Abnormal Development - Fetal Origins Hypothesis

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Maternal derived abnormalities relate to lifestyle, environment and nutrition and while some of these directly effect embryonic development, there is also growing evidence that some effects are more subtle and relate to later life health events. This theory is based on the early statistical analysis carried out by Barker of low birth weight data collected in the early 1900's in the south east of England which he then compared with these same babies later health outcomes. The theory was therefore originally called the "Barker Hypothesis" and has recently been renamed as "fetal origins" or "programming".

There have also been some issues relating to how the data is both collected and analyzed. (see Lucas reference)

Abnormality Links: abnormal development | abnormal genetic | abnormal environmental | Unknown | teratogens | ectopic pregnancy | cardiovascular abnormalities | coelom abnormalities | endocrine abnormalities | gastrointestinal abnormalities | genital abnormalities | head abnormalities | integumentary abnormalities | musculoskeletal abnormalities | limb abnormalities | neural abnormalities | neural crest abnormalities | placenta abnormalities | renal abnormalities | respiratory abnormalities | hearing abnormalities | vision abnormalities | twinning | Developmental Origins of Health and Disease |  ICD-11
Historic Embryology  
1915 Congenital Cardiac Disease | 1917 Frequency of Anomalies in Human Embryos | 1920 Hydatiform Degeneration Tubal Pregnancy | 1921 Anencephalic Embryo | 1921 Rat and Man | 1966 Congenital Malformations

Some Recent Findings

  • Fetal origins of adult diabetes[1] "According to the fetal origin of adult diseases hypothesis, the intrauterine environment through developmental plasticity may permanently influence long-term health and disease. Therefore, intrauterine growth restriction (IUGR), due either to maternal, placental, or genetic factors, may permanently alter the endocrine-metabolic status of the fetus, driving an insulin resistance state that can promote survival at the short term but that facilitates the development of type 2 diabetes mellitus and metabolic syndrome in adult life, especially when the intrauterine nutrient restriction is followed by a postnatal obesogenic environment."
  • Perinatal Risk Factors for Diabetes in Later Life[2] "Low birth weight is consistently associated with an increased risk of non-insulin dependent diabetes mellitus in adulthood, but the individual contributions from poor fetal growth and preterm birth are not known. ....Our results suggest that the association between low birth weight and diabetes is due to factors associated with both poor fetal growth and short gestational age."
  • Persistent epigenetic differences associated with prenatal exposure to famine in humans[3] "Here we show that individuals who were prenatally exposed to famine during the Dutch Hunger Winter in 1944-45 had, 6 decades later, less DNA methylation of the imprinted IGF2 gene compared with their unexposed, same-sex siblings. The association was specific for periconceptional exposure, reinforcing that very early mammalian development is a crucial period for establishing and maintaining epigenetic marks." (More? see also Molecular Development - Epigenetics)
  • The fetal origins hypothesis—10 years on (2005)[4]"In 1995 David Barker wrote: “The fetal origins hypothesis states that fetal undernutrition in middle to late gestation, which leads to disproportionate fetal growth, programmes later coronary heart disease.”1 Now, 10 years later, the importance of events before birth for lifetime health has been confirmed in many populations."

Barker Hypothesis

There were some key papers by David Barker that initially studied UK birth weight data that gave rise to this area of research.[5][6][7]

“The fetal origins hypothesis states that fetal undernutrition in middle to late gestation, which leads to disproportionate fetal growth, programmes later coronary heart disease.”

See also Fetal origins of adult disease-the hypothesis revisited.[8]

  • The hypothesis that adult disease has fetal origins is plausible, but much supportive evidence is flawed by incomplete and incorrect statistical interpretation.
  • When size in early life is related to later health outcomes only after adjustment for current size, it is probably the change in size between these points (postnatal centile crossing) rather than fetal biology that is implicated.
  • Even when birth size is directly related to later outcome, some studies fail to explore whether this is partly or wholly explained by postnatal rather that prenatal factors.
  • These considerations are critical to understanding the biology and timing of "programming," the direction of future research, and future public health interventions.

Fetal Growth Articles

Fetal growth.[9] "Recent epidemiological and experimental studies show that abnormal fetal growth can lead to serious complications, including stillbirth, perinatal morbidity and disorders extending well beyond the neonatal period. It is now clear that the intrauterine milieu is as important as genetic endowment in shaping the future health of the conceptus. Maternal characteristics such as weight, height, parity and ethnic group need to be adjusted for, and pathological factors such as smoking excluded, to establish appropriate standards and improve the distinction between what is normal and abnormal. Currently, the aetiology of growth restriction is not well understood and preventative measures are ineffective. Elective delivery remains the principal management option, which emphasizes the need for better screening techniques for the timely detection of intrauterine growth failure."

Fetal growth and long-term consequences in animal models of growth retardation.[10] "Perturbations of the maternal environment involve an abnormal intrauterine milieu for the developing fetus. The altered fuel supply (depends on substrate availability, placental transport of nutrients and uteroplacental blood flow) from mother to fetus induces alterations in the development of the fetal endocrine pancreas and adaptations of the fetal metabolism to the altered intrauterine environment, resulting in intrauterine growth retardation. The alterations induced by maternal diabetes or maternal malnutrition (protein-calorie or protein deprivation) have consequences for the offspring, persisting into adulthood and into the next generation."

Neural Effects

The hypothesis proposes influences cause permanent changes in embryo/fetus, low birth weight, predisposition to chronic disease in adult life. Malnutrition in utero affects brain development, "low birth weight" or intrauterine growth restricted babies fare less well on measures of mental development in later life studies compared low birth weight babies (<2500 g) with controls, show impairment in neuro developmental tests up to age 11.

Intelligence is a combination of genetic and environmental influences (relative contributions of which are not yet established) and may vary over lifespan.

(Modified Text from[11] Note the commment made by Emeritus Professor P Pharaoh "One caveat that should be borne in mind, concerns the tests that are used to assess cognitive function. What do these tests actually measure? Ideally they measure innate mental ability, whatever that is, at a point in time.")

NCBI Bookshelf

Resources available from online textbooks freely available at National Library of Medicine (USA), National Center for Biotechnology Information.

Health Services/Technology Assessment Text (HSTAT)

Evidence table 3. Studies Evaluating Association of LBW and Cerebral Palsy and Neurological Outcomes Part I

Evidence table 5B. Studies Evaluating Association of LBW of Audiology Outcomes Part II

Birth Terms

  • Premature infant - An infant born before 37 weeks of estimated gestational age
  • Low birth weight - Birth weight < 2,500 g (5 lb, 8 oz)
  • Very low birth weight - Birth weight < 1,500 g (3 lb, 5 oz)
  • Extremely low birth weight - Birth weight < 1,000 g (2 lb, 3 oz)


  1. <pubmed>20840260</pubmed>
  2. <pubmed>19066311</pubmed>
  3. <pubmed>18955703</pubmed>
  4. <pubmed>15891207</pubmed>
  5. <pubmed>2252919</pubmed>
  6. <pubmed>1573367</pubmed>
  7. <pubmed>9158287</pubmed>
  8. <pubmed>10417093</pubmed>| BMJ
  9. <pubmed>10813572</pubmed>
  10. <pubmed>9989859</pubmed>
  11. <pubmed>11517097</pubmed>

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Cite this page: Hill, M.A. (2021, December 6) Embryology Abnormal Development - Fetal Origins Hypothesis. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Abnormal_Development_-_Fetal_Origins_Hypothesis

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© Dr Mark Hill 2021, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G