Vertical transmission of Zika virus (ZIKV) in early pregnancy: two cases, two different courses

Introduction

Zika virus (ZIKV) is an Aedes aegypti mosquito-borne flavivirus. The primary route of transmission is via an infected mosquito bite, however, sexual transmission has been reported [1]. The incubation period of ZIKV is up to 2 weeks after infection and clearance occurs within 21 days. Serum RNA reverse-transcriptase-polymerase- chain-reaction (RT-PCR) will be positive up to a week after symptoms commenced [2]. The majority of infections are asymptomatic; 25% of infected individuals may experience symptoms such as rash, conjunctivitis, fever, joint pain, headaches, myalgia, and Guillain-Barré syndrome. ZIKV RNA has been discovered in several bodily fluids, such as, serum, urine, saliva, and amniotic fluid [3], [4], [5], [6]. A ZIKV outbreak in Central and South America and the Caribbean in 2015–2016 has been associated with microcephaly and first trimester miscarriage, and a definitive causal relationship is increasingly suspected [7], [8].

We describe two unique cases of pregnant women who were exposed to ZIKV early in pregnancy under different circumstances and their clinical courses and outcomes.

Case 1

The patient is a 30-year-old Hispanic gravida 2 para 1 who presented at 14^4/7 weeks for evaluation for possible ZIKV exposure (Figure 1). Before realizing she was pregnant, she had visited Honduras for 2 weeks and noticed bug bites on her legs during the 2nd week. Three days after returning to the US, she experienced body aches, fatigue, and chills and noticed a flat, red rash over her entire body and face that lasted 2 days. She denied fever, nausea, vomiting, diarrhea, sick contacts, respiratory symptoms, or conjunctivitis. At this time, ultrasound showed a normal appearing single fetus with no anomalies with a normal head circumference and intracranial anatomy. Her serum was positive for ZIKV RNA RT-PCR. Her Dengue and Chikungunya testing was negative.

Figure 1:

Clinical time line representing maternal evaluation of Zika virus (ZIKV) infection in the two studied cases.

Diagnostic amniocentesis was offered and performed without complications at 16^2/7 weeks gestation. The amniotic fluid was positive for ZIKV RT-PCR with a normal fetal karyotype, 46 XY. The fetal anatomy was reexamined with attention to intracranial and ocular anatomy, and again appeared normal at 17^3/7 weeks. She opted to terminate the pregnancy. Fetal blood sampling followed by a dilation and evacuation procedure was performed at 18^4/7 weeks gestation without complications. The surgical specimen from the termination contained intermixed fragmented fetal and placental tissue. On gross pathology, there were no abnormalities noted on the products of conception, including the brain and eyes. Histologic examination of the tissue was also normal. However, on further testing with PCR, the products of conception did confirm ZIKV infection in some (skeletal muscle, placenta, bone, umbilical cord), but not all, fetal tissue. The cordocentesis sample also confirmed ZIKV in the fetal serum.

Discussion

The first described case establishes that fetal ZIKV can be diagnosed before abnormalities are detected on fetal ultrasound exam. ZIKV has previously been isolated in the amniotic fluid of two third-trimester fetuses that had multiple abnormalities detected on ultrasound evaluation, including severe microcephaly, although both mothers’ serum specimens were reported negative for ZIKV infection [9]. Our case is unique due to several findings. First, there is certainly a likelihood of contamination of removed tissues by the known positive amniotic fluid and maternal blood. But, the fetus was positive for ZIKA in the serum sample, suggesting actual infection. We postulate that a positive ZIKV RT-PCR in organs such as the bone may relate to blood viral content and not actual intrinsic cellular infection. However, a negative RT-PCR of the brain is intriguing as the brain was fragmented and largely admixed with other tissues. This could reflect less vascularity or contamination; but the lack of viral identification in the brain despite long-standing maternal infection, suggests brain infection does not predictably occur. This is further corroborated by the fact that in our case, despite maternal first-trimester exposure and a positive ZIKV RT-PCR from amniotic fluid, the fetus may not show sonographic evidence of malformations during the second trimester. We have also established that ZIKV can be isolated from amniotic fluid up to 4 weeks after maternal infection via insect bite in an otherwise normal appearing fetus.

In the second case of sexually transmitted ZIKV there was a 4-week interval between her onset of symptoms and the negative amniocentesis. This fetus also has normal sonographic findings, including fetal neural tissue, at 6 weeks following maternal symptoms. These case-specific factors question whether the mode of transmission, direct insect bite ZIKV compared with sexually transmitted ZIKV, influences the viral inoculum, maternal viremic load, and the likelihood of fetal infection.

Both cases demonstrate that early antenatal diagnosis allows maternal consideration for continuation of pregnancy. Discussion and counseling remain difficult at this time, when there is a normal appearing fetus with a concern of only potential fetal injury. It remains highly suspected that maternal ZIKV infection is causal in abnormal newborn neurologic findings. Additionally, amniotic fluid ZIKV isolation in the presence of normal fetal ultrasound and the relationship to future fetal or neonatal pathologic manifestations also remains unclear. Lastly, both of our patients were fortunate enough to present with maternal symptoms to prompt testing; however, the majority of Zika infections remain asymptomatic. Therefore, in patients with risk factors such as recent travel or sexual exposure, maternal testing should be performed regardless of maternal symptoms.

Clinicians who counsel pregnant women suspected to have been exposed to ZIKV should recognize the differences of potential pregnancy courses.