Patel Payal, Yeley Jana, Brown Cynthia, Wesson Melissa, Lesko Barbara G, Slaven James E, Chmiel James F, Jain Raksha, Sanders Don B
Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Int J Neonatal Screen. 2023 Feb 21;9(1):10. doi: 10.3390/ijns9010010.
Most people with cystic fibrosis (CF) are diagnosed following abnormal newborn screening (NBS), which begins with measurement of immunoreactive trypsinogen (IRT) values. A case report found low concentrations of IRT in an infant with CF exposed to the CF transmembrane conductance regulator (CFTR) modulator, elexacaftor-tezacaftor-ivacaftor (ETI), in utero. However, IRT values in infants born to mothers taking ETI have not been systematically assessed. We hypothesized that ETI-exposed infants have lower IRT values than newborns with CF, CFTR-related metabolic syndrome/CF screen positive, inconclusive diagnosis (CRMS/CFSPID), or CF carriers. IRT values were collected from infants born in Indiana between 1 January 2020, and 2 June 2022, with ≥1 CFTR mutation. IRT values were compared to infants born to mothers with CF taking ETI followed at our institution. Compared to infants identified with CF ( = 51), CRMS/CFSPID ( = 21), and CF carriers ( = 489), ETI-exposed infants ( = 19) had lower IRT values ( < 0.001). Infants with normal NBS results for CF had similar median (interquartile range) IRT values, 22.5 (16.8, 30.6) ng/mL, as ETI-exposed infants, 18.9 (15.2, 26.5). IRT values from ETI-exposed infants were lower than for infants with abnormal NBS for CF. We recommend that NBS programs consider performing CFTR variant analysis for all ETI-exposed infants.
大多数囊性纤维化（CF）患者是在新生儿筛查（NBS）异常后被诊断出来的，新生儿筛查首先要测量免疫反应性胰蛋白酶原（IRT）值。一份病例报告发现，一名子宫内接触过CF跨膜传导调节因子（CFTR）调节剂依列卡福-替扎卡福-依伐卡福（ETI）的CF婴儿的IRT浓度较低。然而，对于服用ETI的母亲所生婴儿的IRT值尚未进行系统评估。我们假设，接触ETI的婴儿的IRT值低于患有CF、CFTR相关代谢综合征/囊性纤维化筛查阳性、诊断不明确（CRMS/CFSPID）或CF携带者的新生儿。收集了2020年1月1日至2022年6月2日在印第安纳州出生且携带≥1个CFTR突变的婴儿的IRT值。将这些IRT值与在我们机构接受随访的患有CF且服用ETI的母亲所生婴儿进行比较。与确诊为CF的婴儿（n = 51）、CRMS/CFSPID（n = 21）和CF携带者（n = 489）相比，接触ETI的婴儿（n = 19）的IRT值较低（P < 0.001）。CF新生儿筛查结果正常的婴儿的IRT值中位数（四分位间距）为22.5（16.8，30.6）ng/mL，与接触ETI的婴儿[18.9（15.2，26.5）]相似。接触ETI的婴儿的IRT值低于CF新生儿筛查异常的婴儿。我们建议新生儿筛查项目考虑对所有接触ETI的婴儿进行CFTR变异分析。
