DOI: 10.1111/tog.

12917 2024;26:66–74
The Obstetrician & Gynaecologist
Review
http://onlinetog.org

Sarcoidosis in pregnancy
Joshua Odendaal MRCOG PhD,*a,b Fiona L Mackie MRCOG PhD,
c
Sofia Tosounidou MRCP,
d

Swati Ghosh FRCOG,e Ellen Knox FRCOG

f

a
NIHR Clinical Lecturer, Division of Biomedical Sciences, Clinical Sciences Research Laboratories, Warwick Medical School, University of Warwick,
Coventry CV2 2DX, UK
b
Specialty Registrar in Obstetrics & Gynaecology, University Hospitals Coventry & Warwickshire, Coventry CV2 2DX, UK
c
Subspecialty Trainee in Maternal Fetal Medicine, Birmingham Women’s and Children’s NHS Foundation Trust, Mindelsohn Way, Birmingham
B15 2TG, UK
d
Consultant Rheumatologist, University Hospitals Birmingham, Mindelsohn Way, Birmingham B15 2GW, UK
e
Consultant Obstetrician, Worcestershire Acute Hospitals NHS Trust, Charles Hastings Way, Worcester WR5 1DD, UK
f
Consultant Obstetrician & Subspecialist in Maternal Medicine, Birmingham Women’s and Children’s NHS Foundation Trust, Mindelsohn Way,
Birmingham B15 2TG, UK
*Correspondence: Joshua Odendaal. Email: j.odendaal@doctors.org.uk

Accepted on 2 January 2024.

Key content: Learning objectives:

 Sarcoidosis is an uncommon multi-system disorder characterised
by the presence of non-caseating granulomas. It has a peak
incidence between the ages of 20–40 years old.
 The pathogenesis of sarcoidosis is uncertain; however, it is known
to be associated with an exaggerated T helper 1 (TH1) immune
response leading to systemic inflammation and
granuloma formation.
 Suppression in TH1 responses in pregnancy leads to disease
remission in the majority of pregnancies. Nevertheless, the
potential for decompensation in a subgroup remains,
and consideration should be given to the pre-pregnancy state.
 Sarcoidosis is associated with increased risk of maternal-fetal
morbidity, including growth restriction and pre-eclampsia.
Clinical management should focus on medication optimisation
and mitigation of this increased risk.
 To understand the clinical features, pathogenesis and diagnosis
of sarcoidosis.
 To understand the effect of pregnancy on sarcoidosis.
 To understand the effect of sarcoidosis on pregnancy and the
related obstetric outcomes.
 To understand the management of sarcoidosis in pregnancy.
Ethical issues:
 There can be difficulties in appropriate management of medical
disorders, such as sarcoidosis, with a limited obstetric
evidence base.
 There are challenges in decision-making regarding continuation of
pregnancy in severe disease with an uncertain evidence base.
Keywords: immunomodulators | interstitial lung disease | obstetric
medicine | sarcoidosis | TH1 disorders

Please cite this paper as: Odendaal J, Mackie FL, Tosounidou S, Ghosh S, Knox E. Sarcoidosis in pregnancy. The Obstetrician & Gynaecologist 2024;26:66–74.
https://doi.org/10.1111/tog.12917

dependent on disease stage.5 Maternal deaths secondary to

Introduction
Sarcoidosis is a systemic disease characterised by the presence
of non-caseating granulomatous lesions. It predominantly
occurs as a multisystem disease. The aetiology remains
uncertain, although infectious and genetic contributors to its
pathogenesis have been proposed.1 The prevalence is thought
to be 19 per 100 000 with a reported prevalence in pregnancy
of 1 in 2000 to 1 in 10 464.2, 3 More recent studies have,
however, reported a lower prevalence in pregnancy than was
previously believed.2 Despite this, the overall the incidence is
thought to be increasing, possibly owing to better detection
rates.2 The condition is more common in women, with a
peak age of incidence between 20–40 years old. Women of
a Black African origin are more likely to experience severe
disease.4 The mortality of sarcoidosis varies from <5–10%
neuro- or cardiac sarcoidosis have previously been
reported.6,7 There remains a paucity of guidance on the
management of sarcoidosis in pregnancy. This review aims to
outline the clinical features of sarcoidosis, its impact in
pregnancy and the management of the condition. A key
overview can be seen in Figure 1.
Clinical features of sarcoidosis
The clinical presentation of sarcoidosis is dependent on the site
of presentation. Many patients may remain asymptomatic.
Pulmonary involvement is the most common presentation
in >90% of those affected.8 Pulmonary sarcoidosis is
predominantly an interstitial lung disease (ILD) with
progressive parenchymal fibrosis in up to 20% of people

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provided the original work is properly cited.
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Odendaal et al.

Figure 1. The inter-relationship between pregnancy and sarcoidosis. Upper panel: Regulation of sarcoidosis in pregnancy with increased
stimulation of T-regulatory cells resulting in suppression of TH1-based responses. Higher disease risk in those with pre-existing severe disease.
Lower Panel: Effect of active sarcoidosis on pregnancy.

with the condition.9 A significant subset of patients will also
develop pulmonary artery hypertension, a contraindication to
pregnancy.10 Pulmonary disease can be radiologically staged
using Scadding staging, as seen in Table 1. Extra-pulmonary
symptoms of sarcoidosis are common and include those
affecting the joints, liver, skin, heart, brain and eyes (Table 2).
Skin disease is the most common extra-pulmonary
manifestation of sarcoidosis;11 it may be specific and
associated with granulomas, such as lupus pernio, or non-
specific, including erythema nodosum, erythema multiforme
and nummular eczema.11 Up to 50% of patients will
experience cardiac symptoms, which can manifest as syncope
in women with no cardiac history.12,13 This is due to infiltrative
myocardial disease, which can cause life-threatening
arrhythmias in 2–7% of patients with sarcoidosis and lead to
sudden maternal, and subsequent fetal, death.6,13 Central
nervous system involvement of sarcoidosis can occur in 5–13%
of cases.14 The most common site for involvement is the cranial
nerves. Common symptoms of neurosarcoidosis include facial
nerve palsy, optic nerve dysfunction and papilloedema.
Pathogenesis of sarcoidosis
The pathogenesis of sarcoidosis is uncertain. The disease
represents an exaggerated immune response to an unknown
trigger.1 Acute sarcoidosis is associated with an increased

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Sarcoidosis in pregnancy

Table 1. Scadding staging of pulmonary sarcoidosis Table 2. (Continued)

Stage Features System Symptom

Stage 0 Normal Endocrine Hypothalamic and pituitary disturbances

Stage 1 Bilateral hilar adenopathy Thyroid abnormalities

Stage 2 Hilar adenopathy with pulmonary infiltration Central diabetes insipidus

Stage 3 Pulmonary infiltration without adenopathy Liver Liver granulomas usually asymptomatic

Stage 4 Pulmonary fibrosis Hepatomegaly (20%)

Splenomegaly (less common)

Gastrointestinal Rare but any part of the GI tract can be involved

Neurological Cranial mononeuropathy e.g. facial nerve palsy

Table 2. Symptoms of sarcoidosis (adapted from Frise and Collins)53
Neurosarcoid
System Symptom
Peripheral neuropathy e.g. mononeuritis multiplex

Systemic Fever Musculoskeletal Acute polyarthritis

Pulmonary Breathlessness Migratory polyarthralgia

Cough Electrolytes Hypercalcaemia

Cardiac (up to Syncope

50%)

Heart block and arrhythmias (2–7%) influx of CD14 macrophages.1,15 These have increased
responsiveness to distinct pattern-recognition receptor
Heart failure ligands.1 Organs affected by sarcoidosis display an influx of
Pericardial disease
T helper 1 (TH1) cells with increased cytokine production,
including interferon-c and tumour necrosis factor-a
Sudden cardiac death (TNF-a).16 This TH1 cytokine response is unattenuated, as
reduced expression of regulatory T cells (Tregs) has been
Skin Erythema nodosum (can occur in normal pregnancy)
demonstrated within sarcoidosis.1 Granulomas composed of
Subcutaneous nodules epitheloid cells develop within affected tissue.17 The
development of clusters of sarcoidosis is thought to be
Lupus pernio
evidence of the potential of an antigen-driven disease.
Eyes Uveitis Notable clusters of cases include those affecting the
metal-processing industries and emergency responders
Keratoconjunctivitis secca following the 2001 World Trade Center attacks.18,19
Eyelid or conjunctival granulomas
Diagnosis of sarcoidosis
Renal Calcium deposition and resultant renal failure
The diagnosis of sarcoidosis is predominantly one of
Sarcoid interstitial nephritis
exclusion, although multiple diagnostic scoring systems
Nephrogenic diabetes insipidus exist. The principle of diagnosis is based on three major
criteria: clinical presentation, non-caseating granulomas in
Membranous glomerulonephritis tissue samples and the exclusion of other granulomatous
Lymph Peripheral lymphadenopathy
disease.10 Initial investigations depend on the presenting
feature of concern. During pregnancy, investigations need to
be rationalised based on clinical risk in an attempt to minimise

68 ª 2024 The Authors. The Obstetrician & Gynaecologist published by John Wiley & Sons Ltd on behalf of Royal College of Obstetricians and Gynaecologists.

fetal radiation exposure and reduce risks associated with
obtaining samples for histopathological analysis.20 Chest
radiographs are considered safe during pregnancy and most
commonly will demonstrate bilateral hilar lymphadenopathy,
or fibrosis secondary to pulmonary infiltration. Sometimes the
infiltration is not apparent on chest radiograph, and high-
resolution computerised tomography (CT), bronchoalveolar
lavage and transbronchial biopsy are required to confirm
ILD. The decision to perform these investigations during
pregnancy would require discussion in a multidisciplinary
team and consideration of the risks and benefits to the
pregnant patient and fetus. More advanced imaging including
magnetic resonance imaging (MRI) may be considered. In
non-pregnant patients, serum angiotensin converting enzyme
(ACE) levels can be used for disease monitoring; however, as
ACE levels can be altered in pregnancy, they cannot be used in
pregnant patients.21
If cardiac symptoms are present, an electrocardiogram and
echocardiography are recommended to rule out other
differential diagnoses, but often non-specific changes are
seen in sarcoidosis. Cardiac MRI is useful in pregnant
patients and may demonstrate fibrosis, oedema and
scarring.13 In pregnant women, gadolinium-based contrast
enhancement may aid diagnosis, but as it can cross the
placenta, its use is controversial and a risk-benefit analysis
should be performed.22
If symptoms are suggestive of neurosarcoidosis, a brain
MRI may be useful; however, given the need for contrast, an
individualised approach to risk should be taken. Alternatively,
cerebrospinal fluid analysis may provide additional
information.10 The use of electromyography (EMG) can be
used to diagnose myopathy secondary to sarcoidosis.23
If the sarcoidosis is thought to affect other systems,
consideration needs to be given to the safety of additional
testing and whether it will change current management. For
example, malignancy may be a differential diagnosis which
needs to be ruled out in a timely fashion during pregnancy.
Histopathological confirmation on tissue biopsy may need to
be delayed until after pregnancy.
The effects of pregnancy on sarcoidosis
Pregnancy is widely believed to have no effect on or improve the
course of disease progression in sarcoidosis. Immune changes
associated with pregnancy result in an interaction of pregnancy
with sarcoidosis. Pregnancy induces a shift in immune cytokine
profile, traditionally thought to be from a TH1-expression
pattern to a Th2-expression pattern.24 While this view is
likely simplistic and a more complex interplay between Th
cells has been proposed, the resulting alterations lead to an
improvement in disorders characterised by a TH1 response,
including rheumatoid arthritis, multiple sclerosis and
sarcoidosis.24,25 This immune-mediated improvement has
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Odendaal et al.
borne out in the clinical data on sarcoidosis in pregnancy. An
early 1958 case series assessing 17 pregnancies in 10 women
demonstrated no consistent effect of pregnancy on the
disease.26 Similarly, a case series by Agha et al.27 assessed 35
pregnancies across 18 women with known sarcoidosis and
demonstrated one-third of the women had an improvement in
their symptoms, 9 of 18 showed no change in their disease, and
the remaining three women had a deterioration of their disease.
A more recent case report and review of the literature reported
on radiological regression of sarcoidosis in a 32-year-old
woman with sarcoidosis.28 A review of the literature
demonstrated contradictory reports on the clinical course of
sarcoidosis, with the majority of reported cases demonstrating
an improvement. Although the literature in this area is now
dated, it remains robust in illustrating a clinical improvement in
sarcoidosis in pregnancy in the majority, with risk of
deterioration, however, remaining. It has further been
proposed that this improvement may be secondary to
endogenous corticosteroid production occurring in
pregnancy.28 As with other TH1-mediated disease, a postnatal
flare of sarcoidosis is often seen. This increased risk may be
secondary to a reduction in endogenous maternal
corticosteroids or to a reversion to a TH1-mediated cytokine
state. Selroos et al.29 assessed 252 women presenting with
sarcoidosis over a 29-year period; 38 pregnancies were noted
within this cohort. Of note, 25 of these diagnoses were made
within a year of delivery, highlighting the clinical importance of
this postnatal flare. Careful postnatal planning is therefore
required in this cohort with use of flare suppression.
In addition to the disease process itself, consideration should
be given to the effect of pregnancy on the sequelae of
sarcoidosis, in particular that of severe disease. A common
sequela is ILD. Severe ILD based on a forced vital capacity
(FVC) <1–1.5 L is thought to be associated with increased risk
of maternal mortality.30,31 It has been suggested that in women
with severe ILD the increased oxygen demand in pregnancy
may result in decreased oxygen saturations due to parenchymal
fibrosis.30 This has led to the traditional recommendation of
avoidance of pregnancy in this cohort. A cohort study of
women presenting in pregnancy with pre-existing ILD assessed
86 pregnancies in 60 women.30 The majority of women in the
study (71%) had a diagnosis of sarcoidosis; 30 of these women
underwent echocardiography, which demonstrated evidence
of pulmonary hypertension in 4 women. No maternal deaths
were reported but 11% required supplemental oxygen at
delivery. This led the authors to conclude that in women
without heart failure, pulmonary hypertension or severely
active disease, pregnancy could be considered.
Similarly, cardiac sarcoidosis affects up to 39% of patients.10
The majority are asymptomatic; however, congestive heart
failure, arrhythmia and pericardial effusion may develop.
Cardiac sarcoidosis has a greater maternal risk than other
forms of the disease. While previous, now dated, case series
69

Sarcoidosis in pregnancy
have demonstrated improvement in cardiac sarcoidosis in
pregnancy, several case reports of adverse cardiac outcome
suggest the need for caution and careful multi-disciplinary
management in this cohort.6,13,32 Agrawal et al.13 reported on
the occurrence of syncopal attacks in a 43 year old at 21 weeks’
gestation. A diagnosis of cardiac sarcoidosis was made, and an
implantable cardiac defibrillator (ICD) was implanted to
manage intermittent runs of ventricular arrhythmia. Despite
this, the patient progressed into clinical heart failure. Similarly,
Wallm€ uller et al.6 reported on a case of maternal cardiac arrest
at 32 weeks’ gestation in a woman with known pulmonary
sarcoidosis. The post-mortem demonstrated a fibrotic
mid-ventricular wall scar secondary to sarcoidosis. These
cases reinforce the importance of vigilance in the management
of women at risk in pregnancy. Women with cardiac
sarcoidosis may have an ICD in-situ. Previous work has
demonstrated that pregnancy does not increase the risk of ICD
discharges or ICD-related complications.33 Indeed, the
importance of ICD management remains, and regular device
interrogation and consideration of device deactivation in
labour are advised.34 Although a mainstay of treatment, the use
of corticosteroids in cardiac sarcoidosis outside of pregnancy
has not demonstrated a reduction in the incidence of
ventricular arrhythmias.35,36 While there is no evidence for
their use in pregnancy, it is unlikely to have a differential
impact in comparison to the disease outside of pregnancy and
therefore may be used for similar indications. The use of
anti-TNF agents in refractory cardiac sarcoidosis is increasing.
The effects of sarcoidosis on pregnancy
The presence of sarcoidosis in pregnancy is associated with
adverse pregnancy outcome. Although data are limited by
small numbers, it is likely this effect is most marked in those
with active disease. The majority of current data stems from
two large cohort studies originating from the USA and
Sweden.2,37 These studies demonstrate relatively large sample
sizes for studies assessing sarcoidosis, representing 678 and
182 sarcoidosis cases, respectively. Nevertheless, the
registry-based approach limits conclusions on reproductive
outcomes or the impact of treatment. The studies are
summarised in Table 3. Further prospective registries
collecting this data in the sarcoidosis population would
improve knowledge in this area.
There is limited evidence on pregnancy outcome in
sarcoidosis. A 1999 consensus statement by the American
Thoracic Society reported no increased risk of miscarriage in
sarcoidosis.20 This finding, however, was based on a limited
evidence base of dated studies. A 1998 case series assessed
33 pregnancies in 11 women with sarcoidosis.38 The
study reported five miscarriages across the group, giving a
miscarriage rate of 15%, in keeping with the general
population. Nevertheless, there remains a paucity of current
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studies assessing miscarriage risk in the sarcoidosis cohort.
Similarly, there is no evidence of an increased risk of
intra-uterine death (IUD) or stillbirth in cases of sarcoidosis.
Hadid et al.2 in their US registry study assessed the rate of
IUD in their population amd demonstrated a non-significant
adjusted odds ratio of 1.23 (95% CI 0.61–2.48), while the
Swedish cohort showed <5/182 stillbirths, limiting the power
to definitively establish that there was no effect on
stillbirth rates.37
An increased risk of pregnancy-associated conditions is
ocher et al.’s Swedish registry study,37
seen in sarcoidosis. In K€
an increased risk of pre-eclampsia was identified in women
with sarcoidosis (RR 1.6; 95% CI 1.0–2.6). A similar finding
was also seen in Hadid et al.2 with a reported adjusted OR of
1.62 (95% CI 1.18–2.22). No significant difference was,
however, seen for pregnancy-induced hypertension, further
suggesting this relationship to be pathological in nature.
No significant difference was seen in the development of
gestational diabetes in either cohort.
An increased risk of maternal thromboembolism was seen
in women with sarcoidosis in the Hadid et al. study, with
both the risk of deep vein thrombosis (adjusted OR 4.92;
95% CI 1.58–15.33) and pulmonary embolus (adjusted OR
6.68; 95% CI 3.99–11.21).2 A similar increase in risk was not,
however, seen in K€ ocher et al.’s study, which reported no
cases of venous thromboembolism. These differences may be
secondary to differences in case selection, as Hadid et al.
selected cases with a registry label at the time of delivery,
suggesting a higher proportion with active disease.2,37 An
increased thromboembolic effect has previously been seen in
other systemic inflammatory conditions with active disease,
suggesting the importance of this confounder in clinical
decision making.39
Sarcoidosis has also been associated with increased fetal
risk. A single-centre case series over 11 years assessed 20
pregnancies, and a 10% risk of intrauterine growth restriction
was seen.40 This translates to the findings of larger cohort
studies, with Hadid et al. identifying a significantly increased
risk of fetal growth restriction (adjusted OR 1.62; 95% CI
1.08–2.43)2. An increased risk of preterm delivery was also
seen in both cohorts in women with sarcoidosis in
comparison to without, with an adjusted OR 1.73 (95% CI
1.40–2.15) and adjusted RR 1.7 (95% CI 1.1–2.5) in the US
and Swedish cohort, respectively.2,37 It is unclear, however,
the extent to which this finding was iatrogenic in origin due
to the development of secondary complications.
A similar increase in caesarean section rates was
demonstrated across cohorts with an adjusted OR of 1.20
(95% CI 1.03–1.40) and an adjusted RR of 1.3 (95% CI 1.0–
1.6) in the US and Swedish cohort, respectively.2,37 K€ ocher
et al. further evaluated this risk, demonstrating the increase
stems from emergency caesarean sections, as opposed to
elective procedures with an adjusted RR of 1.4 (95% CI 1.0–
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Odendaal et al.

Table 3. Key studies on the effect of sarcoidosis on pregnancy

Hadid, 20152 € cher, 202037

Ko

Study design Population-based cohort Population-based cohort

Study country USA Sweden

Study period 2003–2010 2002–2013

Sample size 678 182

Factors adjusted for Age, ethnicity, smoking, income and hospital Maternal age, year of delivery and maternal education
level. Additionally, adjusted for BMI and smoking in pre-
eclampsia, preterm birth and birth defects.

Outcomes

Stillbirth OR 1.23 (95% CI: 0.61–2.48) <5 cases

Pre-eclampsia OR 1.62 (95% CI 1.18–2.22) RR 1.6 (95% CI 1.0–2.6)

Venous thromboembolism DVT: OR 4.92 (95% CI 1.58–15.33) 0 cases

PE: OR 6.68 (95% CI 3.99–11.21)

Fetal growth restriction OR 1.62 (95% CI 1.08–2.43) <5 cases

Preterm delivery OR 1.73 (95% CI 1.40–2.15) RR 1.7 (95% CI 1.1–2.5)

Caesarean section OR 1.20 (95% CI 1.03–1.40) RR 1.3 (95% CI; 1.0–1.6)

Postpartum haemorrhage OR 1.69 (1.18,2.43) RR 1.1 (95% CI; 0.6–1.9)

Abbreviations: BMI = body mass index; DVT = deep vein thrombosis; OR = odds ratio; PE = pulmonary embolus; RR = relative risk.

1.9) in comparison with an adjusted RR of 1.3 (95% CI 0.8–

2.0). Of note, however, Hadid et al. assessed the odds of fetal
distress in the US cohort and no increased risk was identified
(adjusted OR 0.53; 95% CI 0.07–3.75).2 The increased risk
may, therefore, relate to alternate fetal or maternal concerns.
The risk of postpartum haemorrhage (PPH) was assessed
in both cohorts. Hadid et al. demonstrated an increased risk
of PPH in women with sarcoidosis (adjusted OR 1.69 [1.18–
2.43]). A similar increased risk was not demonstrated in the
Swedish cohort.37 This may be secondary to the presence of
confounders. A selection bias in favour of active disease has
already been described for the Hadid et al. study.
Furthermore, this study had a higher proportion of African
American women, with an associated independent increased
risk of PPH.41
A tendency to increased risk of fetal structural differences
was seen in K€ ocher et al., with 6.1% affected compared with
3.7% in the control population, although this difference
was not statistically significant when adjusted (RR 1.6; 95%
CI 0.9–2.8).37 No other increased neonatal risk has
been reported.
Management of sarcoidosis in pregnancy
Given its systemic nature, the obstetric management of
sarcoidosis necessitates a multidisciplinary approach. There is
a paucity of guidelines focused on management in pregnancy,
and the evidence on pregnancy-specific management is
currently scarce. The principles of management, however,
are consistent with other high-risk maternal disorders.
Firstly, this is to optimise current disease management,
preferably in a pre-conception setting. Baseline review should
consist of establishing current function and disease activity.
Selected use of pulmonary function tests may be undertaken,
however, these may not reflect disease activity, and, therefore,
use should be based on symptomatic pulmonary disease or
where clinical suspicion of reduced function exists.42 Baseline
investigations should include a full blood count, urea and
electrolytes, liver function tests, serum calcium and ACE
levels. A baseline electrocardiogram may be of benefit.42
Women with a suspected or confirmed diagnosis of cardiac
sarcoidosis should undergo an echocardiogram to exclude
structural disease.42 A 24-hour Holter monitor should be

ª 2024 The Authors. The Obstetrician & Gynaecologist published by John Wiley & Sons Ltd on behalf of Royal College of Obstetricians and Gynaecologists. 71

Sarcoidosis in pregnancy
undertaken in those symptomatic with palpitations.13 A
personalised multidisciplinary risk discussion, including the
woman, should be undertaken in those with severe ILD or
symptomatic cardiac sarcoidosis to determine the risk-to-
benefit ratio of embarking on or continuing with
a pregnancy.
Secondly, optimisation of medical management should be
undertaken. A range of medication are used to manage
sarcoidosis outside of pregnancy, not all of which are safe in
pregnancy. A standard management regime would be to manage
flares of sarcoidosis with suppressive immunotherapy, the most
common regime being the use of high-dose oral corticosteroids.42
Once flare repression is achieved, maintenance management is
through the use of a lower dosage corticosteroid regime. Use of
disease-modifying drugs for both disease suppression and
maintenance is not unusual. These include methotrexate,
mycophenolate mofetil (MMF), leflunomide and azathioprine.
Rarely, biological therapy with anti-TNF agents such as infliximab
is used in refractory sarcoidosis.
The safety profile of long-term corticosteroid use in
pregnancy has previously been well described.43 Dated
research has suggested a potential increase in fetal cleft
palate with corticosteroid use.44 This has not, however, been
seen in more recent studies.42,44,45 Additionally, there is no
increased risk of fetal growth restriction or preterm
delivery.44 An increased risk of gestational diabetes is seen
with long-term use and therefore an oral glucose tolerance
test is indicated.
Azathioprine has demonstrated a good safety profile both
in pregnancy and breastfeeding. A review conducted for the
British Society of Rheumatology demonstrated no increased
risk of fetal structural differences or adverse effect
on birthweight.45
Neither methotrexate nor MMF are safe for use in pregnancy
or breastfeeding. Methotrexate is a known teratogen associated
with both miscarriage and fetal structural differences.45 There is
some suggestion that low-dose methotrexate may carry a lower
risk profile but further data is required.46 MMF has been
associated with both fetal structural differences, including
microtia, facial clefts and micrognathia, and miscarriage.47
Fetal growth restriction has also been seen with MMF therapy.45
Both drugs are secreted in breastmilk and associated with a
theoretical risk to the neonate.45 In the absence of strong
evidence of safety these should be avoided in the breastfeeding
period. Importantly, these drugs also have a washout period
prior to pregnancy which should be considered. MMF should be
stopped at least 6 weeks prior to pregnancy, and methotrexate
should be stopped 4 weeks prior to pregnancy. Where
methotrexate is stopped within 4 weeks of conception,
high-dose folate (5 mg once daily) should be continued up to
12 weeks of pregnancy.45 Leflunomide is also contraindicated in
pregnancy. Animal studies have demonstrated teratogenicity in
those exposed.48 Limited evidence suggests a low risk in humans
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but given lack of clarity in the data it is best avoided.49 A washout
period of 11 days with a cholestyramine washout procedure is
required. It is suggested that when possible women of
reproductive age are switched to an alternate such as
azathioprine. If pregnancy occurs on leflunomide, the drug
should be stopped, a cholestyramine washout procedure given
and onward referral to fetal medicine considered.45
Finally, regarding the use of biologics in pregnancy, the
evidence demonstrates no difference in pregnancy outcome,
including that of fetal structural differences, in those on biologic
treatment, suggesting these as a safe third-line alternative in the
management of disease remission in pregnancy.50 Anti-TNF
agents including adalimumab or infliximab are commonly used
in the management of sarcoidosis. Their use is nuanced by
concern around neonatal immunological effects, particularly the
risk of immunosuppression with avoidance of live vaccines in
early life. This has led to guidance suggesting discontinuation of
infliximab after 20 weeks’ and adalimumab after 28 weeks’
gestation. It is, however, widely acknowledged that continuation
across the pregnancy is safe and usually favourable on a risk–
benefit balance.45,51 A more detailed discussion on the use of
biologics is outside the scope of this review; these are well
summarised by Soh and Moretto.51
Suggested guideline for antenatal,
intrapartum and postnatal care
The obstetric management of women with sarcoidosis is
dependent on the stage of the disease, level of activity and
presence of complications secondary to sarcoidosis. The
majority will be asymptomatic, with disease suppression
throughout pregnancy. Management therefore focuses on
risk stratification with those presenting with complications
managed in a multi-disciplinary fashion.
Pre-conception
Pre-conception care of sarcoidosis involves the optimisation
of management of the disease, including baseline tests, as
outlined previously. Consideration for underlying function
should be taken in making recommendations on proceeding
with pregnancy based on underlying physiological reserve
as discussed.
Antenatal
Women with a history of sarcoidosis should be managed
within a high-risk care pathway. Given the increased risk of
pre-eclampsia and fetal growth restriction, women should be
commenced on prophylactic aspirin from 12-weeks’ gestation.
The use of calcium and vitamin D-based supplements to
mitigate the risk of pre-eclampsia should be avoided in
sarcoidosis owing to abnormal calcium metabolism which
occurs in the disease.52 Serial ultrasound growth surveillance
should be undertaken. Given the increased risk of pre-

eclampsia, an enhanced monitoring regime built around
increased regularity of assessment of blood pressure and urine
should be considered antenatally. One model would be
fortnightly assessment from 24 weeks’ gestation followed by
weekly from 32 weeks’ gestation. The development of
maternal tachycardia or palpitations should be actively
investigated with thyroid function tests, a 24-hour Holter
monitor, maternal echocardiogram and maternal cardiac MRI
considered, dependent on the clinical presentation. As there is
an increased risk of thromboembolism, active sarcoidosis
should be considered a risk factor for VTE. This should be
taken into account in the provision of thromboprophylaxis.
Intrapartum
Intrapartum management in women with medical
complications such as ILD, heart failure or neurosarcoidosis
should be personalised and planned in conjunction with the
multidisciplinary team. Timing of delivery should be
determined based on disease control within pregnancy and
the emergence of complications of pregnancy such as pre-
eclampsia. Consideration of early delivery should be taken in
cases of severe active disease requiring more aggressive medical
therapy. While sarcoidosis alone is not an indication for
caesarean section, the underlying maternal physiological
reserve relating to both cardiac and respiratory disease
should be considered when discussing mode of delivery. An
alternative of vaginal delivery with a shortened second stage
may also be considered. In addition, certain presentations
of neurosarcoidosis may present with features of raised
intracranial pressure; in these cases, a vaginal delivery may be
contraindicated. The use of intrapartum oxygen may be of
benefit in those with known ILD.31 Careful fluid management
in labour is required in those with ILD to ameliorate the risk of
peri- or postpartum heart failure secondary to the fluid shifts
that occur following delivery.3
Postnatal
Postnatal planning should account for the increased risk of
disease flare in the postnatal period. Continuation or
resumption of maintenance therapy should be encouraged
with consideration of the safety profile of the medication in
breastfeeding mothers as outlined previously. Early follow-up
by the medical team should be arranged. Counselling on
postnatal contraception should be undertaken with clinical
decision-making on type based on maternal wishes and
accounting for maternal sequelae of sarcoidosis.
Conclusion
In conclusion, while women with sarcoidosis are likely to
experience remission within pregnancy, they remain at
increased risk of developing serious complications of the
disease both within pregnancy and in the immediate
ª 2024 The Authors. The Obstetrician & Gynaecologist published by John Wiley & Sons Ltd on behalf of Royal College of Obstetricians and Gynaecologists.
17444667, 2024, 2, Downloaded from https://obgyn.onlinelibrary.wiley.com/doi/10.1111/tog.12917, Wiley Online Library on [17/04/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
Odendaal et al.
postnatal period. In addition, they present higher obstetric
risk. Careful multidisciplinary management is therefore
required. There remains, however, a paucity of high-quality
evidence on the management of sarcoidosis in pregnancy,
and further studies are required.
Disclosure of interests
JO has no financial interests to declare. RCOG roles include:
RCOG Elearning Editor (Trainee) and Member of the RCOG
Learners Working Group.
FM has no financial interests to declare. RCOG roles
include: RCOG Elearning Editor (Trainee).
ST has no financial interests to declare. Author on British
Society for Rheumatology guideline on prescribing drugs
in pregnancy.
SG has no financial interests to declare. RCOG role: Part 3
MRCOG Clinical Assessment Sub-committee.
EK has no financial interests to declare.
Contribution to authorship
FM, ST, SG and EK conceived the manuscript. FM undertook
early design. JO undertook further design and manuscript
composition. All authors provided critical feedback on the
manuscript and approved the final version.
Supporting Information
Additional supporting information may be found in the
online version of this article at http://wileyonlinelibrary.
com/journal/tog
Infographic S1. Sarcoidosis in pregnancy.
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