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Albertsson-Wikland K, Niklasson A & Karlberg P (1990): Birth data for patients who later develop growth hormone deficiency: preliminary analysis of a national register. Acta Paediatr. Scand, Suppl. 370, 115-120.

Barnard R, Haynes KM, Werther GA & Waters MJ (1988): The ontogeny of growth hormone receptors in the rabbit tibia. Endocrinology 122, 2562-2569.

Baron J, Oerter KE, Yanovski JA, Novosad JA, Bacher JD & Cutler GB (1993): Catch-up growth is intrinsic to the epiphyseal growth plate. Pediatr. Res., Suppl. 33, S41.

Black RE, Brown KH, Becker S & Yunus M (1982): Longitudinal studies of infectious diseases and physical growth of children in rural Bangladesh. I. Patterns of Morbidity. Am. J. Epidemiol. 155, 305-314.

Cianfarani S & Holly JMP (1989): Somatomedin - binding proteins: what role do they play in the growth process? Eur. J. Paediatr. 149, 76-79.

Copeland KC, Paunier L & Sizonenko PC (1977): The secretion of adrenal androgens and growth patterns of patients with hypogonadotropic hypogonadism and idiopathic delayed puberty. J. Pediatr. 91, 985-990.

Costello AM (1989): Growth velocity and stunting in rural Nepal. Arch. Dis. Child. 64, 1478-1482.

Dean HJ, Schentag CT & Winter JS (1990): Predictive values of short-term growth using knemometry in a large population of healthy children. Acta Paediatr. Scand. 79, 57-63.

Degan R, Sofor S, Klish WJ et al. (1983): Growth and nutritional status of Bedouin infants in Negev Desert, Israel: evidence for marked stunting in the presence of only mild malnutrition. Am. J. Clin. Nutr. 38, 747-756.

Dewey KG, Peerson JM, Heining MJ et al. (1992): Growth patterns of breast-fed infants in affluent (United States) and poor (Peru) communities: implications for timing of complementary feeding. Am. J. Clin. Nutr. 56, 1012-1018.

Eveleth PB & Tanner JM (1976): Worldwide variation in human growth. Cambridge: University Press.

Frasier SD (1983): Human pituitary growth hormone (hGH) therapy in growth hormone deficiency. Endocr. Res. 4, 155-170.

Gluckman PD (1989): Fetal growth: an endocrine perspective. Acta Paediatr. Scand., Suppl. 349, 21-25.

Gluckman PD, Gunn AJ, Wray A et al. (1992): Congenital idiopathic growth hormone deficiency associated with prenatal and early postnatal growth failure. J. Pediatr. 121, 920-923.

Hagekull B, Nazir R, Jalil F & Karlberg J, (1993): Early child health in Lahore, Pakistan. III. Maternal and family situation. Acta Paediatr. Scand, Suppl. 390, 27-37.

Hauspie RC & Pagezy H (1989): Longitudinal study of growth of African babies: An analysis of seasonal variations in the average growth rate and the effects of infectious diseases on individual and average growth patterns. Acta Paediatr. Scand., Suppl. 350, 37-43.

Hermanussen M, Geiger-Benoit K, Burmeister J & Sippell WG (1988): Knemometry in childhood: accuracy and standardization of a new technique of lower leg length measurement. Ann. Hum. Biol. 15, 1-16.

Hill DJ (1989): Cell multiplication and differentiation. Acta Paediatr. Scand, Suppl. 349, 13-20.

Hill DJ, Freemark M Strain AJ, Handwergers S & Milner RDG (1988): Placental lactogen and growth hormone receptors in human fetal tissues: relationship to fetal human placental lactogen concentrations and fetal growth. J. Clin. Endocrinol. Metab. 66, 1283-1290.

Infant mortality rate and neonatal mortality rate of Hong Kong (1946-1992) (1992): Annual departmental report by Director of Medical and Health Services. The Government of Hong Kong 1992.

Jalil F, Karlberg J, Hanson LÅ & Lindblad BS (1989): Growth disturbances in an urban area of Lahore, Pakistan related to feeding patterns, infections and age, sex, socioeconomic factors and seasons. Acta Paediatr. Scand., Suppl. 350, 44-54.

Jalil F, Lindblad BS, Hanson LÅ et al. (1993a): Early child health in Lahore, Pakistan. I. Study design. Acta Paediatr. Scand., Suppl. 390, 3-16.

Jalil F, Lindblad BS, Hanson LÅ, Khan SR, Yaqoob M & Karlberg J (1993b): Early child health in Lahore, Pakistan. IX. Perinatal events. Acta Paediatr., Suppl. 390, 95-107.

Karlberg J (1987): On the modelling of human growth. Stat. Med. 6, 185-192.

Karlberg J (1989a): A biologically-oriented mathematical model (ICP) for human growth. Acta Paediatr. Scand., Suppl. 350, 70-94.

Karlberg J (1989b): On the construction of the infancy-childhood-puberty growth standard. Acta Paediatr. Scand, Suppl. 356, 26-37.

Karlberg J (1990): The infancy-childhood growth spurt. Acta Paediatr. Scand, Suppl. 367, 111-118.

Karlberg J & Wit JM (1991): Linear growth in Sotos syndrome. Acta Paediatr. Scand 80, 956-957.

Karlberg J & Albertsson-Wikland K (1988): Infancy growth pattern related to growth hormone deficiency. Acta Paediatr. Scand. 77, 385-391.

Karlberg J, Jalil F & Lindblad BS (1988): Longitudinal analysis of infantile growth in an urban area of Lahore, Pakistan. Acta Paediatr. Scand. 77, 392-401.

Karlberg J, Albertsson-Wikland K & Naeraa RW (1991): The infancy-childhood-puberty (ICP) model of growth for Turner girls. In Turner syndrome: Growth promoting therapies, eds MB Ranke & RG Rosenfeldt, pp. 89-94. Elsevier Science Publishers.

Karlberg J, Hägglund G & Strömquist, B (1991): Immobilization related to early linear growth. Acta Paediatr. Scand 80, 833-836.

Karlberg J, Kjellmer I & Kristiansson B (1991): Linear growth in children with Cystic Fibrosis. I. Birth to eight years of age. Acta Paediatr. Scand 80, 508-514.

Karlberg J, Engström I, Karlberg P & Fryer JG (1987a): Analysis of linear growth using a mathematical model. I. From birth to three years. Acta Paediatr. Scand. 76, 478-488.

Karlberg J, Fryer JG, Engström I & Karlberg P (1987b): Analysis of linear growth using a mathematical model. II. From 3 to 21 years of age. Acta Paediatr. Scand, Suppl. 337, 12-29.

Karlberg J, Henter J-I, Tassin E & Lindblad BS (1988): Longitudinal analysis of infantile growth in children with celiac disease. Acta Paediatr. Scand. 77, 516-524.

Karlberg J, Albertsson-Wikland K, Nilsson KO, Ritzén EM & Westphal O (1991): Growth in infancy and childhood in girls with Turner's syndrome. Acta Paediatr. Scand. 80, 1158-1165.

Karlberg J, Ashraf RN, Saleemi M, Yaqoob M & Jalil F (1993): Early child health in Lahore, Pakistan. XI. Growth. Acta Paediatr. Scand., Suppl. 390, 119-149.

Keenan BS, Richards GE, Ponder SW, Dallas JS, Nagamani M & Smith ER (1993): Androgen-stimulated pubertal growth: the effects of testosterone and dihydrotestosterone on growth and insulin - like growth factor - I in the treatment of short stature and delayed puberty. J. Clin. Endocrinol. Metab. 76, 996-1001.

Lam BCC, Tam J, Ng MH, Yeung CY & Lo M (1992): The protective role of neonatal rotavirus infection: A prospective longitudinal study. Hong Kong J. Paediatr. 9, 166-171.

Lampl M, Veldhuis JD & Johnson ML (1992): Saltation and stasis: a model of human growth. Science 258, 801-803.

Manwani AH & Agarwal KN (1973): The growth pattern of Indian infants during the first year of life. Hum. Biol. 45, 341-349.

Martorell R & Habicht JP (1986): Growth in early childhood in developing countries. In Human growth, vol. 3, 2nd edn, eds F Falkner & JM Tanner, pp. 241-262. New York: Plenum Press.

Massa G, de Zegter F & Vanderschueren-Lodeweyckx M (1992): Serum growth hormone-binding proteins in the human fetus and infant. Pediatr. Res. 32, 69-72.

Mata LJ (1978): The children of Santa Maria Cauqué: A prospective field study of health and growth. Massachusetts: The MIT Press.

Michaelson KF, Skov L, Badsberg JH & Jorgensen M (1991): Short-term measurement of linear growth in pre-term infants. Validation of a hand-held knemometer. Pediatr. Res. 30, 464-468.

Milner RDG & Hill DJ (1987): Interaction between endocrine and paracrine peptides in prenatal growth control. J. Pediatr. 146, 113-132.

Oerter KE, Bacher JD, Cutler GB & Baron J (1993): Linear growth in the rabbit is continuous, not saltatory. Pediatr. Res., Suppl. 33, S41.

Pescovitz OH (1990): The endocrinology of the pubertal growth spurt. Acta Paediatr. Scand., Suppl. 367, 119-125.

Smith DW (1977): Growth and its disorders (Major problems in clinical pediatrics, vol. 15). Philadelphia, PA: W.B. Saunders Company.

Stanhope R, Pringle PJ & Brook CGD (1988): The mechanism of the adolescent growth spurt induced by low dose pulsatile GnRH treatment. Clin. Endocrinol. 28, 83-91.

Tam JSL, Zheng BJ, Yeung CY et al. (1990): Distinct populations of rotaviruses circulating among neonates and older infants. J. Clin. Microbiol. 28, 1033-1038.

Tse WY, Hindmarsh PC & Brook CGD (1989): The infancy-childhood-puberty model of growth: Clinical aspects. Acta Paediatr. Scand, Suppl. 356, 38-43.

Valk I, Langhout Chabloz A, Smaals AGH, Kloppenborg PWC, Cassorla FG & Schutte EAST (1983): Accurate measurements of the lower leg length and the ulnar length and its application in short term growth measurement. Growth 47, 53-66.

Wales JK & Milner RDG (1987): Knemometry in assessment of linear growth. Arch. Dis. Child 62, 166-171.

Waterlow JC, Ashworth A & Griffiths M (1980): Faltering in infant growth in less-developed countries. Lancet 2, 1176-1178.

Waters MJ, Barnard RT, Lobie PE et al. (1990): Growth hormone receptors - their structure, location and role. Acta Paediatr. Scand, Suppl. 366, 60-72.

Westher GA, Haynes KM & Waters MJ (1991): Growth hormone (GH) receptors are present in human fetal tissues. Proceedings of the 73rd Annual Hormonal Meeting, p. 418. Washington DC: The Endocrine Society.

WHO (1983): Measuring change in nutritional status: guidelines for assessing the nutritional impact of supplementary feeding programmes for vulnerable groups. Geneva: World Health Organization.

WHO Working Group (1986): Use and interpretation of anthropometric indicators of nutritional status. Bull. WHO 64, 929-941.

Wit JM, Teunissen DM, Waelkens JJJ & Grever WJ (1987): Comparison of short-term lower leg growth with statural growth in children treated with growth promoting substances. Acta Paediatr. Scand, Suppl. 337, 40-43.

Zheng BJ, Lo SKF, Tam JS et al. (1989): Prospective study of community-acquired rotavirus infection. J. Clin. Microbiol. 27, 2083-2090.

Zheng BJ, Tm SL, Lam BCC et al. (1991): The effect of maternal antibodies on neonatal rotavirus infection. J. Paediatr. Infect. Dis. 10, 865-868.

Zumrawi FY, Dimond H & Waterlow JC (1987): Faltering in infant growth in Karthoum province, Sudan. Hum. Nutr.: Clin. Nutr. 41, 383-395.


There is still room for discussion about the natural history of stunting. In the Pakistan study there was some fall-off in linear growth even during the 'infancy' phase. This may be related, at least in part, to size at birth (see discussion of paper by Falkner). Deaths during the first month were related to length at birth. The general opinion was that, in this early phase, the problem was not one of nutritional deficiency. In Pakistan, during the first 6 months, only 15% of children had a seriously low weight-for-length (below -2 SD). Therefore it does not seem likely that the deficit in linear growth was a consequence of failure to gain weight. Similarly, in Chile young children get all the food they need and become overweight for length, but still lag behind in linear growth (Uauy).

It seems probable that infections have something to do with early growth retardation. Breast-fed children without diarrhoea gained 1.5 cm more than those who were not breast-fed and did have diarrhoea. Even in the absence of diarrhoea there was a small difference (about 0.5 cm) between children who were or were not breast-fed. Moreover, it must be remembered that there are other benefits from breast-feeding, in addition to the prevention of infection; it provides a special type of emotional bonding, which is very important for the child's growth (see paper by Skuse). Breast-feeding, however, did not give total protection against stunting because these children also received water, and water carries pathogens.

In any case, the main problem is the growth retardation that becomes much more serious after 6 months. In the Pakistan sample, only 3% had a deficit in linear growth between birth and 6 months, compared with 31% between 6 and 20 months. This is the time when weaning foods are being introduced and infections become more frequent. According to one opinion, this could be an adequate explanation of the falling off in growth and there is nothing more to be said (Neumann). Others, however, preferred to dig more deeply. The hypothesis proposed is that there is a lag in the onset of the childhood phase of growth, but what causes this lag? Karlberg's data showed that the children who faltered in the first 6 months were not necessarily those whose growth was most retarded later on. Growth in these two phases appeared to be independent. The correlation between growth velocity at 1 month and at 1 year was only about 0.6. Thus, though short-term changes may be useful for exploring mechanisms, they cannot provide projections.

There followed a discussion of hormonal responses, which may well be mediated by nutritional factors such as amino acids or minerals (see paper by Allen). No measurements of growth hormone were made in the Pakistan study' because it was not considered ethical to take the large number of blood samples needed to give a profile of GH secretion over 24 hours; in the future it may be possible to overcome this difficulty by urine assays - a possibility that is being explored at INCAP (Torun). It is well established that early in severe PEM, GH levels are increased. The hypothesis is that GH fails to stimulate growth in the childhood phase because of a defect in the receptors. One way of investigating this would be to see if there is any change in the amounts of receptor mRNA, but this has not yet been done (Nilsson). Another possibility is that there is no change in receptors, but a reduced production of IGF-1, so that the defect would be at the post-growth hormone receptor level. On either hypothesis, the defect would only appear when growth hormone enters the picture, at about 6 months. One example is coeliac disease; infants with this condition grow perfectly normally from birth to 6 months, but then they do not start the second phase of growth until they have been treated. If they are treated properly, growth resumes after 1-11/2 months (Karlberg). But the question remains: what is holding up entry into the second phase? Even if we accept that the lag results from chronic malnutrition and/or infection, what is the mechanism? This remains a question for the future.

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