Iron deficiency, still a rarity in children with sickle cell anemia in Ile-Ife, Nigeria

ABSTRACT In this study, children with sickle cell anemia were evaluated for iron deficiency. Serum ferritin and free erythrocyte protoporphyrin free erythrocyte protoporphyrin (FEP) levels, mean corpuscular volume mean corpuscular volume (MCV) and mean corpuscular hemoglobin mean corpuscular hemoglobin (MCH) were used in determining their iron status. The study was done at Pediatric Hematology Outpatient Clinic of the Obafemi Awolowo University Teaching Hospitals' Complex, Ile-Ife. Forty-eight HbSS subjects in steady state and 48 apparently well age and sex matched HbAA controls were evaluated. Serum ferritin less than 25 ng/dL FEP greater than cut off for age, mean corpuscular volume MCV and mean corpuscular hemoglobin MCH less than cut off for age were regarded as indicating iron deficiency. Serum ferritin values ranged from 34.2 to 3282.9 µg/L, with a mean of 381.2 (1.0), median 180 µg/L; which was significantly higher than the controls (p = 0.000). FEP was lower in the subjects but none was iron deficient compared with the controls. The mean corpuscular hemoglobin MCH of subjects was significantly lower than the controls. Subjects had lower mean corpuscular volume MCV compared with controls. Iron deficiency was not detected in any of the subjects with sickle cell anemia in comparison to a prevalence of 43.75% in the controls. Iron deficiency anemia (IDA) was found in 16.7% of the controls, using the WHO cut off for anemia which is hemoglobin concentration of <11 g/dl. While a high prevalence of iron deficiency was noted in the control group, patients with sickle cell anemia were largely iron sufficient, despite their anemia. Iron supplementation remains unnecessary as part of routine management of children with sickle cell anemia in our practice.

Algoritmos de laboratorio para el estudio del estado del hierro / Laboratory algorithms for the study of iron status / Algoritmos de laboratório para o estudo do estado do ferro

La disponibilidad adecuada de hierro (Fe) es esencial para el desarrollo humano y la salud en general. El Fe es un componente clave de las proteínas portadoras de oxígeno, tiene un papel fundamental en el metabolismo celular y es esencial para el crecimiento y diferenciación celular. La ingesta inadecuada de Fe en la dieta, las condiciones inflamatorias crónicas o agudas y numerosas patologías están asociadas con alteraciones en la homeostasis de este metal. La regulación estricta del metabolismo del Fe es necesaria pues el Fe libre es altamente tóxico y los seres humanos sólo pueden excretar pequeñas cantidades a través del sudor, la piel, el enterocito y eliminarlo por pérdidas en procesos normales y patológicos. El objetivo de este trabajo es analizar los algoritmos para la evaluación preliminar tanto de la deficiencia como de la sobrecarga de Fe, sobre la base de diferentes parámetros, algunos accesibles, de simple resolución y que pueden ser efectuados en todos los laboratorios de análisis clínicos. Entre ellos, se analizarán el hemograma con los Índices hematimétricos, Reticulocitos, Fe sérico, Capacidad Total de Fijación de Hierro (CTFH) para calcular el Índice de Saturación de Transferrina (ISTf) y también el dosaje de Ferritina (Ft), todas mediciones que integran el "estudio del estado del hierro". Asimismo, se exponen y se consideran otros marcadores de uso poco frecuente en este medio, como la Protoporfirina Eritrocitaria Libre (PEL), la Eritropoyetina (EPO), entre otras, que ayudan desde el laboratorio al diagnóstico de una anemia. En los casos de sospecha de una sobrecarga de Fe, si bien la confirmación diagnóstica se realiza por estudios genéticos, como estudio inicial se reafirma la evaluación del paciente por medio del "estudio del estado del hierro" y especialmente el dosaje de Fe sérico y del ISTf para seguimiento del tratamiento instaurado. En las últimas décadas, se han producido importantes conocimientos sobre el metabolismo del Fe que han permitido descubrir otras proteínas que intervienen en el transporte, absorción, reciclaje y balance del Fe plasmático. Entre estas, existen marcadores séricos que podrían sumarse a los algoritmos propuestos y ellos son el Receptor de Transferrina (RTf) y la Hepcidina (Hp). Como conclusión, se destaca la necesidad de medir más de un marcador del "estado del hierro" para establecer el diagnóstico de una deficiencia o de un exceso de Fe.

Adequate availability of iron (Fe) is essential for human development and overall health. Iron is a key component of the oxygen-carrying proteins, it has a fundamental role in cellular metabolism, and it is essential for cell growth and differentiation. Inadequate intake of Fe in the diet, chronic or acute inflammatory conditions and many diseases are associated with alterations in the homeostasis of this metal. Strict regulation of Fe metabolism is necessary because free Fe is highly toxic and humans can excrete only small amounts through sweat, skin, and enterocyte loss in normal and pathological processes. The objective of this work is to analyze algorithms for the preliminary assessment of both Fe deficiency and overload, based on different parameters, some simple resolution ones that can be performed in all clinical laboratories. Among them, CBC, Hematimetric Indices, Reticulocytes, serum Fe, Total Iron Binding Capacity (TIBC) will be considered to calculate Transferrin Saturation Index (TfSI) and Ferritin Dosage (Ft), all measurements being part of the "study of iron status." Other markers of less frequent use in our region will also be considered, such as Free Erythrocyte Protoporphyrin (FEP), and Erythropoietin (EPO), among others, that help, from the laboratory in the diagnosis of anemia. In cases of suspected Fe overload, although the diagnosis was confirmed by genetic studies performed as initial study, the patient assessment is reaffirmed through the "study of iron status" and especially serum Fe and TfSI dosage for monitoring treatment underway. In recent decades, important insights on Fe metabolism have yielded more knowledge on other proteins involved in the transport, absorption, recycling and plasmatic Fe balance. Among these, there are serum markers that could be added to the proposed algorithms, which are Transferrin Receptor (TfR) and Hepcidin (Hp). In conclusion, the need to measure more than one analyte of the "iron status" is highlighted in order to establish the diagnosis of Fe deficiency or excess.

A disponibilidade adequada de ferro (Fe) é essencial para o desenvolvimento humano e para a saúde em geral. O Fe é um componente fundamental das proteínas transportadoras de oxigénio, tem um papel fundamental no metabolismo celular, e é essencial para o crescimento e diferenciagäo celular. A ingestäo inadequada de Fe na dieta, as condigöes inflamatorias crónicas ou agudas e inúmeras doengas estäo associadas a alteragöes na homeostase deste metal. A regulagäo rigorosa do metabolismo do Fe é necessària porque o Fe livre é altamente tóxico e os seres humanos apenas podem excretar pequenas quantidades através do suor, pele, enterócitos e eliminà-lo por perdas em processos normais e patológicos. O objectivo deste trabalho é analisar algoritmos para a avaliagäo prévia tanto da deficiéncia quanto do excesso de Fe, com base em diferentes parámetros, alguns acessíveis, de simples resolugäo e que podem ser realizados em todos os laboratorios clínicos. Dentre eles seräo analisados o hemograma com Índices hematimétricos, Reticulócitos, Fe sérico, Capacidade Total de Fixagäo do Ferro (CTFF) para calcular o Índice de Saturagäo da Transferrina (IST) e também a dosagem de Ferritina (Ft), todas elas medigóes que integram o "estudo do estado do ferro". Também sào expostos e considerados outros marcadores de uso pouco frequente nesse meio, como a Protoporfirina Eritrocitària Livre (PEL), a Eritropoietina (EPO), dentre outros, que ajudam a partir do laboratório ao diagnóstico de uma anemia. Nos casos de suspeita de um excesso de Fe, embora o diagnóstico seja confirmado através de estudos genéticos, como estudo inicial é reafirmada a avaliagäo do paciente por meio do "estudo do estado do ferro" e especialmente a dosagem de Fe sérico e do IST para o seguimento do tratamento instaurado. Nas últimas décadas, houve importantes co-nhecimentos a respeito do metabolismo do Fe que permitiram descobrir outras proteínas envolvidas no transporte, absorgäo, reciclagem e balango do Fe plasmàtico. Dentre elas, hà marcadores séricos que poderiam se unir aos algoritmos propostos e eles säo o Receptor de Transferrina (Tf) e Hepcidina (Hp). Em conclusäo, destaca-se a necessidade de medir mais de um marcador do "estado do ferro", para estabelecer o diagnóstico de uma deficiéncia ou de um excesso de Fe.

Receptores solubles de transferrina como mejor indicador bioquímico para definir deficiencia de hierro / Soluble transferrin receptors as best biochemical test for iron deficiency / Receptores solúveis de transferrina como o melhor indicador bioquímico para definir deficiência de ferro

Con el propósito de valorar el mejor análisis bioquímico como indicador del perfil de hierro en niños preescolares sin anemia se analizaron 149 muestras de niños y niñas con una edad promedio de 4 años de una comunidad urbana marginal y otra rural de Costa Rica a los que se les realizó análisis de hemoglobina, ferritina, receptores solubles de transferrina, protoporfirina eritrocitaria y proteína C reactiva. El 42% de las muestras presentaron un perfil de hierro dentro de los intervalos de referencia. Sin embargo, se detectó deficiencia de hierro en el 30,8% utilizando receptores solubles de transferrina, en un 14% utilizando la protoporfirina zinc eritrocitaria y en un 10% mediante la ferritina sérica. Además, el 16,8% de las muestras mostraron una elevación inespecífica de la ferritina debido a un proceso infeccioso o inflamatorio agudo y el 5% elevación de la protoporfirina zinc eritrocitaria. Se puede concluir que si se cuantifica únicamente ferritina sérica para evaluar perfil de hierro se estaría diagnosticando mal a una proporción importante de la población (16,8%). Si se considera únicamente la protoporfirina eritrocitaria aumentarían en un 19% las muestras deficientes en hierro pero con un 5% de falsas disminuciones. En cambio, si se evalúan los receptores solubles de transferrina se estaría detectando un número mayor de muestras, un 30,8% con perfil bajo de hierro. Por lo tanto, en la experiencia de estos autores resultó de mayor utilidad usar los receptores solubles de tranferrina como mejor indicador bioquímico para valorar perfil de hierro, ya que la ferritina y la protoporfirina eritrocítica son sensibles a los cambios circadianos y a la presencia de procesos agudos inespecíficos. Asimismo, de acuerdo a los datos obtenidos, no se consideró necesario utilizar intervalos de referencia según sexo y lugar de residencia en niños y niñas de 4 años ya que no hubo diferencia estadísticamente significativa entre sexo y zona urbana marginal y rural para ningún análisis estudiado.

With the aim to evaluate the best biochemical analysis of iron status in preschool children without anemia, a hundred and fortynine samples of boys and girls with an average age of 4 years from an urban marginal community and a rural área from Costa Rica hemoglobin, ferrítin, soluble receptors oí transferrin, erythrocyte protoporphyrln and C reactive proteln were analysed. Forty-two per cent oí the samples presented iron status between the reference interval. Nevertheless, iron deficiency was detected in 30.8% oí the cases using soluble transferrin receptor, 14% with erythrocyte protoporphyrln and 10% with serie ferrítin. In addition, 16.8% of the samples had an unspecified increase in ferrítin due to acute infectious or inflammatory process, and 5% of erythrocyte protoporphyrín. It can be concluded that if serum ferrítin is quantified solely to evalúate iron status, an ímportant portíon of the population (16.8%) would be wrongly díagnosed. If erythrocyte protoporphyrln was considered alone, it would increase the iron deficient samples by 19%, but with 5% of false reductions. However, evaluating the soluble receptors of transferrin we would be detecting a greater number of samples-30.8% with low iron status. In the experience of the authors, it was of major utility use to use the soluble receptors of tranferrin as better biochemical indicators to assess iron status, since ferrítin and erythrocyte protoporphyrln are sensible to circadian changes and to the presence of unspecific acute processes. Because of the data obtained, it was not considered necessary to use different reference valúes for sex or place of residence in four year-old boys and girís because there are no significant statistical differences between sex or resideney for any analysis studied.

Avaliação do estado nutricional de ferro e anemia em crianças menores de 5 anos de creches públicas / Nutritional assessment of iron status and anemia in children under 5 years old at public daycare centers

OBJETIVO: Avaliar o estado nutricional de ferro e a prevalência de anemia em crianças menores de 5 anos de creches públicas da cidade do Recife (PE). MÉTODOS: Estudo transversal, com amostra aleatória sistemática de 162 crianças, de 6 a 59 meses. O estado nutricional de ferro foi avaliado em termos de reservas corporais (ferritina sérica), transferrinemia (ferro sérico, capacidade total de ligação do ferro e por cento de saturação da transferrina), eritropoiese (protoporfirina eritrocitária livre) e hemoglobinogênese (hemoglobina). RESULTADOS: A prevalência de anemia (hemoglobina < 11,0 g/dL) foi de 55,6 por cento (IC95 por cento 47,3-63,5), a redução dos estoques de ferro (ferritina sérica < 12,0 ng/mL) foi evidenciada em 30,8 por cento (IC95 por cento 22,9-39,3), baixa transferrinemia ( por cento de saturação da transferrina < 16) em 60,1 por cento (IC95 por cento 51,7-68,0) e eritropoiese deficiente (protoporfirina eritrocitária livre > 40 æmol/mol heme) em 69,6 por cento (IC95 por cento 61,0-77,1) das crianças. Os parâmetros de ferro não apresentaram correlação com o gênero (p > 0,05). No entanto, crianças < 24 meses apresentaram concentrações mais baixas de hemoglobina (p < 0,00) e níveis mais elevados de protoporfirina eritrocitária livre (p < 0,000) e de capacidade total de ligação do ferro (p < 0,001), quando comparadas às crianças > 24 meses. A significante correlação observada entre reserva, transferrinemia e eritropoiese representa achado compatível com o esperado ciclo de vida do ferro no organismo. CONCLUSÕES: A deficiência de ferro e a anemia parecem ser um importante problema de saúde pública entre as crianças menores de 5 anos de creches públicas do Recife. Logo, ações efetivas direcionadas à prevenção e ao controle dessa deficiência são fortemente recomendadas nesse contexto ecológico.

OBJECTIVE: To assess nutritional iron status and anemia prevalence in children less than 5 years old at public daycare centers in the city of Recife, PE, Brazil. METHODS: A cross-sectional study, with a systematic random sampling of 162 children aged 6 to 59 months. Nutritional iron status was assessed in terms of body iron reserves (serum ferritin), transferrinemia (serum iron, total iron binding capacity, and transferrin saturation percent), erythropoiesis (free erythrocyte protoporphyrin) and hemoglobin production (hemoglobin). RESULTS: The prevalence of anemia (hemoglobin < 11.0 g/dL) was 55.6 percent (95 percentCI 47.3-63.5), evidence was found of depleted iron stocks (serum ferritin < 12.0 ng/mL) in 30.8 percent (95 percentCI 22.9-39.3), low transferrinemia levels (transferrin saturation percent < 16) in 60.1 percent (95 percentCI 51.7-68.0) and deficient erythropoiesis (free erythrocyte protoporphyrin > 40 æmol/mol heme) in 69.6 percent (95 percentCI 61.0-77.1) of the children. Iron parameters were not correlated with sex (p > 0.05). However, children < 24 months exhibited lower hemoglobin concentrations (p < 0.00) and higher levels of free erythrocyte protoporphyrin (p < 0.000) and total iron binding capacity (p < 0.001) when compared with children > 24 months. The significant correlation observed between reserves, transferrinemia and erythropoiesis is a finding that is compatible with the expected lifecycle of iron in the body. CONCLUSIONS: Iron deficiency and anemia appear to be an important public health problem among children less than 5 years old at public daycare centers in Recife. Therefore, effective actions aimed at the prevention and control of this deficiency are strongly recommended in this ecological context.

Free Erythrocyte Protoporphyrin for Diagnosis of Iron Deficiency and Iron Deficiency Anemia in Adolescent Female Athletes / 대한혈액학회지

BACKGROUND: If hemoglobin (Hb) synthesis is impaired by factors other than a deficiency in free erythrocyte protoporphyrin (FEP) synthesis, the amount of FEP might be increased. In this study, we analyzed the statistical values and contribution of FEP for the monitoring and diagnosis of iron deficient anemia in adolescent female athletes according to various sports. METHODS: We collected whole blood from 64 adolescent female athletes 13 to 19 years of age. The FEP was measured fluorometrically. After other hematological indices were evaluated, statistical analysis was performed to compare the data among various athletes. RESULTS: The mean age was 14.8+/-1.7 (13~19) years old. The number of runners, badminton players and shooting athletes were 46.9% (n=30), 12.5% (n=8) and 40.6% (n=26), respectively. The prevalence of anemia, iron deficiency and iron deficiency anemia were 23.4%, 23.4% and 14.0%, respectively. The measured concentration of FEP was 48.7+/-21.1 microgram/dL (12~125). A moderately negative correlation of Hb and FEP was noted and was found to be statistically significant (r=-0.571, P<0.001). Among serum ferritin, TS and FEP, there was no statistically significant correlation. For the diagnosis of iron deficiency anemia, FEP was the most statistically significant index (P<0.001). For iron deficiency, sensitivity, specificity, positive predictive value, and negative predictive value were 88.9%, 30.4%, 33.3%, and 87.5%, respectively. The receiver operating characteristic curves, showed that FEP had excellent diagnostic power to detect iron deficiency. There was a significant difference in the prevalence of iron deficiency among the three athletes, with runners and badminton players tending to be affected more frequently with iron deficiency than static athletes such as the shooters (runners and badminton vs. shooting athletes, 33.3% and 25.0% vs. 19.2%). CONCLUSION: Our results confirmed FEP to be the most significant factor for the diagnosis of iron deficiency in athletes. Proper nutritional counseling and monitoring need to be tailored to various sports, especially in terms of static versus nonstatic sports such as runners and badminton players versus shooting athletes.

Effect of Estradiol on Heme Biosynthetic Pathway in Lead-Poisoned Rabbits

Objectives: To clarify the effect of the female hormone estradiol (Est) on heme biosynthesis in lead-poisoned rabbits, parameters indicating lead exposure, such as free erythrocyte protoporphyrin (FEP) level and δ-aminolevulinic acid dehydratase (ALA-D) activity, were determined. Methods: Twenty-six male Japanese white rabbits (body weight (BW), 3 kg) were divided into four groups: I (control), II (Est), III (Pb), IV (Est+Pb). About 3 weeks after castration, Est (3 mg/kg of BW) was injected intramuscularly, and 2 weeks thereafter, lead (1.2 mg/kg of BW) was injected intravenously. After the initial injection of each of these substances, the same dose of each of these substances was injected once a week until the 9th week. Results: In groups III and IV, FEP level increased and ALA-D activity in the erythrocytes, bone marrow and liver decreased with an increase in lead concentration in blood. FEP level decreased significantly (p<0.01) in the 8th and 10th weeks after Est injection in group IV compared to with that in group III and was not elevated in group II compared with that in group I. ALA-D activity in the erythrocytes, bone marrow and liver increased significantly in group II compared with that in group I, whereas Ht and Hb levels decreased in group II compared with those in group I, and decreased in group IV compared with those in group III. The level of iron in plasma (Fe-P) was within the normal range during experiment. Conclusions: In this study, Est did not increase FEP level. From the above results regarding FEP level and ALA-D activity, Est may prevent an increase in FEP level caused by lead. Ht and Hb levels, which are the parameters of anemia, decreased mainly as a result of Est exposure rather than lead exposure.

Effect of estradiol on heme biosynthetic pathway in lead-poisoned rabbits

<p><b>OBJECTIVES</b>To clarify the effect of the female hormone estradiol (Est) on heme biosynthesis in lead-poisoned rabbits, parameters indicating lead exposure, such as free erythrocyte protoporphyrin (FEP) level and δ-aminolevulinic acid dehydratase (ALA-D) activity, were determined.</p><p><b>METHODS</b>Twenty-six male Japanese white rabbits (body weight (BW), 3kg) were divided into four groups: I (control), II (Est), III (Pb), IV (Est+Pb). About 3 weeks after castration, Est (3 mg/kg of BW) was injected intramuscularly, and 2 weeks thereafter, lead (1.2 mg/kg of BW) was injected intravenously. After the initial injection of each of these substances, the same dose of each of these substances was injected once a week until the 9th week.</p><p><b>RESULTS</b>In groups III and IV, FEP level increased and ALA-D activity in the erythrocytes, bone marrow and liver decreased with an increase in lead concentration in blood. FEP level decreased significantly (p<0.01) in the 8th and 10th weeks after Est injection in group IV compared to with that in group III and was not elevated in group II compared with that in group I. ALA-D activity in the erythrocytes, bone marrow and liver increased significantly in group II compared with that in group I, whereas Ht and Hb levels decreased in group II compared with those in group I, and decreased in group IV compared with those in group III. The level of iron in plasma (Fe-P) was within the normal range during experiment.</p><p><b>CONCLUSIONS</b>In this study, Est did not increase FEP level. From the above results regarding FEP level and ALA-D activity, Est may prevent an increase in FEP level caused by lead. Ht and Hb levels, which are the parameters of anemia, decreased mainly as a result of Est exposure rather than lead exposure.</p>

A Case of Erythropoietic Protoporphyria / 대한피부과학회지

Erythropoietic protoporphyria(EPP) is an inherited inborn error of porphyrin metabolism caused by decreased activity of the enzyme ferrochelatase. EPP is characterized clinically by photosensitivity to visible light commencing in childhood, and biochemically by elevated red cell free protoporphyrin levels. We report herein a case of EPP which occurred in a 44-year-old man and his family. He had suffered from immediate photosensitivity since he was 4 years old. He was presented with burning, erythema, scars and waxy thickening of the sun-exposed skin. Red cell free protoporphyrin level was elevated and urinary porphyrins were normal. Histopathologically, homogeneous eosinophilic materials that stained with PAS were deposited in perivascular area of upper dermis. He was managed with light restriction and sunscreen.

The primary study on the relationship between hemoglobin, erythrocyte protoporphrin and altitude / 实用儿科临床杂志

Objective To ssarch for the relationship between hemoglobulin (Hb),erythrocyte protoporphyrin (EP) and the altitude.Methods The altitudes of Guinan and Maduo county in Qinghai province are respectively 3200m and 4300m. The 122 healthy students aged from 7 to 14 years old were selected, Hb and EP of them were respectively determined by the methods of ferric cyanation and fluorospectrophotometry. The statistical treatment was carry out by t test and matched-pair t test.Results The Hb levels of the healthy children aged from 7 to 14 years old in Guinan and Maduo county are respectively 133 .6?10.1 and 152.8?14.0 g/L (t = 12.31, p＜0.001), the EP levels of them are respectively 320.7 ? 114.9 and 347.8 ? 123.6 ?g/L (t = 1.77, P＞0.05), the value of EP/Hh of them are respectively 2.4 ?0 .9 and 2 .3?0.8 (t = 1.12, p＞0.05). The result of matched-pair t test shows that there are not sexural difFerence for Hb, EP and EP/Hb (P＞0.05).Conclusion Along with the increasing of altitude, the Hb and EP levels of the healthy Children aged from 7 to 14 years old are obviously increased and on sexural difference.

Erythropoietic Protoporphyria in a Family

Erythropoietic protoporphyria (EPP) is an autosomal dominant condition due to decreased activity of ferrochelatase. The disease is characterized by a wide range of photocutaneous changes and occasionally by liver disease. The level of protoporphyin is raised in erythkocytes and it may also be increased in the feces. We report herein a case of EPP present in a family which was diagnosed by a high free erythrocyte protoporphyrin (FEP) count.

Erythropoietic Protoporphyria in a Family

Erythropoietic protoporphyria (EPP) is an autosomal dominant condition due to decreased activity of ferrochelatase. The disease is characterized by a wide range of photocutaneous changes and occasionally by liver disease. The level of protoporphyin is raised in erythkocytes and it may also be increased in the feces. We report herein a case of EPP present in a family which was diagnosed by a high free erythrocyte protoporphyrin (FEP) count.

A case of erythropoietic protoporphyria / 대한피부과학회지

Erythropoietic protoporphyria, sometimes also called erythrohepitic protoporphyria or simple protoporphyria, is a heritable detect of heme synthesis in which the last enzyme of the heme synthetic pathway, ferrochelatase(or heme synthetase), is functioning subopt,imally. A 23-year-old male has experi nced erythema and edema on the fae and hands during or immediately after sun exposure, since 3 years of age. The skin lesions have been accompanied by severe itching, a buring sensation and pain. Severe episodes were followed hy head iche and vomiting. We have seen a case of erythropoietic protoporphyria presenting clinically and histo athologically, wit.h a skin lesion on the sun exposured area, and free erthrocyte protoporphyrin serologically.

DISTRIBUTION AND NORMAL VALUE OF FREEERYTHROCYTE PROTOPORPHYRIN IN NON-IRONDEFICIENT INFANTS AND CHILDREN / 营养学报

0.05, but there was a larger deviation with Model 930.