The impact of intrauterine growth restriction on cytochrome P450 enzyme expression and activity. (15th September 2020)

• Record Type: Journal Article
• Authors: McBride, Grace M.; Wiese, Michael D.; Soo, Jia Yin; Darby, Jack R.T.; Berry, Mary J.; Varcoe, Tamara J.; Morrison, Janna L.
• Is Part Of: Placenta. Volume 99(2020)
• Page Start: 50
• Page End: 62
• Publication Date: 2020-09-15
• Subjects: IUGR -- Cytochrome P450 -- Maternal medications -- Fetal drug metabolism; Placenta -- Periodicals; Reproduction -- Periodicals; Placenta -- Periodicals; Placenta -- Périodiques; Reproduction -- Périodiques; 612.63
• DOI: 10.1016/j.placenta.2020.07.012
• Languages: English
• ISSNs: 0143-4004

Abstract

Abstract: With the increased prevalence of non-communicable disease and availability of medications to treat these and other conditions, a pregnancy free from prescribed medication exposure is rare. Up to 99% of women take at least one medication during pregnancy. These medications can be divided into those used to improve maternal health and wellbeing (e.g., analgesics, antidepressants, antidiabetics, antiasthmatics), and those used to promote the baby's wellbeing in either fetal (e.g., anti-arrhythmics) or postnatal life (e.g., antenatal glucocorticoids). These medications are needed for pre-existing or coincidental illnesses in the mother, maternal conditions induced by the pregnancy itself through to conditions that arise in the fetus or that will be encountered by the newborn. Thus, medications administered to the mother may be used to treat the mother, the fetus or both. Metabolism of medications is regulated by a range of physiological processes that change during pregnancy. Other pathological processes such as placental insufficiency can in turn have both immediate and lifelong adverse health consequences for babies. Individuals born growth restricted are more likely to require medications but may also have an altered ability to metabolise these medications in fetal and postnatal life. This review aims to determine the effect of suboptimal fetal growth on the fetal expression of the drug metabolising enzymes (DMEs) that convert medications into active or inactive metabolites, and the transporters that remove both these medications and their metabolites from the fetal compartment. Highlights: Globally, one in seven babies are born intrauterine growth restricted (IUGR). 99% of women take medications during pregnancy. IUGR alters maternal and fetal physiology, impacting drug metabolism. Hormonal changes due to IUGR alter cytochrome P450 drug metabolising enzymes. Pregnancies impacted by IUGR may need changes to medication guideline for maternal-fetal safety & efficacy.