Thalassemia is an autosomal recessive single gene disorder affecting 200 million people globally with half of this patient group with new cases registered annually having the severe form of the disease (i.e., β-thalassemia major [β-TM]). The disease is spreading to other countries that were not previously considered as endemic for thalassemia due to high population movement, thus becoming a global public health concern [1-3]. Southeast Asia is a known hotspot for thalassemia [2,4]. In India, nearly 12,000 infants born every year have the major form of the disease (10% of global burden) with half of these patients die before reaching adulthood. A large proportion of these early deaths are due to malnutrition [5-7].

Malnutrition in thalassemic children is multifactorial. Existing literature indicated that children with thalassemia have an average energy intake lower than the recommended daily dietary allowances as most of them belong to a more economically impoverished section of the society. As a result, they develop multiple micronutrient deficiencies (hidden hunger). Thus, socioeconomic status (a proxy indicator for food security) and literacy of parents play a major role in this regard [8,9]. On the contrary, suboptimal maintenance of therapeutic indices (i.e., blood hemoglobin [Hb] level, serum ferritin level, etc.) may lead to the development of iron overload-related complications (i.e., endocrinopathy, hepatitis, splenomegaly, and cardiac arrhythmia), which further complicates the growth process, while maintenance of optimal therapeutic indices promotes growth [10].

There are different ways of assessing malnutrition in children (e.g., weight for height, weight for age, and height for age), but body mass index (BMI) is the most frequently used and convenient method for estimating and assessing the level of malnutrition in children. Using BMI, children can be classified into different groups (i.e., obese, overweight, underweight, and normal weight) according to their nutritional status, which helps in designing the interventions for different groups. In this case, we estimated the proportion of children who were either obese, overweight, or underweight in order to determine their malnutrition level. Thus, BMI for age was used to assess the malnutrition level among thalassemic children in the current study [11].

Extensive researches on various aspects of thalassemia have been conducted all over the world, but only a few studies explored the malnutrition level among thalassemic children, especially its impact on their quality of life (QoL). Few existing literatures suggest that malnutrition negatively impacted their QoL; however, to our knowledge, no previous study was conducted in the Indian subcontinent to confirm this issue [12]. With this background, the study aimed to estimate the proportion of β-TM children with malnutrition, its attributes, and impact on their QoL.

The cross-sectional, hospital-based, analytical observational study was conducted in a thalassemia day care unit of Calcutta National Medical College and Hospital in West Bengal, situated in the eastern part of India, from May 2016 to April 2017. A total of 328 β-TM children and their accompanying caregivers participated in the study. The following data were collected by the principal investigator himself following a structured schedule: sociodemographic (age, sex, place of residence, and parents’ educational level), socioeconomic (per capita monthly family income), clinico-therapeutic (blood transfusion frequency, last pre-transfusion Hb level, spleen status, iron chelation status, and hemolytic facies), anthropometric (height and weight), and QoL (assessed using Peds4QL)-related data. Notably, the study was conducted only in children with known β-TM. These children were diagnosed with β-TM by the medical officer in charge of the thalassemia unit based on the following diagnostic criteria: a patient with Hb less than 7 gm% with Hb F ≥70% and Hb A <30% on Hb electrophoresis at the time of diagnosis. After being diagnosed with β-TM, the children were attended at the thalassemia outpatient unit by a medical officer and were assessed to determine if the patients require blood transfusion (by Hb measurement and clinical examination) and other therapeutic interventions (iron chelators, vaccinations, etc.). Most of the visits involved follow-up care.

β-TM children who received at least 1 blood transfusion in the previous year, attended a thalassemia day care unit along with a caregiver during the study period, and consented to participate were included in the study. By contrast, those who were critically ill were excluded. Patients who are “critically ill” refer to thalassemic children who are bedridden and urgently require medical intervention in order to survive. One day in a week was allotted for data collection. On an average thalassemia unit, the outpatient department serves 15–20 β-TM patients every day. Every patient attended at the outpatient department was approached by the principal investigator and recruited for the study. Notably, the principal investigator of the study was a junior resident doctor then. The interview lasted for 15–20 minutes. On average, eight patients and their caregivers could be interviewed on a single day. Before each interview, the study participants were asked if they were interviewed before, to prevent duplication. A total of 41 days were allotted for data collection (excluding public holidays) in 1 year, and an average of 328 parents could be interviewed within the stipulated study period. Details are depicted in Figure 1.

During the study, the participants and their caregivers were acknowledged for participating in the study. Then, they were briefed by the researcher regarding the purpose and importance of the study. A written informed consent was obtained from all caregivers. Assent was also obtained from each child. Then, the caregivers of the study participants were interviewed to obtained the sociodemographic, socioeconomic, and QoL-related data followed by a review of patients’ medical records to collect the clinico-therapeutic data, anthropometric measurements, and results of clinical examinations.

Among the study participants, 48.2% were malnourished with a mean BMI of 13.9±1.6 kg/m2. Notably, all malnourished children in the current study were underweight. None of the children were overweight or obese. Most of the study participants (37.2%) were aged between 11 and 12 years (range, 5–12 years). There was almost equal representation of both sexes. Most of the study participants were diagnosed with thalassemia within the first year of their lives (56.5%) with a mean age at diagnosis of 20.25 months. Three-fifth (61.3%) of them had a palpable spleen with a palpable spleen size of 1–8 cm. Majority of the study participants (63.7%) received blood transfusion once or less than once a month, and most of the patients had a pre-transfusion Hb level of 5.3–5.9 gm/dL (35.4%). One-fifth (20.6%) of participants were taking iron chelators in the last 13–24 months (mean±standard deviation, 35.6±20.2 months) (Table 1).

In the multivariable logistic regression model, the participants with higher age (adjusted odds ratio [AOR], 1.15; 95% CI, 1.02–1.29), who belonged to a scheduled caste (SC)/scheduled tribe (ST) (AOR, 2.11; 95% CI, 1.23–3.60), had mothers who only finished primary school or below (AOR, 2.05; 95% CI, 1.22–3.44), who had frequent blood transfusions (AOR, 1.25; 95% CI, 1.16–1.31), and with a palpable spleen size (AOR, 1.22; 95% CI, 1.08–1.37) were at higher risk of malnutrition after adjusting for pre-transfusion Hb level and hemolytic facies status. The independent variable in the model was the 30.3% variability of the malnutrition level among the study participants with a predictive accuracy rate of 72.6%, while a Hosmer-Lemeshow P-value of 0.310 indicated acceptable goodness of fit (Table 2).

In the multiple linear regression analysis, malnutrition negatively impacted total QoL (B [SE], -4.4 [1.7]; P=0.009) and its various domains, except for social and school domain, after adjusting with for age, sex, caste, place of residence, parents’ educational level, and socioeconomic status (Table 3).

This facility-based cross-sectional study was aimed to determine the proportion of β-TM children with malnutrition, its attributes, and impact on their QoL. In the present study, half (48.2%) of the study participants were malnourished, which was higher than the value reported in a study of Trehan et al. [17] (26.7%) and a study of Pemde et al. [18] (24.2%), lesser than the value reported in a study of Kumari et al. [19] (91.8%) and a study of Sheikh et al. [20] (64.3%), and similar to the value reported in a study of Mirhosseini et al. [21] (44.3%) and a study of Fahim et al. [22] (43.0%). The variability of the findings may be attributed to the differences in the participants’ age, ethnicity, and geographical plausibility.

In the present study, a significant association between study participants age and malnutrition status was observed, which was similar to the findings of a study of Sheikh et al. [20] and a study of Mirhosseini et al. [21] Those who belonged to the SC/ST were more likely to have malnutrition. This may be due to the following reasons: in India, those who belong to a SC/ST are more economically deprived than those in other castes [13]. Similarly, mothers’ educational level also significantly impacted malnutrition level of the study participants, which was inconsistent with the findings of a study of Sheikh et al. [20], which did not find any association between parents’ educational status and growth of their children. The variability of results may be due to the small sample size used in a study of Sheikh et al. [20] As most of the study participants belonged to a more economically impoverished section of the society, such as those living in remote rural areas, the high incidence of malnutrition may not only be due to their illness but also to their inability to afford healthy and nutritious meals. Although their household-level food security was not measured, their caste, socioeconomic status, and educational level may be considered as a proxy indicator.

The implicated therapeutic causes of malnutrition in thalassemia are prolonged use of iron chelators, multiple endocrinopathies, and hypoxia at the cellular level due to anemia, while higher number of blood transfusion further complicates the normal growth process, even in children who are regularly receiving a blood transfusion [23-26]. In the present study, participants’ age and frequency of blood transfusion were significant predictors of malnutrition. Similarly, those who had higher pre-transfusion Hb level had significantly lower chances of being malnourished, which was similar to the reports of Saxena [27]. It was a significant finding as maintenance of optimal Hb level promotes growth and prevents anemia-related complications as demonstrated by Taher et al. [28] Meanwhile, the mean pre-transfusion Hb level of our study participants was lower than that reported in previous studies conducted in India [18,19]. This may due to the higher proportions of undernourished patients in our study. Those who had larger spleen size and thalassemia facies were more likely to be malnourished. It may be because splenomegaly and thalassemia facies both indicate the severity of the disease. Similar observations were reported by Tantawy et al. [29], who reported that the “main indications for splenectomy are growth retardation and poor health,” which supports our findings.

In the present study, malnutrition negatively impacted total QoL and its various domains. This finding was supported by the results of a study of Elalfy et al. [12], which reported higher weight percentile (≥50) as a predictor of better QoL scores. This may be because a well-nourished child is more likely to cope up with the burden of a chronic disease like thalassemia resulting in higher QoL scores.

This study has some strengths; it was among the fewer studies that explored the proportion of β-TM children with malnutrition, its attributes, and impact on their QoL. In addition, the sample size used in this study is larger than that used in previous studies. Additionally, it used an adjusted regression analysis to determine the strength of association, which makes the evidence more conclusive and will further help in prioritizing interventions.

This study has some limitations. This was a cross-sectional study, which cannot establish the causal association between malnutrition and its various attributes; there may be other specific attributes (i.e., dietary factors) of malnutrition in thalassemic children that were not assessed in the study. On the contrary, chronic severe β-TM may itself could lead to anorexia, muscle wasting (e.g., cachexia), and undernutrition. There may be other factors affecting the QoL the thalassemic children, but the current study was designed to explore the impact of nutritional status on QoL of thalassemic children; hence, the other attributes of QoL were not assessed.

In conclusion, almost half of the participants had malnutrition. Malnutrition had a negative impact on their QoL. Therapeutic indices (pre-transfusion Hb level, spleen status, etc.) of the study participants were lower than those reported in previous studies and were considered as significant predictors of malnutrition. These findings expose the real, bitter picture of thalassemia management in our country, which is quite bothering. Maintenance of optimal therapeutic indices (i.e., pre-transfusion Hb level) of these children is warranted to prevent malnutrition and improve QoL.