Running Head: ZIKA VIRUS DURING PREGNANCY

The Effects of Zika Virus on Fetuses during Pregnancy

Kami Alexander
Western Washington University

ZIKA VIRUS DURING PREGNANCY

The Effects of Zika Virus on Fetuses during Pregnancy

Introduction
Zika virus is a global health issue that is becoming increasingly prevalent all over the
world. With the number of cases of Zika virus continuing to increase, there is an alarming
increase in cases of babies born with microcephaly. As of August 4th, 2016, there have been 16
babies born with birth defects and 5 pregnancy losses linked to Zika infection during pregnancy
just in the United States (CDC, 2016). Brazil has the largest number of cases of microcephaly
linked to Zika at 1,806 (PAHO, 2016). This paper will discuss transmission, diagnosis,
prevention and clinical manifestations of Zika virus as well as implications.
Zika virus is a flavivirus transmitted mostly by the female Aedes mosquito but can also
be transmitted through sexual activity (WHO, 2016). Other flaviviruses to which Zika is related
include Dengue, Chikungunya and Yellow Fever (Sikka et al., 2016). In 2015, a major outbreak
of Zika started in Brazil prompting the World health Organization (WHO) to declare a global
health emergency in February 2016 (Soma-Pillay, 2016). Concurrently with the outbreak of Zika,
Brazil noticed a rapid increase in babies born with microcephaly, a condition where babies are
born with an underdeveloped or abnormally developed brain and suffer a wide range of health
problems (CDC, 2016).
History
The first case of Zika virus was discovered in a Rhesus monkey in 1947 in Uganda. The
first detection of the virus in a human was in 1954, also in Uganda (Soma-Pillay, 2016). Zika
virus has been transmitted in Africa and Asia for several years dating back to the 1950s. Just in

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the last ten years there have been large outbreaks in humans in the Yap Islands of Micronesia and
French Polynesia.
Active Zika
Below is a picture from the World Health Organization and Pan American Health
Organization denoting areas with active Zika transmission and number of cases.

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Literature review
Clinical Manifestations
Zika virus can present with any of the following symptoms: maculopapular rash,
conjunctivitis, fever, and generalized achiness. Symptoms can last for 3-7 days and usually
appear 3-12 days after exposure (Soma-Pillay, 2016). Patients may have no symptoms or mild
symptoms and, therefore, may be unaware that they have been exposed to Zika (CDC, 2016).
The most common symptoms in pregnant women include rash, arthralgia, fever, headache, and
conjunctival infection (Soma-Pillay, 2016). When pregnant women are exposed to Zika during
pregnancy, with or without symptoms, they are at higher risk for adverse outcomes including
fetal demise, intrauterine growth restriction, and microcephaly (Soma-Pillay, 2016). In a study
reviewed by Soma-Pillay, an ultrasound was performed on 42 pregnant women who tested
positive for active Zika infection which that determined fetal abnormalities in 12 women (SomaPillay, 2016).
Diagnosis
A positive reverse transcriptase-polymerase chain reaction (RT-PCR) test utilizing blood
is the current standard for diagnosis (Soma-Pillay, 2016). Testing can also be done on amniotic
fluid, however, The sensitivity and specificity of this test for congenital infection is currently
uncertain (Soma-Pillay, 2016). The CDC recommends utilizing the RT-PCR within the first
week of symptom onset (2016). A urine test is also available for diagnosis of Zika and can be
used up to two weeks after symptom onset (CDC, 2016). Pregnant women who have traveled to
or live in areas with active Zika should be tested in the first trimester. Women should also be
tested if their sexual partners have recently traveled to an area with active Zika.

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Treatment
Treatment for Zika is limited to management of symptoms as there is no anti-viral drug at
this time. Symptom based treatments can include antipyretics to treat fever and mild analgesics
to treat body aches. Approximately twenty percent of patients who get Zika are symptomatic and
symptoms usually resolve after one week (Sikka et al., 2016). The mortality rate and number of
hospitalization for Zika related complications are very low for the non-pregnant population
(Buekens et al., 2016). There is currently no available vaccine for Zika.
Recommendations
The CDC is recommending an integrated mosquito management (IMM) program for
areas with Aedes mosquitos. For people that live in or must travel to areas with local Zika
transmission, the CDC recommends avoiding mosquito bites by utilizing air conditioning,
mosquito nets, insect repellent, and clothes with adequate coverage. An IMM program often will
involve the community providing education on disposing of common mosquito breeding areas as
well as proper clothing, proper use of insect spray, and use of mosquito nets. It is also
recommended to use screens on doors and windows. Pregnant women should stay inside during
prime mosquito feeding times. Aedes mosquitos bite humans during the day both indoors and
outdoors (Lupton, 2016). Mosquitos often lay eggs in stagnant water and can include old tires,
pools, gutters, etc. By eliminating breeding areas, the number of overall mosquitos able to
transmit Zika are significantly decreased (CDC, 2016).The CDC is currently recommending that
pregnant women do not travel to places with known Zika transmission. Because Zika can be
passed to partners through sexual activity, it is recommended that couples use condoms if either
partner has recently traveled to an area with local Zika transmission.

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Many areas with a large number of locally transmitted cases of Zika are utilizing
professional adulticide sprays. This is an efficient way to control a large number of mosquitos
and decrease the opportunity to spread viruses like Zika. Due to increasing cases of travel
associated Zika, the US Food and Drug Administration has recommended a 28 day waiting
period for donating blood products or other tissues to avoid transfusion related transmission
(Plourde & Bloch, 2016).
Pregnancy
As mentioned above, microcephaly is a condition where babies are born with an underdeveloped or abnormally developed brain. There is a wide range of implications resulting from
microcephaly. Some common clinical manifestations are hearing and/or vision problems,
dysphagia or other feeding difficulties, intellectual delay and developmental delay. Before the
outbreak in Brazil, there was no suspected correlation between exposure to Zika virus and
microcephaly. During the outbreak in the Yap Islands and in French Polynesia there was no noted
increase in cases of microcephaly initially. When Brazil started to see an increase in cases of
microcephaly, it was originally thought to be correlated to a pesticide, Pyriproxyfen, which is
used locally.
The CDC now states: Pyriproxyfen has been approved for the control of disease-carrying
mosquitoes by the World Health Organization. Pyriproxyfen is a registered pesticide in
Brazil and other countries, it has been used for decades, and it has not been linked with
microcephaly. In addition, exposure to pyriproxyfen would not explain recent study
results showing the presence of Zika virus in the brains of babies born with microcephaly
(2016).

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After Brazil started to investigate the link between Zika exposure and microcephaly,
retrospective studies of the outbreak in French Polynesia showed probable correlations to cases
of microcephaly (Bell, Boyle, & Petersen, 2016). After the report of the Brazilian epidemic of
microcephaly in 2013, French Polynesia authorities looked back and reported central nervous
system malformations in fetuses and newborns born to women who were pregnant during the
Zika outbreak on the island (Paixo, Barreto, Teixeira, Costa, & Rodrigues, 2016).
CDC scientists agree that there is now enough evidence to conclude that there is a
correlation between exposure to Zika virus during pregnancy and microcephaly along with other
negative outcomes (CDC, 2016).
In Brazil, the time frame and geographic birth locations of many of the newborns with
microcephaly correspond well to a large outbreak of Zika virus infection that occurred in
the months earlieraligning with early pregnancy in their mothers. Histopathologic
evaluation of brain tissue from two newborns with congenital microcephaly who died
shortly after birth also revealed the presence of Zika virus (Bell, Boyle, & Petersen,
2016).
According to the Pan American Health Organization (PAHO), between October 22, 2015
and July 8, 2016, a total of 8,451 cases of suspected microcephaly and other congenital
malformations of the central nervous system have been reported in newborns in Brazil. Of those
cases, 1,687 were confirmed positive by Brazils surveillance and Response Protocol for
exposure to Zika virus,. 351 of those cases were stillbirth or neonatal deaths, also testing positive
for presence of the virus (2016).

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Information from cases in French Polynesia suggest that the highest risk to fetuses is in
the first trimester (Buekens et al., 2016). However, the CDC is advising women to avoid
exposure to Zika in any trimester. It should be noted that after the first exposure to Zika, it is
very rare to be affected a second time (CDC, 2016). The fetuses of pregnant women exposed to
Zika at least 28 days pre-conception are not affected. There is no evidence to support that future
pregnancies will be affected after the virus has cleared (Lupton, 2016).
As of July 14th, 2016, there have been 12 infants born with birth defects and 6 infant
deaths reported to the US Zika pregnancy registry. The infants in these cases all tested positive
for Zika but it cannot be definitively determined if the complications are related Zika or another
source (CDC, 2016). These cases are not geographically connected.
Guillain-Barre Syndrome
Along with an increased number of reported cases of microcephaly, there has also been a
dramatic increase in the number of Guillain-Barre Syndrome (GBS) in adults that are thought to
be related to Zika exposure (WHO, 2016). Guillain-Barre Syndrome is an auto-immune disorder
affecting the nervous system. Common symptoms of GBS include muscle weakness in the arms
or legs, sometimes leading to paralysis. GBS often presents with absence of reflexes in addition
to weakness. Some people suffer permanent nerve damage due to GBS but most make a full
recovery (CDC, 2016). GBS is very rare, with only 1-2 cases per 100,000 people in the United
States (CDC, 2016). According to an epidemiology report by PAHO and WHO on July 7th, 2016,
11 countries and territories in the region have reported an increase in number of cases of GBS. 4
other countries and territories have not reported an increase in cases of GBS but have identified
cases of Zika-related cases of GBS (2016).

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Further Research
There are some limitations in the available research correlating Zika virus and
microcephaly. Currently, there is no evidence to support a causal relationship, only a strong
correlation. There is limited research available due to the new nature of the Zika outbreak and
related health implications. According to the CDC (2016), if a pregnant woman is exposed to
Zika virus, it is unknown whether she will get Zika or not. If she does get Zika, it is unknown
how it will affect her and her specific pregnancy. If she does get Zika and pass it on to her fetus,
it is unknown how likely the baby is to be born with birth defects or how severe they may be. It
is also unknown if there is a difference in risk when a woman is exposed by mosquito bite versus
sexual transmission and when or if there is a higher risk to the fetus at a certain time in
pregnancy. There is a need for more research regarding transmission and risk to pregnant
woman. With the cases of Zika in pregnant women increasing rapidly, there will likely be more
information available about specific risks and outcomes.
Conclusion
The World Health Organization estimates millions of cases of Zika in the next twelve
months (WHO, 2016). With many cases of locally transmitted Zika in Puerto Rico, the US Virgin
Islands and now Florida, it is inevitable that Zika will keep moving into new regions. It is crucial
that education is available on prevention, especially for pregnant women and women with the
desire to become pregnant. Revised recommendations need to be made when more extensive
research is available. Preventative measures will need to continue to be a priority for regions
with increasing cases of local Zika transmission. Birth control options need to be provided for
women living in areas with local Zika that do not wish to become pregnant. As the cases of

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microcephaly continue to increase, there will be an increased need for support systems for
families, including:, skilled nursing facilities and home health agencies with an adequate number
of healthcare employees properly educated in caring for young children with microcephaly.

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