Debbie L. Nisbet

Prenatal features of Noonan syndrome

We report six cases of Noonan syndrome which presented prenatally with sonographic abnormalities. These included increased nuchal fluid, short femora, pleural effusions, hydrops, cardiac and renal abnormalities. A review of all cases of Noonan syndrome seen at two regional genetics centres confirms the association with these sonographic abnormalities. These cases demonstrate the diversity of prenatal presentation of Noonan syndrome and highlight the need to consider this diagnosis, particularly when faced with a fetus with a normal karyotype and varying degrees of oedema or hydrops, with a short femur length. Copyright

Noninvasive prenatal testing in routine clinical practice – An audit of NIPT and combined first‐trimester screening in an unselected Australian population

There are limited data regarding noninvasive prenatal testing (NIPT) in low‐risk populations, and the ideal aneuploidy screening model for a pregnant population has yet to be established.

A new syndrome comprising vertebral anomalies and multicystic kidneys

We report a dichorionic twin pregnancy in which both fetuses were affected by a similar pattern of multiple abnormalities. The afrocaribbean parents had a history of infertility, and the pregnancy was conceived using in vitro fertilisation with donor sperm. The features seen in the fetuses do not fit any previously described disorder well. We discuss the differential diagnoses and suggest that this may be an autosomal recessive disorder which has not been previously described.

Auditing ultrasound assessment of fetal nuchal translucency thickness: A review of Australian national data 2002–2008

Background:  Nuchal translucency (NT) measurement is the ultrasound component of first trimester combined screening for Down syndrome. In 2002, a NT ultrasound education and monitoring program was established in Australia. Between 2002 and 2008, a total of 728 502 NT scans were audited through this process.

Factors affecting cell-free DNA fetal fraction and the consequences for test accuracy

Abstract Introduction: Biological factors are known to influence the fetal fraction (FF) of cell-free DNA and may also influence the accuracy of non-invasive prenatal testing. Material and methods: NIPT from 5267 mixed risk women across three specialist clinics in Australia were analyzed. Multivariable regression analysis was used to determine whether maternal characteristics, ultrasound, and placental biomarkers affect FF and test accuracy. Results: FF ranged from 4% to 37% (mean 11.6%). Body mass index (BMI), gestation, and placental biomarkers were found to be significant factors associated with FF. For each unit increase in BMI, the logarithmically transformed FF, (lnFF), mean value decreased by 0.027. Each week increases in gestation, lnFF increased by 0.023. Each unit increase in free BhCG, PAPPA, and PlGF, the lnFF increased by 0.065, 0.050, and 0.17, respectively. There was no significant association between FF with either maternal age or nuchal translucency. The false-positive cases and one false-negative case did not have lower FF than the true-positive cases. Discussion: The fetal fraction in maternal plasma cfDNA increased with gestational age, serum pregnancy-associated plasma protein A (PAPP-A), β-hCG, and PlGF and decreased with increasing maternal BMI. There was no significant correlation between low FF and test accuracy, when FF was above 4%.

Reducing inter-rater variability in the assessment of nuchal translucency image quality.

Introduction: Standardization of first-trimester nuchal translucency (NT) image acquisition is crucial to the success of screening for Down syndrome. Rigorous audit of operator performance and constructive feedback from assessors maintain standards. This process relies on good inter-rater agreement on image assessment. We describe the Australian approach to NT image assessment and evaluate the impact of a targeted intervention on inter-rater agreement. Methods: Between 2002 and 2008 a group of experienced practitioners met nine times to compare their assessment of a series of NT images. Each assessor had previously scored the images according to a system described in 2002. Inter-rater agreement was evaluated before and after an intervention where the assessors were required to refer to a detailed resource manual designed to reduce the subjectivity inherent in image assessment. Results: There was a statistical improvement in inter-rater agreement for all elements of image assessment (original scores and individual component scores) after the intervention, apart from horizontal fetal position. However, even after the intervention, inter-rater agreement levels generally remained moderate (kappa range: 0.14–0.58). Conclusions: This study has shown that provision of detailed resource documentation to experienced assessors can significantly improve inter-rater agreement in all facets of NT image assessment. It also highlights areas of image assessment that require critical review. It is recommended that all audit bodies regularly review their inter-rater agreement to ensure consistent feedback to operators who submit images for expert peer review.

Right‐sided aortic arch in the age of microarray

For fetuses with a diagnosis of right aortic arch and normal cardiac anatomy, we aimed to establish the frequency of chromosomal anomaly diagnosed with single nucleotide polymorphism microarray analysis, particularly focusing on microduplications or microdeletions which would have gone undetected by conventional karyotyping and six‐probe fish (13,18,21, X,Y, TUPLE).

Practice Tips for Measuring the Nuchal Translucency

In some countries, measurement of nuchal translucency (NT) is incorporated into national antenatal screening programmes to help detect pregnancies at increased risk of Down syndrome. Accurate measurement of the NT requires a specific technique. This article is an illustrated practical guide outlining the steps required for measuring the NT; it provides useful tips for improving operator technique and advises how to avoid common pitfalls. Although fetal nasal bone assessment does not currently form part of official Down syndrome screening programmes (in Australia or the UK), it is included here as debate about its usefulness continues.

Quality management of nuchal translucency ultrasound measurement in Australia

Nuchal translucency measurement has an established role in first trimester screening. Accurate measurement requires that technical guidelines are followed. Performance can be monitored by auditing the distribution of measurements obtained in a series of cases.

Prenatal Screening for Down Syndrome in Australia

Prenatal screening for Down syndrome should be offered to all pregnant women. The screening option chosen will be influenced by maternal preference, local availability of tests, and the gestation at which the pregnant woman presents. Screening tests take into account the effect of maternal age on Down syndrome risk. The combined first trimester screen using nuchal translucency and first trimester maternal serum screening can achieve a detection rate for Down syndrome of 90% with a 5% false positive rate, when performed by appropriately trained individuals. Midtrimester maternal serum screening is a good screening option for women unable to undergo the combined first trimester screen.