Iron Deficiency Alters Auditory Recognition Memory in Newborn Infants of Diabetic Mothers

Siddappa, Ashajyothi M.; Georgieff, Michael; Wewerka, Sandi; Worwa, Cathy; Nelson, Charles A.; deRegnier, Raye Ann

doi:10.1203/01.pdr.0000127021.38207.62

Cited by 233 publications

(253 citation statements)

References 48 publications

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“…Together with the studies of Tamura et al 19 and Siddappa et al, 22 our study indicates that prenatal or very early postnatal iron status is related to short-and/or long-term neurobehavioral outcomes in human beings. Further studies with more specific measures of neurodevelopment and potential confounders are needed to confirm the exact nature of the causal relations between low iron status and neurological impairments in premature infants.…”

Section: Discussionsupporting

confidence: 86%

“…While such correlations do not confirm the causal relationship, given the multiple confounders in such study populations (as noted by Fleming,20 and Beard and Connor 21 ), these data suggest the importance of iron status for the developing brain. Siddappa et al 22 recently reported that term and near-term infants of diabetic mothers who were born with low cord ferritin levels had altered auditory recognition memory in the immediate neonatal period and significantly lower psychomotor development score at 1 year. Both these studies support the concept that there is a critical relationship between iron status and shortand long-term neurobehavioral outcomes.…”

Section: Introductionmentioning

confidence: 99%

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Iron Status and Neurobehavioral Development of Premature Infants

et al. 2004

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Section: Discussionsupporting

confidence: 86%

Section: Introductionmentioning

confidence: 99%

Iron Status and Neurobehavioral Development of Premature Infants

et al. 2004

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“…2,5 Children of diabetic pregnancies may also experience disturbed cognitive development and recognition memory, consistent with a hippocampal insult. 6,[9][10][11][12]24 The fetal hippocampus is targeted by hypoxia-ischemia, impaired iron delivery and postnatal hypoglycemia, all of which accompany poorly controlled diabetes during pregnancy. 11,12,25 In diabetes, specific defects in placental function are unable to compensate for increased iron needs accompanying fetal overgrowth and increased erythrocyte mass.…”

Section: Discussionmentioning

confidence: 99%

“…7,8 Recent work shows that long-term cognitive deficits in offspring of women with poorly controlled diabetes are similar to those seen in tissue iron deficiency. [9][10][11][12] The erythrocyte zinc protoporphyrin/heme (ZnPP/H) ratio measures inadequate erythrocyte iron incorporation. Heme is synthesized from iron and protoporphyrin IX.…”

Section: Introductionmentioning

confidence: 99%

Elevated zinc protoporphyrin/heme ratios in umbilical cord blood after diabetic pregnancy

2006

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Objective: Offspring of diabetes patients may suffer from tissue iron deficiency. Erythrocyte zinc protoporphyrin/heme (ZnPP/H) ratios measure impaired iron status. The aim of the study was to examine whether cord ZnPP/H ratios were associated with pregnancy glycemic control.Methods: ZnPP/H was measured in cord blood from 31 pregnancies with insulin-treated diabetes (diabetes group) and compared to population normal values. Maternal glycemic control was assessed by daily glucose log, glycosylated hemoglobin and birth weight.Results: Median cord ZnPP/H was higher in the diabetes group than the population normal values (106 (65.2 to 146.8) mM/M vs 68.2 (37.6 to 98.8) mM/M, P<0.0001). Ratios were directly correlated to surrogates of control (glycosylated hemoglobin, P ¼ 0.05, and birth weight, P<0.04). Cord ZnPP/H ratios from pregnancies with pre-existing and gestational diabetes were similar.Conclusion: Because cord ZnPP/H was higher in large offspring of diabetic pregnancy, it might identify greater iron utilization for fetal erythropoiesis.

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“…Most of these experiments have used rodents, but more recently, studies in human subjects have shown that changes in the cognitive function of babies can be related to maternal iron status (4,21,22) .…”

Section: Consequences Of Deficiencymentioning

confidence: 99%

Iron deficiency during pregnancy: the consequences for placental function and fetal outcome

2013

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This review examines the importance of the placenta in iron metabolism during development and the effect of iron deficiency on maternal and fetal physiology. Iron is an essential micronutrient, required for a wide variety of biological processes. During pregnancy, the mother has to deplete her iron stores in order to provide the baby with adequate amounts. Transplacental iron transfer involves binding transferrin (Tf)-bound iron to the Tf receptor, uptake into an endosome, acidification, release of iron through divalent metal transporter 1, efflux across the basolateral membrane through ferroportin and oxidation of Fe(II) by zyklopen. An additional haem transport system has been hypothesised, which may explain why certain gene knockouts are not lethal for the developing fetus. Iron deficiency is a common phenomenon during pregnancy, and the placenta adapts by up-regulating its transfer systems, maintaining iron at the expense of the mother. Despite these adaptations, deficiency cannot be completely prevented, and the offspring suffers both short-and long-term consequences. Some of these, at least, may arise from decreased expression of genes involved in the cell cycle and altered expression of transcription factors, such as c-myc, which in turn can produce, for example, kidneys with reduced numbers of nephrons. The mechanism whereby these changes are induced is not certain, but may simply be as a result of the reduced availability of iron resulting in decreased enzyme activity. Since these changes are so significant, and because some of the changes are irreversible, we believe that iron prophylaxis should be considered in all pregnancies.

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Iron Deficiency Alters Auditory Recognition Memory in Newborn Infants of Diabetic Mothers

Cited by 233 publications

References 48 publications

Iron Status and Neurobehavioral Development of Premature Infants

Iron Status and Neurobehavioral Development of Premature Infants

Elevated zinc protoporphyrin/heme ratios in umbilical cord blood after diabetic pregnancy

Iron deficiency during pregnancy: the consequences for placental function and fetal outcome

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