March 18, 2024 — In a recent study, researchers successfully introduced pooled saliva polymerase chain reaction (PCR) tests for the universal screening of congenital cytomegalovirus (cCMV) infection. This new method helps detect and intervene early in the most common congenital infection, known for causing hearing loss and developmental issues. The study was led by Hebrew University’s (HU) Prof. Smadar Eventov-Friedman, who was joined by Prof. Dana G. Wolf from the Hebrew University-Hadassah Medical Center and the Lautenberg Center for General and Tumor Immunology, Prof. Moran Yassour, their respective teams, and a neonatology team from Hadassah.

Each year, tens of thousands of newborns are affected by cCMV infection, making it a leading cause of childhood neurologic deficits with lifelong implications. The global burden of cCMV is significant, and the absence of a universal screening method has posed challenges in promptly identifying and addressing cases. Current screening methods focus on high-risk cases, but these methods often miss many asymptomatic infants. With a prevalence of 3.4 per 1,000 births in the studied population, the successful implementation of pooled PCR tests, as demonstrated by the study, signifies a crucial advancement in early detection, potentially transforming the lives of numerous infants annually in a more cost-efficient and accessible manner.

The study, conducted from April 2022 through April 2023 in the Hadassah Medical Center hospitals in Jerusalem, involved the screening of 15,805 infants, constituting an impressive 93.6% of all live newborns. cCMV was identified in 54 neonates, of whom more than half were asymptomatic at birth and would have been otherwise missed. The implementation of pooled saliva PCR tests emerged as a routine screening method during this 13-month period, showcasing its efficacy and reliability. The research also emphasizes the clinical importance of universal screening for early diagnosis, monitoring, and potential treatment of cCMV. While limited to two hospitals, the study suggests that universal screening is crucial to uncover undiagnosed cases (though prevalence estimates may vary across populations). Data from universal screening will help define cCMV burden, risk factors, and outcomes, emphasizing the need for further assessment in different subpopulations due to varying prevalence by race, ethnicity, and maternal seroprevalence (the level of a pathogen in a population, as measured in blood serum).

“cCMV is the most common intrauterine infection. “This project was facilitated by the newly available pooled diagnostic approach and the interdisciplinary collaborations which we had established during the COVID-19 pandemic, which made universal screening of cCMV possible. Our findings project on the wide feasibility and benefits of saliva sample pooling to enhance universal neonatal screening for cCMV. Data derived from the implemented universal screening will serve to define the true burden of cCMV and assess future vaccines,” stated Prof Wolf.

Professor Moran Yassour commented, “This collaboration has seamlessly extended its impact to address new medical challenges. Our transformative pooled-testing approach shifts from testing around 10% of newborns to universal testing of approximately 95%. While adjusting facility infrastructure may pose challenges, it’s a worthwhile, one-time investment with immense benefits for all newborns and their families worldwide.”

The successful implementation of pooled saliva tests represents a significant stride in the field of universal newborn screening for cCMV, offering a promising avenue for early intervention. The research team anticipates that this approach will pave the way for enhanced global efforts in combating the impact of cCMV in newborns.

The research paper titled “Implementation of pooled saliva tests for universal screening of cCMV infection” is now available in Nature Medicine and can be accessed here.

Researchers and Institutions

  1. School of Computer Science and Engineering, The Hebrew University of Jerusalem, Jerusalem, Israel – Lior Merav & Moran Yassour
  2. Department of Microbiology and Molecular Genetics, IMRIC, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel – Lior Merav & Moran Yassour
  3. Clinical Virology Unit, Department of Clinical Microbiology and Infectious Diseases, Hebrew University-Hadassah Medical Center, Jerusalem, Israel –  Lior Merav, Esther Oiknine-Djian, Orit Caplan, Ayala Livneh, Tal Sido, Eden Amir, Kerem Ben Meir, Yutti Daitch, Mila Rivkin, Esther Kripper, Irit Fogel, Hadar Horowitz, Sraya Greenberger, Mevaseret Cohen & Dana G. Wolf
  4. Department of Neonatology, Hebrew University-Hadassah Medical Center, Jerusalem, Israel – Noa Ofek Shlomai, Zivanit Ergaz-Shaltiel & Smadar Eventov Friedman
  5. Hebrew University Faculty of Medicine, Jerusalem, Israel – Noa Ofek Shlomai, Esther Oiknine-Djian, Kerem Ben Meir, Mevaseret Cohen, Oren Gordon, Diana Averbuch, Zivanit Ergaz-Shaltiel, Smadar Eventov Friedman & Dana G. Wolf
  6. Lautenberg Center for General and Tumor Immunology, Jerusalem, Israel – Esther Oiknine-Djian, Kerem Ben Meir, Mevaseret Cohen & Dana G. Wolf
  7. Computing Department of Laboratories and Institutes, Hadassah-Hebrew University Medical Center, Jerusalem, Israel – Amir Peri & Aviad Shtoyer
  8. Speech and Hearing Center, Hadassah-Hebrew University Medical Center, Jerusalem, Israel – Miriam Geal-Dor
  9. Department of Communication Disorders, Hadassah Academic College, Jerusalem, Israel – Miriam Geal-Dor
  10. Pediatric Infectious Diseases, Pediatric Division, Hadassah-Hebrew University Medical Center, Jerusalem, Israel – Oren Gordon & Diana Averbuch