Pre-existing maternal IgG antibodies as a protective factor against congenital cytomegalovirus infection: A mother-child prospective cohort study
Yue Huang,
Jiabao Tang,
Han Wang,
Huan Yu,
Qiaoqiao Song,
Xiaoyi Guo,
Caihong Li,
Jiangding Wang,
Caihong Liang,
Shulian Li,
Shaowei Li,
Zhifeng Lin,
Qi Chen,
Guohua Zhong,
Sijie Zhuang,
Yingying Su,
Tingdong Li,
Ting Wu,
Shengxiang Ge,
Jun Zhang,
Ningshao Xia
Affiliations
Yue Huang
The State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Collaborative Innovation Center of Biologic Products, School of Public Health, Xiamen University, Xiamen 361102, Fujian, China
Jiabao Tang
The State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Collaborative Innovation Center of Biologic Products, School of Public Health, Xiamen University, Xiamen 361102, Fujian, China
Han Wang
The State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Collaborative Innovation Center of Biologic Products, School of Public Health, Xiamen University, Xiamen 361102, Fujian, China
Huan Yu
The State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Collaborative Innovation Center of Biologic Products, School of Public Health, Xiamen University, Xiamen 361102, Fujian, China
Qiaoqiao Song
The State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Collaborative Innovation Center of Biologic Products, School of Public Health, Xiamen University, Xiamen 361102, Fujian, China
Xiaoyi Guo
The State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Collaborative Innovation Center of Biologic Products, School of Public Health, Xiamen University, Xiamen 361102, Fujian, China
Caihong Li
Xinmi Maternal and Child Health Hospital, Xinmi 452300, Henan, China
Jiangding Wang
Jiaxian Maternal and Child Health Hospital, Jiaxian 467100, Henan, China
Caihong Liang
Zhongmu Maternal and Child Health Hospital, Zhongmu 451450, Henan, China
Shulian Li
Huli District Maternal and Child Health Hospital, Xiamen 361006, Fujian, China
Shaowei Li
Huli District Maternal and Child Health Hospital, Xiamen 361006, Fujian, China
Zhifeng Lin
Huli District Maternal and Child Health Hospital, Xiamen 361006, Fujian, China
Qi Chen
The State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Collaborative Innovation Center of Biologic Products, School of Public Health, Xiamen University, Xiamen 361102, Fujian, China
Guohua Zhong
The State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Collaborative Innovation Center of Biologic Products, School of Public Health, Xiamen University, Xiamen 361102, Fujian, China
Sijie Zhuang
The State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Collaborative Innovation Center of Biologic Products, School of Public Health, Xiamen University, Xiamen 361102, Fujian, China
Yingying Su
The State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Collaborative Innovation Center of Biologic Products, School of Public Health, Xiamen University, Xiamen 361102, Fujian, China
Tingdong Li
The State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Collaborative Innovation Center of Biologic Products, School of Public Health, Xiamen University, Xiamen 361102, Fujian, China
Ting Wu
The State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Collaborative Innovation Center of Biologic Products, School of Public Health, Xiamen University, Xiamen 361102, Fujian, China; Corresponding authors.
Shengxiang Ge
The State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Collaborative Innovation Center of Biologic Products, School of Public Health, Xiamen University, Xiamen 361102, Fujian, China; Corresponding authors.
Jun Zhang
The State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Collaborative Innovation Center of Biologic Products, School of Public Health, Xiamen University, Xiamen 361102, Fujian, China; Corresponding authors.
Ningshao Xia
The State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Collaborative Innovation Center of Biologic Products, School of Public Health, Xiamen University, Xiamen 361102, Fujian, China
Summary: Background: An understanding of the correlation between maternal immunity and congenital cytomegalovirus (CMV) infection is critical for informing the design and evaluation of an effective maternal vaccine. This study aimed to quantitatively measure the protective effect of pre-existing maternal immunity against congenital CMV (cCMV) infection. Methods: A mother-child cohort study was conducted in three maternal and child health hospitals in China from 2015 to 2018. Pregnant women were consecutively enrolled, and anti-CMV pp150 IgG concentration at early, middle and late gestational ages were evaluated. Their newborns were screened for cCMV infection by CMV-DNA testing of saliva and urine. Findings: In total, 6729 pregnant women were enrolled, and 6602 of them (98·11%) were positive for CMV IgG at their early gestational age visit (median time: 13 gestational weeks (GW); time range: 6–25 GW). In total, 6228 live newborns were born to seropositive mothers, and 48 (0·77%) of these infants were diagnosed with cCMV infection. The geometric mean concentration (GMC) of CMV IgG at an early gestational age in the women who delivered cCMV-positive newborns (i.e., the transmitters) was 8·54 IU/mL; this was significantly lower than the GMC in the non-transmitters (11·01 IU/mL; P=0·04). In early gestation, the risk of cCMV infection decreased as maternal IgG antibody levels increased (P=0·020); however, the same was not true in middle or late gestation (P>0·05). Using receiver operating characteristic analysis, a CMV IgG concentration of 12·83 IU/mL was established as the optimal diagnostic threshold. Compared to lower levels of CMV IgG (<12·83 IU/mL) in seropositive pregnant women, higher maternal CMV IgG levels (≥12·83 IU/mL) were associated with a 50% reduction in cCMV infection risk in infants (relative risk=0·50; 95% confidence interval: 0·27–0·93; P=0·028). Interpretation: For seropositive women, a higher level of CMV IgG at an early gestational age is associated with a lower risk of cCMV infection in their newborns. Funding: National Natural Science Foundation of China; Science and Technology Key Project in Fujian Province; Merck Sharp & Dohme Corp., Kenilworth, NJ, USA; Fieldwork Funds for graduate students of Xiamen University.
