Immunomodulation During Pregnancy

NCT ID: NCT06882850

Last Updated: 2025-03-19

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 30 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2024-02-01
• Study Completion Date: 2025-03-31

Brief Summary

The goal of this observational study is to learn about the effects of low dose aspirin in immunity Pregnant women taking aspirin for other reasons (preeclampsia prevention) will be studied. The main question it aims to answer is: evaluate the effect of LDA on the modulation of innate immunity cells (NK cells, monocytes, γδ T cells) and/or acquired immunity (B and T lymphocytes, Treg cells, Th cells).

Participants already taking intervention A as part of their regular medical care for RA will answer online survey questions about their joint pain for 5 years.

Detailed Description

The main objective of this study is to evaluate the effect of LDA on the modulation of innate immunity cells (NK cells, monocytes, γδ T cells) and/or acquired immunity (B and T lymphocytes, Treg cells, Th cells). The secondary objectives are to quantify pro-inflammatory and anti-inflammatory cytokines before and after LDA administration, as well as to assess maternal and fetal outcomes, comparing these parameters with those of low-risk PE pregnancies that do not require prophylactic LDA administration.

A prospective longitudinal study will be conducted, lasting a minimum of 40 weeks and a maximum of 24 months. Singleton pregnancies monitored at the Centro Hospitalar e Universitário de Coimbra will be included, with the first consultation occurring before 14 weeks of gestation and gestational age determined by first-trimester ultrasound. The study group will consist of women at high risk of PE according to clinical/historical criteria, who have not yet started LDA intake at the time of recruitment. Pregnant women will be classified as having a low or high risk of PE (risk of ≥ 1 in 50 for preterm PE) using the Fetal Medicine Foundation algorithm. This algorithm evaluates maternal clinical risk factors, mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI), and pregnancy-associated plasma protein A (PAPP-A). Women classified as high-risk will receive prophylactic aspirin (150 mg once daily).

As this is a preliminary study, 30 pregnant women will initially be included: 15 at high risk of PE (study group) and 15 at low risk (control group). Peripheral blood samples will be collected from both groups, utilizing routine pregnancy blood draws, at three time points (1st, 2nd, and 3rd trimesters). This will allow the evaluation of fluctuations in immune cells (NK cells, B and T lymphocytes, Treg cells, Th cells) and cytokine levels (IL-1, IL-6, IL-8, TNF-α, INF-γ, TGF-β, and IL-10). In high-risk PE pregnancies, additional peripheral blood samples will be collected before LDA administration and four weeks afterward.

Flow cytometry methodology will be used to determine immune cell frequencies, while plasma cytokine levels will be measured using ELISA and Luminex methodologies. After delivery, in both groups, histopathological evaluation (immunohistochemical staining) of the placenta will be performed, analyzing the aforementioned immune cells, as well as umbilical cord blood analysis using flow cytometry.

Conditions

Aspirin; Pregnancy Complications; Immunology

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Healthy pregnancies

High-risk preeclampsia pregnencies

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

• Patients attending prenatal consultations at the Obstetrics Service A of CHUC, with the first consultation occurring before 14 weeks of gestation
• Gestational age determined by first-trimester ultrasound
• Study group: Women classified as high risk for PE according to clinical/historical criteria and the Fetal Medicine Foundation algorithm. LDA-naïve.

Exclusion Criteria

• Autoimmune diseases
• Prior use of LDA or other immunomodulatory medication before potential recruitment
• History of spontaneous miscarriages and/or medical termination of pregnancy
• Fetal malformation

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

Unidade Local de Saúde de Coimbra, EPE

OTHER

Sponsor Role: lead

Responsible Party

Ana Luisa Areia

Clinical Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Ana L Areia, PhD MD

Role: PRINCIPAL_INVESTIGATOR

University of Coimbra

Locations

Unidade Local de Saúde de Coimbra, E.P.E.

Coimbra, Coimbra District, Portugal

Site Status: RECRUITING

Countries

Portugal

Central Contacts

Ana L Areia, PhD, MD

Role: CONTACT

analuisareia@gmail.com

+351917212222

João Sargento-Freitas, PhD

Role: CONTACT

joaosargentofreitas@ulscoimbra.min-saude.pt

+351239400488 ext. 12105

Facility Contacts

Ana Areia, PhD, MD

Role: primary

analuisareia@gmail.com

+351917212222

References

1. Cadavid AP. Aspirin: The Mechanism of Action Revisited in the Context of Pregnancy Complications. Front Immunol. 2017;8:261. 2. Mittelberger J, Seefried M, Franitza M, Garrido F, Ditsch N, Jeschke U, et al. The Role of the Immune Checkpoint Molecules PD-1/PD-L1 and TIM-3/Gal-9 in the Pathogenesis of Preeclampsia-A Narrative Review. Medicina (Kaunas). 2022;58(2). 3. Khanabdali R, Shakouri-Motlagh A, Wilkinson S, Murthi P, Georgiou HM, Brennecke SP, et al. Low-dose aspirin treatment enhances the adhesion of preeclamptic decidual mesenchymal stem/stromal cells and reduces their production of pro-inflammatory cytokines. J Mol Med (Berl). 2018;96(11):1215-1225. 4. Panagodage S, Yong HE, Da Silva Costa F, Borg AJ, Kalionis B, Brennecke SP, et al. Low-Dose Acetylsalicylic Acid Treatment Modulates the Production of Cytokines and Improves Trophoblast Function in an in Vitro Model of Early-Onset Preeclampsia. Am J Pathol. 2016;186(12):3217-3224. 5. Robillard PY, Dekker G, Scioscia M, Saito S. Progress in the understanding of the pathophysiology of immunologic maladaptation related to early-onset preeclampsia and metabolic syndrome related to late-onset preeclampsia. Am J Obstet Gynecol. 2022;226(2S):S867-S875. 6. Brox R, Hackstein H. Physiologically relevant aspirin concentrations trigger immunostimulatory cytokine production by human leukocytes. PLoS One. 2021;16(8):e0254606. 7. Dong W, Yin L. Expression of lipoxin A4, TNFalpha and IL-1beta in maternal peripheral blood, umbilical cord blood and placenta, and their significance in pre-eclampsia. Hypertens Pregnancy. 2014;33(4):449-456. 8. Tung YT, Wei CH, Yen CC, Lee PY, Ware LB, Huang HE, et al. Aspirin Attenuates Hyperoxia-Induced Acute Respiratory Distress Syndrome (ARDS) by Suppressing Pulmonary Inflammation via the NF-kappaB Signaling Pathway. Front Pharmacol. 2021;12:793107. 9. Dong W, Liu X, Liu W, Wang C, Zhao S, Wen S, et al. Dual antiplatelet therapy improves functional recovery and inhibits inflammation after ce

Reference Type: BACKGROUND

Areia AL, Almeida J, Alves V, Mota-Pinto A, Sa H. Modulation of Immune Cells by Aspirin During Pregnancy. Immunology. 2025 Oct 14. doi: 10.1111/imm.70051. Online ahead of print.

Reference Type: DERIVED

PMID: 41087834 (View on PubMed)

Other Identifiers

OBS.SF.160/2022

Identifier Type: -

Identifier Source: org_study_id