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Congenital Zika virus infection: Clinical features, evaluation, and management of the neonate
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Congenital Zika virus infection: Clinical features, evaluation, and management of the neonate
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Jan 2017. | This topic last updated: Feb 22, 2017.

INTRODUCTION — Zika virus is an arthropod-borne flavivirus transmitted by mosquitoes. Congenital Zika virus infection is associated with severe congenital anomalies. This topic will discuss issues related to newborns congenitally infected with Zika virus. Zika virus infection in pregnant women and other issues related to Zika virus infection, including epidemiology, travel advisories, and infection in older children and adults are reviewed separately. (See "Zika virus infection: Evaluation and management of pregnant women" and "Zika virus infection: An overview".)

PATHOGENESIS — Zika virus is a neurotropic virus that particularly targets neural progenitor cells [1]. Murine and human placental studies support the hypothesis that maternal infection leads to placental infection and injury, followed by transmission of the virus to the fetal brain, where it kills neuronal progenitor cells and disrupts neuronal proliferation, migration, and differentiation, which slows brain growth and reduces viability of neural cells [1-7]. Zika virus is also associated with a higher rate of fetal loss throughout pregnancy, including stillbirths. Placental insufficiency is the mechanism postulated to induce fetal loss later in pregnancy; however, significant placental inflammation has not been described to date [3,8-10]. (See "Zika virus infection: Evaluation and management of pregnant women", section on 'Adverse pregnancy outcomes'.)

HISTOPATHOLOGY — A series from Brazil described histopathological findings in tissue from two newborns with microcephaly and severe arthrogryposis who died shortly after birth and tissue from a microcephalic infant who died at age two months [11]. In all cases, the mothers lived in Brazil and had symptoms consistent with Zika virus infection in the first trimester. The infants were born at 36, 38, and 38 weeks of gestation. Multiple congenital malformations were noted, including a wide range of brain abnormalities, craniofacial malformations, craniosynostosis, pulmonary hypoplasia, and multiple congenital contractures, consistent with fetal akinesia deformation sequence or severe arthrogryposis. In these three cases, there was immunohistochemical and molecular evidence of virus persistence in the brain. The range of neuropathology included ventriculomegaly, lissencephaly (which commonly aligns with microcephaly), and cerebellar hypoplasia, all of which have been observed in other cases studied [12]. Brains also showed evidence of tissue destruction, including calcifications, gliosis, and necrosis. The presence of necrosis suggests ongoing cellular injury, consistent with the demonstrated continued viral presence. Thus, the patterns of injury are likely to follow from both cellular injury at the time of infection as well as subsequent damage as the brain develops. Evidence from cell culture systems places the neuronal precursor cell as a crucial target for Zika virus infection resulting in cell death [13]. Loss of these cells early in development has been reported to substantially reduce the number of neurons generated and result in small brains without cortical gyration [14].

GEOGRAPHIC DISTRIBUTION — Updates regarding the geographic distribution of Zika virus may be viewed at the United States Centers for Disease Control and Prevention website and the Pan American Health Organization/World Health Organization website.

The epidemiology of Zika virus infection is reviewed in detail separately. (See "Zika virus infection: An overview", section on 'Epidemiology'.)

RISK OF VERTICAL TRANSMISSION — The risk for vertical transmission exists throughout pregnancy and in offspring of both symptomatic and asymptomatic mothers; however, the greatest risk of serious fetal sequelae appears to be with first- and second-trimester infection. The risk of vertical transmission is discussed in greater detail separately. (See "Zika virus infection: Evaluation and management of pregnant women", section on 'Risk of vertical transmission and anomalies'.)

CLINICAL FEATURES OF CONGENITAL ZIKA SYNDROME

In utero — In utero Zika virus infection can result in fetal growth restriction and serious sequelae related to the central nervous system [12,15-23]. In a review of the major findings of 14 studies with adequate radiological assessment of suspected or confirmed Zika virus-infected fetuses, the most common abnormalities among the 66 fetuses were ventriculomegaly (33 percent), microcephaly (24 percent), and intracranial calcifications (27 percent) [5]. (See "Zika virus infection: Evaluation and management of pregnant women", section on 'Fetal ultrasonography'.)

Findings in the newborn

Clinical findings — The principal clinical features of congenital Zika syndrome include microcephaly, facial disproportion, hypertonia/spasticity, hyperreflexia, seizures, irritability, arthrogryposis, ocular abnormalities, and sensorineural hearing loss (SNHL) (picture 1 and table 1) [1,23,24]. In a comprehensive review of published reports (including 11 single case reports, 21 case series, and 1 cohort study), the following were identified as unique features of congenital Zika syndrome that are rarely seen with other congenital infections [25]:

Severe microcephaly with partially collapsed skull

Thin cerebral cortices with subcortical calcifications

Macular scarring and focal pigmentary retinal mottling

Congenital contractures (arthrogryposis)

Marked early hypertonia

However, the full spectrum of the syndrome is still evolving and more subtle manifestations of Zika virus infection may become apparent as infants age [1].

The magnitude of risk of birth defects resulting from in utero exposure to Zika virus is uncertain. Estimates of the overall risk of any birth defect or abnormality among fetuses and infants of women infected with Zika virus during pregnancy range from 6 to 42 percent [16,26]. The wide range likely reflects differences in study design, populations studied, maternal Zika case definition (possible versus confirmed), and the range of clinical abnormalities included. Estimates of the risk of microcephaly with in utero Zika virus exposure range from 1 to 4 percent [16,26,27].

In a report of the United States Zika Pregnancy Registry that included data on 442 pregnant women with predominantly travel-associated Zika virus infection, the overall rate of Zika-related birth defects was 6 percent (5 percent among live-born infants [n = 395] and 11 percent among fetal losses [n = 47]). The most common findings were microcephaly (n = 18) and brain abnormalities (n = 18).

In a study that prospectively followed 134 Brazilian women with confirmed Zika virus infection during pregnancy and 73 women who were not infected (though 42 percent of these women were infected with chikungunya virus), pregnancy outcomes were available for 125 and 61 women, respectively [16]. The rate of fetal loss among Zika virus-infected women was 7 percent, which was similar to the rate in uninfected women. Among 117 live-born infants of Zika virus-infected women, the overall rate of adverse findings was 42 percent. Findings included abnormal brain imaging (24 percent), abnormal neurologic examination (21 percent), small size for gestational age (9 percent), ocular abnormalities (7 percent), dysphagia (3 percent), microcephaly (3 percent), abnormal hearing assessment (3 percent), abnormal electroencephalogram and/or clinical seizures (3 percent), and other dysmorphisms (10 percent). Of note, not all infants in this cohort underwent brain imaging, funduscopy, and hearing evaluation, so the findings may underestimate the prevalence of these abnormalities.

Microcephaly – Microcephaly is an important clinical finding in infants with congenital Zika syndrome; however, normal head circumference does not exclude Zika virus infection [28,29]. The World Health Organization (WHO), the United States Centers for Disease Control and Prevention (CDC), and other scientific groups have concluded that the Zika virus can cause microcephaly [30,31], based on a rapidly increasing body of observational data and identification of Zika virus infection in the cerebrospinal fluid and serum of newborns with microcephaly [17,19,20,32-34].

Both proportionate and disproportionate microcephaly have been reported in infants with congenital Zika virus infection. "Proportionate microcephaly" refers to infants who are born SGA and have a small head circumference and also small weight and height for GA; "disproportionate microcephaly" refers to infants who have a small head circumference but have adequate weight and height parameters for GA. (See 'Assessment for microcephaly' below.)

Microcephaly appears to be a consequence of Zika infection early in pregnancy; however, proportionate microcephaly has been observed in the offspring of women infected as late as the third trimester of pregnancy [16].

Craniofacial disproportion – Craniofacial disproportion is seen in most affected infants and is related to the degree of microcephaly (ie, the face appears large in relation to the small head).

Cutis gyrata – In infants with severe microcephaly, "cutis gyrata," or redundant scalp (skin folds on the scalp due to continued growth of the skin despite poor brain growth) may be observed [1].

Craniosynostosis – In a case series of 23 affected infants, 78 percent had a closed anterior fontanel at birth [23].

Ocular abnormalities – The most commonly reported ocular abnormalities include focal pigmentary mottling, chorioretinal atrophy, and optic nerve abnormalities [25,35-37]. Other reported retinal findings include falciform folds, retinal dysplasia, vascular attenuation, and persistent fetal vasculature. Structural abnormalities (eg, microcornea, microphthalmia, cataracts) and glaucoma have also been reported [18,35-40].

Hearing loss – In a series of 70 children with microcephaly and laboratory evidence of congenital Zika virus infection, five (7 percent) had SNHL of varying severity and laterality when tested at 16 to 315 days of age [41]. One of the cases may have been related, at least in part, to amikacin therapy. All five children with hearing loss were among the 44 children with severe microcephaly. It is not known if progressive hearing loss may occur, as seen in infants with congenital cytomegalovirus infection. (See "Congenital cytomegalovirus infection: Clinical features and diagnosis", section on 'Hearing loss'.)

Arthrogryposis – Arthrogryposis and club foot have been reported and are likely neurogenic in origin (ie, due to fixed posture in utero) [11,42].

Neuromotor abnormalities – Infants with congenital Zika syndrome commonly exhibit hypertonia, spasticity, hyperreflexia, irritability, dysphagia, and feeding difficulties [16,24,43].

Seizures – Seizures may occur due to underlying brain malformations.

Small for gestational age – In a case series of 23 affected infants, 40 percent were SGA [23].

Radiologic findings — Neuroradiologic abnormalities are detected in the majority of infants with congenital Zika syndrome who undergo neuroimaging. Findings may include (image 1 and image 2) [12,22,44-46]:

Intracranial calcifications – These occur most commonly at the junction between the cortical and subcortical white matter and may also occur in other locations

Ventriculomegaly

Reduced brain volume

Delayed myelination

Simplified gyral patterns (eg, polymicrogyria, pachygyria)

Hypogenesis of the corpus callosum

Hypoplasia of the brainstem and cerebellum

Enlargement of the cisterna magna

Increased extra-axial fluid

EVALUATION

Overview — Initial evaluation of infants born to mothers with laboratory evidence of Zika virus infection and infants with findings suggestive of congenital Zika infection in the setting of a maternal epidemiologic link should include (algorithm 1 and table 2) [47]:

A thorough physical examination (with measurement of head [occipitofrontal] circumference, length, and weight; assessment of gestational age; and examination for neurologic abnormalities and dysmorphic features).f

Laboratory testing to detect Zika virus (see 'Laboratory evaluation' below).

Head ultrasonography (see 'Neuroimaging' below).

Standard newborn hearing assessment (see "Screening the newborn for hearing loss").

Additional evaluation (including comprehensive eye examination, laboratory tests, and specialist consultation) is performed in neonates with positive maternal Zika virus testing and clinical evidence of congenital Zika syndrome (see 'Additional evaluation' below).

Assessment for microcephaly — There is no standard definition for diagnosis of microcephaly. (See "Microcephaly in infants and children: Etiology and evaluation".)

The World Health Organization (WHO) has defined microcephaly as follows [48-50]: Occipitofrontal circumference (head circumference) greater than two standard deviations below the mean or less than the 3rd percentile based on standard growth charts for sex, age, and gestational age at birth (eg, INTERGROWTH-21st standards (table 3) [51]).

The United States Centers for Disease Control and Prevention (CDC) also define microcephaly as an occipitofrontal circumference below the 3rd percentile [52]. Although this theoretically identifies 3 percent of infants as possibly abnormal, it is a practical screening tool for microcephaly since percentile growth charts are typically used for assessing growth in pediatric health care, and this is the lowest cut-off on these charts. Both the CDC and WHO recommend careful clinical evaluation of these infants before making a definitive diagnosis of microcephaly and determining appropriate follow-up [53]. If an infant's occipitofrontal circumference is ≥3rd percentile but is notably disproportionate to the length of the infant or if the infant has deficits related to the central nervous system, additional evaluation for Zika virus infection may also be appropriate.

The WHO has defined "Zika virus-related microcephaly" as microcephaly with a molecular or epidemiologic link to Zika virus in the absence of other conditions known to cause microcephaly [54]. A molecular or epidemiologic link to Zika virus is defined as one of the following:

Mother had confirmed case of Zika virus infection during pregnancy.

Mother had sexual contact during pregnancy with a person with confirmed Zika virus infection.

Mother had typical clinical manifestations of Zika virus infection (one or more of the following: maculopapular pruritic rash, arthralgia, conjunctivitis, or fever) and relevant epidemiologic exposure during pregnancy (residence in or travel to an area where mosquito-borne transmission of Zika virus infection has been reported).

Amniocentesis with detection of Zika virus in amniotic fluid via polymerase chain reaction (PCR).

Postmortem detection of Zika virus in fetal brain tissue via PCR.

Laboratory evaluation

Whom to test — Infants who warrant Zika virus laboratory testing include either of the following (algorithm 1) [47]:

Newborns of mothers with laboratory evidence for Zika virus infection during pregnancy.

Newborns who have clinical or neuroimaging findings suggestive of congenital Zika syndrome and a maternal epidemiologic link suggesting possible transmission (which includes paternal exposure), regardless of maternal Zika virus test results. A normal head circumference does not exclude the possibility of Zika virus congenital syndrome [43].

Tests to obtain — Laboratory testing for Zika virus infection in the neonate includes the following [47]:

Serum and urine for Zika virus ribonucleic acid (RNA) via real-time reverse transcription PCR (rRT-PCR).

Serum Zika virus immunoglobulin M (IgM) enzyme-linked immunosorbent assay (ELISA).

If cerebrospinal fluid (CSF) is available, test CSF for Zika virus RNA (via rRT-PCR) as well as Zika virus IgM. CSF specimens need not be collected for the sole purpose of Zika virus testing [47].

The initial samples should be collected from the infant within two days of birth if possible to distinguish between congenital, perinatal, and postnatal infection. Testing infant serum is more accurate than testing cord blood. Testing cord blood is not recommended by the CDC [47]. Instructions for collecting and shipping infant serum are available through the CDC website.

The plaque reduction neutralization test (PRNT) measures virus-specific neutralizing antibodies and should be used to confirm the specificity of IgM antibodies detected against Zika virus and to rule out a false-positive IgM result. If the infant's initial IgM is positive but PRNT was not performed on the mother's sample, PRNT should be performed on the infant's initial sample. Since PRNT cannot distinguish between maternal and infant antibody, it might be necessary to repeat PRNT of an initially positive test when the infant is ≥18 months of age and maternally-acquired antibody will have waned. PRNT assays are not generally performed in routine clinical labs but may be available through state and local health departments. They are also available through the CDC. PRNT assays are complex and cumbersome and need to be performed in laboratories familiar with this technique. Additional resources for testing are available through the CDC website.

In addition to testing the neonate, maternal serum should be tested for Zika virus IgM and neutralizing antibodies and dengue virus IgM and neutralizing antibodies if testing was not already performed during pregnancy. Interpretation of serologic findings, particularly ELISA-based techniques, is complex because of significant cross-reactivity between Zika and dengue antibodies; therefore neutralization assays may be required for confirmatory purposes. Histopathologic examination of the placenta and umbilical cord can also be helpful. (See "Zika virus infection: Evaluation and management of pregnant women", section on 'Laboratory testing' and "Zika virus infection: Evaluation and management of pregnant women", section on 'Placenta'.)

Interpretation — The presence of Zika virus RNA in infant serum, urine, or CSF collected within the first two days of life confirms the diagnosis of congenital Zika virus infection [47]. IgM antibodies may be positive or negative.

The duration of viral shedding in newborns infected in utero is not known. A case report described a newborn who was viremic for at least 67 days after birth [55]. However, a negative rRT-PCR result does not exclude congenital infection because viremia may be transient. A negative rRT-PCR result with positive Zika virus IgM test result indicates probable congenital Zika virus infection; however, false-positive results can occur from cross-reacting IgM antibodies or nonspecific reactivity [56].

If both rRT-PCR and IgM are negative, congenital infection is excluded according to the CDC guidelines [47]. However, additional data are needed to determine if Zika infection can be definitively excluded in this setting, particularly in infants with a known Zika exposure. Some infants may not shed virus in their urine and therefore PCR testing is negative despite confirmed maternal infection by PCR during pregnancy. It is possible that there may be a delay in forming IgM antibodies (as can be seen in congenital rubella and cytomegalovirus infection). Further data are necessary to clarify this question.

Neuroimaging — All neonates with suspected or possible congenital Zika infection should have head ultrasonography performed as an initial screening imaging study. If any abnormalities are detected, additional neuroimaging with computed tomography (CT) and/or magnetic resonance imaging (MRI) may be warranted to provide further detail. CT is most sensitive for detection of intracranial calcifications. MRI is more sensitive for characterization of structural brain disease. Consultation with a neurologist is advised to guide appropriate neuroimaging. (See "Approach to neuroimaging in children".)

If the screening head ultrasound is negative or is not interpretable, yet the clinical findings are suspicious for neurologic involvement (eg, seizures, microcephaly, abnormal or asymmetric tone), a more sensitive imaging study should be performed (ie, CT and/or MRI). Consultation with a neurologist is also advised in these circumstances.

Additional evaluation — For infants with positive maternal laboratory testing for Zika virus and clinical evidence of congenital Zika infection (ie, microcephaly and/or other congenital anomalies consistent with congenital Zika syndrome), a comprehensive evaluation should be performed prior to hospital discharge as recommended by the United States Centers for Disease Control and Prevention (CDC) (algorithm 1 and table 2) [47]. This includes:

Consultation with the following specialists as indicated:

A neurologist for determination of appropriate neuroimaging and additional evaluation.

Ophthalmologist for comprehensive eye examination and evaluation for possible cortical visual impairment prior to discharge from the hospital or within one month of birth.

An infectious disease specialist for diagnostic evaluation of other congenital infections (eg, syphilis, toxoplasmosis, rubella, cytomegalovirus infection, lymphocytic choriomeningitis virus infection, herpes simplex virus infection). (See 'Differential diagnosis' below and "Overview of TORCH infections".)

Endocrinologist for evaluation for hypothalamic or pituitary dysfunction.

Clinical geneticist to evaluate for other causes of microcephaly (table 4) and other anomalies, if present.

Orthopedist, physiatrist, physical and/or occupational therapists for the management of hypertonia, club foot, and arthrogrypotic-like conditions (if present).

Pulmonologist or otolaryngologist if there are concerns about aspiration.

Lactation specialist, nutritionist, gastroenterologist, or speech or occupational therapist for management of feeding issues.

Testing of auditory brain stem response to assess hearing. (See "Screening the newborn for hearing loss", section on 'Automated auditory brainstem response'.)

Laboratory tests, including complete blood count and metabolic panel with liver function tests.

DIAGNOSIS — A definitive diagnosis of congenital Zika virus infection is confirmed by the presence of Zika virus ribonucleic acid (RNA) in infant serum, urine, or cerebrospinal fluid collected within the first two days of life [47]. IgM antibodies may be positive or negative.

A negative rRT-PCR result does not exclude congenital infection. A negative rRT-PCR result with positive Zika virus IgM test result indicates probable congenital Zika virus infection; however, false-positive results can occur from cross-reacting IgM antibodies or nonspecific reactivity [56]. If both rRT-PCR and IgM are negative, congenital infection is excluded based upon the Centers for Disease Control and Prevention (CDC) guidelines [47]; other causes for the clinical findings should be investigated.

DIFFERENTIAL DIAGNOSIS — The differential diagnosis for congenital Zika virus infection includes other congenital infections and other causes of microcephaly.

Other congenital infections – The findings of congenital Zika infection (microcephaly, intracranial calcifications, ocular abnormalities, hearing loss, small for gestational age) could suggest other congenital infections, particularly rubella, cytomegalovirus, and toxoplasmosis. Other congenital infections may have characteristic clinical findings (table 5). In particular, hepatosplenomegaly, thrombocytopenia, and skin lesions are not typical of congenital Zika syndrome (although thrombocytopenia and rash have been reported with perinatal Zika infection) [24,57]. Appropriate virologic and microbiologic studies generally are necessary to make a specific diagnosis. (See "Overview of TORCH infections".)

Microcephaly – A variety of genetic abnormalities and environmental insults can affect brain development, resulting in microcephaly (table 6). The etiology and evaluation of microcephaly in infants is discussed in detail separately. (See "Microcephaly in infants and children: Etiology and evaluation".)

MANAGEMENT — There is no specific treatment for Zika virus infection and management is supportive. Management of the various clinical features of congenital Zika virus are detailed in separate topic reviews:

Spasticity (see "Management and prognosis of cerebral palsy")

Feeding difficulties (see "Sucking and swallowing disorders in the newborn", section on 'Management approach')

Hearing loss (see "Hearing impairment in children: Treatment")

Seizures (see "Treatment of neonatal seizures")

FOLLOW-UP

Symptomatic infants — For infants with laboratory evidence and clinical signs and symptoms consistent with congenital Zika syndrome, follow-up includes the following components (table 2) [47]:

A medical home should be established and visits with the primary care provider should occur monthly for at least the first six months of life. Important aspects of follow-up include: monitoring growth parameters and development; providing routine immunizations, anticipatory guidance, and psychosocial support; and ensuring infants receive necessary testing and consultations. (See "Children with special health care needs", section on 'Medical home'.)

Neurologic examination by the primary care provider at one and two months of age. Referral should be made to a neurologist if neurologic abnormalities are noted or if there are parental or provider concerns. (See "Detailed neurologic assessment of infants and children".)

Referral to a developmental specialist and for early intervention services and close neurodevelopmental follow-up.

Repeat comprehensive ophthalmologic examination at age three months with referral to an ophthalmologist for any abnormal findings or for any parental or provider concerns. (See "Visual development and vision assessment in infants and children".)

Repeat auditory brainstem response (ABR) testing at age four to six months with referral to audiologist for any abnormal findings or for any parental or provider concerns. (See "Hearing impairment in children: Evaluation".)

Repeat testing for hypothyroidism at age two weeks and age three months (even if the initial newborn screening results were normal) with referral to an endocrinologist for any abnormal findings. (See "Clinical features and detection of congenital hypothyroidism", section on 'Serum tests of thyroid function'.)

Continued supportive services for the family.

Asymptomatic infants — For infants with laboratory evidence of congenital Zika infection, but with no clinical findings of congenital Zika syndrome, outpatient follow-up includes the following components (table 2) [47]:

A medical home should be established. Important aspects of follow-up include: monitoring growth parameters and performing developmental screening at each well-child visit. Anticipatory guidance should be provided for families regarding developmental milestones, feeding and growth, sleep and irritability, and abnormal movements. (See "Children with special health care needs", section on 'Medical home'.)

A standardized, validated developmental screening tool should be used at nine months as currently recommended or earlier for any parental or provider concerns. (See "Developmental-behavioral surveillance and screening in primary care".)

Referral to ophthalmology for comprehensive eye examination within one month of birth. Perform vision screening and assess visual regard at every well-child visit, and refer to ophthalmology for any abnormal findings or for any parental or provider concerns. (See "Visual development and vision assessment in infants and children".)

Test ABR within one month of birth. Consider repeat ABR at age four to six months or perform behavioral diagnostic testing at age nine months, and refer to audiologist for any abnormal findings or for any parental or provider concerns. (See "Hearing impairment in children: Evaluation".)

Continued supportive services for the family.

PROGNOSIS — The prognosis of newborns with congenital Zika infection is unclear. In a large Brazilian case series, the reported mortality rate among live-born infants with confirmed and probable congenital Zika infection ranged from four to six percent [43]. The combination of Zika virus-related microcephaly and severe cerebral abnormalities generally has a poor prognosis, but little is known about the prognosis for congenitally infected infants with less severe or no apparent abnormalities at birth [5].

PERINATAL AND POSTNATAL INFECTION

Perinatal exposure — Maternal-fetal transmission of Zika virus can occur during labor and delivery. Two cases of intrapartum Zika virus transmission to infants from mothers infected within two to three days of delivery have been reported; one of these infants had no clinical manifestations, and the other had thrombocytopenia and a diffuse rash [57,58]. There are no reports of Zika virus infection acquired by an infant at the time of delivery leading to microcephaly [59]. Zika virus has been identified in breast milk; however, there is no conclusive data to determine whether transmission can occur via this route [60]. (See "Zika virus infection: Evaluation and management of pregnant women", section on 'Breastfeeding'.)

Maternal and newborn laboratory testing is indicated during the first two weeks of life if the mother had relevant epidemiologic exposure within two weeks of delivery and had ≥2 of the following manifestations of Zika virus infection: rash, conjunctivitis, arthralgia, or fever [58].

If the mother and newborn present <7 days after onset of maternal signs and symptoms, check serum and urine Zika virus ribonucleic acid (RNA) by real-time reverse transcription polymerase chain reaction (rRT-PCR) in both. If mother and newborn present 8 to 14 days after onset of symptoms, check urine Zika rRT-PCR in both. A positive test is diagnostic of infection.

If the rRT-PCR is negative and the mother is ≥4 days after the onset of symptoms, check Zika virus immunoglobulin M (IgM) and neutralizing antibody titers. A positive test indicates probable infection.

If the newborn is symptomatic and the mother is asymptomatic, check maternal Zika virus IgM and neutralizing antibody titers.

If newborn cerebrospinal fluid (CSF) is obtained for other reasons, CSF testing for Zika virus RNA (via rRT-PCR) is appropriate; however, concern for possible Zika exposure alone does not necessitate lumbar puncture [58].

Postnatal infection — Infants and children who acquire Zika virus infection postnatally appear to have a mild course, similar to that in adults [58]. (See "Zika virus infection: An overview", section on 'Children'.)

PREVENTION — There is currently no vaccine against Zika virus. Prevention efforts are aimed at reducing Zika infection during pregnancy, which is discussed separately. (See "Zika virus infection: Evaluation and management of pregnant women", section on 'Prevention'.)

ONLINE RESOURCES — Online updates regarding Zika virus infection may be viewed at the following websites:

United States Centers for Disease Control and Prevention website

European Centre for Disease Prevention and Control website

American College of Obstetricians and Gynecologists website

Pan American Health Organization/World Health Organization website

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Zika virus infection".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

Basics topic (see "Patient education: Zika virus infection (The Basics)")

SUMMARY AND RECOMMENDATIONS

Vertical transmission of Zika virus from mother to fetus during pregnancy has been associated with serious sequelae. The greatest risk of serious fetal sequelae appears to be with first- and second-trimester infection. The rate of vertical transmission and the rate at which infected fetuses manifest complications are unknown. (See 'Risk of vertical transmission' above.)

The clinical features of congenital Zika syndrome include microcephaly, facial disproportion, hypertonia/spasticity, hyperreflexia, irritability, seizures, arthrogryposis, ocular abnormalities, and sensorineural hearing loss (SNHL) (table 1 and picture 1). Microcephaly is a key clinical finding; however, normal head circumference does not exclude Zika virus infection. The features of congenital Zika virus syndrome have been described in case reports and small case series. The full spectrum of the syndrome is still evolving. (See 'Clinical findings' above.)

Neuroradiologic abnormalities are detected in the majority of infants with congenital Zika syndrome who undergo neuroimaging. Findings may include (image 1 and image 2) (see 'Radiologic findings' above):

Intracranial calcifications

Ventriculomegaly

Reduced brain volume

Delayed myelination

Simplified gyral patterns (eg, polymicrogyria, pachygyria)

Hypogenesis of the corpus callosum

Brainstem and cerebellar hypoplasia

Enlargement of the cisterna magna

Increased extraaxial fluid

For all infants with suspected or possible congenital Zika infection, the initial evaluation includes (algorithm 1 and table 2):

A thorough physical examination (with measurement of head [occipitofrontal] circumference, length, and weight; assessment of gestational age; and examination for neurologic abnormalities and dysmorphic features)

Laboratory testing to detect the Zika virus (see 'Laboratory evaluation' above)

Head ultrasonography (see 'Neuroimaging' above)

Standard newborn hearing assessment (see "Screening the newborn for hearing loss")

Laboratory testing for Zika virus infection in the neonate includes the following (see 'Laboratory evaluation' above):

Serum and urine for Zika virus ribonucleic acid (RNA) via real-time reverse transcription polymerase chain reaction (rRT-PCR).

Serum Zika virus immunoglobulin M (IgM) enzyme-linked immunosorbent assay (ELISA). If IgM is positive, plaque reduction neutralization test (PRNT) is used to confirm the specificity of the IgM antibodies against Zika virus and to exclude a false-positive IgM result.

If cerebrospinal fluid (CSF) is available, test CSF for Zika virus RNA (via rRT-PCR) as well as Zika virus IgM. CSF specimens need not be collected for the sole purpose of Zika virus testing but may be reasonable for evaluation of infants with microcephaly or intracranial calcifications.

For infants with positive maternal laboratory testing for Zika virus and clinical evidence of congenital Zika syndrome, a comprehensive evaluation (including ophthalmologic examination, laboratory tests, and specialist consultation) should be performed prior to hospital discharge (algorithm 1 and table 2). (See 'Additional evaluation' above.)

A definitive diagnosis of congenital Zika virus infection is confirmed by the presence of Zika virus RNA in samples of serum, urine, or CSF collected within the first two days of life; IgM antibodies may be positive or negative. A negative rRT-PCR result with positive Zika virus IgM test result indicates probable congenital Zika virus infection. (See 'Diagnosis' above.)

The differential diagnosis for congenital Zika virus infection includes other congenital infections (table 5) and other causes of microcephaly (table 6). (See 'Differential diagnosis' above and "Overview of TORCH infections" and "Microcephaly in infants and children: Etiology and evaluation".)

There is no specific treatment for Zika virus infection and management is supportive. Prevention efforts are aimed at reducing Zika infection during pregnancy. (See 'Management' above and "Zika virus infection: Evaluation and management of pregnant women", section on 'Prevention'.)

For infants with confirmed Zika virus infection, close follow-up is necessary. The appropriate follow-up evaluation depends upon whether or not the infant has clinical signs and symptoms of congenital Zika syndrome. All infants should have close monitoring of growth and development, repeat ophthalmologic examination, and auditory brainstem response testing (algorithm 1 and table 2). (See 'Follow-up' above.)

The prognosis of newborns with congenital Zika infection is unclear. Reported mortality rates among live-born infants range from four to six percent. The combination of Zika virus-related microcephaly and severe cerebral abnormalities generally has a poor prognosis, but little is known about the prognosis for congenitally infected infants with less severe or no apparent abnormalities at birth. (See 'Prognosis' above.)

Maternal-fetal transmission of Zika virus can occur during labor and delivery. There are no reports of Zika virus infection acquired by an infant at the time of delivery leading to microcephaly. There are no data to contraindicate breastfeeding, although the virus has been identified in breast milk. Maternal and newborn laboratory testing is indicated during the first two weeks of life if the mother had relevant epidemiologic exposure within two weeks of delivery and had clinical manifestations of Zika virus infection (eg, rash, conjunctivitis, arthralgia, or fever). Infants and children who acquire Zika virus infection postnatally appear to have a mild course, similar to that seen in adults. (See 'Perinatal and postnatal infection' above.)

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