Pregnant pause: why expectant mothers with medical conditions stop taking medication
The exclusion of pregnant women from drug trials means there is little drug-safety information for them to rely on
About one in 10 pregnant women have a chronic medical condition that requires medication. Photograph: iStock
Vulnerable groups, such as children, prisoners and people with an intellectual disability, are usually excluded from drug trials. And, until recently, it was considered unethical to test drugs on pregnant women, too. The thalidomide scandal – in which a drug for morning sickness led to deformities in exposed babies – hasn’t just influenced drug testing but means doctors are extremely wary about prescribing in pregnancy.
According to the Drugs and Therapeutic Bulletin, about one in 10 pregnant women have a chronic medical condition that requires medication. And at least four in 10 women take some form of medication during their pregnancy. Yet there is little drug-safety information for these women to rely on. Unsurprisingly, some decide not to take their medications while they are pregnant.
Sodium valproate, an effective drug for epilepsy (licensed in the Republic as Epilim) is now contra-indicated in women of childbearing potential unless the terms of a special pregnancy prevention programme are followed. This follows a recent warning issued to doctors by the Health Products Regulatory Authority (HPRA) stating that valproate should not be used in female children and women of childbearing potential unless other treatments are ineffective or not tolerated.
Children exposed to valproate in the womb are at a high risk of serious developmental disorders (up to 30-40 per cent) and of congenital malformations (in about 10 per cent of cases).
In 2014, the warnings and restrictions regarding the use of valproate in women and girls were strengthened to minimise these risks. The European Medicines Agency has now reviewed the impact of these measures following concerns they were not sufficiently effective in reducing exposure to valproate use during pregnancy. In March, it said it considered these concerns were well founded. It has now recommended new contra-indications, strengthened warnings and measures to further prevent valproate exposure during pregnancy.
In effect, this means that for women with epilepsy, valproate is contra-indicated in pregnancy unless there is no suitable alternative treatment. Valproate is also used to treat bipolar disorder; the new guideline means it is now completely contra-indicated for this condition in pregnancy.
The HPRA has stated that “the prescribing specialist must reassess the need for valproate therapy annually in girls who have commenced menstruation and consider alternative treatment options. Patients should be switched to alternative treatment before they reach adulthood. If valproate is the only suitable treatment, the need for effective contraception . . . should be discussed.”
A number of studies over the past 10 years have also reported problems associated with taking antidepressants during pregnancy. These include early delivery and lower birth weight; increased rates of malformations, including heart problems in the baby; and an increased risk of autism in children. One study found that exposure to antidepressants in the womb is associated with a slightly increased risk of speech and language disorders.
When research is likely to have a direct clinical benefit for pregnant woman, an increase over minimal risk to the foetus may be permitted. It’s a potential minefield
But the tide may be turning when it comes to drug-testing in pregnancy. Mackenzie Graham, a research fellow at the University of Oxford, says pregnant women are entitled to high-quality, evidence-based healthcare as much as the rest of the population. He argues they should no longer be considered a vulnerable group – at least, not in the context of drug-testing.
The US Food and Drug Administration recently published a draft guidance for how and when to include pregnant women in drug trials. World Health Organization ethical guidelines state that if research has no prospect of direct benefit to the pregnant woman, the risks to the foetus must be minimal. When research is likely to have a direct clinical benefit for pregnant woman, an increase over minimal risk may be permitted.
It’s a potential minefield.
But Graham says the issue can no longer be avoided. “Ethicists must continue to work to develop frameworks for managing the risk-benefit trade-offs between woman and foetus. Failure to do so will continue to deprive pregnant women of a fair distribution of the benefits of research.”