The First 4 Years – Outcome of Children Identified by Newborn Screening for CF in Germany

Abstract

Background Newborn screening (NBS) has been shown to improve cystic fibrosis (CF) disease course and has been widely implemented worldwide. This monocentric study compared children diagnosed by NBS vs. a cohort preceding the implementation of NBS in Germany in 2016 to evaluate ascribed benefits of NBS.

Methods We compared all children with confirmed CF diagnosis (n=19, “NBS group”) out of all children presenting with positive NBS at our center after implementation of NBS (n=100) to children diagnosed with CF at our center within 4 years before NBS implementation (n=29, “pre-NBS group”) for outcomes of anthropometry, gastrointestinal and pulmonary disease manifestations and respiratory microbiology.

Results Children diagnosed by NBS had a lower incidence of initial difficulty to thrive (15 vs. 41%) and showed higher mean z-scores for Body-Mass-Index (BMI), weight and length at diagnosis and during study period. Children in the pre-NBS group displayed higher proportions of oxygen-dependent pulmonary exacerbations (10 vs. 0%). They show a significantly lower amount of normal bacterial flora (p=0.005) along with a significantly higher number of throat swab cultures positive for Pseudomonas aeruginosa (p=0.0154) in the first year of life. Yet, pulmonary imaging did not reveal less pulmonary morbidity in the NBS group.

Conclusions Our results confirm that NBS for CF leads to earlier diagnosis and improves nutritional outcomes in early childhood. Although trajectories of structural lung damage at early age were unaffected by NBS, NBS positive CF patients at preschool age displayed less pulmonary exacerbations and pathological bacteria in throat swabs.

Zusammenfassung

Hintergrund Das Neugeborenen-Screening (NBS) verbessert nachweislich den Krankheitsverlauf der Mukoviszidose (CF). Diese monozentrische Studie vergleicht Kinder, die durch NBS diagnostiziert wurden, mit einer altersentsprechenden Kohorte vor Einführung des NBS in Deutschland im Jahr 2016, um die Vorteile des NBS zu evaluieren.

Methoden Kinder, die mit positivem NBS (n=100) in unserem Zentrum vorstellig wurden, und bei denen sich die Diagnose Mukoviszidose bestätigte (n=19, "NBS-Gruppe") werden mit Kindern vergleichen, bei denen innerhalb von 4 Jahren vor Einführung des NBS in unserem Zentrum Mukoviszidose diagnostiziert wurde.

Ergebnisse Mittels NBS diagnostizierte Kinder, hatten eine geringere Inzidenz von anfänglichen Ernährungsproblemen (15% gegenüber 41%), einen höheren mittleren z-Score für Body-Mass-Index (BMI), Gewicht und Länge bei Diagnosestellung und während des Studienzeitraums. Kinder in der Prä-NBS-Gruppe wiesen einen höheren Anteil an pulmonalen Exazerbationen (10% gegenüber 0%) auf. Sie wiesen signifikant weniger normale Bakterienflora (p=0,005) sowie eine höhere Rate an Pseudomonas aeruginosa (p=0,0154) im Rachenabstrich auf. Die pulmonale Bildgebung ergab jedoch keine geringere pulmonale Morbidität in der NBS-Gruppe.

Schlussfolgerungen Unsere Ergebnisse bestätigen, dass NBS bei Mukoviszidose zu einer früheren Diagnose führt und die Ernährungssituation im frühen Kindesalter verbessert. Obwohl der Verlauf der strukturellen Lungenschäden im frühen Alter durch NBS nicht beeinflusst wurde, wiesen NBS-positive Mukoviszidose-Patienten im Vorschulalter weniger pulmonale Exazerbationen und pathologische Bakterienbesiedlungen im Rachenabstrichen auf.

Key words

cystic fibrosis - newbornscreening - BMI - NBS - mCN-Score - lung pathologies

Schlüsselwörter

Mukoviszidose - Neugeborenenscreening - BMI - mCN-Score - lungenpathologien - NBS

Publication History

Article published online:
28 January 2022

• References

• 1 Farrell PM, Li Z, Kosorok MR. et al. Bronchopulmonary disease in children with cystic fibrosis after early or delayed diagnosis. Am J Respir Crit Care Med 2003; 168: 1100-1108
• 2 Sims EJ, Clark A, McCormick J. et al. Cystic fibrosis diagnosed after 2 months of age leads to worse outcomes and requires more therapy. Pediatrics 2007; 119: 19-28
• 3 Scotet V, Gutierrez H, Farrell PM. Newborn Screening for CF across the Globe-Where Is It Worthwhile?. Int J Neonatal Screen 2020; 6: 18
• 4 Dijk FN, McKay K, Barzi F. et al. Improved survival in cystic fibrosis patients diagnosed by newborn screening compared to a historical cohort from the same centre. Arch Dis Child 2011; 96: 1118-1123
• 5 Mak DY, Sykes J, Stephenson AL. et al. The benefits of newborn screening for cystic fibrosis: The Canadian experience. J Cyst Fibros 2016; 15: 302-308
• 6 Martin B, Schechter MS, Jaffe A. et al. Comparison of the US and Australian cystic fibrosis registries: the impact of newborn screening. Pediatrics 2012; 129: e348-e355
• 7 Stahl M, Steinke E, Graeber SY. et al. Magnetic Resonance Imaging Detects Progression of Lung Disease and Impact of Newborn Screening in Preschool Children with Cystic Fibrosis. Am J Respir Crit Care Med 2021; 204: 943-953
• 8 Screening auf Mukoviszidose [Internet].; 2018 []. Available from: https://screening-dgns.de/Pdf/m1.pdf
• 9 Deutsches Mukoviszidose-Register Berichtsband 2017 - Patient Registry Annual Data Report 2017 [Internet].; 2017 []. Available from: https://www.muko.info/fileadmin/user_upload/angebote/qualitaetsmanagement/register/berichtsband_2017.pdf
• 10 Rosenstein BJ, Cutting GR. The diagnosis of cystic fibrosis: a consensus statement. Cystic Fibrosis Foundation Consensus Panel. J Pediatr 1998; 132: 589-595
• 11 Castellani C, Duff AJA, Bell SC. et al. ECFS best practice guidelines: the 2018 revision. J Cyst Fibros 2018; 17: 153-78.
• 12 Kromeyer-Hauschild K, Wabitsch M, Kunze D. et al. Perzentile für den Body-mass-Index für das Kindes- und Jugendalter unter Heranziehung verschiedener deutscher Stichproben. Monatsschrift Kinderheilkunde 2001; 149: 807-18.
• 13 Benden C, Wallis C, Owens CM. et al. The Chrispin-Norman score in cystic fibrosis: doing away with the lateral view. Eur Respir J 2005; 26: 894-897
• 14 de Jong PA, Achterberg JA, Kessels OA. et al. Modified Chrispin-Norman chest radiography score for cystic fibrosis: observer agreement and correlation with lung function. Eur Radiol 2011; 21: 722-729
• 15 Podbielski A, Abele-Horn M, Hogardt M. Hrsg MIQ 24: Atemwegsinfektionen bei Mukoviszidose: Qualitätsstandards in der mikrobiologisch-infektiologischen Diagnostik. München: Urban & Fischer; 2019
• 16 Hammermann J, Claßen M, Schmidt S. et al. S3-Leitlinie: Mukoviszidose bei Kindern in den ersten beiden Lebensjahren, Diagnostik und Therapie. AWMF online. 2020 Version vom 6.3.2020;Registernummer 026 – 024; Klasse S3
• 17 Martins JP, Forte GC, Simon MISDS. et al. The role of neonatal screening in nutritional evolution in the first 12 months after diagnosis of cystic fibrosis. Rev Assoc Med Bras (1992) 2018; 64: 1032-1037
• 18 Hauschild DB, Rosa AF, Ventura JC. et al. Association of Nutritional Status with Lung Function and Morbidity in Children and Adolescents with Cystic Fibrosis: a 36-Month Cohort Study. Rev Paul Pediatr 2018; 36: 8
• 19 Peralta GP, Abellan A, Montazeri P. et al. Early childhood growth is associated with lung function at 7 years: a prospective population-based study. Eur Respir J 2020; 56: 2000157
• 20 Wilschanski M, Braegger CP, Colombo C. et al. Highlights of the ESPEN-ESPGHAN-ECFS Guidelines on Nutrition Care for Infants and Children With Cystic Fibrosis. J Pediatr Gastroenterol Nutr 2016; 63: 671-675
• 21 Owen E, Williams JE, Davies G. et al. Growth, Body Composition, and Lung Function in Prepubertal Children with Cystic Fibrosis Diagnosed by Newborn Screening. Nutr Clin Pract 2020;
• 22 Davies G. Does newborn screening improve early lung function in cystic fibrosis?. Paediatr Respir Rev 2020;
• 23 Barreda CB, Farrell PM, Laxova A. et al. Newborn screening alone insufficient to improve pulmonary outcomes for cystic fibrosis. J Cyst Fibros 2021; 3: 492-498
• 24 Collins MS, Abbott MA, Wakefield DB. et al. Improved pulmonary and growth outcomes in cystic fibrosis by newborn screening. Pediatr Pulmonol 2008; 43: 648-655
• 25 Merelle ME, Schouten JP, Gerritsen J. et al. Influence of neonatal screening and centralized treatment on long-term clinical outcome and survival of CF patients. Eur Respir J 2001; 18: 306-315
• 26 Coffey MJ, Whitaker V, Gentin N. et al. Differences in Outcomes between Early and Late Diagnosis of Cystic Fibrosis in the Newborn Screening Era. J Pediatr 2017; 181: 137-145
• 27 Stahl M, Graeber SY, Joachim C. et al. Three-center feasibility of lung clearance index in infants and preschool children with cystic fibrosis and other lung diseases. J Cyst Fibros 2018; 17: 249-55.
• 28 Rosenfeld M, Ratjen F, Brumback L. et al. Inhaled hypertonic saline in infants and children younger than 6 years with cystic fibrosis: the ISIS randomized controlled trial. JAMA 2012; 307: 2269-2277
• 29 Breuer O, Schultz A, Turkovic L. et al. Changing Prevalence of Lower Airway Infections in Young Children with Cystic Fibrosis. Am J Respir Crit Care Med 2019; 200: 590-599
• 30 Gregersen S, Aalokken TM, Mynarek G. et al. High resolution computed tomography and pulmonary function in common variable immunodeficiency. Respir Med 2009; 103: 873-880
• 31 Demirkazik FB, Ariyürek OM, Ozçelik U. et al. High resolution CT in children with cystic fibrosis: correlation with pulmonary functions and radiographic scores. Eur J Radiol 2001; 37: 54-59