Laboratory Medicine, University Hospital Basel, University Basel, Basel, Switzerland.
Ther Drug Monit. 2020 Apr;42(2):255-263. doi: 10.1097/FTD.0000000000000747.
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.
由于怀孕期间药物使用的增加，暴露于治疗性药物的新生儿数量不断增加。近年来，我们对药物胎盘转运的认识不断提高，增加了患有慢性疾病需要药物治疗的母亲生育健康婴儿的可能性。例如，在全球范围内，由于越来越多的 HIV 阳性妇女接受这些药物治疗，2015 年有超过 140 万例妊娠受到抗逆转录病毒药物的影响，特别是在中低收入国家。在大多数情况下，胎儿在子宫内暴露于比母亲哺乳的新生儿高得多的药物剂量。药物通过胎盘的转移通过被动扩散、主动转运或易化转运进行，胎儿循环中的药物浓度可能与母亲血液中的浓度相当。药物排入母乳主要通过被动扩散发生，只允许血液药物浓度中非蛋白结合部分穿透。美国和欧洲的药物机构强烈建议在孕妇或哺乳期妇女中进行临床试验。然而，只有少数药物在这些患者群体中报告了具有统计学意义的数据。关于妊娠的大多数现有结果是通过出生后的观察性研究获得的，评估新生儿的结局或通过测量母亲和脐带血中的药物浓度来获得。在哺乳期，一些研究评估了母乳和母亲及/或婴儿血液中的药物浓度。在这篇综述中，详细讨论了抗逆转录病毒药物、实体器官移植后使用的免疫抑制剂以及抗癫痫药物在妊娠和哺乳期的暴露情况。
