GDF15 linked to maternal risk of nausea and vomiting during pregnancy.
Level 4 - case-series / case-control
Translational study combining human genetic association, observational comparisons, mass spectrometry, and animal models
PubMed 38092039 · doi:10.1038/s41586-023-06921-9
What was done
The authors examined the mechanistic role of GDF15 in nausea and vomiting of pregnancy and hyperemesis gravidarum (HG). They measured maternal blood GDF15 levels, used mass spectrometry to detect a naturally labelled GDF15 variant to determine maternal versus feto-placental origin, and evaluated how rare and common genetic variants affecting non-pregnant GDF15 levels relate to HG risk. They also assessed nausea and vomiting rates in pregnant women with beta-thalassaemia (a condition characterized by chronically elevated baseline GDF15) and tested the effect of pre-existing circulating GDF15 levels on acute food-intake responses to GDF15 boluses in mice.
What was found
The abstract does not provide specific numerical effect sizes, confidence intervals, or p-values. Directionally, maternal plasma GDF15 was confirmed to be elevated in women with vomiting in pregnancy and HG, with the vast majority originating from the feto-placental unit. Carriers of variants linked to low prepregnancy GDF15 levels had an increased risk of developing HG, whereas women with beta-thalassaemia reported very low rates of pregnancy-related nausea and vomiting. In mice, prior exposure to circulating GDF15 bi-directionally altered the acute response to a GDF15 bolus, demonstrating biological desensitization.
Why it matters
This study provides a mechanistic framework for hyperemesis gravidarum, establishing that disease risk is driven by feto-placental hormone production acting on maternal sensitivity predetermined by prepregnancy exposure. This identifies GDF15 signaling and prepregnancy desensitization as tractable targets for therapeutic intervention.
Limits
The abstract provides no sample sizes, effect sizes, or statistical metrics for any of the human cohorts or animal experiments. Human findings rely on observational and genetic association data, and behavioral food-intake responses in rodents serve as an indirect surrogate for human nausea and emesis.
Cited by
- supports GDF15 is the trigger for morning sickness and hyperemesis gravidarum in pregnancy, during which its levels can increase up to 10,000-fold.