Folate, Folate Receptor Autoantibodies, and Neural Tube Defects
We all have heard of the popular recommendation to take folic acid supplements when pregnant. This has stemmed from numerous research reports indicating that folate (vitamin B-9), and more particularly, synthetic folate known as folic acid, prevents neural tube defects. In fact, this is the reason why our food supply, in many instances, is fortified with folic acid – to prevent neural tube defects. Evidently, this has worked in lowering the cases of neural tube defects over several years, but not eliminating them completely.
Oftentimes, a woman may not know that she is pregnant until several weeks after conception. At this early stage, the fetus’ neural tube is continuously forming. The neural tube typically forms very early in fetal development, usually within the first few weeks of post conception. Specifically, it begins to develop around the third week of gestation. By the fourth week, the neural tube usually closes. This structure eventually develops into the brain and spinal cord, making it a critical early stage in the development of the central nervous system.
Folate is incredibly important before pregnancy for several reasons, and proper folate metabolism is critical for both the mother and the fetus. Sufficient folate intake before conception and during early pregnancy significantly reduces the risk of neural tube defects such as spina bifida and anencephaly. Additionally, folate is essential for DNA synthesis and cell division. During pregnancy, there is rapid cell division and growth of the fetus. Besides neural tube defects, folate may also play a role in reducing the risk of other birth defects such as cleft lip and palate, heart defects, and certain limb abnormalities. Adequate folate levels are necessary to support the rapid growth of the fetus, especially in early pregnancy.
Sufficient folate intake is not only important for the baby’s health but also for the mother’s health during pregnancy. Folate helps in the formation of red blood cells and prevents anemia, which is common during pregnancy.
Since neural tube defects occur very early in pregnancy, and often before a woman even knows she’s pregnant, it is recommended for women of childbearing age to ensure they have adequate folate intake even before conception occurs. For these reasons, it’s recommended that women of childbearing age consume sufficient folate through diet or supplements, ideally starting before conception and continuing throughout the early stages of pregnancy. The recommended daily intake of folate for women planning pregnancy is usually higher than for women who are not, to ensure optimal levels are present during the critical early stages of fetal development.
Surely, the intake of folate is very important as is the transport of this folate into the accompanying cells during such a rapid growth period. One extremely interesting discovery, published in the New England Journal of Medicine [1], in January of 2004, was the detection of folate receptor autoantibodies in the serum of women with a pregnancy complicated by a neural tube defect. Could this be a reason for some cases of neural tube defects, considering that folate levels in the blood were deemed to be sufficient?
Folate receptor autoantibodies are antibodies produced by the immune system that target folate receptors. In these instances, the autoantibodies block the main folate receptor alpha and impede proper folate transport into the cells. Clearly, these autoantibodies have been implicated in certain conditions like autoimmune-related pregnancy complications, such as recurrent miscarriages and neural tube defects, but the evidence for their direct role in causing NTDs is not well-established. Folate receptor autoantibodies are not typically considered as primary contributors to neural tube defects (NTDs) at this time, but they may play a significant role. The exact causes of NTDs are considered multifactorial and may involve genetic, environmental, and nutritional factors. Research into the role of folate receptor autoantibodies in pregnancy-related complications and birth defects is ongoing, but at present, the primary focus for preventing NTDs remains ensuring adequate maternal folate intake before and during pregnancy. This is typically achieved through folic acid supplementation and a diet rich in folate-containing foods.
