This piece was prompted by an Article in the student BMJ.
Paediatric and maternal research have always been associated with major ethical dilemmas. It is almost universally agreed that harming children, foetuses or mothers, whether intentional or not, is unethical. Critics agree that exposing children and foetuses to the risks of research for the benefit of others is not justifiable and that we should not exploit those who are unable to comprehend the risks they are being placed under. This leads to a seemingly irresolvable dilemma meaning that during pregnancy and post-partum, the drugs available to treat mothers is limited, as many are left untested due to research cost and ethics.
During my time in Poland with Gap Medics I witnessed a mother and baby suffering from the parasitic disease Toxoplasmosis. The congenital disease had been picked up during pregnancy leading to the baby had been born prematurely. Despite feeding 20 times a day the baby was still far below its expected weight and this was also putting a strain on the mother who was also attempting to recover from the disease. The doctor I was shadowing prescribed a treatment of antibiotics, however he told me that because of ethics council ruling he was unable to give the patient the newer, more effective drugs as they had not been tested on pregnant women or those who were breastfeeding. This is an example of how the limits of ethical testing can compromise patient health and recovery.
Alternatively, some mothers may need to change current treatments all together when they discover they are pregnant, as their medications may have detrimental foetal effects. This can be very stressful for the mothers, especially those who have had a long term use of particular medication or past problems, as it may make them wary of trying alternatives. Also for undiscovered or unexpected pregnancies it may be into the third trimester before any treatment changes are made, at which point it may be too late. Some may have to weigh a balance between the benefit to the mother and risk damage to the baby whilst others may be told that, during treatment all possible effort should be put into avoiding pregnancy. An example of this would be Isotretinoin, more commonly known as Roaccutane- a treatment for severe acne. The medication is known to cause major birth defects and malformation in development, meaning it poses an extremely high risk to unexpected pregnancies. To even be prescribed 30 days of medication women have to first have spent at least a month using a minimum of one, but usually two, effective methods of contraception, for example the pill and condoms. They are also put under strict monthly monitoring not only to look out for any pregnancies but also to ensure liver function and lipid levels are not being compromised.
I spoke to a 17 year old who was currently receiving the medication, to discover their views on the treatment and its associated risks. Having previously used the pill, antibiotics and benzoyl peroxide they found roaccutane to be by far the most effective, especially as their condition developed. Their biggest concern was the actual idea of taking a dug with so many side effects, with the most worrying for them being effects on the liver and cholesterol levels as the risk of pregnancy in this case was extremely low. The patient said that the effect they felt most conscious of was the achiness of their body and that the regular pregnancy testing was not an influencing factor for them as they had chosen to opt out in favour of monthly blood tests.
The BMJ article that prompted this piece spoke about a study carried out in Denmark into whether or not ‘Antiepileptic drugs lead to an increased risk of spontaneous abortion (miscarriage)’. The paper based on numbers from 1st February 1997 to 31st December 2008 and included a cohort of 983305 recorded pregnancies. However, it was only in 0.5% of cases that antiepileptic drugs were being used.16% of women using a form of antiepileptic drug, compared to 13% of women who were not using any, suffered miscarriages. There was no increase for women with an epilepsy diagnosis that used the drugs; however there was an increase for those who did NOT have a diagnosis. In cases where drugs were used in the first pregnancy but not the second, the hazard ratio was 0.83 for exposed pregnancies compared to unexposed, as identified by 18 women. The overall conclusion was that there was no relationship however it was noted that the statistical precision for the experiment was low.
Despite that lack of definitive result within the paper, the importance of research of this type remains. Identifying possible drug effects as soon as possible is paramount to preventing any mass generation wide effects occurring such as those in the past. The most memorable being the thalidomide cases of the late 50s where the unknown relationship between the drug and foetal development lead to over 10,000 known cases of deformity as the drug was prescribed to treat morning sickness in the early stages of pregnancy. In this cases, like many others, despite being aimed at pregnant women, there had been little testing done on pregnant subjects due to ethical complications and following the events there was a significant increase in standards for testing and licensing drugs. In the rules regarding disclosure of all side effects discovered during testing were more strongly enforced and documents such as The Kefauver Harris Amendment and Directive 65/65/EEC laid down the some of the early steps to our modern drug licensing processes.