Petersen Jesper Friis, Tiittanen Vilma, Wittfooth Saara, Løkkegaard Ellen, Friis-Hansen Lennart Jan
Department of Obstetrics and Gynecology, North Zealand Hospital, Dyrehavevej 29, 3400, Hillerød, Denmark.
Department of Clinical Medicine, University of Copenhagen, Denmark.
Pract Lab Med. 2024 Sep 16;42:e00428. doi: 10.1016/j.plabm.2024.e00428. eCollection 2024 Nov.
In combined first trimester screening for Down syndrome, Pregnancy-Associated Plasma Protein A (PAPP-A) is pivotal. PAPP-A tests evaluate total PAPP-A, consisting of the biologically active free PAPP-A (fPAPP-A) and PAPP-A complexed with eosinophil major basic protein's proform (proMBP). While PAPP-A is well-researched, limited understanding persists regarding fPAPP-A's first trimester concentrations and diagnostic utility.
and methods: PAPP-A and fPAPP-A levels were gauged in 602 serum samples at 2-week intervals (gestational weeks 4-14) from 159 women with delivery of a healthy neonate and 80 samples from 37 miscarriages. The final sample at the time of diagnosis from women who miscarried was included in analyses.
During the first trimester, PAPP-A and fPAPP-A levels displayed significant and strong correlation (r = 0.94), with median values doubling weekly. Free PAPP-A constituted only 3.0 % of PAPP-A over gestational weeks. Low fPAPP-A linked to miscarriage (p < 0.001), maternal weight (p < 0.001), and smoking (p = 0.02). For miscarriage prediction fPAPP-A was equal to PAPP-A (area under the receiver operating characteristics curve 0.79 vs. 0.81, p = 0.44).
Investigating fPAPP-A presence and concentration directly in first trimester serum has not been done previously. This study report lower fPAPP-A values than anticipated from prior enzymatic studies of fPAPP-A. fPAPP-A was not superior to PAPP-A as a first trimester biomarker in this dataset.
在孕早期唐氏综合征联合筛查中，妊娠相关血浆蛋白A（PAPP-A）至关重要。PAPP-A检测评估的是总PAPP-A，其由生物活性游离PAPP-A（fPAPP-A）和与嗜酸性粒细胞主要碱性蛋白前体（proMBP）复合的PAPP-A组成。虽然对PAPP-A已有充分研究，但对fPAPP-A在孕早期的浓度及诊断效用仍了解有限。
对159名分娩健康新生儿的女性的602份血清样本，以及37例流产女性的80份样本，每隔2周（孕4至14周）测量PAPP-A和fPAPP-A水平。将流产女性诊断时的最终样本纳入分析。
在孕早期，PAPP-A和fPAPP-A水平呈现显著且强的相关性（r = 0.94），中位数每周翻倍。在孕周范围内，游离PAPP-A仅占PAPP-A的3.0%。低fPAPP-A与流产（p < 0.001）、孕妇体重（p < 0.001）和吸烟（p = 0.02）有关。对于流产预测，fPAPP-A与PAPP-A相当（受试者操作特征曲线下面积分别为0.79和0.81，p = 0.44）。
此前尚未直接研究孕早期血清中fPAPP-A的存在及浓度。本研究报告的fPAPP-A值低于先前对fPAPP-A进行酶学研究预期的值。在该数据集中，fPAPP-A作为孕早期生物标志物并不优于PAPP-A。
