Intravenous immunoglobulin as an adjunct to phototherapy in neonatal haemolytic disease: A systematic review and meta‐analysis

Phototherapy remains the first‐line treatment of haemolytic disease of the newborn (HDN), a potentially life‐threatening condition caused by maternal alloimmunisation. Intravenous immunoglobulin (IVIG) has been proposed as an adjunct to reduce the need for exchange transfusion (ET), a procedure associated with significant risks. This meta‐analysis aims to evaluate the safety and efficacy of IVIG combined with phototherapy versus phototherapy alone in neonates with HDN. A comprehensive search of MEDLINE, EMBASE, CINAHL and the Cochrane Library was conducted up to 24 April 2025. Eligible studies included randomised controlled trials and observational cohorts evaluating IVIG in HDN. Data were pooled using random‐effects models. This study was prospectively registered in Prospective Register of Systematic Reviews (CRD420251025766). Nineteen studies involving 3673 neonates met the inclusion criteria. IVIG reduced the need for ET (odd ratio [OR] = 0.34; confidence interval [CI]: 0.2–0.8; I 2 = 88%) when used as an adjunct to phototherapy compared to phototherapy alone. Subgroup analysis suggested that the reduction in ET was more consistent in Rh‐mediated HDN (OR = 0.2; CI: 0.1–0.8; I 2 = 81%) than in ABO‐mediated HDN (OR = 0.76; CI: 0.1–4.1; I 2 = 89%). There were no differences in the length of hospital stay (mean difference [MD] = −0.1 days; CI: −0.8 to 0.6; I 2 = 98%), duration of phototherapy (MD = −5.1 h; CI: −15.7 to 5.4; I 2 = 98%) or incidence of adverse events (OR = 1.32; CI: 0.2–10.5; I 2 = 91%) between groups. Despite reducing ET requirements, adjunctive IVIG with phototherapy may not provide additional clinical benefits compared with phototherapy alone. Further high‐quality trials are needed to clarify optimal timing, dosing and patient selection.