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PEDIATRICS Vol. 113 No. 6 June 2004, pp. 1811-1812

COMMENTARY

Cystic Fibrosis Newborn Screening: Shifting the Key Question From "Should We Screen?" to "How Should We Screen?"

Philip M. Farrell, MD, PhD

Department of Pediatrics
University of Wisconsin Medical School
Madison, WI 53706

Abbreviations: CF, cystic fibrosis • NENSP, New England Newborn Screening Program • CFTR, cystic fibrosis transmembrane regulator

The report by Comeau et al1 represents a landmark article in the 25-year evolution of cystic fibrosis (CF) newborn screening because it signifies an important shift in research to address questions about how we should achieve early diagnosis through trypsinogen/DNA analysis of neonatal blood specimens. The initial "should we" question has been investigated comprehensively for the past 2 decades, and a large body of supportive evidence has accumulated.2 Consequently, soon after the first CF screening workshop was organized in 1997 by the Centers for Disease Control and Prevention, the New England Newborn Screening Program (NENSP) began intensive preimplementation planning pursuant to the published recommendations.3 At the second Centers for Disease Control and Prevention workshop held in November 2003 (to be published), all the evidence accruing in favor of newborn screening for CF was reviewed, including potential cognitive benefits reported herein by Koscik et al,4 and the possible harms were examined also, so that the benefit-risk relationship could be defined fully.2 It should be emphasized, however, that appealing opportunities for individual patient benefits, including life-saving diagnoses, and CF population benefits achieved only through neonatal screening have been abundantly clear for almost a decade.5 Thus, many pediatricians and CF specialists in the United States have wondered why such a long delay has occurred in CF newborn screening, but the lack of national policies and leadership limitations have inhibited progress. Therefore, the NENSP and Massachusetts CF Centers deserve congratulations for moving ahead to become a role-model CF newborn-screening program and communicating valuable information on best practices.

With shared leadership, recognition of the opportunities for better nutritional and pulmonary outcomes, and the talent to reduce risks, Comeau et al1 reviewed critically the practices of the trailblazing program in Colorado6 and the lessons learned in Wisconsin5,7 before embarking in 1999. Codirectors (R. Parad and A. Comeau) with complementary skills were designated as leaders in the planning phase, and the 5 CF center directors coalesced as a synergistic team. Their experience and findings have advanced the field significantly on how to screen newborns for CF. They have demonstrated 1) the advantages of trypsinogen/DNA (cystic fibrosis transmembrane regulator [CFTR]) multimutation analysis over the trypsinogen/DNA ({Delta}F508) method, its high but imperfect sensitivity, and also the challenges with regard to CF heterozygote detection, 2) the added value of the very high trypsinogen "fail-safe" strategy,7 and 3) the practical advantages of CFTR multimutation analysis, ie, actual genetic diagnosis of the majority of CF patients by 1 week of age (directly from the dried newborn blood specimen) and prediction of low probability of disease (~2%) in the remaining trypsinogen/DNA-positive infants. Knowing the probability of CF in newborns having follow-up sweat tests facilitates planning for initial CF clinic visits and should reduce parental anxiety in the interval between the screening result and the sweat test. The Massachusetts CF Centers also showed how early sweat tests can be used reliably in young infants and the importance of applying the 30 mEq/L discriminator described elsewhere.8 In addition, perhaps one of the NENSP’s most significant findings in screening their diverse population is the higher than "expected" CF incidence among Hispanic-American newborns (1:4115), which underscores the value of diagnosis through CFTR multimutation screening in minority populations who otherwise might experience discrimination.9,10

Hopefully, with more information on how to screen supplementing the "should we" evidence, other states will follow the example of the NENSP and proceed with CF newborn screening. The benefits to CF patients, their parents, and society are indisputable, including saving lives, avoiding diagnostic disparities, reducing expenses, providing genetic counseling, and creating opportunities to prevent malnutrition and intervene with respiratory therapy before irreversible lung disease develops.2,4,5 Because the risks are manageable, "ensuring more good than harm" is feasible,2 and CF centers can routinely maximize the benefits while minimizing the risks. Therefore, now is the time for leadership to emerge in all regions still relying on archaic diagnostic methods to join the 11 states now screening so that future children with CF will routinely benefit and have their best interests served through early diagnosis and treatment. To accept anything less than the best for children with CF seems unethical to me.


   FOOTNOTES
 
Received for publication Mar 3, 2004; Accepted Mar 9, 2004.

Reprint requests to (P.M.F.) University of Wisconsin Medical School, Room 1217 MSC, 1300 University Avenue, Madison, WI 53706. E-mail: pmfarrel{at}facstaff.wisc.edu


   REFERENCES
TOP
 REFERENCES
 

  1. Comeau AM, Parad RB, Dorkin HL, et al. Population-based newborn screening for genetic disorders when multiple mutation DNA testing is incorporated: a cystic fibrosis newborn screening model demonstrating increased sensitivity but more carrier detections. Pediatrics.2004; 113 :1573 –1581[Abstract/Free Full Text]
  2. Farrell MH, Farrell PM. Newborn screening for cystic fibrosis: ensuring more good than harm. J Pediatr.2003; 143 :707 –712[CrossRef][ISI][Medline]
  3. Centers for disease control and prevention. Newborn screening for cystic fibrosis: a paradigm for public health genetics policy development. Proceedings of a 1997 workshop. MMWR Recomm Rep.1997; 46(RR-16) :1 –24
  4. Koscik RL, Farrell PM, Kosorok MR, et al. Cognitive function of children with cystic fibrosis: deleterious effect of malnutrition. Pediatrics.2004 : In press
  5. Farrell PM. Improving the health of patients with cystic fibrosis through newborn screening. Wisconsin Cystic Fibrosis Neonatal Screening Study Group. Adv Pediatr.2000; 47 :79 –115[Medline]
  6. Hammond KB, Abman SH, Sokol RJ, Accurso PJ. Efficacy of statewide neonatal screening for cystic fibrosis by assay of trypsinogen concentrations. N Engl J Med.1991; 325 :769 –774[Abstract]
  7. Farrell PM, Aronson RA, Hoffman GL, Laessig, RH. Newborn screening for cystic fibrosis in Wisconsin: first application of population-based molecular genetics testing. Wis Med J.1994; 93 :415 –421[Medline]
  8. Farrell PM, Koscik RE. Sweat chloride concentrations in infants homozygous or heterozygous for F508 cystic fibrosis. Pediatrics.1996; 97 :524 –528[Abstract/Free Full Text]
  9. Bobadilla JL, Farrell MH, Farrell PM. Applying CFTR molecular genetics to facilitate the diagnosis of cystic fibrosis through neonatal screening. Adv Pediatr.2002; 49 :131 –190[Medline]
  10. Farrell PM, Fost NC. Prenatal screening for cystic fibrosis: Where are we now? J Pediatr.2002; 141 :758 –763[CrossRef][ISI][Medline]
PEDIATRICS (ISSN 1098-4275). ©2004 by the American Academy of Pediatrics



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