Prenatal cranial MR findings in fetuses with suspected CMV infection: Correlation with postnatal outcome and differential diagnostic considerations

Abstract

Purpose: To: (1) Evaluate intrauterine MRI (iuMRI) findings in fetuses with suspected cCMV and correlate these with final diagnosis(es). (2) Correlate iuMRI in cases of confirmed cCMV with clinical outcomes. Methods: Retrospective cohort of iuMRI referrals for suspected cCMV between 2010 and 2018. Confirmed cCMV defined as positive amniotic fluid or postnatal CMV polymerase chain reaction (PCR) test and excluded cCMV defined by negative postnatal PCR. Results: Twenty-nine singleton fetuses had iuMRI for suspected cCMV (median gestation 28 weeks (IQR 24-32). No postnatal outcome (n = 6) and no cCMV ascertainment (n = 5) provided 18 cases for analysis. cCMV positive (n = 11): three fetal deaths occurred, one spontaneous and two terminations of pregnancy (TOP), one for microcephaly and one for extensive polymicrogyria; 4/ 8 survivors had normal US and iuMRI with normal newborn hearing screen (AABR)/ neurological examination; two had polymicrogyria and cerebral palsy (CP) GMFCS II and V; 1 had isolated ventriculomegaly and failed newborn AABR; 1 had ventriculomegaly with germinolytic cysts, normal AABR and development at 3/12. cCMV negative (n = 7): Germinolytic cysts were present in 4 cases with 2/4 also having callosal hypogenesis and postnatal genetic and clinical diagnosis of mitochondrial disorder. The third and fourth had a normal newborn metabolic screen and neurological examination. Three deaths were due to toxoplasmosis (n = 1), TOP for severe ventriculomegaly (n = 1) and bilateral schizencephaly (n = 1). Conclusions: Polymicrogyria in fetuses with cCMV, undetected with prenatal US, was associated with CP. Germinolytic cysts were non-specific for cCMV and due to mitochondrial disorders when callosal hypogenesis was present.

The association between congenital cytomegalovirus infection and cerebral palsy: A systematic review and meta‐analysis

“…One study has bias from poor representativeness and a high percentage of subjects lost follow-up due to fetal deaths or termination of pregnancy. 11 Other common methodological issues of the studies include poor sample representativeness, low sample size and incomplete reporting of the results. Therefore, the grade of evidence of the meta-analysis is very low due to the basis of observational data, high heterogeneity and publication bias.…”

“…The characteristics of the individual included studies are summarised in detail in Table 1. [3][4][5][10][11][12][13][21][22][23][24][25] The studies which were included were from 2005 to 2020. Of these, three studies were from North America, three studies were from Europe, five studies were from Australia and one study was from Japan.…”

“…The quality rating for one study scored 5 out of 9 because the study had a small sample size, bias from poor representativeness and a high percentage of subjects lost follow-up due to fetal deaths or termination of pregnancy. 11 The studies by Gibson et al, 3 Smithers-Sheedy et al 12 and Smithers-Sheedy et al 13 had the highest score with the least bias but were limited by lack of representativeness or lack of selection of non-exposed cohort.…”

“…10 In order to diagnose and identify pregnant women who have primary or reactivation of CMV, a maternal serology is needed. 11 To confirm a fetal cCMV infection, an amniotic fluid polymerase chain reaction (PCR) test is required. However, since prenatal screening for congenital CMV is not routinely done, a fetal ultrasound abnormality is needed in order to probe further investigations.…”

“…However, since prenatal screening for congenital CMV is not routinely done, a fetal ultrasound abnormality is needed in order to probe further investigations. 11 Limited epidemiological studies have been conducted to study the role of congenital CMV infection in the development of cerebral palsy. 4,12,13 However, the results are not conclusive to support congenital CMV infection as Key points 1 The prevalence of patients with cerebral palsy who were diagnosed with congenital cytomegalovirus (CMV) infection was 10.9%, which is significantly higher than the proportion of all newborns diagnosed with congenital CMV infection.…”