Prevalence of Antibodies to Zika Virus in Mothers from Hawaii Who Delivered Babies with and without Microcephaly between 2009-2012

Abstract

Zika virus (ZIKV) is an emerging mosquito-borne pathogen. ZIKV infection is linked to the development of severe fetal abnormalities that include spontaneous abortion, stillbirth, hydranencephaly, and microcephaly. ZIKV outbreaks have been recorded in the United States. We recently demonstrated the first congenital ZIKV infection in the United States. In this study, we investigated archived blood samples from six mothers who gave birth to babies with microcephaly and 12 mothers who gave birth to healthy babies in Hawaii between 2009 and 2012. We tested maternal blood for the presence of ZIKV IgM and IgG antibodies using commercially available human ZIKV IgM and IgG ELISA kits. Blood from one mother who delivered babies with microcephaly tested positive for ZIKV IgM antibody (16.6%) and blood from three mothers tested positive for ZIKV IgG antibody (50%). ZIKV showed a trend toward significance with microcephaly. ZIKV IgG antibody positive mothers were more likely to deliver babies with microcephaly than mothers who were negative for ZIKV IgG antibodies (Odds ratio [OR] = 11.0, 95% confidence interval [CI] = 0.8–147.9, p = 0.083). Similarly, ZIKV IgM antibody positive mothers were also more likely to deliver babies with microcephaly than mothers who were negative for ZIKV IgM antibody (OR = 6.8, 95% CI = 0.2–195.1). These data provide further evidence of a link between ZIKV infection and microcephaly and suggests presence of ZIKV positive cases and associated microcephaly in the United States as early as 2009.

Possible Congenital Zika Syndrome in Older Children Due to Earlier Circulation of Zika Virus

“…A recent retrospective study of six infants with microcephaly born in Hawaii found an association between maternal ZIKV infection and infant microcephaly as early as 2009, although further phenotypic description of these infants with possible CZS was not provided (M. Kumar et al, ). This raises the question that if CZS existed prior to the 2013 French Polynesia outbreak, why was it not recognized earlier?…”

Another piece of the Zika puzzle: Assessing the associated factors to microcephaly in a systematic review and meta-analysis.

“…From those, 138 studies were ruled out based on the exclusion criteria. After the full-text review, a total of 12 observational studies were included in the synthesis of the literature [29][30][31][32][33][34][35][36][37][38][39][40] (Figure 1). Of the 12 eligible studies, six authors provided the primary data [29,34,[37][38][39][40], and therefore were included in the meta-analysis.…”

“…The twelve included studies were published between 2015 and 2018; ten of them had Research Ethics Board approval and two declared themselves exempt from this approval [30,39]. Five were cohort studies [30,[33][34][35][36], three were case-controls studies [31,32,38], three were case-series [29,37,39], and one was a cross-sectional study [40]. The studies de ned as case-series [29,37,39] were conducted based on surveillance data -local surveillance system and hospital-based surveillance -and reported only ZIKV infected cases with varied outcomes.…”

“…All 12 studies were conducted in the Americas: three of them in the United States [30,36,38], one in the Caribbean [29], and eight in South America, i.e., Brazil [31-33, 37, 39, 40], French Guiana [34], and Colombia [35]. The total population enrolled in the included studies is 6154 newborns/fetuses.…”

“…Regarding laboratory evidence, six tested the mothers/pregnant women [33,[35][36][37][38][39], and six studies tested both mothers/pregnant women and newborns/fetuses [29-32, 34, 40] (Table 1). RT-PCR was used in seven studies [29,30,[33][34][35][36][37] in at least one phase of the diagnosis, but only two of them used this test as the con rmation tool for all the cases [29,33].…”