Microcephaly occurs in 1% of women infected with Zika during early pregnancy
Based on data from the 2013-2014 Zika virus outbreak in French Polynesia, researchers estimated that the risk for microcephaly is approximately one in 100 women infected with the virus during their first trimester.
“Our analysis strongly supports the hypothesis that Zika virus infection during the first trimester of pregnancy is associated with an increased risk of microcephaly,” Simon Cauchemez, PhD, of the mathematical modeling of infectious diseases unit at Institut Pasteur in Paris, said in a press release. “It remains to be seen whether our findings apply to other countries in the same way.”
Cauchemez and colleagues performed a retrospective analysis of the Zika virus outbreak that occurred from October 2013 to April 2014 in French Polynesia — the largest documented Zika outbreak before the current epidemic in the Americas — to assess the association between Zika and microcephaly and quantify the risk for microcephaly in the fetuses of mothers infected with the virus.
“Data from French Polynesia are particularly important since the outbreak is already over,” Arnaud Fontanet, MD, DrPH, professor at the Institut Pasteur, said in the release. “This provides us with a small, yet much more complete dataset than data gathered from an ongoing outbreak.”
To determine the magnitude of the outbreak, the researchers analyzed serological and surveillance data and performed an exhaustive search of medical records from Sept. 1, 2013 to July 31, 2015. During that time, more than 31,000 individuals sought consultation for suspected Zika virus infection, although only 8,750 were considered to be suspected cases and 383 were laboratory-confirmed. The seroprevalence of Zika after the end of the outbreak was 66% (95% CI, 62-70) vs. 0.8% before the outbreak.
Eight cases of microcephaly were detected during the study period, seven of which were identified toward the end of the outbreak between March 1 and July 10, 2014. Five of the cases were terminated through medical abortion (median gestational age, 30.1 weeks).
Cauchemez and colleagues developed a mathematical and statistical model to illustrate the association between Zika virus and microcephaly, and examined six risk periods during pregnancy to determine when the risk for microcephaly was greatest.
Three risk periods demonstrated a “satisfactory fit,” and all included the first trimester of pregnancy, the researchers wrote. The model was best fitted for the first trimester, during which the baseline prevalence of microcephaly was two cases (95% CI, 0-8) per 10,000 neonates, and the risk for microcephaly was 95 cases (95% CI, 34-191) per 10,000 women infected during the first trimester, or roughly one case per 100 women (RR = 53.4; 95% CI, 6.5-1,061.2).
“We estimated that the risk of microcephaly was about 1%,” Cauchemez and colleagues wrote. “Zika virus in the general population can be very high during outbreaks. Thus, although infection with Zika virus is associated with a low fetal risk, it is an important public health issue.”
Based on the model, the researchers also determined that the risk for microcephaly was increased during risk periods that included trimesters one or two (50 cases per 10,000 women; 95% CI, 17-101) and in trimesters one, two or three (42 cases per 10,000 women; 95% CI, 13-86). There were no models that supported an increased risk during periods that excluded the first trimester.
“Our analysis strongly supports the hypothesis that infection in the first trimester of pregnancy is associated with an increased risk of microcephaly,” Cauchemez and colleagues concluded. “It will be important to ascertain whether Zika virus is associated with other fetal or neonatal neurological complications.”
In a related editorial, Laura C. Rodrigues, MD, MSc, PhD, suggested that it is “biologically plausible” that the risk for microcephaly is highest during the first trimester due to the timing of brain development and the severity of neurological abnormalities associated with microcephaly. Rodrigues, however, also questioned whether the risk for microcephaly is dependent on other factors such as the clinical severity of Zika virus infection or prior dengue infection.
“Further data will soon be available,” Rodrigues wrote. “The fast production of knowledge during this epidemic is an opportunity to observe science in the making: from formulation of new hypotheses and production of new results that will provide confirmations and contradictions to the refinement of methods and the gradual building of consensus. I expect we will teach our students about the production of science using examples from this Public Health Emergency of International Concern for many years to come.” – by Stephanie Viguers
Disclosure: The researchers report no relevant financial disclosures.