Correspondence

Newborn Screening Showing Decreasing Incidence of Cystic Fibrosis

N Engl J Med 2008; 358:973-974February 28, 2008

Article

To the Editor:

Newborn screening for cystic fibrosis has been universally available in Massachusetts since February 1999.1 The sensitivity of the screening was measured from 1999 to 2002 and was shown to be high, in keeping with predictions derived from historical data of patients in Massachusetts presenting clinically and documented in the national Cystic Fibrosis Foundation Patient Registry.2 We report a decrease in the number of neonates with cystic fibrosis in Massachusetts who were identified by means of newborn screening for cystic fibrosis during the period from 2003 to 2006, along with a significant decrease in the number of infants with the genotype most typically associated with severe cystic fibrosis, ΔF508/ΔF508 (Figure 1Figure 1Newborns with Cystic Fibrosis Identified by Newborn Screening for the Disease in Massachusetts.).

From 1999 to 2006, the number of neonates in annual birth cohorts in Massachusetts remained stable; on average, there were about 80,000 births each year during this period. We made calculations using frequencies derived from patients in Massachusetts included in the Cystic Fibrosis Foundation Patient Registry. For each year, we calculated the expected number of patients with cystic fibrosis by multiplying the number of births by 0.000345. We calculated the expected number of infants with cystic fibrosis with the ΔF508/ΔF508 genotype by multiplying the number of infants with the disease by 0.511. Chi-square analyses for ΔF508/ΔF508 against all other genotypes showed that the observed number of infants with cystic fibrosis equaled the expected number of infants with the disease for the period from 1999 to 2002, when analyzed both annually and collectively. However, a significant decrease in the number of infants with the ΔF508/ΔF508 genotype (P<0.005) was observed in 2003 and continued through 2006. Such a decrease lowers the positive predictive value of newborn screening for cystic fibrosis.

Long-term follow-up evaluations conducted by the New England Newborn Screening Program and the Massachusetts Cystic Fibrosis Newborn Screening Work Group confirm that the observed decrease reflects a change in the makeup of the birth cohort of infants with cystic fibrosis; infants with ΔF508/ΔF508 are unlikely to have been missed by newborn screening for cystic fibrosis, since no additional cases have been identified clinically. We hypothesize that the gradual implementation of the 2001 recommendation by the American College of Medical Genetics, the American College of Obstetricians and Gynecologists, and the National Institutes of Health3 to offer preconception and prenatal screening to the general population in order to identify carriers of cystic fibrosis might have yielded a decrease in the number of births of infants with ΔF508/ΔF508 and births of other children with cystic fibrosis; this decrease would have first been observed in 2003.

As newborn screening for cystic fibrosis becomes more common, care providers for children with this disease are faced with the need for evidence-based standards of care to address a new population — that comprising relatively asymptomatic infants with cystic fibrosis who are identified before clinical presentation. This cohort is likely to be involved in clinical trials of promising treatments.4 At the same time — and apparently unrelated to newborn screening for cystic fibrosis — the composition of the cohort may be changing, with an increasing proportion of infants who have favorable natural histories (i.e., fewer patients with the ΔF508/ΔF508 genotype). Such a change would influence the degree to which improvements in outcomes are directly attributable to early detection or new treatments.

Jaime E. Hale, B.S.
Richard B. Parad, M.D., M.P.H.
Anne Marie Comeau, Ph.D.
New England Newborn Screening Program, Jamaica Plain, MA 02130
anne.comeau@umassmed.edu

Dr. Parad reports receiving lecture fees from MedPro Communications. No other potential conflict of interest relevant to this letter was reported.

4 References

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Citing Articles (11)

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   Peter D. FIELD, Nicole J. MARTIN. (2011) CFTR mutation screening in an assisted reproductive clinic. Australian and New Zealand Journal of Obstetrics and Gynaecology 51:6, 536-539
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   W. Burke, B. Tarini, N. A. Press, J. P. Evans. (2011) Genetic Screening. Epidemiologic Reviews 33:1, 148-164
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   C. J. Bell, D. L. Dinwiddie, N. A. Miller, S. L. Hateley, E. E. Ganusova, J. Mudge, R. J. Langley, L. Zhang, C. C. Lee, F. D. Schilkey, V. Sheth, J. E. Woodward, H. E. Peckham, G. P. Schroth, R. W. Kim, S. F. Kingsmore. (2011) Carrier Testing for Severe Childhood Recessive Diseases by Next-Generation Sequencing. Science Translational Medicine 3:65, 65ra4-65ra4
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   Carlo Castellani, John Massie. (2010) Emerging issues in cystic fibrosis newborn screening. Current Opinion in Pulmonary Medicine 16:6, 584-590
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   Jeffrey S. Dungan. (2010) Carrier Screening for Cystic Fibrosis. Obstetrics and Gynecology Clinics of North America 37:1, 47-59
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   John MASSIE, Vicki PETROU, Robyn FORBES, Lisette CURNOW, Liane IOANNOU, Desiree DUSART, Agnes BANKIER, Martin DELATYCKI. (2009) Population-based carrier screening for cystic fibrosis in Victoria: The first three years experience. Australian and New Zealand Journal of Obstetrics and Gynaecology 49:5, 484-489
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   Brian O'Sullivan, Steven Freedman. (2009) Carrier screening for cystic fibrosis – Authors' reply. The Lancet 374:9694, 978
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   John Massie. (2009) Carrier screening for cystic fibrosis. The Lancet 374:9694, 978
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   Wayne W. Grody. (2009) Cystic Fibrosis Testing Comes of Age. The Journal of Molecular Diagnostics 11:3, 173-175
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    Miroslava Balaščaková, Andrea Holubová, Veronika Skalická, Dana Zemková, Petr Kračmar, Lucie Gonsorčíkova, Jana Čamajová, Tereza Piskáčková, Jan Lebl, Pavel Dřevínek, Vladimír Gregor, Věra Vávrová, Felix Votava, Milan Macek. (2009) Pilot newborn screening project for cystic fibrosis in the Czech Republic: Defining role of the delay in its symptomatic diagnosis and influence of ultrasound-based prenatal diagnosis on the incidence of the disease. Journal of Cystic Fibrosis 8:3, 224-227
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    Godelieve CML Page-Christiaens, Ferdinand Teding van Berkhout. 2008. The patient with cystic fibrosis. , 159-172.
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