Pre-existing anti-polyethylene glycol antibodies in pregnant women and newborns

Pre-existing anti-polyethylene glycol (PEG) antibodies represent risk factors for reduced efficacy and increased adverse reactions in seropositive individuals, but neither the seropositivities, nor levels nor influencing factors have been investigated in pregnant women or newborns. Herein, maternal and cord blood samples were respectively collected from 256 pregnant women and corresponding 256 newborns at the Women’s Hospital, Zhejiang University School of Medicine in China for further determination of pre-existing anti-PEG antibodies, along with questionnaire interviews, demographic and clinical data collections. Our data showed that the seropositivities 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 all blood samples. Median anti-PEG IgG1, IgG2 and IgM concentrations were 273.88 ng/mL, 748.35 ng/mL and 175.07 ng/mL, respectively, in pregnant women. Median anti-PEG IgG1 and IgG2 concentrations were 207.92 ng/mL and 336.52 ng/mL, respectively, in newborns. Interestingly, in-depth statistical analyses revealed that maternal age, take-out food consumption and cosmetic use were influencing factors of maternal anti-PEG antibodies, while newborn anti-PEG antibodies were affected by maternal age and cosmetic use. These seroepidemiological characteristics raise concerns over the clinical use of PEGylated drugs in pregnant women and newborns, and provide valuable insight into the induction of risky pre-existing anti-PEG antibodies. Competing Interest Statement The authors have declared no competing interest. Funding Statement This work was supported by the Zhejiang Provincial Natural Science Foundation of China (LZ23E030003 to Dr. Meihua Sui), National Natural Science Foundation of China (21722405 and 22075243 to Dr. Meihua Sui) and Startup Foundation for Hundred-Talent Program of Zhejiang University (to Dr. Meihua Sui). Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This cross-sectional study carefully followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines and was approved by the Ethics Committee of Women's Hospital, Zhejiang University School of Medicine (approval No. IRB-20210139-R). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Footnotes

updated; Supplemental files updated Data Availability All data produced in the present work are contained in the manuscript