Table 3.

Immunosuppressive medications in pregnancy.⁸⁷

Drug	Mechanism	Placenta	Adverse effects	Pre pregnancy recommendation	Use in pregnancy
Corticosteroids87	Decreases inflammation Exerts effect through genomic mechanisms by binding to DNA	Prednisolone 90% inactivated by placental 11-β hydroxylase (10% crosses placenta) Dexamethasone crosses placenta	Fetal adrenal suppression Congenital cataracts Fetal immunosuppression for 15 weeks postpartum Neonatal CMV infection Preterm delivery if dose >20 mg during late pregnancy Maternal hypertension and gestational diabetes	No need to discontinue	May continue during pregnancy
Azathioprine (Imuran)87	Purine Analog	Crosses placenta but fetus is unable to metabolize to active form	IUGR Bone marrow suppression in fetus Immunosuppression in fetus	No need to discontinue	May continue during pregnancy Dose should not exceed 1.5–2 mg/kg/day
Cyclosporine87	Inhibits DNA transcription	Crosses placenta	Preterm birth Low birth weight No increase in birth defects	No need to discontinue	May continue during pregnancy
Hydroxycholorquine82,87,88	Accumulates in melatonin containing structure in fetus (uveal tract and inner ear)	Crosses placenta	No increase in birth defects No retinal or ototoxicity in fetus	Long elimination half life but no need to discontinue	May continue during pregnancy
Sulfasalazine (Azulfadine)87	Dihydrofolate reductase inhibitor	Crosses placenta	No birth defects No IUGR	No need to discontinue	May continue during pregnancy Maternal dose should not exceed 2 g
Intravenous immunoglobulin89	Decrease antibody mediated disease	No adequate studies in women but most likely IgG fraction crosses placenta	No definite adverse fetal effects related to drug	No need to discontinue	Relatively safe to use in pregnancy Useful for antiphospholipid antibody syndrome
TNF-α antagonists (infliximab or Remicade, etanercept or Enbrel, adalimumab or Humira)87	Biologic agent: binds soluble TNF-α	No adequate studies in women	No birth defects Not teratogenic	Short half life Can be discontinued after the first missed menstrual period	Discontinue after first missed period Unclear if can continue during pregnancy
Cyclophosphamide (Cytoxan)87,90	Alkylating agent	Crosses placenta	Teratogen: causes birth defects if given in first trimester IUGR Developmental delay in childhood IUFD/stillbirth	Stop prior to conception	Contraindicated
Leflunomide (Arava)87	Pyrimidine synthesis inhibitor	Crosses placenta	Congenital malformations	Long half-life Must be removed with cholestyramine or active charcoal and pregnancy attempted only when active plasma metabolite <0.02 mg/dl	Contraindicated Discontinue 9 months prior to conception
Methotrexate (Rheumatrex)87	Folic acid antagonist	Crosses placenta	Miscarriages Congenital anomalies	Remains in tissue for 2 months after stopping	Contraindicated Stop 3 months prior to conception
Mycophenolate mofetil (Cellcept)87	Inhibits purine synthesis	Crosses placenta	Causes miscarriages Causes birth defects	Withdraw prior to conception	Contraindicated

CMV, cytomegalovirus; IUFD, intrauterine fetal demise; IUGR, intrauterine growth restriction; TNF-α, tumor necrosis factor-alpha