Effect of Expanded Newborn Screening for Biochemical Genetic Disorders on Child Outcomes and Parental Stress

Waisbren, Susan E. PhD
Albers, Simone MD
Amato, Steve MD
Ampola, Mary MD
Brewster, Thomas G. MD
Demmer, Laurie MD
Eaton, Roger B. PhD
Greenstein, Robert MD
Korson, Mark MD
Larson, Cecilia MD
Marsden, Deborah MD
Msall, Michael MD
Naylor, Edwin W. PhD
Pueschel, Siegfried MD
Seashore, Margretta MD
Shih, Vivian E. MD
Levy, Harvey L. MD

Children's Hospital Boston, Mass (Drs Waisbren, Marsden, and Levy); University of Munster, Munster, Germany (Dr Albers); Eastern Maine Medical Center, Bangor (Dr Amato); New England Medical Center, Boston (Drs Ampola, Korson, and Demmer); Maine Medical Center, Portland (Dr Brewster); New England Newborn Screening Program of the University of Massachusetts Medical School, Jamaica Plain (Drs Eaton and Larson); Rhode Island Hospital, Providence (Drs Msall and Pueschel); University of Connecticut Health Center, Farmington (Dr Greenstein); Pediatrix Screening Inc, Bridgeville, Pa (Dr Naylor); Yale University School of Medicine, New Haven, Conn (Dr Seashore); Massachusetts General Hospital, Boston (Dr Shih). All authors are also members of the New England Consortium of Metabolic Programs.

Corresponding Author and Reprints: Susan E. Waisbren, PhD, Children's Hospital Boston, IC Smith 108, 300 Longwood Ave, Boston, MA 02115 (e-mail: [email protected]).

Author Contributions: Dr Waisbren had full access to all the data in this study and takes responsibility for the integrity of the data and the accuracy of the data analyses.

Study concept and design: Waisbren, Larson, Shih, Levy.

Acquisition of data: Waisbren, Albers, Amato, Ampola, Brewster, Demmer, Eaton, Greenstein, Korson, Marsden, Msall, Pueschel, Seashore, Shih, Levy.

Analysis and interpretation of data: Waisbren, Albers, Eaton, Larson, Naylor.

Drafting of the manuscript: Waisbren, Marsden, Levy.

Critical revision of the manuscript for important intellectual content: Albers, Amato, Ampola, Brewster, Demmer, Eaton, Greenstein, Korson, Larson, Marsden, Msall, Naylor, Pueschel, Seashore, Shih, Levy.

Statistical expertise: Waisbren, Levy.

Obtained funding: Waisbren, Levy.

Administrative, technical, or material support: Albers, Amato, Demmer, Greenstein, Korson, Larson, Msall, Pueschel, Seashore, Levy.

Study supervision: Waisbren, Marsden, Msall, Naylor, Shih, Levy.

Funding/Support: This study was supported by grants from Maternal and Child Health Bureau (5H46 MC 00158) and the Ethical, Legal and Social Implications (ELSI) division of the Human Genome Project, National Institutes of Health (RO1 HG02085). These organizations approved the original proposal and annual progress reports as a prerequisite for funding. The German Research Foundation (Deutsche Forschungsgemeinschaft AL537/1–1) also provided support for Dr Albers to work on this project. Dr Waisbren is a member of the institutional review board at Children's Hospital Boston. NeoGen Screening/Pediatrix was not a funding sponsor of this study.

Role of Collaborator: NeoGen Screening/Pediatrix did not participate in the design of the study. With the collaboration of Dr Naylor (previous owner of NeoGen), an employee of NeoGen sent out the recruitment packages and conducted the interviews. No one else from NeoGen was permitted to read the notes from the interviews. NeoGen was not directly involved in the analysis of the data. Dr Naylor and the employee of NeoGen reviewed the analyses and made suggestions regarding interpretation of the data. They were not directly involved in the preparation of the manuscript but reviewed the manuscript, made suggestions, and approved the final manuscript.

Acknowledgment: We thank Elizabeth Allred, MS; Mary Andrews, MS, RD; Kevin Antshel, PhD; Isabel Bailey, LICSW; Renee Charbonneau, MS, NP; Nancy Chace, BA; Anne Marie Comeau, PhD; Laura Finkelson, PhD; Sherry Gray, RD; Elizabeth Gurian, BS; Judy Henry, MS, RN; Deborah Lobbregt, BA; Diane Paul, PhD; Jonathan Picker, MD; Michelle Rones, PhD; Robin Schwartz, MS; David Taus, BA; and Pierre Yared, BA.

JAMA: The Journal of the American Medical Association 290(19):p 2564-2572, November 19, 2003.

Context

Tandem mass spectrometry now allows newborn screening for more than 20 biochemical genetic disorders. Questions about the effectiveness and risks of expanded newborn screening for biochemical genetic disorders need to be answered prior to its widespread acceptance as a state-mandated program.

Objectives

To compare newborn identification by expanded screening with clinical identification of biochemical genetic disorders and to assess the impact on families of a false-positive screening result compared with a normal result in the expanded newborn screening program.

Design

Prospective study involving an inception cohort of newly diagnosed children.

Setting

Massachusetts, Maine, and a private laboratory in Pennsylvania with expanded newborn screening; other New England states with limited screening.

Participants

Families of 50 affected children identified through expanded newborn screening (82% of eligible cases); 33 affected children identified clinically (97% of eligible cases); 94 screened children with false-positive results (75% of eligible cases); and 81 screened children with normal results (63% of eligible cases).

Main Outcome Measures

Child's health and development and the Parental Stress Index.

Results

Within the first 6 months of life, 28% of children identified by newborn screening compared with 55% of clinically identified children required hospitalization (P =.02). One child identified by newborn screening compared with 8 (42%) identified clinically performed in the range of mental retardation (P<.001). Mothers in the screened group reported lower overall stress on the Parental Stress Index than mothers in the clinically identified group (z = 3.38, P<.001). Children with false-positive results compared with children with normal results were twice as likely to experience hospitalization (21% [n = 20] vs 10% [n = 8], respectively; P =.06). Mothers of children in the false-positive group compared with mothers of children with normal screening results attained higher scores on the Parental Stress Index (z = 4.25, P<.001) and the Parent-Child Dysfunction subscale (z = 5.30, P<.001).

Conclusions

Expanded newborn screening may lead to improved health outcomes for affected children and lower stress for their parents. However, false-positive screening results may place families at risk for increased stress and parent-child dysfunction.