Dengue

Dengue Infection and Miscarriage: A Prospective Case
Control Study
Peng Chiong Tan1*, May Zaw Soe1, Khaing Si Lay1, Seok Mui Wang2, Shamala Devi Sekaran2, Siti
Zawiah Omar1
1 Department of Obstetrics and Gynaecology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia, 2 Department of Medical Microbiology, Faculty of
Medicine, University of Malaya, Kuala Lumpur, MalaysiaAbstract
Background: Dengue is the most prevalent mosquito borne infection worldwide. Vertical transmissions after maternal
dengue infection to the fetus and pregnancy losses in relation to dengue illness have been reported. The relationship of
dengue to miscarriage is not known.
Method: We aimed to establish the relationship of recent dengue infection and miscarriage. Women who presented withmiscarriage (up to 22 weeks gestation) to our hospital were approached to participate in the study. For each case of
miscarriage, we recruited 3 controls with viable pregnancies at a similar gestation. A brief questionnaire on recent febrile
illness and prior dengue infection was answered. Blood was drawn from participants, processed and the frozen serum was
stored. Stored sera were thawed andthen tested in batches with dengue specific IgM capture ELISA, dengue non-structural
protein 1 (NS1) antigen and dengue specific IgG ELISA tests. Controls remained in the analysis if their pregnancies continued
beyond 22 weeks gestation. Tests were run on 116 case and 341 control sera. One case (a misdiagnosed viable early
pregnancy) plus 45 controls (39 lost to follow up and six subsequent latemiscarriages) were excluded from analysis.
Findings: Dengue specific IgM or dengue NS1 antigen (indicating recent dengue infection) was positive in 6/115 (5?2%)
cases and 5/296 (1?7%) controls RR 3?1 (95% CI 1?0–10) P = 0?047. Maternal age, gestational age, parity and ethnicity were
dissimilar between cases and controls. After adjustments for these factors, recent dengue infection remainedsignificantly
more frequently detected in cases than controls (AOR 4?2 95% CI 1?2–14 P = 0?023).
Interpretation: Recent dengue infections were more frequently detected in women presenting with miscarriage than in
controls whose pregnancies were viable. After adjustments for confounders, the positive association remained.
Citation: Tan PC, Soe MZ, Si Lay K, Wang SM, Sekaran SD, et al. (2012)Dengue Infection and Miscarriage: A Prospective Case Control Study. PLoS Negl Trop
Dis 6(5): e1637. doi:10.1371/journal.pntd.0001637
´
Editor: Maria G. Guzman, Tropical Medicine Institute Pedro Kourı (IPK), Cuba
Received October 14, 2011; Accepted March 23, 2012; Published May 8, 2012
Copyright: ß 2012 Tan et al. This is an open-access article distributed under the terms of the Creative CommonsAttribution License, which permits unrestricted
use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: The research is funded by an internal grant (RG160-09HTM) from the University of Malaya. The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
Competing Interests:The authors have declared that no competing interests exist.
* E-mail: pctan@um.edu.my

of 1000 Malaysian adults aged 35–74, the dengue seroprevalence
rate was 91.6% with a positive age related trend [11].
Severe dengue illness during pregnancy is associated with major
adverse outcome of maternal deaths [12,13], perinatal deaths [12–14],
preterm births [12,14] and haemorrhages in labourwith much of the
data from case reports and small case series [15]. In a large prospective
study of recent dengue infection detected at delivery, the pregnancy
outcome of 63 parturients who were dengue IgM positive is not
different from 2468 IgM negative controls [16]. Vertical transmission
to the fetus (particularly later in pregnancy) is established [15]. The
vertical transmission rate of...