Insights into Clinical Challenges and Management of Primary and Secondary Antibody Deficiency in Pregnancy

Pregnancy in patients with primary or secondary antibody deficiencies presents unique clinical challenges shaped by impaired humoral immunity, increased susceptibility to infection, and decreased maternal-fetal placental IgG transfer. Immunologic shifts across gestation, limited B-cell reconstitution after anti-CD20 therapy, and alterations in IgG metabolism further complicate maternal and neonatal outcomes. While earlier diagnosis, advances in immunoglobulin replacement therapy (IgRT), antimicrobial prophylaxis, and management of infectious/noninfectious complications have enabled many affected patients to reach adulthood and achieve successful pregnancies, the data suggest persistently elevated risks of fetal loss, preterm birth, and neonatal hypogammaglobulinemia, particularly in patients with prior severe infection, those not yet diagnosed with antibody deficiencies, and those not receiving adequate prophylaxis. This review synthesizes current evidence on immunologic adaptation in pregnancy, infection-related and autoimmune complications, medication safety, including IgRT optimization, antimicrobial prophylaxis, and management of immunomodulatory agents. We outline practical strategies for immunologic, obstetric, and neonatal care. Safe and effective management requires individualized planning, careful IgRT dose adjustment, avoidance of teratogenic therapies, and coordinated multidisciplinary care, involving maternal-fetal medicine, immunology, and neonatology. Significant knowledge gaps persist, particularly regarding secondary antibody deficiency, neonatal immune recovery after anti-CD20 exposure, and optimal IgRT dosing across diverse inborn errors of immunity. Prospective registries, harmonized outcome definitions, and consensus-driven guidelines will be essential to improving reproductive care and long-term outcomes for mothers and infants affected by antibody deficiency.