OBJECTIVE: We aimed to compare the prevalence and neonatal mortality associated with large for gestational age (LGA) and macrosomia among 115.6 million live births in 15 countries, between 2000 and 2020. DESIGN: Population-based, multi-country study. SETTING: National healthcare systems. POPULATION: Liveborn infants. METHODS: We used individual-level data identified for the Vulnerable Newborn Measurement Collaboration. We calculated the prevalence and relative risk (RR) of neonatal mortality among live births born at term + LGA (>90th centile, and also >95th and >97th centiles when the data were available) versus term + appropriate for gestational age (AGA, 10th-90th centiles) and macrosomic (≥4000, ≥4500 and ≥5000 g, regardless of gestational age) versus 2500-3999 g. INTERGROWTH 21st served as the reference population. MAIN OUTCOME MEASURES: Prevalence and neonatal mortality risks. RESULTS: Large for gestational age was common (median prevalence 18.2%; interquartile range, IQR, 13.5%-22.0%), and overall was associated with a lower neonatal mortality risk compared with AGA (RR 0.83, 95% CI 0.77-0.89). Around one in ten babies were ≥4000 g (median prevalence 9.6% (IQR 6.4%-13.3%), with 1.2% (IQR 0.7%-2.0%) ≥4500 g and with 0.2% (IQR 0.1%-0.2%) ≥5000 g). Overall, macrosomia of ≥4000 g was not associated with increased neonatal mortality risk (RR 0.80, 95% CI 0.69-0.94); however, a higher risk was observed for birthweights of ≥4500 g (RR 1.52, 95% CI 1.10-2.11) and ≥5000 g (RR 4.54, 95% CI 2.58-7.99), compared with birthweights of 2500-3999 g, with the highest risk observed in the first 7 days of life. CONCLUSIONS: In this population, birthweight of ≥4500 g was the most useful marker for early mortality risk in big babies and could be used to guide clinical management decisions.

Center for Data and Knowledge Integration for Health Instituto Gonçalo Moniz Fiocruz Bahia Fundação Oswaldo Cruz Salvador Brazil

Clinical Epidemiology Division Department of Medicine Solna Karolinska Institutet Stockholm Sweden

Department of Clinical Epidemiology Aarhus University and Aarhus University Hospital Aarhus Denmark

Department of Data Analysis Institute of Health Information and Statistics of the Czech Republic Prague Czech Republic

Department of International Health Johns Hopkins Bloomberg School of Public Health Baltimore Maryland USA

Department of Obstetrics and Gynaecology Institute for the Care of Mother and Child Prague Czech Republic

Department of Obstetrics and Gynaecology University of British Columbia Vancouver British Columbia Canada

Department of Population Health Sciences College of Life Sciences University of Leicester Leicester UK

Department of Wellness and Health Catholic University of Uruguay Montevideo Uruguay

Faculty of Health Sciences Catholic University of Maule Curicó Chile

Faculty of Medicine and Health University of Sydney Camperdown New South Wales Australia

Hamad Medical Corporation Doha Qatar

Maternal Adolescent Reproductive and Child Health Centre London School of Hygiene and Tropical Medicine London UK

Mexican Society of Public Health Mexico City Mexico

National Health and Medical Research Council Centre of Research Excellence in Stillbirth Mater Research Institute The University of Queensland Brisbane Queensland Australia

Perined Utrecht the Netherlands

Pregnancy Birth and Child Health Team Public Health Scotland Edinburgh UK

Queen's Management School Queen's University Belfast Belfast UK

School of Governance Law and Society Estonian Institute for Population Studies Tallinn University Tallinn Estonia

School of Natural and Built Environment Queen's University Belfast Belfast UK

The National Collaborative Perinatal Neonatal Network Coordinating Center at the Department of Pediatrics and Adolescent Medicine American University of Beirut Beirut Lebanon

Usher Institute Edinburgh UK

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