Abnormal Development - Developmental Origins of Health and Disease

From Embryology
Embryology - 1 Dec 2023    Facebook link Pinterest link Twitter link  Expand to Translate  
Google Translate - select your language from the list shown below (this will open a new external page)

العربية | català | 中文 | 中國傳統的 | français | Deutsche | עִברִית | हिंदी | bahasa Indonesia | italiano | 日本語 | 한국어 | မြန်မာ | Pilipino | Polskie | português | ਪੰਜਾਬੀ ਦੇ | Română | русский | Español | Swahili | Svensk | ไทย | Türkçe | اردو | ייִדיש | Tiếng Việt    These external translations are automated and may not be accurate. (More? About Translations)

Introduction

Normal distribution curve on graph
Normal distribution curve (red)

Environmental derived abnormalities relate to maternal 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, now called "developmental origins of health and disease" (DOHAD or DOHaD) and also previously Fetal Origins Hypothesis, is based on the early statistical analysis carried out by David Barker (1938 - 2013) 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". Several origins have been suggested including: fetal undernutrition, endocrine (increased cortisol exposure), genetic susceptibility and accelerated postnatal growth.


More recently, discussion has occurred relating to how the data is both collected and analyzed, suggesting perhaps a smaller effect than original research suggested (see Lucas reference). Statistical methodology aside, these studies long-term periods of accurate data collection and we may have to wait some time for this research to develop.


Some research has now shifted from birth weight emphasis to that of the early postnatal infant growth. (More? Postnatal - Growth Charts)


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

| Birth-Weight

Some Recent Findings

  • Developmental Origins of Metabolic Disease[1] "Almost 2 billion adults in the world are overweight and more than half of them are classified as obese while nearly 1/3 of children globally experience poor growth and development. Given the vast amount of knowledge that has been gleaned from decades of research on growth and development, a number of questions remains as to why the world is now in the midst of a global epidemic of obesity accompanied by the "double burden of malnutrition" where overweight coexists with underweight and micronutrient deficiencies. This challenge to the human condition can be attributed to nutritional and environmental exposures during pregnancy that may program a fetus to have a higher risk of chronic diseases in adulthood. To explore this concept, frequently called the developmental origins of health and disease (DOHaD) or metabolic diseases (DOMD), this review considers a host of factors and physiological mechanisms that drive a fetus or child towards a higher risk of obesity, fatty liver disease, hypertension, and/or type 2 diabetes (T2D). To that end, this review explores the epidemiology of DOHaD with discussions focused on adaptations to human energetics, placental developmental, dysmetabolism, and key environmental exposures that act to promote chronic diseases in adulthood. These areas are complementary and additive in understanding how providing the best conditions for optimal growth can create the best possible conditions for lifelong health. Moreover, understanding both physiological as well as epigenetic and molecular mechanisms for DOMD is vital to most fully address the global issues of obesity and other chronic diseases."

10th Anniversary Edition of the DOHaD Journal[2] DOHaD Journal

  • Epigenetics and the Developmental Origins of Health and Disease: Parental environment signalling to the epigenome, critical time windows and sculpting the adult phenotype.[3] "The literature about Developmental Origins of Health and Disease (DOHaD) studies is considerably growing. Maternal and paternal environment, during all the development of the individual from gametogenesis to weaning and beyond, as well as the psychosocial environment in childhood and teenage, can shape the adult and the elderly person's susceptibility to her/his own environment and diseases. This non-conventional, non-genetic, inheritance is underlain by several mechanisms among which epigenetics is obviously central, due to the notion of memory of early decisional events during development even when this stimulus is gone, that is implied in Waddington's developmental concept. This review first summarizes the different mechanisms by which the environment can model the epigenome: receptor signalling, energy metabolism and signal mechanotransduction from extracellular matrix to chromatin. Then an overview of the epigenetic changes in response to maternal environment during the vulnerability time windows, gametogenesis, early development, placentation and foetal growth, and postnatal period, is described, with the specific example of overnutrition and food deprivation. The implication of epigenetics in DOHaD is obvious, however the precise causal chain from early environment to the epigenome modifications to the phenotype still needs to be deciphered."
  • Prenatal nicotine exposure increases osteoarthritis susceptibility in male elderly offspring rats via low-function programming of the TGFβ signaling pathway[4] "Epidemiological investigations indicate that effects related to prenatal adverse environments on the organs of the offspring could continue to adulthood. This study intends to confirm that prenatal nicotine exposure (PNE) increases the susceptibility of osteoarthritis (OA) in the male offspring, and to explore the potential intrauterine programming mechanism. During pregnancy, rats were divided into a PNE group and a control group. After birth, rats were given a high-fat diet for 6 months and long-distance running for 6 weeks. The rats were euthanized at 18 months after birth (PM18) and on gestational day 20 (GD20), respectively. Knee joints were collected for histochemistry, immunohistochemistry, and quantitative polymerase chain reaction (qPCR) assays. Histological analyses and the Mankin's score showed increased cartilage destruction and accelerated OA progression in adult offspring from the PNE group. Immunohistochemistry results showed decreased expression of transforming growth factor beta (TGFβ) signaling pathway. Furthermore, the expression of apoptosis factors (caspase-3 and caspase-8), inflammatory factors [interleukin (IL)-1, IL-6] and matrix degradation enzymes [matrix metalloproteinase (MMP)-3, MMP-13] were also significantly increased. Traced back to the intrauterine period, it was found that the number of chondrocytes and the contents of Col2A1 and aggrecan in the matrix in the PNE group were decreased. And, the expression of the TGFβ signaling pathway was inhibited. These results suggested that PNE enhanced the susceptibility of OA in male elderly offspring rats by down-regulating TGFβ signaling, which increased articular cartilage local inflammation, matrix degradation, and cell apoptosis. This study confirmed the developmental origin of OA, and clarified the congenital and the living environment impact on the occurrence and development of OA. Our findings provide a theoretical and experimental basis for OA early prevention." smoking TGF-beta
  • Acrylamide: A review about its toxic effects in the light of Developmental Origin of Health and Disease (DOHaD) concept[5] "The endocrine system is highly sensitive to endocrine-disrupting chemicals (EDC) which interfere with metabolism, growth and reproduction throughout different periods of life, especially in the embryonic and pubertal stages, in which gene reprogramming may be associated with impaired development and control of tissues/organs even in adulthood. Acrylamide is considered a potential EDC and its main source comes from fried, baked and roasted foods that are widely consumed by children, teenagers and adults around the world. This review aimed to present some aspects regarding the acrylamide formation, its toxicokinetics, the occurrence of acrylamide in foods, the recent findings about its effects on different systems and the consequences for the human healthy."
  • DOHAD2017 10th anniversary World Congress in Rotterdam.
  • Delivery of a small for gestational age infant and greater maternal risk of ischemic heart disease[6] "Delivery of a small for gestational age (SGA) infant has been associated with increased maternal risk of ischemic heart disease (IHD). ...Risk of maternal IHD was evaluated in a population based cross-sectional study of 6,608 women with a prior live term birth who participated in the National Health and Nutrition Examination Survey (1999-2006), a probability sample of the U.S. population....Giving birth to a SGA infant is strongly and independently associated with IHD and a potential risk factor that precedes IHD by decades. A pregnancy that produces a SGA infant may induce long-term cardiovascular changes that increase risk for IHD." (Note this paper refers to a Maternal not Neonatal Risk).
More recent papers  
Mark Hill.jpg
PubMed logo.gif

This table allows an automated computer search of the external PubMed database using the listed "Search term" text link.

  • This search now requires a manual link as the original PubMed extension has been disabled.
  • The displayed list of references do not reflect any editorial selection of material based on content or relevance.
  • References also appear on this list based upon the date of the actual page viewing.


References listed on the rest of the content page and the associated discussion page (listed under the publication year sub-headings) do include some editorial selection based upon both relevance and availability.

More? References | Discussion Page | Journal Searches | 2019 References | 2020 References

Search term: Developmental Origins of Health and Disease | DoHaH | Barker Hypothesis | Fetal Origins Hypothesis

Older papers  
These papers originally appeared in the Some Recent Findings table, but as that list grew in length have now been shuffled down to this collapsible table.

See also the Discussion Page for other references listed by year and References on this current page.

  • Fetal origins of adult diabetes[7] "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[8] "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[9] "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)[10] "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

David Barker (1938 - 2013)

There were some key papers by David Barker that initially studied UK birth weight data that gave rise to this area of research.[11][12][13]

“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.[14]

  • 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.

David Barker (1938 - 2013)

Professor David Barker FRS, born 29 June 1938; died 27 August 2013.


"David Barker was one of the most influential clinical epidemiologists of our time. He challenged the idea that chronic disorders such as diabetes and cardiovascular disease are explained only by bad genes and unhealthy adult lifestyles. His 'Barker hypothesis' proposed that the fetal environment and early infant health permanently programme the body's metabolism and growth, and thus determine the pathologies of old age. Initially controversial, his ideas triggered an explosion of research worldwide into the relationship between early development and adult disease."[15]
"David Barker received the prestigious Richard Doll Prize in 2011 given by the International Epidemiology Association (IEA). This prize is given to a person who deserved to be a candidate for the Nobel Prize but would probably not be accepted by the Nobel Committee because of the way epidemiologic research is structured and conducted. In epidemiology we can seldom point towards a specific article or even a few articles or a single person who, by himself alone, changes the way we think."[16]


Links: memorial service

Fetal Growth Articles

Fetal growth.[17] "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.[18] "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."

Diabetes

Fetal origins of adult diabetes[7] "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[8] "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."

Renal

The Brenner hypothesis is a clinical hypothesis that states, individuals with a congenital reduction in nephron number have a much greater likelihood of developing adult hypertension and subsequent renal failure.[19] The hypothesis was developed in the 1980's by Barry Brenner a neurologist and researcher at the Brigham and Women's Hospital. This "congenital reduction" also fits with this DOHAD hypothesis.


Links: Renal System Development | Barry Brenner

Cardiovascular

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[20] 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.")

In contrast, a recent study of only postnatal growth (to 3 years of age) identified "Slower infant weight gain was not associated with poorer neurodevelopmental outcomes in healthy, term-born 3-year-old children."[21]

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

  1. ↑ Hoffman DJ, Powell TL, Barrett ES & Hardy DB. (2020). Developmental Origins of Metabolic Disease. Physiol Rev , , . PMID: 33270534 DOI.
  2. ↑ Poston L. (2019). 10th Anniversary Edition of the DOHaD Journal. J Dev Orig Health Dis , 10, 605. PMID: 31615582 DOI.
  3. ↑ Safi-Stibler S & Gabory A. (2019). Epigenetics and the Developmental Origins of Health and Disease: Parental environment signalling to the epigenome, critical time windows and sculpting the adult phenotype. Semin. Cell Dev. Biol. , , . PMID: 31587964 DOI.
  4. ↑ Chen B, Lu KH, Ni QB, Li QX, Gao H, Wang H & Chen LB. (2019). Prenatal nicotine exposure increases osteoarthritis susceptibility in male elderly offspring rats via low-function programming of the TGFβ signaling pathway. Toxicol. Lett. , , . PMID: 31299270 DOI.
  5. ↑ Matoso V, Bargi-Souza P, Ivanski F, Romano MA & Romano RM. (2019). Acrylamide: A review about its toxic effects in the light of Developmental Origin of Health and Disease (DOHaD) concept. Food Chem , 283, 422-430. PMID: 30722893 DOI.
  6. ↑ Bukowski R, Davis KE & Wilson PW. (2012). Delivery of a small for gestational age infant and greater maternal risk of ischemic heart disease. PLoS ONE , 7, e33047. PMID: 22431995 DOI.
  7. ↑ 7.0 7.1 Kanaka-Gantenbein C. (2010). Fetal origins of adult diabetes. Ann. N. Y. Acad. Sci. , 1205, 99-105. PMID: 20840260 DOI.
  8. ↑ 8.0 8.1 Kaijser M, Bonamy AK, Akre O, Cnattingius S, Granath F, Norman M & Ekbom A. (2009). Perinatal risk factors for diabetes in later life. Diabetes , 58, 523-6. PMID: 19066311 DOI.
  9. ↑ Heijmans BT, Tobi EW, Stein AD, Putter H, Blauw GJ, Susser ES, Slagboom PE & Lumey LH. (2008). Persistent epigenetic differences associated with prenatal exposure to famine in humans. Proc. Natl. Acad. Sci. U.S.A. , 105, 17046-9. PMID: 18955703 DOI.
  10. ↑ Eriksson JG. (2005). The fetal origins hypothesis--10 years on. BMJ , 330, 1096-7. PMID: 15891207 DOI.
  11. ↑ Barker DJ. (1990). The fetal and infant origins of adult disease. BMJ , 301, 1111. PMID: 2252919
  12. ↑ Barker DJ & Martyn CN. (1992). The maternal and fetal origins of cardiovascular disease. J Epidemiol Community Health , 46, 8-11. PMID: 1573367
  13. ↑ Barker DJ. (1997). Fetal nutrition and cardiovascular disease in later life. Br. Med. Bull. , 53, 96-108. PMID: 9158287
  14. ↑ Lucas A, Fewtrell MS & Cole TJ. (1999). Fetal origins of adult disease-the hypothesis revisited. BMJ , 319, 245-9. PMID: 10417093
  15. ↑ Cooper C. (2013). David Barker (1938-2013). Nature , 502, 304. PMID: 24132283 DOI.
  16. ↑ Olsen J. (2014). David Barker (1938-2013)--a giant in reproductive epidemiology. Acta Obstet Gynecol Scand , 93, 1077-80. PMID: 24628330 DOI.
  17. ↑ Mongelli M & Gardosi J. (2000). Fetal growth. Curr. Opin. Obstet. Gynecol. , 12, 111-5. PMID: 10813572
  18. ↑ Holemans K, Aerts L & Van Assche FA. (1998). Fetal growth and long-term consequences in animal models of growth retardation. Eur. J. Obstet. Gynecol. Reprod. Biol. , 81, 149-56. PMID: 9989859
  19. ↑ Brenner BM, Garcia DL & Anderson S. (1988). Glomeruli and blood pressure. Less of one, more the other?. Am. J. Hypertens. , 1, 335-47. PMID: 3063284
  20. ↑ Shenkin SD, Starr JM, Pattie A, Rush MA, Whalley LJ & Deary IJ. (2001). Birth weight and cognitive function at age 11 years: the Scottish Mental Survey 1932. Arch. Dis. Child. , 85, 189-96. PMID: 11517097
  21. ↑ Belfort MB, Rifas-Shiman SL, Rich-Edwards JW, Kleinman KP, Oken E & Gillman MW. (2008). Infant growth and child cognition at 3 years of age. Pediatrics , 122, e689-95. PMID: 18762504 DOI.

Journal

Edited by Peter Gluckman, Mark Hanson. Published by Cambridge University Press, Cambridge, 2006, £85.00, pp 519. ISBN 0-521-84743-5

Reviews

Calkins K & Devaskar SU. (2011). Fetal origins of adult disease. Curr Probl Pediatr Adolesc Health Care , 41, 158-76. PMID: 21684471 DOI.

Geelhoed JJ & Jaddoe VW. (2010). Early influences on cardiovascular and renal development. Eur. J. Epidemiol. , 25, 677-92. PMID: 20872047 DOI.

Kanaka-Gantenbein C. (2010). Fetal origins of adult diabetes. Ann. N. Y. Acad. Sci. , 1205, 99-105. PMID: 20840260 DOI.

Cota BM & Allen PJ. (2010). The developmental origins of health and disease hypothesis. Pediatr Nurs , 36, 157-67. PMID: 20687308

Tamashiro KL & Moran TH. (2010). Perinatal environment and its influences on metabolic programming of offspring. Physiol. Behav. , 100, 560-6. PMID: 20394764 DOI.

Langley-Evans SC & McMullen S. (2010). Developmental origins of adult disease. Med Princ Pract , 19, 87-98. PMID: 20134170 DOI.

Wadhwa PD, Buss C, Entringer S & Swanson JM. (2009). Developmental origins of health and disease: brief history of the approach and current focus on epigenetic mechanisms. Semin. Reprod. Med. , 27, 358-68. PMID: 19711246 DOI.

Articles

Mook-Kanamori DO, Steegers EA, Eilers PH, Raat H, Hofman A & Jaddoe VW. (2010). Risk factors and outcomes associated with first-trimester fetal growth restriction. JAMA , 303, 527-34. PMID: 20145229 DOI.

Search Pubmed

Search Pubmed: barker hypothesis | fetal origins hypothesis | fetal programming hypothesis |


External Links

External Links Notice - The dynamic nature of the internet may mean that some of these listed links may no longer function. If the link no longer works search the web with the link text or name. Links to any external commercial sites are provided for information purposes only and should never be considered an endorsement. UNSW Embryology is provided as an educational resource with no clinical information or commercial affiliation.



Glossary Links

Glossary: A | B | C | D | E | F | G | H | I | J | K | L | M | N | O | P | Q | R | S | T | U | V | W | X | Y | Z | Numbers | Symbols | Term Link


Cite this page: Hill, M.A. (2023, December 1) Embryology Abnormal Development - Developmental Origins of Health and Disease. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Abnormal_Development_-_Developmental_Origins_of_Health_and_Disease

What Links Here?
© Dr Mark Hill 2023, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G
Retrieved from ‘https://embryology.med.unsw.edu.au/embryology/index.php?title=Abnormal_Development_-_Developmental_Origins_of_Health_and_Disease&oldid=420657’
Powered by MediaWiki