Research in context
Evidence before this study
Enterovirus A71 (EV-A71) is responsible for a substantial disease burden of hand, foot, and mouth disease (HFMD) in young children in the Asia-Pacific region, particularly in mainland China. An increased circulation of EV-A71 was described in European and North American countries, leading to outbreaks of severe neurological illness, which poses a growing global public health concern. A 2015 systematic review showed that 30% of children in China were seronegative against EV-A71 and thus remained susceptible at age 5 years. Available licensed EV-A71 vaccines in China cannot be given to infants younger than 6 months, among whom a substantial burden of severe disease occurs. Necessity and timing of vaccination in early life is highly related with maternal-derived antibody levels and their persistence. We searched PubMed, Web of Science, China National Knowledge Infrastructure, and Wanfang up to Feb 10, 2020, using the following search terms: (enterovirus 71 OR EV-A71 OR EV-71 OR EV71) AND (seroepidemiology OR seroepidemiologic OR seroepidemiological OR serosurvey OR seroprevalence OR seroprevalent OR seronegative OR seropositive OR serologic OR serological OR seroincidence OR seroconversion OR seroconvert OR GMT) AND (maternal OR maternally OR mother OR transplacental OR placental OR infant OR newborn OR neonate OR neonatal OR child OR children). Only four cross-sectional studies and one longitudinal cohort study reported the correlation between EV-A71 maternal and neonate antibodies in mother–neonate pairs, with one study presenting the transfer ratio. Of these studies, the cohort study alone characterised the half-life of EV-A71 maternal antibodies, but obtained only two blood specimens from neonates within 6 months of age (ie, the cord blood and venous blood at age 6 months). Another cohort study found that 33% of infants aged 3 months and 7% of infants aged 6 months were positive for EV-A71 antibodies. One study reported the seropositivity and antibody titres in neonates aged 2 and 7 months, but could not estimate the dynamics of maternal antibodies because the blood samples were not collected for neonates at birth. No studies were found that addressed the duration of protection conferred by maternal-transferred antibodies.
Added value of this study
In this study, we assessed the transplacental transfer ratio of EV-A71 antibodies, calculated the half-life of maternal-derived EV-A71 antibody titres, and the time to loss of protective immunity in neonates (with a cutoff titre of 16 or higher for protective titres). To our knowledge, this was the largest population-based study of mother–neonate pairs followed up from birth to age 36 months that quantified the transplacental transfer efficiency of EV-A71 antibodies, and measured the dynamics of EV-A71 antibodies in neonates. Our findings show that the mean transplacental transfer ratio was 1·03 (95%CI 0·98–1·08). Although the majority of neonates acquired protective concentrations of EV-A71 antibodies from their mothers, this protection declined rapidly. After the disappearance of maternal antibodies, antibody titres rose because of natural infection, with about a third of children infected by the age of 2·5 years.
Implications of all the available evidence
Our study showed that protective titres of EV-A71 antibodies could be efficiently transferred to neonates from mothers through the placenta. However, maternal antibodies declined rapidly. The findings provide helpful information to guide EV-A71 vaccination programmes and suggest that maternal vaccination could be explored to provide protection to neonates and infants younger than 6 months against EV-A71 through maternal antibodies. Catch-up vaccination between ages 6 months to 5 years could provide protection to the approximately 30–90% of children that have not had natural EV-A71 infection by that age.