Impact of In Utero Exposure to Immunomodulatory Drugs on Neonatal Immune System Development

Official title

Study of the Impact of Intrauterine Exposure to Immunomodulatory Drugs on the Development of the Immune System of Children Born to Mothers With Chronic Inflammatory or Oncologic Diseases: The NEWborn-IMM-PACT Study

Overview

What is this project about? This project aims to better understand how the immune system develops in babies whose mothers received immunomodulatory treatments during pregnancy. These treatments are necessary for women with autoimmune, inflammatory, allergic, or cancer-related diseases who cannot stop their medication while pregnant. Why is it important? Although these treatments help keep the mother and baby healthy, some medications can cross the placenta and affect the baby's immune system. Since pregnant women are usually not included in clinical trials, the investigators still don't know exactly how these drugs might influence the baby's immune development. How will the investigators do it? The investigators will follow a group of pregnant women receiving these treatments and monitor their babies at birth, and at 3, 6, and 12 months. The study will take place in three leading hospitals in Spain: Hospital Sant Joan de Déu, Hospital Clínic, and Vall d'Hebron. The investigators will also use organoid models in the lab to better understand how these drugs affect fetal development. Who will benefit? This study will help parents concerned about the impact of treatments during pregnancy on their child's health. It will also give doctors the evidence they need to make safer treatment decisions, and support the creation of new clinical guidelines to protect both mothers and babies.

Detailed description

The use of immunomodulatory drugs (IMD) in chronic inflammatory or oncologic diseases is increasingly widespread in pregnant women who have gestational desire and need to keep their disease under control for the safety of pregnancy. General objective: analyze the safety of IMD exposure during pregnancy used in clinical practice on the development of the newborn immune system. Specific objectives: 1) To evaluate lymphoid organogenesis, including regulatory T/B populations, and the direct effect on the drug target immune pathway, in cord and peripheral blood of newborns exposed in utero to biologic immunomodulators (bIMD, monoclonals and fusion protein); 2) To evaluate the epigenetic fingerprint in cord and peripheral blood of newborns exposed in utero to bIMD; 3) To develop an in vitro model (organoid-platform) to study the impact of IMD and maternal disease in the fetal period. 4) To develop a guide of specific recommendations, which includes the perspective of the newborn. Methods: Observational multicenter prospective cohort study of infants exposed to bIMD during pregnancy, born to mothers with chronic inflammatory or oncologic diseases. Clinical and analytical follow-up, from birth, at 3,6 and 12 months. Clinical: general health status, data on infections or autoimmune or allergic events. Analytical: serum levels of bIMD, maturation and function of T and B extended lymphocyte populations, integrity of the bIMD target pathway, study of epigenetic changes. The results will be compared with a control population. In vitro study: organoid-based models obtained from hiPSCs differentiated towards hematopoietic components; B-cell maturation will be evaluated after different IMD exposure. The investigators expect to: 1) surmount the knowledge gap on the impact of in utero IMD exposure, to define the newborn infectious risk, of autoimmunity and/or allergy, and 2) to be create and disseminate protocols of follow-up specific to them.

Interventions

• Drug Monoclonal antibody
  non-intervention. Drug used in clinical practice as per practitioner decision

Primary outcome measures

• Growth [Time frame: first 12 months of age]
• Neurodevelopment [Time frame: first 12 months of age]
• Infection history [Time frame: first 12 months of age]
• Vaccine response [Time frame: first 12 months of age]
• Hypersensitivity [Time frame: first 12 months of age]
• Immune Profiling in neonatal samples: Spectral flow cytometry [Time frame: first 12 months of age]
• Immune Profiling in neonatal samples: T cell function [Time frame: first 12 months of age]
• Immune Profiling in neonatal samples: B cell function [Time frame: first 12 months of age]
• Immune Profiling in neonatal samples: Cytokine profiling [Time frame: first 12 months of age]
• Immune Profiling in neonatal samples: IMD Monitoring [Time frame: first 12 months of age]

Eligibility criteria

Inclusion criteria

Pregnant women with immune-mediated inflammatory or oncologic diseases, categorized into:

• High-exposed group: monoclonal treatment throughout pregnancy.
• Low-exposed group: monoclonal treatment limited to the first/second trimester.
• Non-exposed group: No monoclonal exposure or treatment with non-placental-crossing biologics, serving as a control to distinguish immunological changes attributable to maternal disease.

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Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

Spain · 3 centers

• Hospital Sant Joan de Déu — Esplugues de Llobregat
• Hospital Clínic de Barcelona — Barcelona
• Hospital Universitari Vall d'Hebrón — Barcelona

Identifiers

NCT: NCT07033663 · NEWborn-IMM-PACT

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗