Best Practice & Research Clinical Rheumatology 37 (2023) 101868

Contents lists available at ScienceDirect

Best Practice & Research Clinical

Rheumatology
journal homepage: www.elsevierhealth.com/berh

Pregnancy & neonatal outcomes in

spondyloarthritis
Sinead Maguire a, b, Anna Molto c, d, *
a
Department of Rheumatology, Toronto Western Hospital, University Health Network, Toronto, Canada
b
School of Medicine, University of Toronto, Toronto, Canada
c
Rheumatology Department, Cochin Hospital, Assistance Publique Ho ^pitaux de Paris, Paris, France
d
INSERM U-1153, Centre de Recherche en Epid emiologie et Sciences Statistiques (CRESS), Universit
e Paris-
Cit
e, Paris, France

a b s t r a c t
Keywords:
Pregnancy Limited research has been conducted on the impact of spondylitis
Fertility (SpA) on fertility, but some studies suggest a higher risk of sub-
Spondyloarthritis fertility in women with SpA compared to the general population.
Factors associated with impaired fertility in SpA include pain, fa-
tigue, stiffness, functional disorders, depression, anxiety, negative
body image, and the use of nonsteroidal anti-inflammatory drugs
(NSAIDs) preconceptionally, while TNF alpha inhibitors may play a
role in improving fertility in certain cases.
There has been a recent increase in clinical research focused on
pregnancy outcomes in SpA. However, clear trends in terms of risk
of pregnancy and fetal complications have been slow to emerge
and many questions remain for women with SpA planning a
pregnancy. This article discusses the current evidence for risk of
specific pregnancy and fetal complications in women with axial
and psoriatic SpA.
© 2023 Elsevier Ltd. All rights reserved.

^pitaux de Paris, Paris, France.

* Corresponding author. Rheumatology Department, Cochin Hospital, Assistance Publique Ho
E-mail address: anna.molto@aphp.fr (A. Molto).

https://doi.org/10.1016/j.berh.2023.101868
1521-6942/© 2023 Elsevier Ltd. All rights reserved.
S. Maguire, A. Molto Best Practice & Research Clinical Rheumatology 37 (2023) 101868

Preconception period in SpA

Fertility and counseling

Spondyloarthritis (SpA) is the second most prevalent chronic rheumatic inflammatory disease, and
it affects particularly individuals of childbearing age [1]. Disease has a significant impact on patient's
quality of life, causing pain, stiffness, and disability during their reproductive years, and it is, therefore,
crucial to address the issue of pregnancy wish and discuss the possible treatment adaptations to set in
place in this context. While impaired fertility and ovarian dysfunction have been observed in other
chronic rheumatic inflammatory diseases, such as rheumatoid arthritis (RA) [2e4], the knowledge
regarding their impact on fertility in SpA patients remains limited.
Indeed, only a few studies have specifically addressed fertility in women with SpA, as reflected by a
recent systematic literature review on this topic, in which only 4 out of 21 studies included addressed
[5]. They were also all retrospective studies. However, several studies find evidence for a reduced
average number of births and a shortened reproductive period in women with inflammatory arthritis
compared to controls. Moreover, in a recent registry study assessing fertility in 274 women with axial
SpA (axSpA), time-to-conception was greater than 12 months (which it the time period to define
infertility according to the world health organization [6]) in 21% of women with axSpA, and in 32% of
women who were prospectively followed from preconception. These results suggest an increased risk
of subfertility (defined as a time-to-conception greater than 12 months or a non-achievement of
pregnancy) in women with SpA(7). A multicenter observational prospective cohort found also a me-
dian time-to-conception of 16.1 months in 88 women with SpA included during the preconception
period, which is significantly higher than the (rare) data available in the French general population [8].

Factors associated with impaired fertility

Fertility appears to be impaired in SpA, but the factors leading to infertility in this population are not
clear. Firstly, the sexuality of patients with inflammatory arthritis might be negatively impacted by
pain, fatigue, stiffness, functional disorders, depression, anxiety, negative body image, and treatment's
side effects [9].
In the field of rheumatoid arthritis, Brouwer et al. [10] reported several years ago that NSAID
treatment was inversely associated with pregnancy occurrence (HR 0.66 [0.46e0.94]). More recently,
in the field of SpA, in prospective studies specifically investigating fertility in patients wishing to
conceive, longer time-to-conception was associated with older maternal age and nulliparity in most
studies [7]. Use of NSAIDs preconceptionally is also associated with a longer time-to-conception in
women with SpA (but also in women with rheumatoid arthritis) [8,10]. Indeed, in a recent study on a
prospective cohort, SpA patients preconceptionally exposed to NSAIDs had a median 2.6-fold increase
in time-to-conception in comparison to women who were not [8]. The deleterious effect of NSAIDs
persisted statistically after adjustment for maternal age, smoking, SpA form (axial versus peripheral),
and especially exposure to other treatments and disease activity (assessed by the BASDAI score) with a
hazard ratio of 3.01 [2.15e3.85].
This statistically observed association is further supported by the pathophysiological mechanism of
NSAIDs which, through their effect on prostaglandins, which facilitate fertilization and implantation,
are responsible for impaired fertility through inhibition of follicular rupture [11,12]: NSAID, by their
COX-1 and COX-2 inhibition, interfere with the follicle wall rupture and release of the ovum [13,14]
leading to a luteinized unruptured follicle (LUF) syndrome. Indeed, in animal studies, COX-2 knock-out
mice had lower probability of successful embryo implantation after fecundation [15] and, in humans,
some data have reported a prostaglandin synthesis dysregulation in patients repeatedly failing im-
plantation in in-vitro fertilization procedures (IVF) [16]. These findings are particularly relevant in
patients with SpA, as NSAID remain the cornerstone treatment in axial SpA [17e19].
Despite SpA patients are less likely to receive corticosteroids, it is worth mentioning that a dele-
terious effect on fertility of this drug has been reported in patients with RA: in the PARA study [10],
Brouwers et al. showed a dose-ranging effect of corticosteroids preconceptionally, with higher doses
(e.g. > 7.5 mg/day) being associated with longer time-to conception. The negative impact of

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S. Maguire, A. Molto Best Practice & Research Clinical Rheumatology 37 (2023) 101868

corticosteroids on fertility is reported to be due to the suppression of the hypothalamic-pituitary-

gonadal axis, thus inhibiting periconceptional uterine proliferation.
Finally, regarding TNFi and fertility, some data has suggested that fertilization might be difficult in
an environment with TNF alpha over-expression (e.g., rheumatic inflammatory disease flare).
Furthermore, TNF alpha inhibitors have been reported to be efficacious (alone and combined with
intra-venous immunoglobulin therapy) in the treatment of infertility in women with a Th1/Th2
cytokine profile (e.g. with increased TNF alpha) undergoing in-vitro fertilization (IVF) in one study [20].

Management of the preconception period in clinical practice

Data on fertility in SpA patients suggest an altered fertility compared to the general population, of
multifactorial origin. The first element of management is based on planning, by addressing this preg-
nancy wish (and the potential treatment adaptations needed) early on the follow-up of women of
childbearing age with SpA, and more broadly in women with CIRD. Early dialogue with patients can help
to overcome often-unspoken fears about the possibility of conceiving with their disease and treatment.
Secondly, it is crucial to balance good control of disease activity - which is known to be an inde-
pendent risk factor for fertility impairment in rheumatoid arthritis [10] e while adapting treatment
options, especially in view of the negative impact of NSAIDs on time-to-conception. Indeed, good
management of disease activity during the preconception is closely associated with good control of the
disease during pregnancy, which we shall see is likely to have an impact on pregnancy outcomes [21].
In this sense, 2020 ACR guidelines suggest that NSAIDs should be avoided in the preconception period
in women who have difficulties to conceive [22]. Thus, in patients requiring regular NSAIDs to control
disease activity in the preconception period, especially those at risk of infertility (above 35 years of age,
nulliparous patients, etc.) the introduction of TNFi may be discussed on a case-by-case basis, with
preference given to low transplacental-passenger TNFi, such as certolizumab [23].

The preconception consultation

While systematically assessing and discussing pregnancy wishes in SpA patients of childbearing age
in regular clinics is needed, once the pregnancy wish is formalized, a dedicated consult seems indis-
pensable to address different aspects: ensure that disease is in remission (as disease activity has been,
in RA, related with longer TTC), educate on the impact of disease activity and treatments on fertility and
pregnancy outcomes, check supplementations (e.g. folic acid, vitamin D), screen for vaccination status
(e.g. rubeola) and reach a decision on the management plan during both the preconception and
pregnancy periods, including both the treatment itself (ideally a treatment that could be continued (if
clinically needed) throughout the pregnancy), the rheumatology follow-up modalities during preg-
nancy and also the liaison with midwives or gynecologists.
The generalization of such approach (address family planning early after diagnosis and precon-
ception consultation once pregnancy wish is established) should not only improve SpA patients'
experience during this particular period of their lives but also, by planning and deciding on a thera-
peutic strategy, better prepare the pregnancy and ensure its optimal outcome.

Pregnancy outcomes in SpA

Outcomes in axial spondyloarthritis

Symptom onset in axial spondyloarthritis (axSpA) is typically in the third decade of life or the
twenties, which for women is a critical time in their childbearing years [24]. As such, many women
with axSpA will be aware of their diagnosis prior to their pregnancy. Although there has been copious
research focused on pregnancy outcomes in other forms of rheumatic and musculoskeletal diseases
(RMDs), such as rheumatoid arthritis [9] and systemic lupus erythematosus [25], the literature on
pregnancy outcomes in axSpA until recently has been more sparse.
Early research into this topic dates back to the 1980s when axSpA was thought to rarely affect
women. These studies were quite small in size but reassuring in their results regarding risk-adverse

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S. Maguire, A. Molto Best Practice & Research Clinical Rheumatology 37 (2023) 101868

pregnancy outcomes in women with axSpA [26, 27]. However, subsequent studies reported very
heterogeneous results thus limiting Rheumatologists’ ability to provide evidence-based information to
our patients [28].
Over time larger population studies sought to explore this further, on a background of continuous
advances in the field of Obstetrics as well as increased therapeutic agents for the management of axSpA.
Studies on this topic have faced numerous challenges including evolving terminology, new axSpA
classification criteria, and lack of linkage between Rheumatology and Obstetric records. Development of
national registries, growth of national insurance databases, and increased use of electronic patient re-
cords have helped to overcome many of these hurdles by improving patient identification. This has
created prime opportunities to study pregnancy in axSpA on a larger scale than previously possible.
Data from Ireland reported a high overall prevalence of pregnancy complications in pregnancies of
women with axSpA with 48.5% of pregnancies encountering at least one complication [29]. This
increased risk of pregnancy complications in women with axSpA was also reported in studies from the
United States, Denmark and Sweden [30e32]. By contrast, data from the observational prospective
French DESIR (DEvenir des Spondyloarthropathies Indifferenciees Recentes) cohort estimated a life-
time risk of adverse pregnancy outcome of only 16.7% in axSpA women [33]. Similarly, findings from
the European Network of Pregnancy Registries in Rheumatology (EuNeP) reported the prevalence of
pregnancy complications in women with axSpA to be similar to that of the general population [21].

Outcomes in psoriatic arthritis

The age of onset in psoriatic arthritis (PsA) is typically between 30 and 50 years, with a peak
incidence between the age of 40 and 50 years [34]. As a result, a proportion of women with PsA will be
diagnosed in their childbearing years although this is not the most common PsA population
encountered in clinical practice. This presents an additional challenge to collecting data on pregnancy
in PsA as large numbers of pregnancies in women with PsA and controls are needed to reach signifi-
cance in difference of tested outcomes [5,35].
A Canadian study reported not only were pregnant women with PsA older than controls at time of
delivery but were also more likely to have comorbidities including obesity, hypertension, and diabetes
prior to becoming pregnant [36]. Although concerning, this is unsurprising given that PsA is known to
be associated with a higher risk of metabolic syndrome compared to the general population [37]. PsA is
also associated with numerous additional comorbidities which can impact overall health, level of
function and effectiveness of therapeutic agents [38]. For this reason, current guidelines recommend
active screening and management of comorbidities including obesity and cardiovascular disease as
part of the treatment plan in PsA [39].
Presence of comorbidities, especially obesity, has previously been associated with an increased risk
of adverse outcomes for both the mother and neonate in pregnancies of women in the general pop-
ulation [40,41]. Thus, the higher prevalence of comorbidities in addition to the risk of increased disease
activity during pregnancy could in theory place women with PsA at a higher risk of adverse pregnancy
outcomes.
However, there is limited published evidence examining risk of pregnancy and fetal complications
in women with PsA. A systematic review published in 2021 noted 12 of the 13 included studies were
published between 2017 and 2020 [42]. The recent increase in studies examining pregnancy in PsA is
encouraging for patients and Rheumatologists alike, to allow for evidence-based patient education and
decision-making when planning pregnancy. Ongoing research is essential as a meta-analysis reported a
significantly increased risk of a number of pregnancy complications in women with PsA compared to
healthy controls [43]. This result is highly concerning, and the authors called for close monitoring of
women with PsA during their pregnancies to identify and manage complications promptly.
Subsequent studies have since been published from nationwide registry cohorts which have
examined risk of obstetric complications in addition to considering additional factors such as disease
activity and use of anti-rheumatic medications [36,44].
Below we discuss the results of studies that examined prevalence of some of the most commonly
encountered pregnancy complications in pregnancies of women with SpA and the implications of these
results.

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S. Maguire, A. Molto Best Practice & Research Clinical Rheumatology 37 (2023) 101868

Preterm birth

Preterm birth is defined as birth prior to 37 weeks gestation [45]. This outcome has serious health
implications for the neonate and has previously been reported as one of the leading causes of death
among children under the age of 5 years and the most common cause of neonatal deaths worldwide
[46]. It has also been linked with serious long-term health issues including hypertension, impaired
glucose tolerance and lung disease in affected neonates [47]. While the etiology of preterm birth is
complex and often multifactorial, a number of maternal factors including maternal health conditions
are recognized to contribute to an overall increased risk [48,49].
Given this information, the need to capture prevalence of preterm birth in SpA pregnancies and
factors associated with it are clear. A large Danish population register study reported a 55% higher risk
of preterm birth in women with SpA compared to controls (OR 1.55, 95% CI 1.33e1.88) despite simi-
larities in pre-pregnancy BMI, maternal age, and fetal birthweight [32].
Focusing on axSpA, a 2020 meta-analysis reported a significantly increased prevalence of preterm
births in axSpA pregnancies compared to controls (OR 1.33, 95% CI 1.05e1.70) [50]. A follow-up Irish
registry study confirmed this finding with preterm birth observed significantly more often in axSpA
pregnancies compared to global reference norms (OR 2.48, 95% CI 1.61e3.83) [29].
Results of a German study using data from a national health insurance database reported a non-
significant trend toward an increased prevalence of preterm birth (OR 1.29, 95% CI 0.97e1.70) [51].
Although further analysis revealed this difference to be significant in axSpA women treated with
NSAIDs alone (OR 1.88, 95% CI 1.05e3.36) or those treated with NSAIDs and conventional synthetic
Disease Modifying Anti-Rheumatic Medications (csDMARDs), steroids or other analgesia (OR 3.96, 95%
CI 2.17e7.21).
Interestingly, Zbinden et al. reported active disease in the second trimester to be a predictor of
preterm birth in women with axSpA (OR 13.8, 95% CI 1.33e143.9) [52]. This same study reported no
associated increased risk of preterm birth associated with use of antirheumatic therapy including
DMARDs and tumor necrosis factor inhibitors.
Prospective data from the European Network of Pregnancy Registries in Rheumatology (EuNeP)
reported preterm birth in only 4.9% of their population of women with axSpA, which is lower than 8.7%
reported in the general population of the European Union [21]. Additionally, axSpA women with low
inflammatory markers and those on tumor necrosis factor (TNF) blockers reported lower rates of
complications including preterm birth. Thus, advances in care resulting in improved disease control in
pregnancy may have played a role in the lower prevalence of preterm birth observed. This finding is
supported by a Swedish study of pregnancies in axSpA women from 2007 to 2020 which reported a
0.5% annual decrease in risk of preterm birth, cesarean sections and infant infections in the setting of
increasing use of tumor necrosis factor inhibitors [53].
Preterm birth is also a complication of concern in pregnancies of women with PsA. A population
study from Canada and the United States reported PsA was found to confer a significantly increased risk
of both preterm delivery (aRR 1.81, 95% CI 1.10e3.26) and preterm labor (aRR 2.05, 95% CI 1.21e3.48)
[30]. Similar results were reported in a Swedish registry study with elevated risk of preterm birth in
PsA women (adjusted OR 1.69, 95% CI 1.27e2.24) [44]. This study also suggested risk of preterm birth
may be associated with biologic DMARDs, however, this was refuted as more likely reflective of se-
lection bias within the study [54].
A 2021 systematic review on pregnancy outcomes in PsA highlighted that preterm birth was one of
the most commonly investigated outcomes in the included studies, with 3 of the 5 studies reporting a
significant association between PsA and risk of preterm birth [42]. This was confirmed in a later meta-
analysis which also reported a significantly higher pooled prevalence of preterm birth in women with
PsA compared to controls from the 4 included studies (OR 1.48, 95% CI 1.24e1.78) [43](Table 1).
Interestingly, a retrospective study that verified patient-reported pregnancy outcomes via chart
review reported preterm birth was in fact over-reported by patients with PsA, as delivery at 37 weeks
was often misclassified as preterm [35].

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Table 1
Risk of pregnancy complications in women with psoriatic arthritis and axial spondyloarthritis.

Psoriatic Arthritis Axial Spondyloarthritis

Preterm Birth

Pre-eclampsia No consensus

Cesarean Section

Gestational Diabetes No consensus No consensus

Pre-eclampsia, eclampsia & gestational hypertension

Hypertensive disorders of pregnancy including pre-eclampsia are recognized to be leading causes of

morbidity to both mother and neonate [55]. Numerous guidelines from Obstetrics & Gynecology have
been developed to effectively screen for and manage these complications throughout pregnancy [56].
Risk factors for pre-eclampsia include obesity and hypertension [57], both of which are known to be
prevalent in the SpA population [38,58]. Additionally, the presence of chronic maternal systemic
inflammation may also play a role in the development of pre-eclampsia [59].
Given this information, it would be suspected that these issues would be more prevalent in preg-
nancies of women with both PsA and axSpA, however, published results have failed to reach a clear
consensus. A meta-analysis on PsA reported a significantly increased risk of both pre-eclampsia or
eclampsia (OR 1.45, 95% CI 1.13e1.85) and gestational hypertension (OR 1.49, 95% CI 1.09e2.06) [43]. In
axSpA, a meta-analysis detected a non-significant trend toward increased prevalence of pre-eclampsia
(OR 1.35, 95% CI 0.99e1.82) [50]. A subsequent study examined pre-eclampsia risk in the context of
disease activity and use of anti-rheumatic medications [60]. This reported the risk of pre-eclampsia in
PsA pregnancies to be nearly double that of controls (adjusted OR 1.85, 95% CI 1.10e3.12) while in
axSpA pregnancies no significant differences were detected (adjusted OR 1.17, 95% CI 0.76e1.78). Data
on disease activity and pharmacotherapy during pregnancy in this study was limited, however, there
was no indication that treatment with antirheumatic medications increased the risk of pre-eclampsia
in axSpA or PsA.
The increased risk of pre-eclampsia in PsA has been proposed to be reflective of the greater burden
of numerous comorbidities known to be associated with PsA as mentioned above. This is supported by
the higher BMIs recorded in women with PsA during their pregnancy compared to controls [61] and
even women with axSpA(60). Interestingly this association was noted to persist even when adjusted for
these factors as demonstrated by Broms et al. [61], which suggests additional factors at play that may
predispose women with PsA to develop hypertensive disorders in pregnancy.

Cesarean sections

Prevalence of cesarean sections has been rising steadily worldwide, with current global estimates of
cesarean section accounting for up to 21.1% of all births [62]. Reasons for this are multifold with ad-
vances in assisted reproductive therapy, cultural influences, patient preference and medical advances
acknowledged as contributing factors to this rapid increase [63].
Current guidance on cesarean section recommends this intervention should only be used when
deemed medically necessary by the treating physician. The reason for this is that cesarean sections,
even when elective, are major surgical procedures and hence not without risk. Cesarean sections are
associated with a risk of certain morbidities in subsequent pregnancies, including severe hemorrhage
and abnormal placentation [64]. However, in the right clinical scenario, a cesarean section can be a
lifesaving intervention for the mother, neonate, or both.

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Studies in SpA have shown a higher prevalence of both elective and emergency cesarean sections
carried on in women with SpA(32). This is concerning for reasons discussed above but in the case of
women with SpA this incurs additional consequences including prolonged immobilization post-
delivery, increased risk of infections and delay in restarting biologic therapies.
Prevalence of cesarean sections in axSpA has consistently shown to be higher than in deliveries for
women of the general population [50,51]. This higher prevalence of cesarean sections in axSpA women
has been shown to be present whether in cesarean section overall (OR 1.65, 95% CI 1.52e1.80), as well
as both elective (OR 2.31, 95% CI 1.94e2.75) and emergency procedures (OR 1.29, 95% CI 1.06e1.56)
[50].
A higher prevalence of delivery by elective cesarean section in PsA women was first reported by
Broms et al. (aOR 1.49, 95% CI 1.18e1.81) [61]. An overall increased risk of delivery by cesarean section
was also reported by Smith et al. (aRR 1.63, 95% CI 1.26e2.12) [30]. This was confirmed to be signifi-
cantly higher than controls via meta-analyses [5,43].
A recent study examined the prevalence of cesarean sections in women with PsA and axSpA versus
healthy controls using the Medical Birth Registry of Norway [65]. This confirmed the increased fre-
quency of cesarean section delivery in both axSpA and PsA women with higher frequencies noted in
women with active disease in the third trimester regardless of subtype of SpA. One of the highlights of
this study was the follow-up analyses examining risk of elective and emergency cesarean section in the
context of disease activity in SpA.
For women with PsA although elective cesarean sections were more prevalent than controls and
most commonly observed in women with active disease, these differences did not achieve statistical
significance (risk difference 4.3%, p ¼ 0.06). However, emergency cesarean sections were significantly
more frequent mode of delivery in women with PsA with a 10.6% risk difference (p < 0.001) compared
to controls. These differences remained significant for both women with active (15.9%, p ¼ 0.015) and
inactive PsA (10.3%, p ¼ 0.011) in the third trimester.
For women with axSpA risk of emergency cesarean sections was similar to controls (p ¼ 0.17).
Elective cesarean sections were found to be significantly more prevalent in axSpA women (risk dif-
ference 4.4%, p ¼ 0.001) and were most frequent in women with active axSpA in the third trimester
(7.6%, p < 0.001). These results are in keeping with results from Smith et al. who also reported an
increased risk of cesarean section in axSpA women with increased disease activity in pregnancy [30].

Gestational diabetes
The prevalence of gestational diabetes has been rising globally in association with rising levels of
obesity. Gestational diabetes is associated with a ten-fold increased maternal risk of developing type II
diabetes postpartum [66], as well as numerous obstetric complications [67]. Despite being one of the
most commonly encountered obstetric complications in the general population, few studies have
examined this outcome when examining adverse pregnancy outcomes in SpA(43, 50).
A Canadian study using provincial health records reported a similar prevalence of gestational
diabetes in both healthy control and women with SpA (6% vs 6.6%, p ¼ 0.3) [68]. However, studies on
axSpA and PsA exclusively report divergent outcomes.
A Swedish registry study reported a non-significant trend toward an increased prevalence of
gestational diabetes in women with PsA (OR 1.62, 95% CI 0.95e2.77) even when adjusted for smoking
status and maternal body mass index (aOR 1.58, 95% CI 0.91e2.74) [44]. A similar outcome was re-
ported by Smith et al. (aOR 1.41, 95% CI 0.70e2.87) who also adjusted for maternal age and comor-
bidities [30].
In axSpA data is also sparse but has increased rapidly over recent years. A prospective Canadian and
American study failed to detect an increased risk of gestational diabetes in women with axSpA (aOR
0.49, 95% CI 0.18e1.34) [30]. Similar results were also reported from a German study using data from a
national insurance claims database (aOR 0.82, 95% CI 0.63e1.08) [51]. This conflicts with a non-
significant trend reported in a recent Swedish study toward increased risk in axSpA pregnancies
(aOR 1.23, 95% CI 0.84e1.82) [53].

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Neonatal outcomes in SpA

While there has been a dramatic increase in studies capturing outcomes in pregnancies of women
with SpA over recent years, data on neonatal outcomes has been slower to emerge. There are many
reasons for this including a high level of heterogeneity of specific neonatal outcomes captured, lack of
dedicated neonatal outcome studies in women with SpA, and relative rarity of certain neonatal out-
comes resulting in studies being underpowered to detect significant differences.

Low birthweight

Low birthweight (LBW) is defined as less than 2500 g and is associated with adverse health out-
comes and greater healthcare utilization in affected neonates [69]. In PsA, this outcome has been
assessed in studies from Denmark (OR 1.11, 95% CI 0.80e1.54) and North America (aRR 1.52, 95% CI
0.76e3.04) with both reporting no significant increased risk in pregnancies of PsA women [30,61].
Results in axSpA are not as consistent, reflecting the larger number of studies in which this outcome
is captured. A Korean hospital cohort study reported a significantly increased prevalence of LBW in
neonates of axSpA women compared to controls (22.2% vs 8.3%, p ¼ 0.02), while a retrospective
American cohort study reported a non-significant trend toward increased risk of LBW in axSpA
pregnancies (OR 1.96, 95% CI 0.79e4.85) [70,71]. Yet another American study reported no increased risk
(aRR 1.06, 95% CI 0.50e2.27) [30]. Pooling of results in a meta-analysis revealed a non-significant trend
toward an increased risk of LBW in neonates of axSpA women (OR 1.47, 95% CI 0.98e2.21) [50].

Small for gestational age

When discussing neonatal birthweight, small for gestational age (SGA) is often preferred over LBW
as gestational age at birth is taken into account. A non-significant trend toward an increased risk of SGA
in pregnancies of women with SpA was reported by Mork et al. (aOR 1.09, 95% CI 0.97e1.23) [32]. A
similar prevalence of SGA in neonates of axSpA women compared to controls has been reported in
three studies [51,53,70]. However, one additional study reported a non-significant trend toward an
increased prevalence [31], while another reported SGA was significantly increased in neonates of
axSpA mothers (OR 2.06, 95% CI 1.28e3.30) [71].
For neonates of women with PsA, the risk of SGA also remains unclear, with 5 published studies
capturing this outcome. Three studies [44,61,71] reported no increased risk of SGA in neonates of PsA
women, while one detected a non-significant trend toward an increased risk of SGA (aOR 1.72, 95% CI
0.98e3.02) [32] and another reporting an increased risk in PsA pregnancies (aOR 2.42, 95% CI
1.49e3.93) [36].

Admissions to the neonatal intensive care unit

Neonates of women with PsA were found to have no increased risk of admission to the neonatal
intensive care unit (NICU) following delivery by Smith et al. (aRR 1.06, 95% CI 0.60e1.87), although the
same study reported an increased risk of NICU admission in neonates of women with axSpS (aRR 1.67,
95% CI 1.05e2.67) compared to controls [30]. However, a retrospective Turkish case-control study
reported no increased prevalence of NICU admissions for neonates of axSpA women (19% vs 12.5%,
p ¼ 0.34) [72]. Based on this information, it is currently not possible to draw firm conclusions regarding
the risk of NICU admission to neonates of mothers with SpA.

Summary

Managing the preconception period in clinical practice for patients with spondylitis involves early
planning and addressing pregnancy wishes with patients. Preconception consultations should be
dedicated to assessing disease remission, educating patients about the impact of disease activity and
treatments on fertility and pregnancy, checking supplementations, and discussing the management

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plan for the preconception and pregnancy periods. Implementing such an approach should improve
the experience of SpA patients during this period and potentially optimize pregnancy outcomes.
While there has been a recent increase in studies examining pregnancy and neonatal outcomes in
pregnancies of women with SpA, many questions remain. Current evidence suggests women with PsA
have been shown to have a higher prevalence of preterm birth, pre-eclampsia, and cesarean sections
compared to women of the general population. In women with axSpA, there is a higher prevalence of
preterm birth and cesarean sections, with the active disease during pregnancy thought to further
increase the risk of these complications. Limited data exists on the risk of neonatal complications in
pregnancies of women with SpA and this is an area which requires significant exploration. Future
population studies focused on risk factors associated with adverse obstetric outcomes in SpA are
needed to minimize risk of complications in pregnancies of women with SpA to optimize maternal and
neonatal outcomes in this population.

Practice points

- Women with PsA have a higher prevalence of preterm birth, pre-eclampsia, and cesarean
sections compared to the general population.
- Women with axSpA have a higher prevalence of preterm birth and cesarean sections, with
active disease during pregnancy thought to further increase the risk of these complications.

Research agenda

- Further population studies are needed regarding risk factors associated with adverse ob-
stetric outcomes in SpA women, to allow optimization of maternal and neonatal health out-
comes in women with SpA
- The limited published data on neonatal outcomes in pregnancies of women with SpA is a
glaring gap of knowledge in this area, requiring further population-level data to understand

Declaration of competing interest

None.

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