RELATIONSHIPS BETWEEN NUCHAL TRANSLUCENCY AND SECOND TRIMESTER BIOCHEMICAL MARKERS FOR DOWN SYNDROME - A REPORT FROM THE FaST STUDY

Mulvey S, Shekleton P, Oldham J, Woodrow N and Wallace EM on behalf of The FaST Study Group
Department of Obstetrics and Gynaecology, Monash University, Monash Medical Centre

ASUM'99 - Winner of the Meditron Young Investigator Award (Clinical Sonography)

Introduction
Prenatal screening for Down syndrome is an important component of modern antenatal care. Such screening has, until recently, been based upon risk estimates derived from the combination of maternal age and various biochemical markers in maternal serum in the second trimester of pregnancy. Extensive studies have shown that such maternal serum screening (MSS) will detect approximately 70% of Down syndrome pregnancies, for a 5% screen positive rate. More recently, first trimester screening using biochemical and ultrasound markers has been reported. In large prospective series, in both high and low risk populations, Nicolaides and his colleagues have demonstrated that fetal nuchal translucency (NT) consistently affords a detection rate of approximately 70% for a 5% screen positive rate. At present it is not uncommon for women to have both first trimester NT and second trimester MSS tests performed in any given pregnancy. Thus, these women receive two, possibly very different, Down syndrome risks estimates; neither of which is likely to be correct. However, to date possible correlations between second trimester serum markers and nuchal translucency has not been reported and it is therefore not possible to combine the NT and MSS risk estimates with any confidence.

Aim
To prospectively assess possible correlations between four second trimester biochemical markers of Down syndrome (free ?-hCG, inhibin A, alpha feto-protein and unconjugated oestriol) and first trimester nuchal translucency.

Patients and Methods
The nuchal translucency and maternal serum screening results of the first 1000 women recruited to The FaST Study were analysed. The FaST Study is a collaborative research project by Monash University and Monash Medical Centre, funded by The Department of Human Services and Monash University. This study has been established in 1998 to assess the relative merits of First and Second Trimester screening for Down syndrome and thereby to define the optimum Down syndrome screening strategy. The study is approved by the Monash Medical Centre Human Research and Ethics Committee.

After obtaining written consent an ultrasound scan for dating/viability and NT measurement was performed. The NT measurement was performed at 10-14 weeks' gestation using the Fetal Medicine Foundation protocol. Maternal serum screening was performed at 15 weeks gestation according to ultrasound dates. A four marker combination of AFP, f?-hCG, inhibin A and uE3 was performed by the Victorian Clinical Genetics Services laboratory. In 593 cases, both first trimester NT and second trimester MSS results were available for analysis. All five markers were expressed as multiples of the normal median (MoM) and transformed to obtain Gaussian distribution. For the four biochemical markers the log10(MoM) was used in the analyses and for NT the Square root(MoM) was used. Relationships between the markers were explored using simple regression analysis.

Results
The following table outlines the coefficients of correlation [r] between nuchal translucency and the second trimester serum markers.

Conclusions
There is no correlation between NT and the commonly used second trimester serum markers. There is a weak but significant relationship between NT and uE3. These data indicate that it is appropriate to combine risk estimates derived by NT and second trimester biochemistry, as would be done for NT and first trimester biochemical markers. It would be expected that this combined risk estimate would afford women who have both first trimester NT and second trimester MSS a more accurate assessment of their risk of having a Down syndrome fetus than either screening test alone. For reasons of simplicity, and considering the limited value of uE3 when combined with fb-hCG and inhibin A, the data would also argue against the continued use of uE3 in a setting where first trimester ultrasound is offered routinely.

The FaST Study Group: Drs G Atchison, R Burrows, A Edwards, J Grimwade, S Mulvey, C Nagle, J Oldham, P Renou, P Shekleton, C Tippett, E Wallace, N Woodrow, and Ms L Baker.