Down syndrome screening: suitability of a WHO 5 standardized total hCG assay.
OBJECTIVE
To determine how the adoption of the new WHO 5th International Standard (IS 07/364) will affect the suitability of total βhCG as a marker for second trimester Down syndrome screening, compared to the current WHO 3rd IS (75/537).


METHODS
Assays employing both standards were evaluated on the Beckman Coulter DxI platform. Matched βhCG results from 232 fresh second trimester maternal serum samples were compared. In addition, stored samples from 51 Down syndrome and 251 matched control sera were also tested with both assays and results converted to weight-adjusted multiples of the median (MoMs). These results were combined with maternal age and the existing alpha-fetoprotein, unconjugated estriol and inhibin-A MoM levels to compute patient-specific Down syndrome risk.


RESULTS
Correlation between the two sets of results on fresh samples was high (r=0.993), but showed a proportional increase of 33% (95% CI 31% to 35%) in results using the new versus old assay across the range of measurements. βhCG results in the case/control dataset were also highly correlated (0.994) and showed a similar proportional increase (34%). After computing assay-specific MoMs, the resulting 'triple' and 'quadruple' Down syndrome risks were highly correlated, and resulted in no difference in either of the two detection rates (78% and 88%, respectively) or false positive rates (6.4%, 6.8%).


CONCLUSIONS
Laboratories using the DxI platform with the new total βhCG 5th IS assay will need to compute new reference (medians), but can expect no impact on the clinical validity of the associated Down syndrome screening programs.
Division of Medical Screening and Special Testing, Department of Pathology and Laboratory Medicine, Women & Infants Hospital, Alpert Medical School of Brown University, Providence, RI, USA. Electronic address: gpalomaki@ipmms.org.
Glenn E
GE
Palomaki
Division of Medical Screening and Special Testing, Department of Pathology and Laboratory Medicine, Women & Infants Hospital, Alpert Medical School of Brown University, Providence, RI, USA.
Geralyn
G
Lambert-Messerlian
D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000097:blood*; D004314:Down Syndrome / Q000097:blood* / Q000175:diagnosis*; D005260:Female; D005865:Gestational Age; D006801:Humans; D011247:Pregnancy; D011262:Pregnancy Trimester, Second / Q000097:blood
D018997:Chorionic Gonadotropin, beta Subunit, Human
Down syndrome screening; Human chorionic gonadotropin; Multiples of the median; Standardization