Thalidomide was first marketed in 1957 as a sedative and to combat symptoms associated with morning sickness in pregnant women. Multiple reports of limb reduction defects in offspring exposed in utero led to the withdrawal of the drug from the market by 1962. During this time, over 10,000 children were born worldwide with severe malformations including absent, reduced, and/or hypoplastic limbs, dysplasia or absence of internal organs, deformities of the ears, eye defects, facial palsy and congenital heart defects.
Gestational exposure to thalidomide between 20 and 36 days post-fertilisation (36-50 days after LMP) carries the greatest risk of embryopathy, which has been reported after a single dose of 100mg. The overall risk of fetal malformations in live-born infants exposed to thalidomide during this period is reported at 20-50%, with an estimated 40% of affected children dying soon after birth. Thalidomide use in pregnancy has also been associated with increased risk of fetal loss and neurodevelopmental impairment and seizures.
There are no human pregnancy data regarding the safety of thalidomide analogues lenalidomide and pomalidomide, but these are predicted to be teratogenic based upon their similarity to thalidomide and the results of pre-clinical animal studies.
Thalidomide and its analogues are currently licensed for the treatment of multiple myeloma and certain other specific conditions in patients meeting strict criteria. In order to avoid fetal exposure to these drugs, all patients, prescribers and pharmacies are required to register with the manufacturer before the drugs are dispensed, and both female and male patients must comply with the terms of the manufacturer’s Pregnancy Prevention Programme (PPP).
There are no data regarding pregnancy outcome following exposure to thalidomide (or its analogues) later in pregnancy, and potential adverse neurodevelopmental effects from later exposure remain undetermined.
Use of thalidomide and its analogues is strictly contraindicated at all stages of pregnancy. If exposure to thalidomide, lenalidomide or pomalidomide occurs in early pregnancy, due to the extremely high malformation rate associated with such exposures, the option of elective termination of pregnancy should be discussed with the patient. For ongoing pregnancies a detailed anomaly scan of the fetus, including echocardiography, should be offered to the patient to screen for major structural abnormalities. However, it should be stressed that scans will not detect all structural abnormalities and will not identify neurobehavioural effects. 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.
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.