Miley Nguyen, PharmD & Niharika Koppolu
Preeclampsia Management in Pregnancy: The Role of Pharmacogenomics. Can clinicians leverage genetic testing to effectively manage pre-eclampsia in pregnant patients? Recent findings suggest the answer is yes. Pre-eclampsia, a pregnancy complication characterized by high blood pressure and excessive protein in urine, affects 2–5% of pregnancies. If left untreated, it has the potential to progress rapidly to eclampsia, a life-threatening condition (Chaemsaithong et al. 2023 & Luizon et al. 2018). By understanding a patient’s genetic profile, obstetricians can better predict pre-eclampsia risk, personalize treatment strategies, and optimize maternal and fetal outcomes.
Pregnancy alters metabolism. Pregnancy causes unique changes to the body, including increased renal clearance and altered hepatic metabolism, both of which influence drug response (Betcher & George, 2020). Genetic variations not only affect a pregnant patient’s ability to metabolize medications, but it can also alter a patient’s risk for developing pre-eclampsia (Betcher & George, 2020 & Chaemsaithong et al., 2023). The mainstay treatment for pre-eclampsia is antihypertensives. However, most antihypertensives are contraindicated in pregnancy, narrowing down the preferred options to nifedipine or labetalol.
Nifedipine and labetalol in treatment of preeclampsia. Nifedipine and labetalol are both metabolized by CYP450 enzymes. Pregnancy alters enzyme activity, particularly for CYP3A4, CYP2D6, and CYP2C19, complicating drug selection and dosing. Pharmacogenomics (PGx) reveals changes in drug metabolism pathways, allowing clinicians to exercise professional judgement on optimal drug selection based on the genetic profile of a patient. For example, nifedipine is metabolized by CYP2D6. If a provider knows a patient’s CYP2D6 metabolizer status, it enables them to adjust the dose of nifedipine accordingly (Betcher & George, 2020). Similarly, Labetalol, a preferred beta-blocker for managing hypertension in pregnancy, is metabolized by the CYP2C19 enzyme, among others. This is especially significant because variations in CYP2C19 have been linked to therapeutic failures in up to 60% of patients (Luizon et al., 2018). PGx offers a solution to such life-threatening outcomes.
Utility of PGx in pregnant populations is significant and often overlooked. Recognizing metabolic changes that occur during pregnancy allows clinicians to tailor treatments for pre-eclampsia, enhancing both safety and efficacy for patients. This approach not only improves therapeutic outcomes but also underscores the utility of PGx in this particularly susceptible and overlooked population.
Learn more about UGenome’s Personalized Medication Service, ProPEx, or contact UGenome. You can also find case studies for UGenome’s bioinformatics services Metabolite Identification, Bone Metastasis Risk Analysis in Breast Cancer, Survival Analysis with gene signatures in cancer
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