Dengue y Embarazo

First, one must identify how often this type of infection is

apt to occur in a pregnant population
Perret et al. studying
parturients in a highly endemic area, found a seropositivity
rate of 94.7%. Only 0.8% of the study population, however,
showed evidence of having acquired the infection during
pregnancy, and in those cases, the disease occurred early in
the pregnancy.
The seropositivity rate increased with
advancing maternal age, indicating that younger women
were more at risk to contract the disease during pregnancy
while the older patients were more likely to have preexisting
protective immunity.

The next question is if the disease presents during

pregnancy, does it have a different presentation and clinical
course than in the non-pregnant patient?
The available data,
although quite sparse, would seem to indicate not. In these
studies, pregnant patients with dengue fever still were
mostly diagnosed clinically with the diagnosis later being
confirmed by laboratory tests. In a review by Sirinavin et al.
13/14 (93%) cases for which presentation was recorded had
a typical presentation of abrupt fever accompanied by
headache, retro-orbital pain, muscle aches and thrombocytopenia,
in some cases accompanied by hemoconcentration,
pleural effusion and shock.

las manifestaciones hemorrgicas aparecen

desde el primer da de evolucin. Las imgenes
de la ecografa abdominal pueden presentar
edema perivesical, ms las alteraciones
por hepatomegalia, esplenomegalia, y serositis
en el hemorrgico.
Fueron hallazgos frecuentes la presencia de
hepatomegalia, epigastralgia y vmito, que en
la poblacin general se da solo en las formas
graves de dengue. El mayor porcentaje de los casos de
dengue
ocurri en el primero y segundo trimestre
del embarazo.

Next is the question of how the disease process might

affect the pregnant woman.
Data from two authors showed an increase in the rate of
prematurity. Carles et al.11,12 in their review of 38 cases in
French Guiana indicate a significant increase in prematurity
and fetal death. In these cases the timing of the fetal death
led the investigators to assume that death was due to the
dengue, but one patient was also co-infected with malaria.
But this group studied only severely ill, hospitalized
patients. They point out that had they included patients
with milder disease the incidence of fetal death and
prematurity would have been less, more in line with an
earlier study by Mirovsky in Vietnam.13 Ismail et al. in a
recent review also noted a 50% prematurity rate and
reported three maternal deaths out of 16 cases.14

Las mujeres gestantes que sufren de dengue

tienen un riesgo mayor de hemorragia vaginal,
y tendencia a las hemorragias durante
procedimientos quirrgicos, en heridas
quirrgicas,
y sangrado posquirrgico. Las embarazadas con
dengue clsico por lo
general presentan un parto y puerperio normales.
La muerte materna por dengue es un evento
poco frecuente.

fetal

In the Perret study, there appeared to be no fetal effects

from the maternal dengue infection. But only two patients in
the study showed antibody evidence of having had dengue
during the pregnancy. Also, the study was done at the time of
delivery. It is possible that women who get dengue early in
pregnancy miscarry and thus would not present for delivery.
Other reports by Chyes group in 1997 and Restrepo et al.
in 2003 do not indicate a propensity toward premature labor,
fetal death, or other complications of pregnancy, but do
indicate that the signs and symptoms of dengue fever might
easily be confused with those of other pregnancy complications
such as toxemia or its variant, HELLP syndrome
(hemolysis, elevated liver enzymes, low platelets).15,16

 The patients in these studies were women with severe

disease who presented for medical care. The authors
question
whether milder cases of disease occurring earlier in
pregnancy
might have presented instead as miscarriage and have
been
suspected of having a septic abortion. Or would a
preponderance
of milder cases have more firmly demonstrated the
absence of significant effects on pregnancy by dengue?

Sharma et al. reported an increased incidence of neural

tube defects following dengue infection,17 but as this defect
has been demonstrated following other febrile illnesses, it
may well have been due to the fever rather than to any
teratogenic effect of the dengue virus per se.18
Regarding dengue fever in the newborn infant, Perrett et al.
come to the conclusion that serious dengue disease occurs
only
when the mother is at or near term and there is insufficient
time for the maternal production of protective antibodies

There is some evidence that in many viral infections the

placenta is protective to the fetus, but this is not consistent
or complete.19,20 There have been case reports of transplacental
infection of the neonate with dengue virus, the data
being summarized by Sirinavin et al. in their review article.8
Seventeen cases of vertical transmission of dengue were
reviewed. Sixteen of 17 (94%) infants survived without
sequelae, with one (6%) neonatal death from intracerebral
hemorrhage that may have been coincidental to the dengue
infection.
In these studies, when maternal dengue fever was
encountered prior to term it was managed conservatively
without attempting premature delivery of the infant.

 Los recin nacidos cursan con

trombocitopenia,
fiebre, hepatomegalia y grados
variables
de insuficiencia circulatoria, y que
suele diagnosticarse
como sepsis neonatal. Se pueden
presentar trastornos neurolgicos.

Dengue at parturition
Although conservative obstetrical management is usually
advocated,21 of the 17 patients in Sirinavins review in whom
there was vertical transmission of dengue fever, 6/17 (35%)
were delivered by Cesarean section, 4/36 (24%) of whom
required blood transfusions, with 1/36 (3%) suffering a
massive maternal hemorrhage. Of the 11/17 (65%) who were
delivered vaginally, 4/11 (36%) of these also required
transfusions. Post-partum course was not reported for 5/17
(29%) of the patients in this review.

 Thus, Fatimil in a report from

Bangladesh states, A
pregnant woman with fever, myalgia
and/or bleeding
manifestations should raise a high
suspicion that the baby
may develop the disease, and both the
mother and baby
should be closely followed-up.22

Regarding the transfer of maternal antibodies to the

fetus, the following observations were made in these
studies. First, that maternal antibodies are transferred to
the fetus. Regarding the protective efficacy of these
antibodies, one author reports that antibodies with increased
cross-reactivity to other dengue serotypes preferentially
cross the placenta and are protective to the infant
after birth.23 Two other authors conclude that although
these may initially be protective, as their level wanes they
may instead predispose the infant to DHF or DSS.5,24
Secondly, babies of low birth weight were found to have
lower levels of transferred antibodies.7 It is impossible to
tell from the available data whether pre-existing placental
pathology prevented the passage of these antibodies or if
the presence of dengue fever itself caused placental
damage resulting in low birth weight.

Neonatal dengue
If the dengue virus was transferred to the infant via the
vaginal mucosa at parturition, such as with genital herpes
infection, some fetal advantage might be gained by Cesarean
delivery.19 However, studies showing the presence of dengue
virus in fetal and cord blood samples, seem to indicate
intrauterine infection of the neonate.5,13,2527 Thus, a
Cesarean would increase maternal risk without being of any
particular benefit to the infant.

Perret et al. in their paper point out that yall reported

cases of symptomatic congenital dengue infection have
occurred in neonates born to mothers infected very late in
pregnancyymaternal infections occurring close to the time
of delivery would have insufficient protective antibodies to
be transferred and consequently direct viremia into the
fetal blood stream may result.7 They also warn that the
congenital dengue infection rate would be expected to be
higher in any group of patients with less prior infection
and
thus a greater susceptibility to the disease near term.

The course of congenital infection in these studies

indicated that often the diagnosis could eventually be
suspected on clinical grounds and then confirmed in the
laboratory, but initial presentation was often confusing.
In the review by Sirinavin, the onset of fever in the
newborn varied from 1 to 11 days after birth with an
average
of 4 days and lasted 15 days. There did not appear to
be any
significant difference in this whether the mothers
dengue
infection was primary or secondary.

 All of the infants developed fever and

thrombocytopenia,
and 14/17 (82%) were found to have an enlarged
liver.
Eleven of 17 (65%) had at least some evidence of
bleeding,
but none required transfusion despite some very low
platelet counts. Four of the 17 infants (24%)
developed
pleural effusion but only 2/17 (12%) manifested a
rash

Transplacental maternal antibodies are felt to be protective

to the newborn while the titers remain high, typically
for about 6 months. After that, however, the lower titers
may in fact result in immunological enhancement and
predispose the infant to DHF or DSS.31 Breast feeding
might
be somewhat protective as neutralizing activity against
dengue virus was observed in some patients. The degree of
this protection, however, has not been studied.32

Summary of findings
These reports demonstrate that although pregnancy does
not seem to increase the risk of contracting dengue fever, the disease can be severe in pregnancy, with devastating
consequences. Even with what is believed to be primary
disease, it can progress to manifestations typical of DHF.33
Furthermore, those familiar with pregnancy will recognize
that diagnosis and treatment may be hampered by confusion
of dengue fever with other disease processes such as
toxemia and HELLP syndrome or certain forms of sepsis.
In the studies cited, however, the diagnosis of dengue
fever was made on clinical grounds based on a typical
presentation of the disease. The question arises whether in
usual practice a patient with an atypical presentation would
be recognized as having dengue fever and the appropriate
laboratory studies initiated. Teichmann et al. in a German
study of 71 cases cite the diagnostic difficulties encountered
because of the atypical clinical presentation in many of
these patients.34
Effects on the fetus or newborn seem to be variable, with
apparently less fetal harm occurring earlier in pregnancy
when there is time for protective maternal antibodies to the
formed and passed to the infant. When maternal infection
occurs closer to the time of delivery, there is more chance
for the infant to become ill.
Published reports do indicate several fetal and newborn
deaths, but clearer evidence is needed in order to attribute
the deaths to the dengue infection per se. In only one case is
the clinical course of the infant discussed, and there is
reason to believe that the causes of neonatal death in that
case were other than the dengue fever. In the other cases,
the fetal deaths were assumed to be from dengue but no
actual laboratory evaluation was undertaken to establish
this.

Pertinent pregnancy facts

From these data we are reassured that the dengue virus,
unlike for example those of rubella and varicella, poses no
specific threat of fetal malformation or disease-specific
fetal harm. Also it would appear that pregnancy does not
predispose to more severe disease as in the case, for
instance, of malaria.
But misdiagnosis or delay in diagnosis remains a significant
hazard, especially to the busy obstetrician who may be
unfamiliar with dengue fever.
There are several pregnancy-related issues that might
confuse the unsuspecting obstetrician. These include common
alterations in the immune, coagulation and cardiovascular
systems as well as hepatic enzymes and the febrile
response to illness during pregnancy.35
During pregnancy the white blood cell count is typically
elevated and manifests a shift to the left. Thus, such a minor
change due to dengue fever might be overlooked.
Similarly, pregnancy results in an increased tendency
toward coagulability while at the same time the platelet
count is normally low. How these factors might interact with
the course and laboratory findings in a case of DHF is
unclear. And would the hemoconcentration that occurs with
DHF be masked by the normal hemodilution of pregnancy?

 Both dengue fever and pregnancy

typically manifest mild
elevations of liver enzymes. Would
this lend itself toward a
delayed diagnosis of dengue fever?
36 And finally, pregnancy
sometimes blunts the normal febrile
response to illness.

While this might be protective to the fetus, would it also

cause a delay in the diagnosis?
In addition to all this, it would be interesting to know if
Aedes mosquitoes have a special attraction to pregnant
women as has been demonstrated in the case of the
Anopheline mosquitoes that transmit malaria. But such a
study has not yet been undertaken.37
Regarding fetal and neonatal effects, placental passage of
antibodies does occur and may initially be protective to the
infant. But if the infant stays in the endemic area he or she
is eventually at increased risk for DHF and DSS.38
Thus the fact remains that pregnant patients, especially
those without pre-existing immunity, traveling to areas
where dengue fever is prevalent are at significant risk of
contracting the disease. If this occurs, the maternal and
fetal effects include all those of any other severe febrile
illness, plus the potential for hemorrhage and shock. And
there are no specific preventive measures to use, such as
vaccination or prophylactic medication.
Recommendations

Recommendations
Pregnant patients should be advised of these risks and, if
practical, the trip postponed, especially in late pregnancy.
This may be more important for the non-immune pregnant
traveler, or younger pregnant travelers returning to endemic
areas. For pregnant travelers with pre-existing immunity
returning to dengue endemic areas, as may be the case with
emigrants visiting their countries of origin, there will
probably be an increased risk of suffering either DHF or
DSS, which may translate into an increased risk to the fetus.
If such travel cannot be avoided, then the conscientious
application of bite-preventive measures is advised, including
the use of an effective insect repellent. Although there
is a report of mental retardation in a child whose mother
used DEET throughout pregnancy,39 more recent work has
demonstrated the safety of DEET during the second and
third trimesters.40

When such a patient develops a fever or rash a high index

of suspicion for dengue fever is warranted. The early signs
and symptoms of dengue are not unique. Those signs that
might be more helpful might include conjunctival injection,
pharyngeal erythema, lymphadenopathy, and
hepatomegaly.
1 Leukopenia occurs with dengue fever and is a useful
diagnostic feature, as is thrombocytopenia. Mild elevations
of hepatic enzymes might also aid in the diagnosis

Laboratory diagnosis is typically not available in developing

countries and the diagnosis must be suspected and responded
to clinically. The differential diagnosis in such cases would
include influenza, enteroviral infection, other viral exanthems,
malaria, leptospirosis and typhoid fever.42,43
Where appropriate laboratory facilities are available, the
most frequently used serologic tests are the hemagglutination
inhibition (HI) assay and IgG or IgM enzyme immunoassays.
The IgM immunoassay (MAC-ELISA or equivalent) is the
most commonly used for rapid confirmation of the diagnosis.
44 Dengue viruses can be isolated in mosquitoes or
tissue culture if such facilities are available.
Acute and convalescent specimens should be analyzed
together by HI assay or IgG immunoassay to provide a
definitive serologic diagnosis.

 Treatment is supportive with fever reduction measures,

analgesics and careful maintenance of fluid and electrolyte
balance. Added to this would be careful monitoring of
hematologic status and serum albumin and, when necessary,
replacement of blood components. These measures will
hopefully reduce progression to more severe illness and
reduce the risk of pregnancy-specific effects such as neural
tube defects and premature labor.
Prior to term, there seems to be little indication for
induction of labor or other obstetrical intervention. The
fetus while in utero will benefit from the transfer of
maternal antibodies as well as from those treatment
measures instituted for the mother.
At term, there may be some indication for induction of
labor in order to allow for better management of mother
and infant. This is countered, however, by the risk of
precipitating a Cesarean section in an otherwise unstable
patient. This is fraught with anesthetic risks (such as
performing spinal anesthetic in a patient with a bleeding
tendency) as well as the risk of excessive blood loss from the
surgery. Thus, the majority opinion would be for conservative
management unless there is some other obstetrical
reason to intervene.
Care of the neonate under these circumstances would
primarily be a matter of careful observation with a high
index of suspicion, remembering that some neonates have
become ill as long as 11 days after birth. Diagnosis and
treatment can be further complicated in these cases by
confusion with bacterial sepsis, birth trauma and other
causes of neonatal illness.

 When the
disease does occur in pregnancy, keys to successful
management
include a high index of suspicion, prompt diagnosis,
and a team approach to the management of both
mother
and infant. In the absence of other complications the
disease does not appear to be of itself an indication
for
obstetrical intervention.
References

Discussion
This study suggests that dengue during pregnancy can
increase
maternal mortality, as previously reported [11]. It also
suggests
that pregnancy is associated with DHF/DSS and that the
susceptibility to severe disease increases with pregnancy
age.
Severe dengue has been associated with maternal deaths,
with
fatality rates ranging from 2.9%22% [56,1113]. The
maternal
dengue fatality in this study was 7.4%. The differences in
dengue
fatality in pregnant women likely result from differences in

More than half of pregnant women were hospitalized and it

was twice the rate of hospitalization for non-pregnant women,
since it was a recommendation of Rio de Janeiros healthcare
authorities to prevent dengue complications in this group.
Moreover, the proportion of DHF could still be underestimated
as the identification of plasma leakage syndrome through the
hemoconcentration or hypoproteinemia may be compromised
from the seventh to the 32rd week of gestation, by the
physiological increase of intravascular volume of this period
[14].
The reasons for the association of DHF/DSS with pregnancy
were not assessed in this study. The amount of vascular leakage
during early versus late pregnancy may have different effects on
the clinical presentation and on the perceived severity level. The
higher risk for developing severe disease in the 2nd and 3rd
trimesters should be confirmed by prospective studies as the
selection bias related to admission because of risk of preterm
delivery cannot be excluded.
The non-laboratory confirmed dengue cases were not analyzed
to avoid a detection bias, and the confusion of dengue with
pregnancy complications, such as HELLP syndrome.

 CONCLUSION
El dengue durante el embarazo, es un padecimiento
que debe investigarse en toda paciente con fiebre, mialgias,
artralgias, ataque al
estado general en zonas endmicas, ya que
las complicaciones para la madre y su hijo
pueden ser fatales si no se tratan oportunamente;
por ello es importante el diagnstico
materno temprano, fundamentado en la sospecha
clnica y epidemiolgica hasta la confirmacin
mediante pruebas de laboratorio para lograr
un tratamiento adecuado y oportuno, buscando
la mejora clnica de la madre y disminuir
riesgos para los productos de la concepcin

La presentacin clnica del dengue en embarazadas

es semejante a la poblacin general;
las manifestaciones hemorrgicas aparecen
desde el primer da de evolucin. Las imgenes
de la ecografa abdominal pueden presentar
edema perivesical, ms las alteraciones
por hepatomegalia, esplenomegalia, y serositis
en el hemorrgico.
Fueron hallazgos frecuentes la presencia de
hepatomegalia, epigastralgia y vmito, que en
la poblacin general se da solo en las formas
graves de dengue. El mayor porcentaje de los casos de dengue
ocurri en el primero y segundo trimestre
del embarazo.

Estas pacientes presentan con mayor frecuencia

actividad uterina desencadenada por
la infeccin en cualquier trimestre del embarazo
(amenaza de aborto, aborto, amenaza de
parto prematuro y parto prematuro), y desencadenamiento
del trabajo de parto en embarazos
a trminos simultneamente con la infeccin.
Se inform ruptura prematura de membranas;
hipertensin inducida por el embarazo y
empeoramiento de los casos de hipertensin
inducida por el embarazo, preeclampsia,
eclampsia; retardo en el crecimiento intrauterino,partos distcicos,
todos con mayor frecuencia
que en la poblacin general.

Hay mucha controversia sobre si el virus del

dengue es o no de transmisin vertical. Su confirmacin
requiere la presencia de IgG e IgM
especfica tanto en la madre como en el RN.
La transmisin perinatal del dengue es bastante
rara. Al igual que se presentan dudas sobre
si es causante o no de efectos teratognicos,
de sufrimiento fetal, de bajo peso al nacer
y de muerte fetal.
La evaluacin del crecimiento y el desarrollo
de los nios fueron adecuada.

Es difcil explicar el porque de las discrepancias

en cuanto a los efectos del virus del
dengue en el embarazo y en el recin nacido
que existen en los estudios, pero podra plantearse
que la diferencia en los efectos puede
ser reflejo de la severidad variable de las formas
clnicas de la enfermedad, determinadas a
su vez por factores como la infeccin secuencial,
la virulencia de la cepa, las caractersticas
individuales de las personas y otros factores
epidemiolgicos, que pueden tener influencia
en la presentacin y la severidad de los efectos
mrbidos durante la gestacin.