Cytomegalovirus is responsible for the most common congenital infection, affecting 0.5% to 1.0% of live births in Europe. Congenital cytomegalovirus infection can be diagnosed during pregnancy by viral DNA amplification in the amniotic fluid, but the prognosis of fetuses without severe brain abnormalities remains difficult to establish on the basis of prenatal imaging alone. To identify predictors of moderate to severe symptomatic cytomegalovirus infection among fetal blood parameters and to propose an algorithm on the basis of these parameters and on prenatal imaging that would provide the best positive and negative predictive values. Fetal blood sampling at 21–28 weeks gestation was performed in fetuses with congenital cytomegalovirus infection confirmed by amniocentesis after maternal infection in the first-trimester or periconceptional period. We compared the levels of hemoglobin, thrombocytes, γ-glutamyl transpeptidase, aspartate aminotransferase, alanine aminotransferase, β2-microglobulin, immunoglobulins G and M, and cytomegalovirus DNA viral loads in amniotic fluid and fetal blood between those with moderate to severe symptomatic infection and those with asymptomatic to mild infection (median follow-up of 36 months for live births). Among 58 fetuses included, 25 (43%) had a moderate to severe symptomatic infection: 16 with severe cerebral abnormalities, 5 with multiple signs or symptoms at birth, 2 with bilateral sensorineural hearing loss, and 2 with neurodevelopmental delay. The values of thrombocytes, aspartate aminotransferase, β2 microglobulin, Immunoglobulin M, and cytomegalovirus viral loads differed significantly between fetuses with moderate to severe symptomatic infection and those with asymptomatic to mild infection. The optimal strategy to predict moderate to severe symptomatic infection was to first perform fetal brain imaging, followed by fetal blood sampling with the following cutoffs: thrombocytes <120,000/mL, viremia ≥5 log/mL, and β2 microglobulin ≥12 mg/L). This recursive algorithm had a negative predictive value of 100% for moderately to severely symptomatic infection. The combination of thrombocytes, β2-microglobulin, and cytomegalovirus viral load in fetal blood can be used for prognosis determination, particularly in cytomegalovirus-infected fetuses without severe brain abnormalities at the time of prenatal diagnosis. Future studies should evaluate whether these parameters remain useful in infected fetuses who have been treated with valacyclovir before fetal blood sampling.

中文翻译：

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胎儿血液采样对确定先天性巨细胞病毒感染预后的贡献：瑞士的一项病例队列研究

巨细胞病毒是最常见的先天性感染，影响欧洲 0.5% 至 1.0% 的活产婴儿。先天性巨细胞病毒感染可以在怀孕期间通过羊水中的病毒DNA扩增来诊断，但仅根据产前影像学仍难以确定没有严重脑部异常的胎儿的预后。确定胎儿血液参数中中度至重度症状性巨细胞病毒感染的预测因素，并根据这些参数和产前成像提出一种算法，以提供最佳的阳性和阴性预测值。对孕早期或围孕期母体感染后经羊膜穿刺证实患有先天性巨细胞病毒感染的胎儿，在妊娠21-28周时进行胎儿血采样。我们比较了中度至重度症状感染者和胎儿血液中的血红蛋白、血小板、γ-谷氨酰转肽酶、天冬氨酸转氨酶、丙氨酸转氨酶、β2-微球蛋白、免疫球蛋白G和M以及巨细胞病毒DNA病毒载量。无症状至轻度感染（活产的中位随访时间为 36 个月）。在 58 名胎儿中，25 名 (43%) 患有中度至重度症状感染：16 名患有严重脑异常，5 名出生时有多种体征或症状，2 名患有双侧感音神经性听力损失，2 名患有神经发育迟缓。有中度至重度症状感染的胎儿与无症状至轻度感染的胎儿之间，血小板、天冬氨酸转氨酶、β2微球蛋白、免疫球蛋白M和巨细胞病毒载量的值存在显着差异。预测中度至重度症状感染的最佳策略是首先进行胎儿脑成像，然后进行胎儿血液采样，截止值如下：血小板<120,000/mL，病毒血症≥5 log/mL，β2微球蛋白≥12 mg/L） 。这种递归算法对于中度至重度症状感染的阴性预测值为 100%。胎儿血液中血小板、β2-微球蛋白和巨细胞病毒病毒载量的组合可用于判断预后，特别是在产前诊断时没有严重脑异常的巨细胞病毒感染胎儿。未来的研究应评估这些参数对于在胎儿血液采样前接受伐昔洛韦治疗的感染胎儿是否仍然有用。