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

Zobrazit více v PubMed

Abbas F, Kumar R, Mahmood T, Somrongthong R. Impact of children born with low birth weight on stunting and wasting in Sindh province of Pakistan: a propensity score matching approach. Sci Rep. 2021;11(1):19932. PubMed PMC

Paixao ES, Blencowe H, Falcao IR, Ohuma EO, Rocha AS, Alves FJO, et al. Risk of mortality for small newborns in Brazil, 2011–2018: a national birth cohort study of 17.6 million records from routine register‐based linked data. Lancet Reg Health Am. 2021; 3(100045): 1–8. PubMed PMC

Katz J, Lee ACC, Kozuki N, Lawn JE, Cousens S, Blencowe H, et al. Mortality risk in preterm and small‐for‐gestational‐age infants in low‐income and middle‐income countries: a pooled country analysis. Lancet. 2013;382(9890):417–425. PubMed PMC

Fernández de Gamarra‐Oca L, Ojeda N, Gómez‐Gastiasoro A, Peña J, Ibarretxe‐Bilbao N, García‐Guerrero MA, et al. Long‐term neurodevelopmental outcomes after moderate and late preterm birth: a systematic review. J Pediatr. 2021;237:168–176.e11. PubMed

Sacchi C, Marino C, Nosarti C, Vieno A, Visentin S, Simonelli A. Association of intrauterine growth restriction and small for gestational age status with childhood cognitive outcomes: a systematic review and meta‐analysis. JAMA Pediatr. 2020;174(8):772–781. PubMed PMC

Mayer C, Joseph KS. Fetal growth: a review of terms, concepts and issues relevant to obstetrics. Ultrasound Obstet Gynecol. 2013;41(2):136–145. PubMed

Practice bulletin no. 173: fetal macrosomia. Obstet Gynecol. 2016;128(5):e195–e209. PubMed

Beta J, Khan N, Khalil A, Fiolna M, Ramadan G, Akolekar R. Maternal and neonatal complications of fetal macrosomia: systematic review and meta‐analysis. Ultrasound Obstet Gynecol. 2019;54(3):308–318. PubMed

Goldstein RF, Abell SK, Ranasinha S, Misso ML, Boyle JA, Harrison CL, et al. Gestational weight gain across continents and ethnicity: systematic review and meta‐analysis of maternal and infant outcomes in more than one million women. BMC Med. 2018;16(1):153. PubMed PMC

Scifres CM. Short‐ and long‐term outcomes associated with large for gestational age birth weight. Obstet Gynecol Clin North Am. 2021;48(2):325–337. PubMed

Culliney KA, Parry GK, Brown J, Crowther CA. Regimens of fetal surveillance of suspected large‐for‐gestational‐age fetuses for improving health outcomes. Cochrane Database Syst Rev. 2016;4(4):CD011739. PubMed PMC

Magnusson Å, Laivuori H, Loft A, Oldereid NB, Pinborg A, Petzold M, et al. The association between high birth weight and long‐term outcomes‐implications for assisted reproductive technologies: a systematic review and meta‐analysis. Front Pediatr. 2021;9:675775. PubMed PMC

Hong YH, Lee JE. Large for gestational age and obesity‐related comorbidities. J Obes Metab Syndr. 2021;30(2):124–131. PubMed PMC

Boulet SL, Alexander GR, Salihu HM, Pass M. Macrosomic births in the United States: determinants, outcomes, and proposed grades of risk. Am J Obstet Gynecol. 2003;188(5):1372–1378. PubMed

Jamaluddine Z, Sharara E, Helou V, El Rashidi N, Safadi G, El‐Helou N, et al. Effects of size at birth on health, growth and developmental outcomes in children up to age 18: an umbrella review. Arch Dis Child. 2023; 108:956–969. PubMed PMC

World Health Organization . International Classification of Diseases, eleventh revision (ICD‐11). Geneva: World Health Organization; 2022.

Bommarito PA, Cantonwine DE, Stevens DR, Welch BM, Davalos AD, Zhao S, et al. Fetal growth trajectories of babies born large‐for‐gestational age in the LIFECODES Fetal Growth Study. Am J Obstet Gynecol. 2023;228(3):340.e1–340.e20. PubMed PMC

Zhao Y, Li DZ. Born large for gestational age: not just bigger. Am J Obstet Gynecol. 2023;228(3):366–367. PubMed

Younes S, Samara M, Salama N, Al‐Jurf R, Nasrallah G, Al‐Obaidly S, et al. Incidence, risk factors, and feto‐maternal outcomes of inappropriate birth weight for gestational age among singleton live births in Qatar: a population‐based study. PloS One. 2021;16(10):e0258967. PubMed PMC

Hocquette A, Durox M, Wood R, Klungsøyr K, Szamotulska K, Berrut S, et al. International versus national growth charts for identifying small and large‐for‐gestational age newborns: a population‐based study in 15 European countries. Lancet Reg Health Eur. 2021;8:100167. PubMed PMC

Centers for Disease Control and Prevention . Morbidity and Mortality Weekly Report Percentage of large‐for‐gestational‐age births, by race or hispanic ethnicity United States, 2005. 2008;57(12/12/2022):1258.

Villar J, Cheikh Ismail L, Victora CG, Ohuma EO, Bertino E, Altman DG, et al. International standards for newborn weight, length, and head circumference by gestational age and sex: the newborn cross‐sectional study of the INTERGROWTH‐21st Project. Lancet. 2014;384(9946):857–868. PubMed

Vieira MC, Relph S, Persson M, Seed PT, Pasupathy D. Determination of birth‐weight centile thresholds associated with adverse perinatal outcomes using population, customised, and Intergrowth charts: a Swedish population‐based cohort study. PLoS Med. 2019;16(9):e1002902. PubMed PMC

Choi SKY, Gordon A, Hilder L, Henry A, Hyett JA, Brew BK, et al. Performance of six birth‐weight and estimated‐fetal‐weight standards for predicting adverse perinatal outcome: a 10‐year nationwide population‐based study. Ultrasound Obstet Gynecol. 2021;58(2):264–277. PubMed

Koyanagi A, Zhang J, Dagvadorj A, Hirayama F, Shibuya K, Souza JP, et al. Macrosomia in 23 developing countries: an analysis of a multicountry, facility‐based, cross‐sectional survey. Lancet. 2013;381(9865):476–483. PubMed

Henriksen T. The macrosomic fetus: a challenge in current obstetrics. Acta Obstet Gynecol Scand. 2008;87(2):134–145. PubMed

Damhuis SE, Ganzevoort W, Gordijn SJ. Abnormal fetal growth: small for gestational age, fetal growth restriction, large for gestational age: definitions and epidemiology. Obstet Gynecol Clin North Am. 2021;48(2):267–279. PubMed

The International Fetal and Newborn Growth Consortium for the 21st Century. INTERGROWTH‐21st 2020. [Cited June 2023]. Available from: https://intergrowth21.tghn.org/

Villar J, Giuliani F, Fenton TR, Ohuma EO, Ismail LC, Kennedy SH. INTERGROWTH‐21st very preterm size at birth reference charts. Lancet. 2016;387(10021):844–845. PubMed

Papageorghiou AT, Ohuma EO, Altman DG, Todros T, Cheikh Ismail L, Lambert A, et al. International standards for fetal growth based on serial ultrasound measurements: the fetal growth longitudinal study of the INTERGROWTH‐21st Project. Lancet. 2014;384(9946):869–879. PubMed

Ashorn P, Black RE, Lawn JE, Ashorn U, Klein N, Hofmeyr J, et al. The Lancet Small Vulnerable Newborn Series: science for a healthy start. Lancet. 2020;396(10253):743–745. PubMed

Suárez‐Idueta L, Yargawa J, Blencowe H, Bradley E, Okwaraji YB, Pingray V, et al. Vulnerable newborn types: analysis of population‐based registries for 165 million births in 23 countries, 2000–2021. BJOG. 2023:00:1‐15. PubMed PMC

Suárez‐Idueta L, Blencowe H, Okwaraji YB, Yargawa J, Bradley E, Gordon A, et al. Neonatal mortality risk for vulnerable newborn types in 15 countries using 125.5 million nationwide birth outcome records, 2000–2020. BJOG. 2023;. 00:1‐11. PubMed PMC

DerSimonian R, Laird N. Meta‐analysis in clinical trials. Control Clin Trials. 1986;7(3):177–188. PubMed

Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta‐analyses. BMJ. 2003;327(7414):557–560. PubMed PMC

Ye W, Luo C, Huang J, Li C, Liu Z, Liu F. Gestational diabetes mellitus and adverse pregnancy outcomes: systematic review and meta‐analysis. BMJ. 2022;377:e067946. PubMed PMC

Knight‐Agarwal CR, Jani R, Al Foraih M, Eckley D, Lui CKW, Somerset S, et al. Maternal body mass index and country of birth in relation to the adverse outcomes of large for gestational age and gestational diabetes mellitus in a retrospective cohort of Australian pregnant women. BMC Pregnancy Childbirth. 2021;21(1):649. PubMed PMC

Giudicelli M, Hassler M, Blanc J, Zakarian C, Tosello B. Influence of intrapartum maternal fluids on weight loss in breastfed newborns. J Matern Fetal Neonatal Med. 2022;35(4):692–698. PubMed

Wang D, Zhu L, Zhang S, Wu X, Wang X, Lv Q, et al. Predictive macrosomia birthweight thresholds for adverse maternal and neonatal outcomes. J Matern Fetal Neonatal Med. 2016;29(23):3745–3750. PubMed

Ye J, Torloni MR, Ota E, Jayaratne K, Pileggi‐Castro C, Ortiz‐Panozo E, et al. Searching for the definition of macrosomia through an outcome‐based approach in low‐ and middle‐income countries: a secondary analysis of the WHO Global Survey in Africa, Asia and Latin America. BMC Pregnancy Childbirth. 2015;15:324. PubMed PMC

Chen HY, Chauhan SP, Ward TC, Mori N, Gass ET, Cisler RA. Aberrant fetal growth and early, late, and postneonatal mortality: an analysis of Milwaukee births, 1996–2007. Am J Obstet Gynecol. 2011;204(3):261.e1–261.e10. PubMed

Zhang X, Decker A, Platt RW, Kramer MS. How big is too big? The perinatal consequences of fetal macrosomia. Am J Obstet Gynecol. 2008;198(5):517.e1–517.e6. PubMed

Cnattingius S, Villamor E, Lagerros YT, Wikström AK, Granath F. High birth weight and obesity—a vicious circle across generations. Int J Obes (Lond). 2012;36(10):1320–1324. PubMed

Jolly MC, Sebire NJ, Harris JP, Regan L, Robinson S. Risk factors for macrosomia and its clinical consequences: a study of 350,311 pregnancies. Eur J Obstet Gynecol Reprod Biol. 2003;111(1):9–14. PubMed

Lu Y, Zhang J, Lu X, Xi W, Li Z. Secular trends of macrosomia in southeast China, 1994–2005. BMC Public Health. 2011;11:818. PubMed PMC

Bjørstad AR, Irgens‐Hansen K, Daltveit AK, Irgens LM. Macrosomia: mode of delivery and pregnancy outcome. Acta Obstet Gynecol Scand. 2010;89(5):664–669. PubMed

Pillai S, Cheyney M, Everson CL, Bovbjerg ML. Fetal macrosomia in home and birth center births in the United States: maternal, fetal, and newborn outcomes. Birth. 2020;47(4):409–417. PubMed PMC

Macrosomia: ACOG practice bulletin, number 216. Obstet Gynecol. 2020;135(1):e18–e35. PubMed

Khan N, Ciobanu A, Karampitsakos T, Akolekar R, Nicolaides KH. Prediction of large‐for‐gestational‐age neonate by routine third‐trimester ultrasound. Ultrasound Obstet Gynecol. 2019;54(3):326–333. PubMed

Pilalis A, Souka AP, Papastefanou I, Michalitsi V, Panagopoulos P, Chrelias C, et al. Third trimester ultrasound for the prediction of the large for gestational age fetus in low‐risk population and evaluation of contingency strategies. Prenat Diagn. 2012;32(9):846–853. PubMed

Chauhan SP, Rice MM, Grobman WA, Bailit J, Reddy UM, Wapner RJ, et al. Neonatal morbidity of small‐ and large‐for‐gestational‐age neonates born at term in uncomplicated pregnancies. Obstet Gynecol. 2017;130(3):511–519. PubMed PMC

Suárez‐Idueta L, Pita R, Blencowe H, Barranco A, Gonzalez JF, Paixao ES, et al. National data linkage assessment of live births and deaths in Mexico: estimating under‐five mortality rate ratios for vulnerable newborns and trends from 2008 to 2019. Paediatr Perinat Epidemiol. 2023;37(4):266–275. PubMed

Razaz N, John S, Joseph KS. The matrix revolutions: how databases and database linkages will transform epidemiologic research. Paediatr Perinat Epidemiol. 2023;37(4):287–291. PubMed

Mallouli M, Derbel M, Ingrid A, Sahli J, Zedini C, Ajmi T, et al. Associated outcomes to fetal macrosomia: effect of maternal diabetes. Tunis Med. 2017;95(2):120–125. PubMed