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Updated: Aug 2, 2025

Fetal Echocardiography and Pulsed-wave Doppler Ultrasound in a Rabbit Model of Intrauterine Growth Restriction
Published on: June 29, 2013
Inferring fetal growth restriction as rare, severe, and stable over time
Allen J Wilcox1,2, Olga Basso3,4
1Epidemiology Branch, National Institute of Environmental Health Sciences, PO Box 12233, Durham, NC, 27709, USA. wilcox@niehs.nih.gov.
Insights
Pathological fetal growth restriction, a rare condition affecting 0.5% of births, significantly contributes to neonatal mortality. Public health should focus on factors reducing overall neonatal deaths, not just birthweight.
Area of Science:
- Perinatal Medicine
- Neonatalogy
- Public Health
Background:
- Reduced birthweight is linked to impaired growth and survival, but fetal growth restriction (FGR) lacks a clear definition.
- Current understanding suggests FGR is common and preventable, influencing public health strategies.
Purpose of the Study:
- To define pathological FGR by estimating its characteristics based on weight-specific neonatal mortality.
- To re-evaluate the prevalence and impact of pathological FGR on neonatal mortality trends.
Main Methods:
- Utilized a model assuming birthweight has no direct causal effect on neonatal mortality.
- Estimated features of pathological FGR required to explain observed weight-specific mortality patterns.
Main Results:
- Pathological FGR affects approximately 0.5% of U.S. births at term (39-41 weeks), with up to a 220-fold increased neonatal mortality risk.
- This rare condition accounts for about half of all term neonatal deaths.
- Prevalence of pathological FGR remained stable despite a 90% decline in overall U.S. neonatal mortality over decades.
Conclusions:
- Pathological fetal growth restriction is rare and constant, possibly due to developmental errors, contrasting conventional views.
- Declines in neonatal mortality are attributed to reduced baseline mortality, not changes in pathological FGR.
- Public health efforts should shift from increasing birthweight to identifying factors that reduce overall neonatal mortality.
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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