We don't know what we don't study: The case for research on medication effects in pregnancy

Abstract

This Commentary addresses issues related to exposures to teratogens and makes the case for increased research into the safety of medications during pregnancy for mothers and fetuses. Not only are medications commonly used during pregnancy, but evidence points to an increasing prevalence and number of drug exposures experienced by the embryo or fetus, particularly during the critical first trimester of pregnancy. Although the first trimester represents a particularly vulnerable period of organogenesis, exposures during other gestational time periods may also be associated with deleterious outcomes. In addition to the changing (and in many cases unknown) risks to a developing fetus, other challenges to studying medication exposures and their effects during pregnancy include the dramatic changes in physiology that occur in pregnant women and the ethical dilemmas posed by including this vulnerable population in randomized controlled trials of safety and efficacy. However, without adequate knowledge of the pharmacokinetics, pharmacodynamics, efficacy, and safety of medication use in pregnancy, women may be under-dosed to minimize exposure or not treated at all, resulting in inadequate treatment and potential harm to the mother and her baby. The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) is undertaking studies on medications and teratogenic exposures during pregnancy, including alcohol, maternal diabetes, oral hypoglycemic agents, and antiviral medications, through several of its research networks. Although this is a start, there is a critical need for further research on medications used during pregnancy, especially their effects on both the mother and her developing child.

Physiological Aspects of Female Fertility: Role of the Environment, Modern Lifestyle, and Genetics

“…They may be caused by metabolic disturbance, such as diabetes, and may be a physical insult such as ra-diotherapy or exposure to a chemotherapeutic agent. However, the most common teratogens are physician-prescribed medications, as up to two-thirds of women in the United States are prescribed drugs in pregnancy (251). Furthermore, as the most critical window of exposure is the first trimester, often before the woman recognizes she is pregnant, it is imperative that a doctor is vigilant to this factor in treating a woman of reproductive age and prescribes medication sparingly and also manages chronic medical conditions such as thyroid disorder and diabetes in an optimal manner to reduce the fetal exposure to teratogenic medication and also to the harm of an unstable systemic illness.…”

Pharmacological safety during pregnancy: the principles of teratogenesis and teratogenicity of drugs

“…Изучение разнообразных как в проявлении, так и во временных рамках [12] нежелательных эффектов некоторых лекарственных средств на ребенка антена-тально привело ученых к мысли, что не все ВПР связаны с воздействием данного препарата. В большинстве слу-чаев внутриутробные воздействия, приводящие к раз-витию врожденной аномалии, считаются доказанными, поскольку воздействуют на эмбрион во время органо-генеза, однако некоторые тератогены могут оказывать отсроченные эффекты (в более поздние сроки гестации) [2]. При изучении лекарственной безопасности в пери-од беременности важно учитывать, что тератогенный эффект может быть результатом действия нескольких факторов [13].…”

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ВВЕДЕНИЕ В настоящее время в мировой медицинской лите-ратуре крайне мало данных о воздействии лекарствен-ных средств (ЛС) в период беременности -как на организм матери, так и ее будущего ребенка [1,2]. Многие ЛС способствуют развитию таких осложнений беременности, как самопроизвольный выкидыш, пре-ждевременные роды, мертворождение, а также могут вызывать формирование врожденных аномалий разви-тия, церебрального паралича, рождение с низкой мас-сой, задержку умственного развития и поведенческие нарушения в последующем и пр.

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Performing research in pregnancy: Challenges and perspectives

“…1 Because more than half of all pregnancies in the U.S. are unplanned, medication use frequently occurs before a woman is aware she is pregnant. 2 Physiologic changes in pregnancy affect drug metabolism, such that dosing and interval recommendations derived from non-pregnant women are not necessarily appropriate for pregnant women. 3 Unfortunately, there is a paucity of data on medication safety and dosing during pregnancy.…”