Prenatal and newborn screening: more new guidelines from CLSI

Feb. 1, 2012

The Clinical and Laboratory Standards Institute has recently published guidelines on two other topics of great relevance to laboratorians, one related to prenatal screening and the other to newborn screening.

Maternal Serum Screening: Approved Standard—Second Edition (I/LA25-A2) addresses the steps required to provide reliable screening and reporting using examples of serum markers currently in common use (AFP, hCG, uE3, inhibin A, PAPP-A). The revision of I/LA25 was spurred by the emergence of new options for screening techniques since its 2004 publication, including testing in the first trimester, in the second trimester, and testing that combines both the first and second trimester. First-trimester screening is emphasized, in which serum markers PAPP-A and hCGâ are used, and for which the main ultrasound marker is nuchal translucency.

Prenatal screening for serious fetal abnormalities has made significant advances since the 1970s, when laboratorians began using maternal serum alpha-fetoprotein as a screening test for open neural tube defects. I/LA25 reflects these developments by specifying requirements and recommendations for maternal serum aspects of prenatal screening for neural tube defects and trisomy 21, while incorporating ultrasound measurements to ensure that screening methods and quality control procedures are carried out to a high standard. Manufacturers, diagnostic laboratories, regulatory agencies, and public health authorities involved in providing or regulating prenatal screening services to evaluate pregnancies and risks of fetal disease will benefit from the use of I/LA25, which serves as a learning tool across multiple disciplines.

The standard is intended to present necessary considerations of the preanalytical, analytical, and postanalytical (preexamination, examination, and postexamination) processes of maternal serum screening. At the same time, the document strikes a balance between being sufficiently specific but not too prescriptive, allowing laboratory directors to use their professional judgment in setting policy. In this way, I/LA25 helps to ensure test reliability, including risk calculation, outcome evaluation, and the accuracy of information management. If properly applied, the five biochemical determinations and these risk calculations can contribute constructively to the field of prenatal screening and to the welfare of pregnant women and the fetus.

Newborn Screening for Cystic Fibrosis—Approved Guideline (I/LA35-A) describes the use of newborn screening tests to detect risk for cystic fibrosis from newborn dried blood spots (DBS) and addresses both the primary screening tests and the reflex tests performed on DBS. Cystic fibrosis (CF), a relatively common genetic disorder, is due to mutations in the CF transmembrane conductance regulator (CFTR) gene. Early diagnosis through newborn screening is now practiced in the U.S., Australasia, and many western European countries and Canadian provinces.

“The main benefit of this document is that it provides comprehensive guidelines for early diagnosis of cystic fibrosis through newborn screening,” says Philip Farrell, MD, PhD, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, and Chairholder of the committee that developed the document. “Improvements in newborn screening processes can assure that early diagnosis of cystic fibrosis is expedited for almost all patients before symptoms develop and patients can benefit from early therapy.”

The document focuses on the use of immunoreactive trypsinogen (IRT) assays and the detection of specific CFTR mutations with the IRT/deoxyribonucleic acid (DNA) screening strategy. Variations in the IRT/DNA method are also summarized with explanations of their advantages and disadvantages. Special attention is given to CFTR mutations in geographically and ethnically diverse populations. A core panel of CFTR mutations is recommended, with guidance included on its potential expansion.

I/LA35 provides a global resource for newborn screening programs to evaluate current procedures and practices for all aspects of the cystic fibrosis newborn screening system, including follow-up components of sweat chloride testing and genetic counseling. The intended target audience includes newborn screening laboratory and program personnel, regulatory agencies, cystic fibrosis center personnel, neonatologists, primary care providers, organizations responsible for networks of cystic fibrosis centers, and a variety of public health policy makers.

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