Fergus Scott

Prenatal diagnosis using combined quantitative fluorescent polymerase chain reaction and array comparative genomic hybridization analysis as a first-line test: results from over 1000 consecutive cases

First, to assess the performance of a prenatal diagnostic service using quantitative fluorescent polymerase chain reaction (QF‐PCR) and array comparative genomic hybridization (aCGH) as first‐line investigations. Second, to determine the incidence of copy number variants (CNVs) by indication for testing, with particular reference to ultrasound and biochemical parameters measured in combined first‐trimester screening.

Developmental regulation of circulating insulin-like growth factor-binding proteins in normal pregnancies and in pre-eclampsia.

The insulin-like growth factors (IGFs) and their binding properties (IGFBPs) are believed to play important roles in the growth and development of the human fetus. They have been implicated in the pathophysiology of pre-eclampsia. In this study we have characterized the developmental regulation, in normal and pre-eclamptic pregnancies, of IGFs and IGFBPs in maternal serum, neonatal serum and amniotic fluid. In neonatal cord serum IGFBP-1, -2 and -6 decreased with increasing gestational age. In contrast, the ternary complex and its components, IGF-I, IGFBP-3 and ALS increased with gestation. We show that while ALS is an important limiting factor for ternary complex formation in the fetal circulation, there is a fraction of IGFBP-3 which is unable to form this complex. IGFs and IGFBPs in the maternal and fetal circulation were similar in normal and pre-eclamptic pregnancies.

New formula for estimating fetal weight below 1000 g : Comparison with existing formulas

Most estimated fetal weight formulas have been derived and tested with larger fetuses, yet accuracy in predicting birth weight is more critical at the limit of viability. Complete data from 142 pregnancies in which delivery took place within 7 days of an ultrasonographic examination were used to create an appropriate formula for fetuses less than 1000 g and compare it with 10 currently available formulas. Our formula (In [BW] = 0.66 x 1n [HC] + 1.04 x 1n [AC] + 0.985 x 1n [FL]) was significantly more accurate than all other formulas and also performed better on a prospective cohort of 27 fetuses with estimated fetal weight less than 1000 g. Of the existing formulas, the Hadlock formula (using head circumference, abdominal circumference, femur length) was the most accurate, being significantly more accurate than all but the Woo formula with all but the Woo formula.

Prospective evaluation of a first trimester screening program for Down syndrome and other chromosomal abnormalities using maternal age, nuchal translucency and biochemistry in an Australian population

Background:  A combination of maternal age and ultrasound assessment of the nuchal translucency (NT) has been used in the first trimester to screen for chromosomal abnormality. In the United Kingdom, the addition of NT screening was shown to be beneficial.

Maternal uniparental isodisomy for chromosome 14 detected prenatally

Maternal uniparental disomy (UPD) for chromosome 14 (upd(14)mat) has been associated with a distinct phenotype. We describe the first case of maternal uniparental isodisomy for chromosome 14 detected prenatally, in a pregnancy with mosaicism for trisomy 14 observed in both a chorionic villus sample (CVS) and in amniocytes. Detailed analysis of polymorphic microsatellites showed that the fetus was essentially isodisomic for one of the mother’s chromosomes 14 and that recombination had introduced a mid‐long arm region of heterodisomy. The fetus, which died in utero at 18 weeks, showed no apparent pathological features. The case demonstrates for the first time a maternal meiosis II non‐disjunction of chromosome 14 leading to a trisomic conception which has been incompletely corrected by ‘rescue’ in the early embryo. Copyright

Distal gangrene in a polycythemic recipient fetus in twin-twin transfusion

Background Gangrene of an extremity in a twin pregnancy has been attributed to the release of thromboplastin from a dead fetus or to a combination of polycythemia and anomalous vasculature. It has not been described in a situation where both twins survived. Case In a pregnancy complicated by twin-twin transfusion syndrome and managed with repeated amniocenteses, both twins survived. The recipient twin had necrosis of the left lower leg, which had appeared in the antenatal period and was associated with polycythemia, but not anomalous vasculature. Conclusion Antenatally, polycythemia alone may cause necrosis of an extremity. Necrosis could be detected with ultrasound examination and may be an additional argument for laser photocoagulation of the chorioangiopagus.

Assessment of the clinical usefulness of the ‘Queenan’ chart versus the ‘Liley’ chart in predicting severity of rhesus iso‐immunization

In 1961 Liley developed a chart of changing amniotic fluid bilirubin levels (ΔOD450) and gestation, with three zones delineating the severity of rhesus disease. This chart ranged from 27 to 40 weeks and was found to be clinically useful. Extrapolating the use of the Liley chart to earlier gestations however, was unsuccessful. Currently, cordocentesis is the only reliable means of assessing the fetal condition accurately prior to 27 weeks. In 1993, Queenan proposed a chart of ΔOD450 from 14 to 40 weeks, with four zones to guide management. The aim of the current study is to assess the clinical usefulness of the ‘Queenan’ chart vs. the ‘Liley’ chart.

First Trimester Aneuploidy Screening Using Nuchal Iranslucency, Free Beta Human Chorionic Gonadotrophin and Maternal Age

Summary: Screening for aneuploidy using maternal age has a low detection rate and high false positive rate. Second trimester maternal serum screening increases trisomy 21 detection and decreases die false positive rate. First trimester screening would enable definitive diagnosis with chorionic villus sampling, and simple surgical termination of affected pregnancies would still be an option. Nuchal translucency (NT), free beta human chorionic gonadotrophin (fβHCG) and maternal age were assessed in 302 patients before chorionic villus sampling. NT positively and fβHCG negatively correlated with gestation, but neither correlated with maternal age nor with each other. Both NT and fβHCG were increased in trisomy 21. NT was increased and fβHCG was decreased in trisomy 18. Multivariate discriminant analysis enabled 87.5% detection of trisomy 21 in this high‐risk population, for a 14% false positive rate. In a simulated normal population, using a risk cut‐off of 1 in 250, 71% detection was achieved for a 7% false positive rate. The combination of NT, fβHCG and maternal age is a simple, readily available and viable first trimester screening strategy.

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.

Pregnancy outcome in the setting of extremely low first trimester PAPP‐A levels

Background: Serum pregnancy‐associated plasma protein‐A (PAPP‐A) is part of first trimester Down syndrome screening. Low levels have been associated with adverse outcome as well as chromosomal abnormality.