Placental sufficiency is relational: a demand–supply hypothesis for divergent maternal and fetal expressions of gestational disease
- 1Department of Obstetrics and Gynecology, “Victor Babeş” University of Medicine and Pharmacy , ,
- 2Fetal Medicine Center, Medicis/MedLife Hospital , ,
Abstract
Placental insufficiency is usually identified indirectly—through the maternal syndrome, the growth restriction it causes or lesions found after delivery. None of these defines the placenta’s oxygen-transfer function, and each can be absent while fetal support is already inadequate. We propose that this function is relational: it should be defined by the balance between the fetal oxygen requirement, Co(t), and the effective capacity of the integrated maternal–placental–fetal chain to supply oxygen, Os(t), assessed at the fetal receiving end. Their difference, Δ(t) = Co(t) − Os(t), is a latent state rather than a measurable quantity; a positive imbalance denotes insufficiency of the integrated transfer relation and does not by itself identify the limiting component or imply intrinsic placental pathology, which a separate aetiological step must establish. Insufficiency is reached by supply-driven, demand-driven or, most commonly, mixed trajectories—the demand-driven route arising without a previously detectable placental abnormality. We distinguish this latent imbalance from placental signalling, which may reflect or mediate it but is not identical to it, and from its host-dependent clinical expressions. For placental growth factor (PlGF), we advance a falsifiable hypothesis: under a sustained positive imbalance, the highly oxidative placenta may shift towards oxygen-sparing metabolism, and the associated hypoxia-responsive and integrated stress-response signalling may lower PlGF, so that a gestational-age-inappropriate PlGF decline behaves as a delayed signal of sustained mismatch rather than a direct measure of fetal demand. Because the maternal syndrome is a host-dependent expression of the same signalling, its severity is only incompletely coupled to the fetal consequence, and fetal compromise can occur during relative maternal silence. We therefore argue that the reference endpoint for placental oxygen-transfer function should shift from the maternal syndrome to the adequacy of fetal support, with maternal and fetal morbidity remaining co-equal outcomes. The framework yields predictions on biomarker trajectories and maternal–fetal divergence, and explicit, multi-level conditions under which it would fail.
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BibTeX
@article{muresan2026placental,
title = {{Placental sufficiency is relational: a demand–supply hypothesis for divergent maternal and fetal expressions of gestational disease}},
author = {Maria Cezara Mureşan and Marius Bogdan Mureşan},
journal = {Frontiers in physiology},
year = {2026},
month = oct,
doi = {10.3389/fphys.2026.1963994},
url = {https://europepmc.org/article/PMC/PMC13724338},
note = {CC BY},
}
RIS
TY - JOUR
TI - Placental sufficiency is relational: a demand–supply hypothesis for divergent maternal and fetal expressions of gestational disease
AU - Maria Cezara Mureşan
AU - Marius Bogdan Mureşan
PY - 2026
DA - 2026/10/19
JO - Frontiers in physiology
DO - 10.3389/fphys.2026.1963994
UR - https://europepmc.org/article/PMC/PMC13724338
AB - Placental insufficiency is usually identified indirectly—through the maternal syndrome, the growth restriction it causes or lesions found after delivery. None of these defines the placenta’s oxygen-transfer function, and each can be absent while fetal support is already inadequate. We propose that this function is relational: it should be defined by the balance between the fetal oxygen requirement, Co(t), and the effective capacity of the integrated maternal–placental–fetal chain to supply oxygen, Os(t), assessed at the fetal receiving end. Their difference, Δ(t) = Co(t) − Os(t), is a latent state rather than a measurable quantity; a positive imbalance denotes insufficiency of the integrated transfer relation and does not by itself identify the limiting component or imply intrinsic placental pathology, which a separate aetiological step must establish. Insufficiency is reached by supply-driven, demand-driven or, most commonly, mixed trajectories—the demand-driven route arising without a previously detectable placental abnormality. We distinguish this latent imbalance from placental signalling, which may reflect or mediate it but is not identical to it, and from its host-dependent clinical expressions. For placental growth factor (PlGF), we advance a falsifiable hypothesis: under a sustained positive imbalance, the highly oxidative placenta may shift towards oxygen-sparing metabolism, and the associated hypoxia-responsive and integrated stress-response signalling may lower PlGF, so that a gestational-age-inappropriate PlGF decline behaves as a delayed signal of sustained mismatch rather than a direct measure of fetal demand. Because the maternal syndrome is a host-dependent expression of the same signalling, its severity is only incompletely coupled to the fetal consequence, and fetal compromise can occur during relative maternal silence. We therefore argue that the reference endpoint for placental oxygen-transfer function should shift from the maternal syndrome to the adequacy of fetal support, with maternal and fetal morbidity remaining co-equal outcomes. The framework yields predictions on biomarker trajectories and maternal–fetal divergence, and explicit, multi-level conditions under which it would fail.
SN - 1664-042X
ER -