Winter (Volume 28, Number 4)
Top Six Things Rheumatologists Should (And Might Not) Know About Pregnancy and Rheumatic Diseases
By *Neda Amiri, MD, FRCPC, MHSc; Maeve Gamble, MD, FRCPC; Elizabeth Hazel, MDCM, FRCP(C);
Shahin Jamal, MD, FRCPC, MSc; Stephanie Keeling, MD, MSc, FRCPC; Dianne Mosher, MD, FRCPC;
*Viktoria Pavlova, MD, FRCPC; *Sarah Troster, MD, FRCPC; and Ola Wierzbicki, MD, FRCPC
*Members of The Canadian Pregnancy and Rheumatic Diseases Consortium
The Canadian Pregnancy and Rheumatic Diseases Consortium*
is a national database for the prospective observational
study of pregnant patients with rheumatic disease,
with sites at many academic centers across Canada.
The 10th International Conference on Reproduction, Pregnancy and Rheumatic Diseases was held in
Bern, Switzerland from Sept 27-29, 2018, and attended by several Canadian rheumatologists. We, of
course, missed Carl Laskin, who has inspired so many of us! Key learnings include the following:
It is well known that low disease activity prior to conception
results in better pregnancy outcomes, both for mom
and baby. Unfortunately, 40-50% of pregnancies are unplanned.
With the shortage of primary health care in Canada,
the discussion surrounding contraception often falls
to the rheumatologist. The Canadian Contraception Consensus1
is a current and thorough resource to help guide
discussion with patients, particularly those without access
to primary care.
Subfertility is reported in up to 48% of
women with rheumatoid arthritis (RA);
twenty-eight per cent (28%) of which
is due to anovulation and 48% being
unexplained. Higher maternal age,
medication use (such as non-steroidal
anti-inflammatory drugs [NSAIDs])
inhibiting ovulation, and low health-related
quality of life (HRQoL) all contribute.
Infertility treatment (IVF) is a
safe option for women with connective
tissue disease (CTD).
3. Pre-pregnancy Counselling
A key question we should be asking
regularly to all women of childbearing
age is “Would you like to become
pregnant in the next year?” Pregnancy
preparation in our patients is important
and often begins months prior
to conception. Start with a realistic
risk assessment, stop harmful medications, use pregnancy
compatible medications prior to conception, and reassure
the patient. A risk assessment should include: previous
pregnancy complications (preeclampsia), organ damage,
recent/current disease activity, antibody status (lupus anti-
coagulant [LAC], anti-cardiolipin [aCL], beta-2 glycoprotein
1 [2GPI], Ro/La), exposure to fetotoxic drugs, smoking
and other chronic medical conditions.
4. Pregnancy Compatible Medications
“Safe treatment in pregnancy” should be understood as
“no evidence of risk,” and as the safest option among
eligible drugs and compared to the risk of untreated
disease. Refer to the EULAR Points to Consider,2 BSR
Guidelines3 and RheumInfo Pregnancy and Lactation
brochure.4 Prednisone use in any trimester is an independent
risk factor for preterm birth. Higher doses are
associated with shorter gestational length. Medication
use in lactation is poorly studied: LactMed5, a National
Institute of Health (NIH) database, is updated monthly,
and reports drug levels in milk, the infant, and possible
adverse effects to the infant.
5. Peripartum Monitoring
Active CTD can be associated with defective placentation
which leads to placental insufficiency, preeclampsia, intrauterine
growth restriction (IUGR), and HELLP syndrome.
Monitoring during pregnancy may include the following:
- Screening for Ro/La antibodies. Risk of congenital
heart block (CHB) is 1-2% overall and 10-20% in
those with previous CHB. It develops between 18-24
weeks gestation and can be monitored by fetal echo.
Hydroxychloroquine (HCQ) reduces risk by 50%. Once
developed, the only proven treatment is a pacemaker.
- Doppler screening for fetal growth restriction.
- New markers for preeclampsia g (placental growth
factor [PLGF]), soluble fms-like tyrosine kinase-1
6. Pregnancy Behavior with Various Rheumatic Diseases:
- Inflammatory arthritis (IA): Patients with stable IA
generally have good outcomes. In RA, 29% flare during
pregnancy, with higher risk in the third trimester and
postpartum. SpA patients have higher risk of flare in
the second trimester, whereas patients with juvenile
idiopathic arthritis (JIA) tend to flare in the first few
months postpartum. The risk of flare is higher when
there is active disease at conception and when TNF
inhibitors are discontinued.
- Systemic lupus erythematosus (SLE): SLE in pregnancy
mimics SLE prior to pregnancy: Prior to pregnancy you
would want to see quiet nephritis, stable x 6 months,
proteinuria < 1 gram/day, and no active sediment.
Flare risk is low (< 3%) with inactive or stable active
disease at conception and flare is reduced by 50% with
HCQ, which should be continued through pregnancy.
Helpful resources include RheumInfo4 and the Healthy
Outcomes in Pregnancy Hop-Step Program.5
- Obstetric Antiphospholipid Syndrome (OAPS):
OAPS is characterized by defective placentation
(not placental infarction as previously thought).
Beta-2-glycoprotein (ß2GPI) plays a pivotal role in
the pathophysiology of OAPS and has potential as
a screening tool. Seronegative OAPS has also been
described. The soon to be published “Management
of Maternal Antiphospholipid Syndrome”7 includes
treatment options according to clinical features.
Maternal follow-up is recommended, as 20-60% of
women with OAPS will eventually develop thrombosis
- Systemic sclerosis (SSc): Pregnancy has minimal impact
on disease activity of patients with SSc. However, SSc
is associated with higher risk of maternal (gestational
hypertension, preeclampsia) and fetal (miscarriage,
stillbirth, IUGR, preterm birth) complications. Severe
pulmonary arterial hypertension (> 25mm Hg) is an
- Takayasu Arteritis (TA): TA is associated with increased
risk of gestational hypertension and preeclampsia.
Patients with severe aortic valvular disease, aortic
aneurysms and dissections have increased morbidity
and mortality and should be counselled to avoid
- Behcet’s Disease: Patients with Behcet’s Disease have
no apparent increase in maternal, obstetrical or fetal
complications during pregnancy. (See 2018 update of
EULAR recommendations for Behcet’s)8
Sarah Troster, Edmonton AB, Neda Amiri, Vancouver BC, Dianne Mosher, Calgary AB,
Viktoria Pavlova, Hamilton ON, Ola Wierzbicki, Hamilton ON, Elizabeth Hazel, Montreal QC,
Shahin Jamal, Vancouver BC, Stephanie Keeling, Edmonton AB, Maeve Gamble, London ON
The authors would like to thank
Treena Jeffray and UCB Canada Inc. for their financial
support enabling attendance at the meeting and scientific
Neda Amiri, MD, FRCPC, MHSc;
Maeve Gamble, MD, FRCPC;
Elizabeth Hazel, MDCM, FRCP(C);
Shahin Jamal, MD, FRCPC, MSc;
Stephanie Keeling, MD, MSc, FRCPC;
Dianne Mosher, MD, FRCPC;
Viktoria Pavlova, MD, FRCPC;
Sarah Troster, MD, FRCPC; and
Ola Wierzbicki, MD, FRCPC
1. Canadian Consensus on Contraception Available at https://sogc.org/clinical_practice_guidelines_eng/index.html. Accessed November 2018.
2. Skorpen CG, et al. The EULAR Points to consider for use of antirheumatic drugs before pregnancy, and during pregnancy and lactation. Annals of the Rheumatic Diseases 2016; 75:795.
3. Flint J, et al. BSR and BHPR guideline on prescribing drugs in pregnancy and breastfeeding – Part I: standard and biologic disease modifying anti-rheumatic drugs and corticosteroids. Rheumatology 2016; 55:1693.
4. RheumInfo Patient Brochures. Available at https://rheuminfo.com/living-with-arthritis/. Accessed November 2018.
5. LactMed. Available at https://www.toxnet.nlm.nih.gov/newtoxnet/lactmed.htm. Accessed November 2018.
6. Hop Step Program. Available at hopstep.flywheelsites.com (http://lupuspregnancy.org/). Accessed November 2018.
7. Fernandes et al. Management of Maternal Antiphospholipid Syndrome 2018. In press.