Official publication of the Czech Society of Ultrasound in Obstetrics and Gynecology.
Letter to the Editor
A sufficient intake of choline in the mother during this life stage ensures that the fetus/infant is getting sufficient choline that contributes to normal function of the liver and the brain of the newborns and breastfed infants.
Choline is a vitamin-like molecule with unique roles in cell functions. It is an essential nutrient for humans (1). This means that humans cannot produce a sufficient amount of choline in the liver to cover the daily requirements. If choline intake through the diet is insufficient, fatty liver will develop within three weeks. When 500 mg/day choline was provided to the depleted persons, the liver function was normalized. Therefore, a sufficient choline intake is needed for a normal liver function in humans (2,3).
The requirements of choline increase during pregnancy and lactation due to the active transport of choline to the fetus or excretion of high amount of choline in human milk. This has led official authorities (e.g. the US Institute of Medicine (IOM) and the European food and safety authority (EFSA)) to set higher adequate intake of choline for pregnant (EFSA: 480 mg/day) and lactating women (EFSA: 520 mg/day) versus 400 mg/day (EFSA) in non-pregnant adults (1,4). Population based epidemiological studies on women in reproductive age have shown that on average women do not consume sufficient choline through the diet and that the gap in choline intake is approx. 100-150 mg/day (5). Pregnant and lactating women should aim to achieve choline requirements by supplementing this nutrient as part of prenatal supplements.
Choline is involved in three key biochemical reactions that are strictly needed in all body cells.
First, choline is a methyl donor, which is a role similar to that of folate. Choline is oxidized to betaine, the direct methyl donor for homocysteine. Homocysteine is a toxic amino acid that is converted to methionine using the methyl groups of betaine. Sufficient methyl groups in the cell play a key role in numerous enzymatic reactions and regulation of DNA-methylation and expression (1).
Second, choline is a precursor of the neurotransmitter, acetylcholine. Acetylcholine has a role in neuronal function and brain development (1).
Third, choline is used to produce phosphatidylcholine or contribute with its methyl group to synthesizing phosphatidylcholine from phosphatidylethanolamine. Phosphatidylcholine is a structural component of cell membranes, it plays a role in cellular signaling, cell expansion and differentiation (1).
With this in mind, it is important to recognize that when isotope labelled choline is added to the diet of pregnant rats, it was detected in the liver and the brain of the foetus, thereby showing the two fetal organs with most reliance on choline coming from the maternal diet (6). Separate studies have also shown that dietary choline (labelled choline) was taken up and caused an increase in brain acetylcholine (7).
When choline was supplemented to pregnant women, it influenced placental DNA-methylation (8).
It has been shown in animal studies that the liver of pregnant and lactating animals become depleted of choline, while choline accumulates in the same time in the placenta, the fetus or breastmilk. Thus, pregnancy and lactation enhance choline depletion in the mother and predispose the mother to develop choline deficiency related symptoms. For example, a series of animal studies have shown that cutting choline from the diet during late gestation depleted maternal liver choline and caused triglycerides to accumulate in mother’s liver compared to animals fed on a choline-sufficient diet (6,9).
The foetus and the breastfed infants cannot produce sufficient choline to cover their own requirements. They drain choline from the mother through transplacental transport and human milk (1,6).
Liver: Fatty liver is a universal outcome of insufficient choline intake in humans and animals. Thus, sufficient intake of choline in the mother is necessary to ensure normal liver function in the fetus and breastfed infants. This has been shown by depletion studies in pregnant animals, where choline deficient diet during pregnancy caused fatty liver in the mothers and the newborns. This role is obviously analogue to the role of choline as an essential nutrient in human adults. However, it appears that early life is a very critical time window where infants are sensitive to deficiency of choline and other methyl donors such as folate (3).
Brain: Insufficient maternal choline can cause a delay in neuronal cell development and thereby negatively influence brain development. This is due to its role in phospholipid metabolism and acetylcholine synthesis, insufficient choline can cause a delay in neuronal cell development and thereby negatively influence brain development. Studies on genetic defects of choline transport to the brain have shown that infants have microcephaly and retarded brain growth (8,10,11). In addition, epidemiological studies have shown that lower choline intake or plasma concentrations of the mother are associated with 36% higher risk of having a newborn suffering from severe brain/neural tube defects such as spina bifida. This association was independent on supplementing folic acid during pregnancy, suggesting that adding choline to prenatal supplements may have potential to further reduce the risk of brain defects compared to when folate alone is used. Randomized controlled trials to test the effect of choline compared to folic acid are not ethical. However, support to the unique role of choline in early development of the brain comes from experimental choline deficiency in mice embryo and other genetic models, where choline, but not folic acid was able to rescue the neural tube defects (12).
Choline is definitely needed during early life as a methyl donor, to form cell membrane and acetylcholine. Choline requirements increase considerable during pregnancy and even more during lactation compared to outside these life periods. However, young women are not achieving the requirements through the natural diet. Therefore, choline should be included in prenatal supplements (to give roughly 150 mg/d additional intake) to ensure reaching the intake recommendations during this life stage. Adequate choline intake in the mother is necessary for normal function of the liver and the brain of the fetus and breastfed infants.
