Nausea, vomiting and conflict in pregnancy: the adaptive significance of Growth-Differentiation Factor 15

Abstract

Nausea and vomiting in pregnancy (NVP) is heritable, common, and aversive, and its extreme, hyperemesis gravidarum (HG), can be highly deleterious to the mother and fetus. Recent influential studies have demonstrated that HG is caused predominantly by high levels of Growth-Differentiation Factor 15 (GDF15), a hormone produced by the placenta in substantial amounts. This work has led to calls for therapeutic modulation of this hormone, to reduce GDF15 levels and ameliorate HG risk. I describe three main lines of evidence relevant to the hypothesis that GDF15 production is typically adaptive for the fetus, in the context of enhanced placental invasion, reduced rates of miscarriage and preterm birth, and higher birth weight. These considerations highlight the medical implications of maternal-fetal conflict, in the context of tradeoffs between aversive symptoms during gestation, rare disorders of pregnancy with major adverse effects, and moderate fitness-enhancing benefits to fetuses.