Peer-reviewed article
Beyond Deterministic Fetal Programming: Intrauterine Exposures and the Multifactorial Origins of Adiposity.
Gernot Desoye, Ursula Hiden, Evelyn Jantscher-Krenn, Herbert Fluhr, Jonathan C Wells et al. ·
Summary
Written by AI, not yet AICS's view · claude-haiku-4-5-20251001This review examines how conditions during pregnancy, particularly maternal diabetes and obesity, may affect fetal development and later childhood weight gain. The authors argue that while disturbances in the intrauterine environment can influence a child's early adiposity, excess weight in childhood results from multiple factors beyond pregnancy alone, including genetics and postnatal exposures. The paper challenges the idea of simple deterministic fetal programming and calls for more research to understand the complex causes of childhood obesity.
Key points
- Maternal metabolic disturbances early in pregnancy, especially in women with diabetes or obesity, may lead to fetal hyperinsulinaemia and increased neonatal adiposity
- Neonatal adiposity may increase the risk for childhood adiposity, but this relationship is not deterministic
- Postnatal exposures and interaction with genetic background are important contributors to excessive adiposity
- Sensitivity to environmental perturbations varies depending on the developmental stage of the individual
- Causal evidence for deterministic fetal programming of adiposity in humans is currently missing
Limitations
This is a literature review that does not present new empirical data. The document does not evaluate specific interventions or provide evidence of what works to reduce childhood obesity, nor does it discuss implementation or scale-up of any solutions.
Abstract
Excess adiposity is not a recently developed problem but has existed since at least the upper Paleolithic, allowing evolutionary selection pressures to adapt the physiology of the pregnant woman and the feto-placental unit for maternal and fetal protection. Disturbances of the intrauterine environment, in particular metabolic derangements early in pregnancy, such as in women with diabetes and/or obesity, may lead to fetal hyperinsulinaemia. This often results in neonatal adiposity, which may in turn increase the risk for childhood adiposity. In this review, we summarize evidence on possible underlying mechanisms and factors that moderate the association between in utero exposure and childhood adiposity focusing on pregnancies in women with diabetes or obesity. We conclude that in humans causal evidence is missing for fetal programming of adiposity in the deterministic sense as often used and propose a more opportunistic framework. A variety of postnatal exposures and their interaction with the individual's genetic background contribute to the multifactorial problem of excessive adiposity, which may be further compounded by varying sensitivity to environmental perturbations depending on the developmental stage of the individual. We identify research gaps and describe future studies to generate causal evidence necessary.