Pre-existing anti-polyethylene glycol antibodies in pregnant women and newborns
Authors: Wang Haiyang , Feng Yan , Zhang Lin , Yuan Changzheng , Xue Junyang , Li Jicheng , Xu Xiao , Zhou Wenbin , Li Baohua , Wang Yisha , Luo Gan , Zheng Yue , Sui Meihua 
Published: December 2024

AbstractImportancePre-existing anti-polyethylene glycol (PEG) antibodies represent risk factors for reduced efficacy and increased adverse reactions in seropositive individuals receiving PEGylated drugs, but neither their sero-prevalence, nor levels nor potential influencing factors have been investigated in pregnant women or newborns.ObjectiveTo parallelly determine the sero-prevalence and levels of pre-existing anti-PEG antibodies in pregnant women and newborns, and to reveal their independent influencing factors.DesignCross-sectional analysis using data of pregnant women and their newborns enrolled between May 2021 and May 2022.SettingPregnant women admitted for delivery at the Women’s Hospital, Zhejiang University School of Medicine in China, were approached for enrollment.ParticipantsParticipants included 256 pregnant women (volunteers) and corresponding 256 newborns. Major eligibility criteria for pregnant women included an age of 20 years or older, a singleton pregnancy, a full-term pregnancy, no history of unhealthy lifestyle (e.g. smoking, drinking and drug abuse), no contagious disease and no disease requiring drug treatment upon enrollment.ExposuresMaternal and cord blood samples were collected around or immediately after the delivery for further examinations, along with questionnaire interviews, demographic and clinical data collections.Main Outcomes and MeasuresAll blood samples underwent screening and quantification of pre- existing anti-PEG antibodies. Sero-prevalence and levels of total anti-PEG antibodies and each known isotype/subclass were determined. Influencing factors for sero-prevalence and levels of pre- existing anti-PEG antibodies in pregnant women and newborns were respectively revealed with in-depth statistical analysis.ResultsSeropositivities of total anti-PEG antibodies, anti-PEG IgG1 and IgG2, anti-PEG IgM, and coexistence of anti-PEG IgM and IgG were 19.14%, 2.34%, 7.03%, 10.94% and 1.17%, respectively in pregnant women, and 5.47%, 2.73%, 2.73%, 0% and 0%, respectively in newborns. Anti-PEG IgG3, IgG4 and IgE were undetectable in both pregnant women and newborns. Seropositive pregnant women had a median (Range; IQR) anti-PEG IgG1, IgG2 and IgM concentrations of 273.88 ng/mL (183.74-513.90; 191.70-376.08), 748.35 ng/mL (75.54-2604.89; 159.09-1200.81) and 175.07 ng/mL (55.43-23649.14; 95.95-315.19), respectively. Seropositive newborns had a median (Range; IQR) anti-PEG IgG1 and IgG2 concentrations of 207.92 ng/mL (120.40-1513.98; 133.97-524.58) and 336.52 ng/mL (100.24-1069.62; 275.80-527.07), respectively. Furthermore, we revealed that maternal age, take-out food consumption and cosmetic use were influencing factors of prevalence and levels of maternal anti-PEG antibodies, while prevalence or levels of newborn anti-PEG antibodies were affected by maternal age and cosmetic use.Conclusions and RelevanceA proportion of pregnant women and newborns were found seropositive for pre-existing anti-PEG antibodies, raising efficacy and safety concerns over the use of PEGylated drugs in pregnant women and newborns/infants. Several influencing factors on maternal and/or newborn pre-existing anti-PEG antibodies were discovered, providing valuable information for deeper understandings on the induction of risky pre-existing anti-PEG antibodies. Specifically, our data suggest that anti-PEG antibodies may be induced by gastrointestinal exposure to PEG antigens.