Scaling the EVERREST of severe, early-onset fetal growth restriction
Emily J. Su
Emily J. Su
Published September 15, 2023
Citation Information: J Clin Invest. 2023;133(18):e173563. https://doi.org/10.1172/JCI173563.
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Commentary

Scaling the EVERREST of severe, early-onset fetal growth restriction

Abstract

Severe, early-onset fetal growth restriction is a leading cause of medically indicated preterm birth and substantially increases the risk for perinatal death or disability. No treatments exist to improve fetal growth or safely prolong pregnancy. Furthermore, wide-ranging phenotypes limit the accurate prediction of pregnancy outcome. In this issue of the JCI, Spencer and colleagues combine a discovery-science approach with ultrasound parameters to identify the most discriminative models for predicting either the primary outcome of fetal or neonatal death, or a secondary outcome of death or delivery at 28 weeks of gestation or earlier. Their findings can better individualize patient counseling but, just as compellingly, provide the capacity to identify those pregnancies that are at such considerable risk as to justify enrollment in paradigm-shifting interventional trials that are in the pipeline.

Authors

Emily J. Su

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Figure 1

Pathologic mechanisms of severe, early-onset FGR influence key prognostic indicators.

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Pathologic mechanisms of severe, early-onset FGR influence key prognosti...
(A) Inadequate remodeling of the uterine spiral artery and its distal branches early in pregnancy results in malperfusion of the maternal intervillous space. (B) Maternal vascular malperfusion contributes to reduced cytotrophoblast proliferation, diminished syncytial fusion, and increased release of necrotic and apoptotic trophoblastic material. The unhealthy trophoblast layer secretes insufficient levels of growth factors such as PlGF into the maternal vascular compartment and provides inadequate surface area for maternal-fetal exchange. (C) As gestation progresses, concomitant impairments in fetoplacental angiogenesis result in villous vessels that are abnormally elongated and poorly branched. This vascular deficiency not only contributes to improper maternal-fetal exchange but also leads to abnormally elevated fetoplacental vascular resistance. Clinically, umbilical artery Doppler waveforms show deterioration, where forward velocities that normally occur during fetal cardiac diastole progressively diminish, becoming absent or even reversed.