Thalidomide Embryopathy – World Health Organisation report

The World Health Organization (WHO) has just published the report of the meeting of experts on Thalidomide Embryopathy which was held in Geneva earlier this year and organised by the Thalidomide Trust. You can read a copy of the report here

Their full media story is reproduced below:

Thalidomide is back, are we ready for it?

Following extensive consultations involving the UK’s Thalidomide Trust, WHO and the Uppsala Monitoring Centre, experts have identified key actions to develop standardised criteria for diagnosis of birth defects due to thalidomide. Their findings and recommendations are published in a report released today.

Although more than half a century has passed since the risks of thalidomide on the foetus were identified, the risk is very much alive as increasing availability of thalidomide, particularly its use in countries with limited drug regulation and poor health communications, is the cause of a second generation of children born with congenital malformations.

The use of thalidomide in the treatment of skin lesions related to leprosy and certain kinds of cancers and auto-immune conditions call for clearer diagnosis of a direct causal relationship and the exact processes that lead to congenital malformation.

“In order to promote the safe use of medicines, it is crucial that our diagnosis is spot-on so that we can trace the causes of adverse drug reactions,” explained Shanthi Pal, Medicines Safety Programme Manager WHO (HQ). “The report will not only assist in the diagnosis of thalidomide embryopathy, it will also provide a model for diagnosing other types of drug-related embryopathy.”

Poor regulations and lack of health communications

Thalidomide has been licensed in many countries as a treatment for the complications of leprosy and multiple myeloma. In countries like Brazil where millions of pills are distributed each year to treat leprosy, a number of thalidomide-like birth defects have been reported.

Poor health education and the sharing of medicines is a problem leading to inadvertent exposure to thalidomide in pregnant women. It is clear that better regulation and communication is one key to prevent future cases. Such risks demand continuous efforts to inform citizens of the dangers of taking thalidomide during pregnancy. For proper diagnosis, it is crucial that doctors and health professional have access to complete possible drug exposure records throughout pregnancy, as well as details of clinical genetic evaluations

While some researchers believe that the drug is to blame for the birth defects, there are other genetic causes of similar defects which can be confusing. Over the years many cases have been improperly documented, making the establishment of causality problematic. To the layman, questions of causality can seem straightforward when multiple variables and confounders are ignored: this mother took thalidomide during pregnancy and delivered a child with malformations typical of the drug’s effects; therefore thalidomide must be the cause. Sometimes the thinking may take the path of reverse causality: this child has malformations typical of thalidomide’s effects, so the mother must have taken the drug.

Nevertheless, research indicates that some of these birth defects are associated with other causes, some attributable to genetic causes, others potentially attributable to other drugs or maternal factors.

How thalidomide has such a devastating effect on the foetus is still not clear. Determining the birth defects that are definitely associated with thalidomide embryopathy will take us one step further in understanding the mechanism of its effect.

‘We have a duty to those thousands of people who have been affected in the past one way or another, or will be using the drug in the future, to bring greater clarity to our knowledge of the drug’s mechanisms and effects.” said Professor Ralph Edwards, of the Uppsala Monitoring Centre.

A stepping stone

A team from St George’s, University of London, UK, has developed a diagnostic algorithm that will help assess more reliably the likelihood of thalidomide embryopathy. It has now been refined in light of the report’s conclusions and is currently being tested using cases with clear exposure to thalidomide.

Once a clear standard for the diagnosis of a case ‘highly likely’ to have thalidomide embryopathy is agreed, epidemiological and other clinical diagnostic factors, such as genetics, can be taken into consideration to develop a more effective decision-support tool for the ‘probable’, ‘possible’ and ‘highly unlikely’ categories.

“It is especially important that we find ways of having greater confidence in assessing causality which has remained a controversial and neglected area for decades. We now have an agenda of action, including continuing research, and the development of much more effective risk communication and more comprehensive pregnancy records." Edwards added.

Work in this area is now in progress. Such tools and methods provide a sound basis for more accurate human clinical judgement in arriving at decisions.

“Thalidomide has been the cause of much suffering, not only because of its direct and devastating effects, but also because of the many uncertainties that have surrounded it. While we cannot hope to achieve certainty in all things, this collaborative project is now moving us forward towards greater clarity on some of the fundamental issues." said Deborah Jack, Executive Director at The Thalidomide Trust.