European Journal of Obstetrics & Gynecology and Reproductive Biology 261 (2021) 205–210

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European Journal of Obstetrics & Gynecology and

Reproductive Biology
journal homepage: www.elsevier.com/locate/ejogrb

Full length article

Dengue in pregnancy: Review article

Varsha Mulik* , Nimra Dad, Sara Buhmaid
Sidra Medicine, Education City, Al Luqta Street, Doha, Qatar

A R T I C L E I N F O A B S T R A C T

Article history: Dengue is the most common viral mosquito- borne disease. It is a major public health problem, especially
Received 6 November 2020 in tropical and sub-tropical areas worldwide. According to the World Health Organization (WHO),
Received in revised form 16 April 2021 approximately 40% of the world’s population (over 2.5 billion people) live in areas with high risk of
Accepted 23 April 2021
contracting dengue infection. Adults of childbearing age and pregnant women are travelling more
frequently to tropical areas. Therefore exposing themselves to specific arboviral infections such as
Keywords: dengue, which may impact ongoing and future pregnancies. Clinical manifestations of dengue are wide
Dengue
ranging from asymptomatic to needing intensive care in cases of hemorrhagic dengue fever. The effects of
Pregnancy
Perinatal outcome
dengue during and on pregnancy are unclear, moreover there is a lack of a cohesive reference to inform
women of reproductive age who live in or travel to endemic areas and are at risk of contracting dengue.
Here we present review of literature specifically looking at etiology, pathogenesis, clinical
manifestations, management of dengue in pregnancy as well as its effect on maternal health and
fetal outcomes. There is clear evidence to suggest adverse maternal outcomes in women with
symptomatic dengue in low resource countries. A high index of clinical suspicion and early referral to
tertiary center will prevent maternal –fetal serious adverse events in endemic areas.
This review will help Clinicians in advising as well as managing women who travel during pregnancy to
endemic areas as well as clinicians based in endemic areas who are managing women with dengue in
pregnancy.
© 2021 Elsevier B.V. All rights reserved.

Introduction cite that 390 million people have dengue virus infections with 96
million cases annually worldwide, more than three times WHO's
Dengue is a mosquito-borne viral disease that has rapidly 2012 estimate. However, the true disease burden is not well
spread in all regions of World in recent years. According to its known, especially in India, Indonesia, Brazil, China, and Africa [2].
incidence and mortality rate, dengue ranked as the second most (Dengue exacts a high economic burden on both governments and
serious vector-borne disease worldwide, following malaria [1]. individuals. Dengue illness in the Americas costs US$2
1 billion per
Dengue virus (DENV) is transmitted by female mosquitoes mainly year on average, excluding vector control, exceeding costs of other
of the species Aedes aegypti and, to a lesser extent, Aedes viral illnesses. In Southeast Asia, 2
9 million dengue episodes and
albopictus. These mosquitoes are also vectors of chikungunya, 5906 deaths were estimated annually, with an annual economic
yellow fever and Zika viruses. Dengue is caused by a virus of the burden of $950 million [3]. Its rapid global emergence is related to
Flaviviridae family and there are four distinct, but closely related, demographic and societal changes of the past 50–60 years,
serotypes of the virus that cause dengue (DENV-1, DENV-2, DENV- including unprecedented population growth, increasing move-
3 and DENV-4). ment of people (and consequently viruses), urbanization and
The incidence of dengue fever (DF) globally has grown breakdown of public health infrastructure and vector control [4].
dramatically in recent decades. Dengue is endemic in more than The number of cases, including explosive outbreaks, are
100 countries in Southeast Asia, the Americas, the western Pacific, increasing in the regions above. Disease spread has been reported
Africa and the eastern Mediterranean regions, and its incidence has in Europe in recent years. Local transmission was reported for the
increased 30-fold in the past 50 years [1]. Asia represents around first time in France and Croatia in 2010 and imported cases were
70% of the global burden of disease. Recent estimates made in 2013 detected in 3 other European countries [5]. Travelers’ play an
important role in global dengue epidemiology, carrying viruses
from one region to another [6].
* Corresponding author at: Sidra medicine, PO Box 26999, Doha, Qatar. A vast majority of cases are asymptomatic or mild and can be
E-mail address: [email protected] (V. Mulik). self-managed as well as being misdiagnosed as other febrile

https://doi.org/10.1016/j.ejogrb.2021.04.035
0301-2115/© 2021 Elsevier B.V. All rights reserved.
V. Mulik, N. Dad and S. Buhmaid European Journal of Obstetrics & Gynecology and Reproductive Biology 261 (2021) 205–210

illnesses leading under reporting of dengue. Therefore, there is Pathophysiology

sparse data regarding maternal and fetal outcomes in pregnancies
affected by dengue as well as the course of dengue in pregnancy. Dengue is a syndrome and its pathogenesis an interplay
This review addresses both these areas. between virus and host factors that remains incompletely
understood.
Transmission of virus Frequently, more than one type of DENV circulates in a
geographic region at one time (hyperendemicity). Co-circulation
The primary mode of transmission of DENV between humans of more than one type of DENV is thought to be one of the most
are mosquito vectors. Dengue transmission results from inter- important risk factors for the development of more severe disease
actions between people, mosquitoes, viruses, and environmental within a population [11]. Recovery from infection is believed to
factors. A combination of asymptomatic infection in humans and provide lifelong immunity against the specific serotype. Cross-
movement of people are likely to be more important determinants immunity to the other serotypes after recovery is found to be
of dengue's persistence. partial, and temporary. Subsequent infections (secondary infec-
tion) by other serotypes increase the risk of developing severe
Mosquito-to-human transmission dengue.
When sequential DENV infections are closely spaced, there is
The virus is transmitted to humans through the bites of infected significant cross-protection. This cross-protection initially pre-
female mosquitoes, primarily the Aedes aegypti mosquito. Other vents infection by a second DENV but it persists in partial form,
species within the Aedes genus also act as vectors, but their preventing severe dengue as a component of the disease response
contribution is secondary to that of Aedes aegypti. The Aedes for at least two years [12]. As the interval between sequential DENV
mosquitoes have 4 life stages: egg, larva, pupa and adult. infections increases beyond two years, an ever larger fraction of
Mosquitoes can live and reproduce inside and outside the home. second heterotypic DENV 2 and 3 infections have culminated in
The entire life cycle, from an egg to an adult, takes approximately 8 severe dengue. Two risk factors for DHF/DSS are well-established:
to 10 days [6,7]. The mosquito becomes infective approximately severe disease occurs during a second heterotypic DENV infection
seven days after it has bitten a person carrying the virus. This is the or during a first DENV infection in infants born to dengue-immune
extrinsic incubation period, during which time the virus replicates mothers. A large number of hypotheses have been proposed to
in the mosquito and reaches the salivary glands. Once infectious, explain severe dengue disease.
the mosquito is capable of transmitting virus for the duration of its The pathophysiological basis for severe dengue is multifactori-
lifetime. This entire life cycle for a female can last anywhere from al. Protective versus pathological outcome depends on the balance
42 to 56 days. among the host genetic and immunological background and viral
factors [4]. The leading explanation for increased risk of disease in
Human-to-mosquito transmission secondary infection is that non-neutralizing, cross-reactive anti-
bodies elicited by a primary infection bind the virus which then
Mosquitoes can acquire the infection from people who are have greater potential to infect Fc-receptor bearing cells. This
viremic with DENV. This can be someone who has symptomatic phenomenon, called antibody-dependent enhancement (ADE),
dengue infection, someone who is yet to exhibit symptoms (they potentially increases the risks of developing severe disease by
are pre-symptomatic), or someone who has no signs of the illness virtue of increasing the number of virus infected cells and
(they are asymptomatic). After feeding on a DENV-infected person, therefore the viral biomass in vivo [13]. Dengue infection causes
it takes about 8 to 12 days to transmit to a new host. activation of immune system to release of cytokines and chemo-
People with asymptomatic and pre-symptomatic infections kines, endothelial cell autophagy and T cell apoptosis; all of these
have an approximately 100-fold lower 50% mosquito infectious factors lead to endothelial cell dysfunction, which in turn leads to
dose and result in larger viral loads in infected mosquitoes, thus plasma leakage, contraction of intravascular volume and third
increasing transmission potential. Asymptomatic infections had a space fluid loss. Depletion of intravascular volume leads to features
lower average level of viremia, which is thought to be associated of shock and hypoperfusion of various organs, instituting a cascade
with a shorter time window of infectiousness. On the other hand, of hypoxic injury in various organ systems leading to shock and
people without symptoms may be more likely to visit multiple multi-organ dysfunction, which is a frequent cause of death in
locations during their daily routines where they are cumulatively dengue [14].
bitten by more mosquitoes than sick people who are hospitalized
or who stay at home and are exposed to only their resident Clinical features
mosquitoes. Human-to-mosquito transmission can occur 2 days
before someone becomes symptomatic and up to 2 days after the Dengue is a systemic and dynamic disease with a wide clinical
symptoms (and fever) have resolved [8]. spectrum ranging from asymptomatic to mild to severe clinical
manifestations. Clinical features of DENV infection range from a
Other modes of transmission mild flu-like syndrome, referred to as dengue fever (DF), to the
potentially life-threatening dengue shock syndrome (DSS). The
There is evidence however, of the possibility of vertical symptoms of DF include fever, nausea, vomiting, rash, aches and
maternal transmission (from the pregnant mother to her baby). pains, while in DSS severe bleeding and shock can occur and, if
While vertical transmission rates appear low, the risk of untreated, mortality can be as high as 20% [4]. The previous World
vertical transmission seems to be linked to the timing of the Health Organization (WHO) classification of dengue disease states,
dengue infection during the pregnancy. Congenital dengue can was composed of three disease categories: undifferentiated fever,
occur when there is insufficient time for transfer of maternal DF and dengue hemorrhagic fever (DHF) [15]. DHF was then
protective antibodies to the fetus. Average time between further classified into four severity grades, with grades III and IV
maternal fever and neonatal symptoms is reported to be 7 days defined as DSS. A revised WHO case classification was introduced
(range 5-13 days). Pregnant female can pass dengue virus to in 2009 that replaced previous classifications with probable
fetus if she develops fever from 10 days before delivery to 10 dengue, dengue without warning signs, dengue with warning signs
hrs after delivery [9,10]. (abdominal pain, persistent vomiting, fluid accumulation, mucosal

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V. Mulik, N. Dad and S. Buhmaid European Journal of Obstetrics & Gynecology and Reproductive Biology 261 (2021) 205–210

bleeding, lethargy, liver enlargement, increasing hematocrit with masking the disease. These may make it difficult to differentiate
decreasing platelets) and severe (dengue with severe plasma DHF from common obstetric conditions like preeclampsia, HELLP
leakage, severe bleeding, or organ failure) [16]. syndrome leading to misdiagnosis.
About 25% of infected patients will develop symptoms, the
majority will experience dengue fever, which is a self-limiting Laboratory diagnosis of dengue infection
disease. Classic DF is defined by the World Health Organization as
an acute febrile illness with 2 or more of the following signs or Diagnosis of Dengue infection clinically is very challenging due
symptoms: intense headache, retro-orbital pain, myalgia, arthral- to diversity in symptoms presentation. Hence, laboratory tests can
gia, rash, leucopenia, and a hemorrhage [17]. be used to aid in diagnosis. Laboratory confirmation of dengue
Symptoms begin 5–7 days (with a range of 3–10 days) after a infection is crucial as the broad spectrum of clinical presentations,
bite from an infective mosquito; viremia, however, can begin 1
5 ranging from mild febrile illness to several severe syndromes, can
days before the onset of symptoms and could persist for up to a make accurate diagnosis difficult. The type of test depends on stage
week. A small minority of those with dengue fever (5% or less) of disease. During early infection (<5 days), dengue may be
develop severe dengue. The critical phase occurs around the time diagnosed by virus isolation, RNA detection (NAAT: nucleic acid
of defervescence, typically on days 3–7, and is associated with an amplification tests) or detection of antigens such as NS1. Following
increased propensity for capillary leakage and hemorrhage [18]. this period (>5 days after infection), DENV RNA and antigens may
A small proportion of infected persons develop dengue no longer be detectable as antibody responses are mounted.
hemorrhagic fever (DHF), which is characterized by fever, Specific antibody detection using serological methods (detection
thrombocytopenia, hemorrhage, and increased vascular perme- of IgM or IgG) is appropriate at this stage [22] The NS1 antigen may
ability with plasma leakage primarily into the pleural cavity and be detected in some patients for several days after defervescence.
peritoneum. The main clinical feature differentiating DF from DHF
and dengue shock syndrome (DSS) is increased vascular perme- Virus isolation
ability, which, if unrecognized or not judiciously treated may result
in hypovolemic shock, organ impairment, and death. Virus isolation is very specific and can confirm a DENV
Clinical experience of dengue suggests that the illness presents diagnosis. Clinical specimens used for viral isolation may be
as a spectrum of disease instead of distinct phases; overlap whole blood, serum, plasma or homogenized tissue (most often in
between the different manifestations has often been observed. fatal cases). Practical limitations of include (a) it is tedious and
Patients who recover following febrile illness are considered to requires at least 7 days for incubation and confirmational testing;
have non-severe dengue, but those who deteriorate tend to (b) it requires well-established lab facilities with well-trained
manifest warning sign. These individuals are likely to recover with personnel; (c) the window period for sample collection is limited
intravenous rehydration. However, further deterioration is classi- to the acute phase of infection; and (d) a low level of DENV viremia
fied as severe dengue, though recovery is possible if appropriate is not suitable for virus culture [23].
and timely treatment is given [6].
All serotypes are capable of causing the full spectrum of clinical Nucleic acid amplification tests
disease following infection, ranging from an asymptomatic
infection to DF, DHF, and DSS. Nucleic acid amplification tests may be used to diagnose
Although dengue is traditionally a disease that affects young dengue during the acute phase of infection (<5 days) and can
children, many dengue-endemic countries have noted a gradual detect DENV RNA in a clinical specimen within 24–48 h after
shift in peak attack rate toward older age groups, including those of infection. Techniques include RT-PCR, real-time RT-PCR, or
reproductive age. isothermal amplification methods. Although PCR-based methods
Neurological complications are not frequent following dengue are fast and accurate, they require a laboratory with specialized
fever, but cases of Guillain–Barré syndrome, an acute inflammatory equipment and trained staff to perform the analysis. These are not
demyelinating polyneuropathy, which manifests as progressive always an option in resource-poor remote settings where dengue
acute paralysis and may lead to respiratory arrest, have been is endemic. Furthermore, despite the availability of commercial
described [19]. Atypical clinical features of DEN are being more kits, the bulk of reported RT-PCR methods are developed in-house
frequently reported but are probably still underappreciated. These and lack center-to-center standardization [24].
include encephalitis, myocarditis, hepatitis, pancreatitis, retinitis
and the acute respiratory distress syndrome (ARDS) [20]. Detection of antigens
Differential diagnosis of DF includes other common tropical
infections like enteric fever, leptospirosis, typhus fever, malaria. New ELISA and rapid immunochromographic (IC) assays that
Pregnancy is a state of relative maternal immunosuppression to target NS1 have been able to detect primary and secondary DENV
accommodate the fetus. This might make pregnant women prone infection up to 9 days after the onset of illness. In general, NS1-
to dengue infection. The developing fetus may be susceptible to based assays have good diagnostic utility, for both screening for
DENV infection, especially during the critical period of organogen- and confirming DENV infection. These tests have low sensitivity
esis (congenital dengue), or late in the pregnancy (although the during secondary infections, for DENV-4 and DENV-2 (compared to
primary infection may not manifest with overt symptoms in the DENV-1) [25].
mother). Furthermore, infants exposed in utero or at parturition to
DENV, either by becoming infected (primary infection) or through Serological tests
the passive transfer of maternal anti-dengue antibodies, may be at
increased risk of developing more severe infections if infected Serological tests such as hemagglutination inhibition (HI) assay
during infancy, due to the presence of heterologous anti-dengue and ELISA to detect IgM and IgG are more widely used to diagnose
antibodies [21]. dengue in developing countries, as they are simple to perform,
Physiological changes that occur during pregnancy (such as relatively inexpensive and the specimens required are stable at
hemodilution) can mask the thrombocytopenia, leucopoenia, or room temperature. These tests are used from the end of the first
hemoconcentration associated with dengue, and common obstet- week onwards, ideally with demonstration of seroconversion on
ric problems can cause hematological and hepatic issues, further paired samples.

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V. Mulik, N. Dad and S. Buhmaid European Journal of Obstetrics & Gynecology and Reproductive Biology 261 (2021) 205–210

Seroconversion of IgM or IgG antibodies is the standard for only be used to transfer patient to tertiary center, or delay labor in
serologically confirming a dengue infection. The presence of IgM or context of prematurity. It should only be used if needed after
high levels of IgG in acute serum collected from a suspected excluding pre-eclampsia, HELLP syndrome and chorioamnionitis
dengue case suggests a probable dengue infection as these conditions can overlap with dengue infection [27].
Due to varying kinetics of each biomarker, no single test can
diagnose the infection at various stages. Combination approach Effect of dengue on mode of delivery
has shown sensitivity of 100% from disease onset to recovery. The
combination test includes NS1 antigen detection combined with The data addressing mode of delivery is sparse. Most
IgG and IgM [24]. population-based studies are from South America where the
Table 1 describes laboratory diagnostic methods for detection background rate of cesarean section is generally high compared to
of dengue infection. the rest of the world. However, it does indicate increased rate of
cesarean section in women with dengue, this is particularly
Treatment significant in cases of DHF.
This was evident from hospital based prospective observation
There are currently no specific treatments or cures for dengue. cohort study with confirmed laboratory diagnosis of dengue. This
Current treatment options are supportive, and aim to limit the study reported cesarean section rate of 35% [28].
complications and severity of symptoms. Fluid therapy is one such
key therapy in dengue management. Oral fluid replacement is Effect of dengue infection on maternal outcomes
sufficient for DF; in severe dengue, however, intravenous fluid
replacement should be performed for shock prevention as well as The data is mostly from case series reported from low resource
management of bleeding. Antiviral drugs are not eff ;ective [26,17]. countries in Asia and South America.
To date, there is no vaccine to protect against DENV. A population-based cohort study in Brazil aimed to investigate
The development of a universal predictive algorithm for severe the association between symptomatic dengue during pregnancy
disease progression presents numerous challenges given the and maternal deaths from 2007 to 2012. Linking routine records of
significant variables introduced by local virus evolution, the confirmed dengue cases to records of maternal deaths (who had a
subtleties of virus–host interactions, geographic spread of the live birth) showed that dengue during pregnancy tripled the risk of
disease, and regional host genetics. Nevertheless, the current WHO maternal death from 0.1% CI 1.3–5.8). Furthermore, dengue
guidelines aid clinicians in providing a clear set of clinical warning hemorrhagic fever increased the risk of maternal death by 450
signs to help predict severe disease onset. Although not all the times (95% CI 186.9–1088.4) when compared to mortality of
warning signs appear early in disease, when appropriately pregnant women without dengue. This increase in risk occurred
implemented in the clinic, along with accurate laboratory mostly during acute dengue; adjusted OR 71.5 (95% CI 32.8–155.8),
diagnosis, the WHO guidelines provide a strong framework for compared with no dengue cases. The sensitivity to diagnose
effective monitoring of severe disease [24]. dengue in this study was 71%. The acute phase of disease is within
the first 10 days of the disease onset [29]. In a Brazilian cohort in
Management in labor Rio Branco, the maternal mortality ratio in the dengue exposed
group was 13 times the mean maternal mortality ratio of the area
In case of imminent delivery, patients diagnosed with dengue [30] as opposed to above finding of 3 times higher. This may be due
should be transferred to tertiary care hospital due to the risk of to the inclusion of women with less severe disease as well as, the
obstetric hemorrhage. Decision to deliver should be made by exclusion of women with stillbirth or other abortive outcomes.
experienced obstetricians. Consideration should be given to The percentage of maternal deaths among pregnant women
maternal status, severity of the disease, fetal status and gestation with dengue in the case series varied from 6.6% in Sri Lanka [31] to
age. Literature is scarce regarding timing of delivery and use of 15.9% in India [28].
tocolytics in patients with dengue infection due to small sample Preeclampsia was the cause of death in 25% of the patients with
sizes, retrospective data collection and lack of information dengue compared with 19% in the comparison group [29].
regarding neonatal status. One should be cautious regarding The mechanism for the association between dengue and
delivery in active phase of infection due to increased risk of maternal deaths is not clear. One possible explanation is that
perinatal transmission and obstetric hemorrhage. Tocolysis should the clinical aspects of the disease may be different during

Table 1
Laboratory Diagnostic Methods for the Detection of Dengue Infection.

Clinical Sample Diagnostic Approach Methodology Time to Results

Virus and virus product detection Acute serum (1–5 d of fever) and Virus isolation Mosquito or mosquito cell culture inoculation 1 wk or more
necropsy tissue Nucleic acid detection RT-PCR and real-time RT-PCR 1–2 d
Antigen detection NS1 Ag rapid test Minutes
NS1 Ag capture ELISA 1d
Immunohistochemistry 2–5 d
Serological response Paired sera IgM or IgG seroconversion ELISA HI 1–2 d
 S1: acute serum from 1–5 d (S1 to S2) Plaque reduction neutralization test >7 d
 S2: convalescent serum 15–21 d

Serum after day 5 of fever IgM detection MAC-ELISA 1–2 d

IgM rapid tests (lateral flow) Minutes
IgG detection IgG ELISA HI 1–2 d
IgG rapid tests (lateral flow) Minutes

Adapted from the World Health Organization [17].

Abbreviations: Ag, antigen; ELISA, enzyme-linked immunosorbent assay; HI, hemagglutination inhibition assay; IgG, immunoglobulin G; IgM, immunoglobulin M; MAC,
immunoglobulin M antibody capture; NS1, nonstructural protein 1; RT-PCR, reverse-transcription polymerase chain reaction..

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V. Mulik, N. Dad and S. Buhmaid European Journal of Obstetrics & Gynecology and Reproductive Biology 261 (2021) 205–210

pregnancy in a way that increases the susceptibility to DHF. There was some evidence that the risk of dengue in pregnancy
Another hypothesis is that physiological changes during pregnancy on birth outcomes depended on the interval between dengue onset
such as hemoconcentration and the difficultly in distinguishing and birth. The effect of dengue on adverse birth outcomes was
between severe dengue and common obstetric conditions may higher during the acute disease period, with some residual effects
have led to misdiagnosis and a delay in disease treatment that in remaining after the first 10 days for preterm birth and low birth
turn can progress to hypovolemic shock and death. A meta-analysis weight.
of the effect of infection on pregnancy showed that viral infections Above data is at total odds with updated metaanalysis which
can increase the risk of pre-eclampsia, although dengue is not concluded maternal DENV infection might not increase the risk of
specifically mentioned in this study. It is possible that dengue virus adverse fetal outcomes with a pooled RR of 0.96 (95% CI: 0.85–1.09,
leads to the same etiologic pathway of inflammatory modifications I2 = 49.6%) for premature birth, RR of 0.99 (95% CI: 0.87–1.12, I2 =
of placental tissues [32]. 35.1%) for low birth weight, OR of 1.77 (95% CI: 0.99–3.15, I2 = 17.5%)
for miscarriage and RR of 3.42 (95% CI: 0.76–15.49, I2 = 54.8%) for
Effect of dengue infection on fetal outcomes stillbirth [36].

A recent meta-analysis and systematic review looked at Vector control and prevention
possible adverse effects of dengue infection during pregnancy
on fetal outcomes. This showed crude overall OR for miscarriage as Vector control remains the primary method in the prevention of
3.51 (95% CI 1
15–10
77, I2 = 0%, p = 0
765) [33]. dengue infections. This can be achieved through environmental
A meta-analysis for stillbirth was not performed because this interventions, chemical control using insecticides and larvicides,
was investigated in only one study with a comparison group. The and biological control. Environmental interventions involves the
crude relative risk was 6
7 (95% CI 2
1–21
3) in women with reduction in or elimination of natural and man-made vector
symptomatic dengue compared with women without dengue [33]. breeding sites, such as containers and poorly managed waste
In a matched case control study in Brazil association between facilities.
symptomatic dengue infection during pregnancy and fetal death Most endemic countries have a vector control component in
was studied. Symptomatic dengue infection during pregnancy their dengue control and prevention programs but its delivery by
almost doubled the odds of fetal death (OR 1
9, 95% CI 1
6–2
2); public health practitioners is frequently insufficient, ineffective or
Severe dengue infection increased the risk of fetal death by about both. Environmental management is generally considered to be an
five times (4
9, 2
3–10
2) [34]. essential component of dengue prevention and control, particu-
In a prospective cohort study from India reported still birth rate larly when targeting the most productive container habitats of the
of 11.4% [28]. vector. However when infrastructure projects to improve water
Preterm birth (< 37 weeks) and low birthweight (< 2500 g, or and sanitation are undertaken, ministry of public health is seldom
intrauterine growth restriction) were the most common adverse consulted.
pregnancy outcomes for women with dengue infection during Behavioral protective measures for limiting human exposure to
pregnancy. mosquitoes include using insect repellent, wearing full coverage
Five cohort studies were included in the meta-analysis of clothing, and the use of mosquito bed nets and window screens
the association between low birthweight or intrauterine [25].
growth restriction and dengue infection during pregnancy. However, most of these strategies are dependent on compliance
The crude overall OR was 1
41 (95% CI 0
90–2
21, I 2 = 0%, p = and community involvement leading to lack of success. In future
0
543) [33]. public health education as well as increased political recognition of
The meta- analysis for preterm births included five studies; dengue as a public health problem will lead to better organized
three cohort studies, one case control series and one cross- control services using new tools and partnership strategies, based
sectional series. It showed the crude overall OR for the association on the principles of integrated vector management.
between dengue during pregnancy and preterm birth was 1
71
(95% CI 1
06–2
76 I2 = 56
1%, p = 0
058) [33]. Discussion
However, a large population-based cohort study was performed
to investigate the association between symptomatic dengue This review clearly identifies lack of epidemiological studies in
diagnosed during pregnancy and adverse birth outcomes and to this area. This is especially relevant as half of world’s population is
examine the effect of maternal dengue severity on the same susceptible to dengue infection.
controlling confounders [35]. This study showed that maternal There is evidence to show an association between maternal
dengue was associated with a slight increase in the risk of preterm dengue and increased maternal deaths. There are conflicting
birth (from 7.3% to 7.9%, RR 1.1; 95% CI 1.0 to 1.2) and low birth results regards fetal adverse outcomes including preterm birth and
weight (from 7.2% to 8.4%, RR 1.2; 95% CI 1.1 to 1.2), although the CI low birth weight [36,33,28].
was borderline. There was no association between maternal However maternal adverse outcomes are significant in symp-
dengue and small for gestational age. Dengue hemorrhagic fever in tomatic dengue patients requiring hospital admission especially
pregnancy was associated with a doubling of the risk of preterm patients that develop DHF and DSS. The outcomes are especially
birth, from 7.3% to 15.2%); OR 2.4 (95% CI 1.3 to 4.4) and an increase related to acute phase of disease which is first 10 days from onset of
in the odds of low birth weight, from 7.2% to 13.9%; OR 2.1 (95% CI symptoms. The health of pregnant women is a public health
1.1 to 4.0). priority. Hence health professionals attending pregnant women in
No evidence was found for an effect of dengue on small for places where dengue is endemic should observe them more closely
gestational age, even among pregnant women who developed to be able to intervene in a timely way, and avoid death as well as
hemorrhagic disease (8.0%) versus (11.1%); OR 2.5 (95% CI 0.4 to serious maternal morbidity. Dengue should be excluded as
12.2). differential diagnoses when pregnant women present with fever
In a prospective observational study from India showed high in pregnancy.
rates of fetal adverse outcomes with 10% intrauterine growth This information is vital for health education of women
restriction 37.5% pre-term births and 32.5% low birth weight babies travelling or planning to travel to dengue endemic areas during
[28]. pregnancy.

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V. Mulik, N. Dad and S. Buhmaid European Journal of Obstetrics & Gynecology and Reproductive Biology 261 (2021) 205–210

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The authors report no declarations of interest.
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