Joosen Annemiek M C P, van der Linden Ivon J M, Schrauwen Lianne, Theeuwes Alisia, de Groot Monique J M, Ermens Antonius A M
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Clin Chem Lab Med. 2017 Nov 27;56(1):113-119. doi: 10.1515/cclm-2017-0110.
Vasopressin and adrenomedullin and their stable by-products copeptin and midregional part of proadrenomedullin (MR-proADM) are promising biomarkers for the development of preeclampsia. However, clinical use is hampered by the lack of trimester-specific reference intervals. We therefore estimated reference intervals for copeptin and MR-proADM in disease-free Dutch women throughout pregnancy.
Apparently healthy low risk pregnant women were recruited. Exclusion criteria included current or past history of endocrine disease, multiple pregnancy, use of medication known to influence thyroid function and current pregnancy as a result of hormonal stimulation. Women who miscarried, developed hyperemesis gravidarum, hypertension, pre-eclampsia, hemolysis elevated liver enzymes and low platelets, diabetes or other disease, delivered prematurely or had a small for gestational age neonate were excluded from analyses. Blood samples were collected at 9-13 weeks (n=98), 27-29 weeks (n=94) and 36-39 weeks (n=91) of gestation and at 4-13 weeks post-partum (PP) (n=89). Sixty-two women had complete data during pregnancy and PP. All analyses were performed on a Kryptor compact plus.
Copeptin increases during pregnancy, but 97.5th percentiles remain below the non-pregnant upper reference limit (URL) provided by the manufacturer. MR-proADM concentrations increase as well during pregnancy. In trimesters 2 and 3 the 97.5th percentiles are over three times the non-pregnant URL provided by the manufacturer.
Trimester- and assay-specific reference intervals for copeptin and MR-proADM should be used. In addition, consecutive measurements and the time frame between measurements should be considered as the differences seen with or in advance of preeclampsia can be expected to be relatively small compared to the reference intervals.
血管加压素和肾上腺髓质素及其稳定的副产物 copeptin 和肾上腺髓质素原中段（MR-proADM）是子痫前期发展中有前景的生物标志物。然而，缺乏孕龄特异性参考区间阻碍了其临床应用。因此，我们估计了荷兰无病孕妇整个孕期 copeptin 和 MR-proADM 的参考区间。
招募表面健康的低风险孕妇。排除标准包括当前或既往内分泌疾病史、多胎妊娠、使用已知影响甲状腺功能的药物以及因激素刺激导致的当前妊娠。流产、发生妊娠剧吐、高血压、子痫前期、溶血、肝酶升高和血小板减少、糖尿病或其他疾病、早产或新生儿小于胎龄的妇女被排除在分析之外。在妊娠9 - 13周（n = 98）、27 - 29周（n = 94）和36 - 39周（n = 91）以及产后4 - 13周（PP）（n = 89）采集血样。62名妇女在孕期和产后有完整数据。所有分析均在 Kryptor compact plus 上进行。
copeptin 在孕期升高，但第97.5百分位数仍低于制造商提供的非孕上限参考值（URL）。MR-proADM 浓度在孕期也升高。在孕中期和孕晚期，第97.5百分位数是制造商提供的非孕 URL 的三倍多。
应使用 copeptin 和 MR-proADM 的孕龄和检测特异性参考区间。此外，应考虑连续测量以及测量之间的时间框架，因为与参考区间相比，子痫前期时或子痫前期之前出现的差异预计相对较小。
