Women with various autoimmune disease appear to be at higher risk for preterm birth and cesarean delivery, according to a study. The findings may help inform intervention strategies.


 

Women with autoimmune conditions are at increased risk of adverse pregnancy outcomes, according to previous research. Rheumatoid arthritis (RA), psoriatic arthritis, and systemic lupus erythematosus (SLE) have been linked to a higher risk of preterm birth, low birth weight, caesarean delivery, and small for gestational age (SGA) offspring. Other evidence suggests that psoriasis and inflammatory bowel disease (IBD) increase risks for preterm birth and caesarean delivery. Many of these same autoimmune conditions are also associated with other pregnancy complications, including preeclampsia, gestational diabetes, and infections.

According to Gretchen Bandoli, PhD, research is needed to quantify the percentage of excess risk of adverse pregnancy outcomes mediated through pregnancy complications and whether the proportion mediated differs by autoimmune condition. “Knowing which complications increase risks of adverse pregnancy outcomes in these women can help physicians determine who is at higher risk,” she says. “In turn, efforts can be made to mitigate risks with targeted intervention strategies for the respective pregnancy complications.”

Dr. Bandoli and colleagues had a causal mediation analysis published in Arthritis Care & Research that sought to quantify the mediated effects of pregnancy complications on adverse pregnancy outcomes in women with autoimmune conditions. Causal mediation analyses are performed to investigate the underlying mechanisms that contribute to an observed relationship. The authors queried a California cohort of nearly 3 million births in which women with RA, SLE, psoriasis, and IBD were identified. For these cases, the researchers examined rates of pregnancy complications, including preeclampsia/hypertension, gestational diabetes, and infection in pregnancy. Adverse pregnancy outcomes were defined as preterm birth, cesarean delivery, and SGA.

 

Important New Data

All four autoimmune conditions assessed in the study were associated with preterm birth and cesarean delivery, according to the study (Table). RA, SLE, and IBD were also associated with SGA offspring. In general, preeclampsia/hypertension accounted for the largest proportion of excess adverse pregnancy outcomes due to autoimmune conditions, particularly preterm births. “In women with RA, SLE, and psoriasis, 20% to 30% of the excess risk of preterm births and 10% to 20% of the excess risk of cesarean delivery was attributable to preeclampsia,” says Dr. Bandoli. “Interestingly, women with IBD had the same increased risk of preterm birth and cesarean delivery as women with RA, but essentially none of the excess risk of those outcomes was mediated by preeclampsia.”

In general, gestational diabetes and infections in pregnancy contributed to much less of the excess risk of adverse pregnancy outcomes across the autoimmune conditions. “Gestational diabetes and pregnancy infections generally accounted for less than 10% of the excess risk of preterm birth, cesarean deliveries, or SGA offspring with any of the autoimmune conditions,” Dr. Bandoli says. “This suggests that intervention efforts in those areas would do less to prevent these select adverse pregnancy outcomes.”

 

Taking the Next Step

According to Dr. Bandoli, the study results have important clinical implications. “In women with RA, SLE, and psoriasis, physicians should be extra mindful of preeclampsia and the heightened downstream risk of preterm birth and cesarean delivery,” says Dr. Bandoli. “Based on our data, counseling these women early in pregnancy to reduce risk factors associated with preeclampsia would be most beneficial to reducing their risk of a preterm birth or a cesarean delivery. Ideally, intervention and mitigation strategies could be targeted based on the specific autoimmune condition that a woman possesses.”

However, Dr. Bandoli notes that targeting these same pregnancy complications might not have as great an impact on outcomes in women with IBD. “We were unable to identify any pregnancy complications that explained much of the excess risk of adverse pregnancy outcomes in women with IBD,” she says. “This suggests that the disease itself may directly affect risk of these outcomes, or alternatively, there are strong mediators that we have not yet identified. Continued research is needed for each of the conditions individually because although we identified some of the potential causes of excess risk, a much larger percentage still remains unexplained. Thus, there are many unrecognized pathways that likely mediate risk for adverse pregnancy outcomes in these women and are not well understood.”

References

Bandoli G, Singh N, Strouse J, et al. Mediation of adverse pregnancy outcomes in autoimmune conditions by pregnancy complications. Arthritis Care Res (Hoboken). 2019 Aug 2 [Epub ahead of print]. Available at: https://www.ncbi.nlm.nih.gov/pubmed/31373768 or at: https://onlinelibrary.wiley.com/doi/epdf/10.1002/acr.24037?referrer_access_token=ydAtFyLIr25ssFwvW3U54k4keas67K9QMdWULTWMo8NoShhmer5m1QtNF8GAeoucS7eZz44gvep3I4DD4g_20z-DUG3uTP9jHdfMwX1QTgVMp2px3OqxfHdRzzzLYHsxaPO678S8EHle1KYJo3idew%3D%3D.

Valeri L, Vanderweele TJ. Mediation analysis allowing for exposure – mediator interactions and causal interpretation: theoretical assumptions and implementation with SAS and SPSS macros. Psychol Methods. 2013;18:137-150.

Bandoli G, Chambers CD. Autoimmune conditions and comorbid depression in pregnancy: examining the risk of preterm birth and preeclampsia. J Perinatol. 2017;37:1082-1087.