Prenatal screening for trisomy 18 with free beta human chorionic gonadotrophin as a marker

To determine the relation between maternal serum alpha fetoprotein and free beta human chorionic gonadotrophin concentrations in pregnancies complicated by trisomy 18 and establish whether prenatal biochemical screening for this condition could be developed in a way similar to that proposed for trisomy 21.

Serum alpha fetoprotein and free beta human chorionic gonadotrophin concentrations in women with singleton pregnancies affected by cytogenetically confirmed trisomy 18, uncomplicated by neural tube defect or ventral wall defect, were identified from prospective trisomy 21 screening programmes. Additionally, stored maternal serum from similar pregnancies was analysed retrospectively. Analyte concentrations from singleton unaffected pregnancies were identified from a prospective screening programme as controls. Statistical parameters of the affected and unaffected populations were compiled.

Biochemical screening laboratories in Britain and the United States.

52 women with singleton pregnancies complicated by trisomy 18; control population of 6661 women with unaffected singleton pregnancies.

Median values of each analyte and their distribution in the affected and unaffected populations; detection rate of trisomy 18 and the false positive rate.

Maternal serum alpha fetoprotein and free beta human chorionic gonadotrophin concentrations were significantly lower in pregnancies complicated by trisomy 18 (median values 0.71 and 0.37 respectively). By using a multivariate risk algorithm incorporating maternal age risk of trisomy 18 and the concentration of the two biochemical markers it was predicted that 50% of trisomy 18 cases (unaffected by neural tube defect or ventral wall defect) could be detected with a 1% false positive rate.

Second trimester biochemical screening for trisomy 18 could be a valuable addition to trisomy 21 screening programmes.