Table 3:
Use of immunosuppressive medications, including pregnancy categories, transplacental passage, and associated maternal and fetal complications
| Immunosuppressive medication | Category | Transplacental passage | Maternal complications | Fetal complications | Evidence for use in pregnant state |
|---|---|---|---|---|---|
|
Glucocorticoids (Prednisone, prednisolone) |
C | 10% | Increases lower urinary tract infections, gestational diabetes, and gestational hypertension | Earlier associated with cleft palate (not proven), transient adrenal insufficiency, thymic hypoplasia |
Safely used in glomerular diseases as first line of agent and kidney transplant settings Boluses of IV steroids (up to 500 mg/day) in rapidly progressive GNs, otherwise maintenance dosing |
|
Calcineurin inhibitors (Cyclosporine, tacrolimus) |
C | 50–70% (based on drug trough levels in fetus in comparison to mother) | Worsening of gestational hypertension and diabetes (in prone patients) | Some case series have indicated a heightened likelihood of low birth weight and preterm birth with the use of tacrolimus. However, these studies have concluded that this correlation is likely attributable to the maternal state rather than the medications.72,73,84 Due to documented cases of hyperkalemia and renal dysfunction in infants who have been exposed, it is recommended to closely monitor renal function and potassium levels in these newborns. Long-term risk of CKD unknown | In SLE flares, quiescent LN, membranous glomerulonephritis |
| Azathioprine | D | Active metabolite, 6-mercaptopurine does not cross placenta | Gastrointestinal side effects, bone marrow suppression, including cytopenias, increased risk of infections | Transient lymphopenia | In quiescent LN, kidney transplant recipients |
| Mycophenolate mofetil (MMF) | D | Gastrointestinal side effects, bone marrow suppression, activation of viral infections | MMF embryopathy—ear, mouth, fingers, ocular organ malformation (EMFO tetrad) (risk of malformations 20%) | Mycophenolate Mofetil (MMF) should be discontinued six weeks prior to planned pregnancies | |
| Cyclophosphamide | D | Congenital malformations, suppressed bone marrow function, neuronal defects reported | Discontinued 12 weeks prior to pregnancies; anecdotally used in second and third trimesters in severe LN, AAV76 | ||
| Hydroxychloroquine | C | Transferred easily (nearly 100%) with similar maternal and cord blood levels | Gastrointestinal side effects, retinopathy | No increase in congenital malformations in fetus noted | Evidence for use in pregnancy is strong (from systematic review and meta-analysis), also decreases the risk of neonatal heart blocks in pregnant females of SLE positive for Ro antibodies |
| Intravenous immunoglobulins (IVIG) | IgG is transferred most easily (90–160%), more so in the third trimester | Systemic inflammatory and allergic reactions, hemolysis, aseptic meningitis | Normal lymphocyte counts observed in neonates born to mothers administered (IVIG) Intravenous immunoglobulin | Case reports mention use as part of combined protocols with dose of IVIG of 200–400 mg/kg/dose described in LN, AAV45,78 | |
| Rituximab | C | As it is chimeric IgG1, it can cross transplacental barrier easily via Fc receptors | Infusion reactions, peripheral B-cell depletion up to six months | Neonatal B cell depletion and nonspecific malformation syndromes (causation unclear) | Case reports in LN, membranous glomerulonephritis.74 AAV exist of rituximab use during and shortly prior to pregnancy with successful outcomes. Rituximab should be discontinued at least 6–12 months before conception, but use in exceptional circumstances is relatively safer in first trimester than others |
| Eculizumab81 | C | It is likely to cross placenta less well than other monoclonal antibodies as IgG2 (which is present in the drug’s Fc portion) transfers poorly across placenta | Safe with respect to maternal outcomes | None | Used in the management of pregnancy-associated HUS. Due to the limited availability of evidence on eculizumab in pregnancy, it is not possible to entirely rule out potential dangers for both the mother and fetus |
AAV: Antineutrophil cytoplasmic antibody-associated vasculitides, LN: Lupus vasculitis, SLE: Systemic lupus erythematosus, GN: Glomerulonephritis, HUS: Hemolytic uremic syndrome