Association between Zika virus and microcephaly in French Polynesia, 2013-15: a retrospective study

Abstract

Background: The emergence of Zika virus in the Americas has coincided with increased reports of babies born with microcephaly. On Feb 1, 2016, WHO declared the suspected link between Zika virus and microcephaly to be a Public Health Emergency of International Concern. This association, however, has not been precisely quantified.

Methods: We retrospectively analysed data from a Zika virus outbreak in French Polynesia, which was the largest documented outbreak before that in the Americas. We used serological and surveillance data to estimate the probability of infection with Zika virus for each week of the epidemic and searched medical records to identify all cases of microcephaly from September, 2013, to July, 2015. Simple models were used to assess periods of risk in pregnancy when Zika virus might increase the risk of microcephaly and estimate the associated risk.

Findings: The Zika virus outbreak began in October, 2013, and ended in April, 2014, and 66% (95% CI 62-70) of the general population were infected. Of the eight microcephaly cases identified during the 23-month study period, seven (88%) occurred in the 4-month period March 1 to July 10, 2014. The timing of these cases was best explained by a period of risk in the first trimester of pregnancy. In this model, the baseline prevalence of microcephaly was two cases (95% CI 0-8) per 10,000 neonates, and the risk of microcephaly associated with Zika virus infection was 95 cases (34-191) per 10,000 women infected in the first trimester. We could not rule out an increased risk of microcephaly from infection in other trimesters, but models that excluded the first trimester were not supported by the data.

Interpretation: Our findings provide a quantitative estimate of the risk of microcephaly in fetuses and neonates whose mothers are infected with Zika virus.

Funding: Labex-IBEID, NIH-MIDAS, AXA Research fund, EU-PREDEMICS.

Figure 1. Epidemic of ZIKV and timing of microcephaly cases in French Polynesia, September 2013–July 2015

A. Estimated number of weekly consultations for suspected ZIKV infection (black line) along with the timing of microcephaly cases. For each microcephaly case, a red horizontal line indicates the estimated start of pregnancy and the date when it ended (delivery / medical abortion) (red dot). Dashed grey lines indicate the start/end of the study period (September 2013 – July 2015). Dotted black lines show the time period when 95% of consultations for suspected ZIKV infection occurred (14 October 2013 – 17 February 2014). B. Timing of microcephaly cases in French Polynesia (in red) along with predictions from seven models (in orange and black). These models make different assumptions about the ‘period of risk’ in pregnancy when ZIKV infection of the mother leads to an increased risk of microcephaly for the foetus/neonate. Dots indicate the median date while horizontal lines show the 15% and 85% percentiles. Models are sorted according to their AICc with the best fitting model at the top. Predictions of models are in orange when fit is judged satisfying (based on dAICc) and in black otherwise.

Figure 2. Final attack rates in the ZIKV epidemic and strength of the association between ZIKV and microcephaly in French Polynesia

A. Final attack rates (95% CI) in the ZIKV epidemic in French Polynesia. B. Baseline prevalence of microcephaly (number per 10,000 neonates) in French Polynesia and risk of microcephaly associated with ZIKV infection (number per 10,000 women infected in the first trimester of pregnancy).