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Sequential Pathways of Testing After First-Trimester Screening for Trisomy 21

Columbia University Medical Center, Division of Maternal–Fetal Medicine, New York, New York

To the Editor:

The lead article¹ in the October 2004 edition of Obstetrics & Gynecology points out further advances in the field of Down syndrome screening by focusing on step-wise or sequential screening. However, before these published data are used for advancing public health policy it would be important to consider some significant practical issues with uncoordinated sequential screening.

It is inefficient to offer a screening service with independent first- and second-trimester risk assessments for Down syndrome. This occurred in this study because the authors used the maternal age–derived risk for Down syndrome as the a priori risk for interpreting the second-trimester screen. Once a group of patients has completed first-trimester screening, when those same patients return at 15 weeks, 70–90% of the cases of Down syndrome will already have been removed because they were detected earlier. Therefore, the risk quoted to a patient that her fetus has Down syndrome will be inaccurate. Additionally, since both first- and second-trimester screening programs were treated as independent entities, each with its own false positive rate, it was not surprising that the overall false-positive rate was 17%.

It would be important for clinicians to understand that such "uncoordinated sequential screening" should be avoided. There are several methods that can be used to more appropriately provide the benefits of sequential screening to all patients and to minimize both the chances of inaccurate risk assessment and the false-positive rate. The simplest way to achieve this is to use the posttest risk result from first-trimester screening as the new a priori risk for the second-trimester screening program.

A second, and preferred, method to provide sequential screening is to combine the multiples of the median (MoM) values for nuchal translucency and pregnancy-associated plasma protein A (PAPP-A) obtained in the first trimester with the MoM values for the markers obtained in the second trimester, to calculate the most precise Down syndrome risk. This latter approach could be called "comprehensive sequential screening" to avoid mistaking it for the uncoordinated, basic sequential screening as described in the article. Such "comprehensive sequential screening" will allow patients the benefit of early screening results, minimizing the overall invasive testing rate and maximizing the precision of risk estimates provided.

1. Platt LD, Greene N, Johnson A, Zachary J, Thom E, Krantz D, et al. Sequential pathways of testing after first-trimester screening for trisomy 21. Obstet Gynecol 2004;104:661–6.[Abstract/Free Full Text]

doi:10.1097/01.AOG.0000153257.08966.f9

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