The evolution of prenatal screening and diagnosis and its impact on an unselected population over an 18-year period

National Perinatal Epidemiology Unit, University of Oxford, Oxford, UK.
BJOG An International Journal of Obstetrics & Gynaecology (Impact Factor: 3.45). 06/2012; 119(9):1131-40. DOI: 10.1111/j.1471-0528.2012.03373.x
Source: PubMed


To review changes in and impact of prenatal screening and diagnosis.
Population-based congenital anomaly register study.
Congenital anomalies confirmed and those suspected prenatally, delivered 1991-2008.
Analysis of proportions of congenital anomalies confirmed and those suspected prenatally.
Birth prevalence, prenatal detection rates, pregnancy outcomes.
A total of 2651 (2.3%) infants/fetuses had a congenital anomaly diagnosed. There were 3839 suspected or confirmed cases, 2847 due to a prenatal suspicion, of which 1659 had an anomaly confirmed at delivery, and 1188 false-positive diagnoses, 91% due to reporting ultrasound normal variants. The percentage of prenatal notifications rose from 48% in 1991-93 to 83-88% from 1996 to 2003 and dropped to 61% in 2006-08, partly reflecting changes in the reporting of normal variants. Reporting these increased the prenatal diagnosis rate from 53 to 63% with an increase in false-positive rate from 0.09 to 1.04%. A total of 722 (44% of prenatally detected affected fetuses) resulted in termination; 48% of these had chromosome anomalies, 34% had isolated structural anomalies, 7% had multiple anomalies, 10% had familial disorders; 42% had lethal anomalies and 58% would probably have survived the neonatal period giving an estimated 20% reduction in birth prevalence of congenital anomalies compatible with survival because of terminations.
There has been an improvement in prenatal detection of congenital anomalies over the two decades studied. The recognition that reporting normal variants, although increasing prenatal detection rates, leads to an increase in false-positive diagnoses has had an impact on practice that has redressed the balance between these two effects.

Download full-text


Available from: Jennifer J Kurinczuk, Feb 23, 2015
17 Reads
  • Source
    • "Some publications based on these registry data have looked at the sensitivity of prenatal ultrasound screening in the general population [4-6], which rose from 41 to 60% during the 1990s and to 80% over the past decade [7,8]. In the general population, the false-positive rate, all systems combined, has been estimated at 0.5 to 33.0% [9-11]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Congenital malformations occur in 3-4% of live births. Their prenatal detection is performed by ultrasound screening. Any announcement about a suspected malformation is a source of stress for the parents, and misdiagnosis during ultrasound screening can lead to expensive and sometimes iatrogenic medical interventions. In this study, we aim to determine the false-positive rate, first overall and then by anatomical system, of ultrasound screening for congenital malformations in the second and third trimesters of pregnancy. Our sample includes all children born between 1 January, 2006, and 31 December, 2009, in the French region of Auvergne, whose mother had a prenatal ultrasound diagnosis of a congenital malformation during the second or third trimester of pregnancy confirmed by a follow-up ultrasound examination by an expert consultant ultrasonographer. The study included 526 fetuses, divided in 3 groups: false positives, diagnostic misclassifications, and true positives. The rates of false positives and diagnostic misclassifications were calculated for the sample as a whole and then by anatomical system. Overall, the false-positive rate was 8.8% and the rate of diagnostic misclassification 9.2%. The highest false-positive rates were found for renal and gastrointestinal tract malformations, and the highest diagnostic misclassification rates for cerebral and cardiac malformations. The diagnostic misclassification rate was significantly higher than the false-positive rate for cardiac malformations. The false-positive rate during prenatal ultrasound is not insignificant; these misdiagnoses cause psychological stress for the parents and overmedicalisation of the pregnancy and the child.
    BMC Pregnancy and Childbirth 03/2014; 14(1):112. DOI:10.1186/1471-2393-14-112 · 2.19 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Abstract Rapidly developing next-generation sequencing (NGS) technologies produce a large amount of data across the whole human genome and allow a large number of DNA samples to be analyzed simultaneously. Screening cell-free fetal DNA (cffDNA) obtained from maternal blood using NGS technologies has provided new opportunities for non-invasive prenatal diagnosis (NIPD) of fetal aneuploidies. One of the major challenges to the analysis of fetal abnormalities is the development of accurate and reliable algorithms capable of analyzing large numbers of short sequence reads. Several such algorithms have recently been developed. Here, we provide a review of recent NGS-based NIPD methods as well as the available algorithms for short-read sequence analysis. We furthermore introduce the practical application of these algorithms for the detection of different types of fetal aneuploidies, and compare the performance, cost and complexity of each approach for clinical deployment. Our review identifies several main technologies and trends in NGS-based NIPD. The main considerations for clinical development for NIPD and screening tests using DNA sequencing are: accuracy, intellectual property, cost and the ability to screen for a wide range of chromosomal abnormalities and genetic defects. The cost of the diagnostic test depends on the sequencing method, diagnostic algorithm and volume of the tests. If the cost of sequencing equipment and reagents remains at or around current levels, targeted approaches for sequencing-based aneuploidy testing and SNP-based methods are preferred.
    Clinical Chemistry and Laboratory Medicine 09/2012; DOI:10.1515/cclm-2012-0281 · 2.71 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Fetal malformations are very frequent in industrialized countries. Although advanced maternal age may affect pregnancy outcome adversely, 80%-90% of fetal malformations occur in the absence of a specific risk factor for parents. The only effective approach for prenatal screening is currently represented by an ultrasound scan. However, ultrasound methods present two important limitations: the substantial absence of quantitative parameters and the dependence on the sonographer experience. In recent years, together with the improvement in transducer technology, quantitative and objective sonographic markers highly predictive of fetal malformations have been developed. These markers can be detected at early gestation (11-14 wk) and generally are not pathological in themselves but have an increased incidence in abnormal fetuses. Thus, prenatal ultrasonography during the second trimester of gestation provides a "genetic sonogram", including, for instance, nuchal translucency, short humeral length, echogenic bowel, echogenic intracardiac focus and choroid plexus cyst, that is used to identify morphological features of fetal Down's syndrome with a potential sensitivity of more than 90%. Other specific and sensitive markers can be seen in the case of cardiac defects and skeletal anomalies. In the future, sonographic markers could limit even more the use of invasive and dangerous techniques of prenatal diagnosis (amniocentesis, etc.).
    10/2013; 5(10):356-371. DOI:10.4329/wjr.v5.i10.356
Show more