Ursodeoxycholic acid (UDCA) is licensed for the treatment of gallstones and for primary biliary cirrhosis. Off-licence, it is used to treat intrahepatic cholestasis of pregnancy (ICP; also known as obstetric cholestasis). ICP is associated with an increased risk of adverse pregnancy outcome. Data on the use of UDCA needs to be interpreted in this context.
Since ICP typically occurs in late pregnancy, all studies of gestational UDCA use relate to exposures after the first trimester. Rates of miscarriage and infant congenital malformation following first trimester UDCA use are unknown.
There are currently no known associations between gestational UDCA exposure and increased rates of stillbirth, low birth weight or neurodevelopmental delay. There is some evidence of a reduction in stillbirth, preterm delivery, neonatal ICU admission and meconium aspiration following treatment of ICP with UDCA, however the data are limited and the benefit of treatment with UDCA is uncertain. Recent evidence would suggest that UDCA does not reduce perinatal morbidity and provides only a slight improvement in itching.
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.
Ustekinumab is a fully human IgG1κ monoclonal antibody to interleukin (IL)-12/23 produced using recombinant DNA technology. Ustekinumab is licensed for the management of plaque psoriasis, psoriatic arthritis, Crohn’s disease and ulcerative colitis.
Some maternal autoimmune/inflammatory conditions are known to be associated with increased risk of certain adverse pregnancy outcomes, such as miscarriage, preterm delivery and low birth weight. Adequate control of the maternal condition may therefore decrease the risk of such adverse pregnancy outcomes; however, robust data to support this are not available.
Data regarding the safety of ustekinumab use in pregnancy are highly limited, consisting of 61 exposed pregnancies mostly described in uncontrolled studies where ustekinumab was generally discontinued in the first trimester.
The available data do not provide any signal to indicate that ustekinumab use in pregnancy increases the risk of miscarriage, malformation, intrauterine fetal death, preterm delivery, low birth weight or neurodevelopmental impairment. However, it is not currently feasible to provide a reliable evidence-based evaluation of the risk posed to the fetus due to the small number of exposed pregnancies described in the literature.
As ustekinumab is not expected to cross the placenta during the first trimester, congenital malformations due to a direct effect on the fetus would not be anticipated. However, indirect fetal effects cannot be excluded and, due to the lack of human pregnancy data, women who have been exposed to ustekinumab in early pregnancy should be strongly encouraged to attend their routine prenatal monitoring scans.
There is theoretical concern that the use of immunosuppressant antibodies that actively cross the placenta during pregnancy (including ustekinumab) could result in immunosuppression in the newborn and increased risk of infection. Guidance from Public Health England (PHE) [issued 2017] specifies that, following in utero biologic immunosuppressant exposure, live vaccines should not be used until the infant is 6 months old.
Due to the current lack of data, additional fetal monitoring may be warranted on a case-by-case basis. 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. Please report all cases of ustekinumab exposure to UKTIS.