Early Clinical Warning Signs of Inborn Errors of Immunity in the Neonatal Intensive Care Unit: A Retrospective Observational Study
Fatma Iyigun1, Derya Colak1, Ozlem Sahin1, Omer Guran1, Funda Yavanoglu Atay1, Hayrunnisa Bekis Bozkurt2, Ilke Mungan Akin11Department of Neonatology, Ümraniye Training and Research Hospital, İstanbul, Türkiye2Department of Pediatric Allergy and Immunology, Ümraniye Training and Research Hospital, İstanbul, Türkiye
Objectives: Inborn errors of immunity (IEI) may manifest in neonates as severe or unusual infections and syndromic features, yet early recognition remains challenging, especially in settings without routine newborn screening. Early clinical warning signs—in-cluding recurrent or atypical infections, absent thymic shadow, unexplained hydrops fetalis, or treatment-resistant metabolic dis-turbances—can facilitate timely diagnosis. This study aimed to determine the prevalence and subtypes of IEI in a tertiary neonatal intensive care unit (NICU) and to characterize early diagnostic indicators that guide life-saving interventions.
Methods: We conducted a retrospective observational study of neonates diagnosed with IEI between August 2023 and August 2025 in a 61-bed, level 4 NICU. Seventeen infants meeting IUIS and ESID criteria were identified through the immunology–neonatology council registry. Demographic, clinical, laboratory, and outcome data were analyzed descriptively, with an emphasis on early warning signs.
Results: Among 11,276 live births and 2,942 NICU admissions, 17 neonates were diagnosed with IEI (1.51 per 1,000 live births). Combined immunodeficiencies were the most frequent subtype (58.8%). Diagnostic evaluation was primarily prompted by syndromic features or severe/unusual infections. Four infants (23.5%) died, while survivors remained clinically stable with immunoglobulin replacement therapy and antimicrobial prophylaxis. One infant underwent hematopoietic stem cell transplantation (HSCT). Early recognition facilitated the timely initiation of appropriate management strategies.
Conclusion: IEI should be suspected in neonates presenting with syndromic features or atypical infections. Awareness of subtle neonatal warning signs and prompt evaluation for appropriate interventions can improve outcomes, particularly in settings without routine newborn screening.
Keywords: Combined immunodeficiency, early diagnosis, inborn errors of immunity, neonatal intensive care unit, neonate
Manuscript Language: English