The thrifty phenotype hypothesis: The association between ultrasound and Doppler studies in fetal growth restriction and the development of adult disease

  • Jacob Bar
    Affiliations
    Department of Obstetrics and Gynecology, Edith Wolfson Medical Center, Holon, Israel (Dr. Bar, Dr Weiner, and Dr. Levy)

    Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel (Dr. Bar, Dr. Weiner, Dr. Levy, and Dr. Gilboa)
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  • Eran Weiner
    Correspondence
    Corresponding author: Eran Weiner, MD.
    Affiliations
    Department of Obstetrics and Gynecology, Edith Wolfson Medical Center, Holon, Israel (Dr. Bar, Dr Weiner, and Dr. Levy)

    Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel (Dr. Bar, Dr. Weiner, Dr. Levy, and Dr. Gilboa)
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  • Michal Levy
    Affiliations
    Department of Obstetrics and Gynecology, Edith Wolfson Medical Center, Holon, Israel (Dr. Bar, Dr Weiner, and Dr. Levy)
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  • Yinon Gilboa
    Affiliations
    Ultrasound Unit, Helen Schneider Comprehensive Women's Health Center, Rabin Medical Center, Beilinson Campus, Petach Tikva, Israel (Dr. Gilboa)

    Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel (Dr. Bar, Dr. Weiner, Dr. Levy, and Dr. Gilboa)
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Published:September 01, 2021DOI:https://doi.org/10.1016/j.ajogmf.2021.100473
      Barker pioneered the idea that the epidemic of coronary heart disease in Western countries in the 20th century, which paradoxically coincided with improved standards of living and nutrition, has its origin in fetal life. Indeed, there is substantial evidence associating low birthweight because of fetal growth restriction with an increased risk of vascular disease in later adult life. These conclusions led to the second part of the Barker hypothesis, the thrifty phenotype, in which adaptation to undernutrition in fetal life leads to permanent metabolic and endocrine changes. Such changes are beneficial if the undernutrition persists after birth but may predispose the individual to obesity and impaired glucose tolerance if conditions improve. The hypothesis assumes that a poor nutrient supply during a critical period of in utero life may “program” a permanent structural or functional change in the fetus, thereby altering the distribution of cell types, gene expression, or both. The fetus, in response to placental undernutrition and to maintain sufficient vascular supply to the brain, decreases resistance to blood flow in the middle cerebral artery. Simultaneously, because of the limited blood supply to the fetus, the arterial redistribution process is accompanied by increased resistance to flow to other fetal vital organs, such as the heart, kidneys, liver, and pancreas. It may explain why individuals exposed to ischemic changes in utero develop dyslipidemia, lower nephron number, and impaired glucose tolerance, all factors contributing to metabolic syndrome later in life. Nevertheless, support for the hypotheses comes mainly from studies in rodents and retrospective epidemiologic studies. This review focused on ultrasound and Doppler studies of human fetal growth restriction in several fetal organs: the placenta, fetal circulation, brain, heart, kidneys, adrenal glands, liver, and pancreas. Support for the hypothesis was provided by animal studies involving conditions that create fetuses with growth restriction with effects on various fetal organs and by human studies that correlate impaired fetal circulation with the in utero development and function of fetal organs.

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