University of Arkansas at Little Rock

Fetal Origins of Adult Disease

Sasi Cumbie

Professor Connor Pearce

Composition 1

12/04/22
The framework originally labelled ‘the Barker hypothesis’ has become among the more

important frameworks on distal temporal determinants, suggesting that chronic illness is

initiated by processes at prenatal stages. Low birthweight has been consistently shown to

be associated with coronary heart disease and its biological risk factors. The fetal origins

of adult disease hypothesis suggests that risk factors from intrauterine environmental

exposures affect the fetus' development during sensitive periods and increases the risk of

specific diseases in adult life.

In early studies investigating the origins of heart disease, Barker and his colleagues

linked the standardized mortality ratios for cardiovascular disease for 16,000 individuals,

born in Hertfordshire from 1911–1930, to birth data for those individuals. The data

suggested that low weight, small head circumference and low mass/height at birth was

associated with an increased risk for coronary heart disease in adulthood. The effects of

low birthweight are increased by slow infant growth and rapid weight gain in childhood.

The hypothesis that adult disease has fetal origins is probable, but much supported

evidence is flawed by the incomplete and incorrect statistical interpretation. When size in

early life is related to later health outcomes, it is probably the change in size between the

postnatal centile crossing rather than fetal biology that is implicated. Even when the birth

size is directly related to later outcome, some studies fail to explore whether this is partly

or entirely explained by postnatal rather than prenatal factors. These considerations are

critical to understanding the biology and timing of “programming”, the direction of future

research, and future public health interventions.

Low birth weight, poor fetal growth and nutrition are all linked to coronary artery

disease, hypertension, obesity, and insulin resistance. Implications of the FOAD extend
beyond the low-birth-weight population and include babies exposed to stress, both

nutritional and non-nutritional, during different critical periods of development, which

ultimately result in a disease state. Today’s low birth weight is associated with a host of

chronic diseases ranging from type II diabetes mellitus, cancer, osteoporosis, and various

psychiatric illnesses. This theory relies on the fact that there exist specific developmental

periods whereby an organism is “plastic” or “sensitive” to it’s environment.

The first reported links between birth weight and later health illness’s related to blood

pressure. In 1978 Ellison presented data linking lower birth weight and higher blood

pressure in 3,155 prospectively followed 7-year-olds. Genetic factors may also be

involved. For example, genes that determine vascular endothelial function may be related

to both resistance in the fetoplacental circulation and the individuals later risk of

cardiovascular disease risk. It has also been suggested that telomere attrition or variation

in mitochondrial DNA may also be involved.

Potential factors compromising fetal development include chronic placental

insufficiency, undernutrition, hypoxemia, maternal cigarette smoking, infection and

preterm birth. Because preterm birth itself has the potential to result in persistent

alterations in postnatal development, it is necessary to consider the effects of preterm

birth in offspring exposed to intra-uterine growth restriction. In the neonatal period,

preterm birth is associated with an increased risk of respiratory distress syndrome,

periventricular hemorrhage, and hypocalcemia, while longitudinal studies have shown an

increased rate of asthma, cerebral palsy, and impaired cognitive function. It is apparent

that preterm birth, in the presence of placental insufficiency and intra-uterine growth
restriction, can exert additive effects on respiratory and cardiovascular development after

birth.

The FOAD-hypothesis has also been criticized on account of how one should interpret

the statistical association between anthropometric measures at birth, and outcomes in

adulthood. As for any observed association, the relationship could be a result of chance,

bias, confounders, or it may be a genuine causal effect. Many of the early criticisms of

the observed association between anthropometric measures at birth and later disease

concerned the lack of adjustment for important third variables. For example,

socioeconomic status is associated with birthweight, coronary heart disease and life-style

factors such as diet, cigarette smoking and physical exercise. This makes socioeconomic

status a plausible confounder, as it may influence birthweight and disease in adult life,

but also lifestyle factors associated with adult disease such as smoking and physical

exercise. A few later studies have tried to adjust for candidate confounders and propose

that the association remains.

The concept of a fetal origin of adult disease have been extended well beyond coronary

heart disease and being a risk factor for coronary heart disease, and now includes

investigations of the development of the central nervous system, early origins of adult

mental health and cognitive function. Although the FOAD-hypothesis has been expanded,

in depth since its conception, the hypothesis remains controversial, and several objections

have been raised. The FOAD-hypothesis has expanded greatly during the past decades

and is influential in medicine and epidemiology. Recently, the World Health

Organization included low birthweight as a risk for factor for cardiovascular disease. The

heart of the hypothesis, that environmental influences during gestation have an effect on
later development, is a major insight and constitutes a complement to genetic and more

proximal factors (such as adult lifestyle) as causes of adult disease. As the search for

determinants for disease and health continues, the FOAD-hypothesis is likely to remain

an important perspective, it may however be better positioned as part of a life course

epidemiology, than as an independent hypothesis.

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AND PRETERM LAMBS FOLLOWING FETAL GROWTH

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