FETAL ORIGIN OF ADULT DISEASE
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Abstract
“Fetal origins of adult disease”, often called the “Barker hypothesis” after a large proportion
data of Barker and colleagues in Southampton over the last decade, that adverse influences
early in development, and particularly during intrauterine life, can result in permanent changes
in structure, physiology, metabolism, which result in increased disease risk in adulthood. Many
further studies have provided evidence for the hypothesis that size at birth is related to the
risk of developing disease in later life. In particular, links are well established between reduced
birthweight and increased risk of coronary heart disease, diabetes, hypertension and stroke
in adulthood. The most widely accepted mechanisms thought to underlie these relationship
are those of altered fetal nutrition, genetic–epigenetic links, fetal programming and fetal
excess glucocorticoid exposure. It is suggested that the fetus makes physiological adaption in
response to changes in its environment to prepare itself for posnatal life. The “Fetal origin of
adult disease” hypothesis is attractive. It suggests that these diseases could be prevented by
improving maternal health and fetal development
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Keywords
Development origin of adult disease, Chronic diseases, Heart disease, Hypertension, Diabetes, Programming.
References
1. Barker DJ, Osmond C (1986). Infant mortality, childhood nutrition and ischaemic heart disease
in England and Wales. Lancet, 1: 1077- 1081.
2. Barker DJ, Winter FD, Osmond C, Margetts B, Simmonds SJ. (1989). Weight in infancy and
death from ischaemic hear disease. Lancet; 2: 577-580.
3. Barker DJ, Osmmond C, Simmonds SJ, Wield GA. (1993). The relation of small circumference
and thinness at birth to death from cardiovascular disaes in adult life. Br Med J ; 306 :422-426.
4. Barker DJ. (1993). Fetal nutrition and cardiovascular disease in adult, Lancet; 341 : 938
5. Barker DJ and Hales CN. (2001) The thrifty phenotype hypothesis. Br Med Built; 60 : 5-20.
6. Gluckman (2004). Environmental Effects via Developmental Plasticity Types of Response to
Early Environment; Science 305 “ 1733.
7. Barker DJ. (1994). The foetal origins of adult disease. Fetal and Maternal Medicine Review:
671 - 680.
8. Shakti Bhan Khamma, Kiranabala, Swasti, Kaushibi Dwivedeo (2007). Fetal Origin of Adult
Disease. Science; V9, 4 : 206-211.
9. Christopher Lau, John MR, Desai M, Ross MG, (2011). Fetal Programming of Adult Disease.
Implications for Prenatal Care. The American College of Obstetricians and Gynecologists,
V117; 4 : 978 - 984.
10. Hendrina A, De Boo, Harding JE (2006). The Development Origins of Adult Disease (Barker)
Hypothesis. Australian and New Zealand Journal of Obstetrics and Gynecology; 46 : 4 -14.
11. Barker DJ. (2007). The origins of the developmental origin theory. J. Inter Med.; 241:
412.
12. Phillips DIW (1996). Insulin resistance as a programmed response to fetal undernutrition.
Diabetologia; 39 : 1119- 122.
13. Waterland RA, Garza C (1999). Potential mechanisms of metabolic imptinting that lead to
chronic disease. Am J Clin Nutr; 69 : 179 -197.
14. Dover GJ (2009). Relation of birthweight to infant mortality and Complex Adult – Onset
Disease Trans Am Clin Climatol Assoc 120: 199 - 207.
15. Pei CH (2010). Low birthweight and Lung Function in Adulthood : Retrospective Cohort Study in China 1948 - 1996. Pediatrics; 125: 899 - 905.
16. Thompson C. (2001). Bith weight and the risk of depressive dicorder in late life. Br J
Psychiatry; 179 : 450 - 455.
17. Ravelli AC, van der Meulen JH, Osmmond C, Barker DJ, Bleker OP. (1999). Obesity at the
age 50y in men and women exposed to famine prenatally. Am J Clin Nutr; 70 : 811-816.
18. Roseboom TJ, van der Meulen JH, Ravelli AC, Osmmond C, Barker DJ, Bleker OP. (2003).
Perceived health of adults after prenatal exposure ti the Dutch famine. Pediatr Perinal
Epidemiol; 17 : 391-397.
19. Painter RC, Roseboom TJ, Bleker OP, (2005). Prenatal exposure to the Dutch famine and
disease in late life: an overview. Reprod Toxicol; 20 : 345-352.
20. Malaspina C. (2008), Acute maternal stress in pregnancy and schizophrenia in offspring : a
cohort prospective study. BMJ Psychiatry; 8 : 76.
21. Harding JE. (2001). The nutritional basis of the foetal origins of adult disease. Int J Epidemiol;
30 : 15 - 23.
22. Desai M, Crowther NJ, Lucas A, Hales CN. (1996). Organ-selective growth in the offspring
of protein-restricted mothers. Br J Nutr; 76: 59 -603.
23. Woodal SM, Johnston RM, Breier BH, Gluckman PD. (1996). Chronic maternal
undernutrition in the rat lead to delayed posnatal growth and elevated blood pressure of offspring, Pediatr Res; 40 : 438 - 443.
24. Ozanne SE, Hales CN. (1999). The longterm consequencies of intrauterine roteinmalnutrition for glucose metabolism. Proc Nutr Soc; 58; 615 - 619.
25. Kind KL, Clifton PM, Grant PA. (2003), Effect of maternal feed restriction during pregnancy on glucose tolerance in the adult guinea pig. Am J Physiol; 284 : R140 - R152.
26. Gardner DS, Tingey K, Can Bon BW. (2005). Programming of glucoe–insulin metabolism in
adult sheep after maternal undernutrition. Am J Phisiol; 289 : R947 - R954.9
27. Moore VM, Davies MJ, Willson KJ, Worsley A, Robinson JS. (2004). Dietary composition of
pregnant women is related to size of the baby at birth. J Nutr; 134 : 1820 - 1826.
28. Shiell AW, Campell-Brown M, Haselden S, Robinson S, Godfrey KM, Barker DJ. (2001).
High-meat, low- carbohydrate diet in pregnancy relation to adult blood pressure in offspring.
Hypertension; 38: 1282 -1288.
29. Yajnik CS. (2004), Early life - origins of insulin resistance and type 2 diabetes in India
and other Asian countries, J Nutr; 134 : 205 - 210.
30. Gillman MW, Rifas-Shiman SL, Kleinman KP, Rich Edwards JW, Lipshultz SE. (2004) Maternal
calcium intake and offspring blood pressure. Circulation; 110 :1990 - 1995.
31. Sofngwi E, Boudou P, Mauvais-Jarvis F. (2003). Effect of a diabetic environment in utero
on predisposition in type 2 diabetes. Lancet; 361: 1861 - 1865.
32. Buckley AT, Jaquiery AJ, Harding JE. (2005).Nutritional programming of adult disease. Cell
Tissue Res :73-79.
33. Reik W, Dean W, Walter J. (2001). Epigenetic reprogramming in mammalian development.
Science; 293 : 1089-1013.
34. Waterland RA, Jirtle RL. (2004) Early nutrition, epigenetic changes at transposons an
imprinting genes, and enhanced susceptibility in adult chronic diseases. Nutrition; 20 : 63-68.
35. Hales CN, Barker DJ. (1992) Type 2 (non-insuline dependent) diabetes mellitus: the
thrifty phenotype hypothesis. Diabetologia; 35: 695- 901.
36. Phillips DI. (1996): Inmsilinr resistance as a programmed response to foetal undernutrition.
Diabetologia; 39 : 1119 - 1121.
37. Eriksson JG, Forsen T, Tuomilehto J, Osmmonds C, Barker DJ (2003) Early adiposity
rebound in childhood and risk of Type 2 diabetes in adult life. Diabetologia; 46 : 190 - 194.
38. Seckl JR. (2004), Prenatl glucocorticoids and long-term programming. Eur J Endocrinol;
151 : U49 - U62.
39. Levitt NS, Lindsay RS, Holmes MC, Deskl JR. (1996), Dexamethasone in the last
week of pregnancy attenuates hippocarpan glucocorticoid receptor gene expression and
elevates blood pressure in the adult offspring in the rat. Euroendocrinology; 64 : 412 - 418.
40. Thorp JA, Jones PG, Knox E, Clark RH. (2002), Does antenatal corticoid therapy affect
birth weight and head circumference. Obst Gyyneol: 99 : 102 -108.
41. Hatterley AT, Tooke JE. (1999). Yhe foetal insulin hypothesis: an alternative explanation
of low birth weight with diabetes and vascular disease, Lancet; 353 : 1789 - 1792.
42. Day IN, Chen XH, Gaunt TR. (2004), Late life metabolic syndrome, early growth and
common polymorphism in the growth hormone and placental lactogen gene cluster. Endocrinol
Metab; 89 : 5569 - 5576.
43. Stein AD, Luney LH (2000), The relationship between maternal and offspring birth weight
after maternal prenatal famine exposure the Dutch Famine. Birth Cohort Study. Hum Biol; 72:
641 - 651.
44. Ibamez L, Potau N, Enriquez G, de Zegher F. (2000), Reduced uterine and ovarian size in
adolescent girls born small for gestational age. Pediatr Res; 17 : 575 - 577.
45. Reik W, Santos F, Dean W. (2003), Mammalian epigenomic reprogramming
the genomic for development and therapy. Theriogenology; 59 : 21 - 32.
in England and Wales. Lancet, 1: 1077- 1081.
2. Barker DJ, Winter FD, Osmond C, Margetts B, Simmonds SJ. (1989). Weight in infancy and
death from ischaemic hear disease. Lancet; 2: 577-580.
3. Barker DJ, Osmmond C, Simmonds SJ, Wield GA. (1993). The relation of small circumference
and thinness at birth to death from cardiovascular disaes in adult life. Br Med J ; 306 :422-426.
4. Barker DJ. (1993). Fetal nutrition and cardiovascular disease in adult, Lancet; 341 : 938
5. Barker DJ and Hales CN. (2001) The thrifty phenotype hypothesis. Br Med Built; 60 : 5-20.
6. Gluckman (2004). Environmental Effects via Developmental Plasticity Types of Response to
Early Environment; Science 305 “ 1733.
7. Barker DJ. (1994). The foetal origins of adult disease. Fetal and Maternal Medicine Review:
671 - 680.
8. Shakti Bhan Khamma, Kiranabala, Swasti, Kaushibi Dwivedeo (2007). Fetal Origin of Adult
Disease. Science; V9, 4 : 206-211.
9. Christopher Lau, John MR, Desai M, Ross MG, (2011). Fetal Programming of Adult Disease.
Implications for Prenatal Care. The American College of Obstetricians and Gynecologists,
V117; 4 : 978 - 984.
10. Hendrina A, De Boo, Harding JE (2006). The Development Origins of Adult Disease (Barker)
Hypothesis. Australian and New Zealand Journal of Obstetrics and Gynecology; 46 : 4 -14.
11. Barker DJ. (2007). The origins of the developmental origin theory. J. Inter Med.; 241:
412.
12. Phillips DIW (1996). Insulin resistance as a programmed response to fetal undernutrition.
Diabetologia; 39 : 1119- 122.
13. Waterland RA, Garza C (1999). Potential mechanisms of metabolic imptinting that lead to
chronic disease. Am J Clin Nutr; 69 : 179 -197.
14. Dover GJ (2009). Relation of birthweight to infant mortality and Complex Adult – Onset
Disease Trans Am Clin Climatol Assoc 120: 199 - 207.
15. Pei CH (2010). Low birthweight and Lung Function in Adulthood : Retrospective Cohort Study in China 1948 - 1996. Pediatrics; 125: 899 - 905.
16. Thompson C. (2001). Bith weight and the risk of depressive dicorder in late life. Br J
Psychiatry; 179 : 450 - 455.
17. Ravelli AC, van der Meulen JH, Osmmond C, Barker DJ, Bleker OP. (1999). Obesity at the
age 50y in men and women exposed to famine prenatally. Am J Clin Nutr; 70 : 811-816.
18. Roseboom TJ, van der Meulen JH, Ravelli AC, Osmmond C, Barker DJ, Bleker OP. (2003).
Perceived health of adults after prenatal exposure ti the Dutch famine. Pediatr Perinal
Epidemiol; 17 : 391-397.
19. Painter RC, Roseboom TJ, Bleker OP, (2005). Prenatal exposure to the Dutch famine and
disease in late life: an overview. Reprod Toxicol; 20 : 345-352.
20. Malaspina C. (2008), Acute maternal stress in pregnancy and schizophrenia in offspring : a
cohort prospective study. BMJ Psychiatry; 8 : 76.
21. Harding JE. (2001). The nutritional basis of the foetal origins of adult disease. Int J Epidemiol;
30 : 15 - 23.
22. Desai M, Crowther NJ, Lucas A, Hales CN. (1996). Organ-selective growth in the offspring
of protein-restricted mothers. Br J Nutr; 76: 59 -603.
23. Woodal SM, Johnston RM, Breier BH, Gluckman PD. (1996). Chronic maternal
undernutrition in the rat lead to delayed posnatal growth and elevated blood pressure of offspring, Pediatr Res; 40 : 438 - 443.
24. Ozanne SE, Hales CN. (1999). The longterm consequencies of intrauterine roteinmalnutrition for glucose metabolism. Proc Nutr Soc; 58; 615 - 619.
25. Kind KL, Clifton PM, Grant PA. (2003), Effect of maternal feed restriction during pregnancy on glucose tolerance in the adult guinea pig. Am J Physiol; 284 : R140 - R152.
26. Gardner DS, Tingey K, Can Bon BW. (2005). Programming of glucoe–insulin metabolism in
adult sheep after maternal undernutrition. Am J Phisiol; 289 : R947 - R954.9
27. Moore VM, Davies MJ, Willson KJ, Worsley A, Robinson JS. (2004). Dietary composition of
pregnant women is related to size of the baby at birth. J Nutr; 134 : 1820 - 1826.
28. Shiell AW, Campell-Brown M, Haselden S, Robinson S, Godfrey KM, Barker DJ. (2001).
High-meat, low- carbohydrate diet in pregnancy relation to adult blood pressure in offspring.
Hypertension; 38: 1282 -1288.
29. Yajnik CS. (2004), Early life - origins of insulin resistance and type 2 diabetes in India
and other Asian countries, J Nutr; 134 : 205 - 210.
30. Gillman MW, Rifas-Shiman SL, Kleinman KP, Rich Edwards JW, Lipshultz SE. (2004) Maternal
calcium intake and offspring blood pressure. Circulation; 110 :1990 - 1995.
31. Sofngwi E, Boudou P, Mauvais-Jarvis F. (2003). Effect of a diabetic environment in utero
on predisposition in type 2 diabetes. Lancet; 361: 1861 - 1865.
32. Buckley AT, Jaquiery AJ, Harding JE. (2005).Nutritional programming of adult disease. Cell
Tissue Res :73-79.
33. Reik W, Dean W, Walter J. (2001). Epigenetic reprogramming in mammalian development.
Science; 293 : 1089-1013.
34. Waterland RA, Jirtle RL. (2004) Early nutrition, epigenetic changes at transposons an
imprinting genes, and enhanced susceptibility in adult chronic diseases. Nutrition; 20 : 63-68.
35. Hales CN, Barker DJ. (1992) Type 2 (non-insuline dependent) diabetes mellitus: the
thrifty phenotype hypothesis. Diabetologia; 35: 695- 901.
36. Phillips DI. (1996): Inmsilinr resistance as a programmed response to foetal undernutrition.
Diabetologia; 39 : 1119 - 1121.
37. Eriksson JG, Forsen T, Tuomilehto J, Osmmonds C, Barker DJ (2003) Early adiposity
rebound in childhood and risk of Type 2 diabetes in adult life. Diabetologia; 46 : 190 - 194.
38. Seckl JR. (2004), Prenatl glucocorticoids and long-term programming. Eur J Endocrinol;
151 : U49 - U62.
39. Levitt NS, Lindsay RS, Holmes MC, Deskl JR. (1996), Dexamethasone in the last
week of pregnancy attenuates hippocarpan glucocorticoid receptor gene expression and
elevates blood pressure in the adult offspring in the rat. Euroendocrinology; 64 : 412 - 418.
40. Thorp JA, Jones PG, Knox E, Clark RH. (2002), Does antenatal corticoid therapy affect
birth weight and head circumference. Obst Gyyneol: 99 : 102 -108.
41. Hatterley AT, Tooke JE. (1999). Yhe foetal insulin hypothesis: an alternative explanation
of low birth weight with diabetes and vascular disease, Lancet; 353 : 1789 - 1792.
42. Day IN, Chen XH, Gaunt TR. (2004), Late life metabolic syndrome, early growth and
common polymorphism in the growth hormone and placental lactogen gene cluster. Endocrinol
Metab; 89 : 5569 - 5576.
43. Stein AD, Luney LH (2000), The relationship between maternal and offspring birth weight
after maternal prenatal famine exposure the Dutch Famine. Birth Cohort Study. Hum Biol; 72:
641 - 651.
44. Ibamez L, Potau N, Enriquez G, de Zegher F. (2000), Reduced uterine and ovarian size in
adolescent girls born small for gestational age. Pediatr Res; 17 : 575 - 577.
45. Reik W, Santos F, Dean W. (2003), Mammalian epigenomic reprogramming
the genomic for development and therapy. Theriogenology; 59 : 21 - 32.