Early diagnosis of cystic fibrosis through neonatal screening prevents severe malnutrition and improves long-term growth.
Objective. Despite its relative frequency among autosomal recessive diseases and the availability of the sweat test, cystic fibrosis (CF) has been difficult to diagnose in early childhood, and delays can lead to severe malnutrition, lung disease, or even death. The Wisconsin CF Neonatal Screening Pr...
| Publicado en: | Pediatrics Vol. 107; no. 1; pp. 1 - 14 |
|---|---|
| Autores principales: | , , , , , , , , |
| Formato: | research tables/charts Journal Article |
| Publicado: |
American Academy of Pediatrics
Jan2001
|
| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=107017099&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 107017099 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00314005 PDT jtl: Pediatrics issn: 00314005 maglogo: N pubinfo: dt: Jan2001 vid: 107 iid: 1 pid: 1659 pub: American Academy of Pediatrics place: Elk Grove Village, Illinois artinfo: ui: 107017099 107017099 2001035392 10.1542/peds.107.1.1 NLM11134427 107017099 ppf: 1 ppct: 13 formats: tig: atl: Early diagnosis of cystic fibrosis through neonatal screening prevents severe malnutrition and improves long-term growth. aug: au: Farrell PM Kosorok MR Rock MJ Laxova A Zeng L Lai H Hoffman G Laessig RH Splaingard ML affil: Department of Pediatrics, University of Wisconsin Medical School, Room 1217 MSC, 1300 University Ave, Madison, WI 53706. E-mail: pmfarrel@facstaff.wisc.edu sug: subj: Cystic Fibrosis Diagnosis Neonatal Assessment Nutritional Status In Infancy and Childhood Fisher's Exact Test Wisconsin Prospective Studies Convenience Sample Body Weights and Measures Random Assignment Nutritional Assessment Repeated Measures Confidence Intervals Wilcoxon Rank Sum Test Infant, Newborn Funding Source Human Infant, Newborn: birth-1 month ab: Objective. Despite its relative frequency among autosomal recessive diseases and the availability of the sweat test, cystic fibrosis (CF) has been difficult to diagnose in early childhood, and delays can lead to severe malnutrition, lung disease, or even death. The Wisconsin CF Neonatal Screening Project was designed as a randomized clinical trial to assess the benefits and risks of early diagnosis through screening. In addition, the incidence of CF was determined, and the validity of our randomization method assessed by comparing 16 demographic variables.Methodology. Immunoreactive trypsinogen analysis was applied to dried newborn blood specimens for recognition of CF risk from 1985 to 1991 and was coupled to DNA-based detection of the delta F508 mutation from 1991 to 1994. Randomization of 650 341 newborns occurred when their blood specimens reached the Wisconsin screening laboratory. This created 2 groupsan early diagnosis, screened cohort and a standard diagnosis or control group. To avoid selection bias, we devised a unique unblinding method with a surveillance program to completely identify the control subjects. Because sequential analysis of nutritional outcome measures revealed significantly better growth in screened patients during 1996, we accelerated the unblinding and completely identified the control group by April 1998. Having each member of this cohort enrolled and evaluated for at least 1 year and having completed a comprehensive surveillance program, we performed another statistical analysis of anthropometric evaluated indices that includes all CF patients without meconium ileus.Results. The incidence of classical CF, ie, patients diagnosed in this trial with a sweat chloride of 60 mEq/L greater, was 1:4189. By incorporating other CF patients born during the randomization period, including 2 autopsy diagnosed patients and 8 probable patients, we calculate a maximum incidence of 1:3938 (95% confidence interval: 3402-4611). Although there were group differences in the proportion of patients with F508 genotypes and with pancreatic insufficiency, validity of the randomization plan was demonstrated by analyzing 16 demographic variables and finding no significant difference after adjustment for multiple comparisons. Focusing on patients without meconium ileus, we found a marked difference in the mean +/- standard deviation age of diagnosis for screened patients (13 +/- 37 weeks), compared with the standard diagnosis group (100 +/- 117). Anthropometric indices of nutritional status were significantly higher at diagnosis in the screened group, including length/height, weight, and head circumference. During 13 years of study, despite similar nutritional therapy and the inherently better pancreatic status of the control group, analysis of nutritional outcomes revealed significantly greater growth associated with early diagnosis. Most impressively, the screened group had a much lower proportion of patients with weight and height data below the 10th percentile throughout childhood.Conclusions. Although the screened group had a higher proportion of patients with pancreatic insufficiency, their growth indices were significantly better than those of the control group during the 13-year follow-up evaluation and, therefore, this randomized clinical trial of early CF diagnosis must be interpreted as unequivocally positive. Our conclusions did not change when the height and weight data before 4 years of age for the controls detected by unblinding were included in the analysis. Also, comparison of growth outcomes after 4 years of age in all subjects showed persistence of the significant differences. Therefore, selection bias has been eliminated as a potential explanation. In addition, the results show that severe malnutrition persists after delayed diagnosis of CF and that catch-up may not be possible. We conclude that early diagnosis of CF through neonatal screening combined with aggressive nutritional therapy can result in significantly enhanced long-term nutritional status. pubtype: Academic Journal doctype: research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
|---|