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Experts recommend longer follow-up period for children exposed to Zika
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For children with suspected or confirmed exposure to Zika virus in utero, the CDC recommends screening for signs of congenital Zika syndrome and other birth defects by 1 month of age. The agency also recommends evaluating children for microcephaly until age 24 months and older. However, authors of a recent editorial published in Trends in Microbiology are now suggesting that because the effects of Zika virus infection may extend well into childhood, regular screening may be necessary through adolescence.
Approximately one in 10 U.S. pregnant women with confirmed Zika virus infection had a fetus or baby with birth defects in 2016, according to the CDC. The highest risk for birth defects occurred when mothers were infected in the first trimester.
The level of screening recommended by the CDC depends on how confident physicians are that the child was exposed to Zika virus in utero and whether the patient exhibits signs of congenital Zika syndrome. These tests may include a head ultrasound, a comprehensive eye exam by an ophthalmologist and automated auditory brain stem response.
“Microcephaly was the first outcome studied during the Zika virus epidemic because it was most obvious and could be assessed at birth by health care providers using only a measuring tape,” Kristina Adams Waldorf, MD, professor of obstetrics and gynecology and global health at the University of Washington, and an author of the editorial, told Infectious Diseases in Children.
Adams Waldorf said this was very important in many middle- to low-income countries that did not have access to brain imaging technology.
A small study published in JAMA Neurology showed that of 11 infants with developmental abnormalities related to congenital Zika virus infection — with or without microcephaly — all had brain damage confirmed through ultrasonography before birth and MRI. These injuries included a reduction in cerebral volume, ventriculomegaly, cerebellar hypoplasia, lissencephaly with hydrocephalus and arthrogryposis.
“A number of different injuries that we can see can either be compensated for somewhat or develop in new respects over time,” Adams Waldorf said. “We recommend that children who are exposed to Zika virus either in utero or very early childhood be frequently assessed by a developmental specialist not only through the first 2 years of life, but also on a regular basis up to adolescence.”
The authors said they made this recommendation because issues with processing speed, executive functioning and working memory can begin to emerge in adolescence.
Margaret A. Honein, PhD, MPH, director of the Division of Congenital and Developmental Disorders at the CDC’s National Center on Birth Defects and Developmental Disabilities, explained that while the CDC was creating their first set of screening recommendations for children, the agency was still learning about the effects of the virus during pregnancy. To gain as much insight as possible, they worked closely with public health and clinical partners throughout the process.
“We are still in the early stages of understanding the full impact that Zika has when the infection occurs during pregnancy,” she said.
Gaps in knowledge
WHO has acknowledged gaps in research on congenital Zika infection, and it added Zika to its Blueprint list of priority diseases in early 2018. Zika was one of eight diseases that the organization believes could pose an emergency because of its risk for spreading on an epidemic level.
According to Marie-Térèse Little, PhD, a biomedical scientist at 4th Dimension Biomedical and Research Communications and an author of the editorial, more research is specifically needed to determine how the virus is transmitted to the fetus through the mother’s placenta.
“The fallout of the viral infection can really be likened to those caused by HIV, other congenital infections and chemotherapeutic agents,” Little told Infectious Diseases in Children. “It affects the white matter of the brain, knocks out neural stem cells and has devastating and broad-spectrum consequences.”
Adams Waldorf believes the CDC guidelines for screening for abnormalities associated with congenital Zika infection are “too vague, and many health care providers will not have the tools or skills to assess for complex developmental problems during a short examination.”
As a CDC employee, Honein would not comment on the new screening suggestions published in the editorial, but she stressed the importance of brain imaging and ophthalmic exams for children exposed to the virus in utero who continue to experience the effects of congenital Zika infection. She also recommended that physicians should take into consideration each child’s clinical presentation and symptoms when determining if they need screening or additional tests.
“We [at the CDC] see the critical importance of all children getting appropriate care and evaluation,” she said. “Children who have exposure to Zika virus in utero are at risk of serious birth defects and abnormalities, some of which will not be detected without evaluation. It is important that these children have imaging shortly after birth and a head measurement at each well-child visit to make sure that their head is growing and developing correctly.”
Age-appropriate developmental monitoring and screening, Honein added, should be conducted in accordance with AAP recommendations for all children. The organization states that screening should begin at well-child visits when children reach 9, 18, 24 and 30 months of age, regardless of their exposure status.
This advice aligns with recommendations highlighted in the editorial by Adams Waldorf, Little and colleagues.
“We recommend frequent assessment and monitoring of Zika virus-exposed children throughout the first 24 months of age,” the authors wrote. “Because motor, language and cognitive development are highly interrelated in infancy through early childhood, assessment of multiple domains of development — including motor, language and communication, cognition and learning, social-emotional and adaptive development — is needed to fully determine the impact of a fetal brain injury.”
According to Adams Waldorf, fetal brain injury should be monitored across a spectrum of health care specialties — including pediatricians, developmental specialists, and physical, occupational and visual therapists — and should incorporate the same approaches that are currently used for other complex conditions.
Adams Waldorf acknowledged that long-term screening would be time intensive and expensive if not covered by insurance, and that childhood developmental specialists may not be available in endemic countries. Additionally, there may be language and cultural barriers to providing regular screening, she said.
Although the long-term effects of congenital Zika infection are not fully understood, Honein stressed the importance of follow-up.
“We are concerned that there could be miscommunication, and people could think that if the baby is born and does not have microcephaly or a serious birth defect noted right when they are born that there is no problem,” Honein said. “We want to correct that message and make sure that people know that follow-up is necessary to assess for neurologic abnormalities or other problems, they can be picked up and children can be referred to services promptly so that they can have the best outcome.”
The CDC expects to issue a report this month that includes primary data collected from the follow-up of children with congenital Zika infection. – by Katherine Bortz
- References:
- Adams Waldorf KM, et al. Trends Microbiol. 2018;doi:10.106/k.tim.2018.05.011.
- CDC: Zika and Pregnancy - Congenital Zika Syndrome & Other Birth Defects. https://www.cdc.gov/pregnancy/zika/testing-follow-up/zika-syndrome-birth-defects.html. Accessed July 20, 2018.
- CDC: Zika and Pregnancy - Data & Statistics. https://www.cdc.gov/pregnancy/zika/data/index.html. Accessed July 20, 2018.
- CDC: Zika and Pregnancy - Evaluation & Testing. https://www.cdc.gov/pregnancy/zika/testing-follow-up/evaluation-testing.html. Accessed July 20, 2018.
- Melo AS, et al. JAMA Neurol. 2016;doi:10.1001/jamaneurol.2016.3720.
- WHO: List of Blueprint priority diseases. http://www.who.int/blueprint/priority-diseases/en/. Accessed July 20, 2018.
- For more information:
- Kristina Adams Waldorf, MD, can be reached at University of Washington, 908 Jefferson St., Seattle, WA 98104; email: Leila R. Gray at leilag@uw.edu.
- Margaret A. Honein, PhD, MPH, can be reached at the CDC’s National Center on Birth Defects and Developmental Disabilities, 1600 Clifton Rd., Atlanta, GA 30329; email: media@cdc.gov.
- Marie-Térèse Little, PhD, can be reached at 4th Dimension Biomedical and Research Communications; email: mtlittle@4dbrc.com.
Disclosures: Adams Waldorf, Honein and Little report no relevant financial disclosures.