RFA-2019-02 Impact of CMV Infection on Development and Language

DRDC Solicitation #:  RFA-2019-02

Project Title: Impact of congenital CMV infection on neurodevelopmental and language outcomes of children with sensorineural hearing loss

Maximum Budget: Year 1: $88,375 and Year 2: $75,000 in Year 2
(includes direct and indirect costs of applicant)
All awards will be based on merit and are subject to the availability of funding.

Project period:  2 years

Anticipated Number of Awards:  up to 2

Project start date:  September 30, 2019

Application Due Date: March 4, 2019 by 8PM Eastern Time

How to Apply:  https://www.disabilityresearchcenter.com/research/application-instructions/

IMPORTANT! If you have questions about the RFA, please submit them to the DRDC here. For each question, we will consult with the CDC and provide the answer directly to the applicant, and we will also post all questions and answers on the DRDC website here.  Please remember to check this page often.

Eligible Applicants. Proposals are invited from universities, research institutions, non-profit organizations, healthcare entities, and other health professionals. This opportunity is open to applicants from U.S. institutions only.

Center/Division goal(s) and thematic area priorities aligned with this research project. Ensuring that all newborns, infants, and young children are screened and assessed for hearing loss and receive appropriate intervention.

Purpose

To assess the developmental and language outcomes of children with congenital cytomegalovirus (CMV) identified with sensorineural hearing loss (SNHL).

Background 

CMV infection causes a spectrum of impairments and conditions in newborns, including SNHL. In the United States, about 20,000 (5 per 1,000) infants are born with congenital CMV infection each year.1,2 About 10% of infected infants present with symptomatic disease at birth, which is associated with an increased risk of intellectual, hearing and visual impairment. In children with congenital CMV infection, SNHL may be present at birth or develop later, regardless of the presence of other clinical signs of disease; and it is usually progressive. SNHL occurs in roughly 33% of symptomatic and 10% of asymptomatic cases of congenital CMV infection.3 Thus, asymptomatic congenital CMV infection may result in 1800 U.S. infants with SNHL by 12 months of age. Nine hundred (900) of these may develop severe to profound SNHL in at least one ear, compared to 700 SNHL cases in symptomatic infants. Congenital CMV infection is the leading non-genetic cause of SNHL, and it is thought to be responsible for 15-20% of all cases of bilateral moderate to profound SNHL in children. Two percent (2%) of the children with asymptomatic congenital CMV infection will develop hearing loss that is severe enough to cause them to become candidates for cochlear implants.4

Infants with congenital CMV infection are seven times more likely to fail the newborn hearing screening than uninfected infants.5 However, studies that compared newborn hearing screening alone with enhanced screening that included testing for CMV, indicated that omitting CMV screening could miss about 40% of congenital CMV-related SNHL cases, thereby delaying diagnosis. Limited population-based data are available on hearing, language, intelligence, and academic achievement in children with congenital CMV infection. In a longitudinal study of children with congenital CMV infection, who were identified through hospital-based screening of over 32,000 newborns, children who had asymptomatic congenital CMV infection with SNHL by age 2 years of age had significantly lower full-scale intelligence and receptive vocabulary scores than infected or uninfected children without SNHL.4 The study was conducted before widespread implementation of newborn hearing screening, and the number of children with asymptomatic congenital CMV infection and SNHL was small.

All states now have an Early Hearing Detection and Intervention (EHDI) program in place to help ensure that all infants who are deaf and hard of hearing are identified early and receive   intervention as early as possible. Receipt of early intervention has been shown to improve communication, language, and social skills.5,6 However, the impact of increased early identification and intervention on the language and developmental outcomes of children with congenital CMV infection and SNHL is currently unclear.

Research Goals and Objectives

Goals and Objectives:

This funding is intended to study the developmental and language outcomes of children with congenital CMV infection.

Special requirements:

To ensure that the study can be accomplished in 2 years and a presentation and manuscript will be prepared in collaboration with CDC for publication in the final year, applicants should consider the following:

  • Should have access to the infant’s CMV status at birth preferentially from a universal newborn CMV screening approach.
  • Should have access to data from existing surveillance tracking system for children identified with hearing loss.
  • Should have a process in place to track delayed-onset and progressive hearing loss in children for at least 5-6 years or have access to longitudinal hearing loss data.
  • Should have access to maternal demographics (e.g. race, Hispanic origin, age), and developmental and language outcomes of children being followed (e.g. IQ score, receptive and expressive language scores, reading score, or other appropriate documentation of academic achievements or early childhood intervention etc.)
  • Should have access to hearing loss remediation method (e.g. hearing aids or cochlear implant)

Successful applications must include the following:

  • A project plan that includes a description of the study cohorts and type of data that will be collected or are readily available.
  • An analysis plan that details how data will be linked, stratified and analyzed.
  • Timeline for data cleaning, compilation and analysis.
  • Plan for submission of progress and final reports, conference presentation, manuscript preparation and publication.
  • Detailed budget, including identification of any sub-contractors
  • Protection of human subjects (if applicable).
  • Methods of CMV screening must be described.
  • Type of hearing loss data must be described.
  • Type of developmental or academic achievement data must be described.

Definition of terms

  • Symptomatic congenital CMV disease—an infant with CMV-positive results within 3 weeks of birth and one or more of the following CMV-related signs were present at birth: purpura, petechiae, jaundice, hepatosplenomegaly, microcephaly, unexplained neurological abnormality, elevated liver enzymes (alanine aminotransferase >100 IU), hyperbilirubinemia (total bilirubin >3mg/dl), hemolytic anemia, or thrombocytopenia (platelet count <75 000/mm3)3.
  • Asymptomatic congenital CMV infection with isolated SNHL—an infant with CMV-positive results within 3 weeks of birth diagnosed with congenital or delayed-onset SNHL but no congenital CMV-related signs at birth3.

Describe the potential public health impact of this opportunity

It is anticipated that a successfully completed research study will assess the overall language and academic outcome of children with SNHL by congenital CMV infection status, and the impact of early detection and intervention on the developmental outcomes, which will be helpful to inform newborn CMV screening policy. Furthermore, a successful research study may provide data on groups with the highest disease burden from congenital CMV-associated SNHL, which in turn will be helpful in informing future vaccination policy, should a vaccine become available.

References

  1. Boppana SB, Ross SA, Novak Z, Shimamura M, Tolan RW, Jr., Palmer AL, et al. Dried blood spot real-time polymerase chain reaction assays to screen newborns for congenital cytomegalovirus infection. JAMA. 2010;303(14):1375-1382.
  2. Boppana SB, Ross SA, Shimamura M, Palmer AL, Ahmed A, Michaels MG, et al. Saliva polymerase-chain-reaction assay for cytomegalovirus screening in newborns. N Engl J Med. 2011;364(22):2111-2118.
  3. Lanzieri T, Chung W, Flores M, Blum P, Caviness C, Bialek S, Grosse S, Miller J, Demmler-Harrison G. Hearing Loss in Children with Asymptomatic Congenital Cytomegalovirus Infection. 2017;139(3)
  4. Lopez A, Lanzieri T, Claussen A, Vinson S, Turcich M, Lovino I, Voigt R, Caviness C, Miller J, Williamson W, Hales Craig, Bialek S, Demmler-Harrison G. Intelligence and Academic Achievement with Asymptomatic Congenital Cytomegalovirus Infection. Pediatrics Nov, 2017. http://pediatrics.aappublications.org/content/140/5/e20171517
  5. Fowler K, McCollister F, Sabo D, Shoup A, Owen K, Woodruff J, Cox E, Mohamed L, Choo D, Boppana S. A Target Approach for Congenital Cytomegalovirus Screening within Newborn Hearing Screening. Pediatrics 2017;139:e20162128.
  6. Yoshinaga-Itano C, Sedey A, Wiggin M, Chung W. Early Hearing Detection and Intervention (EHDI) and Vocabulary of Children with Hearing Loss. Pediatrics July, 2017. http://pediatrics.aappublications.org/content/early/2017/07/06/peds.2016-2964
  7. Tomblin J, Harrison M, Ambrose S, Walker E, Oleson J, Moeller MP. Language outcomes in young children with mild to severe hearing loss. Ear & Hearing. 2015;36(suppl. 1):76S–91S pmid:2673116