Drug Exposure in Newborns: Effect of Selected Drugs Prescribed to Mothers During Pregnancy and Lactation

摘要

The number of newborns exposed to therapeutic drugs during pregnancy is growing because of the increased use of drugs during pregnancy. In recent years, advances in our understanding of drug placental transfer have augmented the likelihood of a healthy baby in mothers with chronic diseases needing drug therapy. Globally, for example, more than 1.4 million pregnancies in 2015 have been burdened with antiretroviral drugs due to an increasing number of HIV-positive women treated with these drugs, particularly in low- and middle-income countries. In most cases, the fetus is exposed to much higher drug doses in utero than the newborn nursed by the mother. Drug transfer through the placenta takes place by passive diffusion, active transport, or facilitated transport, and drug concentrations in the fetal circulation may be comparable to that in the mother's blood concentration. The excretion of drugs into breastmilk predominantly occurs by passive diffusion, allowing only the non-protein-bound fraction of the blood drug concentration to penetrate. Drug agencies in the United States and Europe highly recommend performing clinical trials in pregnant or breastfeeding women. However, only a few drugs have reported statistically sound data in these patient groups. Most available results concerning pregnancy are obtained from observational studies after birth, assessing outcomes in the newborn or by measuring drug concentrations in the mother and umbilical cord blood. In the case of the lactation period, some studies have evaluated drug concentrations in breastmilk and blood of the mother and/or infant. In this review, exposure to antiretrovirals, immunosuppressants used after solid organ transplantation, and antiepileptics during pregnancy and lactation has been discussed in detail.