Sulfasalazine (sulphasalazine) is a sulphonamide aminosalicylic acid compound which is licensed for the induction and maintenance of remission of ulcerative colitis, and for treating active Crohn’s disease and rheumatoid arthritis.
Most of the data relating to sulfasalazine exposure during pregnancy derive from studies of women undergoing treatment for inflammatory bowel disease. Active (uncontrolled) inflammatory bowel disease has been associated with increased risks of certain adverse pregnancy outcomes, including congenital malformations, preterm delivery, and small for gestational age infants. Control of the maternal condition throughout pregnancy may therefore prove beneficial to both mother and fetus.
The available human data relating to sulfasalazine use in pregnancy do not suggest that maternal use during pregnancy is associated with an increased overall risk of congenital malformation or of a number of specific malformations. Risk of miscarriage is currently undetermined, although a single study of 5-acetylsalicylic acid medications as a class did not identify a significant increased risk. No robust evidence of increased risks of stillbirth, low birth weight, or preterm delivery has been provided from a small number of studies, though additional data are required before suitably evidence-based conclusions can be drawn. No studies have investigated the risk of neurodevelopmental impairment or cancer among infants exposed to sulfasalazine in utero.
There are theoretical concerns regarding an increased risk of neonatal hyperbilirubinaemia following in utero sulfasalazine exposure, although there is no good evidence confirming this association. Sulfasalazine has been shown to actively inhibit the absorption and metabolism of folic acid, which may result in folic acid deficiency. Pregnant women undergoing treatment with sulfasalazine may therefore require supplementary folic acid. At present there are no published guidelines regarding the dose or duration of folate supplementation for pregnant women using sulfasalazine. In general, high dose folic acid (5mg) is recommended periconceptually for all women considered to be at increased risk of folate deficiency (e.g. those with a family history of neural tube defects, concurrent treatment with drugs which interfere with folate metabolism, or maternal obesity). However, no studies have investigated whether there is increased benefit of this higher dose.
Exposure to sulfasalazine at any stage in pregnancy would not usually be regarded as medical grounds for termination of pregnancy or any additional fetal monitoring. However, other risk factors may be present in individual cases which may independently increase the risk of adverse pregnancy outcome. Clinicians are reminded of the importance of consideration of such factors when performing case-specific risk assessments.
This is a summary of the full UKTIS monograph for health care professionals and should not be used in isolation. The full UKTIS monograph and access to any hyperlinked related documents is available to NHS health care professionals who are logged in.
If you have a patient with exposure to a drug or chemical and require assistance in making a patient-specific risk assessment, please telephone UKTIS on 0344 892 0909 to discuss the case with a teratology specialist.
If you would like to report a pregnancy to UKTIS please click here to download our pregnancy reporting form. Please encourage all women to complete an online reporting form.