Long-Term Outcomes of Children With Congenital CMV in New York State (PROACTIVE NYS)

Prospective Observational Study of Asymptomatic cCMV Transmission to Infants for Virological Evaluation in New York State

PROACTIVE NYS is a long-term follow-up study of all infants who test positive for congenital Cytomegalovirus infection (CMV) throughout New York State on the Newborn Screen. By following all infants who screen positive, we will learn important information about the range of symptoms caused by congenital CMV, from those babies with more severe findings to those with no symptoms.

In particular, our study will provide new information about many facets of congenital CMV, including:

• Developmental, hearing, neurologic, and vision outcomes
• The spectrum and timing of symptoms
• The impact congenital CMV has on the baby and its family
• How many babies are infected with congenital CMV in New York State How antiviral medications and other interventions impact outcomes of children with congenital CMV

Throughout the duration of the study, children will undergo routine developmental and hearing assessments, which will assist with early diagnosis of any infection complications.

Any child found to have a neurodevelopmental, hearing, or vision abnormality will be referred for appropriate evaluation and treatment.

Families will also be asked to complete periodic surveys about their experience with congenital CMV, both as a medical diagnosis and as it affects their day-to-day activities.

Study Overview

• Status: Recruiting
• Conditions: Sensorineural Hearing Loss; Congenital CMV Infection

• Study Type: Observational
• Enrollment (Estimated): 1000

Contacts and Locations

• Study Contact: Name: Andrew Handel, MD; Phone Number: 631-444-7692; Email: Andrew.handel@stonybrookmedicine.edu
• Study Contact Backup: Name: Sharon Nachman, MD; Phone Number: 631-444-7692; Email: sharon.nachman@stonybrookmedicine.edu

Study Locations

• United States
  • New York
    • Stony Brook, New York, United States, 11794
      • Recruiting
      • Stony Brook Children's Hospital
      • Contact: Andrew Handel, MD; Phone Number: 631-444-7692; Email: Andrew.handel@stonybrookmedicine.edu
      • Principal Investigator: Andrew Handel, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

All infants referred by the New York State Newborn Screen Program to a clinical care referral site for a positive congenital CMV test will be approached for enrollment in PROACTIVE NYS. In addition, infants who are identified with cCMV as part of routine clinical care during the study period will be eligible to enroll in PROACTIVE NYS.

Description

Inclusion Criteria:

• Neonates born in New York State during cCMV NBS Pilot Program (September 27, 2023 - October 1, 2024)
• cCMV evaluation provided by a designated NYS cCMV clinical referral site
• Family willing and able to complete all study procedures
• Study participants meet criteria for one of the following four categories:
• 1. Category 1 (Confirmed cCMV identified by NBS Program): cCMV NYS newborn screen positive AND cCMV confirmatory test positive
• 2. Category 2 (Confirmed cCMV not identified by NBS Program): cCMV NYS newborn screen negative AND cCMV confirmatory test positive
• 3. Category 3 (False-positive cCMV screen): cCMV NYS newborn screen positive AND negative cCMV confirmatory test
• 4. Category 4 (Premature infants with confirmed CMV infection on late positive NBS): Infant born prior to 37 weeks gestation AND cCMV positive on any NYS newborn screen collected prior to 44 weeks gestational age AND Positive cCMV confirmatory test obtained within 14 days of a positive NBS

Exclusion Criteria:

• Neonate whose parents refuse participation in the long-term follow-up study

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort
Category 1: Confirmed cCMV infection identified by NYS newborn screen; Infants who have both a positive cCMV NYS newborn screen AND are positive for cCMV on confirmatory testing
Category 2: Confirmed cCMV infection NOT identified by NYS newborn screen; Infants who have both a NEGATIVE cCMV NYS newborn screen AND are found to have cCMV on confirmatory testing
Category 3: False-positive cCMV NYS newborn screen; Infants who have both a positive cCMV NYS newborn screen AND are NEGATIVE for cCMV on confirmatory testing
Category 4: Premature infants with confirmed CMV infection on late positive NBS; Infants who are: (a) born prior to 37 weeks gestation AND (b) cCMV positive on any NYS newborn screen collected prior to 44 weeks gestational age AND (c) Have a positive cCMV confirmatory test obtained within 14 days of a positive NYS newborn screen

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Congenital CMV infection rate	To determine the rate of confirmed congenital CMV in a statewide cohort	Study initiation to 1 year time point

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
cCMV neonatal sensorineural hearing loss	Rate of neonatal sensorineural hearing decibel loss as determined by Auditory Brainstem Response testing	Through 4 weeks old
cCMV antiviral therapy utilization	Frequency of antiviral prescriptions	2 years
cCMV acquired sensorineural hearing loss	Rate of acquired sensorineural hearing decibel loss as determined by Auditory Brainstem Response testing	2 years
cCMV neurodevelopmental outcomes	Neurodevelopmental abnormalities as measured by Bayley Scales of Infant & Toddler Development-III. The Bayley-III includes Cognitive, Language, Motor, Social-Emotional, and Adaptive Behavior scales. Age-normalized scores are calculated for each domain, with a lower score indicating greater impairment.	2 years
cCMV-related quality of life	Quality of life score as determined by the Pediatric Quality of Life Inventory Infant Scales (PedsQL). The PedsQL Infant Scales consist of parent-reported psychosocial health symptoms. A higher score on the PedsQL indicates more severe psychosocial health symptoms.	2 years

Collaborators and Investigators

• Sponsor: Stony Brook University
• Collaborators: Frontier Science & Technology Research Foundation, Inc.

Publications and helpful links

General Publications

• Pesch MH, Saunders NA, Abdelnabi S. Cytomegalovirus Infection in Pregnancy: Prevention, Presentation, Management and Neonatal Outcomes. J Midwifery Womens Health. 2021 May;66(3):397-402. doi: 10.1111/jmwh.13228. Epub 2021 May 24.
• Rawlinson WD, Boppana SB, Fowler KB, Kimberlin DW, Lazzarotto T, Alain S, Daly K, Doutre S, Gibson L, Giles ML, Greenlee J, Hamilton ST, Harrison GJ, Hui L, Jones CA, Palasanthiran P, Schleiss MR, Shand AW, van Zuylen WJ. Congenital cytomegalovirus infection in pregnancy and the neonate: consensus recommendations for prevention, diagnosis, and therapy. Lancet Infect Dis. 2017 Jun;17(6):e177-e188. doi: 10.1016/S1473-3099(17)30143-3. Epub 2017 Mar 11.
• Fowler KB, Boppana SB. Congenital cytomegalovirus infection. Semin Perinatol. 2018 Apr;42(3):149-154. doi: 10.1053/j.semperi.2018.02.002. Epub 2018 Mar 2.

Helpful Links

• PROACTIVE NYS Website

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2024
• Primary Completion (Estimated): October 1, 2024
• Study Completion (Estimated): October 1, 2026

Study Registration Dates

• First Submitted: December 19, 2023
• First Submitted That Met QC Criteria: January 23, 2024
• First Posted (Actual): January 26, 2024

Study Record Updates

• Last Update Posted (Actual): April 16, 2024
• Last Update Submitted That Met QC Criteria: April 15, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Sensorineural hearing loss; SNHL; Congenital CMV; Congenital infection; cCMV
• Additional Relevant MeSH Terms: Nervous System Diseases; Virus Diseases; Infections; Neurologic Manifestations; Otorhinolaryngologic Diseases; DNA Virus Infections; Ear Diseases; Sensation Disorders; Herpesviridae Infections; Hearing Disorders; Hearing Loss; Deafness; Hearing Loss, Sensorineural; Cytomegalovirus Infections
• Other Study ID Numbers: 75N94021D00018-75N94023F00001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No