Seidenari Anna, Dionisi Camilla, Nati Marina, Marsico Concetta, Gabrielli Liliana, Capretti Maria Grazia, Toni Francesco, Lazzarotto Tiziana, Simonazzi Giuliana
Obstetric Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.
Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum-University of Bologna, Bologna, Italy.
Prenat Diagn. 2025 Feb;45(2):178-184. doi: 10.1002/pd.6731. Epub 2024 Dec 18.
To determine outcomes at birth and postnatal sequelae of congenital cytomegalovirus (cCMV) infection following maternal primary infection in the first trimester with normal fetal brain imaging at midgestation.
A retrospective, single-center cohort study was conducted, including all cases of proven cCMV infection following maternal primary infection in the first trimester from 2014 until 2021 and normal fetal brain imaging before 22 weeks of gestation. All pregnancies were followed according to our protocol, which offers amniocentesis at least 8 weeks after the onset of infection, serial ultrasound scans, and a fetal MRI in the third trimester. No women received treatment with CMV hyperimmune globulin or Valacyclovir during pregnancy. Follow-up of newborns was obtained, and newborns were classified as symptomatic or asymptomatic at birth. Postnatal sequelae were evaluated, and cases with a follow-up period of less than 12 months were excluded.
We found 42 newborns with cCMV, confirmed at birth by PCR for the CMV genome in neonatal urine samples, and normal fetal brain imaging up to 22 weeks of gestation. Extracerebral signs of infection were present in 3/42 fetuses at the second trimester ultrasound (20-22 weeks of gestation). In the third trimester (28-32 weeks of gestation), none showed abnormal brain sonographic findings, but four exhibited extracerebral signs of CMV infection. Among 42 newborns, 29 were classified as asymptomatic (29/42, 69.1%) and 13 as symptomatic at birth (13/42, 30.9%, 95%CI 17.6%-47.1%). Eight newborns had abnormal cranial ultrasound/MRI (8/42, 19%), one presented abnormal postnatal brain imaging associated with hearing loss and four had sensorineural hearing loss (SNHL) at initial assessment. All were treated with oral Valganciclovir. Four newborns with normal hearing at birth had delayed onset SNHL. One case of hearing loss improved after treatment and returned to normal hearing. At a median follow-up of 35 months, 8 infants had hearing loss (8/42, 19%, 95%CI 8.6%-34.1%) and none presented with severe brain abnormalities.
For infants with congenital CMV following untreated first trimester maternal primary infection, the absence of abnormal prenatal brain ultrasound findings at the mid-trimester morphology scan does not rule out the possibility of postnatal neuroimaging anomalies or the need for treatment after birth. However, no severe brain abnormalities were detected after birth in our cohort, and the only observed sequelae were sensorineural hearing loss.
确定孕早期母体初次感染先天性巨细胞病毒（cCMV）且孕中期胎儿脑成像正常情况下的出生结局及产后后遗症。
进行了一项回顾性单中心队列研究，纳入2014年至2021年期间所有孕早期母体初次感染且确诊为cCMV感染、妊娠22周前胎儿脑成像正常的病例。所有妊娠均按照我们的方案进行随访，该方案在感染发作后至少8周提供羊膜腔穿刺术、系列超声扫描以及孕晚期胎儿磁共振成像（MRI）检查。孕期无女性接受巨细胞病毒高效价免疫球蛋白或伐昔洛韦治疗。对新生儿进行随访，并在出生时将新生儿分为有症状或无症状。评估产后后遗症，排除随访期少于12个月的病例。
我们发现42例cCMV感染的新生儿，出生时通过新生儿尿液样本中CMV基因组的聚合酶链反应（PCR）确诊，且妊娠22周前胎儿脑成像正常。孕中期超声检查（妊娠20 - 22周）时，42例胎儿中有3例出现脑外感染体征。孕晚期（妊娠28 - 32周）时，无脑超声异常表现，但有4例出现CMV感染的脑外体征。42例新生儿中，29例出生时被分类为无症状（29/42，69.1%），13例为有症状（13/42，30.9%，95%置信区间17.6% - 47.1%）。8例新生儿头颅超声/MRI异常（8/42，19%），1例出生后脑部成像异常并伴有听力损失，4例在初始评估时有感音神经性听力损失（SNHL）。所有患儿均接受口服缬更昔洛韦治疗。4例出生时听力正常的新生儿出现迟发性SNHL。1例听力损失患儿治疗后听力改善并恢复正常。中位随访35个月时，8例婴儿有听力损失（8/42，19%，95%置信区间8.6% - 34.1%），无严重脑部异常表现。
对于孕早期母体初次感染未经治疗后先天性CMV感染的婴儿，孕中期形态学扫描时产前脑超声检查无异常发现并不能排除产后神经影像学异常或出生后需要治疗的可能性。然而，我们的队列中出生后未检测到严重脑部异常，唯一观察到的后遗症是感音神经性听力损失。
