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Inferring fetal growth restriction as rare, severe, and stable over time

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Abstract

Reduced birthweight is a marker of pathologies that impair growth and also decrease survival. However, “fetal growth restriction” remains poorly defined. Assuming that birthweight itself has no causal effect on neonatal mortality, we can estimate the features of pathological fetal growth that would be required to produce the observed pattern of weight-specific mortality. Under the simplest possible scenario, we find that at 39–41 weeks, pathological fetal growth restriction affects only about 0.5% of U.S. births, with a neonatal mortality risk up to 220-fold. This surprising concentration of pathology among a tiny subset of babies would account for roughly half of neonatal deaths at term. Moreover, the prevalence of these pathological births appears to have remained relatively stable over recent decades, even as neonatal mortality in the U.S. has declined by 90%. In our model, the decline has been driven by the reduction in baseline mortality (i.e., mortality among babies unaffected by growth pathologies), while the relative risk of death among pathologically grown infants has apparently remained stable. Fetal growth restriction is conventionally regarded as common and preventable. In contrast, our observations suggest that pathological fetal growth is rare and constant over time, perhaps the result of unpreventable stochastic errors in embryonic development. Public health strategies may be more effective by setting aside attempts to increase birthweight, and focusing instead on the discovery and support of factors (unrelated to birthweight) that have produced the striking reductions in neonatal mortality over time.

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Acknowledgements

We thank Drs. Clarice Weinberg and Angel Davalos for mathematical consultation, and Dr. D. Robert McConnaughey for accessing data and creating the figures. Valuable suggestions on earlier drafts of this paper were provided by Drs. Donna Baird, Marianna Cortese, Kelly Ferguson, JW Ganzevoort, Sanne Gordijn, David Haig, Siri Haberg, Quaker Harmon, Jennifer Hutcheon, Mark Klebanoff, Liv Kvalvik, Rolv Terje Lie, Dag Moster, David Savitz, Rolv Skjaerven, Jon Snowden, Ezra Susser, and Clarice Weinberg.

Funding

This project was supported in part by the Intramural Program of the National Institute of Environmental Health Sciences, NIH. Both authors are independent from funders and had full access to all of the data (including statistical reports and tables) in the study. Both authors take responsibility for the integrity of the data and the accuracy of the data analysis.

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Correspondence to Allen J Wilcox.

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Wilcox, A.J., Basso, O. Inferring fetal growth restriction as rare, severe, and stable over time. Eur J Epidemiol 38, 455–464 (2023). https://doi.org/10.1007/s10654-023-00985-7

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