{"doi":"10.1002/jcph.70136","title":"Antibody Transfer From Mother to Fetus/Infant: An Opportunity for Model‐Informed Precision Medicine","abstract":"Therapeutic antibodies have become increasingly important for the treatment of autoimmune disorders, such as inflammatory bowel disease (IBD), in pregnant patients and mothers.1 For example, a retrospective study assessing the pattern of biologics use from pre-pregnancy to postpartum has reported 71.6% have continued biologics use at least once during pregnancy. Compared to patients with rheumatoid arthritis, patients with Crohn's disease and ulcerative colitis were more likely to continue the biologic during pregnancy, while patients with psoriasis or psoriatic arthritis were less likely to continue biologic use. The percentage of pregnant subjects with live birth that continued biologics declined from 68.6% in trimester 1 to 58.8% in trimester 2 to 48.6% in trimester 3.2 While transplacental transfer of endogenous antibodies supports passive immunity against infectious diseases to the fetus and newborn, the long-term safety of therapeutic antibodies that cross the placenta remains poorly understood. The impact of transplacental transfer of therapeutic antibodies and their impact on fetal health represents a substantial knowledge gap in maternal pharmacotherapy with consequences for clinical decision-making.3, 4 The management of chronic disease during pregnancy and lactation has undergone a paradigm shift in recent years with increasing focus on maintaining maternal disease control while ensuring healthy outcomes for the fetus or infant. More robust data is needed to support dosing strategies that optimize the health of both expecting mothers and their children. Currently, most evidence supporting antibody dosing strategies in pregnant patients is based on observational studies, attributable to the ethical challenges of conducting clinical trials during pregnancy. Reliance on observational, or clinically convenient data, has led to inconsistent clinical recommendations for the use and dosing of antibody drugs during pregnancy. Our compilation of selected societal guidelines highlights the variability in recommendations for antibody drug use in selected autoimmune disorders, particularly with respect to dosing schedules (Table S1). Post-approval pregnancy studies, when conducted, tend to prioritize severe congenital malformations as safety endpoints, often challenged with the detection of milder outcomes due to limitations of sample size and/or follow-up time, which could still affect infant health. Meanwhile, hormonal, immunological, and microbial fluctuations during pregnancy can alter the course of autoimmune diseases, influencing risk of relapse, attack severity, and postpartum recovery.5 Drug labeling typically adopts a cautious stance, prioritizing fetal safety over maternal well-being, despite risk signals that are often ambiguous. Data gaps persist, particularly with respect to the mechanisms that govern dynamics of antibody pharmacokinetics and transplacental transfer in pregnant individuals, as well as the implications for drug efficacy and safety. These data gaps underscore the need for advanced tools to balance maternal therapeutic needs and fetal safety. To address these challenges, researchers have increasingly turned to model-based approaches, such as physiologically based pharmacokinetic (PBPK) modeling, to study the pharmacokinetics and transplacental transfer of antibody drugs.6, 7 PBPK modeling is increasingly used as a method for predicting the transfer of small molecules from mother to fetus or infant8-12 that also shows promise for therapeutic antibodies. These models can account for physiological changes during pregnancy in both the mother and in neonates, enabling predictions of antibody transfer and resulting exposures. These predictions are critical to evaluating and optimizing dosing regimens with respect to both maternal efficacy and fetal safety. For instance, Chen et al developed a PBPK model to evaluate the placental transfer of anti-tumor necrosis factor-alpha (anti-TNFα) biologics in pregnant ","journal":"The Journal of Clinical Pharmacology","year":2025,"id":585516,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9519,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":884563,"name":"Tyler Dunlap","orcid":"0000-0003-0385-9219","position":1,"is_corresponding":false},{"id":339554,"name":"Rui Zhong","orcid":"0000-0002-8936-6652","position":2,"is_corresponding":false},{"id":893020,"name":"Jacqueline B. Tiley","orcid":"0000-0002-9977-1184","position":3,"is_corresponding":false},{"id":440083,"name":"Yanguang Cao","orcid":"0000-0002-3974-9073","position":4,"is_corresponding":false},{"id":390716,"name":"Miramar Kardouh","orcid":"0009-0003-0574-1270","position":0,"is_corresponding":true}],"reference_count":19,"raw_metadata":null,"created_at":"2026-07-19T02:59:20.067334Z","pmid":"41405001","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}