|
| Class | Side effects on pregnancy and foetus | Recommendations |
|
| Corticosteroids |
| Prednisolone | (i) Foetal: cleft palate/lip, foetal growth retardation, adrenal suppression, neonate cataract [99, 100]
(ii) Maternal: glucose intolerance, hypertension, osteopenia | (i) Food and Drug Administration Category B drug
(ii) May be used in pregnancy and breastfeeding
(iii) Ideally use prednisolone doses of ≤10 mg/day
(iv) May need stress dosing (hydrocortisone/methylprednisolone) at labour, delivery, immediate postpartum period [63, 101]
(v) Prednisolone level in milk is <0.1% of the prednisolone dose ingested by the mother Minimise exposure by nursing 4 hours after dose is taken if daily dose exceeds 20 mg [102, 103] |
|
| Antimetabolites |
Azathioprine
6-Mercaptopurine | (i) Foetal: the foetal liver lacks the enzyme, inosinate pyrophosphorylase, which converts azathioprine to active metabolites; therefore the fetus is protected from the adverse effects of azathioprine (especially early pregnancy) [104]
(ii) Paternal: male fertility and pregnancy do not seem to be affected [105] | (i) Food and Drug Administration Category D drug
(ii) Has been used in pregnancy for many years [64]
(iii) Ideally use doses <2 mg/kg/day. Consider decreasing dose at 32 weeks [63]
(iv) Breastfeeding is not recommended [106] |
| Methotrexate (MTX) | (i) Foetal: miscarriage, congenital malformations (limb defects, cranial and central nervous system abnormalities) especially in first trimester
(ii) Paternal: oligospermia (may be irreversible) | (i) Food and Drug Administration Category X drug
(ii) Cease 3 months before conception (male and females), continue folic acid after stopping MTX and during pregnancy
(iii) Not considered safe in breastfeeding due to inadequate data |
| Mycophenolate mofetil (MMF) | (i) Foetal: congenital malformations (distinctive MMF embryopathy), abortions (especially in first trimester)
(ii) Paternal: male fertility and pregnancy do not seem to be affected | (i) Food and Drug Administration Category D drug
(ii) Avoid in pregnancy
(iii) Use of MMF in pregnancy has not been widely studied; however available reports suggest avoiding MMF if possible during pregnancy [107–109]
(iv) Cease >6 weeks before conception attempted [63]
(v) MMF is often switched to azathioprine during pregnancy [65]
(vi) Breastfeeding is not recommended [65] |
|
| T-cell inhibitors |
| Cyclosporine | (i) Foetal: infant T-, B-, NK-cell development abnormalities [110]
(ii) Maternal: renal impairment, hypertension, lymphoma
(iii) Paternal: male fertility and pregnancy do not seem to be affected | (i) Food and Drug Administration Category C drug
(ii) May be used during pregnancy
(iii) Dosage 2.5–5 mg/kg/day—not recommended for use in breastfeeding. However, there have been reports of use in breastfeeding without adverse effects [111]
|
| Tacrolimus | (i) Foetal: risk of congenital malformations and abortions | (i) Food and Drug Administration Category C drug
(ii) Insufficient information to recommend use in pregnancy
(iii) Avoid breast feeding |
|
| Interferon |
| Interferon-2a | (i) Foetal: not teratogenic in animal studies | (i) Food and Drug Administration Category C drug
(ii) American College of Paediatricians classifies interferon-2a as safe in pregnancy and breastfeeding
(iii) However, given the limited data on human studies, it should be avoided in pregnancy ideally |
|
| Anti-TNF |
Infliximab
Adalimumab
Etanercept | (i) Foetal: possible risk of VACTERL (vertebral anomalies, anal atresia, cardiac defects, tracheoesophageal fistula, esophageal atresia, renal anomalies, limb dysplasia). Currently effects are still uncertain [62, 112–115]
(ii) TNF antagonists may affect fertility [116] | (i) Food and Drug Administration Category B drug
(ii) Not recommended for use in pregnancy and breastfeeding, unless potential benefits outweigh the potential risks [63]
(iii) Limited data on infliximab use in lactation, therefore should avoid breastfeeding (iv) Cease infliximab for 6 months before starting breastfeeding |
|
| Anti-CD 20 B-cell inhibitor |
| Rituximab | (i) Foetal: case reports of granulocytopenia and lymphopenia | (i) Food and Drug Administration Category C drug
(ii) Not recommended for use in pregnancy and breastfeeding, unless potential benefits outweigh the potential risks
(iii) Cease 1 year before attempting conception |
|
| Interleukin-1 receptor antagonist |
| Anakinra | (i) Foetal: no toxicity demonstrated in animal studies | (i) Food and Drug Administration Category B drug
(ii) Only use in pregnancy and lactation if needed to suppress disease activity |
|
| Alkylating agents |
| Cyclophosphamide | (i) Foetal: congenital malformation (craniofacial and distal limb defects), developmental delay [117]
(ii) Maternal: infertility, amenorrhoea, ovarian failure
(iii) Paternal: oligospermia (may be irreversible) [118–120] | (i) Food and Drug Administration Category X drug
(ii) Absolutely contraindicated in the first trimester but may be used in latter half of pregnancy [64]
(iii) Cease 3 months before attempting conception
(iv) Contraindicated in breastfeeding [121] |
|
| Dihydrofolate reductase inhibitor |
| Sulfasalazine | (i) Foetal: kernicterus, agranulocytosis, no significant increase in congenital abnormalities [62, 122–124]
(ii) Paternal: oligospermia (reversible) | (i) Food and Drug Administration Category B drug
(ii) Probably safe for use in pregnancy [124] and breastfeeding [125, 126] |
|
| Intravenous Immunoglobulin therapy |
| | | (i) Food and Drug Administration Category C drug
(ii) Good safety profile in use during pregnancy (in studies on autoimmune conditions, other than uveitis) |
|
