A systematic review was done of published studies about dengue during pregnancy and adverse fetal outcomes. A total of 16 studies were reviewed, seven of them published during or since 2010. The studies included 6071 pregnant women, 292 of whom had evidence of dengue during pregnancy. (However, some studies included asymptomatic women with serological evidence of new infection.) Analysis was based on rates of miscarriage, stillbirth, prematurity, and low birthweight.
Compared to women without dengue during pregnancy, there was a 3.5 odds ratio of miscarriage in dengue-infected women. Only some of the studies showed a significant link between dengue infection during pregnancy and stillbirth, but there was a clear statistically significant link between severe dengue illness and stillbirth. Symptomatic dengue infection was associated with both preterm birth (odds ratio 2.5, statistically significant) and intrauterine growth restriction (odds ratio 1.8, statistically significant).
The authors wisely point out that several of the studies included in this analysis were simple case series. Further comparative epidemiologic studies will be useful.
COMMENTARY
Even as emerging Zika infection is highlighted in news reports, dengue is already endemic in more than 100 countries and accounts for approximately 100 million bouts of symptomatic illness each year. Unlike Zika, however, dengue during pregnancy has not attracted much attention. Paixao and colleagues have nicely reviewed available literature about dengue during pregnancy. While the data vary from study to study, it does appear that at least severe dengue illness is associated with significant risks for both fatal fetal outcomes and low birthweight at delivery (both from prematurity and from intrauterine growth restriction). Of note, Paixao and colleagues did not evaluate risks of microcephaly and other adverse outcomes.
It is not clear if dengue virus has specific effects in the placenta and fetus or if the risks are “just” due to nonspecific consequences of the mother having fever and altered fluid status. In fact, the statistical risks of poor outcomes are greater with severe illness than with asymptomatic or mild illness — suggesting that the adverse outcomes might relate more to the pregnant woman being sick than to specific action of the dengue virus on the developing child. Nonetheless, as the authors explain, dengue does stimulate increases in levels of pro-inflammatory cytokines, which are known to have significant adverse effects on the placenta.
Even beyond Zika and dengue, other travel-associated infections can have adverse effects on pregnancy outcomes, some due to direct action of the microorganism on the placenta and/or baby.1 Pre-travel consultation should be offered for pregnant women planning to visit parts of Asia, Central and South America, and Africa.
Pregnancy negatively alters malaria immunity, even in previously semi-immune women. Gestational malaria is associated with maternal illness and anemia. Babies born to mothers who had malaria during pregnancy are at risk of neonatal fever and death, low birthweight, anemia, and, subsequently, greater risks of symptomatic malaria.2
Yellow fever has been reported to be transmitted congenitally,1 but yellow fever vaccine is only rarely associated with adverse outcomes during pregnancy.1,3 However, transmission of vaccine-associated yellow fever through breastmilk has been reported following vaccination of lactating women. Japanese encephalitis virus also has been transmitted trans-placentally.1
Careful pre-travel consideration of risks of infections during pregnancy can prompt improved preventive efforts. When risky travel is truly necessary, careful attention to avoidance of insect bites and, for malaria, to appropriate chemoprophylaxis, can reduce risks and improve outcomes of pregnancy.
REFERENCES
- McGovern LM, Boyce TG, Fischer PR. Congenital infections associated with international travel during pregnancy. J Travel Med 2007;14:117-128.
- Hartman TK, Rogerson SJ, Fischer PR. The impact of maternal malaria on newborns. Ann Trop Paediatr 2010;30:271-282.
- Keller-Stanislawski B, Englund JA, Kang G, et al. Safety of immunization during pregnancy: A review of the evidence of selected inactivated and live attenuated vaccines. Vaccine 2014;32:7057-7064.
During pregnancy, dengue infection, especially with symptomatic illness, is associated with increased risks of miscarriage, stillbirth, and low birthweight.
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