Prenatal Urban Environment and Blood Pressure Trajectories From Childhood to Early Adulthood

Background Prenatal urban environmental exposures have been associated with blood pressure in children. The dynamic of these associations across childhood and later ages is unknown. Objectives To assess associations of prenatal urban environmental exposures with blood pressure trajectories from childhood to early adulthood. Methods Repeated measures of systolic (SBP) and diastolic blood pressure (DBP) were collected in up to 7,454 participants from a UK birth cohort. Prenatal urban exposures (n=42) covered measures of noise, air pollution, built environment, natural spaces, traffic, meteorology, and food environment. An exposome-wide association study approach was used. Linear spline mixed-effects models were used to model associations of each exposure with trajectories of blood pressure. Replication was sought in four independent European cohorts (N up to 9,261). Results In discovery analyses, higher humidity was associated with a faster increase (mean yearly change in SBP for an interquartile range [IQR] increase in humidity: 0.29 mmHg/year, 95%CI 0.20; 0.39) and higher temperature with a slower increase (mean yearly change in SBP per IQR increase in temperature: -0.17 mmHg/year, 95%CI -0.28; -0.07) in SBP in childhood. Higher levels of humidity and air pollution were associated with faster increase in DBP in childhood and slower increase in adolescence. There was little evidence of an association of other exposures with change in SBP or DBP. Results for humidity and temperature, but not for air pollution, were replicated in other cohorts. Conclusion Replicated findings suggest that higher prenatal humidity and temperature could modulate blood pressure changes across childhood. ### Competing Interest Statement DAL reported grants from national and international government and charity funders, Roche Diagnostics, and Medtronic Ltd for work unrelated to this publication. The other authors report no conflicts of interest. ### Funding Statement This project received funding from the European Unions Horizon 2020 research and innovation programme (874739 LongITools; 733206 LifeCycle; 874583 ATHLETE; 824989 EUCAN-Connect; 101021566 ART-HEALTH). AGS, AE, DAL, JH and NJT work in a Unit that is funded by the UK Medical Research Council (MC\_UU\_00011/1 and 6) and the University of Bristol. DAL is a National Institute of Health Research Senior Investigator (NF-0616-10102) and is also supported by a British Hear Foundation Chair (CH/F/20/90003). The UK Medical Research Council and Wellcome (Grant ref: 217065/Z/19/Z), and the University of Bristol provide core support for ALSPAC. A comprehensive list of grants funding is available on the ALSPAC website (). The general design of the Generation R Study is made possible by financial support from Erasmus MC, University Medical Center Rotterdam, Erasmus University Rotterdam, the Netherlands Organization for Health Research and Development and the Ministry of Health, Welfare and Sport. SM acknowledges the Academy of Finland competitive funding to strengthen university research profiles (PROFI) for the University of Eastern Finland (grant no. 325022). The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. ### 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: Ethical approval for the study was obtained from the ALSPAC Ethics and Law Committee and the Local Research Ethics Committees. Informed consent for the use of data collected via questionnaires and clinics was obtained from participants following the recommendations of the ALSPAC Ethics and Law Committee at the time. Consent for biological samples has been collected in accordance with the Human Tissue Act (2004). More information on the study ethics is available at . 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 Researchers can apply to use ALSPAC data, including the variables under investigation in this study. Data access information is provided here: * ALSPAC : the Avon Longitudinal Study of Parents and Children CVD : cardiovascular disease DBP : diastolic blood pressure EDEN : Etude des Déterminants pré et post natals précoces du développement psychomoteur et de la santé de l’Enfant ExWAS : exposome-wide association study IQR : interquartile range NFBC1986 : Northern Finland Birth Cohort 1986 PANIC : the Physical Activity and Nutrition in Children SBP : systolic blood pressure SD : standard deviation UK : United Kingdom