Am J Perinatol
DOI: 10.1055/a-2316-9007
Original Article

Large for Gestational Age and Adverse Outcomes: Stratified By Diabetes Status

Sarah A. Nazeer
1   Division of Maternal-Fetal Medicine, Department of Obstetrics, Gynecology, and Reproductive Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, Texas
Han-Yang Chen
1   Division of Maternal-Fetal Medicine, Department of Obstetrics, Gynecology, and Reproductive Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, Texas
Joycelyn Ashby Cornthwaite
1   Division of Maternal-Fetal Medicine, Department of Obstetrics, Gynecology, and Reproductive Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, Texas
Suneet P. Chauhan
4   Department of Obstetrics and Gynecology, Delaware Center of Maternal-Fetal Medicine, Newark, Delaware
Baha Sibai
5   Department of Obstetrics & Gynecology, University of Texas Health Sciences Center at Houston, Houston, Texas
3   Department of Obstetrics and Gynecology, Beth Israel Deaconess Medical Center, Boston, Massachusetts
Michal F. Bartal
1   Division of Maternal-Fetal Medicine, Department of Obstetrics, Gynecology, and Reproductive Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, Texas
2   Department of Obstetrics and Gynecology, Sheba Medical Center, Tel Hashomer, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
› Author Affiliations


Objective To examine the association of adverse outcomes among parturients with large for gestational age (LGA; birth weight ≥ 90th) newborns, stratified by diabetes status. Additionally, we described the temporal trends of adverse outcomes among LGA neonates.

Study Design This retrospective cohort study used the U.S. Vital Statistics dataset between 2014 and 2020. The inclusion criteria were singleton, nonanomalous LGA live births who labored and delivered at 24 to 41 weeks with known diabetes status. The coprimary outcomes were composite neonatal adverse outcomes of the following: Apgar score < 5 at 5 minutes, assisted ventilation > 6 hours, seizure, or neonatal or infant mortality, and maternal adverse outcomes of the following: maternal transfusion, ruptured uterus, unplanned hysterectomy, admission to intensive care unit, or unplanned procedure. Multivariable Poisson regression models were used to estimate adjusted relative risks (aRR) and 95% confidence intervals (CI). Average annual percent change (AAPC) was calculated to assess changes in rates of LGA and morbidity over time.

Results Of 27 million births in 7 years, 1,843,467 (6.8%) met the inclusion criteria. While 1,656,888 (89.9%) did not have diabetes, 186,579 (10.1%) were with diabetes. Composite neonatal adverse outcomes (aRR = 1.48, 95% CI = 1.43, 1.52) and composite maternal adverse outcomes (aRR = 1.37, 95% CI = 1.36, 1.38) were significantly higher among individuals with diabetes, compared with those without diabetes. From 2014 to 2020, the LGA rate was stable among people without diabetes. However, there was a downward trend of LGA in people with diabetes (AAPC = − 2.4, 95% CI = − 3.5, −1.4).

Conclusion In pregnancies with LGA newborns, composite neonatal and maternal morbidities were higher in those with diabetes, compared with those without diabetes.

Key Points

  • Large for gestational age stratified by diabetes status.

  • Composite neonatal and maternal adverse outcomes are worse among individuals with diabetes as compared to those without.

  • During 2014 to 2020, the trend of LGA in individuals without diabetes increased.


This study was presented at the Annual Scientific Meeting of the Society for Maternal-Fetal Medicine February 11, 2023.

Supplementary Material

Publication History

Received: 21 March 2024

Accepted: 26 April 2024

Accepted Manuscript online:
30 April 2024

Article published online:
27 May 2024

© 2024. Thieme. All rights reserved.

Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

  • References

  • 1 Raio L, Ghezzi F, Di Naro E. et al. Perinatal outcome of fetuses with a birth weight greater than 4500  g: an analysis of 3356 cases. Eur J Obstet Gynecol Reprod Biol 2003; 109 (02) 160-165
  • 2 Chauhan SP, Grobman WA, Gherman RA. et al. Suspicion and treatment of the macrosomic fetus: a review. Am J Obstet Gynecol 2005; 193 (02) 332-346
  • 3 Macrosomia: ACOG Practice Bulletin, Number 216. Obstet Gynecol 2020; 135 (01) e18-e35
  • 4 Evers IM, de Valk HW, Mol BW, ter Braak EW, Visser GH. Macrosomia despite good glycaemic control in type I diabetic pregnancy; results of a nationwide study in The Netherlands. Diabetologia 2002; 45 (11) 1484-1489
  • 5 Boghossian NS, Geraci M, Edwards EM, Horbar JD. In-hospital outcomes in large for gestational age infants at 22-29 weeks of gestation. J Pediatr 2018; 198: 174-180.e13
  • 6 Carter EB, Stockburger J, Tuuli MG, Macones GA, Odibo AO, Trudell AS. Large-for-gestational age and stillbirth: is there a role for antenatal testing?. Ultrasound Obstet Gynecol 2019; 54 (03) 334-337
  • 7 Mendez-Figueroa H, Truong VTT, Pedroza C, Chauhan SP. Large for gestational age infants and adverse outcomes among uncomplicated pregnancies at term. Am J Perinatol 2017; 34 (07) 655-662
  • 8 Chauhan SP, Rice MM, Grobman WA. et al; MSCE, for the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Maternal-Fetal Medicine Units (MFMU) Network. Neonatal morbidity of small- and large-for-gestational-age neonates born at term in uncomplicated pregnancies. Obstet Gynecol 2017; 130 (03) 511-519
  • 9 Doty MS, Chen HY, Sibai BM, Chauhan SP. Maternal and neonatal morbidity associated with early term delivery of large-for-gestational-age but nonmacrosomic neonates. Obstet Gynecol 2019; 133 (06) 1160-1166
  • 10 Chen HY, Chauhan SP. Macrosomic newborns delivered at term after labor among nondiabetic women: maternal and neonatal morbidities. Am J Perinatol 2021; 38 (02) 150-157
  • 11 Rosen H, Shmueli A, Ashwal E, Hiersch L, Yogev Y, Aviram A. Delivery outcomes of large-for-gestational-age newborns stratified by the presence or absence of gestational diabetes mellitus. Int J Gynaecol Obstet 2018; 141 (01) 120-125
  • 12 van Zijl MD, Oudijk MA, Ravelli ACJ, Mol BWJ, Pajkrt E, Kazemier BM. Large-for-gestational-age fetuses have an increased risk for spontaneous preterm birth. J Perinatol 2019; 39 (08) 1050-1056
  • 13 Hua XG, Jiang W, Hu R. et al. Large for gestational age and macrosomia in pregnancies without gestational diabetes mellitus. J Matern Fetal Neonatal Med 2020; 33 (21) 3549-3558
  • 14 Wood S, Tang S. Stillbirth and large for gestational age at birth. J Matern Fetal Neonatal Med 2020; 33 (12) 1974-1979
  • 15 Hong YH, Lee JE. Large for gestational age and obesity-related comorbidities. J Obes Metab Syndr 2021; 30 (02) 124-131
  • 16 Mustaniemi S, Nikkinen H, Bloigu A. et al. Normal gestational weight gain protects from large-for-gestational-age birth among women with obesity and gestational diabetes. Front Public Health 2021; 9: 550860
  • 17 Salihu HM, Dongarwar D, King LM, Yusuf KK, Ibrahimi S, Salinas-Miranda AA. Trends in the incidence of fetal macrosomia and its phenotypes in the United States, 1971-2017. Arch Gynecol Obstet 2020; 301 (02) 415-426
  • 18 Tutlam NT, Liu Y, Nelson EJ, Flick LH, Chang JJ. The effects of race and ethnicity on the risk of large-for-gestational-age newborns in women without gestational diabetes by prepregnancy body mass index categories. Matern Child Health J 2017; 21 (08) 1643-1654
  • 19 Venkatesh KK, Lynch CD, Powe CE. et al. Risk of adverse pregnancy outcomes among pregnant individuals with gestational diabetes by race and ethnicity in the United States, 2014-2020. JAMA 2022; 327 (14) 1356-1367
  • 20 Koyanagi A, Zhang J, Dagvadorj A. et al. Macrosomia in 23 developing countries: an analysis of a multicountry, facility-based, cross-sectional survey. Lancet 2013; 381 (9865) 476-483
  • 21 Baer RJ, Rogers EE, Partridge JC. et al. Population-based risks of mortality and preterm morbidity by gestational age and birth weight. J Perinatol 2016; 36 (11) 1008-1013
  • 22 Boriboonhirunsarn D, Kasempipatchai V. Incidence of large for gestational age infants when gestational diabetes mellitus is diagnosed early and late in pregnancy. J Obstet Gynaecol Res 2016; 42 (03) 273-278
  • 23 Gabbe SG, Graves CR. Management of diabetes mellitus complicating pregnancy. Obstet Gynecol 2003; 102 (04) 857-868
  • 24 American College of Obstetricians and Gynecologists' Committee on Practice Bulletins—Obstetrics. ACOG practice bulletin no. 201: pregestational diabetes mellitus. Obstet Gynecol 2018; 132 (06) e228-e248
  • 25 ACOG practice bulletin no. 190: gestational diabetes mellitus. Obstet Gynecol 2018; 131 (02) e49-e64
  • 26 Mitanchez D. Foetal and neonatal complications in gestational diabetes: perinatal mortality, congenital malformations, macrosomia, shoulder dystocia, birth injuries, neonatal complications. Diabetes Metab 2010; 36 (6 Pt 2): 617-627
  • 27 Lampl M, Jeanty P. Exposure to maternal diabetes is associated with altered fetal growth patterns: a hypothesis regarding metabolic allocation to growth under hyperglycemic-hypoxemic conditions. Am J Hum Biol 2004; 16 (03) 237-263
  • 28 Ng M, Fleming T, Robinson M. et al. Global, regional, and national prevalence of overweight and obesity in children and adults during 1980-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet 2014; 384 (9945) 766-781
  • 29 Ford ND, Patel SA, Narayan KM. Obesity in low- and middle-income countries: burden, drivers, and emerging challenges. Annu Rev Public Health 2017; 38: 145-164
  • 30 Lin X, Xu Y, Pan X. et al. Global, regional, and national burden and trend of diabetes in 195 countries and territories: an analysis from 1990 to 2025. Sci Rep 2020; 10 (01) 14790
  • 31 Liu J, Ren ZH, Qiang H. et al. Trends in the incidence of diabetes mellitus: results from the Global Burden of Disease Study 2017 and implications for diabetes mellitus prevention. BMC Public Health 2020; 20 (01) 1415
  • 32 World Health Organization. Global Report on Diabetes. World Health Organization;; 2016
  • 33 Harvey L, van Elburg R, van der Beek EM. Macrosomia and large for gestational age in Asia: one size does not fit all. J Obstet Gynaecol Res 2021; 47 (06) 1929-1945
  • 34 Osterman MJ, Martin JA, Mathews TJ, Hamilton BE. Expanded data from the new birth certificate, 2008. Natl Vital Stat Rep 2011; 59 (07) 1-28
  • 35 Duryea EL, Hawkins JS, McIntire DD, Casey BM, Leveno KJ. A revised birth weight reference for the United States. Obstet Gynecol 2014; 124 (01) 16-22
  • 36 Mamdani M, Sykora K, Li P. et al. Reader's guide to critical appraisal of cohort studies: 2. Assessing potential for confounding. BMJ 2005; 330 (7497) 960-962
  • 37 Austin PC. Using the standardized difference to compare the prevalence of a binary variable between two groups in observational research. Commun Stat Simul Comput 2009; 38 (06) 1228-1234
  • 38 von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP. STROBE Initiative. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. J Clin Epidemiol 2008; 61 (04) 344-349
  • 39 Shour A, Garacci E, Palatnik A. et al. Association between pregestational diabetes and mortality among appropriate-for-gestational age birthweight infants. J Matern Fetal Neonatal Med 2022; 35 (25) 5291-5300
  • 40 Tse BC, Block B, Figueroa H, Yao R. Adverse neonatal outcomes associated with pregestational diabetes mellitus in infants born preterm. Am J Obstet Gynecol MFM 2020; 2 (04) 100213
  • 41 Yeagle KP, O'Brien JM, Curtin WM, Ural SH. Are gestational and type II diabetes mellitus associated with the Apgar scores of full-term neonates?. Int J Womens Health 2018; 10: 603-607
  • 42 Persson M, Shah PS, Rusconi F. et al; International Network for Evaluating Outcomes of Neonates. Association of maternal diabetes with neonatal outcomes of very preterm and very low-birth-weight infants: an international cohort study. JAMA Pediatr 2018; 172 (09) 867-875
  • 43 Nielsen GL, Welinder L, Berg Johansen M. Mortality and morbidity in offspring of mothers with diabetes compared with a population group: a Danish cohort study with 8-35 years of follow-up. Diabet Med 2017; 34 (07) 938-945
  • 44 Metcalfe A, Hutcheon JA, Sabr Y. et al. Timing of delivery in women with diabetes: a population-based study. Acta Obstet Gynecol Scand 2020; 99 (03) 341-349
  • 45 ACOG committee opinion no. 560: medically indicated late-preterm and early-term deliveries. Obstet Gynecol 2013; 121 (04) 908-910
  • 46 Bartáková V, Barátová B, Chalásová K, Janků P, Kaňková K. Morbidity and psychomotor development of offspring of women with gestational diabetes: a 5-year follow-up. BMC Pediatr 2022; 22 (01) 493
  • 47 Baptiste-Roberts K, Nicholson WK, Wang NY, Brancati FL. Gestational diabetes and subsequent growth patterns of offspring: the National Collaborative Perinatal Project. Matern Child Health J 2012; 16 (01) 125-132
  • 48 Torres-Espinola FJ, Berglund SK, García-Valdés LM. et al; PREOBE Team. Maternal obesity, overweight and gestational diabetes affect the offspring neurodevelopment at 6 and 18 months of age–a follow up from the PREOBE cohort. PLoS One 2015; 10 (07) e0133010
  • 49 Sokol RJ, Blackwell SC, Bulletins-Gynecology ACOGCP. American College of Obstetricians and Gynecologists. Committee on Practice Bulletins-Gynecology. ACOG practice bulletin: shoulder dystocia. Number 40, November 2002. (Replaces practice pattern number 7, October 1997). Int J Gynaecol Obstet 2003; 80 (01) 87-92
  • 50 Sagi-Dain L. Obesity in pregnancy: ACOG practice bulletin, number 230. Obstet Gynecol 2021; 138 (03) 489
  • 51 Osterman M, Hamilton B, Martin JA, Driscoll AK, Valenzuela CP. Births: final data for 2020. Natl Vital Stat Rep 2021; 70 (17) 1-50
  • 52 Hamilton BE, Martin JA, Osterman MJK. Births: provisional data for 2021. Vital Statistics Rapid Release no. 20. Hyattsville, MD:: National Center for Health Statistics;; May 2022.
  • 53 Shah NS, Wang MC, Freaney PM. et al. Trends in gestational diabetes at first live birth by race and ethnicity in the US, 2011-2019. JAMA 2021; 326 (07) 660-669
  • 54 Metzger BE, Lowe LP, Dyer AR. et al; HAPO Study Cooperative Research Group. Hyperglycemia and adverse pregnancy outcomes. N Engl J Med 2008; 358 (19) 1991-2002
  • 55 Landon MB, Spong CY, Thom E. et al; Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. A multicenter, randomized trial of treatment for mild gestational diabetes. N Engl J Med 2009; 361 (14) 1339-1348
  • 56 Crowther CA, Hiller JE, Moss JR, McPhee AJ, Jeffries WS, Robinson JS. Australian Carbohydrate Intolerance Study in Pregnant Women (ACHOIS) Trial Group. Effect of treatment of gestational diabetes mellitus on pregnancy outcomes. N Engl J Med 2005; 352 (24) 2477-2486
  • 57 Rossi AC, Mullin P, Prefumo F. Prevention, management, and outcomes of macrosomia: a systematic review of literature and meta-analysis. Obstet Gynecol Surv 2013; 68 (10) 702-709
  • 58 Pedersen J. Weight and length at birth of infants of diabetic mothers. Acta Endocrinol (Copenh) 1954; 16 (04) 330-342
  • 59 Mohsin F, Khan S, Baki MA, Zabeen B, Azad K. Neonatal management of pregnancy complicated by diabetes. J Pak Med Assoc 2016; 66 (9, suppl 1): S81-S84
  • 60 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
  • 61 Beta J, Khan N, Fiolna M, Khalil A, Ramadan G, Akolekar R. Maternal and neonatal complications of fetal macrosomia: cohort study. Ultrasound Obstet Gynecol 2019; 54 (03) 319-325
  • 62 Bukowski R, Hansen NI, Willinger M. et al; Eunice Kennedy Shriver National Institute of Child Health and Human Development Stillbirth Collaborative Research Network. Fetal growth and risk of stillbirth: a population-based case-control study. PLoS Med 2014; 11 (04) e1001633
  • 63 Kc K, Shakya S, Zhang H. Gestational diabetes mellitus and macrosomia: a literature review. Ann Nutr Metab 2015; 66 (Suppl. 02) 14-20
  • 64 Mackin ST, Nelson SM, Kerssens JJ. et al; SDRN Epidemiology Group. Diabetes and pregnancy: national trends over a 15 year period. Diabetologia 2018; 61 (05) 1081-1088
  • 65 Indications for outpatient antenatal fetal surveillance: ACOG committee opinion, number 828. Obstet Gynecol 2021; 137 (06) e177-e197
  • 66 Ashimi Balogun O, Sibai BM, Pedroza C, Blackwell SC, Barrett TL, Chauhan SP. Serial third-trimester ultrasonography compared with routine care in uncomplicated pregnancies: a randomized controlled trial. Obstet Gynecol 2018; 132 (06) 1358-1367
  • 67 Braun D, Braun E, Chiu V. et al. Trends in neonatal intensive care unit utilization in a large integrated health care system. JAMA Netw Open 2020; 3 (06) e205239
  • 68 ACOG committee opinion no. 748: the importance of vital records and statistics for the obstetrician-gynecologist. Obstet Gynecol 2018; 132 (02) e78-e81
  • 69 Grimes DA, Schulz KF. False alarms and pseudo-epidemics: the limitations of observational epidemiology. Obstet Gynecol 2012; 120 (04) 920-927