Metcalf Angela, Martiniano Stacey L, Sagel Scott D, Zaretsky Michael V, Zemanick Edith T, Hoppe Jordana E
Department of Pediatrics, University of Colorado Anschutz Medical Campus and Children's Hospital Colorado, Aurora, CO, United States.
Department of Pediatrics, University of Colorado Anschutz Medical Campus and Children's Hospital Colorado, Aurora, CO, United States.
J Cyst Fibros. 2025 May;24(3):466-468. doi: 10.1016/j.jcf.2024.11.011. Epub 2024 Dec 6.
As cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapies including elexacaftor/tezacaftor/ivacaftor (ETI) have become widely used in eligible patients with cystic fibrosis (CF), the use of these medications in pregnant people has become a critical area of investigation. Since these medications appear generally safe to both mother and fetus when taken by pregnant people with CF, interest has pivoted to the use of ETI in CF carrier mothers to decrease morbidity and mortality from meconium ileus (MI) in fetuses with cystic fibrosis. Here we discuss three infants at our institution with ultrasound findings of MI who were exposed to prenatal ETI through CF carrier mothers for the purposes of treating MI and lowering risk of intestinal complications from this severe manifestation of CF. These cases differ in the timing of ETI initiation, severity of outcome, and accessibility of this off-label medication use to families depending on their insurance. All infants and mothers tolerated the medication well without significant side effects. One infant had complete MI resolution, one had persistent MI at birth with easy clearance with minimally invasive therapies, and one had persistent MI requiring jejunostomy. The infant with the most severe outcome had the shortest duration of ETI exposure and may have been able to receive this medication sooner had a referral to a CF center been made. These cases highlight the potentially life-altering effects of prenatal ETI use and the need for awareness of this clinical situation among fetal care providers.
随着包括依列卡托/替扎卡托/依伐卡托（ETI）在内的囊性纤维化跨膜传导调节因子（CFTR）调节剂疗法已广泛应用于符合条件的囊性纤维化（CF）患者，这些药物在孕妇中的使用已成为一个关键的研究领域。由于CF孕妇服用这些药物时对母亲和胎儿似乎总体安全，人们的兴趣已转向在CF携带者母亲中使用ETI，以降低患有囊性纤维化胎儿胎粪性肠梗阻（MI）的发病率和死亡率。在此，我们讨论了我院的三名婴儿，他们经超声检查发现患有MI，通过CF携带者母亲在产前接触了ETI，目的是治疗MI并降低CF这种严重表现所致肠道并发症的风险。这些病例在ETI开始使用的时间、结局的严重程度以及这种超说明书用药对家庭的可及性（取决于其保险情况）方面存在差异。所有婴儿和母亲对药物耐受性良好，无明显副作用。一名婴儿的MI完全消退，一名婴儿出生时MI持续存在，但通过微创治疗很容易清除，还有一名婴儿的MI持续存在，需要进行空肠造口术。结局最严重的婴儿ETI暴露时间最短，如果转诊至CF中心，可能能够更早接受这种药物治疗。这些病例凸显了产前使用ETI可能改变生命的影响，以及胎儿护理提供者了解这种临床情况的必要性。
