UNSW Embryology

Abnormal Development - Fetal Origins Hypothesis

© Dr Mark Hill (2008)

Acknowledgements

Introduction

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)

See also: Intrauterine Growth Retardation (IUGR) | BMJ Collection of Articles on Barker Hypothesis

Page Links: Introduction | Some Recent Findings | Environmental influences originate in utero | NCBI Bookshelf | Birth Terms | References | References |

Some Recent Findings

Alexander BT. Fetal programming of hypertension. Am J Physiol Regul Integr Comp Physiol. 2006 Jan;290(1):R1-R10.

Environmental influences originate in utero

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: Arch Dis Child 2001;85:189-196

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)

References

• Barker DJ. The fetal and infant origins of adult disease. BMJ. 1990 Nov 17;301(6761):1111.
• Barker DJ, Martyn CN. The maternal and fetal origins of cardiovascular disease. J Epidemiol Community Health. 1992 Feb;46(1):8-11.
• Barker DJ. Fetal nutrition and cardiovascular disease in later life. Br Med Bull. 1997 Jan;53(1):96-108.
• Wilson J. The Barker hypothesis. An analysis. Aust N Z J Obstet Gynaecol. 1999 Feb;39(1):1-7.
• Lucas A, Fewtrell MS, Cole TJ. Fetal origins of adult disease-the hypothesis revisited. BMJ. 1999 Jul 24;319(7204):245-9.
  • Link to full article
  • 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.
• Mongelli M, Gardosi J. Fetal growth. Curr Opin Obstet Gynecol. 2000 Apr;12(2):111-5.
  • 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.
• Holemans K, Aerts L, Van Assche FA. Fetal growth and long-term consequences in animal models of growth retardation. Eur J Obstet Gynecol Reprod Biol. 1998 Dec;81(2):149-56.
  • 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.

References

• Barker DJ. The fetal and infant origins of adult disease. BMJ. 1990 Nov 17;301(6761):1111.
• Barker DJ, Martyn CN. The maternal and fetal origins of cardiovascular disease. J Epidemiol Community Health. 1992 Feb;46(1):8-11.
• Barker DJ. Fetal nutrition and cardiovascular disease in later life. Br Med Bull. 1997 Jan;53(1):96-108.
• Wilson J. The Barker hypothesis. An analysis. Aust N Z J Obstet Gynaecol. 1999 Feb;39(1):1-7.
• Lucas A, Fewtrell MS, Cole TJ. Fetal origins of adult disease-the hypothesis revisited. BMJ. 1999 Jul 24;319(7204):245-9.
  • Link to full article
  • 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.
• Mongelli M, Gardosi J. Fetal growth. Curr Opin Obstet Gynecol. 2000 Apr;12(2):111-5.
  • 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.
• Holemans K, Aerts L, Van Assche FA. Fetal growth and long-term consequences in animal models of growth retardation. Eur J Obstet Gynecol Reprod Biol. 1998 Dec;81(2):149-56.
  • 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.

Quick Links

Development Notes ----------------- Menstrual Cycle Week 1 Week 2 Week 3 Week 4 Placenta Serial Images Genes/DNA Molecular Dev Abnormal Dev Postnatal Dev Notes Index

System Notes ----------------- Heart/Cardiovascular Respiratory Coelomic cavity Gastrointestinal Tract Head and Neck Neural Neural Crest Eye Ear Nose Endocrine Urogenital Musculoskeletal Integumentary

Finally

For those wanting to see dynamic processes of development (and have a reasonably quick connection) then the Movies pages are good for watching changes occur.

Movies ----------------- Embryo Growth Carnegie Stages Ultrasound Images Stage 13/14 Embryo Stage 22 Embryo Heart Septation Neural Neural Crest Other Embryos Larsen Movies

Other Embryos

The study of human development has relied extensively on studying the process in other model animals. For those wanting to see the process of development in other species then the other embryos pages are a good start.

Other Embryos ----------------- Chicken Fly Frog Mouse Rabbit Rat Worm Zebrafish Guinea Pig

UNSW Embryology ISBN: 978 0 7334 2609 4

UNSW CRICOS Provider Code No. 00098G