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Ann Pediatr Endocrinol Metab > Volume 23(1); 2018 > Article
Hong and Chung: Small for gestational age and obesity related comorbidities

Abstract

Infant born small for gestational age (SGA) are at increased risk of perinatal morbidity, persistent short stature and metabolic alterations in later life. The result of SGA followed by rapid weight gain during early postnatal life has been associated with increased long-term risks for central obesity, insulin resistance, impaired glucose tolerance, type 2 diabetes, hypertension, increased fat mass, and cardiovascular disease. We should carefully monitor their weight during infancy and childhood to prevent excessive rates of weight gain. ‘Healthy catch up growth’ may decreased the risk of obesity-related comorbidities in SGA. Establishing the optimal growth patterns in SGA to minimize short- and long-term risks is important, and further studies will be needed. This review discusses recent studies concentrating on obesity-related morbidities in SGA infants that may provide insight into growth monitoring.

Introduction

Childhood obesity is an increasingly important public health issue both worldwide and in Korea. One potential predictor of later obesity is birth weight. Both small for gestational age (SGA) and large for gestational age (LGA) are correlated with obesity and obesity related morbidities over the course of an individual’s life. Those who are born SGA are at risk of developing metabolic disease later in life, particularly obesity, insulin resistance, glucose intolerance, cardiovascular disease, and dyslipidemia [1]. Approximately 85% of SGA infants achieve appropriate catch-up growth [2], and they tend to gain weight more rapidly during the early postnatal period. Catch-up growth and accelerated postnatal weight gain is associated with an increased risk of adiposity and metabolic disease later in life [3-5]. This review discusses recent studies concentrating on obesity related morbidities in SGA infants that may provide insight into growth monitoring.

Obesity and SGA

An association between birth weight and development of obesity has been reported in numerous publications [6-12]. High birth weight is most strongly associated with subsequent childhood obesity [6]. SGA birth is also associated with greater adiposity (percentage body fat and fat mass), obesity, and particularly truncal obesity, in later childhood and adulthood [7,8]. Some studies have suggested that SGA infants remain lighter and have less body fat and others found them to be more likely to exhibit obesity in childhood, in particular with catch-up growth [9-12]. Older studies published from the 1970s to the 1990s, before the obesity epidemic that began in the 1980s, reported long-term reductions in height, weight, body mass index (BMI), and skinfold thickness in SGA [12].

Effects of fetal growth retardation timing in SGA

Human development rates are highest during the first trimester of pregnancy. This period is essential for development of fetal cardiovascular and metabolic organs [13]. Smaller first trimester fetal crown to rump length was reported to be associated with higher total fat mass percentage, android/gynoid fat mass ratio, diastolic blood pressure, and total cholesterol concentration in childhood [14]. The observed associations suggest that the first trimester of pregnancy is a critical period for cardiovascular health in later life. One study documented that the exposure to famine in the first 2 trimesters of pregnancy is associated with increased obesity [15]. In contrast, those exposed to famine during the last trimester of pregnancy have reduced obesity rate [15]. The exact mechanisms for the associations of first trimester fetal growth and risk factors for cardiovascular disease remain unclear, but they may include changes in methylation of DNA and expression of RNA in response to a suboptimal fetal environment [16].

Adiposity in SGA

There are many reports showing an inverse association between birth weight and central fat deposition [7,17-20]. SGA infants have a continuously altered pattern of fat accumulation [21]. At birth, SGA infants included in the study had less adipose tissue than appropriate for gestational age (AGA) infants. Differences in anthropometric indices were continued until 6 weeks of age; however, adipose tissue distribution did not differ between AGA and SGA infants at that time [17]. When Harrington et al. [18] evaluated subcutaneous and intra-abdominal fat distribution in SGA, in contrast to the highly significant differences in subcutaneous fat tissue between AGA and SGA infants, they detected no significant differences in intra-abdominal adipose tissue. SGA infants exhibit a tendency to transition toward central adiposity, which enhances insulin resistance. Yoshikawa et al. [19] reported that the sum thickness of four skinfolds (triceps, biceps, suprailiac, and subscapular) in SGA infants was thinner at birth and caught up to AGA infants within 1 month, which supported a rapid postnatal catch-up fat phenomenon in SGA infants. Even though children born SGA remain slightly smaller than AGA children, they also exhibit reduced lean tissue mass without a reduction in fat mass, and thus have a higher percentage of body fat [7]. Also in adolescents, SGA could be associated with a higher subcutaneous truncal fat distribution [20].
The mechanism of rapid postnatal fat accumulation in SGA infants has been investigated in some studies [19,22]. Some hormonal and metabolic factors may be related to early postnatal increases in fat accumulation. Lipoprotein lipase (LPL)-mediated lipolysis of very-low density lipoprotein (VLDL) and triglyceride (TG) may be one of the major mechanisms of rapid growth in subcutaneous fat tissue exhibited in SGA [19]. A rapid postnatal increase in LPL mediates TG uptake from VLDLs [22]. A marked postnatal increase in insulin-like growth factor-1 observed in SGA infants is one of the causes of rapid postnatal subcutaneous fat accumulation [19].

Role of catch-up growth/fat and obesity-related comorbidities in SGA infants

Catch-up growth refers to cross upwards by at least a one-percentile band on standard growth charts, equivalent to a gain in weight SD score of at least 0.67 [4]. This catch-up growth may be advantageous for survival and may have long-term benefits with regard to cognitive development and stature [23]. However, catch-up growth and rapid postnatal weight gain has been reported to be associated with an increased risk of adiposity and metabolic disease later in life [4]. Patterns in first-year weight gain seem to influence metabolic risk [24,25]. The effects of early, rapid weight gain are similar in non-SGA infants [26,27]. A study of young adults born AGA or SGA found that those who gained weight most rapidly (fast catch-up) during the first 3 months of life had the worst cardiovascular and metabolic risk profile [28]. This sequence of SGA followed by fast catch-up in the first few months, which is the cell division period, has been reported to be associated with increased long-term risk for central obesity, insulin resistance, type 2 diabetes and cardiovascular disease [29].

SGA and metabolic syndrome

The term metabolic syndrome refers to the presence of visceral obesity, dyslipidemia, impaired glucose tolerance or overt type 2 diabetes mellitus and hypertension as a cluster [30]. The fetal origins hypothesis suggests that SGA infants are at higher risk of developing metabolic syndrome later in adulthood [31]. There are conflicting data regarding the association between SGA and metabolic syndrome in children, adolescents and young adults [32-34]. In a study of Korean adolescents, there were no differences in metabolic syndrome components among those that were SGA and non-SGA at birth, possibly due to different eating habits or racial traits [34].
Low-birth-weight, but not catch-up growth, correlates with insulin resistance indices at 12 months, suggesting early occurrence of metabolic abnormalities [35]. Early programming of insulin resistance plays a key role in the development of adult metabolic disease in those who are SGA at birth [36-38]. Insulin resistance or reduced insulin sensitivity may increase the risk of type 2 diabetes in adulthood, especially for SGA infants with catch-up growth and a high BMI [39]. Higher levels of insulin are closely correlated with postnatal height catch-up growth in young SGA children and with weight catch-up growth in older children [40].
SGA children with higher BMI were more insulin resistant than AGA children with similar weight and BMI [41]. Obese SGA children have higher fasting insulin, homeostatic model assessment-insulin resistance, glucose and insulin levels at 120 minutes after a glucose load compared with obese non-SGA children [42]. Overweight SGA children are also at increased risk of components of metabolic syndrome compared with overweight AGA children [43]. These findings suggest that metabolic alterations in SGA are caused by both adverse fetal programming and obesity. In a recent study, school-age children and adolescents with combined fetal growth restriction and prematurity (preterm SGA) exhibited an increased prevalence of glucose risk and metabolic syndrome compared with term SGA or preterm AGA [44]. This indicates that prematurity alone does not impact metabolic risk, while suggesting the influence of being born SGA [44].
Evidence regarding lipid outcomes has been inconsistent [45]. A meta-analysis showed a small but significantly inverse association between total cholesterol and birth weight [46]. De Jong et al. [47] reported a high prevalence of high triglyceride levels at 1 year of age in SGA children compared to AGA children. However, unlike insulin resistance, total cholesterol and low-density lipoprotein cholesterol levels were not significantly different between obese SGA and obese non-SGA children [42]. Most studies reported no association between postnatal growth and lipid levels [45].

Cardiovascular disease in obese SGA

The relationship between birth weight and coronary artery disease has been demonstrated in many studies [9,48-58]. Prenatal growth restriction can result in prenatal circulatory adaptations and altered heart and vascular tree development [48]. Furthermore, hypertension in adult may be caused by a reduction in nephrons, decreased synthesis of elastin in the walls of the aorta, and large arteries due to fetal malnutrition [49,50]. Low birth weight has a tendency to cause high adult blood pressure [51,52]. However, cardiovascular disease risk in SGA children was not yet observed in blood pressure and laboratory measurements at age 6–12 years [9].
Leunissen et al. [53] reported no associations between weight at birth and blood pressure at 21 years, but found positive association between weight gain and intima media thickness of the common carotid artery in young adults. This indicates that childhood weight gain, especially fat mass, rather than SGA itself has a greater influence on young adult blood pressure [53]. There is a stronger association between low birth weight and the risk of coronary heart disease among men with high BMI at adolescence, compared with men with low BMI [54]. This suggests that weight gain in adolescence may influence the relationship between birth weight and coronary heart disease [54]. Intima media thickness of the common carotid artery, which is a well-known marker of subclinical atherosclerosis, was significantly increased in obese children born SGA compared with obese children born AGA of a similar age, sex and BMI [55].

Healthy catch-up growth in SGA infants

As we reviewed above, rapid catch-up growth after birth in SGA infants is related to a number of obesity related metabolic disorders. Persistent poor postnatal growth is associated with more frequent infection, short stature and impaired cognitive development in SGA [56]. Lei et al. [57] suggested that the optimal growth trajectory for SGA may be fast catch-up growth to about the 30th percentile in the first several months, with modest catch-up growth thereafter, to around the 50th percentile by 7 years old. Establishing the optimal growth patterns in SGA to minimize short- and long-term risks is important, and further studies will be needed. For healthy catch-up growth, nutrition guidelines and growth targets are also needed to balance associated risks.

Conclusions

The higher probability of SGA infants developing metabolic alterations could be related to both increased weight gain (catch-up growth) and fetal programming [58]. Even with the same high BMI status, obese SGA individuals have more severe morbidities compared with obese non-SGA individuals. Gains in body fat mass, especially central fat might be predict adverse metabolic outcomes. Birth weight is an endpoint of different fetal exposures and growth patterns and the starting point of childhood growth. To prevent metabolic syndrome and cardiovascular disease, early interventions for obesity and routine monitoring of healthy growth is important in those born SGA. It may be necessary to evaluate metabolic parameters in overweight or obese SGA children.

Notes

Conflict of interest: No potential conflict of interest relevant to this article was reported.

References

1. Varvarigou AA. Intrauterine growth restriction as a potential risk factor for disease onset in adulthood. J Pediatr Endocrinol Metab 2010;23:215–24.
crossref pmid pdf
2. Karlberg J, Albertsson-Wikland K. Growth in full-term small-for-gestational-age infants: from birth to final height. Pediatr Res 1995;38:733–9.
crossref pmid
3. Eriksson JG, Forsén T, Tuomilehto J, Osmond C, Barker DJ. Early growth and coronary heart disease in later life: longitudinal study. BMJ 2001;322:949–53.
crossref pmid pmc
4. Ong KK, Ahmed ML, Emmett PM, Preece MA, Dunger DB. Association between postnatal catch-up growth and obesity in childhood: prospective cohort study. BMJ 2000;320:967–71.
crossref pmid pmc
5. Woo Baidal JA, Locks LM, Cheng ER, Blake-Lamb TL, Perkins ME, Taveras EM. Risk factors for childhood obesity in the first 1,000 days: a systematic review. Am J Prev Med 2016;50:761–79.
crossref pmid
6. Gillman MW, Rifas-Shiman S, Berkey CS, Field AE, Colditz GA. Maternal gestational diabetes, birth weight, and adolescent obesity. Pediatrics 2003;111:e221–6.
crossref pmid
7. Hediger ML, Overpeck MD, Kuczmarski RJ, McGlynn A, Maurer KR, Davis WW. Muscularity and fatness of infants and young children born small- or large-for-gestationalage. Pediatrics 1998;102:E60.
crossref pmid
8. Biosca M, Rodríguez G, Ventura P, Samper MP, Labayen I, Collado MP, et al. Central adiposity in children born small and large for gestational age. Nutr Hosp 2011;26:971–6.
pmid
9. Kuhle S, Maguire B, Ata N, MacInnis N, Dodds L. Birth weight for gestational age, anthropometric measures, and cardiovascular disease markers in children. J Pediatr 2017;182:99–106.
crossref pmid
10. Gallo P, Cioffi L, Limauro R, Farris E, Bianco V, Sassi R, et al. SGA children in pediatric primary care: What is the best choice, large or small? A 10-year prospective longitudinal study. Glob Pediatr Health 2016;3:2333794x16659993.
crossref pmid pmc
11. Yu ZB, Han SP, Zhu GZ, Zhu C, Wang XJ, Cao XG, et al. Birth weight and subsequent risk of obesity: a systematic review and meta-analysis. Obes Rev 2011;12:525–42.
crossref pmid
12. Kramer MS, Martin RM, Bogdanovich N, Vilchuk K, Dahhou M, Oken E. Is restricted fetal growth associated with later adiposity? Observational analysis of a randomized trial. Am J Clin Nutr 2014;100:176–81.
crossref pmid pmc pdf
13. Robinson HP. Sonar measurement of fetal crown-rump length as means of assessing maturity in first trimester of pregnancy. Br Med J 1973;4:28–31.
crossref pmid pmc
14. Jaddoe VW, de Jonge LL, Hofman A, Franco OH, Steegers EA, Gaillard R. First trimester fetal growth restriction and cardiovascular risk factors in school age children: population based cohort study. Bmj 2014;348:g14.
crossref pmid pmc
15. Ravelli GP, Stein ZA, Susser MW. Obesity in young men after famine exposure in utero and early infancy. N Engl J Med 1976;295:349–53.
crossref pmid
16. Gluckman PD, Hanson MA, Cooper C, Thornburg KL. Effect of in utero and early-life conditions on adult health and disease. N Engl J Med 2008;359:61–73.
crossref pmid pmc
17. Modi N, Thomas EL, Harrington TA, Uthaya S, Doré CJ, Bell JD. Determinants of adiposity during preweaning postnatal growth in appropriately grown and growthrestricted term infants. Pediatr Res 2006;60:345–8.
crossref pmid
18. Harrington TA, Thomas EL, Frost G, Modi N, Bell JD. Distribution of adipose tissue in the newborn. Pediatr Res 2004;55:437–41.
crossref pmid
19. Yoshikawa K, Okada T, Munakata S, Okahashi A, Yonezawa R, Makimoto M, et al. Association between serum lipoprotein lipase mass concentration and subcutaneous fat accumulation during neonatal period. Eur J Clin Nutr 2010;64:447–53.
crossref pmid pdf
20. Labayen I, Moreno LA, Ruiz JR, González-Gross M, Wärnberg J, Breidenassel C, et al. Small birth weight and later body composition and fat distribution in adolescents: the Avena study. Obesity (Silver Spring) 2008;16:1680–6.
crossref pmid
21. Ratnasingham A, Eiby YA, Dekker Nitert M, Donovan T, Lingwood BE. Review: is rapid fat accumulation in early life associated with adverse later health outcomes? Placenta 2017;54:125–30.
crossref pmid
22. Okada T, Takahashi S, Nagano N, Yoshikawa K, Usukura Y, Hosono S. Early postnatal alteration of body composition in preterm and small-for-gestational-age infants: implications of catch-up fat. Pediatr Res 2015;77:136–42.
crossref pmid
23. Yeung MY. Postnatal growth, neurodevelopment and altered adiposity after preterm birth--from a clinical nutrition perspective. Acta Paediatr 2006;95:909–17.
crossref pmid
24. Mericq V, Martinez-Aguayo A, Uauy R, Iñiguez G, Van der Steen M, Hokken-Koelega A. Long-term metabolic risk among children born premature or small for gestational age. Nat Rev Endocrinol 2017;13:50–62.
crossref pmid pdf
25. Zheng M, Lamb KE, Grimes C, Laws R, Bolton K, Ong KK, et al. Rapid weight gain during infancy and subsequent adiposity: a systematic review and meta-analysis of evidence. Obes Rev 2018;19:321–32.
crossref pmid
26. Ong KK. Catch-up growth in small for gestational age babies: good or bad? Curr Opin Endocrinol Diabetes Obes 2007;14:30–4.
crossref pmid
27. Chomtho S, Wells JC, Williams JE, Davies PS, Lucas A, Fewtrell MS. Infant growth and later body composition: evidence from the 4-component model. Am J Clin Nutr 2008;87:1776–84.
crossref pmid pdf
28. Leunissen RW, Kerkhof GF, Stijnen T, Hokken-Koelega A. Timing and tempo of first-year rapid growth in relation to cardiovascular and metabolic risk profile in early adulthood. JAMA 2009;301:2234–42.
crossref pmid
29. Ibáñez L, Ong K, Dunger DB, de Zegher F. Early development of adiposity and insulin resistance after catchup weight gain in small-for-gestational-age children. J Clin Endocrinol Metab 2006;91:2153–8.
crossref pmid
30. Alberti KG, Zimmet P, Shaw J. The metabolic syndrome: a new worldwide definition. Lancet 2005;366:1059–62.
crossref pmid
31. Hales CN, Barker DJ. Type 2 (non-insulin-dependent) diabetes mellitus: the thrifty phenotype hypothesis. Diabetologia 1992;35:595–601.
crossref pmid
32. Hirschler V, Bugna J, Roque M, Gilligan T, Gonzalez C. Does low birth weight predict obesity/overweight and metabolic syndrome in elementary school children? Arch Med Res 2008;39:796–802.
crossref pmid
33. Ramadhani MK, Grobbee DE, Bots ML, Castro Cabezas M, Vos LE, Oren A, et al. Lower birth weight predicts metabolic syndrome in young adults: the Atherosclerosis Risk in Young Adults (ARYA)-study. Atherosclerosis 2006;184:21–7.
crossref pmid
34. Cho WK, Jung IA, Suh BK. Current growth status and metabolic parameters of Korean adolescents born small for gestational age: results from the Korea National Health and Nutrition Examination Surveys (KNHANES) 2010-2011. Pediatr Int 2014;56:344–8.
crossref pmid
35. Giapros V, Vavva E, Siomou E, Kolios G, Tsabouri S, Cholevas V, et al. Low-birth-weight, but not catch-up growth, correlates with insulin resistance and resistin level in SGA infants at 12 months. J Matern Fetal Neonatal Med 2017;30:1771–6.
crossref pmid
36. Norris SA, Osmond C, Gigante D, Kuzawa CW, Ramakrishnan L, Lee NR, et al. Size at birth, weight gain in infancy and childhood, and adult diabetes risk in five lowor middle-income country birth cohorts. Diabetes Care 2012;35:72–9.
crossref pmid
37. Zhang Z, Kris-Etherton PM, Hartman TJ. Birth weight and risk factors for cardiovascular disease and type 2 diabetes in US children and adolescents: 10 year results from NHANES. Matern Child Health J 2014;18:1423–32.
crossref pmid
38. Mericq V, Ong KK, Bazaes R, Peña V, Avila A, Salazar T, et al. Longitudinal changes in insulin sensitivity and secretion from birth to age three years in small- and appropriate-forgestational-age children. Diabetologia 2005;48:2609–14.
crossref pmid
39. Veening MA, Van Weissenbruch MM, Delemarre-Van De Waal HA. Glucose tolerance, insulin sensitivity, and insulin secretion in children born small for gestational age. J Clin Endocrinol Metab 2002;87:4657–61.
crossref pmid
40. Deng HZ, Li YH, Su Z, Ma HM, Huang YF, Chen HS, et al. Association between height and weight catch-up growth with insulin resistance in pre-pubertal Chinese children born small for gestational age at two different ages. Eur J Pediatr 2011;170:75–80.
crossref pmid
41. Deng HZ, Deng H, Su Z, Li YH, Ma HM, Chen HS, et al. Insulin resistance and adiponectin levels are associated with height catch-up growth in pre-pubertal Chinese individuals born small for gestational age. Nutr Metab (Lond) 2012;9:107.
crossref pmid pmc
42. Dominguez Hernandez C, Klünder Klünder M, Huang F, Flores Armas EM, Velázquez-López L, Medina-Bravo P. Association between abdominal fat distribution, adipocytokines and metabolic alterations in obese lowbirth-weight children. Pediatr Obes 2016;11:285–91.
crossref pmid
43. Reinehr T, Kleber M, Toschke AM. Small for gestational age status is associated with metabolic syndrome in overweight children. Eur J Endocrinol 2009;160:579–84.
crossref pmid
44. Ramírez-Vélez R, Correa-Bautista JE, Villa-González E, Martínez-Torres J, Hackney AC, García-Hermoso A. Effects of preterm birth and fetal growth retardation on lifecourse cardiovascular risk factors among schoolchildren from Colombia: The FUPRECOL study. Early Hum Dev 2017;106-107:53–8.
crossref pmid
45. Castanys-Muñoz E, Kennedy K, Castañeda-Gutiérrez E, Forsyth S, Godfrey KM, Koletzko B, et al. Systematic review indicates postnatal growth in term infants born small-forgestational-age being associated with later neurocognitive and metabolic outcomes. Acta Paediatr 2017;106:1230–8.
crossref pmid pmc
46. Owen CG, Whincup PH, Odoki K, Gilg JA, Cook DG. Birth weight and blood cholesterol level: a study in adolescents and systematic review. Pediatrics 2003;111(5 Pt 1):1081–9.
crossref
47. de Jong M, Cranendonk A, van Weissenbruch MM. Components of the metabolic syndrome in early childhood in very-low-birth-weight infants and term small and appropriate for gestational age infants. Pediatr Res 2015;78:457–61.
crossref pmid pdf
48. Cohen E, Wong FY, Horne RS, Yiallourou SR. Intrauterine growth restriction: impact on cardiovascular development and function throughout infancy. Pediatr Res 2016;79:821–30.
crossref pmid pdf
49. Zandi-Nejad K, Luyckx VA, Brenner BM. Adult hypertension and kidney disease: the role of fetal programming. Hypertension 2006;47:502–8.
crossref pmid
50. Martyn CN, Greenwald SE. Impaired synthesis of elastin in walls of aorta and large conduit arteries during early development as an initiating event in pathogenesis of systemic hypertension. Lancet 1997;350:953–5.
crossref pmid
51. Chen W, Srinivasan SR, Berenson GS. Amplification of the association between birthweight and blood pressure with age: the Bogalusa Heart Study. J Hypertens 2010;28:2046–52.
crossref pmid pmc
52. Ediriweera DS, Dilina N, Perera U, Flores F, Samita S. Risk of low birth weight on adulthood hypertension: evidence from a tertiary care hospital in a South Asian country, Sri Lanka: a retrospective cohort study. BMC Public Health 2017;17:358.
crossref pmid pmc pdf
53. Leunissen RW, Kerkhof GF, Stijnen T, Hokken-Koelega AC. Effect of birth size and catch-up growth on adult blood pressure and carotid intima-media thickness. Horm Res Paediatr 2012;77:394–401.
crossref pmid
54. Osler M, Lund R, Kriegbaum M, Andersen AM. The influence of birth weight and body mass in early adulthood on early coronary heart disease risk among Danish men born in 1953. Eur J Epidemiol 2009;24:57–61.
crossref pmid
55. Stroescu R, Micle I, Marginean O, Bizerea T, Marazan M, Puiu M, et al. Is small for gestational age status associated with an increased risk of atherogenesis? Maedica (Buchar) 2013;8:315–20.
pmid pmc
56. Saenger P, Czernichow P, Hughes I, Reiter EO. Small for gestational age: short stature and beyond. Endocr Rev 2007;28:219–51.
crossref pmid pdf
57. Lei X, Chen Y, Ye J, Ouyang F, Jiang F, Zhang J. The optimal postnatal growth trajectory for term small for gestational age babies: a prospective cohort study. J Pediatr 2015;166:54–8.
crossref pmid
58. Matta J, Carette C, Levy Marchal C, Bertrand J, Pétéra M, Zins M, et al. Weight for gestational age and metabolically healthy obesity in adults from the Haguenau cohort. BMJ Open 2016;6:e011367.
crossref pmid pmc


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