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Infants With Congenital Zika Virus Infection: A New Challenge for Early Intervention Professionals

Porter, Sallie DNP, PhD, APN; Mimm, Nancy MSN, APHN-BC, RN-BC

doi: 10.1097/IYC.0000000000000084
Original Research/Study
ISEI Article

Zika virus infection-associated microcephaly has generated public health and media concern. Unsettling images emerging from Brazil of infants with abnormally small heads have raised concern among women of childbearing age, international travelers, government officials, and health care professionals. The World Health Organization declared the most recent, ongoing Zika virus infection outbreak a “public health emergency of international concern.” The Centers for Disease Control and Prevention is working to understand the impact of Zika virus infection in the United States and elsewhere. Zika virus is a mosquito-transmitted Flavivirus that can also be transmitted through sexual contact. Congenital Zika virus infection is a cause of microcephaly and other serious neurological harm to the fetus. The early intervention professional should understand Zika virus infection including the geographical risk, etiology, epidemiology, and potential developmental impact. Still evolving clinical, policy, and research implications for early intervention professionals need to be based on the context of emerging scientific information. It is important for early intervention professionals to remain attentive, as scientific knowledge concerning the impact of congenital Zika virus infection in infants and families will be evolving for years to come.

Division of Advanced Nursing Practice, Rutgers School of Nursing, Newark, New Jersey (Dr Porter); and Division of Family Health Services, Reproductive and Perinatal Health Services, New Jersey Department of Health, Trenton (Ms Mimm). Ms Mimm is a Doctor of Nursing Practice student at Rutgers.

Correspondence: Sallie Porter, DNP, PhD, APN, Division of Advanced Nursing Practice, Rutgers School of Nursing, 180 University Ave, Newark, NJ 07102 (portersa@rutgers.edu).

The authors thank Margaret P. Disston for her editing assistance.

The authors report no conflicts of interest.

ZIKA VIRUS (ZIKV) infection-associated microcephaly has created public health and media concern. Unsettling images emerging from Brazil of young infants with abnormally small heads have raised concern among women of childbearing age, international travelers, government officials, and health professionals. Before 2015, health experts believed ZIKV infection to be relatively harmless, often with those infected showing no symptoms (Bell, Boyle, & Petersen, 2016; Costello et al., 2016). The rapid spread of ZIKV infection, along with realization by health care professionals that for some individuals, there are serious ZIKV infection-related health outcomes, has captured the interest of federal and state government officials in the United States and elsewhere (Miner & Diamond, 2016).

On February 1, 2016, the World Health Organization ([WHO], 2016a) declared the most recent, ongoing ZIKV infection outbreak a “public health emergency of international concern.” The Centers for Disease Control and Prevention (CDC) is working to better understand the incidence and impact of ZIKV infection in the United States and elsewhere. States are working to develop and implement plans to address the potential spread as well as health ramifications more locally.

ZIKV infection is a mosquito-transmitted Flavivirus that can also be transmitted through sexual contact. Congenital ZIKV infection is a cause of microcephaly and other serious neurological damage in the fetus and the infant (Cauchemez et al., 2016; Johansson, Mier-y-Teran-Romero, Reefhuis, Gilboa, & Hills, 2016; Rasmussen, Jamieson, Honein, & Petersen, 2016). Early intervention professionals may be called upon to care for infants and young children and families affected by ZIKV infection.

Early intervention professionals potentially have a significant role in documenting and elucidating health and developmental outcomes for infants and young children with congenital ZIKV infection. This important role will be complicated by the evolving knowledge base and the unprecedented nature of the ZIKV outbreak. Early intervention professionals will need to remain alert to epidemiology and etiological knowledge advances, especially as data may change frequently.

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GEOGRAPHY

The ZIKV was first described in humans in 1952 in Uganda (WHO, 2015). Prior to human identification, the ZIKV was identified in a rhesus monkey in 1947 also in Uganda. Since 2007, concerning outbreaks of ZIKV infection have been noted in a number of countries including Micronesia, French Polynesia, Central America, South America, and Cape Verde off the coast of Africa.

As of August 10, 2016, mosquito-borne ZIKV is present in at least 69 countries and territories (WHO, 2016b). Since February 11, 2016, a total of 11 countries have reported person-to-person transmission of ZIKV infection (WHO, 2016a). Weekly updates to the WHO Zika situation report may be found on their website (http://www.who.int/emergencies/zika-virus/situation-report/en). The ZIKV infection spread in the Americas is especially concerning, as the area population has little immunity to ZIKV infection as compared with populations in Africa and Asia.

Brazil is considered the epicenter of the current outbreak in the Americas. As of October 2015, there have been as many as 4,000 cases of microcephaly and other fetal neurological malformations that may be ZIKV infection-related in Brazil (Berkrot, 2016; Melo et al., 2016; Zavis, 2016). The count accuracy of the 4,000 cases of microcephaly is controversial, as case definitions vary among sources and the window for laboratory confirmation of ZIKV infection is time sensitive. In addition, limited health resources in Brazil have delayed and hindered the robust investigation of all presumed congenital ZIKV infection cases. As of August 10, 2016, likely congenital ZIKV infection-associated microcephaly and other anomalies have been reported in 15 countries (WHO, 2016b).

Thirty states encompass habitat friendly to the Aedes mosquito (CDC, 2016a). Mosquitoes that may transmit ZIKV have been identified in almost all 50 states (Malo, 2016). People residing in the southern United States are at higher risk for ZIKV infection, as this geographic area has a large mosquito population. As of mid-August 2016, the ZIKV infection spread by local mosquitoes has been detected in the United States in the state of Florida (CDC, 2016a).

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ETIOLOGY

ZIKV infection has multiple routes of transmission to humans. The vector is primarily the Aedes aegypti mosquito, but the Aedes albopictus and Asian tiger mosquitoes are also a source of ZIKV transmission (Malo, 2016). ZIKV infection can also be spread by sexual contact and laboratory exposure. Transmission through blood transfusion, organ or tissue transplant, and fertility treatment has been theorized (Fleming-Dutra et al., 2016). More information about transmission specifics via sexual, perinatal, transplacental, blood transfusion, saliva, urine, and breast milk is needed (dos Santos & Goldenberg, 2016).

Congenital ZIKV infection is most concerning, as serious health outcomes to the fetus and the infant have been noted. ZIKV outbreaks preface microcephaly outbreaks (Johansson et al., 2016). It is not fully understood whether there is mother-to-infant transmission of ZIKV infection during labor and delivery. ZIKV RNA has been found in breast milk, but at this time, breast-feeding by ZIKV-infected mothers is not contraindicated (Fleming-Dutra et al., 2016).

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EPIDEMIOLOGY

U.S. health officials state that thousands of individuals may have been infected with the ZIKV while traveling internationally and have now arrived back in the United States. Because 80% of people with ZIKV infection have no symptoms, it is likely that many people do not know they are infected (Tavernise, 2016). All these individuals who both know and do not know they have ZIKV infection are potentially able to start an outbreak through the local mosquito population.

World Health Organization believes that potentially many thousands of infants with congenital ZIKV infection, worldwide, will exhibit neurological abnormalities (Berkrot, 2016). These neurological defects may range in severity from moderate to severe. As of August, 31, 2016, the CDC aggregated reports of 1,595 pregnant women with laboratory evidence of possible ZIKV infection including 624 pregnant women residing in the United States and District of Columbia and 971 living in U.S. territories. As of September 1, 2016, a total of 16 infants with laboratory-confirmed congenital ZIKV infection and anomalies have been live-born in the United States (WHO, 2016b). CDC Arborviral Disease Branch updates to the current number of cases may be found at http://www.cdc.gov/zika/geo/united-states.html. The number of infants born with congenital ZIKV infection in the United States and its territories will very likely rise over time.

Experts believe that the ZIKV could infect 25% of the population of Puerto Rico by the end of 2016, with the possibility that hundreds of infants could be affected by microcephaly and other concerning neurological issues (McKay, 2016). Puerto Rico's budget difficulties are hindering ZIKV infection prevention efforts (McKay, 2016). Again, these numbers will very likely change and increase over time.

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ZIKV INFECTION IN PREGNANT WOMEN

Four of five individuals infected with the ZIKV have no symptoms (Rathore, 2016). The incubation period for ZIKV infection is 2–14 days (Rathore, 2016). Symptoms are generally mild and last for a few days to a week and include fever, maculopapular rash, arthralgia, conjunctivitis, myalgia, and headache. The rash is often pruritic and maculopapular (Fleming-Dutra et al., 2016). ZIKV infection has also been linked to neurological disorders in adults including Guillian–Barré syndrome and paralysis-causing myelitis (WHO, 2016a).

In pregnant women, ZIKV infection presents most often with a pruritic descending maculopapular rash, arthralgia, fever, and conjunctivitis (Simeone et al., 2016). World Health Organization (2016a) is advising people in ZIKV infection transmission geographical areas to delay pregnancy. ZIKV infection may damage the developing fetus regardless of whether the pregnant women had symptoms of infection or not. Asymptomatic pregnant women with laboratory evidence of ZIKV infection have delivered infants with microcephaly and other serious brain anomalies (Jamieson & Honein, 2016). Monitoring of at-risk pregnant women will assist in the early identification of some affected infants and adequate mobilization of resources.

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MATERNAL-TO-FETAL TRANSMISSION OF ZIKV INFECTION

Information is accumulating to improve scientific understanding of the precise mechanism of transmission from mother to fetus. The ZIKV has been found in the placenta, amniotic fluid, and fetal brain tissue (Zavis, 2016). Animal models show the ZIKV is neurotropic. Intrapartum transmission has been documented, but a better scientific understanding is needed. There are no reports of transmission through breast-feeding. Absolute certainty about all transmission particulars cannot be concluded at the present.

The evidence is clear that prenatal exposure to the ZIKV especially in the first and second trimesters is associated with severe microcephaly. There is a 1%–13% risk for microcephaly when a mother is infected with the ZIKV during the first trimester (Johansson et al., 2016). Although first-trimester ZIKV infection is a risk factor for microcephaly, an increase in central nervous system abnormalities has been identified that are not gestational age specific (Johansson et al., 2016). ZIKV infection in later pregnancy has been associated with infant's poor growth and possible fetal death (Rasmussen et al., 2016). Preliminary research results out of Colombia suggests that structural defects are not linked to third-trimester ZIKV infection (Pacheco et al., 2016). Evidence is still unclear of the full spectrum of defects that is caused by ZIKV infection. It is important, therefore, for early intervention professionals to maintain awareness and keep abreast of new developments and findings.

In at least one set of twins, born to a woman infected with the ZIKV, only one infant has overt ZIKV infection manifestations (Doce & Garcia, 2016). The health and developmental impact on the apparently unaffected twin is not known. The permeability of the placenta, the resistance of neurons, and genetic predisposition may have an impact on which infants are seriously damaged by ZIKV infection and which infants have no effects or less overt problems from congenital ZIKV exposure (Doce & Garcia, 2016).

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CLINICAL FINDINGS

Congenital ZIKV infection of the human fetus is a cause of microcephaly (WHO, 2016a). Microcephaly, however, is not the only serious outcome exhibited by infants with congenital ZIKV infection. Other serious outcomes in infants with congenital ZIKV infection include spasticity, seizures, irritability, feeding difficulties, visual impairment, and documentation of several brain anomalies (Berkrot, 2016; Costello et al., 2016). The full phenotype spectrum of congenital ZIKV infection in infants is not known (Fleming-Dutra et al., 2016; Rasmussen et al., 2016). Much of what is reported concerning clinical features of congenital ZIKV infection comes from small studies that may not be generalizable. As with all components of ZIKV infection knowledge, the science is still evolving and what is known may change and expand.

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IMPLICATIONS FOR EARLY INTERVENTION PROFESSIONALS

There is not much known about the health and developmental outcomes for infants with congenital ZIKV infection including those born to symptomatic and asymptomatic pregnant women (Simeone et al., 2016). What does seem clear is that early intervention professionals need to plan and prepare for the potential impact of congenital ZIKV-related adverse pregnancy and birth events and the resultant increased demand for services (de Barros Miranda-Filho et al., 2016; Johansson et al., 2016). The cohort of congenitally ZIKV-infected infants may exhibit more intense health and developmental needs than the typical children enrolled in early intervention services. The potential severity and complexity of infants with congenital ZIKV infection may prove challenging for families, professionals, and programs, especially in the midst of evolving scientific knowledge and resource constraints including less than optimal funding and therapist availability.

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CLINICAL IMPLICATIONS

There is a range of clinical findings in infants with congenital ZIKV infection (Table 1). The range of clinical findings is likely to expand as more is learned about the condition and its impact on infants (Costello et al., 2016). Therefore, it behooves early intervention professionals to remain vigilant looking for new scientific knowledge concerning the health and development implications of congenital ZIKV infection. Development-enhancing interventions will need to evolve right along with scientific knowledge. The American Academy of Pediatrics, CDC, state health departments, and other vetted sites are good sources for up-to-date information for professionals as well as resources designed for parents (Table 2). A checklist for early intervention services and support for infants and their families with congenital ZIKV exposure care is available (the Figure). For children with complex health care challenges and their families, a checklist may help organize care and ensure that more basic care needs are not missed.

As with all early intervention infants and families, using a family-centered approach to evaluation and assessment, development of the individualized family services plan, and service provision is essential. Infants with congenital ZIKV infection likely require multiple medical consultation appointments and follow-up visits, so flexibility as to assessment and planning meetings may be especially important. Considering the locales currently most associated with ZIKV infection, Portuguese or Spanish-speaking program staff may be helpful in providing family-centered care.

Early intervention professionals will need to also pay special attention to social determinants of health when arranging for evaluation, meetings, and services (Baptista, Quaghebeur, & Alarcon, 2016). Access to care, neighborhood conditions, and socioeconomic status likely all have an impact on outcomes for infants with ZIKV infection and their families. Low-income and uninsured people are less likely to get ZIKV testing (Santora, 2016). Prior research on sociodemographic and clinical characteristics that influence early intervention enrollment found that infants with more severe disabilities, as may often be the case for infants with congenital ZIKV infection, were less likely to participate fully in early intervention services, so outreach and follow-up may need even closer attention than the typical enrollee family (Litt & Perrin, 2014).

Because of Aedes mosquito behavior, population density and poverty may place people at a greater risk for ZIKV infection. This is especially concerning in Puerto Rico where about half of the population lives in poverty. ZIKV infection appears to flourish in areas that are impoverished. Inadequate housing, lack of air-conditioning, screen-less doors and windows, standing water found in areas with poor drainage, and inadequate trash removal may contribute to conditions that support a habitat for mosquito proliferation. Transportation issues and out-of-pocket expenses may hinder optimal early intervention participation.

The emotional health of infants and families affected by congenital ZIKV infection needs to be a special emphasis both during interviews and treatment. The novel circumstances of infants with congenital ZIKV infection have made some mothers in Brazil leery of attention even from health care professionals (Zavis, 2016). Media interest, social media, and an undercurrent of still evolving scientific information may make parents especially vulnerable to unwanted attention, stigma, and anxiety. Privacy and confidentiality may be challenging. Adequate psychosocial services to address the parent's emotional status as a parent of an infant with complex health and developmental needs are essential.

The CDC offers Interim Guidance for the Evaluation and Management of Infants With Possible Congenital Zika Virus Infection (Russell et al., 2016). As this guidance is likely to change as more is learned about congenital ZIKV infection, it is important for early intervention professionals to confirm they are using the most current evidence-based guidelines. Pediatric health care clinicians are encouraged to refer affected infants and families to early intervention services as soon as possible.

The initial evaluation of infants prior to hospital discharge and recommended outpatient management varies depending upon maternal laboratory evidence of ZIKV infection and infant clinical examination results (Russell et al., 2016). These recommendations include comprehensive physical examination, with special attention to precise occipital-frontal head circumference, weight, length, neurological examination, assessment for dysmorphic features, hearing screen, postnatal head ultrasound study, and ZIKV infection testing for all infants with possible congenital ZIKV infection prior to hospital discharge (Russell et al., 2016). Infants with abnormalities consistent with congenital ZIKV infection should receive all recommended evaluation previously noted plus additional subspecialty care consistent with clinical findings, laboratory testing, ophthalmology examination, audio brainstem response (ABR) test, and consideration of advanced neuroimaging (Russell et al., 2016).

Action on many of these recommendations will likely take place prior to early intervention evaluation, but early intervention professionals should document and follow-up as necessary. Overall, ongoing monitoring of growth parameters, neurological status, nutrition and feeding, vision, and hearing is important throughout at least the infant's first year of life. Consultation reports should be obtained. Parents should be assisted in understanding the consultant's findings and recommendations. Early intervention professionals with experience serving children with other congenital infection sequelae will likely recognize the importance of such documentation, follow-up, and explanation. However, this may be especially important for infants with congenital ZIKV infection due to so many uncertainties about longer term outcomes.

Hearing screening prior to hospital discharge and an ABR at approximately 2 weeks of age, when not done prior to hospital discharge and infant has laboratory evidence of ZIKV infection, are recommended (Russell et al., 2016). A repeat ABR at 4–6 months of age is also recommended (Russell et al., 2016). Retrospective evidence suggests that sensorineural hearing loss occurs at a prevalence of 5.8% in infants with congenital ZIKV infection similar to prevalence rates found with other congenital viral infections (Leal et al., 2016).

Ophthalmology examination prior to hospital discharge or at approximately 2 weeks of age is recommended, as is a repeat ophthalmology examination at 3 months of age for infants with abnormalities consistent with congenital ZIKV infection (Russell et al., 2016). Ideally, both initial hearing and vision evaluations will take place prior to hospital discharge. Involvement with hearing and vision specialists in evaluation, service plan development, and treatment is essential.

Because many infants with congenital ZIKV infection may be small for their age and exhibit poor feeding skills, optimal nutrition intake and management are vital to their overall health and development. Dieticians and those with feeding therapy expertise will be essential as part of the interprofessional team. Nutrition consultation and feeding therapy interventions should not be delayed, as this is a critical period for brain development and overall growth for all infants. At this time, breast-feeding is not contraindicated for this population and early consultation with lactation specialists should be considered along with ongoing encouragement and support for breast-feeding (Russell et al., 2016).

Irritability as a behavioral concern should be addressed. Irritability may affect the infant's sleep patterns as well contribute to parent's poor sleep and emotional health. Nonpharmacological interventions to address infant irritability should be shared, keeping in mind safe sleep and other safety considerations. Parents may need considerable emotional support and opportunities for self-care and respite.

Arthrogryposis has been found in infants with congenital ZIKV infection involving arms and/or legs (van der Linden et al., 2016). Some infants evidence hip dislocation and knee subluxation. Handling and positioning information should be provided early on to family members. Adaptive equipment may be useful, but again keeping in mind safe sleep and other safety considerations.

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POLICY IMPLICATIONS

Early intervention policy makers will need to determine whether health and developmental needs for families with an infant with congenital ZIKV infection-associated microcephaly or another severe outcome have been assessed and planned for and that an appropriate system is in place with the capacity and resources to adequately address those needs (CDC, 2016b). Differing and evolving case definitions for how congenital ZIKV infection is defined may have an impact on inclusion criteria for research studies including efforts to quantify risk, incidence, and prevalence. As the case definition is refined and case numbers change, it may have significant ramifications for policy makers and early intervention program planning. With life span costs of care for children with microcephaly estimated at $4,000,000, even small incidence differences may have substantial economic impact (Ellis, 2016).

To gain further knowledge for future treatment and prevention, the CDC has created the Zika Pregnancy Registry. This registry is a de-identified registry that contains vital information regarding a pregnant woman's exposure and infants born to ZIKV-exposed women. By collecting and analyzing data, researchers can examine pregnancy outcomes and possible future treatment needs. This information should prove helpful for early intervention program planning and advocacy staff to plan and lobby for adequate services for these children and their families.

As the actual need will likely precede the research results, early intervention professionals will need to prepare for a potential influx of infants and young children who will likely need intensive and expensive care from a variety of professionals (de Barros Miranda-Filho et al., 2016). Early intervention professionals as well as policy makers will need to consider the impact of a cohort of infants with congenital ZIKV infection and their families who present all at the same time first for early intervention services and then to the preschool education system at 3 years of age. System functioning improvements coupled with additional funding to create expanded community-based programs including additional therapists are likely needed, as some states already struggle to meet federally mandated evaluation timelines (Sun, 2016). In a way, this may present an opportunity for early intervention systems to improve organization and communication among providers (Ruble, 2016). Advocacy and careful planning to adequately address the enrollment demands, variety of services, and intensity of services such a cohort will need are vital. In addition, additional personnel to handle a potential influx of developmental evaluation requests and repeat developmental screening may be needed.

Planning for transition issues including longer term health and developmental needs will need consideration. Infants born with congenital ZIKV infection-associated microcephaly will likely have intensive health and developmental needs over their life span (Baptista et al., 2016). This necessitates planning not only for the birth to 3 years, but for care transitions, school services, legal, financial, recreational, and adulthood requirements. Because some individuals with congenital ZIKV infection have a shortened life span, palliative and hospice care may be necessary and early intervention professionals may need to adapt to that model of care.

On a more immediate timeline, ZIKV prevention information for all enrolled infants' and families' needs to be provided. The Aedes aegypti mosquitoes are aggressive daytime biters living both indoors and outdoors. This may have implications for programs planning outdoor summer activities including field trips and picnics. Most enrolled children (and their siblings) will likely be susceptible to ZIKV infection. Methods to prevent mosquito bites include air-conditioning use, screens, nets, long sleeves and pants, and approved insect repellants (Schuler-Faccini et al., 2016). Again, safety implications must be considered. Infants younger than 2 months may not safely use DEET-containing products (CDC, 2016c).

Parents and early intervention staff may be planning pregnancies or currently pregnant, so caution should prevail and precautions should be taken during mosquito season, which varies by locale but occurs primarily during the later spring, summer, and early autumn months in the United States. Programs with outdoor play spaces need to take action to eliminate even small amounts of standing water that may serve as a mosquito breeding ground. This may include toys such as pails, tires used as playground equipment and planters, kiddie pools, hollow ride on vehicles, or any other playground equipment that can act as a conduit to hold stagnant water.

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RESEARCH IMPLICATIONS

Research into congenital ZIKV infection has been challenging due to the rapid emergence of the current outbreak, health infrastructure limitations, evolving case definition, and unpublished data. Much is not known about the infant congenitally exposed to ZIKV infection. Basic epidemiological questions still need to be answered. The National Institute for Child Health and Human Development (2016) has launched the Zika in Infants and Pregnancy (ZIP) study. Epidemiological research is very important and will hopefully elucidate the incidence, prevalence, and challenges of congenital ZIKV infection, but there is a role for the early intervention professional. Research queries for early intervention professionals to address include questions such as those that follow: What is the effect of congenital ZIKV infection on long-term health and development? What is the trajectory of neurocognitive and motor development in affected infants (de Barros Miranda-Filho et al., 2016)? Does early intervention participation improve health and developmental outcomes for infants and young children with congenital ZIKV infection exposure? What are the economic cost and societal implications (de Barros Miranda-Filho et al., 2016)? To begin, early intervention researchers should consider using the current standardized case definition for all research endeavors, as it may be helpful in understanding the confirmed ZIKV infection status of the infant and other contextual factors.

In Puerto Rico, scientists are trying to determine risk for pregnant women with ZIKV infection having a child with birth defects and to monitor affected infants through the first 3 years of life to determine whether the infants develop problems not noted before or at birth (McKay, 2016). The latter research focus may benefit from the input of early intervention professionals. The family-centered, interprofessional approach to care used by many early intervention programs may provide a research milieu exceptionally useful to understanding family needs and care coordination issues. Early intervention professionals may contribute information to longer term follow-up studies of affected infants and young children (Costello et al., 2016).

Single case reports describing health and developmental outcomes and intervention strategies may be potentially useful to building the science. The health and developmental trajectory of infants with congenital ZIKV infection is not known. The entire spectrum of congenital ZIKV infection is not known (Bell et al., 2016). Subtler developmental delay or emerging concerns may not be noted or apparent until the child fails to meet certain developmental milestones or begins to demonstrate particular learning disabilities.

Early intervention professionals may also serve as a conduit into clinical trials that may prove informative to the scientific knowledge base and, ideally, ultimately helpful to affected infants and families. However, early intervention professionals and others will need to take care that families are not left feeling that they are just part of an experiment for researchers to collect more data. Truly informed consent and appropriate psychosocial support are essential.

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CONCLUSION

ZIKV infection likely causes a continuum of adverse effects in perinatally exposed infants. The ultimate impact on the early intervention population and programs is not known, but with continued awareness and thoughtful planning, early intervention professionals will be able to provide evidence-based, quality clinical care to this emerging population of high-need infants and families affected by ZIKV infection. Early intervention professionals will also be able to contribute to the scientific evidence base, thus helping infants and families beyond their immediate service locale. Of utmost importance is the recognition by early intervention professionals that scientific knowledge regarding congenital ZIKV infection in infants is evolving and the full impact and implications are still unknown.

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brain calcification; congenital infection; early intervention; microcephaly; Zika virus

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