Pharmacology and pregnancy. Ethical implications
Gonzalo Herranz, group de work of Bioethics, University of Navarra
Session at the VI Course of update for Pharmacy Postgraduates:
Medicines and nutrition in pregnancy and lactation.
School of Pharmacy, University of Navarra. Pamplona, 1988
I have several reasons to thank the organisers of this Course for inviting me to participate with this lecture on the ethical implications of drug treatment in the course of pregnancy. These are:
The first: because it is a sign of appreciation for Bioethics. Bioethics in Spain is at leave . Outside, on the European continent and, above all, in the Anglo-Saxon world, there is a much more lively and vibrant interest in the ethical responsibilities of science and the health professions. It is a good idea to include a lesson from this subject in a Course at update, for there is nothing more topical than concern for Ethics.
Secondly, because it is an interesting topic that still has many open problems. It is logical that it should have them. The physiology, pathology and pharmacology of pregnancy are today in frank progress, discovering more problems than solutions, which is also the case with bioethics, discipline which is barely twenty years old and is in a permanent crisis of growth.
Third: because, within the field of bioethics, the ethics of human procreation, in the circle of which gestation is part, attracts everyone's attention these days. People's ideas about the transmission of human life and about the domain of family programming, their opinions about the moral significance of respect for nascent life, are the subject of continuous discussion. This discussion flares up at times and dies down at others, but it never dies down, for it concerns a crucial point on which the way of being and living of the whole of humanity depends.
To begin with, we could ask ourselves questions such as the following: what conflicts can arise in the relationship between pharmacology and obstetrics to make the intervention of ethics necessary; is there something specific in the pregnant woman to make it necessary to elaborate a special ethical statute for her; do the embryo and the foetus demand care that may conflict with the mother's well-being? Is it morally permissible to use a new drug, the effects of which on the prenatal development are unknown to us?
As we can see, there is no shortage of ethical conflicts. There is no shortage of biological arguments either: the pregnant woman's biology is profoundly transformed; the physiology of pregnancy describes profound adaptations of many apparatuses and systems. For its part, the embryo-fetal organism also has its own characteristics, with its own particular reactivity. To complicate matters, these maternal adaptations and embryo-fetal reactivity change constantly throughout the nine months of the prenatal development .
In order to deal with the problems that arise when treating pregnant women with pharmaceuticals and to determine the scope of our moral obligations, it seems to me that the best way to do this is to bring together the problems around what in my opinion are the two basic duties of Health Science Ethics: the duty to know and the duty to respect. These two commandments summarise the core of Bioethics.
I like to repeat that, for health science professionals, the scientific knowledge is the first of the moral obligations. It is a very demanding obligation, as it imposes, along with the continuous study and the critical assessment of what is published, the duty to inform people of what is most relevant.
At the same time, however, health science professionals are bound by the duty of respect to behave in a way that is attentive to the personal and biological values of human beings, recognising their rights and ethical claims and providing them with the services due to their dignity.
Let us now turn to the content of the duty of science.
I assume that the Professors who have preceded me throughout the day will have emphasised one point: that while we already know a lot about drugs and pregnancy, we still do not know enough. And they were right. I suppose they will also have said that the pregnant woman, on the one hand, and the embryo, foetus and child, on the other, still deserve today the designation coined twenty years ago by Shirkey, when he called them "the orphans of an expanding therapeutic".
There are several reasons why pregnant women and children are, in effect, the disinherited of the modern fortune that is today's Pharmacopoeia. Firstly, they are part of the so-called "special populations". Modern ethical guidelines on research on human beings almost always include the prohibition of using as subjects of research persons who are particularly vulnerable, either biologically or because of their inability to give their consent with full warning and freedom. The pregnant woman and the unborn human being share in this protection, along with minors, the mentally handicapped, prisoners, medical and nursing students, etc. The need to defend them from potential abuse has kept them out of clinical trials. Safety has, to some extent, been paid for by ignorance.
This status is due in large part to the extremely harsh experience of the thalidomide tragedy, the memory of which is still vivid in everyone's mind report . subject Governments and drug control agencies realised then that a catastrophe of such proportions should never be repeated and took the appropriate measures to avoid it, including the obligation to indicate in the package leaflets of almost all medicines warnings such as "Do not use in children", "There is no data about its possible effects on pregnancy, so it should not be administered to pregnant women".
The results of this security policy are clear. On the one hand, people have been reassured. They know that tragedies of global proportions will not happen again. In any case, if any serious reaction occurs when a patient receives a medicine, the public suspects that it is probably due to negligence on the part of the prescribing physician or inadequate monitoring by the manufacturer.
But there are still other reasons to justify the lower development of our knowledge in gestational pharmacology. Women of childbearing age are not an ideal subject for pharmacological research . Any research on drugs, while involving risks, requires a high degree of scientific precision. The woman is not an ideal subject: she is probably more at risk as a subject of research. Many years ago, women were excluded for reasons of chivalry: it was ungentlemanly to abuse the "weaker sex". But researchers have always sought to eliminate the methodological problems arising from the changing metabolic status conditioned by the cyclical changes of the female organism. It is not easy to evaluate the actions of certain types of drugs against a constantly changing biological and psychological background. In addition to these drawbacks, after the thalidomide episode, there was the fear of drug-induced teratogenesis, which was rekindled when it was discovered some time later that diethylstilbestrol, administered precisely to avert the threat of miscarriage in the early stages of pregnancy, was the cause of vaginal cancer which appeared years later in the daughters of the women treated.
If we add to these unfortunate episodes the doctor's fear of being sued for malpractice internship if he is accused of having induced a disorder of the development and the panic of the pharmaceutical industry about the moral and economic effects of a massive lawsuit for damages attributed to one of its products, it is understandable that it has become a general rule to avoid, during pregnancy, the consumption of medicines except in cases of absolute necessity.
This is the current rule : "If possible, no medication should be taken during the first trimester of pregnancy. In addition, the benefits and risks of taking medicines throughout pregnancy and childbirth should be carefully weighed". So begin the guidelines of the December 1986 update of the Committee on Safety of Medicines and the Committee on Review of Medicines (CRM).
In the face of such alarmist recommendations, what happens?
Women pay little attention. A 1973 research showed that 82% of 911 pregnant women not only did not refrain from taking medicines, but took an average of four medicines during their pregnancy. Two thirds of the total were taking non-prescribed drugs.
The pharmacist and the doctor must be duly informed about the safety of the medicinal product during pregnancy, with the aim of providing balanced, objective and comprehensible information on the benefits for the woman and the risks for the foetus, purpose . issue First of all, it should be recalled that only a small number of drugs have a proven teratogenic action in our species: cytotoxic drugs. These are cytotoxic drugs, in particular alkylating agents and methotrexate, and retinoids (etretinate, isotretinoin). There are many others for which there is a more or less justified suspicion, based on data of animal experiments and on inconclusive experience or data of observation in humans. development For data from animal experiments, it is important to know about teratogenicity or other adverse effects, both somatic and behavioural, specifying animal species and patterns of dosage and time of administration of the agent. Published anecdotal or epidemiologically relevant data reports of alterations in humans should not be ignored.
The physician and pharmacist should offer pregnant women a balanced interpretation. While recognising that it is never wrong to advise against the use of medicines during pregnancy unless there is an undeniable clinical need, it is necessary on such occasions to give more specific advice to patients who are pregnant or, in general, to women who may conceive a child during treatment. It should be stated that the use of such a medicine is acceptable, or that it will be used only when the pregnant woman's condition poses a significant risk to her or to the unborn child, or that the medicine is positively contraindicated in pregnancy.