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

Lesser, Karen B.; Schoel, S B; Kling, Pamela J.

doi:10.1038/sj.jp.7211600

Cited by 16 publications

(17 citation statements)

References 34 publications

(52 reference statements)

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“…Consistent with the literature (19, 21, 22), we previously showed that aliquots of whole blood ZnPP/H assayed within- or between-days for up to 10 subsequent days were similar (23). If stored at 4°C, aliquots assayed for top fraction ZnPP/H were also reproducible in human and rat samples within- or between-days for 10 days (Fig.…”

Section: Resultssupporting

confidence: 89%

Reticulocyte Enrichment of Zinc Protoporphyrin/Heme Discriminates Impaired Iron Supply During Early Development

et al. 2008

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ABSTRACT:In infants and children, elevated whole blood zinc protoporphyrin/heme (ZnPP/H) measures iron-deficient (ID) erythropoiesis. Because immature erythrocytes are less dense than mature erythrocytes, we hypothesized that the sensitivity of ZnPP/H is improved if measured in the least dense cells. Blood was collected from control suckling, mildly and severely ID suckling rats. Cord blood was collected after uncomplicated pregnancies (control), diabetic pregnancies (severe ID) and after pregnancies at-risk for iron deficiency (mild ID). ZnPP/H was measured before and after a two-step density centrifugation to obtain the lightest 6.25% of erythrocyte (top fraction). The difference between whole blood and top fraction was defined as ⌬ZnPP/H. In rats, although the whole or top ZnPP/H differed by postnatal age, ⌬ZnPP/H was greatest after the interval with least body iron accrual. In either rats or humans with mild ID, whole blood ZnPP/H was similar to, but ⌬ZnPP/H was greater than controls. In rats and newborn humans, ⌬ZnPP/H is more sensitive than whole blood ZnPP/H in identifying conditions associated with impaired erythrocyte iron delivery and may become a useful tool in measuring erythrocyte iron incorporation in early development. T here is need for a sensitive clinical index of iron-deficient (ID) erythropoiesis in growing premature infants. In premature infants, clinical practices, such as conservative transfusion criteria and erythropoietin therapy may deplete tenuous iron stores (1-4). When iron supply is limited, zinc replaces iron in the protoporphyrin IX ring to form zinc protoporphyrin (ZnPP) (5). An increased ratio of whole blood ZnPP-to-heme (ZnPP/H) reflects impaired erythrocyte iron incorporation (5,6). In older infants, whole blood zinc protoporphyrin/heme (ZnPP/H) is a more sensitive indicator of early, preanemic iron deficiency than Hb or ferritin (7). Whole blood ZnPP/H from cord blood or ill newborns also reflects iron status (4,8). ZnPP/H is higher in newborns born small for dates and offspring of mothers with insulin-treated diabetes (IDM), two conditions commonly exhibiting severely impaired tissue iron content, i.e., severe iron deficiency (severe ID) at birth (4,8). In premature infants, whole blood ZnPP/H falls in response to iron therapy (9) or with indirect delivery of iron via transfusion (3). In premature infants, whole blood ratios are inversely related to gestation (8), a clinical disadvantage because of gestation-based normal values are necessary to guide interpretation (4,8 -10).In mild ID, when Hb levels have not yet fallen, employing a more sensitive test of iron incorporation would be useful to facilitate earlier treatment. When iron demands are great and iron is limited, testing the iron status of reticulocytes, the most recently produced erythrocytes, would decrease the number of false negative assessments and improve the sensitivity of ZnPP/H to detect impaired iron incorporation. Previous work supports that measuring iron incorporation into reticulocytes (reticulocyte Hb,...

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Section: Resultssupporting

confidence: 89%

Reticulocyte Enrichment of Zinc Protoporphyrin/Heme Discriminates Impaired Iron Supply During Early Development

et al. 2008

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“…30 Rather, we confirmed that fetal overgrowth compounded the effect of maternal diabetes on newborn iron status, supporting previous work. 24, 30, 32, 37 The effect of obesity on ZnPP/H, RE-ZnPP/H and serum ferritin was not lost in multivariate analysis, supporting that maternal obesity was independent of diabetes or newborn size in determining biochemical iron status.…”

Section: Discussionmentioning

confidence: 73%

“…31 A direct relationship between BMI and the ratio of Hb/total body iron supports this view. However, iron was still insufficient to fulfill Hb needs because ZnPP/H rose, 24, 32 especially in reticulocytes. Lower cord ferritin values supported poorer iron stores.…”

Section: Discussionmentioning

confidence: 99%

“…24 Prior research found dysfunctional placentae, functionally altered iron transporters, and increased fetal iron demand in pregnancies complicated by insulin-dependent diabetes. 39, 41 However, in contrast to our previous study of mothers with insulin-treated diabetes, 24, 32 the current data indicated that the main effects could be mediated in part through obesity.…”

Section: Discussionmentioning

confidence: 99%

“…Excessive pregnancy weight gain was defined as ≥18 kg (40 lbs), based on ACOG recommendations 22 prior to the 2013 revised IOM statement. 23 Newborn birth weight and gestational age determined the z -score, 24 based on gender-specific, sea level intrauterine growth curves. 25 LGA defined a z -score of >2 and SGA <-2.…”

Section: Methodsmentioning

confidence: 99%

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Neonatal iron status is impaired by maternal obesity and excessive weight gain during pregnancy

et al. 2014

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Objective Maternal iron needs increase 6-fold during pregnancy, but obesity interferes with iron absorption. We hypothesized that maternal obesity impairs fetal iron status. Study Design 316 newborns with risk factors for infantile iron deficiency anemia (IDA) were studied to examine obesity during pregnancy and neonatal iron status. Erythrocyte iron was assessed by cord blood hemoglobin (Hb), zinc protoporphyrin/heme (ZnPP/H) and reticulocyte-ZnPP/H and storage iron by serum ferritin. Results Women with body mass index ≥30 kg/m2, as compared with non-obese women, delivered larger offspring with higher reticulocyte-ZnPP/H, and lower serum ferritin concentrations (p<0.05 for both). With increasing BMI, estimated body iron was relatively lower (mg/kg) and the ratio of total Hb-bound iron (mg)/total body iron (mg) increased. Maternal diabetes compromised infant iron status, but multivariate analysis demonstrated that obesity was an independent predictor. Conclusions Obesity during pregnancy and excessive weight gain are independent risk factors for iron deficiency in the newborn.

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Early iron supplementation and iron sufficiency at one month of age in NICU patients at-risk for iron deficiency

Bahr

Carr

Christensen

et al. 2021

Blood Cells, Molecules, and Diseases

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

Cited by 16 publications

References 34 publications

Reticulocyte Enrichment of Zinc Protoporphyrin/Heme Discriminates Impaired Iron Supply During Early Development

Reticulocyte Enrichment of Zinc Protoporphyrin/Heme Discriminates Impaired Iron Supply During Early Development

Neonatal iron status is impaired by maternal obesity and excessive weight gain during pregnancy

Early iron supplementation and iron sufficiency at one month of age in NICU patients at-risk for iron deficiency

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