Zinc Protoporphyrin/Heme in Large-for-Gestation Newborns

Abstract

Background: Zinc protoporphyrin/heme (ZnPP/H) ratios are indicators of incomplete erythrocyte iron delivery. ZnPP/H is more sensitive than measures of iron stores, such as plasma ferritin, in identifying early pre-anemic iron-deficient erythropoiesis. Cord ZnPP/H ratios are elevated in conditions associated with fetal hypoxia, such as diabetes mellitus during pregnancy. In chronic fetal hypoxemia, erythrocyte and hemoglobin syntheses are accelerated and iron is incorporated into erythrocytes. Cord ZnPP/H ratios are correlated with fetal size after diabetic pregnancy. Because fetal size is a surrogate for diabetes control, it is unclear whether glycemic control in diabetes mellitus or fetal size was the major determinant of ZnPP/H ratios and disturbed erythrocyte iron delivery. Objective: Our goal was to examine whether ZnPP/H ratios were elevated or were associated with growth in large-for-gestation newborns born to mothers without the diagnosis of diabetes mellitus. Methods: In cord blood samples from large and appropriately grown healthy newborns, we measured ZnPP/H and indices of erythropoiesis and iron status. Analyses included simple linear regression, Fisher’s exact, and unpaired t testing. Results: In the absence of diabetes mellitus, ZnPP/H in 25 large and 24 appropriately grown healthy newborns was similar, and the ratios were within the limits of previously reported normal cord ZnPP/H. Ratios were not correlated with plasma ferritin levels. In large newborns, but not appropriately grown newborns, ZnPP/H ratios were positively correlated with fetal growth (p < 0.03) and estimates of body hemoglobin (p <0.04). Conclusions: Despite 33% greater body hemoglobin mass observed in healthy large, compared to appropriately grown newborns, mean ZnPP/H was normal. Iron incorporation into erythrocytes in large newborns appears adequate. Because the association of ZnPP/H with size and estimated body hemoglobin was observed only in large newborns, factors determining ZnPP/H may differ between large and appropriately grown newborns.

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

“…35, 36 Although the occurrence of LGA newborns was more common after pregnancies with maternal obesity, 1 being LGA was not the sole basis for poorer cord iron status. 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.…”

“…30 During accelerated fetal erythropoiesis, transport of available fetal iron is prioritized to the erythrocytes at the expense of other tissues. 31 A direct relationship between BMI and the ratio of Hb/total body iron supports this view.…”

“…We previously found that cord blood iron status worsened with increasing fetal size. 30 Large newborns may also grow more rapidly after birth, with rapid growth increasing risk for developing infantile IDA. 35, 36 Although the occurrence of LGA newborns was more common after pregnancies with maternal obesity, 1 being LGA was not the sole basis for poorer cord iron status.…”

Impact of Multiple Prenatal Risk Factors on Newborn Iron Status at Delivery

“…To provide a reference comparison, we generated cord blood laboratory data from a recent representative population of 188 healthy newborns born at ≥35 weeks of gestation, delivered from mothers of all ethnic backgrounds at Meriter Hospital without other known risk factors for IDA. 6,10,11 …”

“…Birth weight was z -scored for gestational age, and used to ascertain whether the neonate exceeded the criterion for LGA as >2 or SGA as <−2. 10,12 One-way and multiple ANOVA with Fisher post hoc testing were used to compare differences between the groups and the Pearson test was used to evaluate correlations between outcome measures. Chi square analysis was used for nominal demographic variables.…”