USE OF UPADACITINIB IN PREGNANCY
USE OF URSODEOXYCHOLIC ACID IN PREGNANCY
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 some adverse pregnancy outcomes. Data on the use of UDCA needs to be interpreted in this context.
Since ICP typically occurs in late pregnancy, all controlled 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 therefore 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 reduced risks of 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.
USE OF USTEKINUMAB IN PREGNANCY
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 associated with increased risks of 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 fetal safety of ustekinumab use in pregnancy are provided by studies which collectively describe more than 600 exposed pregnancies. However, several of these studies have important methodological limitations which affect the conclusions that can be provided, and the available data do not provide clear evidence that ustekinumab use in pregnancy is causally associated with increased risks of miscarriage, malformation, intrauterine fetal death/stillbirth, preterm delivery, impaired fetal growth or neurodevelopmental impairment. Larger studies utilising advanced analytical methods are required to confirm these findings.
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. Given the available data are methodologically limited, women who have been exposed to ustekinumab in early pregnancy should be particularly 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 infant and increased risk of infection. Guidance from the manufacturer specifies that infants exposed to ustekinumab in utero should avoid live vaccines until twelve months following birth, or until ustekinumab infant serum levels are undetectable. Discussion with UKTIS is recommended in cases where there is a high risk of tuberculosis infection in the infant.
Exposure to ustekinumab 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 which could independently increase the risk of adverse pregnancy outcome may be present in individual cases. Such factors are important to consider when performing case-specific risk assessments.
MANAGEMENT OF URINARY FREQUENCY, ENURESIS & INCONTINENCE IN PREGNANCY
Urinary incontinence, defined as the involuntary leakage of urine, has multiple causes which may require different management strategies. Stress incontinence is common during pregnancy, caused by the hormonal changes of pregnancy and pressure on the bladder from the expanding uterus. Pharmacological treatment is not routinely indicated for urinary stress incontinence that has occurred due to pregnancy.
Women with pre-existing conditions that cause urinary frequency, enuresis and incontinence may require ongoing treatment during pregnancy under specialist supervision. Human pregnancy safety data is limited or lacking for most of the drug options, and the risks and benefits should therefore be considered on a case-by-case basis, taking into account the severity of the woman’s condition and likely effects on her health and quality of life if an established medication regimen is altered.
Oxybutynin is the best studied treatment for urinary frequency during pregnancy, although data are still very limited. Neither of two studies nor a handful of case reports raise concern that oxybutynin exposure is associated with infant congenital malformation. Increased risks of preterm delivery and low infant birth weight were noted in one of the studies but may be related to the underlying maternal condition. These findings require confirmation.
There are no further published human pregnancy exposure data for drugs to treat urinary frequency, enuresis and/or incontinence. A small number of pregnancy outcomes have been reported to UKTIS following prenatal exposure to oxybutynin, solifenacin, tolterodine, fesoterodine, mirabegron, propantheline, and trospium, with no major congenital malformations described. Data are absent for darifenacin, flavoxate, and propiverine.
Adverse fetal effects have been observed in preclinical (animal) studies of darifenacin, propiverine, fesoterodine, mirabegron, oxybutynin, and tolterodine; however, some exposures were at maternally toxic doses.
Exposure to drugs used to reduce symptoms of urinary frequency, enuresis and incontinence at any stage in pregnancy would not usually be regarded as medical grounds for termination of pregnancy; however, due to the lack of data, additional fetal monitoring may be warranted. Other risk factors may also 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.