Comparison of detection strategies for screening and confirming congenital cytomegalovirus infection in newborns in a highly seroprevalent population: a mother-child cohort study

Yue Huang; Han Wang; Tingdong Li; Caihong Li; Jiabao Tang; Huan Yu; Xiaoyi Guo; Qiaoqiao Song; Feixue Wei; Jiangding Wang; Caihong Liang; Fengxian Zheng; Hongjuan Li; Huifeng Li; Hongguo Wu; Zhaoxin Lu; Yingying Su; Ting Wu; Shengxiang Ge; Tong-Ming Fu; Jun Zhang; Ningshao Xia

doi:10.1016/j.lanwpc.2021.100182

Comparison of detection strategies for screening and confirming congenital cytomegalovirus infection in newborns in a highly seroprevalent population: a mother-child cohort study

Lancet Reg Health West Pac. 2021 Jun 9:12:100182. doi: 10.1016/j.lanwpc.2021.100182. eCollection 2021 Jul.

Authors

Yue Huang¹, Han Wang¹, Tingdong Li¹, Caihong Li², Jiabao Tang¹, Huan Yu¹, Xiaoyi Guo¹, Qiaoqiao Song¹, Feixue Wei¹, Jiangding Wang³, Caihong Liang⁴, Fengxian Zheng², Hongjuan Li², Huifeng Li², Hongguo Wu³, Zhaoxin Lu⁴, Yingying Su¹, Ting Wu¹, Shengxiang Ge¹, Tong-Ming Fu⁵, Jun Zhang¹, Ningshao Xia¹

Affiliations

¹ State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Strait Collaborative Innovation Center of Biomedicine and Pharmaceutics, School of Public Health, Xiamen University, Xiamen 361102, Fujian, China.
² Xinmi Maternal and Child Health Hospital, Xinmi 452300, Henan, China.
³ Jiaxian Maternal and Child Health Hospital, Jiaxian 467100, Henan, China.
⁴ Zhongmu Maternal and Child Health Hospital, Zhongmu 451450, Henan, China.
⁵ Texas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine, The University of Texas Health Science Center, Houston, TX 77030, USA.

Abstract

Background: Universal screening of congenital cytomegalovirus (cCMV) infection is important for monitoring and intervention during critical stages of speech and language development. This study aimed to explore the optimal detection strategy for cCMV infection screening.

Methods: Serum samples from pregnant women and saliva and urine samples from their newborns were collected for the anti-CMV IgG and CMV DNA PCR tests, respectively. The sensitivity, specificity, and predictive values as well as the likelihood ratios of 12 potential screening strategies for cCMV infection, based on tests for saliva, urine, and their combination, were evaluated.

Findings: A total of 6729 pregnant women were enrolled, and the seroprevalence was 98.1%. Among 6350 newborns that were followed up, 49 were defined as having cCMV infection. In the screening test, the CMV DNA positivity rate remained similar from day 0 to day 5, increased slowly from day 6 to day 13, and became high in newborns beyond 13 days of birth. In the confirmatory testing, the positive rates increased significantly beyond day 21. For the 49 newborns with cCMV infection, the proportion of agreement between saliva and urine testing was poor. Upon evaluating alternative screening strategies, using saliva and urine screening with saliva and urine confirmation as the reference strategy, saliva screening with saliva and urine confirmation showed good diagnostic accuracy and feasibility, with sensitivity, specificity, positive predictive and negative predictive values of 85.7%, 100.0%, 100.0% and 99.9%, respectively.

Interpretation: In populations with high seroprevalence, saliva screening with saliva and urine confirmation might be an alternative strategy for screening cCMV infections. The suggested timeframes for screening and confirmation are within 13 (ideally 5) and 21 (ideally 13) days of birth, respectively.

Funding: National Natural Science Foundation of China, National Science and Technology Major Project of China and Merck & Co., Inc., Kenilworth, New Jersey, U.S.A.