GDF15, a hormone acting on the brainstem, has been implicated in the nausea and vomiting of pregnancy (NVP) including its most severe form, Hyperemesis Gravidarum (HG), but a full mechanistic understanding is lacking [1-4]. Here we report that fetal production of GDF15, and maternal sensitivity to it, both contribute substantially to the risk of HG. We confirmed that higher GDF15 levels in maternal blood are associated with vomiting in pregnancy and HG. Using mass spectrometry to detect a naturally-labelled GDF15 variant we demonstrate that the vast majority of GDF15 in the maternal plasma is derived from the feto-placental unit. By studying carriers of rare and common genetic variants we found that low levels of GDF15 in the non-pregnant state increase the risk of developing HG. Conversely, women with beta-thalassemia, a condition where GDF15 levels are chronically high [5], report very low levels of NVP. In mice, the acute food intake response to a bolus of GDF15 is influenced bi-dir
Researchers now believe a hormone called GDF15 is behind morning sickness raising the possibility of treatments to stem the risk of the common condition.