Next Article in Journal
Prevalence and Socio-Demographic Correlates of Dental Anxiety among a Group of Adult Patients Attending Dental Outpatient Clinics: A Study from UAE
Previous Article in Journal
Psychosocial Risks among Quebec Healthcare Workers during the COVID-19 Pandemic: A Social Media Analysis
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
IJERPH
Volume 20
Issue 12
10.3390/ijerph20126117
ijerph-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles thumb_up
...
Endorse textsms
...
Comment
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Review

Evaluating the Diagnostic Performance of Hemoglobin in the Diagnosis of Iron Deficiency Anemia in High-Altitude Populations: A Scoping Review

by
Cinthya Vásquez-Velásquez
1,2,*,
Daniel Fernandez-Guzman
3,*,
Carlos Quispe-Vicuña
4,
Brenda Caira-Chuquineyra
5,
Fabricio Ccami-Bernal
5,
Piero Castillo-Gutierrez
4,
Miriam Arredondo-Nontol
6 and
Gustavo F. Gonzales
1,2
1
Laboratorio de Endocrinología y Reproducción, Laboratorios de Investigación y Desarrollo (LID), Departamento de Ciencias Biológicas y Fisiológicas, Facultad de Ciencias y Filosofía Alberto Cazorla Tálleri, Universidad Peruana Cayetano Heredia, Lima 15102, Peru
2
Instituto de Investigaciones de la Altura, Universidad Peruana Cayetano Heredia, Lima 15102, Peru
3
Carrera de Medicina Humana, Universidad Científica del Sur, Lima 15067, Peru
4
Sociedad Científica San Fernando, Universidad Nacional Mayor de San Marcos, Lima 15081, Peru
5
Facultad de Medicina, Universidad Nacional de San Agustín de Arequipa, Arequipa 04001, Peru
6
Escuela Profesional de Medicina Humana, Universidad Nacional de Tumbes, Tumbes 24001, Peru
*
Authors to whom correspondence should be addressed.
Int. J. Environ. Res. Public Health 2023, 20(12), 6117; https://doi.org/10.3390/ijerph20126117
Submission received: 9 January 2023 / Revised: 7 February 2023 / Accepted: 26 February 2023 / Published: 13 June 2023
Browse Figure
Review Reports Versions Notes

Abstract

:
We evaluated the available literature on the diagnostic performance of hemoglobin (Hb) in the diagnosis of iron deficiency anemia (IDA) in high-altitude populations. We searched PubMed, Web of Science, Scopus, Embase, Medline by Ovid, the Cochrane Library, and LILCAS until 3 May 2022. We included studies that evaluated the diagnostic performance (sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), receiver operating characteristic (ROC) curves, and accuracy) of Hb (with and without an altitude correction factor) compared to any iron deficiency (ID) marker (e.g., ferritin, soluble transferrin receptor (sTFR), transferrin saturation, or total body iron (TBI)) in populations residing at altitudes (≥1000 m above sea level). We identified a total of 14 studies (with 4522 participants). We found disagreement in diagnostic performance test values between the studies, both in those comparing hemoglobin with and in those comparing hemoglobin without a correction factor for altitude. Sensitivity ranged from 7% to 100%, whereas specificity ranged from 30% to 100%. Three studies reported higher accuracy of uncorrected versus altitude-corrected hemoglobin. Similarly, two studies found that not correcting hemoglobin for altitude improved the receiver operating characteristic (ROC) curves for the diagnosis of iron deficiency anemia. Available studies on high-altitude populations suggest that the diagnostic accuracy of Hb is higher when altitude correction is not used. In addition, the high prevalence of anemia in altitude regions could be due to diagnostic misclassification.

1. Introduction

Anemia is considered a common problem of public health worldwide [1]. It affects mainly infants and children aged 6–59 months, women of reproductive age, pregnant women, and the elderly population, especially in developing countries [1]. Despite intensive interventions by different governments [2], the official statistics reveal that anemia prevalence has stagnated, and in low- and middle-income countries (LMICs) and developing countries, a trend to increase the prevalence of anemia has been observed [3].
The World Health Organization (WHO) recognizes iron deficiency (ID), mainly due to insufficient iron in the diet, followed by inflammation, as the main causes of anemia [4,5]. For such reason, almost all the governments in the world use iron supplementation and/or food fortification with iron as a strategy to reduce anemia prevalence. However, results are modest [2,6].
There are several explanations for this lack of response, including low adherence and the inefficacy of stakeholders to provide iron to the population, among others [7]. However, in recent years, other explanations have been given, such as the cutoff point to define anemia, but these are inadequate in different populations [8]. For example, the hemoglobin (Hb) cutoff for children aged 6–59 months is 11 g/dL, but this value does not reflect the normal change with age [9,10]. Another case is in pregnancy, in which the Hb cutoff is 1 g/dL lower in pregnant women, but this may not be enough for normal hemodilution in all pregnant women [11]. Finally, WHO recommends a correction of Hb per altitude as a universal rule for all the countries around the world [4]. However, not all populations living at the same altitude have similar Hb values, as observed in the Himalayas, where Tibetans have a lower Hb concentration than people of the Han ethnicity [12]. This is due to the fact that Tibetans have lived for more than 25,000 years in the highlands, whereas Hans have been living there for no more than 70 years [13,14].
Due to these reasons, it is necessary to properly establish the diagnosis of iron deficiency anemia (IDA) to avoid difficulties in the management and treatment of these patients. Therefore, in support of evidence-based decision making, we conducted this study with the aim of evaluating the available literature on the diagnostic accuracy of Hb in the diagnosis of IDA in high-altitude populations, since these populations have presented the highest prevalence of IDA when using Hb correction for altitude [15].

2. Materials and Methods

We performed a scoping review following the guidelines of the Preferred Reporting Items for Systematic and Meta-Analysis extension for Scoping Reviews (PRISMA-ScR) of 2018 [16] and the methodology described by the Joanna Briggs Institute [17]. A review protocol can be obtained from the Open Science Framework (https://osf.io/v7upm/ [accessed on 19 December 2022]).

2.1. Data Sources and Searches

We searched for articles in the following databases: (1) PubMed, (2) Web of Science/Core collection, (3) Scopus, (4) Embase, (5) Medline by Ovid, (6) Cochrane Library, and (7) Latin American and Caribbean Health Sciences Literature (LILCAS). The search was conducted on 3 May 2022. There were no restrictions regarding language or date of publication. Search terms were grouped into 4 categories: altitude, anemia for iron deficiency, Hb, and other hematological parameters of iron status. The full search can be found in Supplementary Material S1.

2.2. Study Selection

We considered studies that evaluated the diagnostic performance of Hb (with and without a correction factor for altitude) in comparison with any ID marker (e.g., ferritin, soluble transferrin receptor (sTFR), transferrin saturation, or total body iron (TBI)) in populations residing at altitudes (≥1000 m above sea level). We also considered for study eligibility those studies that reported some diagnostic performance test, such as sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), receiver operating characteristic (ROC) curves, and accuracy. If the data were sufficient to calculate a diagnostic performance test, they were also included.
Duplicate items were manually removed with Rayyan software [18]. Subsequently, two pairs of authors (FCB and CQV) independently reviewed the titles and abstracts of the studies to identify potentially relevant studies for inclusion. These studies were full-text-reviewed independently by two authors (MAN and PCG). Any disagreement in selection was discussed with another author (DFG) and resolved by consensus. In addition, the reference list of all included studies was reviewed to complement the search. Authors with expertise in the field were contacted for additional studies not included.

2.3. Data Extraction

An extraction sheet was designed in Microsoft Excel, and the data of interest were obtained independently by two authors (CQV and BCC). Discrepancies were resolved with a different author (DFG). First, we extracted report data, such as the title, publication date, first author, and publication type. Second, we extracted methodological data, such as the research design, setting, study period, countries, study population (infants, reproductive-age women, pregnant women, adults), and sample size. Third, we extracted information about the diagnosis of anemia and ID, such as the type of index test (Hb with or without the correction factor for altitude), the reference test (ferritin, soluble transferrin receptor (sTFR), transferrin saturation, total body iron (TBI), sTFR–ferritin index, plasma iron), and the cutoff points used for the diagnosis of anemia or ID. Finally, we extracted or calculated the prevalence of anemia by Hb, and ID by the reference test. The diagnostic performance of Hb (sensitivity, specificity, PPV, NPV, false positive rate, false negative rate, AUC, Youden index, and accuracy) was estimated. We did not plan to perform a formal critical appraisal of studies for this scoping review.

2.4. Data Synthesis

We performed a synthesis of the diagnostic performance of Hb, grouping the studies by altitude of residence and age group (infants, reproductive-age women, pregnant women, adults). For this purpose, the studies were classified into those applying the same diagnostic procedures (e.g., studies comparing Hb to the same reference test), reference altitude (e.g., moderate altitude (1000 to 2500 m), high altitude (2500 to 3500 m), very high altitude (3500 to 5500 m), extreme altitude (>5500 m) [19]), and sample size. Finally, we presented the countries where the studies were performed by means of a map.

3. Results

3.1. Literature Search and Selection Process

In the systematic search, 312 studies were identified after removing duplicates. Of these, 79 full-text studies were reviewed for eligibility. Seven studies were additionally reviewed from other sources (expert recommendation and references of eligible studies). Finally, 14 studies were included in the review. The selection process is summarized in Figure 1. In addition, the reasons for exclusion of full-text studies reviewed are available in Supplementary Material S2.

3.2. Study Characteristics

The number of participants ranged from 66 to 804, with a total of 4522 high-altitude residents and with a predominance of women and children. Five studies evaluated only women of reproductive age [20,21,22,23,24], one study evaluated postpartum women [25], four studies included infants [24,26,27,28], and three studies evaluated the general population [29,30,31]. Regarding the altitude where the studies were conducted, we found six studies that included populations located between 1000 and 2500 m [20,21,22,32,33], four studies that included populations located between 2500 and 3500 m [25,26,29,30,32], and seven studies that evaluated populations located above 3500 m [23,24,27,28,29,30,32]. The characteristics of the studies are listed in Table 1.
Four studies were conducted in Bolivia [23,24,26,28] and three in Peru [27,32,32], while one study each was conducted in Saudi Arabia [20], South Africa [21], Ethiopia [22], Mexico [25], the Democratic Republic of the Congo [33], Papua New Guinea [31], and India [30] (Figure S1).
Of the 14 included studies, 3 [21,27,32] assessed the role of Hb in the diagnosis of anemia at an altitude using ROC curves. The reference standard (ID marker) most frequently evaluated was ferritin in 11 studies [20,21,22,24,25,26,27,28,30,31,33], followed by TBI in 4 studies [22,24,29,32], sTFR in 3 studies [21,22,24], and transferrin saturation in 3 studies [22,23,25]. The cutoff points for these markers were similar between studies according to the age of the population but with heterogeneity when adjusting for inflammation. With regard to the Hb cutoff point to classify as positive for anemia, we found 12 studies [20,21,22,24,25,26,27,28,29,31,32,33] used the correction for altitude recommended by WHO [4]; however, 6 studies [20,21,23,27,29,32] evaluated Hb without using this correction factor (Table 2 and Table 3).

3.3. Diagnostic Performance Tests for IDA

The diagnostic performance of Hb versus other markers of iron status, including the prevalence of disease for each marker, are detailed in Table 2 and Table 3 and are briefly summarized in this section. The number of true and false positive cases and true and false negative cases for each comparator can be reviewed in Supplementary Material S4.
A. Hemoglobin vs. Ferritin, 11 studies.
The sensitivity of the studies ranged from 7% to 100%, the specificity ranged from 71% to 98%, and the accuracy ranged from 30% to 98%. In addition, Alkhaldy et al. reported that after correcting Hb for altitude (2270 m), the prevalence of anemia increased by 14%, well below the reported prevalence of ID [20]. Silubonde et al. (1700 m) found that a cutoff point higher than 12 g/dL of Hb (without correction for altitude) generated a higher discrimination threshold in the ROC curves for diagnosis of IDA [21]. In addition, Gonzales et al. [27] found that when not correcting Hb for altitude (3800 m), the prevalence of anemia and IDA by ferritin was similar, with a difference of 15% vs. ~70% when using the correction factor. The accuracy of Hb without the correction factor was between 63% and 69%. When the correction for altitude was used, the accuracy was between 31% and 77%. Only the study by Okumiya et al. [30] did not report whether the correction factor for altitude was used, and presented an accuracy of 83% in a population located between 2900 and 4900 m in India (Table 2).
B. Hemoglobin vs. sTFR, 3 studies.
The study by Burke et al. [24], performed at 4000 m, found a sensitivity of >90% for Hb, with the correction factor among infants (1 to 19 months) when the sTFR was corrected for inflammation status. In addition, it found a higher accuracy in older-age groups (6 to 19 months), as well as a lower specificity at older ages. However, Silubonde et al. [21] found that a value of 12.35 g/dL of Hb at an altitude of 1700 m for non-pregnant women obtained the highest threshold (ROC = 0.63) for the diagnosis of IDA. Finally, Gebreegziabher et al. [22] reported a sensitivity of 30%, a specificity of 79%, and an accuracy of 77% in non-pregnant women residing at 1708 m (Table 3).
C. Hemoglobin vs. TBI, 4 studies.
Alarcon-Yaquetto et al. [29] reported that the specificity and accuracy were higher for the diagnosis of IDA when the correction factor for altitude (3400 m) was not used. Gebreegziabher et al. [22] reported a higher diagnosis of anemia (21.3%) using Hb with the correction factor for altitude (1708 m) than when ID was evaluated with TBI (5.9%) in non-pregnant women of childbearing age.
However, Choque-Quispe et al. [32] reported that in infants aged 6 to 59 months (altitude: 610–4660 m, only 4 children <1000 m), the accuracy decreased from 93% to 10% when the correction factor for altitude was used. They also found that the ROC had a greater area under the curve when Hb was not corrected, even after controlling for age, sex, and altitude. Finally, in the study by Burke et al. [24], which evaluated a cohort of newborns followed up to 10 to 19 months (4000 m), the authors found that the sensitivity of corrected Hb decreased with increasing age, while specificity and accuracy increased with increasing age (Table 3).
D. Hemoglobin vs. Transferrin saturation (TS), 3 studies.
Gebreegziabher et al. [22] reported in a group of non-pregnant women of childbearing age (1708 m) an accuracy of 73%. Villalpando et al. [25] reported a higher prevalence (62.1%) for Hb with correction versus the prevalence of ID measured by TS (47.0%) in postpartum women (2800 m). Meanwhile, Moreno-Black et al. [23] found that in non-pregnant women (3600 m), the accuracy was 93% when Hb was not corrected for altitude (Table 3).
E. Hemoglobin vs. other tests, 3 studies.
Finally, we highlight the study of Alarcon-Yaquetto et al. [29] that found in residents at 3400 m a higher accuracy for the diagnosis of IDA when the correction factor for altitude was not used (76% vs. 71%). Furthermore, the study by Gebreegziabher et al. [22] evaluated the performance of corrected Hb versus plasma iron (<500 μg/L), while Villalpando et al. compared Hb with a correction factor versus ≥2 indexes (serum ferritin (≤12 g/L), transferrin saturation (≤16%), or mean corpuscular value (MCV; ≤80 fL)); see Table 3.

4. Discussion

This review aimed to evaluate the diagnostic accuracy of Hb in IDA in high-altitude populations. We found 14 studies (with 4522 participants living at an altitude) that evaluated the diagnosis of IDA, comparing the value of Hb against a marker of ID. In general, we found heterogeneity in terms of age group, altitude of residence, and reference test to measure iron status. The prevalence of IDA was higher when only the Hb value was used but was lower when the correction for altitude was not used. Similarly, we found that the accuracy was higher for uncorrected Hb, mainly in populations above 3500 m. Regarding the assessment of the best diagnostic threshold (ROC curves), we found that in two studies [21,32], when Hb was not corrected for altitude, the AUC improved for making the diagnosis of IDA. As previous studies indicate, the high prevalence of anemia in high-altitude populations could be due to a systematic error in using a factor that does not have good diagnostic performance [11,34,35,36]. In addition, the different metabolism of high-altitude residents could cause a lower response rate to iron supplementation [37]).
In 1989, WHO recommended an adjustment for the residence altitude for Hb values for the diagnosis of anemia, starting the correction from an arbitrary point at 1000 m [4,38]. This cutoff point has a basis that is not representative worldwide and, to date, has several problems when used in some high-altitude populations. Thus, populations of greater generational seniority, such as the Ethiopians (Ethiopia) and Tibetans (Nepal, China, and India), have lower Hb than those of lesser generational seniority, due to a possible process of transgenerational genetic adaptation [12]. Similarly, in the Peruvian Andes, epigenetic modifications in DNA have been reported that could explain an adaptation of residents born in the region to altitude [39]. Furthermore, in the older population (Quechua residents of southern Peru), a lower Hb level has been observed than in the residents of central Peru, which would indicate a greater adaptation to altitude [40]. In this sense, the findings of the studies included in this review indicate that the diagnostic value of Hb in IDA in high-altitude residents is better when a correction factor is not considered. This would suggest a possible physiological adaptation process, mainly at altitudes above 3000 m, which would justify re-evaluating the anemia cutoff points for each region with high-altitude population, considering generational seniority.
We found six studies that used Hb not corrected for altitude in the evaluation of the diagnosis of IDA. We observed that not using correction for altitude decreased the prevalence of anemia by 5% to 83% [24,27,29,32], with the greatest drop in high-altitude populations. In this regard, a meta-analysis found that Hb levels increase as one ascends to higher altitudes and that the prevalence of anemia (with use of the correction factor) is the highest in the high Andean regions of the world [41]. In addition, based on population survey data, researchers have found that current recommendations for adjusting Hb levels may under-adjust Hb for occasional smokers and for those residing at lower altitudes and over-adjust Hb for those residing at higher altitudes [42].
Of greater concern is the overadjustment in Andean and Tibetan populations that present a different adaptation phenotype for altitude compared to other populations [43]. In the same sense, it has been reported that correction for altitude should not be used to assess the effects of maternal Hb on newborn outcomes, as this correction could minimize the true risk of presenting erythrocytosis and/or anemia at an altitude [44].
In clinical practice, Hb is used to diagnose anemia. Furthermore, it is common to observe ID as the first cause of anemia [1]. However, in high-altitude residents, problems have been reported in adequately identifying the causes of anemia. For example, in children in the Puno-Peru region (over 3800 m), of a total of 223 children diagnosed with anemia (using the correction factor), the authors estimated that about 22% were attributable to iron deficiency and 28% to inflammatory anemia, with 50% of children diagnosed with anemia but with no identifiable common cause [45]. This would suggest that there is an overestimation in the diagnosis of anemia. It should be recognized that other causes of anemia, such as heredity or infections, should be less prevalent than IDA and would not justify the high proportion of unidentified anemia [1]. Therefore, these findings would suggest that there is an inaccurate diagnosis of IDA in high-altitude residents, which could lead to overdiagnosis and inappropriate iron treatment. It is necessary to highlight that unnecessary treatment with ferrous sulfate could generate negative effects in some populations; for example, in pregnant women, high iron levels could reduce the utero-placental flow and more likely cause intrauterine growth retardation [46].
Our scoping review provides information about the diagnostic value of Hb with and without correction for altitude to predict the IDA status in high-altitude populations. We also discuss the current problem of using corrected cutoff points for the diagnosis of anemia at an altitude and the implications of misdiagnosing IDA. Based on this, we recommend that the established recommendations for diagnosing anemia in high-altitude residents be reevaluated. In addition, consideration should be given to the geographic and ethnic diversity and physiologic adaptations of residents with generational seniority. The use of different iron markers as the gold standard for diagnosing IDA should be used for work-up and research protocols to obtain a clearer and more comparable picture between studies, considering the adjustment of these tests for inflammatory conditions.
The main limitation of the included studies was the small sample size (with a minimum of 66 and a maximum of 492 participants included) from non-randomized enrollments. In addition, 13 of the 14 studies had an analytical cross-sectional design, limiting the understanding of variation over time in the baseline tests. However, the cutoff points and adjustment factors used for Hb and the reference tests were heterogeneous. Finally, only three studies aimed to assess the diagnostic threshold for Hb without a correction factor.
Similarly, our scoping review has some limitations. First, although the primary evidence was not entirely scarce, it was not uniform, as it was mostly concentrated in South American regions, which would prevent us from obtaining a global picture of our problem. Second, the methodological quality of the included studies was not formally evaluated, which would limit the reliability of the reported results. Finally, by including only published studies, there is a possibility of not having covered the totality of studies performed and incurring a publication bias. Despite these limitations, our study also has strengths. First, to the best of our knowledge, this is the first scoping review that provides an overview of the literature in this area. Second, this review was based on the methodological recommendations of the JBI [17] and PRISMA [16]. Finally, we believe that our results can contribute to the scientific evidence on the diagnostic value of Hb for the diagnosis of iron deficiency in high-altitude residents.

5. Conclusions

In summary, limited evidence is available on the diagnostic accuracy of Hb with and without a correction factor for altitude in the diagnosis of IDA. However, available studies in high-altitude populations suggest that the diagnostic accuracy of Hb is higher when altitude correction is not used. In addition, the high prevalence of anemia in high-altitude regions could be due to diagnostic misclassification. Based on this, we recommend that the established recommendations for diagnosing anemia in high-altitude residents be reevaluated, considering the geographic and ethnic diversity and physiological adaptations of residents with generational seniority. We also suggest further evaluation of the topic in order to facilitate a systematic review in the future.

Supplementary Materials

The following supporting information can be downloaded at https://www.mdpi.com/article/10.3390/ijerph20126117/s1: Supplementary Material S1. Search strategy; Supplementary Material S2. Reasons for exclusion of studies; Supplementary Material S3: Figure S1: Heat map of the countries of the included studies; Supplementary Material S4. Tables of the number of true and false positive cases and true and false negative cases for hemoglobin vs. each comparator: Table S1. Results of diagnostic test accuracy of studies—hemoglobin vs. ferritin; Table S2. Results of diagnostic test accuracy of studies—hemoglobin vs. other markers of iron deficiency; Supplementary Material S5. PRISMA-ScR checklist.

Author Contributions

D.F.-G. participated in the conceptualization of the study. D.F.-G., B.C.-C. and C.Q.-V. designed the study. D.F.-G., C.Q.-V., B.C.-C., F.C.-B., P.C.-G. and M.A.-N. participated in the data collection. D.F.-G., C.Q.-V., C.V.-V. and G.F.G. performed the data analyses. All authors have read and agreed to the published version of the manuscript.

Funding

CV-V and GFG receive funding from the Universidad Peruana Cayetano Heredia.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

All data are available in the paper and Supplementary Materials.

Conflicts of Interest

The authors declare that they do not have any conflict of interest.

References

  1. Safiri, S.; Kolahi, A.-A.; Noori, M.; Nejadghaderi, S.A.; Karamzad, N.; Bragazzi, N.L.; Sullman, M.J.M.; Abdollahi, M.; Collins, G.S.; Kaufman, J.S.; et al. Burden of anemia and its underlying causes in 204 countries and territories, 1990–2019: Results from the Global Burden of Disease Study 2019. J. Hematol. Oncol. 2021, 14, 185. [Google Scholar] [CrossRef] [PubMed]
  2. Pasricha, S.-R.; Drakesmith, H.; Black, J.; Hipgrave, D.; Biggs, B.-A. Control of iron deficiency anemia in low- and middle-income countries. Blood 2013, 121, 2607–2617. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  3. Stevens, G.A.; Paciorek, C.J.; Flores-Urrutia, M.C.; Borghi, E.; Namaste, S.; Wirth, J.P.; Suchdev, P.S.; Ezzati, M.; Rohner, F.; Flaxman, S.R.; et al. National, regional, and global estimates of anaemia by severity in women and children for 2000–19: A pooled analysis of population-representative data. Lancet Glob. Health 2022, 10, e627–e639. [Google Scholar] [CrossRef]
  4. World Health Organization. Haemoglobin Concentrations for the Diagnosis of Anaemia and Assessment of Severity. World Health Organization. 2011. Available online: https://apps.who.int/iris/handle/10665/85839 (accessed on 13 November 2022).
  5. Chaparro, C.M.; Suchdev, P.S. Anemia epidemiology, pathophysiology, and etiology in low- and middle-income countries. Ann. N. Y. Acad. Sci. 2019, 1450, 15–31. [Google Scholar] [CrossRef] [Green Version]
  6. Mithra, P.; Khatib, M.N.; Sinha, A.P.; Kumar, N.; Holla, R.; Unnikrishnan, B.; Vijayamma, R.; Nair, N.S.; Gaidhane, A.; Zahiruddin, S.Q. Interventions for Addressing Anemia Among Children and Adolescents: An Overview of Systematic Reviews. Front. Pediatr. 2021, 8, 549549. [Google Scholar] [CrossRef]
  7. Miniero, R.; Talarico, V.; Galati, M.C.; Giancotti, L.; Saracco, P.; Raiola, G. Iron Deficiency and Iron Deficiency Anemia in Children. In Iron Deficiency Anemia; Rodrigo, L., Ed.; IntechOpen: London, UK, 2019. [Google Scholar] [CrossRef] [Green Version]
  8. Sarna, K.; Brittenham, G.M.; Beall, C.M. Detecting anaemia at high altitude. Evol. Med. Public Health 2020, 2020, 68–69. [Google Scholar] [CrossRef]
  9. Ocas-Córdova, S.; Tapia, V.; Gonzales, G.F. Hemoglobin Concentration in Children at Different Altitudes in Peru: Proposal for [Hb] Correction for Altitude to Diagnose Anemia and Polycythemia. High Alt. Med. Biol. 2018, 19, 398–403. [Google Scholar] [CrossRef] [PubMed]
  10. Mantadakis, E. Serum Ferritin Threshold for Iron Deficiency Screening in One-Year-Old Children. J. Pediatr. 2022, 245, 12–14. [Google Scholar] [CrossRef]
  11. Salvi, C.C.B.; Braga, M.C.; Batista Filho, M. Diagnostic accuracy of hemoglobin for iron deficiency in pregnancy: Disclosing results of a cited clinical trial. Rev. Panam. Salud Publica 2014, 36, 110–116. [Google Scholar]
  12. Beall, C.M.; Cavalleri, G.L.; Deng, L.; Elston, R.C.; Gao, Y.; Knight, J.; Li, C.; Li, J.C.; Liang, Y.; McCormack, M.; et al. Natural selection on EPAS1 (HIF2α) associated with low hemoglobin concentration in Tibetan highlanders. Proc. Natl. Acad. Sci. USA 2010, 107, 11459–11464. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  13. Weitz, C.A.; Liu, J.-C.; He, X.; Chin, C.-T.; Garruto, R.M. Responses of Han Migrants Compared to Tibetans at High Altitude: Han and Tibetans at High Altitude. Am. J. Hum. Biol. 2013, 25, 169–178. [Google Scholar] [CrossRef] [PubMed]
  14. Simonson, T.S. Altitude Adaptation: A Glimpse Through Various Lenses. High Alt. Med. Biol. 2015, 16, 125–137. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  15. Accinelli, R.A.; Leon-Abarca, J.A. Age and altitude of residence determine anemia prevalence in Peruvian 6 to 35 months old children. PLoS ONE 2020, 15, e0226846. [Google Scholar] [CrossRef] [Green Version]
  16. Tricco, A.C.; Lillie, E.; Zarin, W.; O’Brien, K.K.; Colquhoun, H.; Levac, D.; Moher, D.; Peters, M.D.J.; Horsley, T.; Weeks, L.; et al. PRISMA Extension for Scoping Reviews (PRISMA-ScR): Checklist and Explanation. Ann. Intern. Med. 2018, 169, 467–473. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  17. Peters, M.; Godfrey, C.; McInerney, P.; Munn, Z.; Tricco, A.; Khalil, H. Chapter 11: Scoping reviews-JBI Manual for Evidence Synthesis. Available online: https://jbi-global-wiki.refined.site/space/MANUAL/4687342/Chapter+11%3A+Scoping+reviews (accessed on 13 November 2022).
  18. Ouzzani, M.; Hammady, H.; Fedorowicz, Z.; Elmagarmid, A. Rayyan—A web and mobile app for systematic reviews. Syst. Rev. 2016, 5, 210. [Google Scholar] [CrossRef] [Green Version]
  19. Sharma, P.; Misra, K. High Altitude and Hypoxia. In Management of High Altitude Pathophysiology; Academic Press: Cambridge, MA, USA, 2018; pp. 3–8. [Google Scholar] [CrossRef]
  20. Alkhaldy, H.Y.; Hadi, R.A.; Alghamdi, K.A.; Alqahtani, S.M.; Al Jabbar, I.S.H.; Al Ghamdi, I.S.; Bakheet, O.S.E.; Saleh, R.A.M.; Shehata, S.F.; Aziz, S. The pattern of iron deficiency with and without anemia among medical college girl students in high altitude southern Saudi Arabia. J. Fam. Med. Prim. Care 2020, 9, 5018–5025. [Google Scholar] [CrossRef]
  21. Silubonde, T.M.; Baumgartner, J.; Ware, L.J.; Malan, L.; Smuts, C.M.; Norris, S. Adjusting Haemoglobin Values for Altitude Maximizes Combined Sensitivity and Specificity to Detect Iron Deficiency among Women of Reproductive Age in Johannesburg, South Africa. Nutrients 2020, 12, 633. [Google Scholar] [CrossRef] [Green Version]
  22. Gebreegziabher, T.; Stoecker, B.J. Iron deficiency was not the major cause of anemia in rural women of reproductive age in Sidama zone, southern Ethiopia: A cross-sectional study. PLoS ONE 2017, 12, e0184742. [Google Scholar] [CrossRef]
  23. Moreno-Black, G.; Quinn, V.; Haas, J.; Franklin, J.; Berard, J. The distribution of haemoglobin concentration in a sample of native high-altitude women. Ann. Hum. Biol. 1984, 11, 317–325. [Google Scholar] [CrossRef]
  24. Burke, R.M.; Rebolledo, P.A.; de Aceituno, A.M.F.; Revollo, R.; Iñiguez, V.; Klein, M.; Drews-Botsch, C.; Leon, J.S.; Suchdev, P.S. Early deterioration of iron status among a cohort of Bolivian infants. Matern. Child Nutr. 2016, 13, e12404. [Google Scholar] [CrossRef] [Green Version]
  25. Villalpando, S.; Latulippe, M.E.; Rosas, G.; Irurita, M.J.; Picciano, M.F.; O’Connor, D.L. Milk folate but not milk iron concentrations may be inadequate for some infants in a rural farming community in San Mateo, Capulhuac, Mexico. Am. J. Clin. Nutr. 2003, 78, 782–789. [Google Scholar] [CrossRef] [Green Version]
  26. Miranda, M.; Olivares, G.M.; Durán-Pérez, J.; Pizarro, A.F. Prevalencia de anemia y estado nutricional de escolares del área periurbana de Sucre, Bolivia. Rev. Chil. Nutr. 2015, 42, 324–327. [Google Scholar] [CrossRef] [Green Version]
  27. Gonzales, G.F.; Begazo, J.; Alarcón-Yaquetto, D.E. Suitability of Haemoglobin Adjustment to Define Anaemia at High Altitudes. Acta Haematol. 2020, 143, 511–512. [Google Scholar] [CrossRef] [PubMed]
  28. Burke, R.M.; Rebolledo, P.A.; Aceituno, A.M.; Revollo, R.; Iñiguez, V.; Klein, M.; Drews-Botsch, C.; Leon, J.S.; Suchdev, P.S. Effect of infant feeding practices on iron status in a cohort study of Bolivian infants. BMC Pediatr. 2018, 18, 107. [Google Scholar] [CrossRef]
  29. Alarcón-Yaquetto, D.E.; Figueroa-Mujica, R.; Valverde-Bruffau, V.; Vásquez-Velásquez, C.; Sánchez-Huamán, J.J.; Jimenez-Troncoso, L.; Rozas-Gamarra, R.; Gonzales, G.F. Hematological Parameters and Iron Status in Adult Men and Women Using Altitude Adjusted and Unadjusted Hemoglobin Values for Anemia Diagnosis in Cusco, Peru (3400 MASL). Physiologia 2022, 2, 1–19. [Google Scholar] [CrossRef]
  30. Okumiya, K.; Sakamoto, R.; Ishikawa, M.; Kimura, Y.; Fukutomi, E.; Ishimoto, Y.; Chen, W.-L.; Imai, H.; Kato, E.; Kasahara, Y.; et al. J-Curve Association Between Glucose Intolerance and Hemoglobin and Ferritin Levels at High Altitude. J. Am. Geriatr. Soc. 2016, 64, 207–210. [Google Scholar] [CrossRef] [Green Version]
  31. Vaterlaws, A.L.; Shield, J.M.; Kimber, R.J.; Payne, R.; Casey, G.J.; Blunden, R.W.; Kutkaite, D. Some haematological and physical characteristics of a group of Papua New Guinea highlanders. Papua New Guin. Med. J. 1981, 24, 4–18. [Google Scholar]
  32. Choque-Quispe, B.M.; Alarcón-Yaquetto, D.E.; Paredes-Ugarte, W.; Zaira, A.; Ochoa, A.; Gonzales, G.F. Is the prevalence of anemia in children living at high altitudes real? An observational study in Peru. Ann. N. Y. Acad. Sci. 2020, 1473, 35–47. [Google Scholar] [CrossRef] [PubMed]
  33. Bahizire, E.; Bahwere, P.; Donnen, P.; Tugirimana, P.L.; Balol’ebwami, S.; Dramaix, M.; Nfundiko, C.; Chirimwami, R.; Mubagwa, K. High Prevalence of Anemia but Low Level of Iron Deficiency in Preschool Children during a Low Transmission Period of Malaria in Rural Kivu, Democratic Republic of the Congo. Am. J. Trop. Med. Hyg. 2017, 97, 489–496. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  34. Barrera-Reyes, P.K.; Tejero, M.E. Genetic variation influencing hemoglobin levels and risk for anemia across populations. Ann. New York Acad. Sci. 2019, 1450, 32–46. [Google Scholar] [CrossRef] [Green Version]
  35. Gonzales, G.F.; Fano, D.; Velásquez, C.V. Necesidades de investigación para el diagnóstico de anemia en poblaciones de altura. Rev. Peru. Med. Exp. Salud Publica 2017, 34, 699–708. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  36. Dang, S.N.; Yan, H.; Wang, X.L. Study on the hemoglobin levels of children under the age of three years and the prevalence of anemia at high altitude in Tibet of China. Zhonghua Liu Xing Bing Xue Za Zhi 2003, 24, 1108–1111. [Google Scholar]
  37. Muckenthaler, M.U.; Mairbäurl, H.; Gassmann, M. Iron metabolism in high-altitude residents. J. Appl. Physiol. 2020, 129, 920–925. [Google Scholar] [CrossRef]
  38. Centers for Disease Control (CDC). CDC criteria for anemia in children and childbearing-aged women. MMWR Morb. Mortal. Wkly. Rep. 1989, 38, 400–404. [Google Scholar]
  39. Childebayeva, A.; Jones, T.R.; Goodrich, J.M.; Leon-Velarde, F.; Rivera-Chira, M.; Kiyamu, M.; Brutsaert, T.D.; Dolinoy, D.C.; Bigham, A.W. LINE-1 and EPAS1 DNA methylation associations with high-altitude exposure. Epigenetics 2019, 14, 1–15. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  40. Mairbäurl, H.; Gassmann, M.; Muckenthaler, M.U. Geographical ancestry affects normal hemoglobin values in high-altitude residents. J. Appl. Physiol. 2020, 129, 1451–1459. [Google Scholar] [CrossRef]
  41. Gassmann, M.; Mairbäurl, H.; Livshits, L.; Seide, S.; Hackbusch, M.; Malczyk, M.; Kraut, S.; Gassmann, N.N.; Weissmann, N.; Muckenthaler, M.U. The increase in hemoglobin concentration with altitude varies among human populations. Ann. N. Y. Acad. Sci. 2019, 1450, 204–220. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  42. Sharma, A.J.; Addo, O.; Mei, Z.; Suchdev, P. Reexamination of hemoglobin adjustments to define anemia: Altitude and smoking. Ann. N. Y. Acad. Sci. 2019, 1450, 190–203. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  43. Beall, C.M. Andean, Tibetan, and Ethiopian patterns of adaptation to high-altitude hypoxia. Integr. Comp. Biol. 2006, 46, 18–24. [Google Scholar] [CrossRef] [Green Version]
  44. Gonzales, G.F.; Steenland, K.; Tapia, V. Maternal hemoglobin level and fetal outcome at low and high altitudes. Am. J. Physiol. Integr. Comp. Physiol. 2009, 297, R1477–R1485. [Google Scholar] [CrossRef] [Green Version]
  45. Choque-Quispe, B.M.; Paz, V.; Gonzales, G.F. Proportion of anemia attributable to iron deficiency in high-altitude infant populations. Ann. Hematol. 2019, 98, 2601–2603. [Google Scholar] [CrossRef] [PubMed]
  46. Gonzales, G.F.; Tapia, V.; Gasco, M.; Carrillo, C. Hemoglobina materna en el Perú: Diferencias regionales y su asociación con resultados adversos perinatales. Rev. Perú. Med. Exp. Salud Publica 2011, 28, 484–491. [Google Scholar] [CrossRef] [PubMed]
Ijerph 20 06117 g001 550
Figure 1. Flow diagram summarizing the process of literature search and selection.
Figure 1. Flow diagram summarizing the process of literature search and selection.
Ijerph 20 06117 g001
Table
Table 1. Characteristics of diagnostic test accuracy of studies: 14 studies and 7 comparisons.
Table 1. Characteristics of diagnostic test accuracy of studies: 14 studies and 7 comparisons.
SourceStudy DesignCountryAltitude (m)SettingSponsorPopulationReference Standard Evaluated (Marker of Iron Deficiency)
Patient Population or SubpopulationNAge: Mean ± SD or RangeMales (%)Type of Test
Alarcon-Yaquetto et al. (2022) [29]Cross-sectionalPeru (Cusco)3400CommunityYesMale or female over 18 years, born and living in Cusco34545.4 ± 15.6 years45.2sTFR–ferritin index (sTFR/log ferritin) and TBI
Alkhaldy et al. (2020) [20]Cross-sectionalSaudi Arabia (Aseer—Abha)2270CommunityNoFemale medical students20020.4 ± 1.5 years0.0Ferritin
Choque-Quispe et al. (2020) [32]Cross-sectionalPeru (Puno)610–4660CommunityYesChildren under 5 years (only 4 children living at <1000 m)40334.5 ± 1.5 months48.9TBI
Silubonde et al. (2020) [21]Cross-sectionalSouth Africa (Gauteng)1700CommunityNoWomen of African descent, generally healthy and not pregnant49221 ± 3 years0.0Ferritin, sTFR
Gonzales et al. (2020) * [27]Cross-sectional lettersPeru (Puno)3800CommunityYesInfants1336–24 monthsNRFerritin
Burke et al. (2018) [28]Cross-sectionalBolivia (El Alto)4000HospitalYesInfants2707 ± 1 months52.6Ferritin
Bahizire et al. (2017) [33]Cross-sectionalDemocratic Republic of the Congo (Kivu—Miti-Murhesa)1500–2000CommunityYesInfants from rural malaria-endemic areas8046–59 months0.1Ferritin
Burke et al. (2016) [24]CohortBolivia (El Alto)4000HospitalYesInfants1601–5 months53.1Ferritin, sTFR, TBI
6–10 months
10–19 months
Mothers of enrolled infants25025.3 ± 6.3 years0.0Ferritin, sTFR, TBI
Gebreegziabher et al. (2017) [22]Cross-sectionalEthiopia (Sidama)1708CommunityYesNon-pregnant women over 18 years20230.8 ± 7.8 years0.0Ferritin, sTFR, transferrin saturation, TBI, plasma iron
Okumiya (2016) [30]Cross-sectional * letterIndia (Ladakh)2900–4900CommunityYesFarmers and nomads from India and migrants from Tibet50055.9 ± 10.9 years43.6Ferritin
Miranda et al. (2015) [26]Cross-sectionalBolivia (Sucre)2750SchoolNoSchoolchildren from 6 to 10 years in the peri-urban area1958.3 ± 1.3 years54.9Ferritin
Villalpando et al. (2003) [25]Cross-sectionalMexico (Capulhuac)2800HospitalNoPostpartum women6624 ± 5 years0.0Ferritin, transferrin saturation, serum iron
Moreno-Black et al. (1984) [23]Cross-sectionalBolivia (La Paz)3600CommunityYesWomen participating in the “Mothers’ Club” in Bolivia15233.8 ± 5.7 years0.0Transferrin saturation
Vaterlaws et al. (1981) [31]Cross-sectionalPapua New Guinea (Goroka)1500CommunityNoRural areas35015–60 years96.9Ferritin
sTFR: soluble transferrin receptor; TBI: total body iron; NR: not reported. * The studies in question complement information from the same evaluated population.
Table
Table 2. Results of diagnostic test accuracy of studies—hemoglobin vs. ferritin.
Table 2. Results of diagnostic test accuracy of studies—hemoglobin vs. ferritin.
SourcePatient PopulationHemoglobin with Factor CorrectionCutoff of Reference StandardPrevalence of AnemiaPrevalence of Iron DeficiencySeSpPPVNPVFPRFNRROCAccuracy
n (%)n (%)
A. Population: Adults over 18 years of age, not pregnant
Alkhaldy et al. (2020) [20]Female medical students from 19 to 27 years of age (n = 200); altitude 2270 mYes<15 ng/mL41 (20.5)105 (52.5)0.330.940.850.560.670.06NR0.62
Yes<20 ng/mL41 (20.5)126 (63.0)0.30.960.930.450.70.04NR0.55
No (12.00 g/dL)<15 ng/mL13 (6.5)116 (58.0)NRNRNRNRNRNRNRNR
Silubonde et al. (2020) [21]Women of African descent, generally healthy and not pregnant, between 18 and 25 years (n = 492); altitude 1700 mNo (12.45 g/dL)<15 µg/L192 (39)178 (36.2)0.580.710.520.760.420.290.680.67
Yes<15 µg/L *192 (39)185 (37.6)0.570.720.550.730.430.28NR0.66
No (12.00 g/dL)<15 µg/L *91 (18.5)185 (37.6)0.340.910.680.690.660.09NR0.69
No (12.35 g/dL)<15 µg/L *183 (37.2)185 (37.6)0.560.740.560.730.440.260.680.67
No (12.45 g/dL)<30 µg/L192 (39)254 (51.6)0.520.740.680.590.480.260.650.63
Gebreegziabher et al. (2017) [22]Non-pregnant women over 18 years; altitude 1708 mYes≤15 µg/L *43 (21.3)36 (17.8)0.280.80.230.840.720.2NR0.71
Okumiya (2016) [30]Farmers and nomads from India and migrants from Tibet; altitude 2900–4900 mNR≤12 ng/mL59 (11.8)116 (23.2)0.40.970.780.840.60.03NR0.83
Vaterlaws et al. (1981) [31]Adults in rural areas; altitude 1500 mYes<30 ug/L10 (2.9)64 (18.3)0.070.980.60.770.930.02NR0.77
B. Population: Postpartum women
Villalpando et al. (2003) [25]Postpartum women; altitude 2800 mYes≤12 µg/L41 (62.1)35 (53)NRNRNRNRNRNRNRNR
C. Population: Children under 5 years of age
Gonzales et al. (2020) [27]Infants 6 to 24 months old; altitude 3800 mYes≤12 ng/ml126 (94.7)35 (26.3)0.541NRNR0.4600.680.58
No (11.0 g/dL)≤12 ng/ml15 (11.3)35 (26.3)NRNRNRNRNRNRNRNR
Burke et al. (2018) [28]Infants; altitude 4000 mYes≤12 µg/L *204 (75.6)151 (55.9)0.830.340.610.610.170.66NR0.61
Bahizire et al. (2017) [33]Infants 6 to 59 months old; altitude 1500–2000 mYes≤12 ug/L377 (46.9)17 (2.1)0.880.540.0410.120.46NR0.55
Yes<30 ug/L *377 (46.9)82 (10.2)0.760.560.160.950.240.44NR0.58
Burke R.M. et al. (2016) [24]Infants 1–5 months old; altitude 4000 mYes≤ 12 μg/L112 (70.0)1 (0.5)10.30.01100.7NR0.31
Yes≤ 12 μg/L *112 (70.0)1 (0.5)10.30.01100.7NR0.31
Infants 6–10 months old; altitude 4000 mYes≤ 12 μg/L121 (75.6)64 (40.3)0.860.320.460.770.140.68NR0.54
Yes≤ 12 μg/L *121 (75.6)89 (55.5)0.830.340.610.610.170.66NR0.61
Infants 10–19 months old; altitude 4000 mYes≤ 12 μg/L130 (81.3)105 (65.5)0.880.310.710.570.120.69NR0.68
Yes≤ 12 μg/L *130 (81.3)127 (79.2)0.850.350.830.390.150.65NR0.75
D. Population: Children from 6 to 10 years old
Miranda M. et al. (2015) [26]Schoolchildren from 6 to 10 years of age in the peri-urban area; altitude 2750 mYes<30 μg/L *35 (17.9)38 (19.5)0.440.990.970.730.560.01NR0.77
Se: sensitivity; Sp: specificity; PPV: positive predictive value; NPV: negative predictive value; FPR: false positive rate; FNR: false negative rate; ROC: receiver operating characteristic; NR: not reported; * adjusted for inflammation.
Table
Table 3. Results of diagnostic test accuracy of studies—hemoglobin vs. other markers of iron deficiency.
Table 3. Results of diagnostic test accuracy of studies—hemoglobin vs. other markers of iron deficiency.
SourcePatient Population Hemoglobin with Factor CorrectionCutoff of Reference StandardPrevalence of AnemiaPrevalence of Iron DeficiencySeSpPPVNPV FPRFNRROC Accuracy
n (%)n (%)
A. hemoglobin vs. sTFR
Silubonde et al. (2020) [21]Women of African descent, generally healthy and not pregnant (n = 492); altitude 1700 m No (12.35 g/dL)≥8.3 mg/L183 (37.2)204 (41.5)NRNRNRNRNRNR0.633NR
Gebreegziabher et al. (2017) [22]Non-pregnant women over 18 years; altitude 1708 m Yes≥8.3 mg/L43 (21.3)10 (5)0.30.790.070.960.70.21NR0.77
Burke et al. (2016) [24]Infants 1–5 months old; altitude 4000 m Yes≥8.3 mg/L112 (70.0)2 (1.4)0.570.30.010.980.430.7NR0.3
Yes≥8.3 mg/L *112 (70.0)1 (0.6)1.280.30.011.01−0.280.7NR0.31
Infants 6–10 months old; altitude 4000 m Yes≥8.3 mg/L121 (75.6)13 (8.4)0.960.260.110.990.040.74NR0.32
Yes≥8.3 mg/L *121 (75.6)12 (7.4)0.960.260.090.990.040.74NR0.31
Infants 10–19 months old; altitude 4000 m Yes≥8.3 mg/L130 (81.3)39 (24.4)0.950.230.280.930.050.77NR0.4
Yes≥8.3 mg/L *130 (81.3)43 (26.8)0.940.230.310.910.060.77NR0.42
B. hemoglobin vs. Transferrin saturation
Gebreegziabher et al. (2017) [22]Non-pregnant women over 18 years; altitude 1708 m Yes<15%43 (21.3)32 (15.8)0.310.810.230.860.690.19NR0.73
Villalpando et al. (2003) [25]Postpartum women; altitude 2800 m Yes≤16%41 (62.1)31 (47.0)NRNRNRNRNRNRNRNR
Moreno-Black et al. (1984) [23]Women participating in the “Mothers’ Club” in Bolivia; altitude 3600 m.No (13.0 g/dL)<15%6 (3.9)17 (11.1)0.35110.920.650NR0.93
C. hemoglobin vs. TBI (mg/kg) = −[log10 (sTfR × 1000/ferritin) − 2.8229]/0.1207.
Alarcon-Yaquetto et al. (2022) [29]Male or female over 18 years, born and living in Cusco (n = 345); altitude 3400 m No (12.0 for women and 13.0 g/dL for men)<0 (mg/kg) *2 (0.6)0 (0.0)00.9900.7710.01NR0.76
Yes<0 (mg/kg) *21 (6.1)0 (0.0)00.8600.7410.14NR0.66
Choque-Quispe et al. (2020) [32]Infants 6–59 months old (n = 403); altitude 610–4660 m No (11.0 g/dL)<0 (mg/kg) *14 (3.5)5 (2.5)0.60.940.210.990.40.06NR0.93
Yes<0 (mg/kg) *182 (45.2)8 (4.1)0.750.070.030.870.250.93NR0.1
Infants 6–35 months old (n = 200); altitude 610–4660 m No (11.0 g/dL)<0 (mg/kg) *12 (6.0)NRNRNRNRNRNRNR0.66 (0.41–0.90)NR
Yes<0 (mg/kg) *122 (61.2)NRNRNRNRNRNRNR0.62 (0.52–0.71)NR
Infants 36–59 months old (n = 203); altitude 610–4660 m No (11.0 g/dL)<0 (mg/kg) *8 (3.9)NRNRNRNRNRNRNR0.88 (0.77–0.99)NR
Yes<0 (mg/kg) *138 (68.0)NRNRNRNRNRNRNR0.63 (0.54–0.72)NR
Infants 36–59 months old without inflammation (n = NR); altitude 610–4660 m No (11.0 g/dL)<0 (mg/kg) *NRNR0.330.970.330.97NRNR0.81 (0.79–0.84)NR
Yes<0 (mg/kg) *NRNR0.830.330.040.98NRNR0.63 (0.62–0.64)NR
Burke et al. (2016) [24]Infants 1–5 months old; altitude 4000 m Yes<0 (mg/kg)112 (70.0)1 (0.6)10.30.01100.7NR0.31
Yes<0 (mg/kg) *112 (70.0)1 (0.6)10.30.01100.7NR0.31
Infants 6–10 months old; altitude 4000 m Yes<0 (mg/kg)121 (75.6)44 (27.7)0.930.310.340.920.070.69NR0.48
Yes<0 (mg/kg) *121 (75.6)62 (39.0)0.910.340.470.860.090.66NR0.56
Infants 10–19 months old; altitude 4000 m Yes<0 (mg/kg)130 (81.3)88 (54.8)0.950.360.640.860.050.64NR0.68
Yes<0 (mg/kg) *130 (81.3)108 (67.3)0.910.380.750.670.090.62NR0.74
Gebreegziabher et al. (2017) [22]Non-pregnant women over 18 years; altitude 1708 m Yes<0 (mg/kg) *43 (21.3)12 (5.9)NRNRNRNRNRNRNRNR
D. Hemoglobin vs. sTFR–ferritin index = sTfR/log ferritin
Alarcon-Yaquetto et al. (2022) [29]Male or female over 18 years of age, born in the city of Cusco and living permanently in the city (n = 345); altitude 3400 m NoTFR-F index < 1.0 and IL-6 < 50 pg/mL2 (0.6)12 (3.5)0.020.990.50.760.980.01NR0.76
YesTFR-F index < 1.0 and IL-6 < 50 pg/mL21 (6.1)12 (3.5)0.190.930.520.730.810.07NR0.71
E. Hemoglobin vs. plasma iron
Gebreegziabher et al. (2017) [22]Non-pregnant women 18–52 years of age; altitude 1708 m Yes<500 μg/L43 (21.3)53 (26.2)0.30.820.370.770.70.18NR0.68
F. Hemoglobin vs. ≥2 indexes (serum ferritin (≤12 g/L), transferrin saturation (≤16%), or MCV (≤80 fL))
Villalpando et al. (2003) [25]Postpartum women; altitude 2800 m Yes ≥2 indexes 41 (62.1)26 (39.4)0.920.580.590.920.080.43NR0.71
sTFR: soluble transferrin receptor; TBI: total body iron; Se: sensitivity; Sp: specificity; PPV: positive predictive value; NPV: negative predictive value; FPR: false positive rate; FNR: false negative rate; ROC: receiver operating characteristic; NR: not reported; MCV: mean corpuscular volume; * adjusted for inflammation.
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.

Share and Cite

MDPI and ACS Style

Vásquez-Velásquez, C.; Fernandez-Guzman, D.; Quispe-Vicuña, C.; Caira-Chuquineyra, B.; Ccami-Bernal, F.; Castillo-Gutierrez, P.; Arredondo-Nontol, M.; Gonzales, G.F. Evaluating the Diagnostic Performance of Hemoglobin in the Diagnosis of Iron Deficiency Anemia in High-Altitude Populations: A Scoping Review. Int. J. Environ. Res. Public Health 2023, 20, 6117. https://doi.org/10.3390/ijerph20126117

AMA Style

Vásquez-Velásquez C, Fernandez-Guzman D, Quispe-Vicuña C, Caira-Chuquineyra B, Ccami-Bernal F, Castillo-Gutierrez P, Arredondo-Nontol M, Gonzales GF. Evaluating the Diagnostic Performance of Hemoglobin in the Diagnosis of Iron Deficiency Anemia in High-Altitude Populations: A Scoping Review. International Journal of Environmental Research and Public Health. 2023; 20(12):6117. https://doi.org/10.3390/ijerph20126117

Chicago/Turabian Style

Vásquez-Velásquez, Cinthya, Daniel Fernandez-Guzman, Carlos Quispe-Vicuña, Brenda Caira-Chuquineyra, Fabricio Ccami-Bernal, Piero Castillo-Gutierrez, Miriam Arredondo-Nontol, and Gustavo F. Gonzales. 2023. "Evaluating the Diagnostic Performance of Hemoglobin in the Diagnosis of Iron Deficiency Anemia in High-Altitude Populations: A Scoping Review" International Journal of Environmental Research and Public Health 20, no. 12: 6117. https://doi.org/10.3390/ijerph20126117

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop