Maternal cardiovascular and haematological complications alter the risk associations between environmental exposure and adverse pregnancy outcomes

Given China's recent introduction of the "three-child policy" in response to population ageing, safeguarding perinatal health has become an urgent priority. Previous epidemiological research seldom explored the risk factors of maternal cardiovascular and haematological diseases, or its impact on adverse pregnancy outcomes (APO). To fill the literature gap, here we conducted systematic epidemiological analyses on 121,090 pregnant women and their neonates from the ZEBRA Chinese prospective maternity cohort. We find that incremental exposure in PM2.5, O3, and green space modify the risks of APO, including congenital heart disease, by 11.2%, 7.8%, and -5.5%, respectively. Maternal cardiovascular and haematological complications during pregnancy significantly aggravate the risk of APO by 66.2%, and also modify the environment-APO risk associations by amplifying the hazards of air pollution and weakening the protective effect of greenness accessibility. Our research findings support the Sustainable Development Goals (e.g. SDG3) by providing first-hand epidemiological evidence and clinical guidance for protecting maternal and neonatal health. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study is funded by the Zhejiang Province Health Innovative Talent Project (A0466), International Cooperation Seed Program of Women's Hospital, Zhejiang University (GH2022B008-01), Key Projects of the Science and Technology Co-construction by National Administration of Traditional Chinese Medicine and Zhejiang Provincial Administration of Traditional Chinese Medicine (GZY-ZJ-KJ-23082), Australian Research Council (DP210102076), and Australian National Health and Medical Research Council (APP2000581). Haitong Sun also thanks generous support from the U.S. Fulbright Program. Yuming Guo is supported by a Career Development Fellowship of the Australian National Health and Medical Research Council (APP1163693). Special appreciations to Professor Weiguo Lu, the director of the Key Laboratory of Women's Reproductive Health, for his comprehensive supports in establishing and coordinating the maternity cohort. ### 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: The current cohort-based study was approved by the ethics committee of the Women's Hospital, Zhejiang University School of Medicine (IRB-20220189-R) and we obtained written informed consent from all cohort participants upon enrolment. 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 The information of the ZEBRA maternity cohort participants for privacy protection it is not disclosed for public use. Researchers interested in accessing the data are encouraged to contact the principal investigators with a brief research proposal. Access to the data will be granted after approval by the ZEBRA committee and the Health Commission of Zhejiang Province. The codes for analysis can be shared upon request.