- Autoimmune diseases during
pregnancy can cause complications, leading to preterm birth, and even spontaneous abortion.
- An observational cohort study reveals that pregnant women with
systemic inflammatory conditions could have a risk of serious infections
regarding the use of steroids, non-biologics and tumor necrosis factor α
- High-dose steroid use is an independent
risk factor for serious infections in pregnancy.
Autoimmune disease develops when your immune system
attacks healthy cells in your body. However, the exact
cause of this disease is unknown.
It is estimated that in the US more than 4.5 million
patients are affected by autoimmune disorders
includes diseases such as rheumatoid arthritis systemic lupus erythematosus
(SLE), tumor necrosis factor α (TNF), celiac disease, scleroderma, and pernicious anemia, amongst others.
‘Pregnancy and autoimmune disease could potentially be a dangerous combination!’
Research reveals that nearly 75% of those affected with
autoimmune disorders are women and that flare-up are commonly seen during
pregnancy. Control of disease activity is essential during pregnancy to avoid
potential complications including preterm birth, intrauterine growth
restriction and spontaneous abortions.
There is only limited information available on the
safety of immunosuppressive drugs in pregnancy and many are contraindicated for
use during pregnancy due to their teratogenic potential. Hence it is important
to understand the risk of infections in pregnant women using immunosuppressive
agents to be able to guide them appropriately in treatment selection.
from Brigham and Women's Hospital at Harvard University in Boston conducted an
observational cohort study to compare the risk of serious infections in
pregnant women taking steroids, non-biologic immunosuppressive agents, or tumor
necrosis factor α (TNF) inhibitors to treat various autoimmune conditions.
Data obtained from two large US health insurance databases, Medicaid and Optum
Clinformatics were studied. Participants included 4961 pregnant
women with a mean age of 29 years and were treated with immunosuppressive drugs
for rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis
psoriatic arthritis, or inflammatory bowel disease.
Patients were classified into steroid, non-biologic, or
TNF inhibitors based on first filled prescription of these immunosuppressive
agents during pregnancy. The date when the immunosuppressive prescription was filled for the first time during pregnancy was defined as the index
date. Since TNF inhibitors are not used to treat
systemic lupus erythematosus, women with this condition were excluded from
comparisons involving TNF inhibitors.
of the Study
The objective of the study was to see if any serious
infections occurred after the index date during pregnancy. Infections leading
to hospitalization such as bacterial
infection (meningitis, encephalitis, cellulitis, endocarditis, pneumonia,
pyelonephritis, septic arthritis, osteomyelitis, and bacteremia) or
opportunistic infections (tuberculosis, systemic candidiasis, cryptococcosis,
aspergillosis) were considered serious in nature.
Hazard ratios between immunosuppressive treatment and
risk of serious infections were derived using Cox proportional hazard
regression models after adjustment for confounding with propensity score fine
Dose-response analysis was conducted in women filling
at least one steroid prescription using a logistic regression model.
- The study results revealed that
out of 4961 participants who were treated with immunosuppressive agents,
71 participants (0.2%) experienced serious infections.
- Amongst the 2598 steroid users,
1587 non-biologic users and 776 TNF inhibitors users included in this
study, the crude incidence rates of serious infections per 100 person
years were reported to be 3.4 (95%), 2.3 (, and 1.5, respectively.
- In the adjusted primary analyses,
no statistically significant differences were observed in the risk of
serious infections during pregnancy amongst the three immunosuppressive
- Non-biologics vs. steroids,
hazard ratio 0.81 (95%)
- TNF inhibitors vs. steroids,
hazard ratio 0.91
- TNF inhibitors vs. non-biologics,
hazard ratio 1.36
- The dose-response analysis showed
that high-dose steroid use was an independent risk factor for serious
infections during pregnancy.
- The results also revealed that
risk of serious infections was significantly
higher in the later months of pregnancy in all three groups.
of the Study
- This is the first study of its
kind to systematically analyze risk of serious infections in pregnant
women undergoing treatment with immunosuppressive agents.
- The sample size used was large
enough to be able to conduct additional stratified analysis by underlying
inflammatory conditions as well as compare the results using meta-analytic
of the Study
- The study only included women with
a live-born infant and did not take into consideration use of some
non-biologic agents which could result in abortions such as methotrexate, mycophenolate mofetil,
- The results of this population-based cohort study revealed no significant difference in the
risk of serious infections in pregnant women who used steroid monotherapy,
non-biologics (monotherapy or in combination with steroids), and tumor
necrosis factor α (TNF) inhibitors (monotherapy or in combination with
steroids or non-biologics).
- On the other hand, steroid dose
was found to be an independent risk factor for
serious infections during pregnancy.
- Rishi J Desai, Brian T Bateman, Krista F Huybrechts, Elisabetta Patorno, Sonia Hernandez-Diaz, Yoonyoung Park, Sara Z Dejene, Jacqueline Cohen, Helen Mogun, Seoyoung C Kim. "Risk of serious infections associated with use of immunosuppressive agents in pregnant women with autoimmune inflammatory conditions: cohort study." The British Medical Journal (2017); 356 doi: https:doi.org/10.1136/bmj.j895.