Cord-blood ANA-IFA positivity and first-year clinical findings in a selected lower-risk population: an exploratory prospective cohort study

The clinical significance of broad antinuclear antibody (ANA) reactivity in cord blood from neonates without known high-risk maternal autoimmune disease remains uncertain. We assessed the prevalence of cord-blood ANA by indirect immunofluorescence (ANA-IFA), antigen-specific panel reactivities, and clinical findings through 12 months. This single-center prospective cohort study enrolled 171 neonates from March 2023 to March 2024, excluding neonates whose mothers had active or newly diagnosed autoimmune disease or a disease flare during pregnancy. Cord-blood samples underwent ANA-IFA. ANA-IFA-positive infants received a multiparameter antigen-specific antibody panel and protocol-based hematologic, hepatic, electrocardiographic, echocardiographic, and clinical evaluation through 12 months. Mothers of positive infants underwent ANA-IFA; antigen-specific testing was limited to positive mothers. ANA-IFA-negative infants received clinical follow-up, with investigations performed only when indicated and not systematically recorded. Analyses were exploratory. Cord-blood ANA-IFA was positive in 26/171 neonates (15.2%; exact 95% CI, 10.2%-21.5%). Four of 26 positive infants had antigen-specific panel reactivity (15.4%; exact 95% CI, 4.4%-34.9%): anti-dsDNA in all four, anti-histone in two, and anti-nucleosome, anti-Jo-1, and anti-Ro52 in one each; none had anti-Ro60 or anti-La/SSB reactivity. All 26 ANA-IFA-positive infants completed evaluation and follow-up. Four had transient liver enzyme abnormalities that normalized within one month. No relevant autoimmune manifestations were clinically detected (0/26; exact 95% CI, 0.0%-13.2%). None was recorded among 145 ANA-IFA-negative infants; however, subclinical abnormalities could not be excluded because systematic investigations were not performed. Maternal ANA-IFA was positive in 3/26 mothers, all of whom had infants with antigen-specific panel reactivity; incomplete maternal antigen-specific testing prevented a comprehensive concordance assessment. In this selected, clinically lower-risk cohort, isolated cord-blood ANA-IFA positivity was relatively frequent but nonspecific. Differential outcome ascertainment, small sample size, incomplete maternal testing, and limited run-level assay documentation preclude firm risk estimates. These findings do not support routine ANA-IFA testing of asymptomatic neonates or changes to established surveillance for confirmed maternal anti-Ro/SSA or anti-La/SSB exposure. Larger multicenter studies with paired maternal-neonatal testing, uniform assessment, documented assays, serial antibody measurements, and longer follow-up are needed.