Topline
Researchers now believe morning sickness is linked to a hormone that pregnant mothers are exposed to through the placenta, according to a study published in Nature, helping to answer a longstanding medical question—and raising the possibility of staving off the common illness by exposing patients to the same hormone pre-pregnancy.
Key Facts
The hormone, known as growth and differentiation factor 15 (GDF15), is a protein produced by humans throughout their lives that sends signals to the part of the brain responsible for feeling appetite and nausea, and is found abundantly in a mother’s placenta.
The severity of a woman’s morning sickness is directly related to the amount of GDF15 made by the fetus—which increases with gestational age—and how sensitive the mother is to the hormone’s nauseating effects, which is influenced by how much GDF15 she’s exposed to before pregnancy, according to the Cambridge University-led study published Wednesday.
Though all humans produce GDF15, factors like age, intense exercise, cancer, smoking and certain medications like diabetes drug metformin are known to increase GDF15 levels.
Morning sickness is very common—affecting between 70% to 80% of pregnant women—but the exact cause was unknown, though some previously thought low blood sugar and hormonal imbalances may have been the culprits.
The Cambridge researchers believe long-term exposure to GDF15 can reduce the risk of developing a severe form of morning sickness called hyperemesis gravidarum (HG): They tested this theory by administering injections of GDF15 to mice, and those who were previously exposed reduced their chances of HG by almost 50% compared to the control group.
Women carriers of a rare GDF15 mutation called C211G have a 10-fold increased risk of developing HG because the mutation lowers levels of GDF15 pre-pregnancy, thus increasing the risk of HG during pregnancy.
What To Watch For
Clinical trials using metformin as an agent for increasing GDF15 levels in women pre-pregnancy are underway, the Cambridge researchers said. Metformin increases GDF15 levels in diabetics by around 2.5% after taking it for two weeks, according to a 2020 Nature study.
Key Background
A study published earlier this year that awaits peer-review linked elevated GDF15 levels in the placenta to more severe morning sickness like HG. However, Wednesday’s study is the first peer-reviewed study to find increased exposure to GDF15 prior to pregnancy can significantly reduce morning sickness. HG is the most severe and rare form of morning sickness, affecting between 0.3% and 10.8% of all pregnancies, according to a study published in Frontiers in Medicine. The illness is associated with premature delivery and low birth weights, and causes severe nausea, vomiting, weight loss and electrolyte disturbance, and can lead to hospitalization, according to the American Pregnancy Association. Symptoms usually arise between four to six weeks of pregnancy and peak between nine and 13 weeks. The disorder can be genetic and often occurs in multiple pregnancies.
Tangent
The Cambridge researchers believe the high concentration of GDF15 in the placenta may serve the purpose of preventing women from eating foods with teratogens—anything ingested or exposed to during pregnancy known to cause fetal abnormalities—or infectious organisms during early pregnancy. Over 90% of women report food aversions during early pregnancy, mainly for meat and alkaline drinks, according to O’Rahilly. Though this may have helped keep the infant and mother safe during the early stages of evolution, it doesn’t serve much purpose now with modern food production.
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