Effect of Anemia on Work Productivity in Both Labor- and Nonlabor-Intensive Occupations: A Systematic Narrative Synthesis

Abstract

Background:

Anemia is highly prevalent particularly in low- and middle-income countries. Iron deficiency contributes to an estimated 50% of anemia cases. Iron interventions have become central to global anemia treatment and prevention; however, few iron interventions have been scaled up to the national level, despite their proven effectiveness. While both cross-sectional and interventional studies on the effect of anemia and iron supplementation on worker productivity have been conducted, there have been few systematic reviews conducted. As such, a synthesis of previously conducted primary research is warranted and may provide a more comprehensive overview of the strength of currently available evidence, potentially helping to inform national policy on matters relating to funding and legislation for population-level iron interventions.

Objectives:

The objective of this study was to synthesize available evidence on the effect of both anemia and therapeutic iron interventions on productivity in working adults.

Methods:

All relevant English language studies were systematically obtained from both MEDLINE and EMBASE and assessed for evidence of differing productivity levels across groups stratified by iron intervention or anemia status. Potential mediating variables were reported, and the results were narratively summarized.

Results:

The available data from 12 included studies provide strong evidence that anemia negatively impacts occupational performance and that therapeutic iron interventions can yield substantial productivity gains.

Conclusions:

Despite their limitations, these findings make an important contribution to the literature highlighting the impact of iron deficiency and population-wide iron interventions on work productivity and occupational performance.

Keywords

anemia iron interventions productivity occupational performance

Introduction

Anemia, a condition characterized by an abnormally low hemoglobin (Hb) concentration in peripheral blood, constitutes a major global public health issue.¹ It is estimated that almost a quarter of the world’s population is anemic, amounting to more than 1.6 billion cases worldwide.² According to the World Health Organization, 42% of pregnant women, 30% of nonpregnant women (aged 15-50 years), 47% of preschool children (aged 0-5 years), and 12.7% of men older than 15 years are anemic.²

The high rates of iron deficiency, in combination with widespread infections such as malaria, helminth diseases, and HIV, result in a disproportionate anemia burden in the developing world.¹ Anemia is reported to account for three-quarters of a million deaths per year in Africa and South East Asia.¹ In addition, anemia is also responsible for a significant source of global morbidity due to its adverse impacts on physical and cognitive development in early childhood.^2,3

While the causes of anemia are multifactorial, it is estimated that iron deficiency accounts for about half of the world’s anemia burden, making it the most common cause of anemia worldwide.^2,4 Acknowledging its significance, leading global players such as the United Nations Children’s Fund, Nutrition International, and other members of civil society have launched numerous initiatives to address iron deficiency anemia (IDA), including but not limited to interventions such as daily and intermittent iron supplementation, home fortification with micronutrient powders, fortification of staple foods and condiments, and activities to improve food security and dietary diversity, many of which have proven highly effective in reducing anemia prevalence.² Yet without support from domestic governments, the potential for scale-up and expanded coverage of well-established iron programs is limited especially in low- and middle-income countries (LMICs) where high IDA rates render an even greater need for such programs.

In 2017, there were only 75 countries with mandatory legislation to fortify wheat flour with iron and folic acid, highlighting the need for greater national policy support in this domain.⁵ This sentiment is backed by the 2015 Arusha Statement on Food Fortification in which the central argument is made that “food fortification should become a critical player of national food and nutrition security plans,” followed by calls for the generation of more evidence to guide fortification policy and program design and to continue advocacy efforts to galvanize greater government support.⁶ In responding to such calls, focus should not only be placed on research concerning the science of effective program implementation but also on the generation of evidence-based advocacy tools that would resonate with national governments, such as those linking legislative action to downstream economic and/or human capital gains.

While the pathophysiological consequences of IDA in relation to oxygen transport have been well established,⁷ the scope of research relating to the direct effect of anemia and/or iron deficiency status on more tangible functional parameters such as occupational performance and work productivity is more limited. As such functional outcomes hold clear economic and societal significance, their relation to IDA is an important area to explore in the pursuit of developing more robust evidence to support the growing economic and cost-effectiveness assessment of national investment in population-wide iron interventions.

While both cross-sectional and interventional studies on the effect of anemia and iron supplementation on worker productivity have been conducted, there have been few systematic reviews conducted on the topic. As such, a synthesis of previously conducted primary research is warranted and may provide a more comprehensive overview of the strength of currently available evidence, potentially helping to inform national policy on matters relating to funding and legislation for population-level iron interventions, as needed to support their national scale-up. Thus, the objective of this study was to synthesize available evidence on the effect of both anemia and therapeutic iron interventions on productivity in working adults.

Methods

This study was conducted in accordance with the methodology outlined in the “guidance for the conduct of narrative synthesis in systematic reviews” provided by the Economic and Social Research Council Methods Programme.⁸

Literature Review

To identify studies for inclusion in this review, searches were conducted within 2 databases: MEDLINE (OVID interface, 1948 onward) and EMBASE (OVID interface, 1980 onward). The search strategies used were adapted to each database’s specific medical subject headings and can be found in Figure 1. No study design, date, or language limitations were imposed on the search. To ensure literature saturation, reference lists of included studies and other identified reviews were additionally scanned for relevant titles which were then subjected to a standardized screening process including successive screening by title, abstract, and full text.

Figure 1.

Search strategies.

Inclusion Criteria

While there were no restrictions by year of study or study setting, only studies reported and/or available in the English language were included due to resource constraints. Due to the limited available relevant literature, the decision was made not to impose date restrictions on the search.

Included studies were limited to placebo-controlled randomized or nonrandomized trials, where test groups were assigned to iron fortification or supplementation interventions, and cross-sectional studies, where participants were stratified according to anemia status or blood Hb levels, and comparatively assessed on work productivity. Placebo-controlled trials which also conducted cross-sectional analyses at baseline were also included.

Only studies conducted in healthy working adults were included, thus, for example, studies involving patients on renal dialysis or cancer patients were excluded. Studies conducted on individuals employed in both labor- and nonlabor-intensive occupations were included to assess the consistency of identified trends in various occupational contexts.

Iron fortification or supplementation interventions in placebo-controlled trials could be delivered in any chemical form (ie, any ferrous compound or elemental iron), in any consumptive form (ie, pill, fortified food, or drink), and at any dose. Control interventions could include placebos or other non-iron-fortified consumptives. Studies involving co-interventions or multiple micronutrient supplementation/fortification were included, albeit with the requirement that only treatment groups received iron while control groups did not.

All outcome measures had to relate directly to work productivity. Specifically, they had to be quantitative measures of labor-output relevant to the occupational context (eg, mass of product collected, number of tasks, or area of construction completed per unit of time). All studies measuring worker activity as a function of nonlabor-related outcomes (eg, general physical activity throughout work day) were excluded to limit the scope of the study to the direct effects of anemia or iron interventions on worker productivity as opposed to general physical performance.

Developing a Preliminary Synthesis

Data from the included studies was extracted using a standard data collection sheet with the following headings: design, setting and time period, population, methodology, method of exposure measurement (for cross-sectional studies) or characteristics of intervention (for placebo-controlled trials), productivity-related outcome measures, and quantitative findings. The collected data were then analyzed for trends by way of categorizing findings according to the direction of observed effects.

Exploring Relationships in the Data

To consider the factors that might explain any differences in the direction and size of effects observed across the included studies, the hypothesized and observed effects of potential mediating variables, as reported in the studies themselves, were summarized in a narrative form and assessed for overlapping themes.

Developing a Theoretical Model

To conceptualize the observed trends, the scientific literature on the physiological effects of anemia was consulted. Additionally, the potential social implications of low productivity were considered, not only in the context of national economic output but also in relation to individual well-being with a focus on mechanisms underlying a hypothesized anemia productivity feedback loop.

Assessing the Robustness of the Synthesis Product

All studies for which full texts were available were rated for risk of bias (ROB) to obtain an estimate of the robustness of the synthesized data. All placebo-controlled trials (including those with baseline cross-sectional analyses) were assessed using the Cochrane Effective Practice and Organization of Care (EPOC) tool while all cross-sectional studies were assessed using the Newcastle-Ottawa Quality Assessment Scale.

Results

Literature Review

A total of 12 studies^{9

-20} were found to meet the inclusion criteria. The results of each stage of the screening process and the characteristics of the 12 included studies can be seen in Figure 2 and Table 1, respectively. While full reports were available for 11 of the 12 studies, one study¹⁰ was only available in abstract format, and hence, corresponding extraction of supplementary data was limited and only key findings were documented.

Figure 2.

Search flow diagram.

Table 1.

Characteristics of Included Studies.

Ref No.	Location, population, and occupation	Design	Intervention or exposure measurement	Productivity assessment
9	Location: West Java, Indonesia Population: 302 male rubber plantation workers Job(s): Tapping: collecting latex from rubber trees Weeding: clearing and digging jungle roots around rubber trees	Cross-sectional analysis: Baseline hematocrit <38% vs >38% Comparison: Productivity at baseline (5h workday) Interventional trial: Treatment vs. control Comparison: Productivity at endpoint (5h workday)	Exposure measurement: Hematocrit (method not specified) Intervention: Treatment (n = 153): - 100 mg ferrous sulfate in dextrose tablet - Administered daily for 60 days Control (n = 149): - Identical dextrose tablet without ferrous sulfate - Administered daily for 60 days	Wage-based: Tappers: monthly payment; determined by weight of latex delivered to weighing huts/day Output-based: Weeders: area of trenches dug in parallel rows/day
10	Location: Darjeeling District, northern West Bengal, India Population: 212 experienced tea pluckers from a large tea estate Job(s): Tea picking: plucking tea leaves from bushes and collecting them in a basket	Interventional trial: Treatment vs control Comparison: Productivity change from baseline	Intervention: Treatment: - Iodized salt fortified with microencapsulated ferrous fumarate (3.3 mg/g salt) - Salt used for 10-month period Control: - Salt fortified with potassium iodate - Salt used for 10-month period	Output-based: Average amount of tea plucked in kg/d
11	Location: Nyeri and Kwale Districts, Kenya Population: 281 road construction workers, 102 from the Nyeri District and 179 from the Kwale District Job(s): Wheelbarrow work: moving wheelbarrows filled with dirt Ditch digging: excavating dirt to build ditches Earth excavation: digging soil from a hill slope	Cross-sectional analysis: Statistical association: Hb concentration and work productivity (8h workday)	Exposure measurement: Hb (method not specified)	Time-based: Mean time taken to complete one of three assigned tasks: Wheelbarrow work: shifting 100 wheelbarrows filled to a marked line a distance of about 90 m Ditch digging: digging a ditch 30 m in length, 1 m wide and 50 cm in depth Earth excavation: digging out 4 m³ of soil from a hill slope
12	Location: Kandy area, Sri Lanka Population: 199 tea pluckers from Oodawella tea estate Job(s): Tea picking: plucking tea leaves from bushes and collecting them in a basket	Cross-sectional analysis: Baseline Hb concentration <9.0 g/dL vs 9-10 g/dL vs >11.0 g/dL Comparison: Productivity average (last 12 months) Interventional trial: Treatment vs control ^bGroup crossover half-way through trial Comparison: Productivity change in 1 month	Exposure measurement: Hb (cyanmethemoglobin method) Intervention: Treatment (n = 103): - 200 mg tablet ferrous sulfate - Administered daily for 1 month Control (n = 96): - 300 mg tablet calcium lactate - Administered daily for 1 month	Output-based: Average amount of tea plucked in kg/d
13	Location: Metropolitan Manila area, Philippines Population: 118 operators in the sewing departments of 6 of the largest garment factories in the metropolitan Manila area Job(s): Garment sewing: using automated sewing machine to stitch various clothing garments	Interventional trial: Treatment vs control Comparison: Productivity change from baseline (measured after each month)	Intervention: Treatment (n = 81) - Tablet containing 525 mg ferrous sulfate and 500 mg of vitamin C - Administered daily (except for weekends) for 3 months Control (n = 37): - Tablet containing table sugar - Administered daily (except for weekends) for 3 months	Output-based: Efficiency rating (ER); determined by multiplying number of garments produced per day by standard allowable minutes to complete a piece divided by total working minutes in a day
14	Location: Northeast Bangladesh Population: 553 nonpregnant and non-breastfeeding tea pluckers Job(s): Tea picking: plucking tea leaves from bushes and collecting them in a basket	Cross-sectional analysis: Pretrial: Hb <120 g/L vs >120 g/L Comparison: Productivity average (first half of trial) Posttrial: Serum Fe <12 mg/mL vs >12 mg/mL Comparison: Productivity average (second half of trial, entire trial duration) Interventional trial: Treatment and antihelminth vs treatment alone vs antihelminth alone vs control Comparison: Productivity average (each half of trial, entire trial duration)	Exposure measurement: Pretrial: Hb (HemoCue Photometer) Posttrial: Serum ferritin (NovaPath Ferritin Enzyme Immunoassay) Intervention: Treatment and antihelminth (n = 130): - Capsule containing 200 mg ferrous fumarate and 200 mg folic acid - Administered weekly for 24 weeks - Anthelmintic treatment (albendazole) - Administered at beginning of trial and after 12 weeks Treatment Alone (n=139): - Capsule containing 200 mg ferrous fumarate and 200 mg folic acid - Administered weekly for 24 weeks Antihelminth alone (n = 143): - Anthelmintic treatment (albendazole) - Administered at beginning of trial and after 12 weeks Control (n = 141): - Placebo tablet - Administered weekly for 24 weeks, at beginning of trial, and after 12 weeks	Wage-based: Average wages in takas earned per plucking day (TK/PLD) Output-based: Average amount of tea plucked in kg/d Time-based: Number of days a) on sick leave and b) absent from work
15	Location: Beijing, China Population: 80 iron-deficient female workers in a cotton mill in Beijing Job(s): Cotton mill operation: walking along cotton spinning machines to join the ends of torn yarn, change the rove, clean the machine, and take off the spindles when they are full of yarn	Interventional trial: Treatment vs control Comparison: Productivity change from baseline (based on averages 1 month before and 1 month after trial)	Intervention: Treatment (n = 40): - Ferrous sulphate tablet containing 60 mg Fe - Administered daily for 12 weeks - ^cID and mild IDA subjects→1 tablet/day; moderate IDA→ 2 tablets/day Control (n = 40): - Placebo pill - Administered daily for 12 weeks ^cID and mild IDA subjects→1 tablet/day; moderate IDA→ 2 tablets/day	Wage-based: Production efficiency (PE); determined by dividing average wage earned in yuan/day (function of quantity and quality of yarn produced daily) by total energy expenditure in megajoules/day
16	Location: Bicol region, Philippines Population: 38 labor-intensive road construction workers Job(s): Loading: lifting dirt from an area near the road site onto bullock carts Unloading: unloading dirt from the carts onto the site Tamping: using a tamping instrument to pack the soil onto the road site	Cross-sectional analysis: Hb concentration <13 g/100mL vs. >13 g/100mL Comparison: Productivity average (2 work days) Statistical association: Hb concentration and days absent during prior 6-week period	Exposure measurement: Hb (method not specified)	Output-based: Cubic meters of soil loaded, unloaded or tamped Time-based: Average daily number of active vs. rest minutes and number of days absent from work
17	Location: Valparai, South India Population: 793 permanent workers on a tea estate Job(s): Tea picking: plucking tea leaves from bushes and collecting them in a basket	Interventional trial: Treatment vs control Comparison: Productivity average (each half of trial)	Intervention: Treatment (n = 385): - Iron- and iodine-fortified salt - Salt used for 9-month period following 3 months of unfortified salt use ^cHalf of group also received deworming treatment Control (n = 408): - Unfortified salt - Salt used for a 12-month period ^cHalf of group also received deworming treatment	Output-based: Average amount of tea plucked in kg/d
18	Location: Jakarta, Indonesia Population: 92 nonpregnant female loom operators from a jute mill on the outskirts of Jakarta, Indonesia Job(s): Loom operation: operating loom machines producing jute material	Cross-sectional analysis: Statistical association: Hb concentration and work productivity (average from 2-week period)	Exposure measurement: Hb (cyanmethemoglobin method)	Output-based: Average amount of jute material produced/day, standardized according to machine type
19	Location: District of Kudus, Central Java Province, Indonesia Population: 230 nonpregnant and non-lactating females over 18 years working in a clove cigarette rolling factory Job(s): Cigarette rolling: operating equipment designed to roll cigarettes	Cross-sectional analysis: Hb concentration <120 g/L vs >120 g/L Comparison: Productivity average (6 work days)	Exposure measurement: Hb (cyanmethemoglobin method)	Output-based: Average number of cigarettes rolled/day
20	Location: Namibia Population: 7666 employees of 42 companies across seven industry sectors Job(s): Retail and trade (n = 2086) Agriculture (n = 465) Fishing (n = 1869) Electricity, gas, and water (n = 1140) Motor vehicle trade and repair (n = 1031) Hotels and restaurants (n = 300) Transport, storage, and communication (n = 775)	Cross-sectional analysis: Anemic vs non-anemic (diagnostic criteria not specified) Comparison: Number of days absent from work for health reasons in last 90 days	Exposure measurement: Hb (HemoCue Hb 201 + Analyzer and HemoCue Hb 201+ microcuvettes)	Time-based: Number of days absent from work for health reasons in last 90 days

Abbreviations: Hb, hemoglobin; IDA, iron deficiency anemia.

^a Yellow, cross-sectional analysis. Blue, placebo-controlled trial. Green, cross-sectional analysis and placebo-controlled trial.

Characteristics of Included Studies

Of the 12 studies included in this review, five^11,16,18
-20 were cross-sectional studies, four^10,13,15,17 were placebo-controlled trials, and three^9,12,14 were comprised of both placebo-controlled trials and cross-sectional analyses. Of the 7 studies that included interventional trials, 5 involved the administration of iron supplementation interventions (four^9,12,13,15 tested ferrous sulfate and one¹⁴ tested ferrous fumarate supplementation) and 2 involved iron fortification interventions (both^10,17 tested iron-fortified salt specifically). The studies collectively covered a total of 8 countries, with 3 studies conducted in Indonesia,^9,18,19 2 studies conducted each in India^10,17 and Philippines,^13,16 and 1 study conducted in Kenya,¹¹ Sri Lanka,¹² Bangladesh,¹⁴ China,¹⁵ and Namibia.²⁰ All study manuscripts were written in English. Notably, the majority of the studies were relatively old, with five^9,11
-13,16 having been published in the 1970s to 1980s and three^15,18,19 having been published in the 1990s.

The average age of the workers across the five^{12,14,15,19,20} studies that reported participant age data was 32.9 years. Based on the eight^{9,12,14,15,17

-20} studies that reported the sex of participants, the female:male gender ratio was approximately 3:1. Using data from the six^{11,13
-15,18,19} studies that reported the baseline anemia prevalence in the study population, the mean and median prevalence rates were 42% and 45.2%, respectively. However, different definitions and cutoff points for anemia were used, hence these pooled estimated may not be truly representative. Finally, of the 12 included studies, 3 were conducted on participants employed in physically labor-intensive occupations (road construction,¹⁶ digging/lifting/excavating dirt,^9,11 and rubber tapping⁹), 8 involved workers with less physically labor-intensive jobs (tea picking,^10,12,14,17 garment sewing,¹³ machine operation,^15,18 and cigarette rolling¹⁹), and one²⁰ involved workers employed in various sectors, encompassing a balanced distribution of occupational tasks.

Preliminary Data Synthesis

The major findings from the 12 included studies are presented in detail in Table 2. Results are divided into 3 general categories according to the productivity measures on which they are based to enable greater comparability. These categories include output-based (eg, quantity of product collected or produced), wage-based (eg, daily worker pay), and time-based (eg, time to complete task, days of work missed).

Table 2.

Summary of Findings.

Productivity outcome measure	Studies reporting only significant findings	Studies reporting mixed findings	Studies reporting only insignificant findings
Output-based	4 studies Edgerton et al Significant increase in av. kg/d tea plucked following treatment (P < .05) Significant difference in av. kg/d tea plucked in preceding 12 months b/w Hb <9.0 g/dL and Hb >11.0 g/dL subjects (15.6 vs 16.2, P < .01) Popkin Significant difference in m³ soil moved b/w anemic and non-anemic workers (1.28 vs 1.54, P < .05) Scholz et al Significant positive linear relationship b/w Hb concentration and work output (P < .001); 9.1% of the variability in output attributable to Hb concentration Low and medium producers both anemic; normal mean Hb only seen in high producers Unturo et al Av. #cigarettes rolled/day 4.9% higher in non-anemic workers (P = .009)	4 studies Basta et al Anemic weeders cultivated approx. 25% less area than non-anemic weeders at baseline (77.39 m² vs 96.98 m²) No significant difference in area cultivated b/w treatment and control weeders after intervention Florencio Significant mean ER increases seen in moderately/severely anemic workers receiving supplement but not placebo Significant mean ER increases not seen in mildly anemic workers receiving supplement Gilgen et al Anemic workers plucked av. 1.8 kg/d less tea than non-anemic workers throughout first 12 weeks of trial (P < .05) Significant differences not seen in av. kg/d tea plucked b/w iron-deficient and non-iron deficient workers No significant variation b/w 4 groups in av. kg/d tea plucked during entire trial period Rajagopalan and Vinodkumar No significant interaction effect of iron and deworming on picking average in first 6 months of trial Significant difference in mean picking average of experimental vs control dewormed group in second six months of trial	1 study Blakstad et al No significant association b/w serum Fe and av. kg/d tea plucked
Wage-based	2 studies Basta et al Both iron and placebo-treated anemic tappers showed higher wage earnings in response to payment incentive after treatment, but only iron group reached level of non-anemic Linear correlation b/w Hb concentration and bonus monthly payments paid to latex tappers at baseline Li et al Significant increase in PE of intervention group during trial period (2.77-3.42 yuan/MJ, P < .001) vs slight decrease in PE of placebo group during trial period (2.96-2.81 yuan/MJ, P > .05)	1 study Gilgen et al Anemic workers earned daily average of 1.1 takas less than non-anemic workers throughout first 12 weeks of trial (P < .05) Statistically significant negative association b/w Hb concentration and daily wages earned in second 12 weeks of trial No significant difference in average daily wage of iron-deficient vs non-iron-deficient workers	No studies
Time-based	1 study Popkin Significant positive linear relationship b/w Hb concentration and av. time worked; workers with Hb > 14 g/100 mL worked 0.67 more days during 6-week period than workers with lower Hb Significant positive linear relationship b/w Hb concentration and % active work time Guariguata et al Anemia associated with significant increase in number of sick days (IRR: 1.82, 95%CI: 1.21-2.23); largest effect on worker absenteeism of all risk factors examined Highest rate of both worker absenteeism and anemia in fishers	2 studies Brooks et al Significant positive association b/w Hb concentration and work time in Kwale district (P < .05) No significant association b/w Hb concentration and work time in Nyeri district (P > .05) Gilgen et al Anemic workers sick av. 0.3 days more than non-anemic workers during first 12 weeks of trial (P < .05) Anemic workers absent av. 0.9 days more than non-anemic workers during first 12 weeks of trial (P < .05) Statistically significant positive association b/w Hb concentration and number of days sick and/or absent in second 12 weeks of trial No significant associations b/w serum Fe and number of days sick and/or absent No significant differences in number of plucking days b/w 4 intervention groups throughout trial	No studies

Abbreviation: Hb, hemoglobin.

Of the 9 studies that collected data on output-based productivity variables, 4 reported significantly improved productivity, four^12,16,18,19 reported mixed findings, and one¹⁰ showed no effect. Meanwhile, two^9,15 of the 3 studies which based findings on wage-based productivity data reported a statistically significant positive impact on wages earned and the other¹⁴ reported mixed findings. The results were similar for those studies reporting on time-based productivity outcomes, with two^16,20 reporting only statistically significant findings and two^11,14 reporting mixed findings. The result is a total of six^{12,15,16,18,19,20} studies reporting only statistically significant findings, five^{9,11,13,14,17} reporting mixed findings, and one¹⁰ reporting only statistically insignificant findings. As shown in Table 2, those studies reporting mixed findings did so on the basis of a variety of discrepancies including differences in results obtained from cross-sectional and effect size analyses and differences in effect size data obtained at different time periods or from groups with different baseline anemia status, among others factors.

Role of Potential Mediating Variables

Across the included studies, a total of 6 mediating factors were either quantitatively or qualitatively reported for their potential effect on anemia and worker productivity levels. The potential mediating variables identified are shown in Table 3, along with a summary of relevant findings pertaining to their effects reported by the study authors themselves.

Table 3.

Potential Mediating Variables.

Mediating variable	Studies reporting on its effect
Duration of iron intervention	Gilgen et al “No significant difference in labour productivity was observed between the four intervention groups. It might not only take months for haemoglobin levels to increase significantly, but also additional time to have a measurable effect on labour productivity.” Rajagopalan and Vinodkumar “At the end of the second six months, the mean picking average of the experimental dewormed group was significantly higher than that of the control dewormed group. The picking average for the first six months did not significantly differ in the experimental and control groups.”
Baseline anemia status	Florencio “The results found among the moderately/severely anemic workers suggest that if iron supplementation does affect efficiency at all, the improvement is unlikely to be apparent unless the initial hemoglobin level is less than 11 g/100 mL.” Edgerton et al “The subjects with lower Hb concentrations initially seem to have experienced the greatest increase in productivity.” Brooks et al “As might be expected, the lack of a significant relationship between haemoglobin levels and work time in Nyeri was presumably because no workers in Nyeri had haemoglobins below 13 g/dL.”
Prevalence of helminths in study population	Rajagopalan and Vinodkumar “The interaction effect between deworming and iron supplementation on the picking average was not seen in the first six months of the trial, whereas the deworming and non-deworming component gave a value at 95%. In any community with a high incidence of worm infestation, iron supplementation at the level of daily requirements may not have any effect, because iron absorption is limited when parasitic worm infestation is high.”
Other nutritional factors	Gilgen et al “The effects of iron supplementation were contradicted by the seasonal nutritional stress during the rainy season which resulted in a decrease in weight and ferritin concentrations.” Basta et al “Instead (of being due to iron supplementation), improvements (in productivity of the control group) are accounted for by the higher consumption of iron-rich foods made possible by the income supplement paid to study participants. Dietary survey data indicate that a large part of this supplement went for the purchase of food, particularly leaves, which are sources of both iron and vitamin C.”
Degree of motivation for improved productivity	Basta et al “Treatment with ferrous iron and a small incentive payment resulted in greater improvements than the placebo plus payment, although both were effective in anemic subjects.” Unturo et al “The work productivity of the subjects in this study was related to their marital status. The fact that married women produced on average about 50 cigarettes per hour more than single women could not be explained by the data gathered in this study, but may be related to work motivation.”
Presence of technical restraints on improved productivity	Gilgen et al The reduction in yield of the tea bushes in the last weeks of the trial meant that the pluckers were not under as much pressure as at the beginning of the trial, so that differential Hb concentration, were not as strongly associated with labour productivity any more. Li et al “Because the work pace in the cotton mill was determined by machines, the productivity, expressed as the pay of the workers, was not improved after iron supplementation as significantly as it was in the rubber workers in Indonesia.” Unturo et al “The work productivity of the subjects in this study was related to their work experience. Apparently, before the required skill is obtained to produce about 600 cigarettes per hour sufficient experience is needed.”

Abbreviation: Hb, hemoglobin.

Both Gilgen et al¹⁴ and Rajagopalan and Vinodkumar¹⁷ demonstrated evidence of a time-sensitive response to iron interventions. Gilgen et al¹⁴ did not show effects of an iron intervention and explained the lack of effect on insufficient time for effects to be seen. Rajagopalan and Vinodkumar¹⁷ reported findings that only reached statistical significance in the latter half of the intervention period. Meanwhile, Florencio,¹³ Edgerton et al,¹² and Brooks et al¹¹ all suggested that the ability to detect either significant responses to iron interventions or Hb-dependent productivity trends was contingent on workers having sufficiently low baseline Hb levels to experience therapeutic responses to iron interventions or significant and hence detectable deficits in productivity.

Meanwhile, Rajagopalan and Vinodkumar¹⁷ found a direct effect of the presence of helminths on the response potential to iron interventions by way of an interaction effect between deworming and iron supplementation. There were similar interactive effects of other nutritional factors in studies conducted by Basta et al⁹ and Gilgen et al.¹⁴ Specifically, Gilgen et al¹⁴ found that “the effects of iron supplementation were compounded by the seasonal nutritional stress during the rainy season which resulted in a decrease in weight and ferritin concentrations.” Meanwhile, Basta et al⁹ postulated that improvements in dietary intake resulting from new food purchases using incentive payments augmented the already therapeutic effect of iron supplementation.

Finally, external factors that serve to promote or restrain improved worker performance were also found to augment or impede productivity changes following iron supplementation. In studies conducted by Gilgen et al,¹⁴ Li et al,¹⁵ Basta et al,⁹ and Unturo et al,¹⁹ it appeared that incentives for improved productivity such as monetary rewards may enable iron-treated workers to achieve maximal productivity gains while restraints on improved productivity such as capped machine operating rates or limited worker skill/experience may have the opposite effect.

Assessment of ROB of Included Studies

The 5 exclusively cross-sectional studies were assessed for bias using the Newcastle-Ottawa Quality Assessment Scale, while 6 studies which included placebo-controlled trials were assessed using the Cochrane EPOC tool. Risk of bias assessment was done on only 11 of the 12 included studies since insufficient information could be obtained from the one¹⁰ study for which only an abstract was available. Based on the Newcastle-Ottawa Quality Assessment Scale, two^11,16 studies were given 6/10 stars, one²⁰ was given 7/10 stars, and two^18,19 were given 8/10 stars. On the other hand, four^12
-14,17 studies were rated medium risk, one¹⁵ study was rated low risk, and one⁹ study was rated high risk using the Cochrane EPOC tool.

Discussion

From the findings of the 12 included studies, it is apparent that there exists a relatively large evidence base to support the contention that anemia adversely affects worker productivity, while iron interventions can have a positive effect on occupational performance. This is based on the fact that all of the studies with the exception of one provide at least some evidence in favor of this assertion. Seven of the studies included in the review reported statistically significant positive associations between worker Hb levels and efficiency of task performance, while in other studies, similar associations were found between Hb levels and worker pay, a proxy measure of worker productivity. In a novel study published on Indian Tea Estate workers since this review was conducted, similar findings were attained. Namely, authors found that an increase of 1.0 g/L in Hb concentration predicted 0.71 kg (3.3%) more tea plucked over 3 hours, providing additional affirmative evidence to support our own conclusions.²¹

Interestingly, strong positive associations were also found between Hb levels and the quantity of active work time, assessed directly or as a function of worker absenteeism. This suggests that anemia may not only result in greater worker fatigue but may also be implicated in more severe comorbidities which can interfere with one’s ability to attend work regularly—a potential representation of the far-reaching consequences of anemia for employee health. Meanwhile, the potential positive effects of iron interventions on worker productivity are supported by studies which showed that increasing dietary iron yielded statistically significant improvements in the efficiency of task performance among workers, whether assessed directly or through payment-based proxy measures. As these findings represent worker performance in tasks requiring varying levels of physical exertion, the aforementioned findings can be extrapolated to a variety of occupations. This is further supported by the results of the subgroup analysis which found no significant differences in results ascertained from physically demanding and non-physically demanding occupations.

The strong associations found in many of the included studies are further substantiated by well-established biological evidence. Anemia is associated with low levels of oxygen-carrying Hb, thus resulting in less oxygenation of body tissues.^22
-24 The result is that both brain and muscle tissues may be deprived of sufficient oxygen to function at maximal capacity, manifesting as physical lethargy and possibly mental fatigue as well.^22
-24 This may explain why many of the observed associations were also seen in occupations involving relatively low physical demand but a higher degree of mental focus. The adverse effects of anemia on cognitive and motor development in early childhood have also been widely reported in clinical and biological studies.^25

-32 Thus, it is plausible that productivity deficits observed in anemic workers may not only be the result of its immediate effects on oxygen-carrying capacity but may also be rooted in its long-term cognitive and motor consequences, assuming anemia onset occurred in early childhood. This linkage of the pathophysiology of anemia renders the findings more plausible on a biological level.

It should be noted that not all of the reported results were statistically significant. Three studies^9,10,14 failed to find statistically significant differences between iron intervention and control groups on assessed productivity outcomes. In 2 placebo-controlled trials,^13,17 results were mixed with significant differences between study groups only found in moderately/severely anemic workers¹³ and in the second 6 months of intervention,¹⁷ while 2 other cross-sectional studies reported mixed results which lacked statistical significance. These studies were conducted in subcohorts of workers, namely those comprised of workers from select villages or having iron-deficiency but not anemia, respectively.

While there is compelling evidence to suggest that iron interventions in adult working populations may prove highly cost-effective, iron intervention in early childhood may similarly result in long-term human capital gains with economic significance. Research supports the existence of an association between iron deficiency and/or anemia and poor physical performance in children, as measured by other physical performance indicators applicable to non-working child/adolescent populations. In a study conducted on migrant schoolchildren in the suburbs of Beijing, severe iron deficiency was found to significantly affect maximum work time throughout the school day.³³ This same study also reported that iron-deficient children had significantly lower VO₂ max and spent significantly less time on aerobic activity outside of school, possibly due to greater fatigue.³³ These findings are supported by other studies showing that heart rate, a measure of aerobic fitness and the efficiency of oxygen delivery, was significantly higher in anemic children,³⁴ while Hb levels were positively related to endurance capacity in rural adolescent girls.³⁵ Reduced physical activity as a result of fatigue and poor oxygen delivery may ultimately have a long-term effect on cardiovascular health in adulthood and may impede cognitive development in young children who may be less likely to actively explore their environment.

Integrated iron interventions, particularly for anemic populations, may have far-reaching implications for worker productivity and ultimately for national economic output. According to calculations made by Li et al,¹⁵ 15 years ago, there was a 20% difference in productivity levels between anemic and non-anemic workers. Thus, an investment of US $0.17 in iron supplements could yield an extra US$44.00 in the amount of latex obtained per hectare. This is of relevance, since in 2019, Thailand produced more than 4 million metric tons of latex.³⁶ Similar extrapolations were made by Rajagopalan and Vinodkumar¹⁷ who estimated that just US$215 spent on iron-fortified salt provision to South Indian tea workers could yield an additional 300 000 kg of extra tea leaves picked per year. Such conclusions are also in line with those drawn by other researchers and health economists. In an analysis of 10 developing countries, the median value of annual productivity losses due to IDA was US$0.32 per capita or 0.57% of the gross domestic product.³⁷ Other researchers have estimated that productivity gains accrued by Vietnamese workers given both iron-folic acid supplementation and deworming treatment would have a benefit:cost ratio of 6.7:1,³⁸ while additional estimates have been made that malaria prophylaxis and iron supplementation combined would cost only US$9.7 per disability-adjusted life year averted, a rate considered highly cost-effective, as defined by the World Bank’s proposed threshold of less than US$25 per DALY for comparative assessments.³⁹

While the breadth of literature covered in this review was not extensive, it was sufficient to provide a diverse array of evidence pertaining to the effect of anemia or iron interventions on productivity in adult workers. The fact that many of the studies were quite old is likely testament to the time period in which this research area was of greatest focus and perhaps corresponds with the launch of the first large-scale iron interventions.

The relatively high mean anemia prevalence (42%) in the study population is indicative of the anemia burden borne by many LMICs in which these studies are primarily based and is comparable to estimated rates in the developing world today,^1,2 despite many of the studies being old. However, it is important to note that this prevalence rate varied dramatically across the included studies, ranging from as low as 5.3% (cross-group mean) in the Namibian study²⁰ to as high as 86% in the study conducted in Bangladesh.¹⁴ Finally, the wide range of occupations included in these studies allow us to construct a comprehensive picture of iron’s role in occupational performance in diverse contexts.

Insignificant findings must be viewed in light of the array of potential variables which may mediate the effect of anemia status or iron interventions on worker productivity. Taking into account the findings summarized in Table 3, it is apparent that there are numerous factors worth considering when designing an iron intervention program aimed at yielding maximal productivity gains in working adults. Most importantly, findings from the 12 included studies suggest that such programs should not only be long term and targeted primarily toward anemic populations but also horizontally integrated with other public health initiatives such as deworming treatments and supports for improving nutritional diversity and overall dietary intake. This is further substantiated by biological evidence showing that intestinal parasites inhibit host iron absorption through a process of competitive “capture and uptake” of host iron.⁴⁰

Findings must also be viewed in light of several other notable limitations. As significant sources of bias were identified in many of the included studies, conclusions must not be overstated. For example, the high dropout rate in some studies^9,13,16 may have introduced attrition bias, the effects of which could not be ascertained without knowledge of the characteristics of nonrespondents. Additionally, the frequent exclusion of key subsets of the worker population such as new, frequently absent, or very overweight workers for practicality or safety reasons may have rendered certain study populations unrepresentative of the full workforce. Other concerning sources of bias included significant and important differences in baseline characteristics of study groups that were not controlled for in the final analyses and the possibility that workers knew their group assignment due to the inevitably detectable differences in placebo and treatment interventions administered in certain studies—an effect which would have appeared particularly prominent when assessing productivity outcomes. Such sources of bias in addition to the already small number of highly heterogeneous studies included in this review ultimately limit the voracity of the findings.

Conclusion

This review aimed to collate an array of evidence from the available literature pertaining to the effect of anemia and iron interventions on productivity in adult workers. Having included 12 studies conducted in various countries and diverse occupational contexts, this review is both comprehensive in scope and relatively widespread in applicability. Specifically, this review provides evidence that anemia adversely effects occupational performance. While findings pertaining to the positive effect of iron interventions on worker productivity are less conclusive, they still suggest that, when implemented effectively and integrated horizontally with other anemia-targeted public health initiatives, such interventions may confer substantial productivity benefits to adult workers and ultimately prove lucrative for national economies. While the limitations of these findings must be taken into account when considering their utility as evidence-based advocacy tools for national scale-up of iron interventions, their implications may be far-reaching should they ultimately be used, alongside the growing amount of other supportive evidence, to galvanize needed legislative action.

Footnotes

Authors’ Note

Dr Stanley Zlotkin and Claudia Schauer offered expert guidance in the design of the study, provided intellectual input throughout its completion, approved all protocols to be followed, and contributed to final manuscript editing and revisioning. Hannah Marcus conducted the literature review and was the primary contributor to the processes of data abstraction and analysis and of drafting the final manuscript.

Acknowledgments

The authors would like to thank Emily C. Keats for her technical guidance with conducting the literature reviews, developing database-specific search strategies, and identifying and applying appropriate ROB assessment tools for the diverse studies included.

Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. Ms Marcus was supported by Chair’s funding from Dr Zlotkin’s Mining4Life Chair in Mineral and Vitamin Nutrition.

ORCID iD

Stanley Zlotkin

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