Dr. Carl Laskin reviewed his approach to pregnancy in rheumatic disease by walking us through three patients with different rheumatic diseases, including RA, SLE and AS. Common to all rheumatic conditions is the pre-pregnancy assessment. This should include evaluation of clinical disease activity, last disease flare, recent lab profile, and medications. Patients with clinically and laboratory quiet disease, who are not on concerning medications, can then be given a “green light” to proceed with pregnancy. Patients with active disease should be optimized prior to pregnancy and potentially teratogenic medications should be stopped. The challenge, always, is when patients who are not “optimized” for pregnancy become pregnant anyways and the decision to terminate should be made on a case by case basis.
Rheumatoid arthritis typically improves during pregnancy with a high risk of flare post-partum. AS can remain quiet, improve or worsen during pregnancy. Labor and delivery decisions should be left to the obstetrician.
Pregnancy with lupus is more complex. If patients have stable disease in the prior 6 months, their risk of lupus flare during pregnancy is the same as if they were not pregnant. As there is a higher risk of pre-eclampsia and preterm labor (particularly in those with renal disease), low dose ASA is recommended throughout pregnancy. It is also important to remember that anyone with underlying renal disease will have increasing proteinuria around 20wk gestation because of changes in renal plasma flow and NOT because of active nephritis. This is an independent risk factor for pre-eclampsia. Lupus flare can be difficult to differentiate from pre-eclampsia. The differences are listed below:
Lupus Flare | Pre-eclampsia |
Low complement | High complement |
Normal uric acid | High uric acid |
Proteinuria and active urine sediment | Proteinuria |
Extra-renal manifestations | Elevated BP |
How they presented is how they flare | Hyperreflexia |
Elevated dsDNA | Elevated LFTs |
Using the cases, Dr. Laskin went on to review safety of our medications during pregnancy.
MTX: Methotrexate is teratogenic with a rate of fetal anomalies ranging from 9-17%. A study of 49 pregnancies published in January 2015 reported a rate of anomalies in pre-conception exposure of 3.5%, regardless of when MTX was discontinued. The rate in post-conception was 6.6%. Based on this data, we may not need to hold MTX for an entire 3 months prior to conception. More data is needed before we can change how we counsel patients. However, if someone becomes pregnant before the 3-month period, we probably don’t need to advise termination. MTX should be stopped with breastfeeding.
Prednisone: The risk of clefting is 1 in 400-500 women taking prednisone in the first trimester. The risk in the general population is 1 in 800-1000. In the third trimester, there is a risk of hypertension and prematurity with prednisone.
NSAIDs: Naproxen and ibuprofen are the preferred NSAIDs in pregnancy. They can affect rupture of follicular ovulation in 10%, leading to difficulty with conception. They are generally safe in the second trimester but should be stopped 6-8 weeks before delivery as there is increased risk of oligohydramnios, prolonged labor, premature closure of the ductus arteriosus, gastroschisis, bleeding at delivery and fetal intracranial hemorrhage.
Biologics: These are likely safe in the pre-conception period and throughout pregnancy. Tocilizumab, abatacept and anakinra can theoretically affect implantation. The excretion of biologics in breast milk varies between products. Compared to maternal concentrations, the concentrations of etanercept in breast milk was 30%, infliximab 100% and certolizumab 0%.
Dr. Jamal is a Clinical Associate Professor at the University of British Columbia and an active staff physician at Vancouver Coastal Health. Her interests include diagnosis and prognosis of early inflammatory arthritis, and timely assessment and access to care for patients with rheumatoid arthritis.
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