Wells, Jonathan CK;
Desoye, Gernot;
Leon, David A;
(2024)
Reconsidering the developmental origins of adult disease paradigm: the ‘metabolic coordination of childbirth’ hypothesis.
Evolution, Medicine, and Public Health
, 12
(1)
pp. 50-66.
10.1093/emph/eoae002.
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Abstract
In uncomplicated pregnancies, birthweight is inversely associated with adult non-communicable disease (NCD) risk. One proposed mechanism is maternal malnutrition during pregnancy. Another explanation is that shared genes link birthweight with NCDs. Both hypotheses are supported, but evolutionary perspectives address only the environmental pathway. We propose that genetic and environmental associations of birthweight with NCD risk reflect coordinated regulatory systems between mother and fetus, that evolved to reduce risks of obstructed labour. First, the fetus must tailor its growth to maternal metabolic signals, as it cannot predict the size of the birth canal from its own genome. Second, we predict that maternal alleles that promote placental nutrient supply have been selected to constrain fetal growth and gestation length when fetally expressed. Conversely, maternal alleles that increase birth canal size have been selected to promote fetal growth and gestation when fetally expressed. Evidence supports these hypotheses. These regulatory mechanisms may have undergone powerful selection as hominin neonates evolved larger size and encephalisation, since every mother is at risk of gestating a baby excessive for her pelvis. Our perspective can explain the inverse association of birthweight with NCD risk across most of the birthweight range: any constraint of birthweight, through plastic or genetic mechanisms, may reduce the capacity for homeostasis and increase NCD susceptibility. However, maternal obesity and diabetes can overwhelm this coordination system, challenging vaginal delivery while increasing offspring NCD risk. We argue that selection on viable vaginal delivery played an over-arching role in shaping the association of birthweight with NCD risk.
| Type: | Article |
|---|---|
| Title: | Reconsidering the developmental origins of adult disease paradigm: the ‘metabolic coordination of childbirth’ hypothesis |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1093/emph/eoae002 |
| Publisher version: | http://dx.doi.org/10.1093/emph/eoae002 |
| Language: | English |
| Additional information: | © The Author(s) 2024. Published by Oxford University Press on behalf of the Foundation for Evolution, Medicine, and Public Health. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
| Keywords: | obstructed labour, fetal growth, noncommunicable disease, gestation, genetic conflict, DOHaD hypothesis |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Population, Policy and Practice Dept |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10186697 |
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