Strategic Pregnancy Delays Can Mitigate Zika-Related Birth Defects

Diana Phillips

July 29, 2016

The effectiveness of mass pregnancy delays as a strategy to reduce prenatal Zika virus infections and subsequent, associated birth abnormalities depends on the timing of the initiation of the strategy relative to the peak of the outbreak in the affected region, the duration of the delay, and adherence to the recommended policy, a study has shown.

Health ministries in regions most affected by Zika virus outbreaks, including those across Latin America and the Caribbean, have advised women to postpone pregnancy to reduce the risk for birth defects related to Zika virus infection. Depending on the region, the ministries are recommending pregnancy delays ranging from 6 months to 2 years, although some do not specify any duration, Martial L. Ndeffo-Mbah, PhD, from the Yale School of Public Health, Yale University, and colleagues report in an article published online July 26 in the Annals of Internal Medicine.

To evaluate the effectiveness of this delay strategy in reducing the incidence and prevalence of prenatal Zika virus infection, the researchers developed a data-driven Zika virus transmission model, using epidemiologic data on Zika virus infection in Colombia from 2015 to 2016. The disease transmission model included both human and mosquito population dynamics, the authors explain.

The reported cases of Zika virus that were fitted to the transmission model comprised weekly suspected and laboratory-confirmed cases of the disease reported by the National Institute of Health of Colombia. Suspected cases included individuals presenting with fever, rash, and at least one of the following symptoms: nonpurulent conjunctivitis or conjunctival hyperemia, arthralgia, myalgia, headache, or malaise. "In addition, they had to have been in a place at less than 2200 m elevation with autochthonous Zika virus transmission within the 15 days before symptom onset," the authors write.

The researchers calculated the basic reproductive ratio of the ongoing Zika virus epidemic in Colombia and used the fitted model to estimate the number of cases of symptomatic and asymptomatic Zika virus infection and prenatal infections that would occur by the end of 2016 if the outbreak continued.

According to these calculations, the projected overall Zika virus infections and prenatal infections during the first trimester of pregnancy in currently affected communities were 1.18 million cases (95% credible interval [CrI], 0.50 - 2.07 million cases) and 11,768 (CrI, 6907 - 22,300), respectively.

"Applying the risk for microcephaly associated with Zika virus infection during the first trimester from the French Polynesia outbreak, we estimated that 112 (CrI, 50 to 446) microcephaly cases will occur in Colombia from prenatal infection in 2016 from both symptomatic and asymptomatic cases," the authors write. "Alternatively, if the risk for microcephaly is associated with infection at any time during pregnancy, the estimate of prenatal infections increases to 29,230 (CrI, 17,760 to 56,500) in 2016, leading to 278 (CrI, 126 to 860) microcephaly cases."

In their evaluation of the effect of mass pregnancy-delay strategies ranging from 3 to 24 months from the onset of the outbreak until June 2017, "[w]e found that if the delay was initiated 1 week after the onset of the epidemic, delays of 6 months or less were likely to increase prenatal exposure and the prevalence of microcephaly cases compared with no delay," the authors report.

Of note, the greater the adherence to the short-duration strategies, the less effective the strategies were. "This paradoxical exacerbation arises because the surge in pregnancies after the period of abstinence would occur near the incidence peak of the epidemic," the authors write.

In comparing the effectiveness of mass strategies vs individual-based strategies, the former were more effective at reducing prenatal infections for delays of 9 months or longer, but less effective for delays of 6 months or less, the authors report.

Specifically, based on calculations for 50% adherence to recommendations to delay pregnancy for 3 to 6 months, the projected incidence of prenatal exposure increased by 2.1% to 7.6% for mass strategies and decreased by 7.5% to 8.9% for individual-based strategies.

The projected incidence for prenatal exposure associated with delays of 9 to 24 months decreased by 16.8% to 43.8% for mass strategies and decreased by 9.5% to 10.3% for individual-based efforts.

Incremental reductions in prenatal infections were observed for extended individual delays after a 6-month mass strategy delay, the authors state.

With respect to the timing of the delay, "[w]e found that the optimal timing for initiation of a recommended delay depended on its duration," the authors write. "A 6-month delay was most effective when it was initiated 4 months into the outbreak, whereas the optimal timing of initiation of a 9-month delay was 2 months into the outbreak." Regardless of the stage of the epidemic, "a delay of more than 6 months was shown to be more effective in reducing prenatal exposure than a shorter delay," they stress.

In addition, the model identified important relationships between the time to peak incidence and the number of microcephaly cases, suggesting that "vector-control measures that reduce A aegypti density or contacts with women of reproductive age not only could reduce microcephaly incidence but may also postpone the timing to the incidence peak of the epidemic," the authors write.

The findings of the current evaluation suggest that delaying pregnancy without other interventions "will probably be insufficient to curtail Zika-related birth abnormalities," the authors write. "In the absence of a vaccine or therapeutic drugs for Zika virus infection, a combination of mass and individual pregnancy-delay strategies with effective vector-control measures is needed to curtail the spread and burden of the ongoing outbreak in the Americas." Delaying pregnancy can be an effective component of a multifaceted strategy for reducing Zika-related birth defects, they conclude.

The authors have disclosed no relevant financial relationships.

Ann Intern Med. Published online July 26, 2016. Full text

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