The present study assessed, using CT, the radiographic progression of the spine and SIJs in women with AS with and without delivery. We found that the interval changes in the CT scores of the spine and SIJs were not significantly different between AS patients with and without delivery. The interaction between biomechanical stress and the innate immune response has been proposed as a cause of AS. According to animal models, mechanical strain can contribute to entheseal inflammation and new bone formation [3]. During pregnancy, the combination of mechanical and hormonal changes causes excessive load on the spine and pelvis and alterations of the pelvic ligaments, leading to pelvic and low back pain [16]. Ursin et al. reported that 70% of pregnant women with axial spondyloarthritis in the third trimester did not take any medication. Discontinuation of TNFIs has been reported to be associated with disease flares in parous women with AS [8]. Therefore, we hypothesized that biomechanical stress and discontinuation of treatment could affect the radiographic progression of the SIJs and spine in patients with AS during pregnancy. However, our study results showed no association between childbirth and structural damage in women with AS.
A major advantage of using CT for the assessment of syndesmophytes is that CT visualizes the whole spine in the sagittal and coronal axes with many slices. CT imaging studies have shown that more extensive syndesmophytes and more progression occur in the thoracic spine than in the cervical or lumbar spine [17]. Indeed, the CTSS is a more detailed score for syndesmophyte growth, indicating a height reaching > 50% or < 50% of the IDS, than the mSASSS, which indicates only the presence or absence of syndesmophytes [9]. Radiographic assessment of spinal progression in AS has been reported to have limited reliability [11]. However, we found that the CT scores had excellent interobserver reliability, consistent with a previous CTSS study [9]. With respect to SIJs, conventional radiography underestimated sacroiliitis compared with CT in the SIMACT (SacroIliac Magnetic resonance CT) study [13]. Although CT provides complete visualization of structural damage, concerns about radiation exposure have traditionally limited its use in AS patients. However, the development of low-dose CT has led to a reduction in radiation dose and noise. The effective dose in low-dose CT of the whole spine was estimated to be approximately 4 mSv, which is still higher than that of radiography (4 mSv: total dose from cervical, lumbar, and pelvic radiography) [9]. Diekhoff et al. showed that the mean radiation exposure with low-dose CT of the SIJs was similar to that with conventional radiography (0.51 vs. 0.52 mSv), with a higher detection rate for sacroiliitis [13]. Indeed, an oblique scanning method for the SIJs could avoid radiation exposure to the ovaries and require fewer slices to cover the whole SIJs compared with axial scanning [18]. Improvement in software together with the ability to reduce the radiation dose could make CT a feasible method for the evaluation of structural damage in the spine and SIJs in the near future.
Spinal progression was found to be associated with the presence of baseline syndesmophytes, male sex, old age, smoking, high disease activity at baseline, and time-averaged CRP levels [19, 20]. An observational 2-year follow-up study on patients with AS using data from the SIAS (Sensitive Imaging in Ankylosing Spondylitis) study showed a mean (standard deviation [SD]) CTSS change score of 16 (21). In our study, the median (Q1-Q3) CTSS change in the delivery group and controls was 1 (0–3) and 0 (0–1), respectively, during a similar interval. In the SIAS study, 84% of the enrolled patients were men with a mean (SD) age of 50 (9.8) years, and 37% of the patients had elevated CRP levels at baseline and higher CTSS (whole spine mean [SD] score: 163 [126]). However, in our study, all patients with AS were women of a young age with a much lower CTSS at baseline (median [Q1-Q3] in the delivery group and controls: 19 [16–23] and 20 [13.25–27.75], respectively). Indeed, the median time-averaged CRP levels were within the normal range in both groups. The discrepancy in baseline characteristics could explain the different results of CTSS changes.
In a previous study, ~ 60% of women presenting with postpartum back pain without axial spondyloarthritis had positive magnetic resonance imaging (MRI) findings for sacroiliitis according to the Assessment of SpondyloArthritis International Society definition [21]. Eshed et al. also found that bone marrow edema (46%) and subchondral sclerosis (26%) were prevalent peripartum MRI findings [22]. However, we could not find a link between these inflammatory changes in the peripartum period and the structural progression of SIJs. Although conventional radiography has limitations in evaluating the SIJs owing to their irregular outline and obliquity, CT is a sensitive method for detecting erosions, bone sclerosis, and ankylosis, which also represent the reference standards for the detection of bony alterations in AS [23]. Although radiographic progression of the SIJs was detected by CT in both AS patients with and without delivery, no significant differences in the interval changes of total, erosion, sclerosis, and JSN scores of the SIJs were found in our study. We expected that women with AS would have increased sclerosis in the SIJs after delivery, such as osteitis condensans ilii [24]. However, the SIJ scores for sclerosis in the delivery group did not significantly change. Although the score changes were small, the changes in the JSN scores in the delivery group and in the erosion and sclerosis scores in the control group were significant. Semiquantitative scores were used to evaluate the structural damage of the SIJs. Further studies with detailed quantitative measurements, such as the number and size of erosions or the exact thickness of sclerosis, are needed to confirm our study results.
Our study suggested that the delivery method (CS or VD) does not affect the radiographic progression of SIJs in patients with AS. A recent study using a medical claims database also showed that changes in prescription did not significantly differ between CS and VD [25]. The SIJs are not a part of the pelvic inlet and cannot be mechanically affected during delivery. In the present study, the rate of CS (n = 9, 75%) was much higher than that of VD (n = 3, 25%) in women with AS. However, the small sample size, especially in the VD group, limited the assessment of structural changes of the SIJs according to the delivery method.
The effect of nonsteroidal anti-inflammatory drugs (NSAIDs) on the inhibition of radiographic progression in AS is controversial. A randomized controlled trial of diclofenac failed to show that this NSAID can prevent structural progression in AS [26]. A post hoc analysis of the celecoxib trial identified that AS patients with elevated acute-phase reactants benefited from treatment with celecoxib with respect to radiographic progression [27]. In our study, most AS patients in the delivery group stopped their medications after the confirmation of pregnancy. NSAIDs were the most prescribed medications, and the proportion of patients taking TNFIs was small in both groups. Indeed, the median time-averaged CRP levels were within the normal range in both groups. Owing to the low disease activity and low use of TNFIs in our study population, treatment discontinuation in pregnancy could not make a significant difference in structural progression between the two groups.
Although it provided insights into the association of pregnancy and delivery with radiographic progression in AS, our study had several limitations. First, the statistical power was limited by the small sample size. The small number of patients with at least two CT evaluations in 2-4-year intervals, the relatively low prevalence of AS in female patients, and the low birth rate in Korea made it difficult to enroll participants in our study [28]. Second, the retrospective design of this study is a shortcoming. Certain clinical parameters, such as the Bath Ankylosing Spondylitis Disease Activity Index and the Ankylosing Spondylitis Disease Activity Score, could not be evaluated through retrospective chart reviews. Information on the delivery method was missing for nine patients. Third, the present study utilized preexisting scans, and the radiation dose of CT was not uniform between the two centers. Images were not reformatted into an oblique coronal view oriented parallel and perpendicular to the long axis of the sacrum. A total of 24 regions of the SIJs were scored in the SIMACT study [13]. However, only four segments with coronal and sagittal views were analyzed in our study, which could have led to a low detection of radiographic progression in the SIJs.