Interim Guidance for Evaluating and Managing Infants Born to Pregnant People with Confirmed or Probable Oropouche Virus Disease

Effect on infants

The data on congenital Oropouche are currently limited. In case reports from Brazil and Cuba, findings among people with Oropouche virus infection during pregnancy have included stillbirth and congenital anomalies of the central nervous system (e.g., severe microcephaly). Additional findings among six infants with microcephaly who had evidence of recent Oropouche virus infection included hydrops, ventriculomegaly/hydrocephalus, corpus collosum anomalies, loose redundant skin folds on the head, arthrogryposis, and talipes equinovarus (club foot). One of these infants had findings of severe viral meningoencephalitis. Most mothers with affected infants reported an Oropouche-like illness during their first trimester. However, it is unclear if the timing of the exposure might affect findings.

Other congenital infections caused by viruses include Zika virus and cytomegalovirus. These congenital infections can cause microcephaly, brain anomalies, eye anomalies, hearing loss, and arthrogryposis. The highest risk of Zika-associated birth defects is with first or second trimester infections; however, adverse effects have been reported across all trimesters.

Initial evaluation of infants

Infants born to people with confirmed or probable Oropouche during pregnancy

All infants born to people with confirmed or probable Oropouche during pregnancy should receive a comprehensive evaluation by a healthcare provider at birth and at each well-child visit. A comprehensive evaluation should include

• Documentation of gestational parent's exposure to and laboratory testing for Oropouche in the newborn's record at delivery
• A comprehensive newborn physical exam, including
  • A complete neurological and joint exam (assessing for arthrogryposis)
  • A careful measurement of weight, length, and head circumference, with a low threshold to obtain a head ultrasound in the setting of microcephaly or an abnormal neurologic exam
  • A thorough eye exam with an ophthalmoscope, with a low threshold for ophthalmology referral, especially in the setting of neurologic findings
• A standard newborn hearing screening at birth, preferably using auditory brainstem response (ABR) method
• Thorough developmental monitoring, surveillance, and screening as standard recommendations by the American Academy of Pediatrics
• Infants with congenital anomalies or other signs suggestive of congenital infection should undergo routine evaluation including testing for other infectious (such as Zika virus, cytomegalovirus, herpes simplex virus, Toxoplasma gondii, etc.) and non-infectious etiologies (such as fetal alcohol spectrum disorder or genetic etiologies)
• Oropouche viral RNA testing by real-time reverse transcription-polymerase chain reaction (RT-PCR) can be considered in consultation with your state or local health department and CDC (See Testing for Infants below).

Infants and children with congenital anomalies might benefit from multidisciplinary care including the following specialists:

• Pediatric Infectious Disease Specialists
• Clinical Genetics
• Pediatric Neurology
• Pediatric Ophthalmology
• Developmental Specialists

Infants born to people with potential exposure to Oropouche virus during pregnancy

For infants born to people who developed a clinically compatible illness while traveling in or within 2 weeks of their return from travel to an area with suspected or confirmed Oropouche virus transmission, the gestational parent (rather than the infant) should be tested according to the interim testing guidance for Oropouche virus disease. If the gestational parent tests positive for evidence of infection with Oropouche virus, the infant should undergo an evaluation and testing as described above.

Testing for infants

Currently, serum or CSF samples can be tested for the presence of viral RNA or neutralizing antibodies. An assay to detect immunoglobulin M (IgM) antibodies is not currently available. This guidance will be updated as new assays and approved diagnostic testing on additional specimen types becomes available

• RT-PCR testing: Infants born to people with confirmed or probable Oropouche during pregnancy should have serum collected as close to birth as possible for RT-PCR testing. Cord blood should not be used for testing, because cord blood results are associated with both false positives and false negatives for other congenital infections. If CSF is obtained for other purposes, RT-PCR should also be performed on CSF. Of note, negative PCR testing does not exclude in utero exposure to Oropouche virus. Given the brief window of RT-PCR positivity for other similar viruses, virus exposure early in pregnancy is possible even with a negative molecular test. Despite this, testing is still recommended, because a positive test might prompt specialist referral if an infant has concerning physical exam findings and can guide future management.
• PRNT: Plaque reduction neutralization testing (PRNT) cannot distinguish between gestational parent and infant antibodies in specimens collected from infants at or near birth. Currently, PRNT testing of specimens from infants is not recommended. Testing of the specimens from the gestational parent of affected infants should be conducted, if not already performed, and results documented with the infant's medical record.

In cases of fetal or neonatal demise, additional testing might be available. Contact your state or local health department and CDC for additional guidance.

It is not known if Oropouche virus can be transmitted through bodily fluids. Standard precautions should be practiced when caring for these infants. Currently, infant isolation is not recommended.

Diagnostic testing is available at some public health laboratories and at CDC. Healthcare providers should consult with their state or local health department regarding testing availability. For current testing and case reporting guidance, please visit the CDC's website.

Breastfeeding

Resources

1. Brazil Ministry of Health. Nota Técnica Conjunta nº 135/2024-SVSA/SAPS/SAES/MS — Ministério da Saúde (www.gov.br) 14 August 2024.
2. Clinical Overview of Oropouche Virus Disease | Oropouche | CDC
3. Epidemiological Alert Oropouche in the Region of the Americas: vertical transmission event under investigation in Brazil - 17 July 2024 - PAHO/WHO | Pan American Health Organization
4. Epidemiological Update Oropouche in the Americas Region - 6 September 2024 - PAHO/WHO | Pan American Health Organization
5. Patel DK & Rasmussen SA. Case 11.3.1 - Craniofacial Cases: Congenital Microcephaly. A Practical Guide to Genetic Testing, Evaluation, and Counseling. Academic Press; 2024: 189-191.
6. das Neves Martins, Fernanda Eduarda et al. 2024. Newborns with microcephaly in Brazil and potential vertical transmission of Oropouche virus: a case series. The Lancet Infectious Diseases, ePub 15 Oct 2024
7. Epidemiological Update Oropouche in the Americas Region - 15 October 2024 - PAHO/WHO | Pan American Health Organization