Zinc erythrocyte protoporphyrin as marker of malaria risk in pregnancy - a retrospective cross-sectional and longitudinal study

Senga, Edward; Koshy, Gibby; Brabin, Bernard

doi:10.1186/1475-2875-11-249

“… PPV, Positive predictive value; NA, Not applicable; NPV, Negative predictive value. a Defined as serum ferritin concentration <15 μg/L; b Analysis restricted to women without inflammation, Plasmodium infection or HIV infection; c Cut-off point corresponding to 2.7 μg/g, which has been selected to define the presence of iron-deficient erythropoiesis [ 23 ]; d Cut-off point selected for screening, with a sensitivity of 95%; e Cut-off points selected to yield unbiased estimates of the prevalence of iron deficiency (see text); f Recommended range to indicate iron deficiency in the absence of infection [ 24 ]; g Cut-off point recommended to distinguish between iron deficient erythropoiesis and iron sufficient erythropoiesis [ 2 ]; h Cut-off point selected for screening, with a sensitivity of 95%; i Cut-off points selected to yield unbiased estimates of the prevalence of iron deficiency (see text). …”

Section: Resultsmentioning

confidence: 99%

Diagnostic utility of zinc protoporphyrin to detect iron deficiency in Kenyan pregnant women

Mwangi

¹

,

Maskey

²

,

Andang’o

³

et al. 2014

BMC Med

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BackgroundIron-deficient erythropoiesis results in excess formation of zinc protoporphyrin (ZPP), which can be measured instantly and at low assay cost using portable haematofluorometers. ZPP is used as a screening marker of iron deficiency in individual pregnant women and children, but also to assess population iron status in combination with haemoglobin concentration. We examined associations between ZPP and disorders that are common in Africa. In addition, we assessed the diagnostic utility of ZPP (measured in whole blood and erythrocytes), alone or in combination with haemoglobin concentration, in detecting iron deficiency (plasma ferritin concentration <15 μg/L).MethodsSingle blood samples were collected from a population sample of 470 rural Kenyan women with singleton pregnancies, gestational age 13 to 23 weeks, and haemoglobin concentration ≥90 g/L. We used linear regression analysis to assess associations between ZPP and iron markers (including anaemia), factors known or suspected to be associated with iron status, inflammation markers (plasma concentrations of C-reactive protein and α1-acid glycoprotein), infections (Plasmodium infection, HIV infection), and other disorders (α+-thalassaemia, plasma concentrations of total bilirubin, and lactate dehydrogenase). Subsequently, in those without inflammation, Plasmodium infection, or HIV infection, we used logistic discriminant analysis and examined receiver operating characteristics curves with corresponding area-under-the-curve to assess diagnostic performance of ZPP, alone and in combination with haemoglobin concentration.ResultsIndividually, whole blood ZPP, erythrocyte ZPP, and erythrocyte protoporphyrin had limited ability to discriminate between women with and without iron deficiency. Combining each of these markers with haemoglobin concentration had no additional diagnostic value. Conventional cut off points for whole blood ZPP (>70 μmol/mol haem) resulted in gross overestimates of the prevalence of iron deficiency.ConclusionsErythrocyte ZPP has limited value to rule out iron deficiency when used for screening in conditions with a low prevalence (e.g., 10%). ZPP is of unreliable diagnostic utility when discriminating between pregnant women with and without iron deficiency. Based on these findings, guidelines on the use of ZPP to assess iron status in individuals or populations of pregnant women need review.Trial registrationNCT01308112 (2 March 2011).

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“…Furthermore, erythrocyte ZPP was reported to be a sensitive and specific indicator in the detection of iron deficiency in non-pregnant women and young children aged 1 to 5 years in the USA and in areas where the prevalence of elevated blood lead concentration is not high [25]. Defined as serum ferritin concentration <15 μg/L; b Analysis restricted to women without inflammation, Plasmodium infection or HIV infection; c Cut-off point corresponding to 2.7 μg/g, which has been selected to define the presence of iron-deficient erythropoiesis [23]; d Cut-off point selected for screening, with a sensitivity of 95%; e Cut-off points selected to yield unbiased estimates of the prevalence of iron deficiency (see text); f Recommended range to indicate iron deficiency in the absence of infection [24]; g Cut-off point recommended to distinguish between iron deficient erythropoiesis and iron sufficient erythropoiesis [2]; h Cut-off point selected for screening, with a sensitivity of 95%; i Cut-off points selected to yield unbiased estimates of the prevalence of iron deficiency (see text).…”

Section: Discussionmentioning

confidence: 99%

Diagnostic utility of zinc protoporphyrin to detect iron deficiency in Kenyan pregnant women

Mwangi

¹

,

Maskey

²

,

Andang’o

³

et al. 2014

View full text Add to dashboard Cite

BackgroundIron-deficient erythropoiesis results in excess formation of zinc protoporphyrin (ZPP), which can be measured instantly and at low assay cost using portable haematofluorometers. ZPP is used as a screening marker of iron deficiency in individual pregnant women and children, but also to assess population iron status in combination with haemoglobin concentration. We examined associations between ZPP and disorders that are common in Africa. In addition, we assessed the diagnostic utility of ZPP (measured in whole blood and erythrocytes), alone or in combination with haemoglobin concentration, in detecting iron deficiency (plasma ferritin concentration <15 μg/L).MethodsSingle blood samples were collected from a population sample of 470 rural Kenyan women with singleton pregnancies, gestational age 13 to 23 weeks, and haemoglobin concentration ≥90 g/L. We used linear regression analysis to assess associations between ZPP and iron markers (including anaemia), factors known or suspected to be associated with iron status, inflammation markers (plasma concentrations of C-reactive protein and α1-acid glycoprotein), infections (Plasmodium infection, HIV infection), and other disorders (α+-thalassaemia, plasma concentrations of total bilirubin, and lactate dehydrogenase). Subsequently, in those without inflammation, Plasmodium infection, or HIV infection, we used logistic discriminant analysis and examined receiver operating characteristics curves with corresponding area-under-the-curve to assess diagnostic performance of ZPP, alone and in combination with haemoglobin concentration.ResultsIndividually, whole blood ZPP, erythrocyte ZPP, and erythrocyte protoporphyrin had limited ability to discriminate between women with and without iron deficiency. Combining each of these markers with haemoglobin concentration had no additional diagnostic value. Conventional cut off points for whole blood ZPP (>70 μmol/mol haem) resulted in gross overestimates of the prevalence of iron deficiency.ConclusionsErythrocyte ZPP has limited value to rule out iron deficiency when used for screening in conditions with a low prevalence (e.g., 10%). ZPP is of unreliable diagnostic utility when discriminating between pregnant women with and without iron deficiency. Based on these findings, guidelines on the use of ZPP to assess iron status in individuals or populations of pregnant women need review.Trial registrationNCT01308112 (2 March 2011).

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“…In areas with high exposure to infection, there is a specific need for evaluation of iron biomarkers as potential correlates of infection risk during pregnancy along with a need to clarify their utility in correlating iron status with inflammation in pregnancy. A recent example of this is assessment of the utility of free erythrocyte protoporphyrin in whole blood as a marker of malaria risk in pregnancy . This biomarker has been related to malaria risk in children under 3 years of age …”

Section: Research and Policy Implicationsmentioning

confidence: 99%

“…A recent example of this is assessment of the utility of free erythrocyte protoporphyrin in whole blood as a marker of malaria risk in pregnancy. 179 This biomarker has been related to malaria risk in children under 3 years of age. 180 Assessment of lactoferrin supplementation.…”

Section: Identification Of Iron-replete Nonanemic Women Prior To Commmentioning

confidence: 99%

Influence of iron status on risk of maternal or neonatal infection and on neonatal mortality with an emphasis on developing countries

Brabin

¹

,

Brabin

²

,

Gies

³

2013

Self Cite

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Infection is a major cause of neonatal death in developing countries. We address the question whether host iron status affects maternal and/or neonatal infection risk, potentially contributing to neonatal death. We summarize the iron acquisition mechanisms described for pathogens causing stillbirth, preterm birth, and congenital infection. There is in vitro evidence that iron availability influences severity and chronicity of infections that cause these outcomes. The risk in vivo is unknown as relevant studies of maternal iron supplementation have not assessed infection risk. Reducing iron deficiency anemia among women is beneficial and should improve the iron stores of babies, but there is evidence that iron status in young children predicts malaria risk and possibly invasive bacterial diseases. Caution with maternal iron supplementation is indicated in iron-replete women who have high infection exposure, although distinguishing iron-replete and iron-deficient women is currently difficult. Further research is indicated to investigate infection risk in relation to iron status in mothers and babies in order to avoid iron intervention strategies that result in detrimental birth outcomes for some groups of women.

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Zinc erythrocyte protoporphyrin as marker of malaria risk in pregnancy - a retrospective cross-sectional and longitudinal study

Cited by 13 publications

References 24 publications

Diagnostic utility of zinc protoporphyrin to detect iron deficiency in Kenyan pregnant women

Diagnostic utility of zinc protoporphyrin to detect iron deficiency in Kenyan pregnant women

Diagnostic utility of zinc protoporphyrin to detect iron deficiency in Kenyan pregnant women

Influence of iron status on risk of maternal or neonatal infection and on neonatal mortality with an emphasis on developing countries

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