Neurological and growth outcomes in South African children with congenital cytomegalovirus: A cohort study

Abstract

Objectives To assess neurological sequelae and growth in the first 12 months of life in a cohort of congenital cytomegalovirus (cCMV) infected infants compared to cCMV uninfected infants. Study design This was a prospective matched cohort study conducted in Soweto, South Africa where forty-six confirmed cCMV cases were matched on HIV-exposure, gender and gestational age (±two weeks) to 84 cCMV-uninfected controls in a 1:2 ratio. Cases and controls were followed up until 12 months of age to assess anthropometry, hearing and neurodevelopmental outcomes. Results Thirty-four (73.9%) cCMV cases and 74 (88.1%) controls, completed all assessments at 12 months age. At 12 months, one cCMV case had died, none of the children in either group had SNHL and neurodevelopmental delay was present in a similar percentage of cCMV cases (n = 2; 6%) and controls (n = 1, 4%; OR 1.09, 95% CI 0.04-27.84, p = 0.958). Anthropometry did not differ between cases and controls overall throughout the follow up period. HIV-exposed cases had smaller head circumference for age at 6 and 12 months when compared with HIV-exposed controls.

What are the neurodevelopmental outcomes of children with asymptomatic congenital cytomegalovirus infection at birth? A systematic literature review

“…These include prospective ( n = 20), 18 , 20 , 21 , 24 , 25 , 26 , 27 , 28 , 30 , 32 , 33 , 34 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 45 retrospective ( n = 7) 22 , 23 , 29 , 31 , 35 , 43 , 44 and cross‐sectional studies ( n = 1), 19 conducted in 18 different countries; by region, 16 studies were conducted in Europe, 18 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 28 , 30 , 32 , 34 , 36 , 43 , 44 , 45 five in East Asia, 27 , 29 , 37 , 38 , 39 four in North America 31 , 40 , 41 ...…”

“…The age at last follow‐up ranged between 1 month and 18 years, with 6/28 studies (from three cohorts) including populations with at least 5 years of follow‐up 40 , 41 , 42 , 43 , 44 , 45 (duration unclear for one study). 19 cCMV was identified among children in the included studies via population screening ( n = 13), 18 , 21 , 27 , 29 , 33 , 34 , 38 , 39 , 41 , 42 , 43 , 44 , 45 diagnostic testing of populations with suspected infection or clinical indications ( n = 4), 19 , 20 , 22 , 26 testing of infants born to women with primary CMV infection during pregnancy ( n = 5) 23 , 24 , 32 , 35 , 37 or a combination of these ( n = 6). 25 , 28 , 30 , 31 , 36 , 40 Four studies only included infants born to women with primary maternal CMV infection, 23 , 24 , 32 , 35 whereas eight studies reported the proportion of children born to women with primary and non‐primary maternal CMV infections during pregnancy, 21 , 26 , 28 , 30 , 31 , 33 ...…”

“… 19 cCMV was identified among children in the included studies via population screening ( n = 13), 18 , 21 , 27 , 29 , 33 , 34 , 38 , 39 , 41 , 42 , 43 , 44 , 45 diagnostic testing of populations with suspected infection or clinical indications ( n = 4), 19 , 20 , 22 , 26 testing of infants born to women with primary CMV infection during pregnancy ( n = 5) 23 , 24 , 32 , 35 , 37 or a combination of these ( n = 6). 25 , 28 , 30 , 31 , 36 , 40 Four studies only included infants born to women with primary maternal CMV infection, 23 , 24 , 32 , 35 whereas eight studies reported the proportion of children born to women with primary and non‐primary maternal CMV infections during pregnancy, 21 , 26 , 28 , 30 , 31 , 33 , 34 , 45 although not all reported neurodevelopmental outcomes by these groups. The majority of studies did not report type or timing of maternal infection ( n = 16).…”

Association between Congenital Cytomegalovirus Infection and Brain Injury in Neonates: A Meta-analysis of Cohort Studies

“…We did not find association between congenital CMV infection and increasing risk of neurodevelopmental delay. Likewise, a cohort study, aiming to evaluate neurological and growth outcomes in South African children with congenital CMV, found that there was no significant difference in neurodevelopment between cases and controls at 12 months of age [33]. Bartlett et al did prospective studies of asymptomatic congenital CMV infected children with follow-up of one to 6 years and reported a cumulative incidence of neurodevelopmental impairment between 0% and 9.1% [34].…”

Neurodevelopmental outcomes in congenital and perinatal infections

“…Meta-analysis showed that 14% of asymptomatic newborns following maternal primary CMV infection had neurodevelopmental disorders in childhood [52]. However, in a South African cohort of infants with predominantly asymptomatic cCMV, the rates of hearing loss or neurodevelopmental issues on the Bayley-III at 6 and 12 months of age were similar compared with infants without cCMV [56]. There are thus conflicting studies regarding neurodevelopmental outcomes in asymptomatic infants.…”