Abstract：
BACKGROUND: Early diagnosis of congenital CMV infection (cCMVI) allows for early intervention and follow-up to detect delayed hearing loss. While CMV PCR in urine is the gold standard for cCMVI diagnosis, saliva testing is often performed.
OBJECTIVE: Our aim was to determine (i) if swab saliva sampling needed standardization, (ii) if a threshold value in \"virus copies per million cells (Mc)\" in saliva samples could improve clinical specificity, and (iii) to establish a correlation between viral load in saliva and symptomatology/outcome of cCMVI.
METHODS: In our institution, universal newborn screening is performed on saliva swabs at delivery or until day 3 of life. If positive, CMV PCR in urine is done within 2 weeks to confirm or exclude cCMVI.
RESULTS: Cell quantification showed that saliva swab sampling was well performed as 95.4 % samples had more than 100 cells/10 µL. There was a good correlation between saliva viral load in copies/mL and in copies/Mc (Pearson\'s r = 0.96, p < 0.0001). However, threshold values, established to determine a viral load level at which we could confidently identify infected newborns, did not improve positive predictive value (21.8 % for copies/mL and 21 % for copies/Mc vs 25.4 % without threshold) but instead reduced sensitivity (88 % and 85% vs 100 % without threshold). Samples collected on day 2 or 3 had better positive predictive value (38.7 %) compared to those collected on day 1 (23.8 %). Symptomatology at birth was not significantly associated with viral load in saliva at diagnosis. However, sequelae occurrence was associated with viral load in saliva (copies/Mc).
CONCLUSIONS: Our results confirm that saliva swab is a suitable sample for universal neonatal screening. However, identifying newborns that will develop sequelae remains an issue in the management of cCMVI.
OBJECTIVE: Our aim was to determine (i) if swab saliva sampling needed standardization, (ii) if a threshold value in \"virus copies per million cells (Mc)\" in saliva samples could improve clinical specificity, and (iii) to establish a correlation between viral load in saliva and symptomatology/outcome of cCMVI.
METHODS: In our institution, universal newborn screening is performed on saliva swabs at delivery or until day 3 of life. If positive, CMV PCR in urine is done within 2 weeks to confirm or exclude cCMVI.
RESULTS: Cell quantification showed that saliva swab sampling was well performed as 95.4 % samples had more than 100 cells/10 µL. There was a good correlation between saliva viral load in copies/mL and in copies/Mc (Pearson\'s r = 0.96, p < 0.0001). However, threshold values, established to determine a viral load level at which we could confidently identify infected newborns, did not improve positive predictive value (21.8 % for copies/mL and 21 % for copies/Mc vs 25.4 % without threshold) but instead reduced sensitivity (88 % and 85% vs 100 % without threshold). Samples collected on day 2 or 3 had better positive predictive value (38.7 %) compared to those collected on day 1 (23.8 %). Symptomatology at birth was not significantly associated with viral load in saliva at diagnosis. However, sequelae occurrence was associated with viral load in saliva (copies/Mc).
CONCLUSIONS: Our results confirm that saliva swab is a suitable sample for universal neonatal screening. However, identifying newborns that will develop sequelae remains an issue in the management of cCMVI.
摘要：
背景：先天性CMV感染（cCMVI）的早期诊断允许早期干预和随访以发现延迟性听力损失。虽然尿液中的CMVPCR是cCMVI诊断的金标准，经常进行唾液测试。
目的：我们的目的是确定（i）拭子唾液采样是否需要标准化，（ii）如果唾液样本中的“每百万细胞病毒拷贝（Mc）”阈值可以提高临床特异性，和(iii)建立唾液中的病毒载量与cCMVI的症状学/结果之间的相关性。
方法：在我们的机构中，新生儿普遍筛查是在分娩时或出生后第3天对唾液拭子进行的。如果是积极的，在2周内完成尿液中的CMVPCR以确认或排除cCMVI。
结果：细胞定量表明，唾液拭子采样进行得很好，因为95.4%的样品具有超过100个细胞/10µL。唾液病毒载量(拷贝/mL)和拷贝/Mc之间存在良好的相关性(Pearson'sr=0.96,p<0.0001)。然而,阈值，为了确定病毒载量水平，我们可以自信地识别受感染的新生儿，没有提高阳性预测值（拷贝/mL为21.8％，拷贝/Mc为21％，无阈值为25.4％），而是降低了灵敏度（88％和85％，无阈值为100％）。与在第1天收集的样品(23.8%)相比,在第2天或第3天收集的样品具有更好的阳性预测值(38.7%)。出生时的症状与诊断时唾液中的病毒载量没有显着相关。然而,后遗症的发生与唾液中的病毒载量（拷贝数/Mc）有关。
结论：我们的结果证实，唾液拭子是普遍新生儿筛查的合适样本。然而,确定会出现后遗症的新生儿仍然是cCMVI管理中的一个问题。
目的：我们的目的是确定（i）拭子唾液采样是否需要标准化，（ii）如果唾液样本中的“每百万细胞病毒拷贝（Mc）”阈值可以提高临床特异性，和(iii)建立唾液中的病毒载量与cCMVI的症状学/结果之间的相关性。
方法：在我们的机构中，新生儿普遍筛查是在分娩时或出生后第3天对唾液拭子进行的。如果是积极的，在2周内完成尿液中的CMVPCR以确认或排除cCMVI。
结果：细胞定量表明，唾液拭子采样进行得很好，因为95.4%的样品具有超过100个细胞/10µL。唾液病毒载量(拷贝/mL)和拷贝/Mc之间存在良好的相关性(Pearson'sr=0.96,p<0.0001)。然而,阈值，为了确定病毒载量水平，我们可以自信地识别受感染的新生儿，没有提高阳性预测值（拷贝/mL为21.8％，拷贝/Mc为21％，无阈值为25.4％），而是降低了灵敏度（88％和85％，无阈值为100％）。与在第1天收集的样品(23.8%)相比,在第2天或第3天收集的样品具有更好的阳性预测值(38.7%)。出生时的症状与诊断时唾液中的病毒载量没有显着相关。然而,后遗症的发生与唾液中的病毒载量（拷贝数/Mc）有关。
结论：我们的结果证实，唾液拭子是普遍新生儿筛查的合适样本。然而,确定会出现后遗症的新生儿仍然是cCMVI管理中的一个问题。
