Maternal Interleukin-17 and disease activity influence pregnancy outcomes in women with psoriatic arthritis and ankylosing spondylitis

Psoriatic arthritis (PsA) and ankylosing spondylitis (AS) are chronic inflammatory disorders that affect males and females at younger ages than other rheumatic diseases. Women with PsA and AS usually have normal pregnancy outcomes, although high disease activity during pregnancy may increase adverse pregnancy outcomes, according to 2004–2018 data from the Organization of Teratology Information Specialists (OTIS) Autoimmune Disease Project [1].

Psoriatic arthritis typically has varied joint and skin forms and variable degrees of severity and is a linked set of diseases called spondylarthritis [2]. Ankylosing spondylitis disease characterized by pain and reduced axial bone flexibility and peripheral arthritic, extra-articular symptoms or enthesitis, all of which can lead to limitations of activity, disability, or poor quality of life. Management involves physiotherapy and medication with nonsteroidal anti-inflammatory medicines (NSAIDs), inhibitors of tumor necrosis factor (TNF) and disease-modifying antirheumatic drugs (DMARDs). All of these variables can lead to poor pregnancy results for women [3]. Many reports have indicated that immune responses mediated by interleukin 17A (IL-17A) play a significant role in both diseases. The substantial clinical effectiveness seen in IL-17A inhibitors in the treatment of SpA and PsA is the best demonstration. However, there are many defects in understanding the effect of IL-17A on the pathophysiology of spondylarthritis, bone erosion, and bone development, and, an explanation for the uneven effect of IL-17A inhibition was identified. Registered studies in Norway cohorts have shown lower fertility in women with chronic arthritis and poor birth outcomes such as intrauterine growth retardation, preterm labour and Caesarean delivery [4]. The majority of ankylosing spondylitis patients from 6 weeks to 6 months after birth, developed an exacerbation of this condition. Limited studies have been carried out in prenatal and neonatal AS patients with a relatively small number of patients [5].

Overall, RA research reveals elevated risks of preterm birth, small-for-gestational-age (SGA), pre-eclampsia and caesarean deliveries from an overall perspective of chronic arthritis and pregnancy results [6]. AS studies and pregnancy outcomes are sparse however the latest research indicated that preterm birth and caesarean delivery chances had been elevated [7, 8].

We aimed in this study to evaluate the impact of maternal interleukin -17A and the activity of the illness on pregnancy outcomes in AS and PsA patients.

This prospective cohort study involved 48 pregnant women with psoriatic arthritis and ankylosing spondylitis attending the inpatient and outpatient clinics of Rheumatology & Rehabilitation and Obstetrics & Gynecology Departments, Faculty of Medicine, Zagazig University Hospital in Egypt and 30 apparently healthy age- and sex-matched pregnant women between January 12,018, and December 31, 2019.

All patients enrolled in this study provided informed consent before joining our study and all had the right to take away from the study without any interruption of their treatment plan and rights. All personal data of our enrolled patients were preserved and kept away from data retrieving personnel. A detailed flowchart (Fig. 1) was made for study demonstration.

The study group patients were diagnosed using modified New York criteria for ankylosing spondylitis [9] and classification for psoriatic arthritis (CASPAR) criteria [10].

Information was gathered in advance preconception (3 months to 1 year), throughout the 1st trimester (8–12 weeks), 2nd trimester (16–24 weeks) and 3rd trimester (28–34 weeks of pregnancy).

All pregnant women who consented to participate were enrolled at the 4 time points:

Complete medical history, medication exposures during pregnancy, obstetric history including maternal age, expected date of delivery, gravity, parity, gestational age at enrollment and at labour, pregnancy by ICSI, and previous preterm delivery or intrauterine growth retardation., family history, preconception body mass index (BMI), and socioeconomic status. Medication included start and end dates, indications, variations in dose and frequency, use of caffeine, nutritional supplements, folic acid intakes, infections, or antenatal investigation or other medical intervention. Any woman with other autoimmune diseases or other chronic diseases was excluded from the study.

General and local musculoskeletal examination.

Laboratory investigations.

The erythrocyte sedimentation rate (ESR) was determined by the Westergren method, the C-reactive protein (CRP) level was determined by the latex agglutination test, and HLA B27 (ELISA Kit) was estimated by collecting blood samples which stored at − 20 °C until tested for human HLA B27 using the Sunlong Biotech kit, China (catalog number: SL1056Hu).

IL-17A ELISA: ELISA is an enzyme-linked immunosorbent assay for the quantitative detection of human IL-17A. The kit was supplied by IBL International GmbH (Flughafenstr. 52A, 22,335 Hamburg, Germany).

Disease activity.

Using patient-reported assessments, including the Health Assessment Questionnaire (HAQ) [11] on a scale from 0 to 3, as well as pain score and patient global disease activity assessment on a scale from 0 to 100, the study group was evaluated at the same obstetric evaluation time points (pre-conceptional, first trimester, and third trimester). Next, the total pain score was divided by 10 for a range of 0–10, and the patient global assessment was performed in the same way. Cumulative Routine Assessment of Patient Index Data 3 (RAPID3) had three markers of disease activity and each marker was combined to yield a RAPID3 score ranging from 1 to 30, with active disease defined as a RAPID3 score ≥ 7 [12]. Active disease was defined as a HAQ score greater than 0.5.

Measures of pregnancy outcomes:

Premature birth (delivery before 37 weeks of gestation), small for gestational age (SGA—fetal weight is projected to be smaller than the 10th percentile for the child’s gestational age and sex), and delivery methods (vaginal or cesarean).

Inclusion criteria included a singleton pregnancy aged ≥18 years, with diagnosis of AS or PsA for at least 6 months, without major fetal anomalies, known chromosomal abnormalities or other autoimmune diseases, and gestational age of 28–40 weeks. Patients with a history of preterm labour, or any medical disorder were excluded from the study.

Ultrasound biometry measurements such as the biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC), and femur length (FL) were taken on each fetus. Hadlock’s formula gives the estimated fetal weight (EFW). William’s tables were used to obtain the overall EFW percentile. The tables determine the birth weight percentile by gestational age and sex, and they are from a large population-based study with a sample size large enough to calculate the percentile in question [13, 14].

The maternal age mean ± SD was 30.21 ± 2.13, 33.42 ± 5.11, and 31.34 ± 3.15 weeks in the control, psoriatic arthritis, and ankylosing spondylitis groups respectively. The mean ± SD of BMI (kg/m2) was 23.25 ± 4.17, 38.21 ± 3.15, and 24.81 ± 5.13 respectively. The maternal weight gain (kg) mean ± SD was 23.25 ± 4.17, 38.21 ± 3.15, and 24.81 ± 5.13 respectively. The socioeconomic score N (%) was 25 (83.3%), 24 (92.3%), and 20 (90.9%) respectively. There was a statistically significant increase in the Psoriatic Arthritis patients compared with the healthy group with regard to age, BMI and Socioeconomic Score (Table 1).

Regarding parity, primigravida N (%), and multigravida N (%), they were significantly higher in Ankylosing Spondylitis group 17 (77.2) and 14 (63.6) than in control groups 14 (46.6) and 9 (30). Abortion N (%) was significantly lower in Psoriatic Arthritis group 2 (7.6%) than in control group 5 (16.7%). Regarding a history of preterm labour N (%), gestational diabetes N (%) and preeclampsia N (%) there was no significant difference between the control group and the psoriatic arthritis, and the ankylosing spondylitis groups (Table 2).

The mean ± SD of Disease duration (years) was 5.32 ± 5.61, and 6.37 ± 4.15 in the psoriatic arthritis, and ankylosing spondylitis groups respectively. Additionally, HLA B27 positive testing was higher in the PsA group than in the AS group. The disease was active according to Routine Assessment Patient Index Data with 3 measures in 10 (38.5%) and 9 (41%) patients, and according to the Health Assessment Questionnaire the disease was active in 4 (15.4%) and 6 (27.2%) patients in the PsA, and AS groups respectively. Regarding the medications usage distribution, in the psoriatic arthritis group 21 (80.7%) were using biologic DMARDs, 3 (11.5%) were using DMARDs and 10 (38.4%) were using NSAIDs, while in the ankylosing spondylitis group, 18(81.8%) were using biologic DMARDs, 6 (27.2%) were using DMARDs and 8 (36.3%) were using NSAIDs (Table 3).

There was a significant difference between the control group and the psoriatic arthritis, and the ankylosing spondylitis groups at preconception, and the 1st,2nd and 3rd trimesters regarding CRP and IL-17A (Fig. 2) while there was no statistically significant difference between preconception, and the 1st,2nd and 3rd trimesters with regard to CRP and IL-17A (Table 4).

Additionally, there was no significant difference between the control and study groups regarding the RAPID 3 score and HAQ score (Figs. 3 & 4) in the preconception, 1st,2nd and 3rd trimesters (Table 4).

Comparing to healthy controls, the Women in the study groups had a higher risk of preterm labour (32–36 weeks gestation) (aRR 1.80, 95% CI 0.79–4.17), oligohydramnios (aRR 3.15, 95% CI 1.26–8.42), and cesarean delivery (Fig. 5) (aRR 1.57, 95% CI 1.41–2.68) and a higher risk of SGA fetuses (aRR 7.04, 95% CI 2.36–12.42) (Table 5). The Caesarean delivery indication was related only to failed labour progress with early fetal distress without any maternal pelvic abnormality or fetal malposition or malpresentation.