Dear Editor

The paper by Ibrahim M et al.[1] puts forward the important concept that preterm infants, particularly babies very low birth weight babies, are in negative iodine balance on current standard regimens of total parenteral nutrition (TPN). The resulting consequence is low postnatal serum iodothyroxine levels, and a greater risk of neurodevelopmental problems, including cerebral palsy.

There is enough quality information to extend the conclusion these authors make about iodine to vitamin A, vitamin D, vitamin K, inositol, and glutamine.

The 5th edition of Pediatric Nutrition Handbook, a handbook of the American Academy of Pediatrics states that if a commercially available multivitamin TPN component (Astra) is used as 2 cc/kg for prematures then, "We do not provide enough vitamin A, vitamin D”.[2] This is unfortunate as several studies have indicated that normal vitamin A status reduces the incidence and severity of lung disease in the preterm baby [2,3] and some experts recommend 1640 USP/kg/day of vitamin A for babies less than 1 kg.[4]

In addition, our work from one neonatal unit in the Mayo Health System shows that with current practice too much vitamin K is administered to premature infants even when a low initial dosage (0.5 mg) of phylloquinone is administered shortly after birth5. Our report finds that premature infants (22-32 weeks gestational age) who had Day 2 plasma levels of vitamin K were 1900 to 2600 times higher on average, and the Day 10 vitamin K levels 550-600 times higher on average, relative to normal adult plasma values (0.5 ng/ml) with current clinical practice. In the study, the vitamin K of the multivitamins additive of TPN provides 90% of the vitamin K administered intravenous excluding what vitamin K is given on the first day of life. Vitamin K has a role in the brain growth factor receptor system,[6] and menaquinone is present in the brain, and that conversion of dietary phylloquinone to tissue menaquinone is not dependent on gut bacteria, so the future dosing recommendations will have to consider than just the best dose for an immature coagulation system.[7] Micropremature babies get too much vitamin K, and to decrease intakes in this population, new components of total parenteral nutrition multivitamins need to be commercially available.[5,8,9]

Furthermore, why not add inositol? For example, in our vitamin K study,[5] all babies of 22 to 32 weeks born at our center survived. Ninety- six percent of the mothers in our study received antenatal steroids, but 90% of the babies had mild, moderate, or severe respiratory distress syndrome (intracellular surfactant deficiency) and thus were at high risk for death, bronchopulmonary dysplasia and retinopathy of prematurity. There is good evidence that a new reformulation of TPN multivitamins could benefit premature babies by including inositol as a total parenteral nutrition component. Several studies, including the Hallman et al. study of 221 babies 24 to 32 weeks gestational age, in a randomized, placebo-controlled, double-blind trial to determine the effects of inositol (80 mg/kg/day) during the first five days of life.[10] The Hallman et al. study shows that the inositol group had increased survival without bronchopulmonary dysplasia and a decreased incidence of retinopathy of prematurity. Surfactant is a wonderful drug, with a response rate of 80%, but what of the other 20% of patients. The inclusion of the pulmonary surfactant into the modern practice of neonatology has not decreased chronic lung disease, but perhaps TPN components with more vitamin A and inositol would make a difference.

The new TPN components might as well contain glutamine. Glutamine is a primary fuel, and one prospective, randomized, double-blind trial showed that glutamine was conditionally essential, with babies having birth weights below 800 grams needing fewer days of TPN (13 versus 21 days), a shorter time to full enteral feeds (8 versus 14 days), and less days on mechanical ventilation (38 versus 47 days).[11]

This concept of new TPN components for the neonatal patients, especially the extremely premature infant is an application of what we know,[12] and what we should do to meet the special nutrition challenges of neonatal patients.

References

1. Ibrahim M, de Escobar GM, Visser TJ, Duran S, van Toor H, Strachan J, Williams FL, Hume R Iodine deficiency associated with parenteral nutrition in extreme preterm infants.

Arch Dis Child Fetal Neonatal Ed. 2003 Jan;88(1):F56-7. 2. American Academy of Pediatrics. Nutritional Needs of the Preterm Infant. In: Kleinman RE, Editor American Academy of Pediatrics. Elk Grove, IL 2004. Pediatric Nutrition Handbook. 5th edition.

3. American Academy of Pediatrics, The American College of Obstetricians and Gynecologists. Larry C. Gilstrap, MD, FACOG and William Oh, MD, FAAP editors. Care of the Neonate. In: Guidelines for Perinatal Care 5th edition. Chapter 7; page 203.

4. Schanler RJ. Current Status of Vitamin A and E Supplementation in the Extremely Low Birthweight Infant. Hansen TN, McIntosh N editors. Current Topics in Neonatology No. 4 W B Saunders 2000:44-71.

5. Costakos DT, Greer FR, Love LA, Dahlen LR, Suttie JW. Vitamin K Prophylaxis for Premature Infants: 1 mg versus -.5 mg. American Journal of Perinatology. November 2003, Vol. 20; No. 8:485-490.

6. Ferland G. The vitamin K-dependent proteins: An Update. Nutrition Reviews. Washington; August 1999;1-9.

7. Davidson RT, Foley AL, Engelke JA, Suttie JW. Conversion of dietary phylloquinone to tissue menaquinone-4 in rats is not dependent on gut bacteria. Nutrient Metabolism-Research Communication. Manuscript October 27, 1997:220-223.

8. Greer FR. Vitamin K in Nutritional Needs of the Preterm Infant Scientific Basis and Practical Guidelines. RC Tsang, A Lucas, R Uauy, S Zlotkin editors. Baltimore: Williams and Wilkins, 1993:111-119.

9. Kumar D, Greer FR, Super DM, Suttie JW, Moore JJ. Vitamin K status of premature infants: Implications for current recommendations. Pediatrics 2001 November Vol. 108;No. 5:1117-112.

10. Hallman M, Bry K, Hoppu K, Lappi M, Pohjavuori M. Inositol supplementation in premature infants with respiratory distress syndrome. N Engl J Med. 1992 May; 326(119):1285-7.

11. Lacey JM, Crouch JB, Benfell K, Ringer SA, Wilmore CK, Maguire D, Wilmore DW. The effects of glutamine-supplemented parenteral nutrition in premature infants. J Parenter Enteral Nutr. 1996 January-February; 20(1):74-80.

12. Lenfant C. Shattuck lecture—clinical research to clinical practice—lost in translation? N Engl J Med. 2003 August 28; 349(9):868- 74.