Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Childhood obesity and adverse cardiometabolic risk in large for gestational age infants and potential early preventive strategies: a narrative review

Abstract

Accumulating evidence indicates that obesity and cardiometabolic risks become established early in life due to developmental programming and infants born as large for gestational age (LGA) are particularly at risk. This review summarizes the recent literature connecting LGA infants and early childhood obesity and cardiometabolic risk and explores potential preventive interventions in early infancy. With the rising obesity rates in women of childbearing age, the LGA birth rate is about 10%. Recent literature continues to support the higher rates of obesity in LGA infants. However, there is a knowledge gap for their lifetime risk for adverse cardiometabolic outcomes. Potential factors that may modify the risk in early infancy include catch-down early postnatal growth, reduction in body fat growth trajectory, longer breastfeeding duration, and presence of a healthy gut microbiome. The early postnatal period may be a critical window of opportunity for active interventions to mitigate or prevent obesity and potential adverse metabolic consequences in later life. A variety of promising candidate biomarkers for the early identification of metabolic alterations in LGA infants is also discussed.

Impact

  • LGA infants are the greatest risk category for future obesity, especially if they experience rapid postnatal growth during infancy.

  • Potential risk modifying secondary prevention strategies in early infancy in LGA infants include catch-down early postnatal growth, reduction in body fat growth trajectory, longer breastfeeding duration, and presence of a healthy gut microbiome.

  • LGA infants may be potential low-hanging fruit targets for early preventive interventions in the fight against childhood obesity.

Your institute does not have access to this article

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

All prices are NET prices.

Fig. 1: Current understanding of the early life developmental programming associated with obesity and cardiometabolic diseases in large for gestational age (LGA) infants.

References

  1. (NCD-RisC) NRFC. Worldwide trends in body-mass index, underweight, overweight, and obesity from 1975 to 2016: a pooled analysis of 2416 population-based measurement studies in 128·9 million children, adolescents, and adults. Lancet 390, 2627–2642 (2017).

    Google Scholar 

  2. Lobstein, T. et al. Child and adolescent obesity: part of a bigger picture. Lancet 385, 2510–2520 (2015).

    PubMed  PubMed Central  Google Scholar 

  3. Di Cesare, M. et al. The epidemiological burden of obesity in childhood: a worldwide epidemic requiring urgent action. BMC Med. 17, 212 (2019).

    PubMed  PubMed Central  Google Scholar 

  4. Barton, M. Force UPST Screening for obesity in children and adolescents: US Preventive Services Task Force recommendation statement. Pediatrics 125, 361–367 (2010).

    PubMed  Google Scholar 

  5. Grossman, D. C. et al. Screening for obesity in children and adolescents: US Preventive Services Task Force recommendation statement. JAMA 317, 2417–2426 (2017).

    PubMed  Google Scholar 

  6. Daniels, S. R. & Hassink, S. G. Nutrition CO: the role of the pediatrician in primary prevention of obesity. Pediatrics 136, e275–e292 (2015).

    PubMed  Google Scholar 

  7. Smego, A. et al. High body mass index in infancy may predict severe obesity in early childhood. J. Pediatr. 183, 87–93.e1 (2017).

    PubMed  Google Scholar 

  8. Cunningham, S. A., Kramer, M. R. & Narayan, K. M. Incidence of childhood obesity in the United States. N. Engl. J. Med. 370, 1660–1661 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Geserick, M. et al. Acceleration of BMI in early childhood and risk of sustained obesity. N. Engl. J. Med. 379, 1303–1312 (2018).

    PubMed  Google Scholar 

  10. Balagopal, P. B. et al. Nontraditional risk factors and biomarkers for cardiovascular disease: mechanistic, research, and clinical considerations for youth: a scientific statement from the American Heart Association. Circulation 123, 2749–2769 (2011).

    PubMed  Google Scholar 

  11. Kelly, A. S. et al. Severe obesity in children and adolescents: identification, associated health risks, and treatment approaches: a scientific statement from the American Heart Association. Circulation 128, 1689–1712 (2013).

    PubMed  Google Scholar 

  12. Daniels, S. R. et al. Promoting cardiovascular health in early childhood and transitions in childhood through adolescence: a workshop report. J. Pediatr. 209, 240–51.e1 (2019).

    PubMed  Google Scholar 

  13. Lycett, K. et al. Body Mass index from early to late childhood and cardiometabolic measurements at 11 to 12 years. Pediatrics 146, e20193666 (2020).

  14. Armstrong, S., Li, J. S. & Skinner, A. C. Flattening the (BMI) curve: timing of child obesity onset and cardiovascular risk. Pediatrics 146, e20201353 (2020).

  15. Matthews, E. K., Wei, J. & Cunningham, S. A. Relationship between prenatal growth, postnatal growth and childhood obesity: a review. Eur. J. Clin. Nutr. 71, 919–930 (2017).

    CAS  PubMed  Google Scholar 

  16. Woo, J. G. et al. Prediction of adult class II/III obesity from childhood BMI: the i3C consortium. Int J. Obes. 44, 1164–1172 (2020).

    Google Scholar 

  17. Barker, D. J. & Osmond, C. Infant mortality, childhood nutrition, and ischaemic heart disease in England and Wales. Lancet 1, 1077–1081 (1986).

    CAS  PubMed  Google Scholar 

  18. Ludvigsson, J. F., Lu, D., Hammarström, L., Cnattingius, S. & Fang, F. Small for gestational age and risk of childhood mortality: a Swedish population study. PLoS Med. 15, e1002717 (2018).

    PubMed  PubMed Central  Google Scholar 

  19. Derraik, J. G. B. et al. Large-for-gestational-age phenotypes and obesity risk in adulthood: a study of 195,936 women. Sci. Rep. 10, 2157 (2020).

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Barker, D. J. The fetal and infant origins of adult disease. BMJ 301, 1111 (1990).

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Ibáñez, L., Ong, K., Dunger, D. B. & de Zegher, F. Early development of adiposity and insulin resistance after catch-up weight gain in small-for-gestational-age children. J. Clin. Endocrinol. Metab. 91, 2153–2158 (2006).

    PubMed  Google Scholar 

  22. Okada, T. et al. Early postnatal alteration of body composition in preterm and small-for-gestational-age infants: implications of catch-up fat. Pediatr. Res. 77, 136–142 (2015).

    PubMed  Google Scholar 

  23. Lavery, J. A., Friedman, A. M., Keyes, K. M., Wright, J. D. & Ananth, C. V. Gestational diabetes in the United States: temporal changes in prevalence rates between 1979 and 2010. BJOG 124, 804–813 (2017).

    CAS  PubMed  Google Scholar 

  24. Tolosa, J. N. & Calhoun, D. A. Maternal and neonatal demographics of macrosomic infants admitted to the neonatal intensive care unit. J. Perinatol. 37, 1292–1296 (2017).

    CAS  PubMed  Google Scholar 

  25. Tutlam, N. T., Liu, Y., Nelson, E. J., Flick, L. H. & Chang, J. J. 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. 21, 1643–1654 (2017).

    PubMed  Google Scholar 

  26. Koyanagi, A. et al. Macrosomia in 23 developing countries: an analysis of a multicountry, facility-based, cross-sectional survey. Lancet 381, 476–483 (2013).

    PubMed  Google Scholar 

  27. Patro Golab, B. et al. Influence of maternal obesity on the association between common pregnancy complications and risk of childhood obesity: an individual participant data meta-analysis. Lancet Child Adolesc. Health 2, 812–821 (2018).

    PubMed  Google Scholar 

  28. Voerman, E. et al. Maternal body mass index, gestational weight gain, and the risk of overweight and obesity across childhood: an individual participant data meta-analysis. PLoS Med. 16, e1002744 (2019).

    PubMed  PubMed Central  Google Scholar 

  29. Badon, S. E., Quesenberry, C. P., Xu, F., Avalos, L. A. & Hedderson, M. M. Gestational weight gain, birthweight and early-childhood obesity: between- and within-family comparisons. Int. J. Epidemiol. 49, 1682–1690 (2020).

    PubMed  PubMed Central  Google Scholar 

  30. Hales, C. M., Carroll, M. D., Fryar, C. D. & Ogden, C. L. Prevalence of obesity and severe obesity among adults: United States, 2017–2018. NCHS Data Brief. 360, 1–8 (2020).

  31. Åmark, H., Westgren, M. & Persson, M. Prediction of large-for-gestational-age infants in pregnancies complicated by obesity: a population-based cohort study. Acta Obstet. Gynecol. Scand. 98, 769–776 (2019).

    PubMed  Google Scholar 

  32. Weschenfelder, F., Lehmann, T., Schleussner, E. & Groten, T. Gestational weight gain particularly affects the risk of large for gestational age infants in non-obese mothers. Geburtshilfe Frauenheilkd. 79, 1183–1190 (2019).

    PubMed  PubMed Central  Google Scholar 

  33. Deputy, N. P., Kim, S. Y., Conrey, E. J. & Bullard, K. M. Prevalence and changes in preexisting diabetes and gestational diabetes among women who had a live birth - United States, 2012-2016. MMWR Morb. Mortal. Wkly Rep. 67, 1201–1207 (2018).

    PubMed  PubMed Central  Google Scholar 

  34. Mastroeni, M. F. et al. The independent importance of pre-pregnancy weight and gestational weight gain for the prevention of large-for gestational age Brazilian newborns. Matern. Child Health J. 21, 705–714 (2017).

    PubMed  Google Scholar 

  35. Ouyang, F. et al. Maternal BMI, gestational diabetes, and weight gain in relation to childhood obesity: the mediation effect of placental weight. Obesity 24, 938–946 (2016).

    PubMed  Google Scholar 

  36. Castillo-Castrejon, M. & Powell, T. L. Placental nutrient transport in gestational diabetic pregnancies. Front. Endocrinol. 8, 306 (2017).

    Google Scholar 

  37. Lawlor, D. A. The Society for Social Medicine John Pemberton Lecture 2011. Developmental overnutrition–an old hypothesis with new importance? Int J. Epidemiol. 42, 7–29 (2013).

    PubMed  Google Scholar 

  38. Maron, B. A., Maron, J. L. & Abman, S. H. The case for bringing birthweight to adult cardiovascular medicine. Am. J. Cardiol. 127, 191–192 (2020).

    PubMed  PubMed Central  Google Scholar 

  39. Mehta, S. H., Kruger, M. & Sokol, R. J. Being too large for gestational age precedes childhood obesity in African Americans. Am. J. Obstet. Gynecol. 204, 265.e1–5 (2011).

    Google Scholar 

  40. Cnattingius, S., Villamor, E., Lagerros, Y. T., Wikström, A. K. & Granath, F. High birth weight and obesity–a vicious circle across generations. Int. J. Obes. 36, 1320–1324 (2012).

    CAS  Google Scholar 

  41. Chiavaroli, V. et al. Progression of cardio-metabolic risk factors in subjects born small and large for gestational age. PLoS ONE 9, e104278 (2014).

    PubMed  PubMed Central  Google Scholar 

  42. Kuciene, R., Dulskiene, V. & Medzioniene, J. Associations between high birth weight, being large for gestational age, and high blood pressure among adolescents: a cross-sectional study. Eur. J. Nutr. 57, 373–381 (2018).

    PubMed  Google Scholar 

  43. Kapral, N., Miller, S. E., Scharf, R. J., Gurka, M. J. & DeBoer, M. D. Associations between birthweight and overweight and obesity in school-age children. Pediatr. Obes. 13, 333–341 (2018).

    CAS  PubMed  Google Scholar 

  44. Salahuddin, M. et al. Predictors of severe obesity in low-income, predominantly Hispanic/Latino children: The Texas Childhood Obesity Research Demonstration Study. Prev. Chronic Dis. 14, E141 (2017).

    PubMed  PubMed Central  Google Scholar 

  45. Hammoud, N. M. et al. Long-term BMI and growth profiles in offspring of women with gestational diabetes. Diabetologia 61, 1037–1045 (2018).

    PubMed  PubMed Central  Google Scholar 

  46. Kaul, P. et al. Association between maternal diabetes, being large for gestational age and breast-feeding on being overweight or obese in childhood. Diabetologia 62, 249–258 (2019).

    CAS  PubMed  Google Scholar 

  47. Chen, Y. L. et al. Adverse pregnancy outcomes on the risk of overweight offspring: a population-based retrospective study in Xiamen, China. Sci. Rep. 10, 1549 (2020).

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Broccoli, S. et al. Early life weight patterns and risk of obesity at 5 years: a population-based cohort study. Prev. Med. 134, 106024 (2020).

    PubMed  Google Scholar 

  49. Cusick, S. E. & Georgieff, M. K. The role of nutrition in brain development: the golden opportunity of the “first 1000 days”. J. Pediatr. 175, 16–21 (2016).

    PubMed  PubMed Central  Google Scholar 

  50. American Academy of Pediatrics. Pediatric Nutrition Handbook 8th edn (American Academy of Pediatrics, Elk Grove Village, IL, 2019).

  51. Wang, G. et al. Weight gain in infancy and overweight or obesity in childhood across the gestational spectrum: a prospective birth cohort study. Sci. Rep. 6, 29867 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  52. Lyons-Reid, J., Albert, B. B., Kenealy, T. & Cutfield, W. S. Birth size and rapid infant weight gain-where does the obesity risk lie? J. Pediatr. 230, 238–243 (2021).

    PubMed  Google Scholar 

  53. Zheng, M. et al. Rapid weight gain during infancy and subsequent adiposity: a systematic review and meta-analysis of evidence. Obes. Rev. 19, 321–332 (2018).

    CAS  PubMed  Google Scholar 

  54. Lu, Y., Pearce, A. & Li, L. Weight gain in early years and subsequent body mass index trajectories across birth weight groups: a prospective longitudinal study. Eur. J. Public Health 30, 316–322 (2020).

    PubMed  PubMed Central  Google Scholar 

  55. Woo, J. G. Infant growth and long-term cardiometabolic health: a review of recent findings. Curr. Nutr. Rep. 8, 29–41 (2019).

    PubMed  Google Scholar 

  56. Druet, C. et al. Prediction of childhood obesity by infancy weight gain: an individual-level meta-analysis. Paediatr. Perinat. Epidemiol. 26, 19–26 (2012).

    PubMed  Google Scholar 

  57. Chiavaroli, V. et al. Infants born large-for-gestational-age display slower growth in early infancy, but no epigenetic changes at birth. Sci. Rep. 5, 14540 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  58. Nakagawa, Y. et al. Postnatal BMI changes in children with different birthweights: a trial study for detecting early predictive factors for pediatric obesity. Clin. Pediatr. Endocrinol. 27, 19–29 (2018).

    PubMed  PubMed Central  Google Scholar 

  59. Lei, X. et al. Childhood health outcomes in term, large-for-gestational-age babies with different postnatal growth patterns. Am. J. Epidemiol. 187, 507–514 (2018).

    PubMed  Google Scholar 

  60. Taal, H. R., Vd Heijden, A. J., Steegers, E. A., Hofman, A. & Jaddoe, V. W. Small and large size for gestational age at birth, infant growth, and childhood overweight. Obesity 21, 1261–1268 (2013).

    PubMed  Google Scholar 

  61. Renom Espineira, A. et al. Postnatal growth and cardiometabolic profile in young adults born large for gestational age. Clin. Endocrinol. 75, 335–341 (2011).

    Google Scholar 

  62. Hales, C. N. & Barker, D. J. The thrifty phenotype hypothesis. Br. Med. Bull. 60, 5–20 (2001).

    CAS  PubMed  Google Scholar 

  63. Moreno-Mendez, E., Quintero-Fabian, S., Fernandez-Mejia, C. & Lazo-de-la-Vega-Monroy, M. L. Early-life programming of adipose tissue. Nutr. Res. Rev. 33, 244–259 (2020).

    PubMed  Google Scholar 

  64. Kislal, S., Shook, L. L. & Edlow, A. G. Perinatal exposure to maternal obesity: lasting cardiometabolic impact on offspring. Prenat. Diagn. 40, 1109–1125 (2020).

    PubMed  PubMed Central  Google Scholar 

  65. Chiarelli, F. & Marcovecchio, M. L. Insulin resistance and obesity in childhood. Eur. J. Endocrinol. 159, S67–74 (2008).

    CAS  PubMed  Google Scholar 

  66. Logan, K. M., Gale, C., Hyde, M. J., Santhakumaran, S. & Modi, N. Diabetes in pregnancy and infant adiposity: systematic review and meta-analysis. Arch. Dis. Child Fetal Neonatal Ed. 102, F65–F72 (2017).

    PubMed  Google Scholar 

  67. Larsson, A., Ottosson, P., Törnqvist, C. & Olhager, E. Body composition and growth in full-term small for gestational age and large for gestational age Swedish infants assessed with air displacement plethysmography at birth and at 3-4 months of age. PLoS ONE 14, e0207978 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  68. Donnelley, E. L., Raynes-Greenow, C. H., Turner, R. M., Carberry, A. E. & Jeffery, H. E. Antenatal predictors and body composition of large-for-gestational-age newborns: perinatal health outcomes. J. Perinatol. 34, 698–704 (2014).

    CAS  PubMed  Google Scholar 

  69. Moore, B. F., Harrall, K. K., Sauder, K. A., Glueck, D. H. & Dabelea D. Neonatal adiposity and childhood obesity. Pediatrics 146, e20200737 (2020).

  70. Ratnasingham, A., Eiby, Y. A., Dekker Nitert, M., Donovan, T. & Lingwood, B. E. Review: is rapid fat accumulation in early life associated with adverse later health outcomes? Placenta 54, 125–130 (2017).

    PubMed  Google Scholar 

  71. Toro-Ramos, T., Paley, C., Pi-Sunyer, F. X. & Gallagher, D. Body composition during fetal development and infancy through the age of 5 years. Eur. J. Clin. Nutr. 69, 1279–1289 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  72. de Fluiter, K. S., van Beijsterveldt, I. A. L. P., Breij, L. M., Acton, D. & Hokken-Koelega, A. C. S. Association between fat mass in early life and later fat mass trajectories. JAMA Pediatr. 174, 1141–1148 (2020). 12.

    PubMed  Google Scholar 

  73. de Zegher, F. et al. Large for gestational age newborns from mothers without diabetes mellitus tend to become tall and lean toddlers. J. Pediatr. 178, 278–280 (2016).

    PubMed  Google Scholar 

  74. Short, K. R., Teague, A. M., Fields, D. A., Lyons, T. & Chernausek, S. D. Lower resting energy expenditure and fat oxidation in Native American and Hispanic infants born to mothers with diabetes. J. Pediatr. 166, 884–889 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  75. Verma, S., Bailey, S. M., Mally, P. V. & Howell, H. B. Longitudinal measurements of resting energy expenditure by indirect calorimetry in healthy term infants during the first 2 months of life. Am. J. Perinatol. 36, 918–923 (2019). 07.

    PubMed  Google Scholar 

  76. Rodgers, G. P. & Collins, F. S. Precision nutrition-the answer to “what to eat to stay healthy”. JAMA 324, 735–736 (2020).

    PubMed  Google Scholar 

  77. Lobelo, F. Fetal programming and risk of metabolic syndrome: prevention efforts for high-risk populations. Pediatrics 116, 519 (2005).

    PubMed  Google Scholar 

  78. O’Brien, J., Hayder, H., Zayed, Y. & Peng, C. Overview of microRNA biogenesis, mechanisms of actions, and circulation. Front. Endocrinol. 9, 402 (2018).

    Google Scholar 

  79. Mori, M. A., Ludwig, R. G., Garcia-Martin, R., Brandão, B. B. & Kahn, C. R. Extracellular miRNAs: from biomarkers to mediators of physiology and disease. Cell Metab. 30, 656–673 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  80. Rodil-Garcia, P., Arellanes-Licea, E. D. C., Montoya-Contreras, A. & Salazar-Olivo, L. A. Analysis of microRNA expression in newborns with differential birth weight using newborn screening cards. Int. J. Mol. Sci. 18, 2552 (2017).

  81. Ortiz-Dosal, A., Arellanes-Licea, E. D. C., Rodil-García, P. & Salazar-Olivo, L. A. Circulating microRNAs overexpressed in macrosomia: an experimental and bioinformatic approach. J. Dev. Orig. Health Dis. 11, 464–472 (2020).

    CAS  PubMed  Google Scholar 

  82. Perng, W. et al. Associations of cord blood metabolites with perinatal characteristics, newborn anthropometry, and cord blood hormones in project viva. Metabolism 76, 11–22 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  83. Kadakia, R. et al. Cord blood metabolites associated with newborn adiposity and hyperinsulinemia. J. Pediatr. 203, 144–9.e1 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  84. Wang, G. et al. Inter-generational link of obesity in term and preterm births: role of maternal plasma acylcarnitines. Int. J. Obes. 43, 1967–1977 (2019).

    CAS  Google Scholar 

  85. Briana, D. D. et al. Potential prognostic biomarkers of cardiovascular disease in fetal macrosomia: the impact of gestational diabetes. J. Matern. Fetal Neonatal Med. 31, 895–900 (2018).

    CAS  PubMed  Google Scholar 

  86. Papathanasiou, A. E. et al. Cord blood fatty acid-binding protein-4 levels are upregulated at both ends of the birthweight spectrum. Acta Paediatr. 108, 2083–2088 (2019).

    CAS  PubMed  Google Scholar 

  87. Lausten-Thomsen, U., Christiansen, M., Hedley, P. L., Holm, J. C. & Schmiegelow, K. Adipokines in umbilical cord blood from children born large for gestational age. J. Pediatr. Endocrinol. Metab. 29, 33–37 (2016).

    CAS  PubMed  Google Scholar 

  88. Dong, Y. et al. Large-for-gestational-age may be associated with lower fetal insulin sensitivity and β-cell function linked to leptin. J. Clin. Endocrinol. Metab. 103, 3837–3844 (2018).

    PubMed  PubMed Central  Google Scholar 

  89. Higgins, M., Mc & Auliffe, F. A review of maternal and fetal growth factors in diabetic pregnancy. Curr. Diabetes Rev. 6, 116–125 (2010).

    CAS  PubMed  Google Scholar 

  90. Cekmez, F. et al. Apelin, vaspin, visfatin and adiponectin in large for gestational age infants with insulin resistance. Cytokine 56, 387–391 (2011).

    CAS  PubMed  Google Scholar 

  91. Boutsikou, T. et al. Cord blood chemerin and obestatin levels in large for gestational age infants. J. Matern. Fetal Neonatal Med. 26, 123–126 (2013).

    CAS  PubMed  Google Scholar 

  92. Simental-Mendía, L. E., Castañeda-Chacón, A., Rodríguez-Morán, M. & Guerrero-Romero, F. Birth-weight, insulin levels, and HOMA-IR in newborns at term. BMC Pediatr. 12, 94 (2012).

    PubMed  PubMed Central  Google Scholar 

  93. Walewski, J. L. et al. Spexin is a novel human peptide that reduces adipocyte uptake of long chain fatty acids and causes weight loss in rodents with diet-induced obesity. Obesity 22, 1643–1652 (2014).

    CAS  PubMed  Google Scholar 

  94. Kumar, S. et al. Decreased circulating levels of spexin in obese children. J. Clin. Endocrinol. Metab. 101, 2931–2936 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  95. Kumar, S., Hossain, M. J., Javed, A., Kullo, I. J. & Balagopal, P. B. Relationship of circulating spexin with markers of cardiovascular disease: a pilot study in adolescents with obesity. Pediatr. Obes. 13, 374–380 (2018).

    CAS  PubMed  Google Scholar 

  96. Yavuzkir, S. et al. Maternal and umbilical cord blood subfatin and spexin levels in patients with gestational diabetes mellitus. Peptides 126, 170277 (2020).

    CAS  PubMed  Google Scholar 

  97. Akbas, M. et al. Serum levels of spexin are increased in the third trimester pregnancy with gestational diabetes mellitus. Gynecol. Endocrinol. 35, 1050–1053 (2019).

    CAS  PubMed  Google Scholar 

  98. Al-Daghri, N. M. et al. Associations of Spexin and cardiometabolic parameters among women with and without gestational diabetes mellitus. Saudi J. Biol. Sci. 25, 710–714 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  99. Gohir, W., Ratcliffe, E. M. & Sloboda, D. M. Of the bugs that shape us: maternal obesity, the gut microbiome, and long-term disease risk. Pediatr. Res. 77, 196–204 (2015).

    PubMed  Google Scholar 

  100. Murugesan, S. et al. Gut microbiome production of short-chain fatty acids and obesity in children. Eur. J. Clin. Microbiol. Infect. Dis. 37, 621–625 (2018).

    CAS  PubMed  Google Scholar 

  101. Wei, Y. et al. The associations of the gut microbiome composition and short-chain fatty acid concentrations with body fat distribution in children. Clin. Nutr. 40, 3379–3390 (2020).

  102. Zhou, L. & Xiao, X. The role of gut microbiota in the effects of maternal obesity during pregnancy on offspring metabolism. Biosci. Rep. 38, BSR20171234 (2018).

  103. Zheng, J. et al. Correlation of placental microbiota with fetal macrosomia and clinical characteristics in mothers and newborns. Oncotarget 8, 82314–82325 (2017).

    PubMed  PubMed Central  Google Scholar 

  104. Tun, H. M. et al. Roles of birth mode and infant gut microbiota in intergenerational transmission of overweight and obesity from mother to offspring. JAMA Pediatr. 172, 368–377 (2018).

    PubMed  PubMed Central  Google Scholar 

  105. Santacruz, A. et al. Interplay between weight loss and gut microbiota composition in overweight adolescents. Obesity 17, 1906–1915 (2009).

    PubMed  Google Scholar 

  106. Everard, A. et al. Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity. Proc. Natl Acad. Sci. USA 110, 9066–9071 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  107. Donnelly, J. M., Walsh, J. M., Byrne, J., Molloy, E. J. & McAuliffe, F. M. Impact of maternal diet on neonatal anthropometry: a randomized controlled trial. Pediatr. Obes. 10, 52–56 (2015).

    CAS  PubMed  Google Scholar 

  108. Dodd, J. M. et al. The effects of antenatal dietary and lifestyle advice for women who are overweight or obese on neonatal health outcomes: the LIMIT randomised trial. BMC Med. 12, 163 (2014).

    PubMed  PubMed Central  Google Scholar 

  109. Goetz, A. R., Rybak, T. M., Peugh, J. L. & Stark, L. J. Early-life determinants of excess weight in children born heavy. Pediatr. Obes. 15, e12580 (2020).

    PubMed  Google Scholar 

  110. Rito, A. I. et al. Association between characteristics at birth, breastfeeding and obesity in 22 countries: The WHO European Childhood Obesity Surveillance Initiative - COSI 2015/2017. Obes. Facts 12, 226–243 (2019).

    PubMed  PubMed Central  Google Scholar 

  111. Woo, J. G. & Martin, L. J. Does breastfeeding protect against childhood obesity? Moving beyond observational evidence. Curr. Obes. Rep. 4, 207–216 (2015).

    PubMed  Google Scholar 

  112. Doughty, K. N. & Taylor, S. N. Barriers and benefits to breastfeeding with gestational diabetes. Semin. Perinatol. 45, 151385 (2021).

    PubMed  Google Scholar 

  113. Nommsen-Rivers, L. A. Does insulin explain the relation between maternal obesity and poor lactation outcomes? An overview of the literature. Adv. Nutr. 7, 407–414 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  114. Preusting, I., Brumley, J., Odibo, L., Spatz, D. L. & Louis, J. M. Obesity as a predictor of delayed lactogenesis II. J. Hum. Lact. 33, 684–691 (2017).

    PubMed  Google Scholar 

  115. Dewey, K. G. et al. Breastfeeding and risk of overweight in childhood and beyond: a systematic review with emphasis on sibling-pair and intervention studies. Am. J. Clin. Nutr. 114, 1774–1790 (2021).

  116. Wood, C. T. et al. Association between bottle size and formula intake in 2-month-old infants. Acad. Pediatr. 16, 254–259 (2016).

    PubMed  Google Scholar 

  117. Mennella, J. A., Ventura, A. K. & Beauchamp, G. K. Differential growth patterns among healthy infants fed protein hydrolysate or cow-milk formulas. Pediatrics 127, 110–118 (2011).

    PubMed  Google Scholar 

  118. Weber, M. et al. Lower protein content in infant formula reduces BMI and obesity risk at school age: follow-up of a randomized trial. Am. J. Clin. Nutr. 99, 1041–1051 (2014).

    CAS  Google Scholar 

  119. Inostroza, J. et al. Low-protein formula slows weight gain in infants of overweight mothers. J. Pediatr. Gastroenterol. Nutr. 59, 70–77 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  120. Ziauddeen, N., Wilding, S., Roderick, P. J., Macklon, N. S. & Alwan, N. A. Is maternal weight gain between pregnancies associated with risk of large-for-gestational age birth? Analysis of a UK population-based cohort. BMJ Open 9, e026220 (2019).

    PubMed  PubMed Central  Google Scholar 

  121. Alwan, N. A., Grove, G., Taylor, E. & Ziauddeen, N. Maternal weight change between successive pregnancies: an opportunity for lifecourse obesity prevention. Proc. Nutr. Soc. 79, 272–282 (2020).

    PubMed  Google Scholar 

  122. Uzan-Yulzari, A. et al. Neonatal antibiotic exposure impairs child growth during the first six years of life by perturbing intestinal microbial colonization. Nat. Commun. 12, 443 (2021).

    CAS  PubMed  PubMed Central  Google Scholar 

  123. Angelakis, E. & Raoult, D. Gut microbiota modifications and weight gain in early life. Hum. Microbiome J. 10, 1–5 (2018).

    Google Scholar 

Download references

Acknowledgements

Our sincere thanks to Ms. Olivia DiLeonardo, MLS, Medical Librarian, Nemours Children’s Hospital, Orlando, FL, for help with the literature search.

Author information

Authors and Affiliations

Authors

Contributions

S.V. conceived the study, screened articles, interpreted the results, and wrote the first draft of the complete manuscript. K.M. conceived the study, screened articles, and assessed article quality. K.M. and D.C. screened articles and assessed article quality. J.G.W. and B.B. interpreted the results and acted as subject experts. All authors gave constructive comments, reviewed, edited, and approved the final submitted manuscript.

Corresponding author

Correspondence to Sreekanth Viswanathan.

Ethics declarations

Competing interests

Guarantor of the article: Sreekanth Viswanathan. The remaining authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Viswanathan, S., McNelis, K., Makker, K. et al. Childhood obesity and adverse cardiometabolic risk in large for gestational age infants and potential early preventive strategies: a narrative review. Pediatr Res (2021). https://doi.org/10.1038/s41390-021-01904-w

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1038/s41390-021-01904-w

Further reading

Search

Quick links