Development of Maternal Antibodies Post ZIKV in Pregnancy is Associated with Lower Risk of Microcephaly and Structural Brain Abnormalities in Exposed Infants.

Abstract

BACKGROUND We investigated the association between maternal neutralizing antibodies (nAb) to Zika virus (ZIKV) in pregnancy and neonatal outcomes. METHODS In pregnant participants with confirmed ZIKV infection, we determined trimester of infection, collected sera longitudinally, and measured nAbs via plaque reduction. In neonates, adverse outcomes included microcephaly (MC), structural brain abnormalities (SBA), hearing, and eye abnormalities. Associations between trimester of infection, nAbs, and neonatal outcomes were analyzed with Cox regression. RESULTS In total, 137 ZIKV-positive pregnant participants had neutralization assays performed during pregnancy and postdelivery. Infection rates were 29% in the first, 50% in the second, and 21% in the third trimester. Mean ZIKV nAb titer >2 weeks postinfection was 64 258 (SD 213 288). Ten percent of 90% plaque reduction neutralization assays (PRNT90) titers were <500, 10% 500-1000, 73% > 1000, and 7% did not have serologic follow-up; 15%. of infants had adverse findings. Protective factors against MC in 88 mothers with nAb titers available during pregnancy included infection later in gestation (adjusted hazard ratio [aHR], 0.06; P = .036) and adequate nAb titers (aHR, 0.17; P = .014). No SBA was associated with later infection in pregnancy (aHR, 0.16; P = .017) and adequate nAb titers (aHR, 0.34; P = .012). Adjusting for trimester, higher maternal nAb titers were associated with lower risk of MC and SBA. Seven of 137 participants (5.1%) had positive serum ZIKV polymerase chain reaction (PCR) results beyond 14 days (range, 35-269 days). Participants with ZIKV PCR positivity >60 days (n = 2) had infants with MC/SBA. CONCLUSIONS MC and SBA were less frequent in infants of mothers with higher ZIKV nAb titers during pregnancy.