Unit 2: Nutritional Requirements of the Preterm Infant

B₁- Thiamine

Vitamin B₁ can be found in large quantities in a variety of foods (vegetables, rice, cereals, pork, etc). Thiamine is an essential co-enzyme participating in the metabolism of carbohydrates. B₁ also participates in nerve conduction and neurophysiology. It can be transported passively (when in high concentration), or actively (in the intestine).
Clinical manifestations of B₁ deficiency include the Beriberi, characterized by peripheral neuropathy, and Wernicke-Korsakoff syndrome (a central neurological manifestation of thiamine deficiency with encephalopathy) (IOM 1998).

There is no significant B₁ storage in the preterm infant. Deficiency can occur within the first week in preterm infants fed parenterally without thiamine supply. Thiamine deficiency is often misdiagnosed as acidosis. B₁ can be directly measured in the plasma, or indirectly ("transkelotase test”) (Leaf & Lansdowne 2014).

B₂ - Riboflavin 

Vitamin B₂ is a member of the flavins. It is supplied in many foods, including green vegetables, meats, fish, eggs and milk. It participates in the oxidation chain in mitochondria. B₂ also works as a co-enzyme and as a co-factor for others enzymes such as xanthine oxidase and NADH dehydrogenase (IOM 1998).

Riboflavin deficiency is rare in preterm infants. Urinary riboflavin excretion and red blood cell glutathione reductase activity are used to measure sufficiency (Leaf & Lansdowne 2014). High levels of B₂ are found in most preterm infants on parenteral nutrition or receiving preterm infant formula. Current standard regimens should possibly be revisited since they seem to be excessive for the preterm infant with immature renal function (Porcelli et al. 2000).

Vitamin B₃ - Niacin

Nicotinamide and nicotinic acid are the two common forms of vitamin B₃. They form in the mitochondria the very important co-enzymes nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP). They are essential in the oxidation of fatty acids and for oxidative phosphorylation. Niacin can be also be endogenously synthesized from tryptophan in the liver (Leaf & Lansdowne 2014).

Main diet sources are meats (especially liver), yeast and vegetables. Although extremely rare nowadays in industrialized countries, pellagra is the clinical manifestation of extreme B₃ deficiency. The disease is characterized by a pigmented rash that develops symmetrically, vomiting and neurological symptoms (IOM 1998).

Deficiency in the preterm infant is rare and evidence is lacking for optimal intakes in this group. Niacin adequacy tests are: red cell NAD concentration, urinary N-methylnicotinamide, and fasting plasma tryptophan (Leaf & Lansdowne 2014).

B₅ - Pantothenic acid

B₅ is a component of coenzyme A and it is an essential cofactor in the tricarboxylic acid cycle and in lipid metabolism. In the diet, pantothenic acid is found in egg yolk, meats, broccoli, milk, potatoes and whole grains. It can also be synthetized in the colon by bacteria. Deficiency is very rare and toxicity is not known. Urinary B₅ excretion is used to determine adequacy (Leaf & Lansdowne 2014, IOM 1998).

B₆ - Pyridoxine

Vitamin B₆ comprises a group of three related compounds: pyridoxal, pyridoxine, pyridoxamine. They all have their respective 5'-phosphate forms. Meat, whole grains vegetables and nuts are the main sources of vitamin B₆. It is a co-enzyme for more than 100 enzymes involved in amino acid metabolism. B₆ also plays a role in the release of glucose from glycogen and in the formation of sphingomyelin and phosphatidylcholine.

Classical symptoms for B₆ deficiency are: dermatitis, microcytic anemia, neurological dysfunctions, including seizures, depression and confusion and growth impairment. Toxicity is rare and tests of sufficiency are: urinary metabolites and plasma of pyridoxal 5'-phosphate (Leaf & Lansdowne 2014, IOM 1998).

B₇- Biotin

Biotin can be found in a variety of plants, and in higher concentrations in liver, egg yolk and soybean. It is also found in human milk, however its concentration is lower than in cow's milk.  Biotin can also be endogenously synthetized by the intestinal flora. B₇ is a co-enzyme for carboxylase reactions in the metabolism of fats, amino acids and carbohydrates. Increased cholesterol and 3-hydroxyisovaleric are  found in biotin deficiency.

Clinical manifestations are rare but include dermatitis, conjunctivitis, alopecia and abnormalities of the neural system, including depression. Measure of adequacy is made by urinary biotin (Leaf & Lansdowne 2014, IOM 1998).

B₉ - Folate

Folate is the generic term given to a group of compounds which function in reactions of single carbon transfers (methyl transfer) in purine and pyrimidine synthesis. It is essential in cell division and DNA synthesis. Folic acid is rarely found in foods but is normally the folate form used in vitamin supplements. Additionally, it is the most oxidized and stable form of folate. Natural dietary sources of folate include green leafy vegetables and fruits, however, currently, the main dietary source are enriched cereals and flours (IOM 1998). Folates are absorbed in the small intestine and are found in high concentrations in  erythrocytes.

Adult folate deficiency clinical manifestations are rare, but occur in the elderly, malnourished and alcoholics. Folate deficiency causes megaloblastic anemia. During pregnancy, folate requirements increase substantially. Folic acid supplementation should start before conception in order to avoid neural tube defects (NTD), please refer to module 1 for additional information in this subject. Folate measurements are done either in plasma, which indicates recent intake, or in red cells, which reflects cellular folate status (Leaf & Lansdowne 2014, IOM 1998).

B₁₂ - Cobalamin

Vitamin B₁₂ mainly functions as a co-enzyme involved in the methyl transfer reaction that converts homocysteine to methionine and CoA to succinyl-CoA. B₁₂ sufficiency is required for normal blood formation and neurological function. Animal products (meat and dairy products) are the main source of cobalamin in the diet. Absorption takes place in the small intestine, and require an 'intrinsic factor' produced by parietal cells in the stomach.

Because of its high retention, deficiency is rare but it can occur in infants of mothers following a vegan diet or lacking intrinsic factor. B₁₂ deficiency causes pernicious anemia, which is a megaloblastic anemia (characterized by red blood cells with mean corpuscular volume greater than 100 fL) with inefficient erythropoiesis. Vitamin B₁₂ deficiency can cause also neurological complications due to impaired myelination, including sensory disturbances in the extremities, motor disturbances, and cognitive changes involving memory loss, disorientation and even frank dementia. Serum plasma concentration can be measured to assess adequacy (Leaf & Lansdowne 2014; IOM 1998).