Closing the gap: Research advances medication safety in pregnancy

Micheline Piquette-Miller receives Canadian Society of Pharmacology and Therapeutics award recognizing research to improve medication use in pregnancy

During pregnancy, taking any kind of medication can feel like a big risk. Various studies have estimated that up to 90 per cent of pregnant people take at least one medication during their pregnancy, but many medications aren’t tested in pregnancy. Information about the safety of drugs on the mother and fetus is important for informed decision-making, but in many cases is not available.

Micheline Piquette-Miller, professor and associate dean of research at U of T’s Leslie Dan Faculty of Pharmacy, leads work to help clarify the risks and benefits of medications in pregnancy, particularly in those who have underlying health conditions.

“Some of the work we’re doing is looking in disease areas in which women have to take medication, to stay healthy during pregnancy and support the health of their babies,” she says. “Understanding how drugs are transported to the fetus gives crucial information to help women and their health care providers make more informed choices about their medications.”

Piquette-Miller earned a degree in pharmacy before pursuing graduate studies in clinical pharmacology. Throughout her career, Piquette-Miller has focused her research on women’s health, including preclinical drug development for breast and ovarian cancers and studying drug transport proteins in the placenta. Her work has helped to improve researchers’ understanding of how drugs are transported through the body, especially the placenta, and how diseases and environmental factors might change drug transport. This work is helping to inform how treatments for serious conditions such as autoimmune diseases are delivered during pregnancy.

Piquette-Miller was recently recognized with the Canadian Society of Pharmacology and Therapeutics (CSPT) Senior Investigator Award, which recognizes a researcher who has made significant contributions to the advancement and extension of knowledge in the field. The award will be presented at the CSPT Annual Meeting, which will be held from June 2 to 5 in Vancouver.

Research uncovers role of inflammation in how drugs are transported into cells

Drug transporters are proteins in the cell membrane that move drugs into and out of the cell. The amount of drug transporters and how well they function determine how much of a drug is absorbed into the body, where it goes, and how fast it is eliminated. During pregnancy, drug transporters in the placenta may change how much of a medication reaches the fetus.

Piquette-Miller’s research has shown that inflammation – which is a component of many diseases including infectious diseases and chronic metabolic conditions like diabetes – particularly impacts drug transporters. This discovery helps to explain why some patients respond to drugs differently than others: underlying health conditions that result in inflammation may change the expression of drug transporters and the body’s uptake of the medication.

In recent years, she and her team have examined autoimmune diseases during pregnancy and the effect that these conditions have on drug transporters in the placenta. In a 2024 paper in Drug Metabolism and Disposition, she and her research team were the first to show that autoimmune diseases, including systemic lupus erythematosus (lupus), reduce the amount of P-glycoprotein drug transporters and change the set of proteins found in the placenta.

Piquette-Miller says that more knowledge about the molecular mechanisms that lead to these changes in drug transporter expression will not only provide patients and health care providers with more awareness and knowledge about which medications are safe during pregnancy, but also what treatments to pair their essential drugs to reduce the risk of adverse effects.

“Autoimmune diseases occur most frequently in women of reproductive age, and there’s such a lack of information on drug disposition and the impact on fetal drug exposure during pregnancy in this population.”

“Autoimmune diseases occur most frequently in women of reproductive age, and there’s such a lack of information on drug disposition and the impact on fetal drug exposure during pregnancy in this population,” she says.

“By identifying the molecular mechanisms involved in drug uptake in the placenta, our hope is that we can actually mitigate fetal exposure to drugs. We’re looking at whether nutritional supplementation could reduce the local inflammation and dysregulation of drug transporters and whether these and other compounds could be taken during pregnancy to result in a safer way of taking essential medications.”

Throughout her career, Piquette-Miller’s pharmacology research has always maintained a translational focus. Her collaborations with clinicians and research using patient samples have ensured that findings from her team can be applied to patients, and she is currently collaborating with colleagues from the Leslie Dan Faculty of Pharmacy to establish a preclinical research centre to move promising drug discovery and formulation research closer to benefiting patients.

“With my background in pharmacy and pharmacology, I take a translational approach so that we can look at questions from many different angles, but it’s important for me to always think about the clinical question,” she says. “My research is always driven by a clinical need.”