Barker’s hypothesis: Fetal origins of adult disease

Barker’s hypothesis: Fetal origins of adult disease

Fetal origins of adult disease is popularly known as Barker’s hypothesis. The concept was proposed by David Barker in 1990 and was noted in his book “Fetal and Infant Origins of Adult Disease”, published in 1992. The hypothesis proposed that adverse nutrition in early life as measured by birth weight increased susceptibility to adult diseases like metabolic syndrome with risk for coronary artery disease and stroke. An article by Barker DJ et al in 2009 mentioned that there is clear evidence that the pace and pathway of early growth is a major risk factor for development of chronic diseases including coronary artery disease, stroke, type 2 diabetes mellitus and hypertension [1].

They mentioned that malnutrition during fetal life, infancy and early childhood permanently change the structure and function of the body by ‘programming’. They reviewed the findings of the Helsinki Birth Cohort which had over thirteen thousand persons born during 1934 to 1944. There was an older cohort of over seven thousand persons born between 1924 to 1933. It was found that children who develop coronary artery disease and diabetes mellitus later grow slowly during fetal life and infancy. Thereafter their body mass indices increase rapidly.

Those who develop stroke later was found to grow slowly in fetal life, infancy and childhood. The authors also reviewed how the growth of girls during infancy, childhood and at puberty influences chronic disease in the next generation.

Calkins K et al who reviewed the concept in 2019 noted that clues to the fetal origin of adult disease concept originally arose from large 20th century European registries [2]. They mention that large diverse human cohorts and various animal models have extensively replicated these original observations. They considered that the implications were beyond the low birth weight population and include babies exposed to nutritional and non-nutritional stress during critical periods of development. Several diseases other than cardiovascular disorders also come under the purview of this concept.

The so-called ‘catch-up growth’ of low birth weight children may not be that ideal though caregivers often consider it as comforting. Catch-up growth reflects body’s natural response to nutrient deprivation. But this exponential childhood growth increases the risk for metabolic syndrome characterized by obesity, insulin resistance, dyslipidemia and hypertension.

The thrifty phenotype hypothesis proposes that poor nutrition in early life produces permanent changes in glucose-insulin metabolism. This is considered as the reason for epidemiological associations between poor fetal growth and later development of type 2 diabetes and metabolic syndrome. There is reduced capacity to secrete insulin and insulin resistance. These combined with effects of obesity, ageing and physical inactivity are the most important factors determining the development of type 2 diabetes [3].

References

1. Barker DJ, Osmond C, Kajantie E, Eriksson JG. Growth and chronic disease: findings in the Helsinki Birth Cohort. Ann Hum Biol. 2009 Sep-Oct;36(5):445-58. doi: 10.1080/03014460902980295. PMID: 19562567.
2. Calkins K, Devaskar SU. Fetal origins of adult disease. Curr Probl Pediatr Adolesc Health Care. 2011 Jul;41(6):158-76. doi: 10.1016/j.cppeds.2011.01.001. PMID: 21684471; PMCID: PMC4608552.
3. Hales CN, Barker DJ. The thrifty phenotype hypothesis. Br Med Bull. 2001;60:5-20. doi: 10.1093/bmb/60.1.5. PMID: 11809615.