Medicines for mothers-to-be: research during pregnancy
It takes an average of 27 years until a new medicine can be recommended for use by pregnant women. Why is that?
The safety of unborn babies has long been considered one of the most serious and controversial ethical issues when researching new medicines. Because of the unknown risks, pregnant women are very rarely included in clinical research studies, and women taking part in research are usually asked to avoid becoming pregnant.1 As a result, when a new medicine is approved, very little is known about its suitability for use during pregnancy.1,2
Information about use of new medicines in pregnancy is built up carefully, over many years, after the medicine becomes widely available. It takes an average of 27 years until a new medicine can be recommended for use by pregnant women.3 This means that women sometimes face a difficult choice between managing their health without the latest medicines, or taking a medicine when information about its use in pregnancy is limited.2,4,5
Why is it important to carry out research in pregnant women?
Like everyone else, pregnant women sometimes need to take medicines – they may be managing a long-term condition such as diabetes or epilepsy; treating an infection; or perhaps battling a life-threatening illness like cancer.6 They may also have medical needs related to their pregnancy, such as morning sickness. It is estimated that 6 out of every 10 women will need to take at least one prescription medicine during their pregnancy.7,8
A pregnant woman who takes a medicine needs to consider its possible effects on her unborn child. The mother’s blood and the baby’s blood are connected through the placenta and some (but not all) medicines that the mother takes can pass into the baby’s blood. There is a risk that certain medicines that are harmless to adults can affect the health or development of an unborn baby – sometimes irreversibly.9 For this reason, everyone involved in a clinical study – the research team, the participants and the committees that approve the study – are a lot more cautious than usual.
Clinical research in pregnant women will allow doctors and patients to make better decisions about the use of medication during pregnancy.
The other consideration is the potential effect of a medicine on the pregnant woman herself. Women’s bodies also change during pregnancy: they have extra fluid in their blood (an additional 30-50%), their hearts beat faster and more strongly, their kidneys work harder, and their stomach releases food more slowly. All of these things mean that pregnant women process medicines in a different way from other adults.9,10 Because for many drugs there haven’t been any or not enough clinical studies in pregnancy, the usual advice for pregnant women is to check with their pharmacist, midwife or doctor before taking any new medicine. If there is only limited information about its use during pregnancy, the woman and her doctor will need to weigh up any available evidence and decide what is right for her. Women who are managing a long-term health problem are advised to discuss their treatment with a specialist ideally before they try to conceive but at least as soon as they find out they are pregnant.11,12
How does research on medicines during pregnancy work?
Information about the safety and effectiveness of medicines for pregnant women is collected in special types of studies that are designed to protect the health of the mother and the baby. Often the earliest information about the effect of a medicine during pregnancy comes from studies on animals or animal cells. This is done as part of basic research on the new medicine, to find out if it might have a harmful effect on growing or developing tissues.3 Scientists may also look at the structure of the medicine to see whether it is likely to cross the placenta from the mother into the baby.3 Studies in animals can be helpful for ruling out medicines that appear to have too high a risk of causing harm, but it is still necessary to carry out research in pregnant women to find out if the medicine is truly safe and effective in pregnancy. Sometimes a small number of pregnant volunteers agree to have blood tests after they have taken an investigational medicine in carefully controlled conditions. The blood tests show how pregnant women process the medicine, and how it affects their bodies.13
Another common way to look at the effect of medicines in pregnancy is through observational studies (sometimes called pregnancy registries).14,15 This type of study collects health information from pregnant women after they have personally chosen (or been advised) to take a particular medicine for their own benefit. They are not given the medicine as part of the research. Cohort studies are a type of observational study that typically involve a large number of women, who may or may not have taken the medicine as part of their routine treatment. This type of study relies on medical records or questions answered by the pregnant woman to generate information. The information is analyzed to look for possible links between medication use and health effects on mothers or babies.14,15
What does taking part in an observational pregnancy study involve?
Observational studies usually do not require the mother-to-be to take any medicines or have any medical treatment that she wouldn’t otherwise have. Instead, she is asked to provide information about her use of the medicine, as well as information about her health and what is known about the health of her baby. In many cases, the study only requires permission for the researchers to look at the mother’s and baby’s medical records. In other cases, additional tests and assessments may be done, such as blood tests or physical examinations. Researchers may also keep track of the baby’s mental and physical development for the first few years of life in case a medicine taken during their mother’s pregnancy turns out to have long-term effects.1,4,5
However the studies are done, clinical research in pregnant women means that doctors and patients will ultimately be able to make much better decisions about taking a particular medicine during pregnancy.1
- Lyerly AD, Faden RR. Mothers Matter: Ethics and Research during Pregnancy. Virtual Mentor 2013;15(9): 775-778.
- Thall Bastow, BD. Teratology and Drug Use During Pregnancy. 2016. Available from: http://emedicine.medscape.com/article/260725-overview
- Adam NP, Polifka JE, Friedman JM. Evolving knowledge of teratogenic risk of medications in human pregnancy. Am J Med Genet C Semin Med Genet. 2011;157(3):175-182.
- Foulkes MA, Grady C, Spong CY, Clinical Research Enrolling Pregnant Women: A Workshop Summary. J Womens Health (Larchmt) 2011; 20(10): 1429–1432.
- Blehar MC, Spong C, Grady C, Enrolling Pregnant Women: Issues in Clinical Research. Womens Health Issues. 2013; 23(1): e39–e45.
- Pregnancy and Chronic Health Conditions. National Health Service. Available from: http://www.nhs.uk/conditions/pregnancy-and-baby/pages/pregnant-chronic-health-condition.aspx
- Daw JR, Mintzes B, Law MR, et al. Prescription drug use in pregnancy: a retrospective, population-based study in British Columbia, Canada (2001-2006). Clin Ther 2012;34:239–249.
- Ethical Considerations for Including Women as Research Participants. The American College of Obstetricians and Gynecologists. Nov 2015. Available from: http://www.acog.org/Resources-And-Publications/Committee-Opinions/Committee-on-Ethics/Ethical-Considerations-for-Including-Women-as-Research-Participants
- Sachdeva P, Patel BG, Patel BK. Drug Use in Pregnancy; a Point to Ponder! Indian J Pharm Sci. 2009; 71(1): 1–7.
- Williams DJ. Physiological changes of normal pregnancy. Available from: http://oxfordmedicine.com/view/10.1093/med/9780199204854.001.1/med-9780199204854-chapter-1401
- Best Use of Medicines in Pregnancy. UK Teratology Information Service. Available from: http://www.medicinesinpregnancy.org/Medicine—pregnancy/
- Medicines in Pregnancy. National Health Service. Available from: http://www.nhs.uk/conditions/pregnancy-and-baby/Pages/medicines-in-pregnancy.aspx
- Guidance for industry: Pharmacokinetics in pregnancy. Food and Drug Administration. 2004. Available from: www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm072133.pdf
- Cardonick E. Usmani A. Ghaffar S. Perinatal outcomes of a pregnancy complicated by cancer, including neonatal follow-up after in utero exposure to chemotherapy. Results of an international registry. Am J Clin Oncol. 2010;33:221–228.
- Donegan K, Safety of pertussis vaccination in pregnant women in UK: observational study. BMJ 2014;349:g4219.