Management of Rheumatologic Diseases in Pregnancy

Oier Ateka-Barrutia; Catherine Nelson-Piercy

Int J Clin Rheumatol. 2012;7(5):541-558.

Abstract

Rheumatic diseases include a variety of chronic multisystem disorders with a high percentage of autoimmune conditions. Many of these diseases affect women of child-bearing age, and so pregnancy poses an important challenge for doctors looking after these women. Knowledge about medication safety, the effect of pregnancy on such diseases, and vice versa, together with preconception counseling and multidisciplinary team care, are basic pillars needed to provide the best obstetric and medical care to these women. In this review, the management of the most common autoimmune rheumatic diseases prior, during and after pregnancy will be discussed, along with the most relevant issues regarding medications.

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Table 1. Safety of drugs in rheumatic diseases in pregnancy and breastfeeding.
Drug	US FDA class	Safety
		Pregnancy	Breastfeeding
NSAIDs	B (but D if >30 weeks of gestation)	Safe (if <30 weeks and intermittent use)	Safe
COX-II inhibitors	C (but D if >30 weeks of gestation)	Unknown	Unknown
Aspirin/dipyridamole	B	Safe	Safe
Clopidogrel/ticlopidine	B	Safe (but stop prior to delivery)	Probably
Hydroxychloroquine	C	Safe	Safe
Prednisolone/methylprednisolone	C	Safe	Safe
Azathioprine	D	Safe	Safe
Sulfasalazine	B	Safe (folate 5 mg once daily supplementation preconception and throughout pregnancy)	Safe
Ciclosporin	C	Safe	Probably
Tacrolimus	C	Safe	Probably
Mycophenolate	D	Avoid (consider in second–third trimester if severe disease)	Avoid
Methotrexate	X	Avoid	Avoid
Leflunomide	X	Avoid	Avoid
Cyclophosphamide	D	Avoid (consider in second–third trimester if severe disease)	Avoid
Anti-TNF agents	B	Safe (first and second trimesters)	Safe (not excreted in breast milk and probably broken down by the baby's GI tract)
Certolizumab	B	Probably	Probably
Anakinra	B	Probably	Probably
Rituximab	C	Avoid (consider in severe disease)	Unknown (probably)
Abatacept	C	Unknown	Unknown (probably)
Tocilizumab	C	Unknown	Unknown (probably)
Belimumab	C	Unknown	Unknown (probably)
Intravenous immunoglobulins	C	Safe	Safe
Endothelin receptor antagonists	X	Avoid	Avoid
Phosphodiesterase 5-inhibitors	B	Safe	Safe
Prostaglandin derivatives	B	Safe	Safe
Labetalol	C	Safe	Safe
Methyldopa	B	Safe	Safe
Nifedipine/amlodipine	C	Safe	Safe
Hydralazine	C	Safe	Safe
Doxazosin	C	Safe	Avoid if possible
Angiotensin converting enzyme inhibitors	C (first trimester)/D (second–third trimesters)	Avoid	Safe
Angiotensin receptor blockers	C (first trimester)/D (second–third trimesters)	Avoid	Probably
Warfarin	X	Avoid	Safe
Bisphosphonates (oral/iv.)	C/D	Avoid	Avoid
Statins	X	Avoid	Avoid

GI: Gastrointestinal; iv.: Intravenous.

Sidebar

Executive Summary

Fertility in women with rheumatic diseases is generally not affected, although chronic kidney disease, amenorrhea due to cyclophosphamide, active disease and NSAIDs may reduce fertility.

Systemic Lupus Erythematosus

Pregnancy should be planned when the disease has been in remission for at least 6 months.
Unless there are contraindications, all systemic lupus erythematosus patients should remain on hydroxychloroquine throughout and after pregnancy.
Systemic lupus erythematosus patients are at risk of multiple medical and obstetric complications during pregnancy, especially those with active disease and/or nonreversible organ damage.

Rheumatoid Arthritis & Other Arthritides

Approximaetly 50–66% of women with rheumatoid arthritis, and the majority of women with psoriatic arthritis and junior rheumatoid arthritis improve in pregnancy. By contrast, most women with ankylosing spondylitis stay unaltered or worsen.
Postpartum flares occur within the first 4 months in most patients with chronic inflammatory arthritides.
Women with chronic inflammatory arthritides, especially those with active disease, have higher risk of preterm delivery and small for gestational age babies. Patients with rheumatoid arthritis have a higher risk of hypertensive disorders in pregnancy.

Scleroderma/Systemic Sclerosis

Pregnancy does not seem to affect disease activity in the majority of women with systemic sclerosis.
Systemic sclerosis is associated with increased risk of developing hypertensive disorders in pregnancy and higher rates of adverse pregnancy outcome.
A previous renal crisis does not contraindicate further pregnancies, but pregnancy should be delayed for several years until the disease stabilizes.
Corticosteroids for fetal lung maturation should not be given as they may precipitate a renal crisis.

Vasculitis

Overall, if the disease is in remission pre-pregnancy a low rate of complications and good pregnancy outcomes are reported.
Hypertensive disorders, including preeclampsia, are associated with poorer outcomes.

Antiphospholipid Antibodies & Antiphospholipid Syndrome

Antiphospholipid antibodies represent one of the major risk factors for poor obstetric outcome.
Women with double or triple positivity, and/or those with thrombotic antiphospholipid syndrome have the worst obstetric outcomes.

Undifferentiated Connective Tissue Disease, Polymyositis/Dermatomyositis & Mixed Connective Tissue Disease

Outcomes of patients with undifferentiated connective tissue disease and mixed connective tissue disease resemble those seen in systemic lupus erythematosus.
Active polymyositis/dermatomyositis is related to preterm delivery and pregnancy loss.

Neonatal Lupus Syndromes

In patients with anti-Ro and/or anti-La, cutaneous neonatal lupus is seen in approximately 5% of their offspring, whereas congenital heart block is seen in approximately 2%.
Repeated fetal echocardiograms from the 18th week of gestation are recommended in women with these antibodies.

Medications

Azathioprine, sulfasalazine, ciclosporin and tacrolimus are safe in pregnancy and lactation.
Steroids are safe but related to side effects and complications if used for long periods and at doses of prednisolone >7.5 mg/day. Limited boluses of methylprednisolone are safe.
Among biologics, anti-TNF agents seem to be safe in the first and second trimesters and lactation.

Pregnancy Management Plan

Pre-pregnancy assessment is vital, with emphasis on previous obstetric and medical history, serology profile, disease activity and the extent of any organ damage.
An individual antenatal and postnatal plan and multidisciplinary team input are essential to achieve good maternal and fetal outcomes.

Postpartum

Close surveillance for 2–3 months after delivery is important owing to the high risk of disease flare and thrombosis.
Counseling on contraception should be incorporated as routine care at this stage.