Pharmacogenomics of nifedipine therapy in threatened spontaneous preterm birth: opportunities for maternal precision medicine

Ana Datcu ¹, Mihaela Raluca Radu ^{2 *}, Alina Pradatu ², Catalina Micu ²

¹ Department of Medical Genetics, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
² Fetal Medicine Excellence Research Center, Alessandrescu-Rusescu National Institute for Mother and Child Health, Bucharest, Romania
* Correspondence to: Mihaela Raluca Radu, Fetal Medicine Excellence Research Center, Alessandrescu-Rusescu National Institute for Mother and Child Health, 020395, Bucharest, Romania. E-mail: ralucamihaelaradu@gmail.com

Abstract

Spontaneous preterm birth (sPTB) is a multifactorial syndrome driven by intersecting biological pathways, including inflammation, cervical remodeling, extracellular matrix dysregulation, and myometrial activation. Acute tocolysis is used to delay delivery long enough to complete antenatal corticosteroid administration and, when needed, enable maternal transfer to an appropriate level of care. Among first-line tocolytics, nifedipine is widely used because it is orally administered, inexpensive, and generally well tolerated; however, response is heterogeneous, and dose-limiting adverse effects (notably hypotension and tachycardia) occur in a subset of patients. Pregnancy introduces major physiological changes in drug disposition, and genetic variability in drug-metabolizing enzymes, transporters, and pharmacodynamic targets may further contribute to interindividual differences in nifedipine exposure and uterine response. This narrative review integrates evidence on the contemporary role of nifedipine in acute tocolysis, maternal genomic pathways associated with sPTB risk, and pharmacogenomic signals relevant to nifedipine pharmacokinetics and pharmacodynamics, with particular emphasis on CYP3A4/5-mediated metabolism and biologically plausible variation in L-type calcium channel signaling. We propose a precision tocolysis framework that links maternal genotype, pregnancy physiology, and clinical response phenotypes to support future prospective studies and ultimately improve individualized obstetric therapeutics.