OPTIMIZATION OF ANTIRHEUMATIC DRUG-TREATMENT IN PREGNANCY

Active rheumatic disease during pregnancy may require drug treatment to ensure the mother's health is maintained and that there is a good outcome for the fetus. However, knowledge on the use of antirheumatic drugs during pregnancy is limited, rendering decision making difficult both for the patient and the physician. The effect of nonsteroidal anti-inflammatory drugs (NSAIDs) in the treatment of rheumatoid arthritis has been investigated in depth for aspirin (acetylsalicylic acid) and indomethacin only. Information about the use of ibuprofen, sulindac, ketoprofen and diclofenac during pregnancy is scanty and there is no such information for newer agents such as the fenemates and oxicams. There is no evidence for teratogenicity of any NSAID in humans. However, due to the shared property of inhibition of prostaglandin synthesis, adverse effects such as constriction of the ductus arteriosus in utero, persistent pulmonary hypertension in the neonate and prolongation of pregnancy and labour are possible. When administered to pregnant patients, NSAIDs should be given in the lowest effective dose, and should be withdrawn within the 8 weeks prior to expected delivery. Transplacental passage varies for different corticosteroids. Because of the inability of the fetal liver to convert prednisone to its active metabolite and the ability of the placenta to convert prednisolone to the inactive prednisone, both prednisolone and prednisone are drugs of choice in pregnant patients requiring corticosteroid treatment. Corticosteroids do not increase the risk of congenital malformations. Possible adverse effects are perinatal infection and adrenal insufficiency in the newborn. Both events are only rarely reported in the literature, which comprises information on more than 1000 pregnancies. The clinical experience on the effect of slow-acting antirheumatic drugs (SAARDs) on pregnancy is insufficient to draw substantial conclusions. Available data from the literature give no clear evidence of an increased risk of teratogenicity for any of these drugs. Rheumatologists differ in their view on the advisability of using SAARDs during pregnancy. Hydroxychloroquine, which is regarded as less toxic than chloroquine, is recommended by some rheumatologists far the treatment of pregnant patients with active systemic lupus erythematosus (SLE) or rheumatoid arthritis. Sulfasalazine can be continued during pregnancy. Data on gold compounds and penicillamine are sparse and inconclusive. A reasonable approach is to stop these agents as soon as pregnancy is confirmed. The limited experience with cyclosporin has been obtained when the drug was used to prevent allograft rejection. Further data regarding the use of this drug in pregnant patients with rheumatic diseases are needed. With the exception of azathioprine, which is not teratogenic in humans, the alkylating antitumour agents and methotrexate increase the risk of congenital malformations when given during the early stages of pregnancy. Cyclophosphamide, chlorambucil and methotrexate should not be prescribed to women of childbearing potential, unless effective birth control is being practised.