PEDIATRICS Vol. 107 No. 6 June 2001, pp. 1492

Early Diagnosis of Cystic Fibrosis

To the Editor.

Farrell et al¹ demonstrate that children with cystic fibrosis (CF) identified through newborn screening are significantly less likely to experience growth retardation, although no less likely to experience acute malnutrition, as indicated by low weight-for-height. They conclude that this evidence is sufficient to justify screening newborns for CF and cite a 1997 workshop convened at the Centers for Disease Control and Prevention (CDC) as supporting this recommendation: "Therefore, we suggest that more regions begin to initiate such screening programs, as recommended by the Centers for Disease Control and Prevention."^a

The participants in the 1997 CDC workshop, "Newborn Screening for Cystic Fibrosis: A Paradigm for Public Health Genetics Policy Development," recommended that several states consider initiating screening for CF as pilot projects to gather data.² In particular, it was recommended, "Pilot CF screening programs for newborns should be approached and promoted as research endeavors, for which participation is not mandatory and informed consent is emphasized."

The CDC's position, stated in the 1997 workshop report, is that evidence of improved nutritional status without improved health or developmental status is not sufficient to recommend that state newborn screening programs include CF in a standard panel of tests:

Before recommending universal CF screening for newborns as a routine public health intervention, policymakers will need more compelling data about its effectiveness. This evidence might include a better description of the consequences of delayed diagnosis, information regarding cognitive development differences caused by malnutrition, data establishing pulmonary benefits of early diagnosis, and the cost-effectiveness of early diagnosis through screening.

The evidence for newborn screening for CF remains inconclusive 4 years after the CDC workshop. To date, we have not seen published data from a controlled trial that early detection can slow the deterioration of lung function in children with CF. One outcome that has been shown to not differ with early identification of CF is acquisition of Pseudomonas aeruginosa, the major pathogen contributing to pulmonary disease and decline in pulmonary function in CF patients.^3,4 We would welcome the publication of data from the Wisconsin study on cognitive outcomes, cost savings, or medical or psychosocial benefits of early diagnosis that could clearly demonstrate a public health rationale for screening newborns for CF.

Scott D. Grosse, PhD
Muin J. Khoury, MD, PhD
W. Harry Hannon, PhD
Coleen A. Boyle, PhD
Office of Planning, Evaluation, and Legislation
National Center for Environmental Health
Atlanta, GA 30341 USA

REFERENCES

1. Farrell PM, Kosorok MR, Rock MJ, Early diagnosis of cystic fibrosis through neonatal screening prevents severe malnutrition and improves long-term growth. Pediatrics. 2001; 107:1-13 [Abstract/Free Full Text]
2. Cono J, Qualls NL, Khoury MJ, et al. Newborn screening for cystic fibrosis: a paradigm for public health genetics policy development. Proceedings of a 1997 workshop. MMWR Morb Mortal Wkly Rep. 1997;46(RR16):1-22
3. Farrell PM, Shen G, Splaingard M, et al. Acquisition of Pseudomonas aeruginosa in children with cystic fibrosis. Pediatrics. 1997;100(5). URL: http://www.pediatrics.org/cgi/content/full/100/5/ez
4. Wang SS, FitzSimmons SC, O'Leary LA, Rock MJ, Gwinn ML, Khoury MJ Early diagnosis of cystic fibrosis in the newborn period and risk of Pseudomonas aeruginosa acquisition in the first 10 years of life: a registry-based longitudinal study. Pediatrics. 2001; 107:274-279 [Abstract/Free Full Text]

In Reply.

I and my co-authors appreciate the 2 concerns expressed by Grosse et al about the article published in the January 2001 issue,¹ and we thank them for their views on newborn screening for cystic fibrosis (CF). We were also surprised by the mistake under "Acknowledgments," which occurred inadvertently during the final processing of the page proofs, as an attached listing of authors for reference 48² was erroneously translocated. We have asked to have the Web version corrected immediately.

As for the second concern, Grosse et al assert that the "CDC's position" is that "the evidence for newborn screening for CF remains inconclusive ... that evidence of improved nutritional status without improved health or developmental status is not sufficient ... and pilot CF screening programs should be approached and promoted as research endeavors." They base their views on the 1997 CDC report.² As one of the contributing authors of the CDC report, I'm well aware of what was concluded in January 1997 at the workshop and the policy recommendations that ensued as the publication was distributed in December 1997. Indeed, an earlier, more lengthy version of our manuscript and some of our other publications³ contain more information on the CDC report, including reference to "pilot" programs in keeping with the statement that "the workshop participants concluded that sufficient evidence exists to recommend pilot state-based demonstration programs."² Editorial downsizing, however, led to a shorter statement. We apologize to the CDC for implying a stronger policy recommendation than was incorporated into the report of the workshop participants.

The crucial issue is what is the most appropriate policy for CF neonatal screening as we go forward in 2001, especially because we are now more than 4 years beyond the CDC workshop. In other words, what method of diagnosis is in the best interest of children with CF, ie, early recognition through screening or delayed diagnosis by traditional methods? It should be pointed out that this question takes on special significance when one recognizes "the long period of planning required for implementing screening programs for newborns," as stated in the CDC report² leading to the recommendation that "it would be appropriate for some states to initiate pilot research projects for CF screening among newborns." It should also be emphasized the CDC report recommends that "within 2 years, a national consensus panel should be convened ..."which hasn't occurred. During the 4-year interval, many countries (eg, France and Ireland) and states (eg, Massachusetts, New York, and California) are apparently moving ahead with implementation of CF neonatal screening. They have recognized that there is substantially more evidence of benefits, including opportunities to alleviate or prevent lung disease, and that the nutritional benefits we found are long-term and do reflect "improved health."^3-5 Indeed, our first publication⁶ was a preliminary disclosure of evidence that was presented at the CDC workshop, and we have now demonstrated more than 15 years of significantly better nutritional status in screened patients compared with controls.¹

Pediatricians and health policymakers will have to reach their own conclusions about whether or not there is a compelling reason to use the excellent tests available and screen newborns for CF based on clear evidence of nutritional benefits from a positive randomized clinical trial and no indication of unmanageable risks. Decisions about whether to screen or not to screen are likely to be made on a region-by-region basis, and we will probably see the typical pattern of states taking variable courses of action. It is this ad hoc approach that accounts for a disturbing degree of inconsistencies and disparities in newborn screening programs throughout the United States.^7,8 Nonetheless, in other publications,² we have stated our view clearly and assert that the criteria for "assessing the effectiveness of community screening programs"⁹ have been met through the evidence accumulated thus far, leading us to state that "the burden of proof is on those who argue against neonatal screening for cystic fibrosis."² I, therefore, close by placing the "burden of proof" on Grosse et al and reject their judgment about the limited significance of nutritional benefits. Every pediatrician knows that prolonged growth retardation is generally a sign of poor health and that severe malnutrition in young children should be prevented whenever possible.

Philip M. Farrell, MD, PhD
Alfred Dorrance Daniels Professor on Diseases of Children
Dean, Univeristy of Wisconsin Medical School
Madison, WI 53706

REFERENCES

1. Farrell PM, Kosorok MR, Rock MJ, Early diagnosis of cystic fibrosis through neonatal screening prevents severe malnutrition and improves long-term growth. Pediatrics. 2001; 107:1-13
2. Cono J, Qualls NL, Khoury MJ, Hannon WH, Farrell PM. Newborn screening for cystic fibrosis: a paradigm for public health genetics policy development. MMWR Marb Mortal Wkly Rep. 1997;46(RR-16)
3. Farrell PM Improving the health of patients with cystic fibrosis through newborn screening. Adv Pediatr. 2000; 47:79-115 [Medline]
4. Wilcken B, Travert G Neonatal screening for cystic fibrosis: present and future. Acta Paediatr. 1999; 432:33-35 [CrossRef]
5. Waters DL, Wilcken B, Irwig L, Clinical outcomes of newborn screening for cystic fibrosis. Arch Dis Child Fetal Neonatal Ed. 1999; 80:F1-F7 [Abstract/Free Full Text]
6. Farrell PM, Kosorok MR, Laxova A, Nutritional benefits of neonatal screening for cystic fibrosis. N Engl J Med. 1997; 337:963-969 [Abstract/Free Full Text]
7. Kwon C, Farrell PM The magnitude and challenge of false-positive newborn screening test results. Arch Pediatr Adoles Med. 2000; 154:714-718 [Abstract/Free Full Text]
8. Farrell MH, Certain LK, Farrell PM Genetic counseling and other risk communication services by newborn screening programs. Arch Pediatr Adolesc Med. 2001; 155:120-126 [Abstract/Free Full Text]
9. Cadman D, Chambers L, Feldman W, Sackett D Assessing the effectiveness of community screening programs. JAMA. 1984; 251:1580-1585 [Abstract/Free Full Text]