Background Adverse early life exposures might negatively affect foetal and infant development, predisposing children to obesity. We aimed to systematically identify and evaluate risk factors for childhood obesity in preconception, pregnancy, and infancy, and assess their potential as targets for future prediction and prevention strategies. Methods This systematic review (PROSPERO, CRD42022355152) included longitudinal studies from selected electronic databases published between inception and August 17th, 2022, identifying maternal, paternal, or infant risk factors from preconception until infancy for childhood obesity between 2 and 18 years. Screening and data extraction was performed through standardized extraction forms. We assessed risk factor quality on modifiability and predictive power using a piloted criteria template from ILSI-Europe-Marker-Validation-Initiative. Findings We identified 172 observational and 5 intervention studies involving n=1.879.971 children from 37, predominantly high-income, countries. 59%, 25% and 16% of studies measured childhood obesity between 2- <6 years, 6-10 years, and >10 -18 years respectively. Average reported childhood obesity prevalence was 11.1%. Pregnancy and infancy risk factors were mostly studied. We identified 59 potential risk factors, 24 of which were consistently associated with childhood obesity risk. Higher maternal prepregnancy weight (n=28/31 positive associations from 31 studies, respectively), higher gestational weight gain (n=18/21), maternal smoking during pregnancy (n=23/29), higher birth weight (n=20/28), LGA (n=17/18), no breastfeeding (n=20/31), and higher infant weight gain (n=12/12) were the strongest risk factors, which may aid in prediction or be targets for prevention. Level of evidence was generally moderate due to unreliable exposure measurement, short follow-up/loss-to-follow up, and risk of confounding. Interpretation We identified 7 early life risk factors, which were strongly associated with a higher risk of childhood obesity, and can contribute to future prediction and prevention strategies. These findings support implementation of prevention strategies targeting these early-life risk factors from a clinical and population perspective, where possible integrated with implementation studies. Funding This work was conducted by an expert group of the European branch of the International Life Sciences Institute, ILSI Europe.

RG received funding from the Netherlands Organization for Health Research and Development (ZonMW, grant number 543003109) and funding from the European Unions Horizon 2020 research and innovation program under the ERA-NET Cofund action (No. 727565), European Joint Programming Initiative A Healthy Diet for a Healthy Life (JPI HDHL), EndObesity, ZonMW Netherlands (No. 529051026). SMB was supported by the KNAW Ter Meulen Grant/KNAW Medical Science Fund, Royal Netherlands Academy of Arts & Sciences, and by ILSI Europe. ASJK was supported by ISLI Europe. MCC acknowledges the support by the Spanish Ministry of Science and Innovation (MCIN) research grant (ref. PID2022-139475OB-I00) and the award from MCIN/AEI to the Institute of Agrochemistry and Food Technology (IATA-CSIC) as Centre of Excellence Severo Ochoa (CEX2021-001189-S MCIN/AEI /10.13039/ 501100011033). EFV was supported by a Predoctoral grant awarded by the Spanish Ministry of Science and Innovation and the European Social Fund Plus (ESF+) for the training of doctors within the framework of the State Plan for Scientific, Technical and Innovation Research 2021 - 2023. (ref. CEX2021-001189-S-20-1). FJRO was supported by the Spanish Goverment (Juan de la Cierva programm, Ministry of Science and Innovation). This Project was executed in collaboration with Early Nutrition and Long-term Health Task Force of the European Branch of the International Life Sciences Institute (ILSI Europe). Industry members of this task force are listed on the website www.ilsi.eu. For more information, please contact ILSI Europe by email info@ilsieurope.be or call +32 2 771.00.14. The opinions expressed herein, and the conclusion of the project are those of the authors and do not necessarily represent the view of ILSI Europe nor those of its member companies.

This work was conducted by an expert group of the European branch of the International Life Sciences Institute, ILSI Europe. This publication was coordinated by the Early Nutrition and Long-term Health Task Force. Industry members of this task force are listed on the ILSI Europe website at https://ilsi.eu/scientific-activities/nutrition/early-nutrition-and-long-term-health/. Experts are not paid for the time spent on this work. However, the nonindustry members within the expert group were offered support for travel on costs from the Early Nutrition and Long-term Health Task Force to attend 1 live meeting to discuss the manuscript. The expert group carried out the work, that is collecting/analysing data/information and writing the scientific paper separate to other activities of the task force. The research reported is the result of a scientific evaluation in line with ILSI Europes framework to provide a precompetitive setting for public-private partnership. ILSI Europe facilitated scientific meetings and coordinated the overall project management and administrative tasks relating to the completion of this work. For further information about ILSI Europe, please email info@ilsieurope.be or call +3227710014. The opinions expressed herein and the conclusions of this publication are those of the authors and do not necessarily represent the views of ILSI Europe nor those of its member companies or any regulatory authority.

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