Background: Autoinflammatory diseases (AIDs) predominantly affect young patients who are likely to become pregnant. For many inflammatory diseases, pregnancy is known to destabilize the disease and may lead to complications for the mother or unborn child. There is a paucity of prospective large cohort data on pregnancy outcomes in patients with AIDs, especially in the most common of these, familial Mediterranean fever (FMF) [1-3].

Objectives: To prospectively study pregnancies outcomes in patients with AIDs.

Methods: The French multicenter prospective pregnancy observational cohort (GR2 study) included patients with AIDs between 2016 and 2024. Disease activity, treatment, pregnancy outcome, delivery and neonatal health were analyzed.

Results: 115 pregnancies, including 5 twin pregnancies, in 97 women followed for AID with, in descending order of frequency: FMF (n=79), Undifferentiated systemic autoinflammatory diseases (USAID) (n=21), Tumour necrosis factor (TNF) receptor-associated periodic syndrome (TRAPS) (n=5), cryopyrin-associated periodic syndromes (CAPS) (n=3), Still’s disease (n=2), recurrent pericarditis (n=2), Mevalonate kinase deficiency (MKD) (n=1), A20 haploinsufficiency (HA20) (n=2), and pyogenic arthritis, pyoderma gangrenosum and acne (PAPA) syndrome (n=1). Patients had a median age at onset of pregnancy of 31 years [min 20-max 44] and a median BMI of 22.3 [min 16.4-max 35.8]. Pregnancies were achieved after assisted reproduction in 10.8% of cases, including only FMF. Patients had signs of disease activity in the year prior to pregnancy in 57.7% of cases and had flares during pregnancy in 59.1% of cases. Sixteen pregnancies were terminated before the 37th week of gestation including 2 foetal deaths in utero, 2 therapeutic abortions due to chromosomal abnormalities, and 1 spontaneous abortion. In the USAID patients (n=21), the median age of disease onset was 14 years [0-32] and gestational age was 30 years [20-37]; half were receiving colchicine. Mean CRP at enrolment was 8.9 mg/dl [0-25]. Biotherapy was discontinued upon discovery of pregnancy (n=2: anakinra, tocilizumab). Three pregnancies (14%) were terminated prematurely due to late miscarriage, foetal death in utero , and medical abortion due to monosomy X. Of the newborns, only one had a birth weight <10th percentile. For FMF patients, the median age at FMF symptom onset was 6 years and at pregnancy was 31 years. The median dose of colchicine was 2 mg/d [min 1- max 2.5]. Patients were carriers of 2 pathogenic variants of MEFV (79.4%) or only one (20.5%). They reported a mean of 4 attacks/year in the year prior to pregnancy. Mean CRP at enrolment was 22.5mg/L. At least one spontaneous miscarriage <22AW prior to this pregnancy was reported in 13.9% of patients, and 15% had undergone assisted reproduction for their pregnancy, 83% of them by in vitro fertilization. Inflammatory symptoms occurred during pregnancy in 65.7% of cases, including 3 prolonged febrile myalgia syndromes. Seven patients (8%) received anakinra on demand for persistent attacks. Pregnancy complications reported were one risk of preterm delivery in a twin pregnancy; one anamnios and one oligohydramnios in the same patient during both of her pregnancies. 17% of patients delivered before 37 AW, including 4 twin pregnancies, one miscarriage <22 AW and one unexplained foetal death in utero at 26 AW. Regarding the newborns: 22.4% had a birth weight below the 10th percentile, including none of the twins.

Conclusion: This national prospective study demonstrates the importance of monitoring inflammation during pregnancy. During FMF, there was more recourse to assisted reproduction, 17% preterm delivery and 22.4% intrauterine growth retardation, which are higher than the figures for the general French population (7 and 7.1% respectively). This supports the need for closer monitoring of the pregnancy, in collaboration between the FMF referral physician and the obstetrician.

REFERENCES: [1] Yurdakul FG, Bodur H, Çay HF, Uçar Ü, Keskin Y, Sargin B, et al. Familial Mediterranean fever: perspective on female fertility and disease course in pregnancy from a multicenter nationwide network. Rheumatol Int. 2 sept 2023;

[2] Deniz R, Deniz F, Ekmen ŞA, Sevinç-Özgür D, Akkuzu G, Karaalioğlu B, et al. Retrospective evaluation of obstetric processes in patients with Familial Mediterranean Fever’s disease: The three years experience of a tertiary rheumatology clinic. Taiwan J Obstet Gynecol. nov 2024;63(6):900‑3.

[3] Hirahira Y, Yamaguchi M, Takase-Minegishi K, Kirino Y, Aoki S, Hirahara L, et al. Pregnancy outcomes in patients with familial Mediterranean fever: systematic review and meta-analysis. Rheumatology (Oxford). 1 févr 2024;63(2):277‑84.

Acknowledgements: NIL.

Disclosure of Interests: Léa Savey: None declared, Marion Delplanque: None declared, Katia stankok@ch-blois.fr: None declared, Vincent Sobanski: None declared, Adrien Bigot: None declared, Catherine Grandpeix-guyodo: None declared, Alban Deroux: None declared, Estibaliz Lazaro: None declared, Antoine Froissart: None declared, Arsene Mekinian: None declared, Olivier Fain: None declared, Eric Hachulla: None declared, Guillaume Moulis Alpine, Amgen, Argenx, Grifols, Novartis, Sanofi, Sobi, UCB, research: Amgen, Argenx, Grifols, Novartis, Sanofi, Hervé Levesque: None declared, Maelle Le Besnerais: None declared, Odile Souchaud-Debouverie: None declared, Julien Campagne: None declared, Perrine Smets: None declared, Luc Mouthon: None declared, Nathalie Costedoat-Chalumeau BMS, Roche, UCB, Gaelle Guettrot Imbert: None declared, Sophie Georgin-Lavialle NOVARTIS, SOBI.

© The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ). Neither EULAR nor the publisher make any representation as to the accuracy of the content. The authors are solely responsible for the content in their abstract including accuracy of the facts, statements, results, conclusion, citing resources etc.