Secondary Logo

Share this article on:

Zika Virus Infection: A Vector-Borne Threat to Pregnant Women and Infants

Grazel, Regina, MSN, RN, BC, APN-C; Harris-Haman, Pamela, DNP, CRNP, NNP-BC

Section Editor(s): Newberry, Desi M.

doi: 10.1097/ANC.0000000000000557
Special Series: Congenital Infections

Background: Zika virus (ZIKV) is an emergent flavivirus, transmitted predominately by Aedes genus mosquitos that recently reached the Americas and was soon implicated in an increase in microcephaly and other serious birth defects.

Purpose: This report provides updated information and recommendations on testing, screening, and care for pregnant women and infants affected by ZIKV.

Methods: Current published recommendations from the Centers for Disease Control and Prevention, the World Health Organization, and the American Academy of Pediatrics were reviewed and included in this report.

Results: Although largely a self-limiting disease usually without symptoms, pregnant women and their fetuses are at greatest risk. Maternal transmission of ZIKV to the fetus can lead to congenital Zika infection with potentially devastating sequelae to the infant. The available evidence suggests that infection during the first trimester of pregnancy, in which the fetus' central nervous system is being formed, is associated with higher risk of brain abnormalities and perinatal loss.

Implications for Practice: Uncertainties remain about the course of the disease, and the full spectrum of effects of the virus on the developing infant is not yet understood. Infants with congenital Zika syndrome need coordinated follow-up and long-term specialty care, as well as support for the family.

Implications for Research: There is no known cure for ZIKV infection and no vaccine is currently available. The full spectrum of developmental disabilities and other adverse early childhood outcomes associated with congenital ZIKV infection needs to be studied.

New Jersey Chapter, American Academy of Pediatrics, East Windsor, and former consultant, New Jersey Department of Health Critical Congenital Heart Defects Screening Program and Zika Infant Surveillance, Trenton (Ms Grazel); and Thomas Jefferson School of Nursing, Philadelphia, Pennsylvania, and Duke-Johnson & Johnson Nurse Leadership, Division of Community Health, Durham, North Carolina, and Geisinger Holy Spirit Hospital, Middletown, Pennsylvania (Dr Harris-Haman).

Correspondence: Pamela Harris-Haman, DNP, CRNP, NNP-BC, 115 Providence Circle, Middletown, PA 17057 (pahhnnp@aol.com).

The authors declare no conflicts of interest.

Zika virus (ZIKV) is an emergent flavivirus primarily transmitted by Aedes aegypti mosquitos that can also spread dengue, chikungunya, and other viruses. Aedes albopictus mosquitos are a potential competent vector, but less likely to spread disease.1–6 Both mosquito's species are found in many states in the contiguous United States, with A. aegypti found primarily in southern states. A. aegypti mosquitos are aggressive daytime, as well as night feeders, live in and around human households, are difficult to eradicate and can reproduce in small water containers.3 , 5 , 6

The incubation period for ZIKV ranges from 3 to 14 days after the bite of an infected mosquito. A lack of symptoms does not negate the possibility of infection.3–7 An estimated 80% of persons infected with ZIKV are asymptomatic. When present, symptoms usually last for several days to 1 week and are generally mild and self-limiting, with 50% of cases developing symptoms 1 week after exposure.7 Common signs and symptoms include fever, pruritic maculopapular rash, arthralgia, and conjunctival hyperemia. Other clinical findings of myalgia, headache, vomiting, retro-orbital pain, and lymphedema have also been reported. Clinical laboratory abnormalities are uncommon in symptomatic patients but can include thrombocytopenia, leukopenia, and increased liver transaminase concentrations. Severe disease requiring hospitalization is infrequent and fatalities are rare.2 , 3 , 5 , 7 Guillain-Barre syndrome and reports of other neurologic complications have been associated with ZIKV (meningoencephalitis, myelitis, and uveitis). No specific antiviral treatment is indicated for ZIKV infection. Care is supportive including rest, fluids, and symptomatic treatment. Currently, there is no vaccine to prevent ZIKV infection.5

Widespread vector-borne transmission of ZIKV was observed in Brazil in late 2014. In October 2015, an increase in the number of cases of microcephaly, a congenital malformation resulting in smaller than normal head size for age and sex, was reported to Brazilian health officials.8 By January 2016, more than 3500 suspected microcephaly cases were reported in Brazil, many of which occurred in infants born to women who lived in or had visited areas where ZIKV transmission was active. The first local spread of ZIKV in the continental United States occurred in July 2016, with 4 confirmed cases of Zika infection in Miami, Florida.9 In the latter half of 2016, the Centers for Disease Control and Prevention (CDC) reported an exponential increase of pregnant women with laboratory evidence of Zika infection10 (see Figure 1).

FIGURE 1

FIGURE 1

Back to Top | Article Outline

METHODS

Transmission

The primary mode of transmission of ZIKV is from the bite of an infected mosquito. It can also spread via sex with an infected partner and transplacentally from a pregnant woman to the developing fetus. Concerns regarding maternal-fetal transmission of ZIKV have increased as the association between possible ZIKV infection and fetal/newborn microcephaly and other brain anomalies have been documented.11 , 12

ZIKV has been detected in blood, semen, amniotic fluid, saliva, and human milk.7 , 10–13 ZIKV continues to replicate regardless of viremic status or presence or absence of symptoms. It is not known if ZIKV can be transmitted through other body fluids that may be exchanged through oral or anal sex or whether sexual transmission of ZIKV poses a different risk for congenital infection than that of mosquito born transmission.14

Perinatal transmission is possible during delivery, breastfeeding, or exchange of saliva or other body fluids. Perinatal transmission of Zika should be suspected in an infant in the first 2 weeks of life if the infant's mother traveled to or resided in an affected area within 2 weeks of delivery and the infant has symptoms typical of ZIKV.15–17 There have been no reports of microcephaly from ZIKV transmission around the time of birth.1 Case reports describe mild disease presenting in 2 newborns whose mothers were viremic at delivery.2 , 5 , 15–17 A study of 4 breastfeeding mothers with laboratory-proven ZIKV showed no disease or symptoms in 3 of 4 infants despite detectable illness. One infant developed fever and cutaneous exanthema lasting 2 days; however, the infant's serum sample was found to be negative for Zika.15–17 , 23 Breastfeeding is not contraindicated for mothers or infants with ZIKV infection. The World Health Organization and the CDC support breastfeeding for mothers with suspected, probable, or confirmed Zika infection. The beneficial effects of breastfeeding preponderate any potential risk of Zika transmission via human milk.11 , 17

Postnatal ZIKV disease should be suspected in an infant or child younger than 18 years who (1) traveled to or resided in an area with risk of ZIKV infection within the 2 weeks preceding and (2) has one or more of the following manifestations: fever, rash, conjunctivitis, and arthralgia. Arthralgia can be difficult to detect in infants and young children and can manifest as irritability, restricted mobility of extremities, or pain on palpation or movement of the affected joint. Clinical features of ZIKV infection can resemble common childhood illness, which may make diagnosis in children difficult.14 , 18 , 19 Guidance for testing and clinical management of infants and children with postnatal ZIKV infection is in accordance with testing and clinical management recommendations for adults.4

Back to Top | Article Outline

Recommendations for Prevention for Pregnant Women

Pregnant women are cautioned to avoid travel to any area where ZIKV is active. Pregnant women who must travel to or live in Zika-prevalent areas are advised to talk to their healthcare provider before traveling and should follow strict steps to prevent mosquito bites and sexual transmission of the virus. There is no restriction on the use of insect repellents by pregnant women when used in accordance with the manufactures' guidelines.2 , 5 The American College of Obstetricians and Gynecologists recommends the use of approved mosquito repellants, wearing long sleeves to protect skin, staying in air-conditioned places, or screened in areas when possible.16 Recommendations for delaying pregnancy to minimize risk for sexual transmission of the virus are 2 months after ZIKV exposure or symptom onset for women and 3 months for men before engaging in unprotected sex. Previous guidance was based on the maximum duration of detection of ZIKV RNA in semen. New research suggests that the period ZIKV can be transmitted through sexual contact might be shorter than was estimated from the earlier studies. Recommendations for men with possible ZIKV exposure whose partner is pregnant remain unchanged; these couples should be advised to consistently and correctly use condoms during sex or abstain from sex for the duration of the pregnancy. CDC advocates for shared patient-provider decision making, whereby couples and health care providers work together to make decisions about timing of conception after possible ZIKV exposure based on individual circumstances (e.g., age, fertility, or details of possible exposure), clinical judgment, and a balanced assessment of risks and expected outcomes.20

Back to Top | Article Outline

RESULTS

Risk of Birth Defects

Congenital Zika syndrome is a discrete pattern of birth defects among fetuses and infants infected before birth. This syndrome is associated with 5 types of birth defects that are either not seen or occur rarely with other infections during pregnancy: (1) severe microcephaly with partially collapsed skull, (2) thin cerebral cortices with subcortical calcifications, (3) eye anomalies—macular scarring, focal pigmentary retinal mottling, (4) congenital contractures or limited range of motion, and (5) marked early hypertonia and symptoms of extrapyramidal involvement.

In collaboration with state, tribal, local, and territorial health departments, the CDC established the US Zika Pregnancy and Infant Registry (USZPIR) to monitor pregnant woman with laboratory evidence of possible ZIKV infection and their infants.11 In 2016, a total of 1297 pregnancies with possible ZIKV infection were reported to the USZPIR from 44 states. ZIKV-associated birth defects were reported for 51 (5%) of the 972 fetuses/infants from completed pregnancies with laboratory evidence of possible recent ZIKV infection. When restricted to pregnancies with laboratory-confirmed ZIKV infection, the proportion of fetuses/infants with ZIKV associated birth defects increased to one in ten (24 of 250). The percentages of fetuses or infants with ZIKV linked birth defects were highest among those acquiring infection during the first trimester. Birth defects were reported in 15% of fetuses/infants of completed pregnancies, with confirmed ZIKV infection in the first trimester.19 Outcomes from 2360 completed pregnancies with laboratory evidence of possible ZIKV infection from December 1, 2015, to March 31, 2018, in the USZPIR, show 116 (5%) live-born infants with birth defects and 9 (0.4%) pregnancy losses with birth defects associated with possible ZIKV infection.21

Birth defects surveillance systems identified a total of 2962 infants and fetuses (3.0 per 1000 live births, 95% confidence interval = 2.9-3.2) who met the case definition of ZIKV infection. US states and territories with local transmission had a 21% increase in Zika-associated birth defects from July to December 2016 compared with the first half of the year. CDC researchers found that about 3 of every 1000 babies born had a birth defect caused by Zika or other factors. Among these infants about half (49%) were born with brain abnormalities and/or microcephaly, 2 in 10 (20%) had neural tube defects and other early brain abnormalities, 1 in 10 (9%) had eye abnormalities without brain abnormalities, and more than 2 in 10 (22%) had nervous system damage, including joint problems and deafness, without brain or eye abnormalities.22 , 24

ZIKV infection during pregnancy has been shown to cause a multitude of neurologic abnormalities; however, the magnitude of the risk is unknown.15 The clear majority of pregnancies exposed to ZIKV result in normal-appearing infants at birth. The estimated prevalence of microcephaly is between 2.0% and 3.0%, depending on the stratification used.4 The probability of microcephaly occurring increases if Zika infection is contracted in the first trimester of pregnancy.11 The mechanisms of ZIKV intrauterine transmission, replication, and its tropism and persistence in tissues are poorly understood. Cellular targets of viral replication, and the pathogenesis that leads to microcephaly and other congenital malformations, have not yet been completely elucidated. ZIKV antigen has been detected in placental, fetal, and neonatal brain tissue, yet the presence of antigens does not necessarily indicate virus replication.7 The total number of mothers and infants in the United States affected by possible congenital ZIKV infection is likely much higher than reported because many women with exposure to ZIKV in pregnancy were not tested or were not tested in a timeframe that allowed identification of the infection.

Although the disease is generally mild in the nonpregnant population, ZIKV infection during pregnancy has been linked to fetal loss and devastating birth defects including microcephaly.6 Clinical findings reported in infants with confirmed congenital ZIKV infection include brain anomalies (subcortical calcifications, ventriculomegaly, abnormal gyral patterns, corpus callosum agenesis, and cerebellar hypoplasia), ocular and visual problems5 , 12 , 14 (microphthalmia, cataracts, chorioretinal atrophy, and optic nerve hypoplasia), musculoskeletal deformities (clubfoot, arthrogryposis), and neurologic involvement (hypertonia, hypotonia, irritability, tremors, swallowing dysfunction, and hearing loss).8 , 9 , 11–19 , 22 , 24–28 Among infants with substantial loss of brain volume, severe microcephaly and partial collapse of the bones of the upper cranium produce a distinctive physical appearance.29

Back to Top | Article Outline

Testing for Zika

The need for multifaceted viral testing procedures and interpretation renders the diagnosis of ZIKV infection complex and at times inconclusive.13 , 30 Timing of the specimen collection is crucial to obtaining the most reliable results. ZIKV RNA is only detectable in serum during viremic periods, occurring most often during the first 7 days of illness. Nucleic acid testing (NAT) of serum for viral RNA within the first week is preferred for laboratory confirmation of Zika infection. NAT may also be useful on pathologic specimens. The reverse transcription polymerase chain reaction (RT-PCR) technique is a commonly used method of NAT to detect viral RNA.31 For most persons with suspected ZIKV disease, a positive NAT result confirms acute ZIKV infection although false-positive results are possible. In addition, because ZIKV RNA is cleared from blood and other body fluids and tissues, a negative NAT result does not exclude acute Zika infection. RNA and NAT are the most sensitive tests available to detect acute (current) ZIKV.28 , 32

Anti-Zika immunoglobulin M (IgM) typically manifests soon after onset of symptoms and is most likely to be detected for approximately 12 weeks following infection. Several assays can be used to identify ZIKV IgM antibodies in serum or cerebrospinal fluid (CSF) although results can be challenging to interpret because of false-positives and cross-reactivity with other flaviviruses (eg, dengue and yellow fever viruses).28 , 32 Some individuals have prolonged detection of IgM antibodies for months after the initial infection, making it difficult to distinguish the timing of ZIKV acquisition.6 , 27 , 28 Conversely, a negative IgM serologic test result does not rule out ZIKV infection, as the test may have been performed before the development of IgM antibodies or after the antibodies have waned.27 The CDC analyzed the bodily fluids (blood, urine, and saliva) of 150 people infected with ZIKV. In 85% of the participants, ZIKV RNA was no longer detected in the blood after 54 days, the urine after 39 days, and few people had traces of RNA in the saliva.14 , 32

ZIKV IgM serology can be positive due to antibodies against related flaviviruses and should be followed by a plaque reduction neutralization test (PRNT). PRNT measures virus-specific neutralizing antibody titers and can help distinguish ZIKV in patients without ongoing exposure or vaccination against other flaviviruses. PRNT is also performed when IgM antibody serology test results are inconclusive. Without confirmatory PRNT testing, it is not possible to determine whether ZIKV IgM antibody testing reflects recent infection or a false-positive result.13 , 32

IgM should be tested as part of a multitest algorithm recommended by the CDC. Assay results are for the persistence of ZIKV IgM antibodies and are a qualitative result identifying the ZIKV IgM antibodies. Reactive results that are not definitive results should not be used as the sole basis for patient management. Management must be combined with clinical observation, patient history, epidemiological information, and laboratory evidence.8 , 11 , 27 , 33

In 2016, ZIKV infection was made a nationally notifiable disease. All positive testing should be reported according to state and local health department-specific guidelines. Healthcare providers should work with state and local health departments to ensure test results are interpreted correctly.8 , 11 , 27

Back to Top | Article Outline

Testing for Congenital Infection

Testing in Pregnancy

The number of persons affected by Zika in the US and American territories has declined since the peak in 2016, and ZIKV antibodies have been found to persist in some pregnant women confounding the interpretation of testing results regarding timing of the possible ZIKV infection and risk to the fetus. During periods of low disease prevalence and when the risk of exposure to ZIKV is low, testing may lead to a higher proportion of false-positive results, due to the gaps in presentation to care and testing. These experiences and data from the USZPIR informed the CDC's updated ZIKV testing recommendations for pregnant women.27

The revised guidance for pregnant women incorporates a shared decision-making model for testing and screening where patients and providers work together to make decisions based on patient preferences, values, clinical judgment, assessment of risk, and jurisdictional recommendations. When deciding whether ZIKV testing is appropriate, healthcare providers should consider the patient's duration and type of travel, use of regular protection measures, timing of pregnancy, and intensity of active ZIKV transmission in the area of travel. All pregnant women should be screened for exposure to ZIKV at every prenatal visit, and questioned about length of exposure and possible symptoms as applicable. Awareness of a pregnant woman's possible exposure to ZIKV before and during pregnancy is critical contextual information that should be used to tailor pretest and posttest counseling and interpretation of test results for pregnant women.6 , 27

NAT of both serum and urine and concurrent ZIKV IgM serologic antibody testing is recommended for pregnant women with Zika symptoms as soon as possible through 12 weeks after symptom onset to confirm the diagnosis of acute ZIKV infection. For women who enter care greater than 12 weeks after the beginning of symptoms, ZIKV IgM testing may be considered; however, a negative result does not rule out an infection during pregnancy because IgM levels decline over time. A positive serologic result should be interpreted within the context of the known limitations of the testing.3 , 28

Regardless of history of symptoms, testing should be performed on pregnant women with possible Zika exposure who have a fetus with prenatal ultrasound findings consistent with congenital ZIKV infection. If amniocentesis is performed, NAT of amniocentesis specimens should also be performed. Testing of placental tissue is not routinely recommended but may be considered for women without laboratory-confirmed ZIKV infection who have a fetus or infant with possible Zika-associated birth defects.27 , 30

For asymptomatic pregnant women with ongoing exposure to ZIKV through residence or frequent travel, Zika RNA NAT should be offered at the first prenatal care visit and 2 additional tests offered during subsequent routine prenatal care. Zika antibody IgM testing is no longer recommended for this group, as the presence of Zika antibodies cannot identify whether the infection occurred before or during the pregnancy.28

Given the increased possibility of false-positive results, Zika testing is no longer recommended for pregnant women without symptoms who have recent but not ongoing ZIKV exposure. ZIKV testing is also not recommended for nonpregnant asymptomatic individuals and preconception screening. Healthcare professionals are urged to remain vigilant and consistently consider possible exposure to ZIKV during pregnancy, regardless of the availability of testing results. Many women are not tested or not tested at the right time to detect infection.13 , 28 When laboratory testing is performed, results should not be released until all testing steps are complete. Healthcare providers are encouraged to utilize patient history, appropriate testing and completed testing results as applicable, to make decisions about care and follow-up according to recommended guidance28 , 30 (see Tables 1, 2 and 3).

TABLE 1

TABLE 1

TABLE 2

TABLE 2

TABLE 3

TABLE 3

Back to Top | Article Outline

Infant Testing

Optimal testing assays, specimen types, and timing to test for congenital ZIKV infection are still being determined. Some infants with positive clinical findings consistent with congenital Zika syndrome have negative laboratory testing results. Negative testing results in these situations may be due to several reasons—the clinical findings are attributed to another cause, incomplete testing, suboptimal specimen collection, testing outside the suggested timeframe, or lack of IgM antibody response in the fetus. NAT may not detect Zika infection in a newborn who was infected in utero if the period of viremia has passed.4 , 11 , 27 There is no specific treatment for ZIKV infection and treatment is predominately supportive.

Testing is recommended for infants with birth defects consistent with congenital Zika syndrome born to mothers with possible ZIKV exposure during pregnancy (regardless of the mother's ZIKV testing results) and for infants without birth defects associated with congenital Zika syndrome who were born to mothers with laboratory evidence of possible ZIKV infection during pregnancy.10 Concurrent ZIKV RNA testing (NAT) of serum and urine and Zika IgM antibody testing of serum should be performed within a few days after birth, when possible. In addition, if CSF is collected for other purposes, NAT and IgM antibody testing should also be performed on CSF. Testing of cord blood is not recommended due to the possibility of false-positive and false-negative results. Specimens collected within the first few weeks to months after birth may still be useful in the evaluation for possible congenital ZIKV infection; however, it may be difficult to distinguish between congenital, perinatal, and postnatal infection in infants who reside in areas with ongoing ZIKV transmission and are not tested shortly after birth.

A ZIKV NAT-positive result (see Table 2) on an infant specimen confirms congenital ZIKV infection. Congenital ZIKV infection is unlikely with negative NAT and negative IgM testing results from appropriate specimens within a few days of birth.4 ZIKV IgM detected in an infant with a negative NAT result should be interpreted as probable congenital ZIKV infection. If PRNT was not done on the mother's sample, PRNT for ZIKV should be performed on the infant's initial sample. Negative PRNT suggests the infant's ZIKV IgM test result is a false positive.6 PRNT on an initial specimen shortly after birth, however, cannot distinguish between maternal or infant antibodies. Maternal antibodies in the infant are expected to diminish by 18 months.3 , 4 Therefore, ZIKV PRNT testing at 18 months of age is used to help confirm or rule out infection in situations where (1) Zika IgM was detected in the infant's initial specimen and neutralizing antibodies were detected by PRNT in either the infant's or mother's sample, or (2) the initial sample was negative for IgM antibodies and NAT, but clinical concerns such as microcephaly remain and other known causes have been eliminated. PRNT after maternal antibodies have dissipated is also useful to confirm or rule out congenital ZIKV infection for infants with findings associated with congenital Zika syndrome or those with maternal evidence of possible ZIKV infection during pregnancy, and were not initially tested.6 Infants with negative PRNT results at 18 months are considered not to have congenital ZIKV infection. Congenital ZIKV infection is presumed with positive PRNT results at 18 months, but postnatal infection cannot be excluded, especially among infants living in an area with active Zika transmission.3 , 4

Back to Top | Article Outline

IMPLICATIONS FOR PRACTICE

Clinical Management of Infants

Evaluation of infants exposed to ZIKV during pregnancy is guided by laboratory and clinical findings. The initial evaluation may be performed before the infant's hospital discharge or as an outpatient depending on the capabilities of the facility and the family's needs. Infants requiring evaluation can be categorized into 3 groups: those with clinical findings consistent with congenital Zika syndrome regardless of mother's testing status, those without birth defects associated with congenital Zika syndrome born to mothers with laboratory evidence of possible ZIKV infection, and those without birth defects associated with congenital Zika syndrome born to mothers without laboratory evidence of ZIKV infection.

All infants born to mothers with possible ZIKV exposure during pregnancy should receive a standard evaluation at birth and at each well-child visit that includes comprehensive physical examination, growth parameter monitoring, age-appropriate vision screening, developmental screening and monitoring, and a standard newborn hearing screening at birth, preferably using auditory brainstem response (ABR) methodology.

Additional clinical evaluation is recommended for infants with abnormalities consistent with congenital Zika infection: ZIKV testing preferably within a few days after birth, and by 1 month of age, a head ultrasound and comprehensive ophthalmologic examination by an ophthalmologist with expertise in assessing infants. Infants should be referred for automated ABR testing by 1 month of age if the newborn hearing screen was passed using only otoacoustic emission methodology.18 Referrals to a developmental specialist and early intervention services are recommended. Additional consultation by infectious disease, clinical genetics, and neurology should be considered with potential advanced neuroimaging and electroencephalography within 1 month of age. Follow-up eye examinations are guided by ophthalmologic recommendations. Vigilance for other potential problems such as signs of increased intracranial pressure, difficulty feeding, and diaphragmatic paralysis among infants with respiratory distress should be maintained4 , 13 , 22 (see Table 4).

TABLE 4

TABLE 4

TABLE 5

TABLE 5

Infants without apparent clinical findings consistent with congenital Zika syndrome but with maternal laboratory evidence of possible infection during pregnancy require evaluation and follow-up for potential postnatally acquired conditions. ZIKV testing should ideally be performed within a few days of birth, head ultrasound by 1 month of age to detect subclinical brain findings, and ABR testing by 1 month if only otoacoustic emission screening was completed. These infants also need a comprehensive ophthalmologic examination by 1 month of age, with further follow-up per ophthalmology suggestions (see Table 5). Subsequent referrals to specialists are indicated for management of any clinical abnormalities associated with congenital ZIKV infection3 (see Table 4).

For infants without clinical signs of congenital Zika infection born to mothers without laboratory evidence of infection during pregnancy, laboratory testing and clinical assessment beyond standard evaluation are not routinely recommended. If findings consistent with congenital ZIKV infection occur at any time, appropriate referrals should be made at that time.2 , 4 , 30

The health and development of children with Zika-associated microcephaly have not been well characterized beyond infancy. Nineteen children with laboratory-positive congenital ZIKV infection and microcephaly were identified through surveillance in Brazil and evaluated at a median age of 22 months (range 19-24 months). At the time of follow-up evaluation, problems identified at birth persisted and all children had at least 1 adverse outcome. Most children had severe motor impairment, seizures, hearing and vision problems, and sleep difficulties.34 Infants with birth defects associated with congenital Zika infection face a myriad of challenges and require complex care and coordination of services from a multidisciplinary team. Anticipatory guidance for families regarding potential and emerging problems is warranted. Families should be empowered to be active participants in their infant's care.

Back to Top | Article Outline

Implications for Providers

Congenital ZIKV infection has been linked with serious brain anomalies, microcephaly, and congenital Zika syndrome. ZIKV infection during pregnancy is also associated with other structural and functional neurologic sequelae in the infant. Couples planning pregnancy and pregnant women are advised to avoid travel to areas with active ZIKV. Patients and providers can access the CDC's interactive map (https://wwwnc.cdc.gov/travel/page/zika-information) to determine areas of risk before making travel plans. Protective measures to prevent mosquito bites and sexual transmission of the virus are recommended for men and women who reside in or travel to areas with Zika. All pregnant women should be screened for possible ZIKV exposure at every prenatal care visit. Pediatric providers are directed to ask about potential maternal and congenital Zika exposure for every newborn.14 Communication between obstetric and pediatric healthcare providers regarding possible maternal–fetal ZIKV transmission and strategies to enhance coordination of care is critical.

There is currently no evidence that a previous maternal ZIKV infection increases the risks for congenital birth defects in subsequent pregnancies.1 ZIKV infection is likely to confer prolonged and possibly lifelong immunity.27

Clinical judgment should be exercised when evaluating infants with abnormalities born to mothers who travel to or reside in areas with local Zika transmission or who have sex partners who traveled to or resided in these areas.3 Infants with maternal laboratory evidence of possible infection during pregnancy but lack clinical findings at birth should be followed up carefully.6 , 24 Alertness for findings consistent with congenital Zika syndrome that could develop over time—seizures, impaired visual acuity and function, poor head growth, and developmental delay—should be maintained.2 , 3 Case reports describe infants born with normal head circumference who developed postnatal-onset microcephaly following congenital ZIKV infection.25 Later development of hydrocephalus in infants born with microcephaly, abnormalities on sleep electroencephalograph, and diaphragmatic paralysis in infants with microcephaly and arthrogryposis have occurred.4

Back to Top | Article Outline

IMPLICATIONS FOR RESEARCH

The full spectrum of developmental disabilities and other adverse early childhood outcomes associated with congenital ZIKV infection in the United States can only be determined by following affected infants and children, as they develop. Anticipatory guidance and care coordination for an array of medical, functional, and developmental problems is needed. As critical members of the care team, families should be empowered to be active participants in their child's monitoring and care. The range of morbidities of infants diagnosed with congenital ZIKV infection may have far-reaching implications for other Zika-exposed infants whose infection was not identified during pregnancy or at birth.24 Continued surveillance for birth defects potentially related to ZIKV infection is an important public health function. Most pregnancies affected by ZIKV were completed in 2017. Outcomes data from these pregnancies and infant follow-up will help evaluate the health and development of affected children, plan for needed resources, and link the patients and families to resources.22

Back to Top | Article Outline

CONCLUSION

Although the epidemic has receded from its peak in 2016, the consequences of congenital Zika infection remain, and public health systems are essential to monitoring the full effect on infants and children.20 The USZPIR can provide scientific findings regarding clinical characteristics and manifestations of infants and fetuses with potential congenital infection. More than 7000 pregnancies with laboratory evidence of ZIKV infection have been reported and the CDC is monitoring pregnancy and infant adverse outcomes. Established birth defects surveillance systems can adapt to monitor other emerging pregnancy, infant, and newborn outcomes of concern beyond structural birth defects, including functional neurologic problems, and can provide additional clinical information through standardized data collection and clinical review.15 , 19 , 22

Infants with congenital Zika syndrome will have profound developmental delays and face multiple challenges35 (see Table 6). Ongoing surveillance is needed to determine the extent to which congenitally exposed infants without apparent birth defects will experience similar or other developmental issues.15 , 22 Developmental milestones need to be closely monitored for infants born following pregnancies complicated by Zika who appear healthy at birth, because some may have developmental problems that become evident later.

TABLE 6

TABLE 6

Back to Top | Article Outline

References

1. Coelho AV, Crovella S. Microcephaly prevalence in infants born to Zika virus-infected women: a systematic review and meta-analysis of infected women. Int J Mol Sci. 2017;18(8).
2. Wu J, Huang DY, Ma JT, Ma YH, Hu YF. Available evidence of association between Zika virus and microcephaly. Chin Med J. 2016;129(10):2347–2356. doi:10.4103/0366-6999.190672.
3. Centers for Disease Control and Prevention. Potential Range in the U.S.https://www.cdc.gov/zika/vector/range.html. Accessed May 1, 2018.
4. Wang J, Ling F. Zika virus infection and microcephaly: evidence for a causal link. Int J Environ Res Public Health. 2016;13(10). doi:10.3390/ijerph13101031.
5. Grischott F, Puhan M, Hatz C, Schlagenhauf P. Non-vector-borne transmission of Zika virus: a systematic review. Travel Med Infect Dis. 2016;14(4):313–330. https://www.travelmedicinejournal.com/article/S1477-8939(16)30080-1/fulltext.
6. Centers for Disease Control and Prevention. Media relations. Florida investigation links four recent Zika cases to local mosquito-borne virus transmission. http://www.cdc.gov/media/releases/2016/p0729-florida-zika-cases.html. Published July 29, 2016. Accessed May 31, 2018.
7. Adebanjo T, Godfred-Cato S, Viens L, et al Update: interim guidance for the diagnosis, evaluation, and management of infants with possible congenital Zika virus infection—United States, October 2017. MMWR Morb Mortal Wkly Rep. 2017;66(41):1089–1099. https://www.cdc.gov/mmwr/volumes/66/wr/mm6641a1.htm.
8. Kleber de Oliveira W, Cortez-Escalante J, De Oliveira WT, et al Increase in reported prevalence of microcephaly in infants born to women living in areas with confirmed Zika virus transmission during the first trimester of pregnancy: Brazil, 2015. MMWR Morb Mortal Wkly Rep. 2016;65(9):242–247. doi:http://dx.doi.org/10.15585/mmwr.mm6509e2.
9. Mlakar J, Korva M, Tul N, et al Zika virus associated with microcephaly. N Engl J Med. 2016;374(10):951–958. doi:10.1056/NEJMoal600651.
10. Red Book. 2018 Report of the Committee on Infectious Diseases. https://redbook.solutions.aap.org/pdfaccess.ashx?url=/data/books/2205. Published 2018.
11. Citil Dogan A, Wayne S, Bauer S, et al The Zika virus and pregnancy: evidence, management, and prevention. J Matern Fetal Neonatal Med. 2017;30(4):386–396. doi:10.3109/14767058.2016.1174210.
12. Schuker-Faccii L, Sanseverino M, Vianna F, et al Zika virus: a new human teratogen? Implications for women of reproductive age. Clin Pharmacol Ther. 2016;100(1):28–30.
13. Centers for Disease Control and Prevention. Zika and Pregnancy. https://www.cdc.gov/pregnancy/zika/testing-follow-up/evaluation-testing.html. Accessed April 1, 2018.
14. Karwowski MP, Nelson JM, Staples JE, et al Zika virus disease: a CDC update for pediatric health care providers. Pediatrics. 2016;137(5).
15. Pfaender S, Vielle NJ, Ebert N, Steinman E, Alves MP, Thiel V. Inactivation of Zika virus in human breast milk by prolonged storage or pasteurization. Virus Res. 2017;228:58–60. http://www.sciencedirect.com/science/article/pii/SO168170216306542.
16. US ZIKA Pregnancy Registry Collaboration. Birth defects among fetuses and infants of US women with evidence of possible Zika virus infection during pregnancy. JAMA. 2016;317(1):59–68. doi:10.1001/jama.2016.19006.
17. Cavalcanti MG, Cabral-Castro MJ, Gonçalves JLS, et al Zika virus shedding in human milk during lactation: an unlikely source of infection? Int J Infect Dis. 2017;57:70–72. doi:10.1016/j.ijid.2017.01.042.
18. Centers for Disease Control and Prevention. Women and Their Partners Trying to Become Pregnant. https://www.cdc.gov/pregnancy/zika/women-and-their-partners.html. Accessed April 1, 2018.
19. Alfaro-Murillo JA, Parpia AS, Fitzpatrick MC, et al A cost-effective tool for informing policies on Zika virus control. PLoS Negl Trop Dis. 2016;10(5):e0004743. doi:10.1371/journa.pntd.00004743.
20. Polen KD, Gilboa SM, Hills S, et al Update: Interim Guidance for Preconception Counseling and Prevention of Sexual Transmission of Zika Virus for Men with Possible Zika Virus Exposure — United States, August 2018. MMWR Morb Mortal Wkly Rep. ePub: 7. August 2018. doi:http://dx.doi.org/10.15585/mmwr.mm6731e2.
21. Moore CA, Staples JE, Dobyns WB, et al Characterizing the pattern of anomalies in congenital Zika syndrome for pediatric clinicians. JAMA Pediatr. 2017;171(3):288–295. doi:10.1001/jamapediatrics.2016.3982.
22. Reynolds MR, Jones AM, Peterson FF, et al Vital signs: update on Zika virus-associated birth defects and evaluation of all U.S. infants with congenital Zika virus exposure—U.S. Zika pregnancy registry. MMWR Morb Mortal Wkly Rep. 2017;66(13):366–373. doi:http://dx.doi.org/10.15585/mmwr.mm6613e1.
23. Colt S, Garcia-Casal MN, Pena-Rosas JP, et al Transmission of Zika virus through breast milk and other breastfeeding-related body fluids: a systematic review. PLoS Negl Trop Dis. 2017;11(4):e0005528. doi:10.1371/journal.pntd.0005528.
24. Delaney A, Mai C, Smoots A, et al Population-based surveillance of birth defects potentially related to Zika virus infction-15 states and U.S. territories. MMWR Weekly Morbi Mortality Wkly Rep. 2018;67(3):91–96. https://www.cdc.gov/mmwr/volumes/67/wr/mm6703a2.htm?s_cid=mm6706a2_w.
25. Fitzgerald B, Boyle C, Honein MA. Birth defects potentially related to Zika virus infection during pregnancy in the United States. JAMA. 2018;319(12):1195–1196. doi:0.1001/jama.2018.0126.
26. Shapiro-Mendoza CK, Rice ME, Galang RE, et al Pregnancy outcomes after maternal Zika virus infection during pregnancy—U.S. territories, January 1, 2016-April 25, 2017. MMWR Morb Mortal Wkly Rep. 2017;66(23):615–621. http://dx.doi.org/10.15585/mmwr.mm6623e1.
27. Cavalherio S, Lopez A, Serrs S, et al Microcephaly and Zika virus: neonatal neuroradiological aspects. Childs Nerv Syst. 2016;32(6):1057–1060. doi:10.1007/s00381-016-3074-6.
28. Oduyebo T, Polen KD, Walke HT, et al Update: interim guidance for health care providers caring for pregnant women with possible Zika virus exposure-United States (including U.S. territories), July 2017. MMWR Morb Mortal Wkly Rep. 2017;66(29):781–793, https://doi.org/10.15585/mmwr.mm6629e1.
29. Zorrilla CD, Mosquerra AM, Rabionet S, Rivera-Vinas VJ. HIV and Zika in pregnancy: parallel stories and new challenges. Obstet Gynecol Int J. 2017;5(6). doi:10.15406/ogij.2016.05.00180.
30. Satterfield-Nash A, Kotzky K, Allen J, et al Health and development at age 19–24 months of 19 children who were born with microcephaly and laboratory evidence of congenital Zika virus infection during the 2015 Zika virus outbreak—Brazil, 2017. MMWR Morb Mortal Wkly Rep. 2017;66(49):1347–1351. doi:http://dx.doi.org/10.15585/mmwr.mm6649a2.
31. Centers for Disease Control and Prevention. Types of Zika Virus Tests. https://www.cdc.gov/zika/laboratories/types-of-tests.html. Accessed September 5, 2018.
32. Centers for Disease Control and Prevention. Outcomes of pregnancies with laboratory evidence of possible Zika virus infection, 2015-2018. https://www.cdc.gov/pregnancy/zika/data/pregnancy-outcomes.html. Accessed April 1, 2018.
33. Centers for Disease Control and Prevention. For Health Care Providers. http://www.cdc.gov/zika/hc-providers/. Accessed May 31, 2018.
34. Rabe IB, Staples JE, Villanueva J, et al Interim guidelines for interpretation of Zika virus antibody test results. MMWR Morb Mortal Wkly Rep. 2016:65(21). doi:http://dx.doi.org/10.15585/mmwr.num6521e1.
35. Washburn L, Alvarado M. After Zika: raising a baby with microcephaly. https://www.northjersey.com/story/news/health/2018/04/12/zika-baby-severe-birth-defects/385116002/ Accessed May 5, 2018.
Keywords:

congenital Zika infection; infants; pregnancy; Zika virus; ZIKV

© 2018 by The National Association of Neonatal Nurses