Incidence of Umbilical Cord Blood Absolute Lymphopenia in Newborns and Its Role in Screening for Severe Combined Immunodeficiency Disease: A 1-Year Longitudinal Study

Abstract

Background

Severe combined immunodeficiency disease (SCID) is a serious inherited primary immunodeficiency disorder (PID) affecting T- and B-cells, leading to recurrent infections in infancy. Though newborns appear healthy, serious infections arise within the first year. Measuring absolute lymphocyte count (ALC) in umbilical cord blood enables early, cost-effective detection, which is crucial in resource-limited settings. This study presents India’s first SCID screening and the fourth globally, highlighting the potential to improve survival through early diagnosis and timely treatment.

Objectives

To estimate the incidence of absolute lymphopenia in umbilical cord blood samples of newborns and determine its utility in screening for SCID, and to evaluate other causes of lymphopenia in newborns.

Methodology

A longitudinal study was conducted on 1,550 newborns with gestational ages above 32 weeks, at a tertiary care center in North Karnataka. Umbilical cord blood (2 mL) was collected at delivery and subjected to complete blood count (CBC) analysis. Neonates with absolute lymphopenia underwent detailed history-taking, clinical examination, additional investigations, and follow-up according to the study protocol.

Results

In this study of 1,550 newborns, 6.67% had absolute lymphopenia (ALC <2,500/µL), exceeding the rates in three other global studies, potentially related to the region’s higher consanguinity rate. Causes of lymphopenia included prematurity, sepsis, congenital anomalies, and idiopathic factors, with a higher prevalence in males and a significant association with consanguinity. The mode of delivery did not impact lymphopenia rates. Lymphopenic infants required active resuscitation, had lower birth weights, and poorer APGAR (appearance, pulse, grimace, activity, and respiration) scores. Significantly lower levels of hemoglobin, white blood cell (WBC) count, and absolute neutrophil count (ANC) were noted in lymphopenic newborns.

Conclusion

The incidence of absolute lymphopenia was greater than in three other studies done worldwide. We advocate for incorporating the measurement of ALC in umbilical cord blood as part of standard screening protocols for early detection and management of PIDs, including SCID.