Folic Acid

Late last year, geneticists made the discovery that morning sickness's most serious presentation, hyperemesis gravidarum (HG), is caused by the hormone GDF15, not human chorionic gonadotropin as previously thought. Researchers dispel common morning sickness myths and discusses potential treatments, including sensitizing people to GDF15 prior to pregnancy, similar to the way we treat allergies. Late last year, geneticist Marlena Fejzo and colleagues made the discovery that morning sickness's most serious presentation, hyperemesis gravidarum (HG), is caused by the hormone GDF15, not human chorionic gonadotropin as previously thought. In a peer-reviewed opinion article publishing May 22 in the journal Trends in Molecular Medicine, Fejzo dispels common morning sickness myths and discusses potential treatments, including sensitizing people to GDF15 prior to pregnancy, similar to the way we treat allergies. "HG can be life threatening and is associated with adverse outcomes that need to be taken seriously," says Fejzo of the Keck School of Medicine of the University of Southern California. "Now that we know that GDF15 is the most likely cause of HG, we are on the cusp of having treatments that target this hormonal pathway and end the suffering." Myth 1: Severe morning sickness is harmless and normal Pregnant people with HG are essentially starving, Fejzo says, and an increasing number of studies have demonstrated that this has serious short- and long-term clinical implications for both the parent and child. HG is a top predictor of postnatal depression, and 26% of pregnant people with HG report suicidal ideation while 18% meet the full criteria for post-traumatic stress disorder. For the child, HG is associated with preterm birth, low birth weight, and later in life, autism spectrum disorder, ADHD, depression, social problems, in addition to an increased risk of childhood cancer and respiratory and cardiovascular disease. Still, pregnant people with the condition are often dismissed by their clinicians and families. "It really is like a teratogen in pregnancy, a factor which interferes with normal fetal development, but it's still not taken seriously by a lot of medical professionals," Fejzo says. "A lot of people are brushed off and told, 'oh that's normal, it's okay, just don't take your pre-natal vitamins; you don't need them.'" At its most extreme, individuals with HG can develop Wernicke encephalopathy, a life-threatening swelling of the brain due to thymine (vitamin B1) deficiency. Since individuals with HG can have trouble even swallowing vitamins, the American College of Obstetricians and Gynecologists currently recommends that they replace broad spectrum prenatal vitamins with folic acid, but Fejzo warns that this is likely insufficient, and that thiamine supplementation is also warranted for individuals with HG. "I believe all women who have hyperemesis should be given vitamin B1 to avoid this serious brain swelling that can lead to permanent brain damage and often leads to fetal death," Fejzo says. Myth 2: Morning sickness is caused by human chorionic gonadotropic hormone (hCG) or is psychosomatic Though it was long thought that morning sickness is caused by hCG, the recent breakthrough has shown that HG's main cause is actually the hormone GDF15, which is part of a normal stress response. Usually, GDF15 is expressed only in very small amounts, but during early pregnancy it spikes by a huge amount, then wanes, and finally rises again during the third trimester. A recent Nature study co-authored by Fejzo showed that individuals who suffer from HG can have genetic variants that causes them to have lower levels of circulating GDF15 prior to pregnancy, which makes them extra sensitive when they become pregnant and are suddenly exposed to high levels. This finding has clinical implications for preventing and treating HG, since preliminary research suggests that it might be safe to manipulate GDF15 during or even prior to pregnancy. "GDF15 may be safe to manipulate in pregnancy or even prior to pregnancy," says Fejzo. "If we can increase levels of GDF15 before someone becomes pregnant, that might desensitize them, similar to how we try to desensitize people to allergens who have severe allergies," says Fejzo. "And during pregnancy, we may be able to minimize or get rid of symptoms by blocking GDF15 or its receptors in the brain stem." Myth 3: Only humans experience morning sickness Nausea and appetite loss during gestation is not a uniquely human trait -- these symptoms have been observed throughout the animal kingdom, from monkeys, dogs, and cats, to chickens, vipers, and octopuses. "I always think it's interesting that the recommendation for cats is that if they're unable to eat for a day, you should contact your veterinarian, but we don't have that recommendation out there for women with hyperemesis," says Fejzo. "If you call your doctor's office and say you haven't eaten for a day, they'll say, 'that's normal' and won't do anything. There's more proactive care for cats than humans." In addition to preventing ingestion of harmful foods, Fejzo speculates that pregnancy-induced nausea likely evolved to prevent dangerous foraging trips. "This condition likely evolved because it was probably beneficial to avoid going out searching for food during pregnancy," says Fejzo. "That may still be true for animals, but people don't need this anymore, so let's end the suffering once and for all if we can." Now, Fejzo is working toward developing and testing the proposed GDF15-based treatments. She also plans to investigate other genes and variants of GDF15 that might contribute to HG.

AAN, AES and SMFM Collaborate to Develop Updated Guidance MINNEAPOLIS, May 15, 2024 /PRNewswire/ -- A new guideline has been issued to help neurologists and other clinicians determine the best antiseizure medications for people with epilepsy who may become pregnant. The guideline is published in the May 15, 2024, online issue of Neurology®, the medical journal of the American Academy of Neurology (AAN), and was developed through a collaboration between the AAN, the American Epilepsy Society (AES) and the Society for Maternal-Fetal Medicine (SMFM). It was endorsed by the Child Neurology Society. The guideline partially updates two 2009 AAN and AES guidelines on the management of epilepsy during pregnancy, specifically regarding malformations at birth and the development of children born to people with epilepsy. "Most children born to people with epilepsy are healthy, but there is a small risk of pregnancy-related problems, partly due to seizures and partly due to the effects of antiseizure medications," said author Alison M. Pack, MD, MPH, of Columbia University in New York City, a Fellow of the American Academy of Neurology and a member of the American Epilepsy Society. "This guideline provides recommendations regarding the effects of antiseizure medications and folic acid supplementation on malformations at birth and the development of children during pregnancy so that doctors and people with epilepsy can determine which treatments may be best for them." The guideline recommendations are based on a review of all available evidence on the topic. Risks can include major congenital malformations, or birth defects, fetal growth issues and neurodevelopmental effects such as autism or lower IQ scores. The guideline states when treating people with epilepsy who may become pregnant, doctors should recommend medications and doses that optimize both seizure control and fetal development at the earliest possible opportunity before pregnancy. During pregnancy, it recommends minimizing the occurrence of tonic-clonic seizures, seizures with full body spasms, to minimize risks to the parent and fetus. It also says stopping medications during pregnancy may increase the frequency of seizures, which may harm the parent and fetus. For medications, the guideline recommends using lamotrigine, levetiracetam or oxcarbazepine when appropriate to minimize risk of major birth defects. It recommends avoiding valproic acid, phenobarbital and topiramate when possible. To reduce the risk of poor neurodevelopmental outcomes, including autism spectrum disorder and lower IQ scores, the guideline recommends clinicians avoid prescribing valproic acid, when possible, to people with epilepsy who may become pregnant. The guideline recommends that people with epilepsy who may become pregnant take at least 0.4 milligrams of folic acid daily before and during pregnancy to decrease the risk of neural tube defects and possibly improve neurodevelopmental outcomes. However, it notes further studies are needed to clarify the optimal dose and timing of folic acid supplementation. "People with epilepsy who may become pregnant want to ensure the best health of their child while still managing and minimizing their seizures," said Pack. "This is why it is important to discuss plans for pregnancy with your doctor before becoming pregnant and notify your doctor as soon as possible if you discover you are pregnant. Don't stop or change your medications. Talk with your doctor about any concerns you have about your medications." There are some medications that did not have enough evidence to be evaluated and need more research about their associated risk. The guideline was funded by the American Academy of Neurology. About the American Academy of Neurology The American Academy of Neurology is the world's largest association of neurologists and neuroscience professionals, with over 40,000 members. The AAN's mission is to enhance member career fulfillment and promote brain health for all. A neurologist is a doctor with specialized training in diagnosing, treating and managing disorders of the brain and nervous system such as Alzheimer's disease, stroke, concussion, epilepsy, Parkinson's disease, multiple sclerosis, headache and migraine. For more information about the American Academy of Neurology, visit AAN.com or find us on Facebook, Twitter, Instagram, LinkedIn and YouTube. About the American Epilepsy Society Founded in 1936, the American Epilepsy Society is a medical and scientific society whose members are dedicated to advancing research and education for preventing, treating and curing epilepsy. AES is an inclusive global forum where professionals from academia, private practice, not-for-profit, government and industry can learn, share and grow to eradicate epilepsy and its consequences. About the Society for Maternal-Fetal Medicine (SMFM) The Society for Maternal-Fetal Medicine (SMFM), founded in 1977, is the medical professional society for maternal-fetal medicine subspecialists, who are obstetricians with additional training in high-risk pregnancies. SMFM represents more than 7,000 members who care for high-risk pregnant people and provides education, promotes research, and engages in advocacy to advance optimal and equitable perinatal outcomes for all people who desire and experience pregnancy. For more information, visit SMFM.org. SOURCE American Academy of Neurology