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

NCT07033663 | Recruiting DMC FDA Drug

• 1 other identifier: NEWborn-IMM-PACT
• Study Type: observational
• Target: 90
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Pregnancy Related; Immune-mediated Diseases

Keywords

monoclonal antibodies; pregnancy; immunomodulators

Outcome Measures

Primary Outcomes (11)

• Growth

  Growth will be measured with OMS scale. The World Health Organization (WHO) Child Growth Standards (0-5 years) and WHO Growth Reference (5-19 years) use Z-scores to assess growth, typically ranging from -6 to +6, with most values between -3 and +3. Higher scores indicate greater body size, which can mean better growth (e.g., height-for-age) or a worse outcome (e.g., overweight or obesity in BMI-for-age), depending on the growth index used.

  first 12 months of age

• Neurodevelopment

  Neurodevelopment will be measured with Haizea-Llevant scale. The Haizea-Llevant scale is a standardized tool used in Spain to assess neurodevelopment in children aged 0 to 5 years, based on the Denver Developmental Screening Test. It evaluates development across four domains, and scores are reported as age of acquisition of milestones or percentile ranges, with higher scores indicating better neurodevelopmental outcomes; there is no fixed minimum or maximum, as it depends on age-specific milestones. A child scoring below the 3rd percentile in one or more areas may indicate developmental delay and require further evaluation.

  first 12 months of age

• Infection history

  Number and type of infections will be recorded

  first 12 months of age

• Vaccine response

  IgG responses to tetanus, diphtheria and pneumococcus

  first 12 months of age

• Hypersensitivity

  Atopy, food allergy will be recorded. Atopy and food allergy will be assessed based on clinical history obtained through structured clinical interview and findings from physical examination, following standard diagnostic criteria. No specific questionnaire or scale will be used, as data will be collected descriptively during routine clinical evaluation.

  first 12 months of age

• Immune Profiling in neonatal samples: Spectral flow cytometry

  Investigators will perform a comprehensive immune cell phenotype (T/B/NK cells, T and B regulatory subsets) from cord and peripheral blood samples and evaluate de % of each cell type to be compared to age-matched healthy controls reference values

  first 12 months of age

• Immune Profiling in neonatal samples: T cell function

  Investigators will evaluate T cell response to stimulants (PHA, PWM, ConA) and calculate the proliferation capacity in % compared to age-matched healthy controls.

  first 12 months of age

• Immune Profiling in neonatal samples: B cell function

  Investigators will evaluate B cell function by performing Plasmablast differentiation and measuring immunoglobulin production (IgG, IgA, IgM).

  first 12 months of age

• Immune Profiling in neonatal samples: Cytokine profiling

  Investigators will perform a 92-cytokine panel (Olink platform, advanced PCR technology) to measure different cytokine abundance in serum samples

  first 12 months of age

• Immune Profiling in neonatal samples: IMD Monitoring

  Investigators will perform an ELISA-based maternal/neonatal IMD (immunomodulatory drug) concentration analysis to measure drug levels in serum samples

  first 12 months of age

• Immune Profiling in neonatal samples: Vaccine responses

  Investigators will measure Antibody titers for tetanus, diphtheria, pneumococcus using commercial kits. à afegeix (IgG) despres de antibody titers.

  first 12 months of age

Study Arms (1)

Pregnant women with chronic inflammatory and/or oncological diseases exposed to mAb during pregnancy

Study Population: Inclusion criteria: Pregnant women with immune-mediated inflammatory or oncologic diseases, categorized into: 1. High-exposed group: IMD treatment throughout pregnancy. 2. Low-exposed group: IMD treatment limited to the first/second trimester. 3. Non-exposed group: No IMD exposure or treatment with non-placental-crossing biologics, serving as a control to distinguish immunological changes attributable to maternal disease. Newborns and an age- and sex-matched healthy control group (0-12 months) will be included. Exclusion criteria for mother and child: lack of signed informed consent, primary immunodeficiencies, active infection at the time of sampling or significant comorbidities.

Drug: Monoclonal antibody

Interventions

Monoclonal antibody DRUG

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

Also known as: non-intervention. Drug used in clinical practice

Pregnant women with chronic inflammatory and/or oncological diseases exposed to mAb during pregnancy

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Pregnant women with immune-mediated inflammatory or oncologic diseases. 90 mother-child pairs: 15 per each of the 6 disease groups: rheumatology, neuroimmunology, dermatology, inflammatory bowel disease, allergy, and oncology.

You may qualify if:

• 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.

Sponsors & Collaborators

• Fundació Sant Joan de Déu: lead
• Hospital Clinic of Barcelona: collaborator
• Hospital Vall d'Hebron: collaborator

Study Sites (3)

Hospital Sant Joan de Déu

Esplugues de Llobregat, Barcelona, 08950, Spain

RECRUITING

Hospital Clínic de Barcelona

Barcelona, 08035, Spain

RECRUITING

Hospital Universitari Vall d'Hebrón

Barcelona, 08035, Spain

RECRUITING

Biospecimen

Retention: SAMPLES WITHOUT DNA

Serum, plasma, PBMCs, RNA

MeSH Terms

Interventions

Antibodies, Monoclonal

Intervention Hierarchy (Ancestors)

Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Central Study Contacts

Laia Alsina, MD, PhD

CONTACT

+34 936009733; frecerca.aro@sjd.es

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 12 Months
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 28, 2025
• First Posted: June 24, 2025
• Study Start: June 1, 2018
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): May 1, 2028
• Last Updated: August 15, 2025

Record last verified: 2025-05

Locations

ES (3)