Introducing the MIRACLE Task Force: Maternal Immunity, Reproduction, and Inborn Errors of Immunity Collaboration

Introduction The MIRACLE Task Force is a multidisciplinary, multi-institutional work group comprising immunology, genetics, obstetrics/gynecology, and maternal fetal medicine providers dedicated to understanding reproductive and pregnancy outcomes in individuals with inborn errors of immunity (IEIs). Methods The first study is a retrospective cohort analysis using data from the National Inpatient Sample (2016–2022), a database capturing approximately 20% of hospital discharges in the United States. Delivery admissions, comorbidities, severe maternal morbidity (SMM), and IEI diagnoses were identified through ICD-10 codes. A multivariable binary logistic regression was used to assess the impact of IEI on SMM, while controlling for comorbidities. The second study involved qualitative interviews with individuals with IEIs who had been cared for during pregnancy in a single health system to capture reproductive experiences. Results For study #1, a total of 5,026,871 delivery hospitalizations were identified. Diagnosis of IEI was found in 931 admissions. The most common IEIs represented included primary antibody deficiencies (30%) and DiGeorge syndrome (10%). Obstetrical comorbidities were more common among patients with IEI vs. without, notably asthma (21.0 vs. 5.7%), major mental health disorders (22.0 vs. 8.9%), anemia (21.0 vs. 14.0%), gastrointestinal disease (19.0 vs. 5.9%), and bleeding disorders (11.0 vs. 2.3%). SMM occurred in 7.4% of patients with IEI versus 1.6% without, mostly driven by immune-related comorbidities. In the logistic regression model, IEI was associated with SMM even after controlling for the number of comorbidities (odds ratio [OR] 2.66, 95% confidence interval [CI] 2.04–3.42, p < 0.001). For study #2, 5 females with CVID, 3 primigravida, and 2 multigravidas were included. All individuals were concerned about passing their immune disease onto their offspring, and all had undergone preconception genetic testing. During pregnancy, 4 out of the 5 felt their OBGYN team disregarded how their IEI affected their health, particularly regarding the treatment of infections. Complications arose during birth and postpartum in 4 participants, including cytopenias and infections. All participants endorsed the need for better knowledge of IEI by the OBGYN team. Conclusions These two reports demonstrate that IEI is associated with severe maternal morbidity, and better communication between immunology and OBGYN is critical in the care of pregnant IEI patients. Tabular data are included as downloadable supplement files.