Pregnancy and the Risk of Autoimmune Disease

Ali S Khashan,Thomas M Laursen,Uzma Mahmood,Tine B Henriksen,Preben B Mortensen,Keelin O'Donoghue,Louise C Kenny,Pablo Villoslada

doi:10.1371/journal.pone.0019658

Ali S Khashan, Thomas M Laursen + Show 6 more

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https://doi.org/10.1371/journal.pone.0019658

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Abstract

Autoimmune diseases (AID) predominantly affect women of reproductive age. While basic molecular studies have implicated persisting fetal cells in the mother in some AID, supportive epidemiological evidence is limited. We investigated the effect of vaginal delivery, caesarean section (CS) and induced abortion on the risk of subsequent maternal AID. Using the Danish Civil Registration System (CRS) we identified women who were born between 1960 and1992. We performed data linkage between the CRS other Danish national registers to identify women who had a pregnancy and those who developed AID. Women were categorised into 4 groups; nulligravida (control group), women who had 1st child by vaginal delivery, whose 1st delivery was by CS and who had abortions. Log-linear Poisson regression with person-years was used for data analysis adjusting for several potential confounders. There were 1,035,639 women aged >14 years and 25,570 developed AID: 43.4% nulligravida, 44.3% had their first pregnancy delivered vaginally, 7.6% CS and 4.1% abortions. The risk of AID was significantly higher in the 1st year after vaginal delivery (RR = 1.1[1.0, 1.2]) and CS (RR = 1.3[1.1, 1.5]) but significantly lower in the 1st year following abortion (RR = 0.7[0.6, 0.9]). These results suggest an association between pregnancy and the risk of subsequent maternal AID. Increased risks of AID after CS may be explained by amplified fetal cell traffic at delivery, while decreased risks after abortion may be due to the transfer of more primitive fetal stem cells. The increased risk of AID in the first year after delivery may also be related to greater testing during pregnancy.

Highlights

Autoimmune diseases (AID) are most common among women and increase in incidence following their reproductive years [1]
It appears that women who were pregnant had a higher incidence of AID than those who had no pregnancy records and women who had singletons had slightly higher incidence of AID than those who had multiple gestation
In this study we report the risk of autoimmune disease during and after pregnancy

Summary

Introduction

Autoimmune diseases (AID) are most common among women and increase in incidence following their reproductive years [1]. AID are caused by an immune reaction against self–antigens due to disturbances in T or B cell regulation or function, and autoimmunity may occur in a genetically susceptible individual if an antigen is inadvertently targeted by T or B cells potentially due to environmental or other factors triggering a break in tolerance [2] Those autoimmune diseases more common in women include systemic lupus erythematosus (SLE; 9:1), autoimmune thyroid disease (8:1), scleroderma (5:1), rheumatoid arthritis (4:1) and multiple sclerosis (3:1), while type 1 diabetes and inflammatory bowel diseases have almost the same female to male ratios of 1:1 and primary sclerosing cholangitis is more prevalent in men. It is unlikely that the difference in sex hormones between women and men alone explains the preponderance of AID in women; most AID occur after reproductive years and administration of sex steroids does not have disease-altering effects [2]

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