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False negative newborn screen and neonatal cholestasis in a premature child with cystic fibrosis


Newborn screening for cystic fibrosis enables early diagnosis and treatment, leading to better outcomes for patients with cystic fibrosis. Although the sensitivity of several screening protocols is high, false negative screening results of the newborn patient still occur, which can lead to a significant delay in diagnosis when the awareness for presenting symptoms of cystic fibrosis declines. Neonatal cholestasis is one of the presenting symptoms of cystic fibrosis but can be easily missed when total parenteral nutrition has been given. Premature newborns are probably more at risk of a missed underlying diagnosis than term babies because their co-pathologies and management are often more complex. We present a case of a 10-week-old premature boy with a false negative newborn screening for cystic fibrosis, in whom cystic fibrosis presented with neonatal cholestasis. In this case, the immunoreactive trypsinogen/pancreatitis-associated protein/35 cystic fibrosis transmembrane regulator mutation analysis/sequencing method was used. Furthermore, an overview of the literature on missed diagnosis of cystic fibrosis due to a false negative newborn screen is provided. Conclusion: Cystic fibrosis (CF) should be considered in infants with neonatal cholestasis even when the newborn screening for CF is reported to be negative.

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Newborn screening


Cystic fibrosis


Total parenteral nutrition


Immunoreactive trypsinogen


Pancreatitis-associated protein


Cystic fibrosis transmembrane conductance regulator


  1. 1.

    Castellani C, Southern KW, Brownlee K (2009) European best practice guidelines for cystic fibrosis neonatal screening. J Cyst Fibros 8:153–173

  2. 2.

    Collaco JM, Panny SR, Hamosh A, Mogayzel PJ Jr (2010) False negative cystic fibrosis newborn screen. Clin Pediatr 49:214–216

  3. 3.

    Dijk FN, McKay K, Barzi F, Gaskin KJ, Fitzgerald DA (2011) Improved survival in cystic fibrosis patients diagnosed by newborn screening compared to a historical cohort from the same centre. Arch Dis Child 96:1118–1123

  4. 4.

    Dunn CT, Skrypek MM, Powers AL, Laguna TA (2011) The need for vigilance: the case of a false-negative newborn screen for cystic fibrosis. Pediatrics 128:e446–e449

  5. 5.

    Evans JS, George DE, Mollit D (1991) Biliary infusion therapy in the inspissated bile syndrome of cystic fibrosis. Pediatr Gastroenterol Nutr 12:131–135

  6. 6.

    Fritz A, Farrell P (2012) Estimating the annual number of false negative cystic fibrosis newborn screening tests. Pediatr Pulmonol 47:207–208

  7. 7.

    Kloosterboer M, Hoffman G, Rock M, Gershan W, Laxova A, Li Z, Farrell PM (2009) Clarification of laboratory and clinical variables that influence cystic fibrosis newborn screening with initial analysis of immunoreactive trypsinogen. Pediatrics 123:e338

  8. 8.

    Lu KD, Engmann C, Moya F, Muhlebach M (2011) Cystic fibrosis in premature infants. J Perinatol 31:504–506

  9. 9.

    Padoan R, Genoni S, Moretti E, Seia M, Giunta A, Corbetta C (2002) Genetic and clinical features of false-negative infants in a neonatal screening programme for cystic fibrosis. Acta Paediatr 91:82–87

  10. 10.

    Rock MJ, Levy H, Zaleski C, Farrell PM (2011) Factors accounting for a missed diagnosis of cystic fibrosis after newborn screening. Pediatr Pulmonol 46:1166–1174

  11. 11.

    Sontag MK, Corey M, Hokanson JE, Marshall JA, Sommer SS (2006) Genetic and physiologic correlates of longitudinal immunoreactive trypsinogen decline in infants with cystic fibrosis identified through newborn screening. J Pediatr 149:650–657

  12. 12.

    Vernooij-van Langen AM, Loeber JG, Elvers B, Triepels RH, Gille JJ, Van der Ploeg CP, Reijntjens S, Dompeling E, Dankert-Roelse JE, CHOPIN Study Group (2012) Novel strategies in newborn screening for cystic fibrosis: a prospective controlled study. Thorax 67:289–295

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The authors declare that they have no conflict of interest.

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Correspondence to I. De Vreede.

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Heidendael, J.F., Tabbers, M.M. & De Vreede, I. False negative newborn screen and neonatal cholestasis in a premature child with cystic fibrosis. Eur J Pediatr 173, 1581–1583 (2014).

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  • Newborn screening
  • Cystic fibrosis
  • Neonatal cholestasis
  • Prematurity