To estimate patterns of total hCG and inhibin A levels in the late first trimester of Down syndrome pregnancies, compare them with that of free β-hCG, and assess screening performance of these markers individually and in combination with pregnancy-associated plasma protein-A (PAPP-A) and nuchal translucency.
Seventy-nine matched case–control sets of maternal serum samples (each Down syndrome case matched to 5 controls) from 11 through 13 completed weeks of gestation were taken from the sample bank of the First and Second Trimester Evaluation of Risk Consortium, a population-based study, and assayed for levels of free β-hCG, total hCG, and inhibin A. Distribution characteristics and correlations of the multiples of the median values were estimated in cases and controls. Screening performance for each marker, alone and in combination with PAPP-A, nuchal translucency, and maternal age, was calculated.
Median multiples of the median levels of free β-hCG, total hCG, and inhibin A in cases were more elevated as gestation increased from 11 to 13 weeks, with univariate detection rates of 31%, 23%, and 29%, respectively, at a 5% false-positive rate. At 12 weeks, the multivariate detection rates at a 5% false-positive rate for nuchal translucency and PAPP-A (with maternal age) with either free β-hCG, total hCG, or inhibin A were 84%, 83%, and 85%, respectively. The improvement in performance from nuchal translucency and PAPP-A to any of the three-marker tests was significant, while performance of any of the three-marker combinations was not significantly different from each other.
Although levels of free β-hCG in affected pregnancies were higher earlier than the levels of either total hCG or inhibin A, there was no significant difference in screening performance when either of the three markers was used with nuchal translucency and PAPP-A at 11–13 weeks of pregnancy.
Nuchal translucency, pregnancy-associated plasma protein A, total hCG, and inhibin A, in combination, provide first-trimester Down syndrome screening performance similar to that of nuchal translucency, pregnancy-associated plasma protein A, and free β-hCG, in combination.
From the 1Women and Infants Hospital and Brown Medical School, Providence, Rhode Island; 2Columbia University College of Physicians and Surgeons, New York, New York; 3Royal College of Surgeons in Ireland, Dublin, Ireland; 4University of Utah and Intermountain Healthcare, Salt Lake City, Utah; 5University of California at San Francisco, San Francisco, California; 6Swedish Medical Center, Seattle, Washington; 7William Beaumont Hospital, Royal Oak, Michigan; 8University of Texas Medical Branch, Galveston, Texas; 9Mount Sinai School of Medicine, New York, New York; 10Montefiore Medical School/Albert Einstein College of Medicine, Bronx, New York; 11University of Colorado Health Sciences Center, Denver, Colorado; 12Tufts University School of Medicine, Boston, Massachusetts; 13New York University School of Medicine, New York, New York; 14University of North Carolina Medical Center, Chapel Hill, North Carolina.
* For members of the First and Second Trimester Evaluation of Risk Consortium, see the Appendix.
Funded by the National Institute of Child Health and Human Development (R01 HD 38652).
Corresponding author: Prof. Fergal D. Malone, Department of Obstetrics and Gynaecology, Royal College of Surgeons in Ireland, the Rotunda Hospital, Parnell Square, Dublin 1, Ireland; e-mail: firstname.lastname@example.org.