Background

Anemia is a condition in which the amount of hemoglobin in the blood decreases along with a decrease in the red blood cell mass [1]. There are several forms of anemia; however, iron deficiency anemia frequently occurs. Iron deficiency may result from a single or a combination of several major factors: (I) insufficient dietary iron consumption and/or decreased dietary bioavailability [2]. (ii) A surge in iron requirements by the body, e.g., during pregnancy and periods of rapid growth in young children and adolescents; [3], (iii) chronic iron loss, e.g., during menstruation in women of reproductive age or due to ulceration and parasitic infestation; and [4, 5], (iv) impaired iron utilization after ingestion, as occurs with chronic and recurrent infections. Other causes of nutritional anemia in addition to iron deficiency include folic acid, vitamin C, copper, and vitamin B2 and B12 deficiencies [6, 7].

Iron deficiency anemia (IDA) is characterized by hemoglobin levels below a specific threshold. The WHO recommends a hemoglobin level of 120 gm/L for nonpregnant women (aged 15 years and older), 110 gm/L for pregnant women, and 130 gm/L for males (aged 15 years and older) [1]. Additionally, there are three types of iron deficiency: mild, moderate, and severe. Mild deficiency is defined as having reduced deposits with an average production of hemoglobin and iron-dependent protein. The cutoff values for nonpregnant women are 11–11.9, and for pregnant women 10–10.9, marginal deficiency is characterized by average Hb concentrations, reduced iron reserves, and impaired synthesis of iron-dependent proteins [2]. When iron stores are further depleted and Hb levels decline, anemia progresses to a moderate state, if it remains untreated, subsequently leading to severe forms, the cutoff values in pregnant women are 7–9.9, moderate and severe < 7; however, in nonpregnant women, the values are 8–10.9 for moderate anemia and < 8 for severe anemia [3].

One-third of the world’s population is anemic and iron deficiency accounts for half of the cases [4]. It is a critical problem for global public health that affects physical health, referral to medical specialists, and maternal and infant mortality. The vulnerable population included pregnant females, young females of childbearing age, and children [5]. Iron deficiency anemia is frequently linked to several chronic conditions, including cancer, inflammatory bowel disease (IBD), kidney disorders, and chronic heart failure [6, 7]. Anemia is related to unfortunate immediate and long-term health consequences [16].

Despite current community, financial, and health-related developments, anemia remains a widespread international health problem that affects people at every stage of life and has serious implications for health and life [17]. Although women and young children are the populations most affected by anemia, they do not have enough access to interventions and supplementation in underdeveloped countries or in certain developing countries. According to a World Bank analysis, the prevalence of anemia in women increases almost everywhere in the world as income declines. In several countries, the prevalence is twice as high among poor people as among those from good socioeconomic backgrounds. [18, 19].

The incidence of anemia is an important indicator for both advanced and underdeveloped countries [8], with a prevalence of 9% in developed countries and 43% in underdeveloped countries [20]. The global prevalence in women is approximately 15–18% [21], 78.5–78.8% in adolescent girls, and 33% in women of childbearing age 15 to 49 years worldwide [22], increasingly posing a threat to population health [23]. Anemia in developing countries has a variety of causes and effects described in the literature, although they are not all summarized in one place [24].

Therefore, the objective of this systematic review was to review and synthesize the literature on the incidence of IDA in Pakistan over the last 15 years.

Research methodology

A systematic review and meta-analysis of eligible published studies was conducted to determine the pooled prevalence of anemia among females in Pakistan.

Identifying the research question

The present study investigated the prevalence of IDA among pregnant females and nonpregnant adult/adolescent females in Pakistan.

Search strategy and guidelines

A review procedure, including a strategy for search and data-gathering methods, was created. The Population, Intervention, Comparison, Outcomes, and Study Design (PICOS) section was established based on review questions to identify search keywords.

The search also included a gray literature search, and references were searched manually for selected articles. A search was conducted from January 2022 to May 2022. The PubMed, Scopus, ScienceDirect, and Google Scholar databases were searched using the PICOS identifiers for the research questions and associated terms. ((Prevalence, OR “Frequency*” OR “Incidence”) AND (“Iron deficiency anemia OR anemia OR IDA)) AND (“Adolescent girls” OR nonpregnant females”) AND (“pregnant*”) AND (“Pakistan”)).

Inclusion criteria

Studies that included descriptive and cross-sectional designs were included. Only papers published between 2007 and 2021 were considered because our focus was on the most recent developments and previous publications were difficult to find. We also searched ScienceDirect for more articles because the number of publications was low. The reference lists of the publications that were included, as well as editorials found through the searches, were scanned. We also looked for reports of large-scale health surveys on relevant websites and in the Google search engine however, studies with secondary data and unpublished studies were not included.

This review reviewed community-based studies from everywhere in Pakistan as well as national health surveys. Language was not a criterion for excluding studies. Retrospective studies including hospital/clinic attending populations, specifically pregnant women who visited hospitals/clinics for antenatal follow-up, were also included.

All published studies that documented the incidence of iron deficiency anemia were included in the analysis. The titles and abstracts of all search results were reviewed to establish study eligibility. At this stage, all studies that had been included were thoroughly evaluated. The corresponding authors of interest were contacted with a request for the entire paper for papers whose full text was not openly available. Studies with small sample sizes were also included because we had very limited available data in our area of interest.

Exclusion criteria

Studies focusing on any type other than iron deficiency anemia (e.g., sickle cell anemia), research on patients receiving hemodialysis patients with thalassemia or cancer, or selective subpopulations were not considered.

Outcome of interest

The primary outcome of interest was iron deficiency among nonpregnant adolescent/adult females and the prevalence of anemia in pregnant females, hemoglobin concentration less than 12 mg/dl is the cutoff for pregnant/adolescent females, and a hemoglobin concentration of 11 mg/dl is the cutoff for pregnant females.

Screening of articles

Three reviewers, BM, and TS FS were independently involved in the screening of the articles included in this study by using Rayyan software, and their blinding was maintained during the screening process. By adhering to PRISMA guidelines, the identification procedure and selection criteria for the publications are summarized in Fig. 1.

Risk of bias

The quality of the included studies was evaluated by an independent reviewer, conflicts on study selection were resolved through discussion, studies with mutual consensus were included, and two independent reviewers conducted critical assessments and cross-checked the results with a third reviewer by using the Newcastle Ottawa (NCOS) tool. The characteristics of the studies were evaluated using the following indicators. The evaluation findings were calculated using the average scores of the two authors.

Heterogeneity assessment

I2 test statistics were used to evaluate the heterogeneity of the studies. 25%, 50%, and 75% I2 test statistics were regarded as indicating low, moderate, and significant heterogeneity, respectively. To analyze the test findings that showed heterogeneity, the random effect model was applied.

Data extraction

To extract the quality-related data and the fundamental study data, two distinct proformas were used in Microsoft Excel: clear objectives; proper methodology, including design, sampling methodologies, and data collection; appropriate analysis; method of hb estimation; risk of bias in selection; and constraints, which were all covered on the checklist. Prevalence data as percentages of anemia were collected individually for adolescent girls and pregnant women. A study was removed when there was a significant reason to doubt its validity, and tables were created to summarize the information.

Results

Results synthesis

The authors first extracted the relevant data from the selected studies, entered the data into Microsoft Excel 2016, and used R statistical software to assess the outcomes. A table and a forest plot were used to represent and report the results. By applying the binomial distribution formula, the standard error of the incidence of anemia for each original study was calculated. Using the I2 test, any potential heterogeneity was investigated in the stated prevalence of the studies. A random effects model was employed to estimate the Der Simonian and Laird’s pooled effect.

Study selection

A literature search revealed a total of 102 studies on various kinds of anemia risk factor prevention, etc. Due to duplication, 10 of them were eliminated. Another 26 studies were eliminated after the titles and abstracts were screened because the content was irrelevant to the goal of our review, as we were bound to include studies on IDA prevalence in females. We eliminated 37 of the 66 preselected papers because they did not match the selection criteria.

Study characteristics

Two National Health Surveys were considered: NNS 2011 and NNS 2018. Eleven studies on nonpregnant women/adolescent girls with 2,294 participants were included, and sixteen studies on IDA incidence among pregnant women with 9,263 participants were included in this systematic review. The data were obtained from seven studies conducted in Sindh, ten studies from Punjab, five studies from KPK, two studies from Baluchistan, two studies from AJK, and two national nutritional health surveys that show prevalence throughout the whole country. According to the WHO criteria, 12 mg/dl is the cutoff for pregnant/adolescent females, and 11 mg/dl is the cutoff for pregnant females [9].

Quality assessment of studies

The studies included in the current review were cross-sectional. The New Castle Ottawa tool was used to assess overall quality. Among the group of adolescent girls, 11 studies were included. Of these 11 studies, five were identified as high-quality, with scores of 09 and 07, four studies were classified as moderate with a score of 5, and two studies were classified as low-quality, with scores of 04. Among the second group of pregnant females, 16 studies were included, among which six studies had high-quality scores of 7 and 8, seven had moderate quality scores of 05 and 06, and three had low-quality scores of 04 and less than 04.

Figure 1 shows the selection process for the studies involved. The following databases were used for the search: Google Scholar, PubMed, Scopus, and ScienceDirect.

Fig. 1
figure 1

Flowchart describing the details of the papers included in the review

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Table 1 PICOS identifiers with keywords and additional terms used to generate data from databases
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Data were extracted from studies conducted in different geographical regions of Pakistan by using various key terms from the PICOS. The frequency, rates, prevalence, proportion, and magnitude of iron deficiency in young females are shown in Table 1.

Table 2 Prevalence of anemia in Pakistan according to the National Nutrition Survey (NNS)
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Table 2 shows the results of two national nutrition surveys, which depict anemia incidence from various geographical locations in Pakistan. In both surveys, the population residing in rural settings had a greater prevalence than the females residing in urban areas, and a similar pattern was observed in pregnant and nonpregnant individuals in both groups. A survey in the 2011 Sindh Province revealed a greater prevalence of anemia in both groups, with 59.7% in pregnant females and 62.0% in the adolescent/WRA group; however, in the survey in the 2018 Baluchistan Province, the highest prevalence was 53.9% and 61.8%, respectively.

Table 3 Studies on the prevalence of anemia among adolescent girls/nonpregnant women in Pakistan with demographic details
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Table 3 presents the characteristics of a total of 11 studies on adolescents/nonpregnant individuals, with 2,294 sample size studies representing mostly large cities and their peripheries; no single study from Gilgit Baltistan has been conducted on IDA prevalence to date to provide figures.

In the northern areas of Pakistan, a study conducted in Peshawar had a sample size of 259 reported 23.9% and the study conducted in Mardan had a sample size of 50 reported 10% showing less prevalence; however, studies performed in Lahore and Rawalpindi have shown a higher prevalence of anemia in the non-pregnant/adolescent group (84% and 71.2%, respectively).

Meta-analysis

To provide a visual summary of the data, a forest plot (Fig. 2) was generated to evaluate the pooled effect size of each study with their respective confidence intervals (CIs). The forest plot of the 11 studies included in this analysis revealed that the pooled prevalence of anemia among nonpregnant adult/adolescent females was 54.6% (95% CI: 0.422, 0.669). We detected significant heterogeneity among the included studies, as indicated by the I2 statistic (I2 = 97.8%, p value < 0.001). Because the DerSimonian and Laird random effects model provides more conservative effect sizes, we used it to estimate the total pooled prevalence of anemia among nonpregnant adult/adolescent females.

Fig. 2
figure 2

Forest plot showing the pooled prevalence among nonpregnant females

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Subgroup analysis

The pooled prevalence of anemia across studies with various sample sizes was revealed by subgroup analysis by sample size (Table 4). With a broad confidence interval indicating considerable uncertainty, the estimated pooled prevalence for studies with sample sizes under 200 was greater at 60.5%. The pooled prevalence is also lower—44.4%—for studies with sample sizes over 200—again, with a confidence interval that considers this heterogeneity.

Significant variability among studies within each category is indicated by the subgroups’ notably high I2 values (97.23% and 97.26%) and extremely low p-values (0.001). The socioeconomic status subgroup analysis sheds light on how anemia prevalence changes between various socioeconomic categories. In this analysis, studies with participants from mixed backgrounds showed a higher prevalence. There was considerable heterogeneity among the studies within each of the three categories, as indicated by the large I2 values and extremely low p-values (0.001) for all three subgroups.

Table 4 Subgroup analysis of a group of adult/adolescent nonpregnant females
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Table 5 Characteristics of the study participants (pregnant women
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Table 5 represents a total of sixteen studies with 9,263 participants on the incidence of anemia in pregnant females in Pakistan by year, population, SES, and technique used for Hb estimation. The same pattern is observed here; almost all studies represent large cities or their peripheries. Most of these studies do not use Hb estimation techniques. A study from Rawalpindi showed the lowest prevalence rate of anemia which was 46.7%, with a sample size of 860, and the highest prevalence was reported by a study conducted in AJK, which was 91% in pregnant females with a sample size of 1000. The prevalence of anemia by city of residence showed significant differences when compared with studies conducted in comparatively small cities, as studies conducted in Karachi, Lahore, Islamabad, and Quetta showed a lower frequency when compared with small cities and peripheries.

Meta-analysis of studies on pregnant women

To offer a visual summary of the data in this meta-analysis, a forest plot (Fig. 3) was generated to evaluate the pooled effect size of each study with their respective confidence intervals (CIs). The pooled prevalence of anemia among pregnant women by using the Der Simonian and Laird random-effects model, was 70.4% (95% CI: 0.619, 0.789) as shown by the forest plot of the 39 studies included in this analysis. We discovered significant heterogeneity among the included studies, (I2 = 99.0, p-value = 0.001).

Fig. 3
figure 3

Forest plot showing the pooled prevalence among pregnant females

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Subgroup analysis

The subgroup analysis by region reported in Table 6 highlights the prevalence of anemia differs across the different regions. The pooled prevalence estimate, confidence interval, and measures of heterogeneity differ for each region. A higher prevalence was reported in Punjab Province, among other regions77.4 (0.630,0.918). Strong I2 values and extremely low p-values (0.001) illustrate the significant heterogeneity among the studies within each region. The Baluchistan region is the exception: no observed heterogeneity exists (I2 = 0.00%). Trimester-wise subgroup analysis of the second trimester reported a greater pooled prevalence.

Table 6 Subgroup analysis of pregnant females
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Discussion

The pathological condition of anemia is characterized by abnormalities in the concentration of red blood cells per unit volume, hemoglobin, hematocrit, and erythrocytes compared with reference values [6, 44]. These values may vary due to certain factors, such as sex, hormonal stimulation, age, developmental stage, and life stage.

According to recent study results, the mean prevalence of anemia in adolescents is 54.6%. The minimum and maximum prevalence in the adolescent/nonpregnant group were 10% and 84%, respectively. The maximum and minimum prevalence of anemia reported during pregnancy were 91% and 46.7%, respectively. However, in a subgroup analysis of pregnant women in Punjab Province, a higher prevalence was found, which may be due to changes in diet and lifestyle, as most of the studies from Punjab measured prevalence in metropolitan areas. When socioeconomic status was compared, pregnant women from lower classes were found to be more prevalent than middle-class women, which could be due to the use of nutritional supplements or proper antenatal care that helps women become aware of their iron status. In pregnant women, the etiology of iron insufficiency is constant over time [38]. The high prevalence of IDA was caused by multiparity, close birth intervals, low socioeconomic status, and lack of education. In addition, most pregnant women visited the clinic in the later trimesters. Therefore, they were deficient in iron at the time of conception. Iron supplement noncompliance was also found to be a significant contributing factor. Although almost all South Asian nations, including Pakistan, have national anemia control programs, this issue still exists.

Among the adolescent/adult nonpregnant group, a severe prevalence was observed in the age group between 11 and 15 years in various studies, possibly due to menarche. Most of the research on adolescent age groups showed that the mean hemoglobin levels for those age groups, or those 13 to 14 years of age [39, 40], were the lowest [41]. This may have been related to the start of menstruation after reaching menarche age. Overall, IDA-positive women showed a similar pattern, with the highest prevalence observed in our study.

Although there is no discernible difference between the nutritional status and consumption of boys and girls, difficulties do occur for females in adolescence and adulthood, according to the National Nutritional Survey Pakistan (NNS) in 2011 [10]. Moderate to severe anemia can result from inadequate nutritional consumption. Adolescent girls and women of childbearing age are more at risk for iron deficiency due to the fetal requirement of iron and blood loss during menstruation, pregnancy, and childbirth [42]. According to NNSs in Pakistan, more than half (56.6%) of adolescent females have anemia yet only 0.9% of them have severe anemia. Similarly, young women in rural areas are more likely than their peers (58.1%) to be anemic compared to urban areas (54.2%).

Although we cannot rule out the possibility that some of the observed anemia is caused by other factors, anemia is characterized by a poor synthesis of hemoglobin in an advanced stage of iron deficiency [43]. Iron deficiency can also be caused by certain hemoglobinopathies, and anemia has been linked to other nutritional deficits. Furthermore, iron is sequestered, and its mobilization for erythropoiesis is reduced because of vitamin A insufficiency, which is thought to be the second most common cause of moderate anemia [44]. Additionally, studies have shown that riboflavin, folate, and vitamin B12 deficiency might result in anemia [45].

All studies have demonstrated a substantial proportion of anemia cases even though anemia estimates vary significantly due to different methodologies and measurement procedures. Therefore, immediate action to address this issue is needed. When the prevalence of anemia is greater than 40%, the WHO and UNICEF strongly recommend that universal supplementation be implemented.

Conclusion

The current study illustrates the significant burden of anemia on public health in Pakistan, especially for adolescent females/women of reproductive age and pregnant mothers. However, this study cannot conclusively determine the precise etiology of individual studies, but it offers comprehensive details on the frequency and possible causes, such as dietary patterns, age-associated vulnerabilities, and disparities in socioeconomic status. These data provide a strong foundation for planning comprehensive strategies that help to address the challenge of combating IDA in Pakistan.

A multifaceted strategy is needed for effective treatments. It is critical to address the underlying social, economic, and educational issues affecting women and girls. This includes measures to increase the availability of iron-rich nutrition, and iron supplementation, strengthen the healthcare system, and encourage public awareness of the value of prenatal care and healthy eating habits. The government must act decisively to improve educational standards, the socioeconomic status of women, the availability of health professionals, and the intensity of public education. Changes in health behaviors are needed, as is compliance with government-recommended programs. Furthermore, additional research is required to determine the precise impact that hemoglobinopathies and vitamin deficiencies have on regional variations in the prevalence of anemia. By implementing these combined initiatives, the disease burden can be significantly reduced, and the health and well-being of the Pakistani population can be improved.

Limitations

Certain limitations should also be discussed. Numerous studies on females in the reproductive age range that included both pregnant and nonpregnant women were omitted due to the mixed population. Furthermore, several relevant articles that were listed on search engines were not accessible; if they could be accessible, a clearer picture would be possible. Although we have found most of the data through our methodical methodology, there may still be numerous results regarding the prevalence of anemia that have not been published or made available online. Substantial heterogeneity was found while performing metanalysis and the use of various sample procedures for hemoglobin measurement may be one of several factors contributing to the observed variation within the examined research. Because different approaches, tools, and protocols are used in different studies, the procedure for measuring hemoglobin levels can change greatly between these methods. The different methods used to assess hemoglobin may cause variations in the prevalence of anemia that are reported. Additionally, the sampling strategy itself may be a factor in causing variance; however, the employed studies were cross-sectional but used different sampling techniques. The subjective evaluation of quality assessment limited the review as well. Even though the data were unsuitable for meta-analysis, the systematic approach is a valuable and understandable way to summarize the data and clearly show where gaps exist. Creating the best mitigation methods for this issue requires precise estimations of the present anemia prevalence. It would be helpful to use perspective and standardized data gathering, preferably from samples of the total population, to better understand the prevalence of anemia in Pakistan.