Congenital Cytomegalovirus Infection Following Second and Third Trimester Maternal Infection Is Associated With Mild Childhood Adverse Outcome Not Predicted by Prenatal Imaging

Abstract

Background While it is clear that first trimester congenital cytomegalovirus (CMV) infection can lead to serious neonatal and childhood adverse outcome, the extent of the effect of second and third trimester congenital CMV infection is still unclear. Our aim was to study the short- and long-term outcomes following second and third trimester infection and to evaluate the contribution of prenatal imaging in a prospective cohort. Methods We studied pregnant women with primary CMV infection in the second and third trimesters, as diagnosed by well-dated seroconversion, and proof of vertical CMV transmission. All patients underwent serial prenatal ultrasound (US) and most of them fetal magnetic resonance imaging (MRI). Follow-up information was obtained from hospital charts and by telephone interviews with parents. Results Primary CMV infection occurred in 135 patients, 107 and 28 with second and third trimester infection, respectively. The incidence proportion of composite outcome (hearing loss or neurodevelopmental impairment) following second trimester infection was 7% (7/100, after excluding cases that were terminated) with a 3% incidence of partial unilateral sensory neural hearing loss and a 5% incidence of minor neurodevelopmental abnormalities, including slight verbal and motor delay. Following third trimester infection, there was one case of a very mild motor delay. The incidence proportion of abnormal prenatal findings on US or MRI was not significantly correlated to hearing loss or neurodevelopmental abnormalities. Conclusions Second trimester infection is associated with a slight risk of developing mild childhood sequelae, mostly partial unilateral hearing loss, which may develop late in childhood. Prenatal imaging failed to predict the development of childhood adverse outcome.

Neurodevelopmental outcomes in congenital and perinatal infections

“…The absence of abnormalities on fetal ultrasound and MRI in the context of maternal CMV infection decreases the risk of hearing and neurodevelopmental issues but not completely [17,57 ▪▪ ]. In one study, children with normal and abnormal fetal imaging after maternal primary CMV infection had SNHL or neurodevelopmental issues at similar rates [58 ▪ ]. On the contrary, according to meta-analysis of 557 infants, a negative CMV PCR on amniocentesis was associated with normal hearing and neurodevelopment [59 ▪▪ ].…”

The Role of Fetal Brain Magnetic Resonance Imaging in Current Fetal Medicine

“…In fetuses infected with CMV in the first trimester, there is an increased risk of sensorineural hearing loss and impaired cognitive development [ 1 2 57 58 59 60 61 ]. Neurosonography (NSG) is the most important modality in the follow-up of fetuses with confirmed first-trimester CMV-infection [ 59 ].…”

“…Fetal magnetic resonance imaging (MRI) has become an important adjunct to prenatal ultrasound in the assessment of fetal abnormalities of the central nervous system. It has become clear that both modalities are complementary, allowing better understanding of the disease process, classification of abnormalities, and determination of prognosis and management options [ 1 2 3 ]. Over the last decades, several in utero treatment options have been proven beneficial and effective, including laser coagulation in monochorionic pregnancies complicated by twin-to-twin transfusion syndrome (TTTS), in utero closure of spina bifida aperta and, most recently fetoscopic endoluminal tracheal occlusion in congenital diaphragmatic hernia (CDH).…”

The Placental Response to Guinea Pig Cytomegalovirus Depends Upon the Timing of Maternal Infection

“…cCMV is also a cause of intrauterine growth restriction, preterm birth, and fetal demise (4)(5)(6)(7)(8). The timing of maternal human cytomegalovirus (HCMV) infection during pregnancy affects the rate of congenital transmission and fetal outcomes post-infection (9)(10)(11)(12)(13)(14)(15)(16)(17)(18). Neurologic sequelae are most frequently observed in congenitally infected children when maternal infection occurs in the first trimester (14)(15)(16)(17).…”

“…Neurologic sequelae are most frequently observed in congenitally infected children when maternal infection occurs in the first trimester ( 14 – 17 ). Maternal infection late in pregnancy is associated with the highest rates of intrauterine growth restriction (IUGR) and congenital infection ( 9 – 13 , 15 , 18 ).…”