DENGUE VIRUS

MAJOR CONGENITAL ANOMALIES

The frequency of major malformations overall was not higher than expected among the infants of 987 women who had symptomatic dengue infection during the first trimester of pregnancy in a Brazilian record-linkage study (Nascimento et al., 2017). The reported rates of congenital anomalies in both infants of the dengue-positive (0.8%) and control (1.0%) groups in this study were much lower than expected, so underascertainment of birth defect outcomes is likely. In another report from the same dataset, the frequency of congenital neurological anomalies among liveborn infants of women who had symptomatic dengue infection during pregnancy was not significantly increased compared to uninfected pregnant women (Paixao et al., 2018). In their analyses, the authors looked specifically at categories of central nervous system malformations, and found no associations with anencephaly, microcephaly, encephalocele, or congenital hydrocephalus in infants of infected mothers, but a significant association with other congenital malformations of the brain was reported (odds ratio=4.5, 95% confidence interval 1.7-11.3).

VERTICAL TRANSMISSION

The risk of transplacental transmission of the dengue virus from mother to infant is greater with greater maternal viral load and also varies by viral strain (Ahuja et al., 2023). Higher rates of transmission have been reported when infection occurs near delivery (Arragain et al., 2017; Basurko et al., 2018).

ADVERSE PREGNANCY AND NEONATAL OUTCOMES

Symptomatic dengue infection during pregnancy almost doubled the odds of fetal death (adjusted odds ratio=1.9, 95% confidence interval 1.6-2.2) and was even higher if the mother’s infection was severe (adjusted odds ratio=4.9, 95% confidence interval 2.3-10.2) in a nested case-control study based on Brazilian linked registry data (Paixao et al., 2017). Four (9%) infants of 44 women who had confirmed dengue infection in pregnancy in one series were stillborn (Brar et al., 2021). In another series, a higher rate of death was found among fetuses of women with suspected or confirmed dengue infections during pregnancy when compared to the expected fetal death rate at a French Guiana hospital (13.6% vs 1.9%) (Carles et al., 1999).

In a retrospective case-control study conducted in a hospital setting, the frequency of maternal dengue infection in early pregnancy was higher among 116 women who presented with miscarriages at or before 22 weeks of gestation compared to 348 matched women with viable pregnancies (adjusted odds ratio=4.2, 95% confidence interval 1.2-14.0) (Tan et al., 2012). An increased frequency of preterm birth among 3821 pregnant women with symptomatic dengue infection was reported in a Brazilian retrospective record-linkage study (odds ratio=1.26, 95% confidence interval 1.06-1.49) (Nascimento et al., 2017). In a different study using the same dataset, a doubling of the risk of preterm birth (odds ratio=2.4, 95% confidence interval 1.3-4.4) and of low birth weight (odds ratio=2.1, 95% confidence interval 1.1-4.0) was found with severe maternal dengue infection in pregnancy (Paixao et al., 2019). Premature delivery occurred in 15 (34%) and low birth weight in 13 (30%) of the infants of 44 pregnant women who tested positive for dengue virus (Brar et al., 2021). A systematic review and meta-analysis of earlier controlled observational studies showed an association of maternal symptomatic dengue infection during pregnancy with preterm birth (odds ratio=2.5, 95% confidence interval 1.4-4.3) and low birth weight (odds ratio=1.8, 95% confidence interval 1.0-3.2) (Paixao et al., 2016).

ANIMAL TERATOLOGY STUDIES

Animal teratology studies of dengue viruses have not been published in the peer-reviewed literature.