Newborn Screening for Cystic Fibrosis in New York State: In Reply

(1)

experience with CPAP the incidence of BPD was only 6%.1_{Similar figures for BPD have been published for the} CPAP experience at Columbia University.2 _Therefore, the use of the currently available CPAP is vastly success-ful. Our goal is to focus on making these BPD figures universally replicable in all units. Once this milestone is established, efforts should then be focused on optimizing the “ventilatory pump” to further lower BPD to⬍6%. At the current stage, I find it distracting to focus on different medications and ventilatory approaches while the avail-able CPAP technique can be feasible and successful in our population. Subsequent efforts that can support pre-mature lungs and/or ventilatory pump should be ad-dressed only after passing this first important milestone. Hany Aly, MD

Department of Newborn Services George Washington University Hospital and Children’s National Medical Center Washington, DC 20037

REFERENCES

1. Aly H, Massaro AN, Patel K, El-Mohandes AA. Is it safer to intubate premature infants in the delivery room? Pediatrics. 2005;115:1660 –1665

2. Van Marter LJ, Allred EN, Pagano M, et al. Do clinical markers of barotrauma and oxygen toxicity explain interhospital varia-tion in rates of chronic lung disease? The Neonatology Commit-tee for the Developmental Network. Pediatrics. 2000;105: 1194 –1201

doi:10.1542/peds.2007-1163

Newborn Screening for Cystic

Fibrosis in New York State

To the Editor.—

We wish to rectify numerous inaccuracies in the recent article by Giusti et al.1_{Although there is no “state} coor-dinator” per se for cystic fibrosis (CF), a follow-up CF team does exist to provide assistance to anyone who contacts the screening program. The authors asserted that an immunoreactive trypsinogen value was unavail-able for 1 cited infant; however, to our knowledge, no inquiry was made to the program in that individual case. Section 69 –1.7 of the New York State Public Health Law 2500a specifies the roles of specialized care centers, also known as treatment centers. Status as a designated treat-ment center is voluntary, not mandated. With respect to reimbursement for genetic counseling services, New York State has the Genetic Services Program, which awards monies so that every state resident has access to genetic counseling services. Only 1 CF center lacks an award through this program.

The statement that the program will not accept a second specimen was erroneous. In fact, we receive ⬎15 000 “repeat” specimens annually, corresponding to

⬃6% of New York State births. The program requests some of these specimens if either the original sample provided a borderline value or it was unsuitable for analysis because of poor/early collection. The rest, flagged as unsolicited repeats, are screened for the entire panel unless otherwise indicated. All repeat specimens are linked to the original samples in our computer sys-tem, and we request the results of any subsequent test-ing performed so that we can close those cases and ensure that all infants received the medical attention to which they are entitled under the law.

Last, the statement that “the 5/7/9T variant is not a reflex test in the New York state protocol” was incorrect. Screening began on October 7, 2002, and every report of an R117H variant includes the intron-8 polymorphism status.2,3_{At the time of the original publication,}1_reflex testing for 3199del6 was under regulatory review; it has since been implemented in New York State.

The general strategy of the program has been to pro-ceed conservatively until sufficient data have been col-lected to warrant changes. For example, we began me-dium-chain acyl-coenzyme A dehydrogenase deficiency screening in 2002. After review of our data, we reduced the number of referrals from 73 in 2003 to 41 in 2005, a ⬎40% reduction. Similar changes to the CF screening protocol are forthcoming in New York State.

Michele Caggana, ScD, FACMG Laura Helton, MD, MPH

New York State Newborn Screening Program Wadsworth Center New York State Department of Health Albany, NY 12201

REFERENCES

1. Giusti R, Badgwell A, Iglesias AD; New York State Cystic Fibrosis Newborn Screening Consortium. New York State Cystic Fibrosis Consortium: the first 2.5 years of experience with cystic fi-brosis newborn screening in an ethnically diverse population. Pediatrics. 2007;119(2). Available at: www.pediatrics.org/cgi/ content/full/119/2/e460

2. Grody WW, Cutting GR, Klinger KW, et al. Laboratory standards and guidelines for population-based cystic fibrosis carrier screening.Genet Med.2001;3:149 –154

3. Watson MS, Cutting GR, Desnick RJ, et al. Cystic fibrosis pop-ulation carrier screening: 2004 revision of American College of Medical Genetics mutation panel.Genet Med.2004;6:387–391

doi:10.1542/peds.2007-1048

In Reply.—

We are happy to reply to the letter to the editor submit-ted by Drs Caggana and Helton. The purpose of writing our article was to report on cystic fibrosis (CF) newborn screening in a state with an ethnically diverse popula-tion, to make recommendations to improve the sensitiv-ity of the screening algorithm, and to help physicians in states that are in the planning stages of a CF newborn

PEDIATRICS Volume 120, Number 1, July 2007 241 at Viet Nam:AAP Sponsored on August 29, 2020

www.aappublications.org/news

(2)

screening program to address some of the problems that we encountered.

In reference to the absence of a “state coordinator,” we fully agree that the Wadsworth Center has a well established team to provide assistance related to the newborn screening program. However, in our article, we were referring to the fact that there is no funding to support a coordinator to facilitate the referral of screen-positive infants to regional CF care centers, where a diagnostic sweat test can be performed. Other states, such as Massachusetts, have developed funding mecha-nisms to support such a position, which has facilitated making contact with screen-positive infants and assuring timely sweat testing.1_{It is our opinion that developing a} funding source for such a position would be an effective intervention to help resolve the large number of cases that have been lost to follow-up in New York. We rec-ommend that any state that is in the planning stage of a CF newborn screening program consider the benefit of establishing such a position.

With regard to reimbursement for genetic counseling services, we acknowledge that the New York State De-partment of Health provides funding to many hospitals in the state for genetic counseling services. However, the CF care centers, where the bulk of the counseling and coordination for follow-up of positive CF-screened in-fants occurs, do not receive any funding to help defer the cost of additional time committed by staff members to ensure that the screening program runs effectively. Other states, such as New Jersey (R. Zanni, MD, personal communication, April 2007), have been successful in acquiring additional funding for the CF care centers to help pay for the manpower needs of their screening program. Once again, we recommend that any state that is in the planning stage of a CF newborn screening program consider a mechanism to generate additional funds for this purpose.

We acknowledge that the Wadsworth Center per-forms repeat specimen testing. However, in our article we raised the issue of developing a mechanism to accept a repeat immunoreactive trypsinogen (IRT) result at 2 weeks of age to close a case without the need for a referral for a sweat test. The screening program in Col-orado collects a repeat specimen obtained at 2 weeks of age. We believe that accepting a repeat IRT at 2 weeks of age could be a solution to the high false-positive rate that we have experienced in New York State during the first 21_⁄₂ _{years of screening for CF.}2 _{The large number of} screen-positive infants with an elevated IRT and no CF mutations detected would be suitable for requesting re-peat IRT testing.

We acknowledge that currently in New York State the intron-8 polymorphism is reported whenever the R117H mutation is detected. However, the issue that we raised in our article was whether 7T/9T polymorphisms should be reported as screen-positive. In view of the high

fre-quency of R117H-7T identified by CF newborn screen-ing, the uncertain outcome of the asymptomatic chil-dren, and physicians’ difficulty in managing these situations, Scotet et al3_{proposed the withdrawal of the} R117H variant from the panels of CF transmembrane conductance regulator (CFTR) mutations used in CF newborn screening. Any state that is planning a CF newborn screening program must be aware that “[u]se of mutations associated with milder phenotypes may lead to results that are difficult to interpret.”4 _We ac-knowledge that this is a controversial issue that needs to be considered by states that are in the planning stages of a CF newborn screening program.

We fully agree with the general strategy of proceeding in a conservative manner; however, we support the recommendation of the Centers for Disease Control and Prevention report on newborn screening for CF: “states that implement newborn screening for CF should collect follow-up data in collaboration with CF care centers and analyze this information to monitor and improve the quality of CF newborn screening.”5 _{Such an} annual-review mechanism would facilitate making adjustments to the screening algorithm with the goal of improving the sensitivity of the program. We are happy to report that in New York State we currently have monthly con-ference calls and have annual meetings planned.

Robert Giusti, MD

Department of Pediatrics

Ashley Badgwell, MS

Department of Obstetrics/Gynecology Long Island College Hospital Brooklyn, NY 11231

Alejandro D. Iglesias, MD

Department of Pediatrics Beth Israel Medical Center New York, NY 10003

REFERENCES

1. Comeau AM, Parad RB, Dorkin HL, et al. Population-based newborn screening for genetic disorders when multiple muta-tion DNA testing is incorporated: a cystic fibrosis screening model demonstrating increased sensitivity but more carrier de-tections.Pediatrics.2004;113:1573–1581

2. Sontag MK, Hammond KB, Zielenski J, Wagener JS, Accurso F. Two-tiered immunoreactive trypsinogen-based newborn screening for cystic fibrosis in Colorado: screening efficacy and diagnostic outcomes.J Pediatr.2005;147(3 suppl):S83–S88 3. Scotet V, Audre´zet MP, Roussey M, et al. Immunoreactive

trypsin/DNA newborn screening for cystic fibrosis: should the R117H variant be included inCFTRmutation panels?Pediatrics. 2006;118(5). Available at: www.pediatrics.org/cgi/content/full/ 118/5/e1523

4. Comeau AM, Accurso FJ, White TB, et al. Guidelines for implementation of cystic fibrosis newborn screening pro-grams: Cystic Fibrosis Foundation workshop report.Pediatrics. 2007;119(2). Available at: www.pediatrics.org/cgi/content/ full/119/2/e495

5. Grosse SD, Boyle CA, Botkin JR, et al. Newborn screening for cystic fibrosis: evaluation of benefits and risks and

recommen-242 LETTERS TO THE EDITOR

at Viet Nam:AAP Sponsored on August 29, 2020

(3)

dations for state newborn screening programs.MMWR Recomm Rep.2004;53(RR-13):1–36

doi:10.1542/peds.2007-1183

Prenatal Chlorpyrifos and Early

Neurodevelopment: How Good Is

the Science?

To the Editor.—

In their article, Rauh et al1_{drew many false conclusions} and implicated prenatal exposure to chlorpyrifos as the cause of deficits in Mental Developmental Index and Psychomotor Development Index 3 years later. The con-clusions were false because:

1. The mean Mental Developmental Index scores (see their Table 1) between the high- and low-exposure groups are clinically meaningless: 94 and 94 at 12 months; 84 and 85 at 24 months; and 87 and 90 at 36 months.

2. The average high- and low-exposure Psychomotor Development Index scores were 93 and 97 at 12 months, 99 and 97 at 24 months, and 96 and 102 at 36 months; and measured IQ levels ranged between 9 and 30 points (profound mental retardation [MR]: 0 –29; severe MR: 20 –29; moderate MR: 30 – 49; mild MR: 50 – 69; dull normal: 70 – 89; normal: 90 –110; bright normal: 111–119; superior: 120 –139; very su-perior: 140 toⱖ160).

3. With no standards defining “high” and “low” expo-sure, the authors concluded falsely that 20.6% of the sample had high exposure to chlorpyrifos.

4. The authors tried to eliminate maternal education bias by dichotomizing maternal education into high school graduate or nongraduate. This dubious ma-neuver masked, but did not eliminate, educational bias. The authors should have used a better index of socioeconomic status, such as family income. 5. The sample mean was substituted for intelligence

scores that were missing for 29 women. Of 14 meth-ods of data imputation, Engels and Diehr2_concluded that: “Imputations that used no information specific to the person, such as using the sample mean, had the worst performance.”

6. A correlation of 0.76 means that the variability in umbilical cord samples explains only 0.762_{or 58% of}

the variability in maternal plasma, which indicates that the authors’ substitution of 1 variable for the other is not valid.

7. The high- and low-exposure groups (see their Table 1) were grossly different in race/ethnicity character-istics: the high-exposure group contained 24% black and 15% Dominican mothers, whereas the

lower-exposure group was comprised of 76% black and 85% Dominican mothers. These huge differences in-extricably confound race/ethnicity with exposure level and, therefore, served to negate the role of chlorpyrifos as an etiologic factor for later deficits in psychomotor and cognitive performance.

8. The finding that high-exposure children had more attention-deficit/hyperactivity disorder problems is also meaningless, because, as the authors themselves concluded, theDiagnostic and Statistical Manual of Men-tal Disorders, Fourth Edition “has low sensitivity for as-sessing the inattentiveness of preschool-aged children.” Domenic V. Cicchetti, PhD

Child Study Center Departments of Psychiatry and Biometry Yale School of Medicine New Haven, CT 06512

REFERENCES

1. Rauh VA, Garfinkel R, Perera FP, et al. Impact of prenatal chlorpyrifos exposure on neurodevelopment in the first 3 years of life among inner-city children.Pediatrics. 118(6). Available at: www.pediatrics.org/cgi/content/full/118/6/e1845

2. Engels JM, Diehr P. Imputation of missing longitudinal data: a comparison of methods.J Clin Epidemiol.2003;56:968 –976

doi:10.1542/peds.2007-0689

In Reply.—

We reported that inner-city children who were highly exposed in utero to the insecticide chlorpyrifos were significantly more likely than lower-exposed children to experience motor and mental delays and behavior problems related to attention, attention-deficit/hyper-activity, and pervasive developmental disorders.

In response to Dr Cicchetti’s remarks:

1. We strongly disagree with Dr Cicchetti’s claim that the significant chlorpyrifos effect on mental develop-ment was “clinically meaningless.” A Bayley devel-opmental score of⬍85 prompts referral to early in-tervention services and is far from trivial.1_Exposures that produce small shifts in the mean often result in more children who meet diagnostic criteria, which is an outcome that is of great concern to clinicians. 2. Contrary to Dr Cicchetti’s point, we used a clearly

stated, a priori standard for high chlorpyrifos expo-sure, defined as ⱖ6.17 pg/g, based on a previous report of reduced birth weight among children with exposures above this level.2

3. We do not understand why Dr Cicchetti thinks that using high-school degree to adjust for maternal edu-cational level is a “dubious maneuver” and note his own use of this variable in an analysis of cocaine effects on development.3 _{Because our sample was} uniformly low income, education was the preferred covariate for social class.

PEDIATRICS Volume 120, Number 1, July 2007 243 at Viet Nam:AAP Sponsored on August 29, 2020

(4)

DOI: 10.1542/peds.2007-1183

2007;120;241

Pediatrics

Robert Giusti, Ashley Badgwell and Alejandro D. Iglesias

Newborn Screening for Cystic Fibrosis in New York State: In Reply

Services

Updated Information &

http://pediatrics.aappublications.org/content/120/1/241.2 including high resolution figures, can be found at:

References

http://pediatrics.aappublications.org/content/120/1/241.2#BIBL This article cites 3 articles, 1 of which you can access for free at:

Subspecialty Collections

http://www.aappublications.org/cgi/collection/pulmonology_sub Pulmonology

http://www.aappublications.org/cgi/collection/genetics_sub Genetics

sub

http://www.aappublications.org/cgi/collection/fetus:newborn_infant_ Fetus/Newborn Infant

following collection(s):

This article, along with others on similar topics, appears in the

Permissions & Licensing

http://www.aappublications.org/site/misc/Permissions.xhtml in its entirety can be found online at:

Information about reproducing this article in parts (figures, tables) or

Reprints

http://www.aappublications.org/site/misc/reprints.xhtml Information about ordering reprints can be found online:

(5)

DOI: 10.1542/peds.2007-1183

2007;120;241

Pediatrics

Robert Giusti, Ashley Badgwell and Alejandro D. Iglesias

Newborn Screening for Cystic Fibrosis in New York State: In Reply

http://pediatrics.aappublications.org/content/120/1/241.2

located on the World Wide Web at:

The online version of this article, along with updated information and services, is

the American Academy of Pediatrics, 345 Park Avenue, Itasca, Illinois, 60143. Copyright © 2007 has been published continuously since 1948. Pediatrics is owned, published, and trademarked by Pediatrics is the official journal of the American Academy of Pediatrics. A monthly publication, it