Benefits and limitations of prenatal screening for Prader–Willi syndrome

This review summarizes the status of genetic laboratory testing in Prader–Willi syndrome (PWS) with different genetic subtypes, most often a paternally derived 15q11–q13 deletion and discusses benefits and limitations related to prenatal screening. Medical literature was searched for prenatal screening and genetic laboratory testing methods in use or under development and discussed in relationship to PWS. Genetic testing includes six established laboratory diagnostic approaches for PWS with direct application to prenatal screening. Ultrasonographic, obstetric and cytogenetic reports were summarized in relationship to the cause of PWS and identification of specific genetic subtypes including maternal disomy 15. Advances in genetic technology were described for diagnosing PWS specifically DNA methylation and high-resolution chromosomal SNP microarrays as current tools for genetic screening and incorporating next generation DNA sequencing for noninvasive prenatal testing (NIPT) using cell-free fetal DNA. Positive experiences are reported with NIPT for detection of numerical chromosomal problems (aneuploidies) but not for structural problems (microdeletions). These reports will be discussed along with future directions for genetic screening of PWS. In summary, this review describes and discusses the status of established and ongoing genetic testing options for PWS applicable in prenatal screening including NIPT and future directions for early diagnosis in PWS. © 2016 John Wiley & Sons, Ltd.     

Does an educational video for aneuploidy screening improve informed choice among pregnant women? A randomised controlled trial

Background

Poor knowledge and the lack of deliberation have been cited as reasons for women making uninformed choices about aneuploidy screening. Adequate pre-test counselling is of particular importance where non-invasive prenatal screening (NIPS) is being increasingly offered as a primary screening test.

Design

Women attending the antenatal clinic with a singleton pregnancy below 14 weeks were randomised to receive routine counselling or the intervention—a 16-min educational video on aneuploidy screening before their consult. The primary outcome, rate of informed choice, was assessed using an adapted multidimensional measure of informed choice questionnaire, where informed choice was defined as good knowledge and value-consistent behaviour. Secondary outcomes included informed choice with deliberation, decisional conflict and anxiety.

Results

Two hundred and eighty-six women were recruited. 69.8% of women in the intervention group made an informed choice compared with 53.6% in the control group (Risk Ratio [RR] 1.30, p = 0.014). A significantly higher number of women in the intervention group had good knowledge compared to controls (81% vs. 60.9%; RR 1.33, p = 0.001). Decisional conflict did not differ between groups, but women in the intervention group had higher anxiety scores (p < 0.001).

Conclusion

The study intervention was effective in helping women make informed choice. Qualitative studies to determine the reason for increased anxiety are needed.

Trial registration

Trial registry: ClinicalTrials.gov ; Identifier: NCT05492981.     

Role of the second-trimester ‘genetic sonogram’ for Down syndrome screen in the era of first-trimester screening and noninvasive prenatal testing

Ultrasonography for the screening of Down syndrome was first introduced about 25 years ago. Different combinations of markers detectable at second-trimester ultrasonography have been proposed under the banner of ‘genetic sonogram’. In recent years, several developments in first-trimester screening and the recent introduction of noninvasive prenatal testing for aneuploidy screening have had important implications for the prevalence of these conditions in the second-trimester and the screening performance of a genetic sonogram. Several second-trimester sonographic markers for Down syndrome have been reported; meta-analysis has shown that the most powerful predictors are mild ventriculomegaly, increased nuchal fold, hyperechoic bowel, and absent or hypoplastic nasal bone. Whereas use of individual markers should be discouraged and scoring systems of multiple markers are now obsolete, use of combined likelihood ratio and logistic regression analysis formulae provides better accuracy. However, there is significant heterogeneity in results among studies. Despite such limitations, the genetic sonogram will continue to have a place in prenatal screening, particularly in twin and higher-order multiple pregnancies, in countries with limited access to the most recent genetic screening tests, in cases with borderline results at maternal serum screening tests, and as noninvasive supplementary test for high-risk women reluctant to undergo invasive diagnostic testing. © 2014 John Wiley & Sons, Ltd.     

Is there still a role for nuchal translucency measurement in the changing paradigm of first trimester screening?

Objectives

To give an overview of the genetic and structural abnormalities occurring in fetuses with nuchal translucency (NT) measurement exceeding the 95th percentile at first-trimester screening and to investigate which of these abnormalities would be missed if cell-free fetal DNA (cfDNA) were used as a first-tier screening test for chromosomal abnormalities.

Methods

This is a national study including 1901 pregnancies with NT≥95th percentile referred to seven university hospitals in the Netherlands between 1 January 2010 and 1 January 2016. All cases with unknown pregnancy outcome were excluded. Results of detailed ultrasound examinations, karyotyping, genotyping, pregnancy and neonatal outcomes, investigation by a clinical geneticist and post-mortem investigations were collected.

Results

In total, 821 (43%) pregnancies had at least one abnormality. The rate of abnormalities was 21% for fetuses with NT between 95^th and 99^th percentile and 62% for fetuses with NT≥99^th percentile. Prevalence of single-gene disorders, submicroscopic, chromosomal and structural abnormalities was 2%, 2%, 30% and 9%, respectively.

Conclusion

Although cfDNA is superior to the combined test, especially for the detection of trisomy 21, 34% of the congenital abnormalities occurring in fetuses with increased NT may remain undetected in the first trimester of pregnancy, unless cfDNA is used in combination with fetal sonographic assessment, including NT measurement.     

Association between serum levels of TSH and free T4 and per-and polyfluoroalkyl compounds concentrations in pregnant women

Many per-and polyfluoralkyl substances(PFASs) may disrupt maternal thyroid hormone homeostasis in pregnancy. Concerns should be raised regarding the PFASs exposure in pregnant women because thyroid hormones are involved in the early development of the fetus. In this study, we measured the concentrations of 13 PFASs, including five novel shortchain PFASs, in serum from 123 pregnant women in Beijing, China. Linear regression models were used to investigate the association between thyroid-stimulati...