THE JOURNAL OF PEDIATRICS
19.
20.
21. 22.
www.jpeds.com
of problem behavior in 5-to 6-year-old children. Pediatrics 2012;130: e305-13. Schmeck K, Poustka F, Dopfner M, Pluck J, Berner W, Lehmkuhl G, et al. Discriminant validity of the child behaviour checklist CBCL-4/18 in German samples. Eur Child Adolesc Psychiatry 2001;10:240-7. van Eijsden M, Hornstra G, van der Wal MF, Bonsel GJ. Ethnic differences in early pregnancy maternal n-3 and n-6 fatty acid concentrations: an explorative analysis. Br J Nutr 2009;101:1761-8. Spielberger CD, Gorsuch RL, Lushene RE. STAI Manual for the State-Trait Anxiety Inventory. Palo Alto (CA): Consulting Psychologists Press; 1970. Al MD, van Houwelingen AC, Kester AD, Hasaart TH, de Jong AE, Hornstra G. Maternal essential fatty acid patterns during normal pregnancy and their relationship to the neonatal essential fatty acid status. Br J Nutr 1995;74:55-68.
Vol. 164, No. 4 23. Visser GH, Eilers PH, Elferink-Stinkens PM, Merkus HM, Wit JM. New Dutch reference curves for birthweight by gestational age. Early Hum Dev 2009;85:737-44. 24. Szklo M, Nieto FJ. Epidemiology: Beyond the basics. Gaithersburg (MD): Aspen Publishers; 2000. 25. McLoyd VC. Socioeconomic disadvantage and child development. Am Psychol 1998;53:185-204. 26. Perinatal Care in the Netherlands. 2011 ed. Utrecht: National Institute for Public Health and the Environment (RIVM); 2008. 27. Caspi A, Williams B, Kim-Cohen J, Craig IW, Milne BJ, Poulton R, et al. Moderation of breastfeeding effects on the IQ by genetic variation in fatty acid metabolism. Proc Natl Acad Sci U S A 2007;104: 18860-5.
50 Years Ago in THE JOURNAL OF PEDIATRICS Iron Metabolism in Premature Infants: II. Prevention of Iron Deficiency Gorten MK, Cross ER. J Pediatr 1964;64:509-20
F
ifty years ago, Gorten and Cross described early “anemia of prematurity” and, at 16 months, iron deficiency anemia. These findings remain relevant today. Early anemia of prematurity is caused in part by inadequate erythropoietin production from greater ex utero oxygenation. However, timing of the early anemia is greatly affected by the ratio of phlebotomy loss to neonatal weight, making it in essence an “anemia of phlebotomy.” Late iron deficiency anemia is a story of supply (fetal endowment plus postnatal intake) and demand (especially with rapid growth rates and phlebotomy losses). With the advent of iron-fortified formula, late iron deficiency anemia is now seen in preterm infants fed human milk with no iron supplementation. The fetal iron endowment is normally depleted with doubling of the birth weight, a much earlier occurrence in nontransfused preterm infants than in term infants. In current practice, the infants of most concern are late preterm infants, the greatest contributor to this 1964 study and also to our current neonatal intensive care unit population. This is of concern given the increasing population of late preterm infants, a cohort that commonly masquerades as term infants in the minds of most care providers. What Gorten and Cross did not know is that infantile iron deficiency is not a hematologic disease, but a developmental disrupter that exerts long-term neurocognitive deficits. The good news is that the deficits can be minimized by earlier supplementation. In 1964, the investigators were hamstrung by inadequate laboratory tools to study iron. Hemoglobin and erythrocyte indices are relatively crude and late markers in the course of iron deficiency. Today investigators remain limited by challenges in interpreting normal values in the clinically available tools (developmental differences in plasma ferritin levels) or without access to more sensitive tools, such as reticulocyte hemoglobin or zinc protoporphyrin/heme ratio. The almost exclusive use of hemoglobin and erythrocyte indices in 2013 demonstrates how little progress has been made, a problem when the neurodevelopmental stakes are so high. Although the American Academy of Pediatrics recommends earlier screening of preterm infants than of healthy term infants, the key is enacting this recommendation and using the available tools to diagnose iron deficiency long before progression to anemia, to prevent neurodevelopmental sequelae. Pamela J. Kling, MD Neonatology Department of Pediatrics University of Wisconsin-Madison Madison, Wisconsin http://dx.doi.org/10.1016/j.jpeds.2013.10.040
768
Loomans et al
19.
20.
21. 22.
www.jpeds.com
of problem behavior in 5-to 6-year-old children. Pediatrics 2012;130: e305-13. Schmeck K, Poustka F, Dopfner M, Pluck J, Berner W, Lehmkuhl G, et al. Discriminant validity of the child behaviour checklist CBCL-4/18 in German samples. Eur Child Adolesc Psychiatry 2001;10:240-7. van Eijsden M, Hornstra G, van der Wal MF, Bonsel GJ. Ethnic differences in early pregnancy maternal n-3 and n-6 fatty acid concentrations: an explorative analysis. Br J Nutr 2009;101:1761-8. Spielberger CD, Gorsuch RL, Lushene RE. STAI Manual for the State-Trait Anxiety Inventory. Palo Alto (CA): Consulting Psychologists Press; 1970. Al MD, van Houwelingen AC, Kester AD, Hasaart TH, de Jong AE, Hornstra G. Maternal essential fatty acid patterns during normal pregnancy and their relationship to the neonatal essential fatty acid status. Br J Nutr 1995;74:55-68.
Vol. 164, No. 4 23. Visser GH, Eilers PH, Elferink-Stinkens PM, Merkus HM, Wit JM. New Dutch reference curves for birthweight by gestational age. Early Hum Dev 2009;85:737-44. 24. Szklo M, Nieto FJ. Epidemiology: Beyond the basics. Gaithersburg (MD): Aspen Publishers; 2000. 25. McLoyd VC. Socioeconomic disadvantage and child development. Am Psychol 1998;53:185-204. 26. Perinatal Care in the Netherlands. 2011 ed. Utrecht: National Institute for Public Health and the Environment (RIVM); 2008. 27. Caspi A, Williams B, Kim-Cohen J, Craig IW, Milne BJ, Poulton R, et al. Moderation of breastfeeding effects on the IQ by genetic variation in fatty acid metabolism. Proc Natl Acad Sci U S A 2007;104: 18860-5.
50 Years Ago in THE JOURNAL OF PEDIATRICS Iron Metabolism in Premature Infants: II. Prevention of Iron Deficiency Gorten MK, Cross ER. J Pediatr 1964;64:509-20
F
ifty years ago, Gorten and Cross described early “anemia of prematurity” and, at 16 months, iron deficiency anemia. These findings remain relevant today. Early anemia of prematurity is caused in part by inadequate erythropoietin production from greater ex utero oxygenation. However, timing of the early anemia is greatly affected by the ratio of phlebotomy loss to neonatal weight, making it in essence an “anemia of phlebotomy.” Late iron deficiency anemia is a story of supply (fetal endowment plus postnatal intake) and demand (especially with rapid growth rates and phlebotomy losses). With the advent of iron-fortified formula, late iron deficiency anemia is now seen in preterm infants fed human milk with no iron supplementation. The fetal iron endowment is normally depleted with doubling of the birth weight, a much earlier occurrence in nontransfused preterm infants than in term infants. In current practice, the infants of most concern are late preterm infants, the greatest contributor to this 1964 study and also to our current neonatal intensive care unit population. This is of concern given the increasing population of late preterm infants, a cohort that commonly masquerades as term infants in the minds of most care providers. What Gorten and Cross did not know is that infantile iron deficiency is not a hematologic disease, but a developmental disrupter that exerts long-term neurocognitive deficits. The good news is that the deficits can be minimized by earlier supplementation. In 1964, the investigators were hamstrung by inadequate laboratory tools to study iron. Hemoglobin and erythrocyte indices are relatively crude and late markers in the course of iron deficiency. Today investigators remain limited by challenges in interpreting normal values in the clinically available tools (developmental differences in plasma ferritin levels) or without access to more sensitive tools, such as reticulocyte hemoglobin or zinc protoporphyrin/heme ratio. The almost exclusive use of hemoglobin and erythrocyte indices in 2013 demonstrates how little progress has been made, a problem when the neurodevelopmental stakes are so high. Although the American Academy of Pediatrics recommends earlier screening of preterm infants than of healthy term infants, the key is enacting this recommendation and using the available tools to diagnose iron deficiency long before progression to anemia, to prevent neurodevelopmental sequelae. Pamela J. Kling, MD Neonatology Department of Pediatrics University of Wisconsin-Madison Madison, Wisconsin http://dx.doi.org/10.1016/j.jpeds.2013.10.040
768
Loomans et al
