred and ninety-eight pregnant women were recruited and underwent iuMRI of 205 fetuses. Brain abnormalities were shown on iuMRI in two fetuses that were not recognised on USS (one case of a focal cortical abnormality and one case of mild ventriculomegaly). The negative predictive value for USS was 99.5% and 100% for iuMRI.Conclusions: To the authors' knowledge, this is the first study comparing USS and iuMRI in low-risk pregnancies. USS has a comparatively high rule-out for fetal brain abnormalities and should remain the screening tool of choice. [ABSTRACT FROM AUTHOR]

‘Experiential knowledge’ is increasingly recognised as an important influence on reproductive decision-making. ‘Experiential knowledge of disability’ in particular is a significant resource within prenatal testing/screening contexts, enabling prospective parents to imagine and appraise future lives affected by disability. However, the concept of ‘experiential knowledge’ has been widely critiqued for its idiosyncrasy, its impermanence and consequently its perceived inferiority to (medical) knowledge. This paper explores some of these key critiques of experiential knowledge through an analysis of its constitution and uses in the context of reproductive decision-making. Seventeen UK-resident women with Spinal Muscular Atrophy (SMA), or with SMA in their family, took part in two in-depth interviews: one in 2007–9 and the other in 2013–4. By comparing and contrasting these women's accounts at two time points, this paper demonstrates the stark contrast between ‘lived experience’ of SMA (the visceral everyday realities of life with the condition) and the various way(s) this experience was transformed into, and presented as, ‘knowledge’ through the processes of making, and accounting, for reproductive decisions. The analysis highlights that multiple, distinct and sometimes competing experiential frameworks are used to conceptualise SMA across time and context. However, rather than evidence of its fallibility, this finding highlights that ‘knowledge’ is an inappropriate vessel with which to capture and transfer ‘experiential knowledge’. Rather, we need to consider how to value such insight in ways that harnesses its inherent strength without leaving it vulnerable to the epistemological critiques attracted by labelling it ‘knowledge’. [ABSTRACT FROM AUTHOR]

Abstract: There has been a striking growth in the availability of health-related information based on personal experience in recent years and internet users are often drawn towards other people’s stories about their health. Accounts of other people’s experiences might convey social and emotional information that is not otherwise available but little is known about how it is used or the implications of its use in practice. This paper examines how people refer to information about other people’s experiences when accounting for decisions about antenatal diagnostic testing for foetal abnormality. We conducted a secondary analysis of 37 qualitative interviews undertaken across the UK with 36 women and nine of their male partners (eight couples were interviewed together) who talked about diagnostic testing for foetal abnormality in 55 pregnancies. When describing their decisions, respondents referred to examples of knowledge gleaned from their own and other individuals’ experiences as well as information based on biomedical or clinical-epidemiological research (usually about the probabilities of having a child affected by health problems or the probability of diagnostic tests causing miscarriage). Both forms of knowledge were employed in people’s accounts to illustrate the legitimacy and internal coherence of decisions taken. The analysis demonstrates the personally idiosyncratic ways that people reflect on and incorporate different types of information to add meaning to abstract ideas about risk, to imagine the consequences for their own lives and to help them to make sense of the decisions they faced. [Copyright &y& Elsevier]

Adenylosuccinate lyase deficiency is an autosomal recessive disorder of purine metabolism resulting from mutations in the ADSL gene on chromosome subband 22q13.1 and associated with a wide range of clinical manifestations. Although there is currently no effective treatment of ADSL deficiency, recognition of the condition is important, because prenatal genetic diagnosis can be offered to affected families. Reported here are the cases of the only three children diagnosed to date in the United Kingdom with adenylosuccinate lyase deficiency, to further delineate the clinical phenotype and to raise awareness of this disorder. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: The aim of this study was to update the incidence data of beta thalassaemia mutations in various populations and compare it to the spectrum of mutations in the United Kingdom (UK) population in order to determine the impact of immigration. Design and methods: Published data for the β-thalassaemia mutation spectrum and allele frequencies for 60 other countries was updated and collated into regional tables. The β-thalassaemia mutations in the UK population have been characterised in 1712 unrelated carriers referred for antenatal screening. Similarly, the α-thalassaemia mutations in the UK population have been characterised in 2500 possible α-thalassaemia carriers. Results: A total of 68 different β-thalassaemia mutations were identified in couples requiring screening for antenatal diagnosis in the UK population. Of these mutations, 59 were found in immigrants to the UK, from all major ethnic groups with a high incidence of haemoglobinopathies. A total of 40 different α-thalassaemia mutations were characterised in the UK population. Ten deletion mutations were identified, including all the Southeast Asian and Mediterranean α0-thalassaemia mutations. In addition, 30 non-deletion α+-thalassaemia mutations were discovered, accounting for 46% of the worldwide known non-deletion mutations. Conclusions: The impact of immigration has resulted in the UK population having a higher number of β-thalassaemia mutations and α-thalassaemia mutations than any of the 60 other countries with a published spectrum of mutations, including both endemic countries and the non-endemic countries of Northern Europe. The racial heterogeneity of the immigrant population in a non-endemic country significantly increases the spectrum of haemoglobinopathy mutations and their combinations found in individuals, making the provision of a molecular diagnostic prenatal diagnosis service more challenging. [Copyright &y& Elsevier]

Ultrasound examinations for foetal brain abnormalities have been a part of the routine antenatal screening programme in the UK for many years. In utero brain magnetic resonance imaging (MRI) is now being used increasingly successfully to clarify abnormal ultrasound findings, often resulting in a change of diagnosis or treatment plan. Interpretation requires an understanding of foetal brain development, malformations and acquired diseases. In this paper we will outline the technique of foetal MRI, relevant aspects of brain development and provide illustrated examples of foetal brain pathology. [Copyright &y& Elsevier]

Abstract: Through the lens of the ‘welfare of the child’ assessment, this paper explores how staff working in the area of in vitro fertilisation and preimplantation genetic diagnosis (IVF/PGD) balance reflexive relations of legitimacy and accountability between the public and private spheres, and between medicine, the citizen and the state. The wider research of which this analysis is a part uses multiple methods to study two National Health Service Assisted Conception Units in England. Research methods used included observation clinics and interviews with staff from a range of disciplines. We illustrate how the staff reveal tensions between their views that the welfare of the child assessment can be seen as intrusive and discriminatory, and on the other hand that medical intervention in reproduction should be socially and professionally accountable. These tensions can be understood sociologically in terms of a gradual movement from socially based solutions to fertility problems and disabilities, towards a biomedical, and arguably genetically oriented worldview of such problems. Rather than being viewed as discrete, these two orientations should be seen as indicating an emergent direction of travel along a continuum, with elements of both being present in the accounts. We argue that consideration of the welfare of the child involves staff in ethical boundary-work across the two orientations and between the accountabilities and responsibilities of healthcare professionals, individuals and the state. [Copyright &y& Elsevier]

Objective: The objective of this study was to explore the relationship between the number of antenatal visits made by a representative sample of British women and adverse perinatal outcomes. Study design: A total of 20,771 women with a singleton pregnancy were recruited from nine representative maternity units in Northern England and North Wales. A record of each woman’s antenatal care and the adverse perinatal outcomes of interest were extracted retrospectively from their case notes. Multivariate binomial regression was used to model the probability of adverse outcomes with respect to the absolute number of antenatal visits, after controlling for potentially confounding factors. Separate analyses were performed for primiparae and multiparae, and for low- and high-risk women within each parous group. Results: The study revealed an inverse association between the number of antenatal visits and delivery of a low birthweight infant, infant admission to a special care baby unit and perinatal mortality over the 4–14 antenatal visit range, which dissipated at higher levels of antenatal visits. The study also revealed a significant positive association between the number of antenatal visits and delivery by caesarean section (P<0.01). Similar trends in the probabilities of adverse outcomes were observed for low- and high-risk women within each parous group. Conclusion: Further experimental research is required to ascertain whether a causal relationship exists between antenatal visiting schedules and adverse perinatal outcomes. [Copyright &y& Elsevier]

The aim of this prospective study is to assess the reliability and validity of a multi-dimensional measure of informed choice (MMIC). Participants were 225 pregnant women in two general hospitals in the UK, women receiving low-risk results following serum screening for Down syndrome. The MMIC was administered before testing and the Ottawa Decisional Conflict Scale was administered 6 weeks later. The component scales of the MMIC, knowledge and attitude, were internally consistent (alpha values of 0.68 and 0.78, respectively). Those who made a choice categorised as informed using the MMIC rated their decision 6 weeks later as being more informed, better supported and of higher quality than women whose choice was categorised as uninformed. This provides evidence of predictive validity, whilst the lack of association between the MMIC and anxiety shows construct (discriminant) validity. Thus, the MMIC has been shown to be psychometrically robust in pregnant women offered the choice to undergo prenatal screening for Down syndrome and receiving a low-risk result. Replication of this finding in other groups, facing other decisions, with other outcomes, should be assessed in future research. [Copyright &y& Elsevier]

Explores the difficulties encountered by health practitioners about nondirectiveness within the context of antenatal screening and testing in Great Britain. Principles of nondirectiveness; Changes in the delivery of the organizational aspects of antenatal screening; Gap between choice and coercion.