Commentary
Catch-up growth in low-birthweight infants: friend or foe? Stamatis P. Efstathiou Center for the Prevention of Cardiovascular Disease, Hygeias Melathron Infirmary, Athens, Greece
Invited commentary on ‘Low birthweight or rapid catch-up growth: which is more associated with cardiovascular disease and its risk factors in later life: A systematic review and cryptanalysis’, Kelishadi et al. It has long been recognised that size at birth and growth in early infancy are important indicators of maternal and child health, early childhood survival and diseases in adult life, such as type 2 diabetes and cardiovascular disease.1 In this issue of Pediatrics and International Child Health, Kelishadi et al. report on the role of rapid postnatal catch-up growth in low-birthweight neonates as a more crucial risk factor for the development of cardiometabolic disease than low birthweight alone.2 They demonstrated that 79.6% of cardiometabolic risk factors or diseases are statistically significant in the catch-up hypothesis and 58.5% in the lowbirthweight hypothesis.2 More than 20 years ago, Barker and colleagues first showed that slow rates of pre-natal growth predict cardiovascular mortality, indicating that cardiovascular disease may originate from programming in fetal life and infancy.3 Subsequently, a large body of literature has confirmed that birthweight is inversely associated with coronary heart disease, stroke, hypertension, insulin resistance, metabolic syndrome, type 2 diabetes, dyslipidaemia and non-alcoholic fatty liver.4 These associations gave impetus to the concept of ‘developmental origins of disease’ according to which early exposure of the fetus to poor nutrition leads to permanent changes in insulin metabolism and body structure, resulting in increased adult susceptibility to cardiometabolic diseases.3 It has been suggested that alterations in cortisol and growth hormone, insulinlike growth factors and the sympathetic nervous Correspondence to: S P Efstathiou, Center for the Prevention of Cardiovascular Disease Hygeias Melathron Infirmary, Athens, Greece. Email: [email protected]
ß W. S. Maney & Son Ltd 2015
DOI 10.1179/2046905515Y.0000000011
system could mediate the observed link between birth size and later central obesity.4 On the other hand, the ‘thrifty genotype’ hypothesis was originally proposed by Neel in 1962 to explain the remarkably high prevalence of type 2 diabetes in recently westernised, previously undernourished populations.5 In this respect, the insulin gene VNTR polymorphism has been associated with postnatal weight gain, insulin resistance, central fat deposition and type 2 diabetes.6 Growth data from large contemporary birth cohorts confirm much earlier observations in smaller studies that around 25% of all newborn infants will show a significant degree of postnatal rapid or ‘catch-up’ growth.6 Catch-up growth in the first few months of life is seen almost ubiquitously in infants who are small for their gestational age and is conventionally considered highly desirable as it erases the growth deficit. Recently, greater catch-up growth in the first year of life has been associated with better cognition, fewer disabilities and greater height in young adulthood.7 Nevertheless, such growth has been related to an increased risk of later adiposity, insulin resistance and cardiovascular disease in both low- and high-income countries.8 Accumulating evidence suggests that catch-up growth occurs because growth-inhibiting conditions delay progression of the physiological mechanisms which normally cause body growth to slow and cease with age. As a result, following the period of growth inhibition, tissues retain a greater proliferative capacity than normal, and therefore grow more rapidly than normal for age.8 The major contribution of Kelishadi et al.’s review is that it is the first study to clearly compare the impact of birthweight to that of growth trajectory in early life on the incidence of cardiometabolic disease and the relevant risk factors. To date, three previously published systematic reviews have shown that both low birthweight and increased early weight gain amplify the risk of future cardiometabolic derangements,9–11 but no data were available on the relative contribution of intra-uterine growth retardation and initial growth in infancy on cardiometabolic risk.9–11 Kelishadi et al.’s carefully conducted systematic review discloses interesting information with clinically important implications. Yet, the importance of its findings is undermined by the fact that the study design was
Paediatrics and International Child Health
2015
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Stamatis P. Efstathiou
Catch-up growth in low-birthweight infants
not comparative. Moreover, the authors did not conduct a meta-analysis owing to the large degree of heterogeneity of parameters, of variations in causal relationships and in the age at which outcomes had been assessed, and of differences in the sample size and in the design of primary studies. Unfortunately, all the above are inherent limitations of such studies. Furthermore, the impact of missing information on the findings was not assessed and the authors were unable to determine any publication bias because meta-analysis was not possible. However, their systematic review provides additional support to the notion that low birthweight, notably when accompanied by rapid postnatal catch-up growth, can be considered to be a modifiable risk factor for cardiometabolic diseases in later life. What the article does not tell us is whether the pre- or post-natal environment would be the more appropriate target for intervention. Early identification of modifiable risk factors for low birthweight which affect the maternal uterine environment, such as maternal undernutrition and smoking during pregnancy, would be a crucial challenge for all health professionals involved in the pregnancy process. On the other hand, there is evidence that post-natal patterns of weight gain are driven by satiety, as indicated by early feeding studies in infants,12 and by the ALSPAC Study finding13 that blood leptin predicts weight gain in infancy. Therefore, early counselling for controlling rapid early growth during the first months of life, when feeding patterns are strongly influenced by the infant and growth is regulated by nutrition, could counterbalance to some extent the ominous growth trajectory. Which strategy would be more feasible in practice remains to be proved in long-term interventional studies on pregnancies at high risk of low-birthweight delivery as well as on post-natal growth of lowbirthweight newborns. Most small-for-gestational-age infants show rapid early post-natal growth and weight gain. Increasing trends towards childhood overweight and its metabolic consequences as well as their epidemiological associations with lower birthweight have led to critical assessment of the benefits and disadvantages of rapid early growth.14 Although systematic reviews like that of Kelishadi et al. have described the consistent association between rapid growth in infancy and the risk of subsequent obesity in childhood and later life, long-term randomised trials of growth hormone therapy in
82
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children who were small for gestational age have persistently demonstrated short stature and significant adult height deficit in untreated children without early spontaneous catch-up.14 Even in modern societies with low rates of childhood infection and mortality, the smallfor-gestational-age infant may face a dilemma over whether or not to catch up. Current nutritional strategies that promote catch-up growth should include some monitoring of weight-for-length and adiposity, and future research should seek to determine what is ‘healthy catch-up growth’.
References 1 Jain V, Singhal A. Catch up growth in low birth weight infants: striking a healthy balance. Rev Endocr Metab Disord. 2012;13: 141 –7. 2 Kelishadi R, Haghdoost AA, Jamshidi F, Aliramezany M, Moosazadeh M. Low birthweight or rapid catch-up growth: which is more associated with cardiovascular disease and its risk factors in later life? A systematic review and cryptanalysis. Paediatr Int Child Health. 2015;35. 3 Barker DJ, Osmond C, Simmonds SJ, Wield GA. The relation of small head circumference and thinness at birth to death from cardiovascular disease in adult life. Br Med J. 1993;306:422–6. 4 Efstathiou SP, Skeva II, Zorbala E, Georgiou E, Mountokalakis TD. Metabolic syndrome in adolescence: can it be predicted from natal and parental profile? The Prediction of Metabolic Syndrome in Adolescence (PREMA) study. Circulation. 2012; 125:902–10. 5 Neel JV. Diabetes mellitus: a ‘thrifty’ genotype rendered detrimental by ‘progress’? Am J Hum Genet. 1962;14:353–62. 6 Ong KK, Dunger DB. Birth weight, infant growth and insulin resistance. Eur J Endocrinol. 2004;151:U131– 9. 7 van Dommelen P, van der Pal SM, Bennebroek Gravenhorst J, Walther FJ, Wit JM, van der Pal de Bruin KM. The effect of early catch-up growth on health and well-being in young adults. Ann Nutr Metab. 2014;65:220–6. 8 Finkielstain GP, Lui JC, Baron J. Catch-up growth: cellular and molecular mechanisms. World Rev Nutr Diet. 2013;106: 100 –4. 9 Nobili V, Alisi A, Panera N, Agostoni C. Low birth weight and catch-up-growth associated with metabolic syndrome: a ten year systematic review. Pediatr Endocrinol Rev. 2008;6:241–7. 10 Newsome CA, Shiell AW, Fall CH, Phillips DI, Shier R, Law CM. Is birth weight related to later glucose and insulin metabolism? – A systematic review. Diabet Med. 2003;20: 339 –48. 11 Harder T, Roepke K, Diller N, Stechling Y, Dudenhausen JW, Plagemann A. Birth weight, early weight gain, and subsequent risk of type 1 diabetes: systematic review and meta-analysis. Am J Epidemiol. 2009;169:1428–36. 12 Ounsted M, Sleigh G. The infant’s self-regulation of food intake and weight gain. Difference in metabolic balance after growth constraint or acceleration in utero. Lancet. 1975;1: 1393–7. 13 Ong KK, Ahmed ML, Sherriff A, Woods KA, Watts A, Golding J, Dunger DB. The ALSPAC Study Team. Cord blood leptin is associated with size at birth and predicts infancy weight gain in humans. J Clin Endocrinol Metabol. 1999;84: 1145–8. 14 Ong KK. Catch-up growth in small for gestational age babies: good or bad? Curr Opin Endocrinol Diabetes Obes. 2007;14: 30 –4.
NO .
2
Copyright of Paediatrics & International Child Health is the property of Maney Publishing and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
Catch-up growth in low-birthweight infants: friend or foe? Stamatis P. Efstathiou Center for the Prevention of Cardiovascular Disease, Hygeias Melathron Infirmary, Athens, Greece
Invited commentary on ‘Low birthweight or rapid catch-up growth: which is more associated with cardiovascular disease and its risk factors in later life: A systematic review and cryptanalysis’, Kelishadi et al. It has long been recognised that size at birth and growth in early infancy are important indicators of maternal and child health, early childhood survival and diseases in adult life, such as type 2 diabetes and cardiovascular disease.1 In this issue of Pediatrics and International Child Health, Kelishadi et al. report on the role of rapid postnatal catch-up growth in low-birthweight neonates as a more crucial risk factor for the development of cardiometabolic disease than low birthweight alone.2 They demonstrated that 79.6% of cardiometabolic risk factors or diseases are statistically significant in the catch-up hypothesis and 58.5% in the lowbirthweight hypothesis.2 More than 20 years ago, Barker and colleagues first showed that slow rates of pre-natal growth predict cardiovascular mortality, indicating that cardiovascular disease may originate from programming in fetal life and infancy.3 Subsequently, a large body of literature has confirmed that birthweight is inversely associated with coronary heart disease, stroke, hypertension, insulin resistance, metabolic syndrome, type 2 diabetes, dyslipidaemia and non-alcoholic fatty liver.4 These associations gave impetus to the concept of ‘developmental origins of disease’ according to which early exposure of the fetus to poor nutrition leads to permanent changes in insulin metabolism and body structure, resulting in increased adult susceptibility to cardiometabolic diseases.3 It has been suggested that alterations in cortisol and growth hormone, insulinlike growth factors and the sympathetic nervous Correspondence to: S P Efstathiou, Center for the Prevention of Cardiovascular Disease Hygeias Melathron Infirmary, Athens, Greece. Email: [email protected]
ß W. S. Maney & Son Ltd 2015
DOI 10.1179/2046905515Y.0000000011
system could mediate the observed link between birth size and later central obesity.4 On the other hand, the ‘thrifty genotype’ hypothesis was originally proposed by Neel in 1962 to explain the remarkably high prevalence of type 2 diabetes in recently westernised, previously undernourished populations.5 In this respect, the insulin gene VNTR polymorphism has been associated with postnatal weight gain, insulin resistance, central fat deposition and type 2 diabetes.6 Growth data from large contemporary birth cohorts confirm much earlier observations in smaller studies that around 25% of all newborn infants will show a significant degree of postnatal rapid or ‘catch-up’ growth.6 Catch-up growth in the first few months of life is seen almost ubiquitously in infants who are small for their gestational age and is conventionally considered highly desirable as it erases the growth deficit. Recently, greater catch-up growth in the first year of life has been associated with better cognition, fewer disabilities and greater height in young adulthood.7 Nevertheless, such growth has been related to an increased risk of later adiposity, insulin resistance and cardiovascular disease in both low- and high-income countries.8 Accumulating evidence suggests that catch-up growth occurs because growth-inhibiting conditions delay progression of the physiological mechanisms which normally cause body growth to slow and cease with age. As a result, following the period of growth inhibition, tissues retain a greater proliferative capacity than normal, and therefore grow more rapidly than normal for age.8 The major contribution of Kelishadi et al.’s review is that it is the first study to clearly compare the impact of birthweight to that of growth trajectory in early life on the incidence of cardiometabolic disease and the relevant risk factors. To date, three previously published systematic reviews have shown that both low birthweight and increased early weight gain amplify the risk of future cardiometabolic derangements,9–11 but no data were available on the relative contribution of intra-uterine growth retardation and initial growth in infancy on cardiometabolic risk.9–11 Kelishadi et al.’s carefully conducted systematic review discloses interesting information with clinically important implications. Yet, the importance of its findings is undermined by the fact that the study design was
Paediatrics and International Child Health
2015
VOL .
35
NO .
2
81
Stamatis P. Efstathiou
Catch-up growth in low-birthweight infants
not comparative. Moreover, the authors did not conduct a meta-analysis owing to the large degree of heterogeneity of parameters, of variations in causal relationships and in the age at which outcomes had been assessed, and of differences in the sample size and in the design of primary studies. Unfortunately, all the above are inherent limitations of such studies. Furthermore, the impact of missing information on the findings was not assessed and the authors were unable to determine any publication bias because meta-analysis was not possible. However, their systematic review provides additional support to the notion that low birthweight, notably when accompanied by rapid postnatal catch-up growth, can be considered to be a modifiable risk factor for cardiometabolic diseases in later life. What the article does not tell us is whether the pre- or post-natal environment would be the more appropriate target for intervention. Early identification of modifiable risk factors for low birthweight which affect the maternal uterine environment, such as maternal undernutrition and smoking during pregnancy, would be a crucial challenge for all health professionals involved in the pregnancy process. On the other hand, there is evidence that post-natal patterns of weight gain are driven by satiety, as indicated by early feeding studies in infants,12 and by the ALSPAC Study finding13 that blood leptin predicts weight gain in infancy. Therefore, early counselling for controlling rapid early growth during the first months of life, when feeding patterns are strongly influenced by the infant and growth is regulated by nutrition, could counterbalance to some extent the ominous growth trajectory. Which strategy would be more feasible in practice remains to be proved in long-term interventional studies on pregnancies at high risk of low-birthweight delivery as well as on post-natal growth of lowbirthweight newborns. Most small-for-gestational-age infants show rapid early post-natal growth and weight gain. Increasing trends towards childhood overweight and its metabolic consequences as well as their epidemiological associations with lower birthweight have led to critical assessment of the benefits and disadvantages of rapid early growth.14 Although systematic reviews like that of Kelishadi et al. have described the consistent association between rapid growth in infancy and the risk of subsequent obesity in childhood and later life, long-term randomised trials of growth hormone therapy in
82
Paediatrics and International Child Health
2015
VOL .
35
children who were small for gestational age have persistently demonstrated short stature and significant adult height deficit in untreated children without early spontaneous catch-up.14 Even in modern societies with low rates of childhood infection and mortality, the smallfor-gestational-age infant may face a dilemma over whether or not to catch up. Current nutritional strategies that promote catch-up growth should include some monitoring of weight-for-length and adiposity, and future research should seek to determine what is ‘healthy catch-up growth’.
References 1 Jain V, Singhal A. Catch up growth in low birth weight infants: striking a healthy balance. Rev Endocr Metab Disord. 2012;13: 141 –7. 2 Kelishadi R, Haghdoost AA, Jamshidi F, Aliramezany M, Moosazadeh M. Low birthweight or rapid catch-up growth: which is more associated with cardiovascular disease and its risk factors in later life? A systematic review and cryptanalysis. Paediatr Int Child Health. 2015;35. 3 Barker DJ, Osmond C, Simmonds SJ, Wield GA. The relation of small head circumference and thinness at birth to death from cardiovascular disease in adult life. Br Med J. 1993;306:422–6. 4 Efstathiou SP, Skeva II, Zorbala E, Georgiou E, Mountokalakis TD. Metabolic syndrome in adolescence: can it be predicted from natal and parental profile? The Prediction of Metabolic Syndrome in Adolescence (PREMA) study. Circulation. 2012; 125:902–10. 5 Neel JV. Diabetes mellitus: a ‘thrifty’ genotype rendered detrimental by ‘progress’? Am J Hum Genet. 1962;14:353–62. 6 Ong KK, Dunger DB. Birth weight, infant growth and insulin resistance. Eur J Endocrinol. 2004;151:U131– 9. 7 van Dommelen P, van der Pal SM, Bennebroek Gravenhorst J, Walther FJ, Wit JM, van der Pal de Bruin KM. The effect of early catch-up growth on health and well-being in young adults. Ann Nutr Metab. 2014;65:220–6. 8 Finkielstain GP, Lui JC, Baron J. Catch-up growth: cellular and molecular mechanisms. World Rev Nutr Diet. 2013;106: 100 –4. 9 Nobili V, Alisi A, Panera N, Agostoni C. Low birth weight and catch-up-growth associated with metabolic syndrome: a ten year systematic review. Pediatr Endocrinol Rev. 2008;6:241–7. 10 Newsome CA, Shiell AW, Fall CH, Phillips DI, Shier R, Law CM. Is birth weight related to later glucose and insulin metabolism? – A systematic review. Diabet Med. 2003;20: 339 –48. 11 Harder T, Roepke K, Diller N, Stechling Y, Dudenhausen JW, Plagemann A. Birth weight, early weight gain, and subsequent risk of type 1 diabetes: systematic review and meta-analysis. Am J Epidemiol. 2009;169:1428–36. 12 Ounsted M, Sleigh G. The infant’s self-regulation of food intake and weight gain. Difference in metabolic balance after growth constraint or acceleration in utero. Lancet. 1975;1: 1393–7. 13 Ong KK, Ahmed ML, Sherriff A, Woods KA, Watts A, Golding J, Dunger DB. The ALSPAC Study Team. Cord blood leptin is associated with size at birth and predicts infancy weight gain in humans. J Clin Endocrinol Metabol. 1999;84: 1145–8. 14 Ong KK. Catch-up growth in small for gestational age babies: good or bad? Curr Opin Endocrinol Diabetes Obes. 2007;14: 30 –4.
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Copyright of Paediatrics & International Child Health is the property of Maney Publishing and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
