Use of serum citrulline concentrations from routine newborn screen as a biomarker for necrotizing enterocolitis

  • Sharmila Babu
  • Malavika Prasad
  • Malki Miller
  • Mark Morrissey
  • Alok Bhutada
  • Mary Rojas
  • Shantanu RastogiEmail author
Original Article



Necrotizing enterocolitis (NEC), a leading cause of mortality and morbidity in preterm neonates, lacks a reliable biomarker. Citrulline is primarily produced by enterocytes and correlates with intestinal function. Serum citrulline concentration (CIT) is routinely measured in routine newborn screening (NBS). The purpose of the study is to test if CIT from NBS may predict the occurrence of NEC and whether it correlates with the time to full feeds (TTFF) and length of stay (LOS), serving as a biomarker of NEC and intestinal health.


In a retrospective case control study conducted on neonates with gestational age of 26–32 weeks, we compared CIT levels between cases (neonates with NEC) and controls (next-born neonate). NBS was collected within first 24 h, at day 5 and when the neonates achieved full feeds and were compared using non-parametric tests.


There was no difference in CIT between the controls and cases on day 1 [11.42 (7.42–14.84 vs. 11.93 (6.85–18.8) µmol/L, p = 0.55], on day 5 [11.99 (7.99–16.55) vs. 13.70 (7.42–26.83) µmol/L, p = 0.05], or at full feeds [14.86 (6.85–25.69) vs. 15.7 (7.42–26.26) µmol/L, p = 0.87]. CIT on day 1 did not correlate with TTFF (r = 0.08, p = 0.53) or LOS (r = 0.23, p = 0.06), respectively).


CIT from routine NBS does not serve as a biomarker to predict NEC in preterm neonates.


Citrulline Newborn screen Tandem mass spectroscopy Necrotizing enterocolitis Biomarker 



No external funding was secured for this study. The authors have indicated they have no financial relationships to disclose relevant to this article.

Compliance with ethical standards

Conflict of interest

The authors have no conflict of interest.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Maimonides Medical CenterMaimonides Infant and Children’s HospitalBrooklynUSA
  2. 2.Morgan Stanley Children’s Hospital of New YorkColumbia UniversityNew YorkUSA
  3. 3.Wadsworth Center, NYS DOHAlbanyUSA
  4. 4.Department of PediatricsSUNY-HSC at BrooklynBrooklynUSA

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