Zika virus congenital infection: Guidance for neonatologists and paediatricians
Guidance for managing neonates of mothers with possible Zika virus exposure.
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This guidance provides recommendations for the management of neonates of mothers with possible exposure to Zika virus during pregnancy or within 8 weeks before conception.
It is intended for neonatologists and paediatricians in England. It supersedes the guidance published by Public Health England (predecessor to UK Health Security Agency (UKHSA)) and a Zika virus working group in 2016, and updated in 2019.
Overview
Since 2017, cases of Zika virus disease have declined globally, however transmission continues at low levels in the Americas and in other endemic regions. Further information is available here.
Symptomatic Zika virus infection is typically mild and short-lived in most individuals, but particular attention is required for women who are pregnant or who are considering a pregnancy because of the risk to the developing fetus associated with Zika virus infection in pregnancy.
Almost all cases of Zika virus disease are acquired via mosquito bites; however, a small number of cases of sexual transmission have been reported. Zika virus has been shown to be present in semen and vaginal secretions. The virus persists longer in semen than in the female genital tract, but the viral RNA detected is not necessarily infectious. The risk of sexual transmission of Zika virus is thought to be low. Therefore, if available, the travel history of both the mother and partner should be considered in the evaluation of a neonatal case.
Viable virus has been detected in breast milk and possible Zika virus infections have been identified in breastfeeding infants, but Zika virus transmission through breast milk has not been confirmed. Therefore, the benefits of breastfeeding are likely to outweigh the risks of Zika virus infection in infants.
Diagnostic laboratory testing is available from the Rare and Imported Pathogens Laboratory (RIPL), UKHSA, and testing advice can be found in Zika virus: sample testing advice - GOV.UK.
Zika virus and congenital Zika virus syndrome
A number of congenital abnormalities associated with maternal Zika virus infection during pregnancy have been described (see Table 1).
Table 1. Reported fetal and neonatal abnormalities potentially associated with Zika virus infection
| Imaging | On examination |
|---|---|
| Cerebral and cerebellar atrophy | Microcephaly |
| Cerebral calcifications | Craniofacial disproportion |
| Cortical and white matter abnormalities (eg agyria, pachygyria, lissencephaly) | Redundant scalp skin |
| Ventriculomegaly | Closed anterior fontanelle |
| Internal hydrocephalus | Exuberant external occipital protuberance |
| Periventricular cysts | Intrauterine growth restriction |
| Choroid plexus cyst | Contractures |
| Blakes’s cyst | Talipes |
| Mega cisterna magna | Umbilical hernia |
| Vermian dys/agenesis | Hypertonia or spasticity |
| Callosal abnormalities | Hyperreflexia |
| Brain stem/spinal cord degeneration | Irritability |
| Ocular abnormalities (intraocular calcifications, cataracts, microphthalmia, macular alterations, optic nerve abnormalities | Convulsions, tremors |
| Hearing and visual abnormalities |
Paediatricians should work closely with obstetric colleagues to identify confirmed and potentially infected infants born to parents who had travelled to areas with active Zika virus transmission. Guidance on the obstetric assessment of pregnant women with a history of travel during pregnancy can be found in the Zika virus risk: algorithm for assessing pregnant women. Evidence of fetal infection should be sought as detailed below.
Recommendations for the management of neonates of mothers with possible exposure to Zika virus during pregnancy or within 8 weeks before conception
Information on the risk of Zika virus in each country is available from the NaTHNaC Country Information pages (see the ‘Other Risks’ section in the relevant country page(s). As the risk of Zika virus can change in countries, this should be checked regularly.
Countries with current or past cases of Zika virus transmission have been given one of three ratings: risk, very low risk, or negligible risk. These ratings are based on the reporting of Zika virus disease cases and the assessed risk to UK travellers. The greatest likelihood of acquiring Zika virus infection is in a country classified as risk. The individual risk of infection may be lowered when mosquito bite avoidance measures are followed scrupulously.
Clinicians need to establish if the mother developed an illness compatible with Zika virus disease during pregnancy (including a combination of the following symptoms: rash; itching/pruritus; fever; headache; arthralgia/arthritis; myalgia; conjunctivitis; lower back pain; retro-orbital pain) and confirm if Zika virus testing and/or an antenatal ultrasound scan has been done.
In cases where maternal Zika virus infection, with or without fetal abnormality, was diagnosed prenatally, or where fetal abnormalities were diagnosed prenatally, neonatologists and obstetricians need to collaborate with RIPL prior to delivery to agree a plan for the collection of samples for Zika virus testing and other investigations at birth.
Following live birth of an infant without evident abnormalities where maternal Zika virus serology or PCR tests were positive, or the birth of an infant with abnormalities to a mother with possible exposure to Zika virus during pregnancy (regardless of maternal Zika virus test results), samples should be sent to RIPL for testing. Cases must be discussed with RIPL (usually by the local infectious disease specialist) prior to sample submission.
Clinical assessment should include:
- Physical examination: check for lymphadenopathy, hepatosplenomegaly, dysmorphic features, rash or other skin abnormalities, perform a complete neurological examination
- Growth measurements: head circumference, length and weight
- Ophthalmological evaluation: including examination of the retina; if abnormal, repeat at appropriate intervals (as per ophthalmologist’s decision)
- Hearing assessment: ensure a hearing test is performed prior to discharge
- Additional evaluations: consider other assessments specific to the infant’s clinical presentation
Investigations at birth:
- Collect neonatal samples in line with the prenatally agreed Zika virus testing plan. Confirm with the relevant local infectious disease specialist that they are liaising with RIPL to arrange testing of all appropriate maternal and neonatal samples.
- If a neonatal abnormality is identified only on postnatal examination in an infant born to a mother who, despite potential exposure, had no Zika virus testing during pregnancy, discuss the case urgently with the local infectious disease specialist.
- Request histopathological examination of the placenta and umbilical cord.
- Ensure placental tissue and umbilical cord tissue are taken for Zika virus PCR (samples must be unfixed).
- In an infant with abnormalities, collect samples for testing for syphilis, toxoplasma, rubella, cytomegalovirus and herpes simplex virus infections
- Collect samples for full blood count, clotting, urea & electrolytes, liver function tests and C-reactive protein.
- Perform cranial ultrasound; if microcephaly or intracranial abnormalities are present, arrange MRI of the brain.
- Consider investigations for differential diagnosis of microcephaly (e.g. chromosomal, genetic, metabolic, environmental exposure to toxins, radiation)
- Consider consultation with a paediatric geneticist, infectious disease specialist, neurologist, endocrinologist according to test results
Follow-up of an infant with abnormalities where Zika virus cannot be excluded or an infant without abnormalities who has laboratory evidence of Zika virus infection:
- Follow up at 3 months, then every 3 months up to 12 months if clinically stable, or more frequently if symptomatic (e.g. seizures)
- Follow up Zika virus testing as advised by RIPL (note that an infant whose mother tested positive for Zika virus by PCR or serology is likely to test positive for Zika IgG because of placental transfer; serological follow up will be required until loss of maternal antibody is observed)
- Perform a hearing test at 3 to 6 months if initially normal; refer to audiologist for further evaluation if abnormal
- Perform ophthalmology review at 6 months if initially normal, liaise with ophthalmologist about further follow-up if abnormal
- Discuss with local neurologist and radiologist to determine the most appropriate imaging and frequency of intracranial imaging
- Consider performing an EEG if clinically indicated
- Arrange early referral to community paediatric team for neuro-developmental assessment and long-term support
- Continue follow-up into childhood to identify and monitor long-term adverse sequelae
Follow-up of an infant without evident abnormalities whose mother had symptoms compatible with Zika virus infection whilst travelling or within 2 weeks of return, and no Zika virus antibody test was performed:
- Appropriate samples for diagnostic testing will be advised by RIPL on a case-by- case basis
- If maternal Zika virus infection cannot be excluded, review the infant at 3 months of age
- If any issues become apparent, tailor follow-up accordingly
- If the infant remains well, refer to primary care/health visitor with advice to refer back to secondary care early if any concerns arise -Review at 12 months by a neonatologist or paediatrician
Follow-up of an infant without evident abnormalities whose mother was symptomatic whilst travelling or within 2 weeks after return and maternal Zika virus antibody testing was negative 4 weeks or more after her last possible exposure to Zika virus, or whose mother was previously asymptomatic:
- Record and inform primary care provider of maternal history
- Provide routine care
- If concerns arise during routine investigations (eg hearing test), follow up accordingly
Updates to this page
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Updated the guidance and algorithm.
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Rebranded page to UKHSA. No change to content.
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Updated guidance and flowchart.
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Updated to reflect changes in travel and sexual transmission advice and revised Zika virus risk ratings.
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Revised (v3) with changes in laboratory testing.
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Updated information on Zika congenital syndrome; sexual transmission; symptoms. Added surveillance and details on management of potentially affected infants.
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First published.