ABSTRACT.
Children with malnutrition present with aberrant laboratory parameters. This study aimed to identify high-risk diarrheal children with varied nutritional status. The data were obtained from the electronic database of Dhaka Hospital, International Centre for Diarrhoeal Disease Research, Bangladesh from 2019 to 2021. Among 1,068 children under 5 years of age with diarrhea, 177 (14%) had severe acute malnutrition (SAM; weight-for-length/height Z score < −3), 239 children (17%) had severe stunting (SS; length/height-for-age Z score < −3), and 652 did not have malnutrition (weight-for-length/height and weight-for-age and length/height-for-age Z score > −2). We independently assessed the relationship of nutritional profiles with each clinical and laboratory parameter. After adjustment for age and sex in the multiple regression model, hyponatremia (adjusted odds ratio [aOR] = 2.37 [95% CI: 1.52–3.68]; P < 0.001) and dehydration (aOR = 2.42 [95% CI: 1.67–3.52]; P < 0.001) were independently associated with SAM compared with children without malnutrition. In comparison to non-malnutrition, SS was less likely to be associated with acute watery diarrhea (aOR = 0.66 [95% CI: 0.47–0.92]; P = 0.014) but was significantly associated with anemia (aOR = 2.18 [95% CI: 1.57–3.02]; P < 0.001) and thrombocytosis (aOR = 2.43 [95% CI: 1.78–3.32]; P < 0.001). The presence of hypernatremia was substantially lower in children with SAM (aOR = 0.38 [95% CI: 0.22–0.65]; P < 0.001) or SS (aOR = 0.56 [95% CI: 0.35–0.88]; P = 0.012) than in children without malnutrition. Severe stunting was less likely to be associated with dehydration (aOR = 0.44 [95% CI: 0.29–0.67]; P < 0.001) in contrast to SAM. Therefore, children hospitalized with diarrhea may have different clinical and laboratory manifestations depending on their nutritional status and may require differential treatment.
INTRODUCTION
Malnutrition remains a significant public health concern for children. In 2020, 45.4 million children under 5 years of age worldwide had acute malnutrition, including 13.6 million with severe acute malnutrition, whereas 149.2 million children under 5 years of age had stunting.1 Mortality is 9 to 11 times higher in children with severe acute malnutrition than in those who are not severely malnourished.2–4 For low- and middle-income countries, malnutrition is still a cause of great suffering.5 More than half of severely malnourished children and more than one-third of severely stunted children live in South Asia.6 In 2007, severe acute malnutrition and severe stunting rates were 43% and 15%, respectively, in Bangladesh.7 But in 2018, according to the Director General of Health Services of Bangladesh, the estimates had dropped to 31% for stunted children and 8% for severe acute malnourished children.8 Recent data showed children with severe acute malnutrition had increased to 11% in 2022.9 The trend of malnutrition has slightly increased, and we have yet to achieve our target. Severe acute malnutrition is correlated with an unbalanced diet.10 Malnourished children are 1.5 times more prone to infections, especially diarrhea with dehydration and respiratory tract infections.11 A hidden or overt infection is the leading cause of death in children with severe acute malnutrition.12 Research suggests that malnutrition can cause clinical indicators to change. A common disease condition of malnourished children, such as acute watery diarrhea, can result in high mortality.13 In addition, infection with stunting affects children’s cognitive development and impairs learning.14
According to research, several types of malnutrition can influence biochemical and hematological results.15,16 However, few publications offer test evidence of severe acute malnutrition and severe stunting in Bangladesh, leaving a knowledge gap. Previous research showed serum albumin, transferrin, ceruloplasmin, and T cell levels were all significantly lower in severely malnourished children, whereas immunoglobulin A levels were higher.17 Another study showed that severely malnourished children had a 2.2-fold rise in the percentage of reticulocyte counts and a 2.1-fold increase in the frequency of micronucleated reticulocytes in comparison to infected well-nourished children.18 Malnourished children used to have a low hemoglobin level and higher leukocyte and platelet counts.19 Consequently, severe acute malnourished children suffer from microcytic hypochromic anemia.20,21 An Ethiopian study showed that almost 24% of undernourished children have thrombocytosis,15 and children with malnutrition and diarrhea are more likely to have hyponatremia and hypokalemia.22 Also, the inclusion of an inflammatory state results in more fatal outcomes.23 However, there is a scarcity of data related to laboratory-based research on malnourished children in Bangladesh.
We aimed to evaluate the clinical features and laboratory-based investigation findings of children under 5 years of age with different forms of malnutrition with diarrhea.
MATERIALS AND METHODS
Study design.
This was a retrospective descriptive study, and analysis was done following a case-control design. Participants in the study were selected from the Dhaka Hospital of the International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b) database system. They were hospitalized between March 2019 and December 2021. Out of 1,881 children under 5 years of age, we selected 177 children with severe acute malnutrition, 239 with severe stunting, and 652 without malnutrition (Figure 1 presents the study design).
Figure 1.
Study design. Malnutrition was identified according to the WHO’s Z-score value. LAZ/HAZ = length/height for age; WAZ = weight for age; WLZ/WHZ = weight for length/height.
Selection criteria.
Children under 5 years of age with or without diarrhea who were admitted to the hospital inpatient ward with available weight-for-age Z score (WAZ), length/height-for-age Z score (LAZ/HAZ), and weight-for-length/height Z score (WLZ/WHZ) data and hematological and biochemical reports were included in this study. Children missing Z-score values or laboratory data and moderate acute malnutrition cases were excluded. The mid-upper arm circumference (MUAC) was not used to select participants.
Study setting.
At the Dhaka Hospital of the icddr,b in 2020, 97,024 patients received medical attention.24 More than half of the patients (68.7%) were children under 5 years of age.24 Patients travel across the country to receive better care from this hospital. A significant fraction of patients are under 5 years of age every year. The icddr,b has a Short Stay Unit (SSU) and an inpatient ward. The majority of the patient admits to the SSU for diarrheal management are discharged within 24 hours or after dehydration correction. Patients who present with other clinical features, such as sepsis, severe pneumonia, and septic shock with diarrhea, are shifted to the inpatient ward for further evaluation. However, in this study, patients admitted to the inpatient ward who had anthropometric data (except for MUAC) after the correction of dehydration and laboratory reports were recruited. Almost all patients suffered from diarrhea with or without malnutrition. A nutrition rehabilitation unit provided quality care and supervision to children with severe acute malnutrition. In addition, the icddr,b is a world-class research organization that offers all patients free care.
Definitions.
Severe acute malnutrition: Severe acute malnutrition was defined as a WLZ/WHZ below −3 according to WHO growth standards. It is also termed severe wasting.25
Severe stunting: Severe stunting was defined as a LAZ/HAZ below −3 in children according to the WHO growth standard. It has another name: short stature.25–27
Without malnutrition: Without malnutrition was defined as a LAZ/HAZ ≥ −2, WAZ ≥ −2, and WLZ/WHZ ≥ −2.
Invasive diarrhea: Diarrhea presenting with frequent blood–mixed loose stools. It is also termed dysentery.25
Dehydration: This was defined and assessed according to the Dhaka method.28
Anemia: Hemoglobin level < 11.0 g/dL
Leukopenia: Total leukocyte count < 4.0 × 10^9/L
Leukocytosis: Total leukocyte count > 10.0 × 10^9/L
Thrombocytopenia: Platelet count < 150 × 10^9/L
Thrombocytosis: Platelet count > 400 × 10^9/L
Hyponatremia: Serum sodium level < 135.0 mmol/L
Hypernatremia: Serum sodium level > 145.0 mmol/L
Hypokalemia: Serum potassium level < 3.5 mmol/L
Hyperkalemia: Serum potassium level > 5.5 mmol/L
Low total carbon dioxide content (tCO2): Serum tCO2 level < 16 mmol/L for children < 24 months of age and < 20 mmol/L for children > 24 months of age
Raised creatinine: Serum creatinine level > 35 µmol/L for children < 12 months of age and > 65 µmol/L for children < 12 months of age
Hypoglycemia: Random blood sugar < 3.0 mmol/L for acute malnourished children and < 2.5 mmol/L for other malnourished children.
The laboratory parameters were stated per Nuzhat et al.29 and the diagnostic unit of Dhaka Hospital of the icddr,b.
DATA ANALYSIS
Version 15.0 of STATA was used for data analysis. The outcome variables (Y) for this analysis were diarrhea on admission, presence of dehydration, fever on admission, hypoglycemia, anemia, thrombocytopenia, thrombocytosis, leukopenia, leukocytosis, hypernatremia, hyponatremia, hyperkalemia, hypokalemia, low tCO2, raised creatinine level, acute watery diarrhea, invasive diarrhea, and death. The exposure variables (X) were severe acute malnutrition, severe stunting, and without malnutrition. Two covariates, age and sex, were adjusted in the final model.
For qualitative data, frequency and percentage were used to summarize categorical data, and mean, SD, median, and interquartile range were used to summarize quantitative data, depending on the data distribution. Regarding the categorical data, the χ2 test was done. The study used multiple logistic regression analyses to assess the relationship between various outcome variables and the exposure variable after adjustments for age and sex. By incorporating these adjustments, we aimed to provide a more comprehensive understanding of the associations between the outcome variables and the exposure variable while controlling for the potential influence of age and sex. Because our independent variables were age, sex, and nutritional status, multicollinearity was unaffected.
To ascertain the directions and magnitude of the effects, 95% CIs were generated with a significance threshold of 0.05. “Sidak correction” was used to control the varied malnutrition error rate. The new level of significance was calculated as αnew = 1 − (1 − αold)1/n = 1 − (1 − 0.05)1/17 = 0.003.30
RESULTS
Based on the selection criteria, 1,068 children under 5 years of age were recruited from 1,881 inpatient ward–admitted children in the specified period. A total of 813 were excluded because of absence of available data. Among them, 682 eligible children (36%) were male. Among the hospitalized children under 5 years of age, the prevalence of severe acute malnutrition, severe stunting, and non-malnutrition was 9%, 13%, and 35%, respectively.
Severe acute malnutrition.
Compared with those without malnutrition, severe acute malnutrition cases had a significantly higher percentage of dehydration, anemia, leukocytosis, thrombocytosis, hyponatremia, and hyperkalemia. After adjustments for age and sex in the logistic regression analysis, severe acute malnutrition was significantly associated with dehydration (adjusted odds ratio [aOR] = 2.42 [95% CI: 1.67–3.52]; P < 0.001), hyponatremia (aOR = 2.37 [95% CI: 1.52–3.68]; P < 0.001), and thrombocytosis (aOR = 1.48 [95% CI: 1.03–2.11]; P = 0.032) (Table 1). Fever (aOR = 0.57 [95% CI: 0.40–0.81]; P = 0.002), hypernatremia (aOR = 0.38 [95% CI: 0.22–0.65]; P < 0.001), and raised creatinine (aOR = 0.53 [95% CI: 0.30–0.92]; P = 0.023) were less likely to be associated with severe acute malnutrition (Table 1). The percentage of death was higher among those with severe acute malnutrition than among those without malnutrition (aOR = 1.65 [95% CI: 0.83–3.30]; P = 0.154). However, it was not statistically significant (Table 1). After the Sidak correction, the presence of dehydration, fever on admission, hyponatremia, and hypernatremia was statistically significant in comparison to without malnutrition (P < 0.003) (Table 1).
Table 1.
Association of clinical characteristics, death, and laboratory investigations with severe acute malnutrition
| Outcome variables* | Severe acute malnutrition n = 177 | Without malnutrition n = 652 | P value | Severe acute malnutrition n = 177 | |||
|---|---|---|---|---|---|---|---|
| Unadjusted odds ratio (95% CI)† | P value | Adjusted odds ratio (95% CI)‡ | P value | ||||
| Clinical, n (%) | |||||||
| Acute watery diarrhea | 132 (74.58) | 466 (71.47) | 0.414 | 1.17 (0.80–1.71) | 0.414 | 1.00 (0.67–1.47) | 0.981 |
| Invasive diarrhea | 18 (10.17) | 86 (13.19) | 0.282 | 0.75 (0.44–1.28) | 0.283 | 0.95 (0.54–1.67) | 0.862 |
| Presence of dehydration | 113 (68.90) | 277 (48.34) | < 0.001 | 2.37 (1.64–3.42) | < 0.001 | 2.42 (1.67–3.52) | < 0.001 |
| Fever on admission | 60 (33.90) | 327 (50.15) | < 0.001 | 0.51 (0.36–0.72) | < 0.001 | 0.57 (0.40–0.81) | 0.002 |
| Laboratory, n (%) | |||||||
| Anemia (hemoglobin level < 11.0 g/dL) | 106 (60.57) | 333 (51.39) | 0.031 | 1.45 (1.03–2.04) | 0.031 | 1.33 (0.94–1.87) | 0.111 |
| Leukopenia (total leukocyte count < 4.0 × 10^9/L) | 6 (3.45) | 21 (3.24) | 0.892 | 1.07 (0.42–2.68) | 0.892 | 1.35 (0.53–3.48) | 0.532 |
| Leukocytosis (total leukocyte count > 10.0 × 10^9/L) | 124 (71.26) | 405 (62.50) | 0.032 | 1.49 (1.03–2.14) | 0.033 | 1.21 (0.82–1.78) | 0.330 |
| Thrombocytopenia (platelet count < 150 × 10^9/L) | 18 (10.23) | 68 (10.43) | 0.938 | 0.98 (0.57–1.69) | 0.938 | 1.10 (0.63–1.91) | 0.747 |
| Thrombocytosis (platelet count > 400 × 10^9/L) | 73 (41.48) | 188 (28.83) | 0.001 | 1.75 (1.24–2.47) | 0.001 | 1.48 (1.03–2.11) | 0.032 |
| Hyponatremia (serum sodium level < 135.0 mmol/L) | 70 (58.82) | 201 (46.21) | 0.015 | 1.66 (1.10–2.51) | 0.015 | 2.37 (1.52–3.68) | < 0.001 |
| Hypernatremia (serum sodium level > 145.0 mmol/L) | 20 (16.81) | 128 (29.43) | 0.006 | 0.48 (0.29–0.82) | 0.007 | 0.38 (0.22–0.65) | < 0.001 |
| Hypokalemia (serum potassium level < 3.5 mmol/L) | 45 (37.82) | 128 (29.43) | 0.080 | 1.46 (0.95–2.23) | 0.081 | 1.51 (0.98–2.32) | 0.061 |
| Hyperkalemia (serum potassium level > 5.5 mmol/L) | 15 (12.61) | 21 (4.83) | 0.002 | 2.84 (1.42–5.71) | 0.003 | 1.97 (0.93–4.19) | 0.077 |
| Low tCO2 (serum tCO2 level < 16 mmol/L for children < 24 months of age and < 20 mmol/L for children > 24 months) | 84 (67.20) | 280 (63.78) | 0.481 | 1.16 (0.76–1.77) | 0.481 | 1.25 (0.82–1.93) | 0.303 |
| Raised creatinine (serum creatinine level > 35 µmol/L for children < 12 months of age and > 65 µmol/L for children < 12 months of age) | 24 (29.63) | 111 (39.50) | 0.105 | 0.64 (0.38–1.10) | 0.107 | 0.53 (0.30–0.92) | 0.023 |
| Hypoglycemia (random blood sugar < 3.0 mmol/L for acute malnourished children, random blood sugar < 2.5 mmol/L for other malnourished children) | 3 (1.75) | 15 (2.53) | 0.556 | 0.69 (0.20–2.41) | 0.558 | 0.79 (0.22–2.78) | 0.711 |
| Outcome, n (%) | |||||||
| Death | 13 (7.34) | 28 (4.29) | 0.097 | 1.77 (0.90–3.49) | 0.101 | 1.65 (0.83–3.30) | 0.154 |
tCO2 = total carbon dioxide content. P value < 0.050 is statistically significant.
For each outcome variable, separate logistic regression models were used.
Unadjusted odds ratios were estimated using simple logistic regression analyses, where the outcome variables were given in the first column and the exposure variable was severe acute malnutrition (severe acute malnutrition = 1 and without malnutrition = 0 as a reference in the model).
Adjusted odds ratios were estimated using multiple logistic regression analyses for each outcome variable after adjustments for age and sex.
Severe stunting.
In comparison to those without malnutrition, severe stunted cases had a significantly higher percentage of anemia, leukocytosis, thrombocytosis, and hyperkalemia. After adjustments for age and sex in the logistic regression analysis, severe stunting was significantly associated with anemia (aOR = 2.18 [95% CI: 1.57–3.02]; P < 0.001), leukocytosis (aOR = 1.49 [95% CI: 1.05–2.11]; P = 0.027), and thrombocytosis (aOR = 2.43 [95% CI: 1.78–3.32]; P < 0.001) (Table 2). Acute watery diarrhea (aOR = 0.66 [95% CI: 0.47–0.92]; P = 0.014), fever (aOR = 0.51 [95% CI: 0.37–0.70]; P < 0.001), and thrombocytopenia (aOR = 0.48 [95% CI: 0.25–0.93]; P = 0.030) were less likely to be associated with severe stunting (Table 2). Severe stunting cases had a lower percentage of death than non-malnourished cases (aOR = 0.97 [95% CI: 0.47–1.99]; P = 0.928). However, this was not statistically significant (Table 2). After the Sidak correction, fever on admission, anemia, and thrombocytosis were statistically significant in comparison to without malnutrition (P < 0.003) (Table 2).
Table 2.
Association of clinical characteristics, death, and laboratory investigations with severe stunting
| Outcome variables* | Severe stunting n = 239 | Without malnutrition n = 652 | P value | Severe stunting n = 239 | |||
|---|---|---|---|---|---|---|---|
| Unadjusted odds ratio (95% CI)† | P value | Adjusted odds ratio (95% CI)‡ | P value | ||||
| Clinical, n (%) | |||||||
| Acute watery diarrhea | 160 (66.95) | 466 (71.47) | 0.190 | 0.98 (0.72–1.33) | 0.873 | 0.66 (0.47–0.92) | 0.014 |
| Invasive diarrhea | 16 (6.69) | 86 (13.19) | 0.007 | 0.81 (0.59–1.11) | 0.191 | 0.61 (0.35–1.09) | 0.097 |
| Presence of dehydration | 114 (50.00) | 277 (48.34) | 0.672 | 0.47 (0.27–0.82) | 0.008 | 1.05 (0.77–1.44) | 0.748 |
| Fever on admission | 76 (31.80) | 327 (50.15) | < 0.001 | 1.07 (0.79–1.45) | 0.672 | 0.51 (0.37–0.70) | < 0.001 |
| Laboratory, n (%) | |||||||
| Anemia (hemoglobin level < 11.0 g/dL) | 171 (71.85) | 333 (51.39) | < 0.001 | 2.41 (1.75–3.33) | < 0.001 | 2.18 (1.57–3.02) | < 0.001 |
| Leukopenia (total leukocyte count < 4.0 × 10^9/L) | 3 (1.28) | 21 (3.24) | 0.113 | 0.39 (0.11–1.31) | 0.126 | 0.51 (0.15–1.75) | 0.282 |
| Leukocytosis (total leukocyte count > 10.0 × 10^9/L) | 177 (75.32) | 405 (62.50) | < 0.001 | 1.83 (1.31–2.56) | < 0.001 | 1.49 (1.05–2.11) | 0.027 |
| Thrombocytopenia (platelet count < 150 × 10^9/L) | 11 (4.60) | 68 (10.43) | 0.007 | 0.41 (0.22–0.80) | 0.008 | 0.48 (0.25–0.93) | 0.030 |
| Thrombocytosis (platelet count > 400 × 10^9/L) | 127 (53.14) | 188 (28.83) | < 0.001 | 2.80 (2.06–3.80) | < 0.001 | 2.43 (1.78–3.32) | < 0.001 |
| Hyponatremia (serum sodium level < 135.0 mmol/L) | 60 (43.17) | 201 (46.21) | 0.531 | 0.88 (0.60–1.30) | 0.531 | 1.33 (0.87–2.02) | 0.182 |
| Hypernatremia (serum sodium level > 145.0 mmol/L) | 34 (24.46) | 128 (29.43) | 0.258 | 0.78 (0.50–1.20) | 0.258 | 0.56 (0.35–0.88) | 0.012 |
| Hypokalemia (serum potassium level < 3.5 mmol/L) | 46 (33.09) | 128 (29.43) | 0.413 | 1.19 (0.79–1.79) | 0.413 | 1.26 (0.83–1.92) | 0.273 |
| Hyperkalemia (serum potassium level > 5.5 mmol/L) | 14 (10.07) | 21 (4.83) | 0.024 | 2.21 (1.09–4.47) | 0.028 | 1.43 (0.68–3.00) | 0.342 |
| Low tCO2 (serum tCO2 level < 16 mmol/L for children < 24 months of age and < 20 mmol/L for children > 24 months of age) | 96 (69.06) | 280 (63.78) | 0.255 | 1.27 (0.84–1.91) | 0.255 | 1.37 (0.90–2.08) | 0.139 |
| Raised creatinine (serum creatinine level > 35 µmol/L for children < 12 months of age and > 65 µmol/L for children < 12 months of age) | 35 (40.70) | 111 (39.50) | 0.843 | 1.05 (0.64–1.72) | 0.843 | 0.84 (0.50–1.39) | 0.490 |
| Hypoglycemia (random blood sugar < 3.0 mmol/L for acute malnourished children, random blood sugar < 2.5 mmol/L for other malnourished children) | 6 (3.31) | 15 (2.53) | 0.569 | 1.32 (0.50–3.46) | 0.570 | 1.48 (0.56–3.96) | 0.430 |
| Outcome, n (%) | |||||||
| Death | 11 (4.60) | 28 (4.29) | 0.842 | 1.08 (0.53–2.20) | 0.842 | 0.97 (0.47–1.99) | 0.928 |
tCO2 = total carbon dioxide content. P value < 0.050 is statistically significant.
For each outcome variable, separate logistic regression models were used.
Unadjusted odds ratios were estimated using simple logistic regression analyses, where the outcome variables were given in the first column and the exposure variable was severe stunting (severe stunting = 1 and without malnutrition = 0 as a reference in the model).
Adjusted odds ratios were estimated using multiple logistic regression analyses for each outcome variable after adjustments for age and sex.
Compared with severe acute malnutrition, severe stunting had significantly lower percentages of dehydration (50% versus 69%), hyponatremia (43% versus 59%), and thrombocytopenia (5% versus 10%). On the contrary, anemia (72% versus 61%), leukocytosis (75% versus 71%), and thrombocytosis (53% versus 41%) were higher among severe stunting cases than among their counterparts (Table 3). After adjustments for age and sex, anemia (aOR = 1.69 [95% CI: 1.12–2.57]; P = 0.013) and thrombocytosis (aOR = 1.61 [95% CI: 1.08–2.40]; P = 0.019) were significantly associated with severe stunting, whereas dehydration (aOR = 0.44 [95% CI: 0.29–0.67]; P < 0.001), thrombocytopenia (aOR = 0.42 [95% CI: 0.19–0.91]; P = 0.028), and hyponatremia (aOR = 0.53 [95% CI: 0.32–0.88]; P = 0.014) were less likely to be associated with severe stunting (Table 3). Severe stunting was associated with a lower percentage of death than severe acute malnutrition (aOR = 0.58 [95% CI: 0.25–1.34]; P = 0.204). However, this was not statistically significant (Table 3). After Sidak correction, the presence of dehydration was statistically significant compared with severe acute malnutrition (P < 0.003) (Table 3).
Table 3.
Association of clinical characteristics, death, and laboratory investigations with severe stunting
| Outcome variables* | Severe stunting n = 239 | Severe acute malnutrition n = 177 | P value | Severe stunting n = 239 | |||
|---|---|---|---|---|---|---|---|
| Unadjusted odds ratio (95% CI)† | P value | Adjusted odds ratio (95% CI)‡ | P value | ||||
| Clinical, n (%) | |||||||
| Acute watery diarrhea | 160 (66.95) | 132 (74.58) | 0.093 | 0.69 (0.45–1.06) | 0.093 | 0.66 (0.43–1.03) | 0.068 |
| Invasive diarrhea | 16 (6.69) | 18 (10.17) | 0.201 | 0.63 (0.31–1.28) | 0.204 | 0.64 (0.31–1.32) | 0.225 |
| Presence of dehydration | 114 (50.00) | 113 (68.90) | < 0.001 | 0.45 (0.30–0.69) | < 0.001 | 0.44 (0.29–0.67) | < 0.001 |
| Fever on admission | 76 (31.80) | 60 (33.90) | 0.652 | 0.91 (0.60–1.37) | 0.652 | 0.91 (0.60–1.37) | 0.641 |
| Laboratory, n (%) | |||||||
| Anemia (hemoglobin level < 11.0 g/dL) | 171 (71.85) | 106 (60.57) | 0.016 | 1.66 (1.10–2.51) | 0.016 | 1.69 (1.12–2.57) | 0.013 |
| Leukopenia (total leukocyte count < 4.0 × 10^9/L) | 3 (1.28) | 6 (3.45) | 0.139 | 0.36 (0.09–1.47) | 0.155 | 0.39 (0.09–1.75) | 0.219 |
| Leukocytosis (total leukocyte count > 10.0 × 10^9/L) | 177 (75.32) | 124 (71.26) | 0.358 | 1.23 (0.79–1.92) | 0.358 | 1.22 (0.77–1.92) | 0.391 |
| Thrombocytopenia (platelet count < 150 × 10^9/L) | 11 (4.60) | 18 (10.23) | 0.026 | 0.42 (0.19–0.92) | 0.030 | 0.42 (0.19–0.91) | 0.028 |
| Thrombocytosis (platelet count > 400 × 10^9/L) | 127 (53.14) | 73 (41.48) | 0.019 | 1.60 (1.08–2.37) | 0.019 | 1.61 (1.08–2.40) | 0.019 |
| Hyponatremia (serum sodium level < 135.0 mmol/L) | 60 (43.17) | 70 (58.82) | 0.012 | 0.53 (0.32–0.87) | 0.013 | 0.53 (0.32–0.88) | 0.014 |
| Hypernatremia (serum sodium level > 145.0 mmol/L) | 34 (24.46) | 20 (16.81) | 0.132 | 1.60 (0.87–2.97) | 0.134 | 1.57 (0.85–2.93) | 0.152 |
| Hypokalemia (serum potassium level < 3.5 mmol/L) | 46 (33.09) | 45 (37.82) | 0.429 | 0.81 (0.49–1.36) | 0.429 | 0.81 (0.49–1.36) | 0.435 |
| Hyperkalemia (serum potassium level > 5.5 mmol/L) | 14 (10.07) | 15 (12.61) | 0.521 | 0.78 (0.36–1.68) | 0.522 | 0.71 (0.32–1.58) | 0.400 |
| Low tCO2 (serum tCO2 level < 16 mmol/L for children < 24 months of age and < 20 mmol/L for children > 24 months of age) | 96 (69.06) | 84 (67.20) | 0.745 | 1.09 (0.65–1.83) | 0.745 | 1.09 (0.65–1.83) | 0.751 |
| Raised creatinine (serum creatinine level > 35 µmol/L for children < 12 months of age and > 65 µmol/L for children < 12 months of age) | 35 (40.70) | 24 (29.63) | 0.135 | 1.63 (0.86–3.10) | 0.136 | 1.62 (0.82–3.17) | 0.162 |
| Hypoglycemia (random blood sugar < 3.0 mmol/L for acute malnourished children, random blood sugar < 2.5 mmol/L for other malnourished children) | 6 (3.31) | 3 (1.75) | 0.354 | 1.92 (0.47–7.80) | 0.362 | 1.73 (0.42–7.10) | 0.449 |
| Outcome, n (%) | |||||||
| Death | 11 (4.60) | 13 (7.34) | 0.236 | 0.61 (0.27–1.39) | 0.240 | 0.58 (0.25–1.34) | 0.204 |
tCO2 = total carbon dioxide content. P value < 0.050 is statistically significant.
For each outcome variable, separate logistic regression models were used.
Unadjusted odds ratios were estimated using simple logistic regression analyses, where the outcome variables were given in the first column and the exposure variable was severe stunting (severe stunting = 1 and severe acute malnutrition = 0 as a reference in the model).
Adjusted odds ratios were estimated using multiple logistic regression analyses for each outcome variable after adjustment for age and sex.
DISCUSSION
Our study aimed to explore the laboratory findings and consequences of various forms of malnutrition. Compared with non-malnourished and severely stunted cases, severe acute malnutrition cases were more likely to be associated with dehydration and hyponatremia. Fever was less likely to be associated with severe acute malnutrition or severe stunting without malnutrition. Anemia and thrombocytosis were more marked in severe stunting than in non-malnutrition or severe acute malnutrition.
Dehydrating diarrhea is common in children with malnutrition as they have an increased area of gut mucosal surface compared with their body, which results in a higher purging rate and greater stool output during diarrhea.31 Their socioeconomic status, sanitation, and hygiene make them more vulnerable to serious illness. A significant reason for dehydration in severe acute malnutrition is that children consume more water per day than adults because of their higher levels of metabolism and their kidneys’ inability to conserve water.32 The Global Enteric Multicenter Study of children with moderate to severe diarrhea reported an inverse association between HAZ and mortality.33 Nonetheless, a Kenyan study found no correlation between stunting and clinical severity or the existence of any particular pathogen.34 Our findings are consistent with a recent study from Bangladesh that found that people with wasting or severe acute malnutrition are more likely to experience dehydrating diarrhea than stunting.35
When admitted, those with severe acute malnutrition and severe stunting were less likely to present with fever than those without malnutrition. According to a study, fever improves immune cell function and puts pathogens and infected cells under direct stress.36 A systemic review suggests that malnutrition frequently has poor gut-barrier function, diminished exocrine secretion of protective chemicals, low plasma complement levels, atrophy of the lymphatic tissues, and diminished delayed-type hypersensitivity responses, which may be a possible explanation for the severely stunted group in our study.37 According to a WHO pocket book,25 people with severe acute malnutrition often face afebrile conditions and even hypothermia, which can be caused by serious infections. Our observations were also comparable in cases of severe acute malnutrition.
We found that those with severe acute malnutrition had a higher likelihood of having hyponatremia than those without malnutrition. Our study was conducted in a hospital for diarrheal disease, and children presented with diarrhea. The regression model showed a higher prevalence of dehydration. This group of children commonly presents with vomiting and diarrhea that cause a significant loss of sodium.38 According to a study by Sameen and Moorani,39 hyponatremia (22.6%) and diarrhea (50%) were the most frequent electrolyte abnormality and infection, respectively, in severe acute malnutrition. Malnutrition and diarrheal disease can synergistically affect the risk of hyponatremia because both can cause dehydration, electrolyte imbalances, and impaired renal function.40 Zogg et al.41 reported that in comparison to comparable normonatremic controls, hyponatremia in those under 5 years of age with radiological or clinical pneumonia and severe acute malnutrition was linked with older age, the presence of diarrhea, and respiratory difficulties at admission. In our study, patients with severe acute malnutrition frequently had hyponatremia, similar to previous reports; however, because of a lack of previous research, it was not possible to explain the cause of the lower odds of hyponatremia in severe stunting compared with severe acute malnutrition. Further prospective studies may determine the cause.
Another important observation of this study is that severe stunting was significantly associated with thrombocytosis and anemia as opposed to both non-malnutrition and severe acute malnutrition. Previously, a study carried out in Ethiopia showed a correlation between anemia and stunting, which was connected with consuming lower amounts of vitamin A, fruits, vegetables, and meat and the frequency of meals in children under 5 years of age.42 Another study conducted among children under 5 years of age in Ethiopia reported that 53.4%, 23.9%, and 8% of the undernourished had anemia, thrombocytosis, and thrombocytopenia, respectively.43 Here, undoubtedly, anemia predominated. It was already reported from previous research that children in Bangladesh who are malnourished frequently experience iron deficiency anemia.44 Likewise, research in Pakistan has demonstrated that iron deficiency anemia is more frequent in children under 5 years of age.45 The study concluded that thrombocytosis and anemia have a meaningful correlation. This iron deficiency anemia can be caused by a lack of breastfeeding and a diet low in iron that fails to meet the daily requirement.46,47 However, we could not rule out the patients’ iron profiles, peripheral blood films, or other congenital disorders, which was a drawback of this study. In contrast to thrombocytosis, a substantial link with lower respiratory tract infection has been reported in Indian research.48 In addition, it was also observed in our study that patients with severe acute malnutrition had a higher prevalence of anemia and thrombocytosis than those without malnutrition, which has been well explained by other studies.19,20,49–51 However, anemia did not reach statistical significance for this group.
Limitations.
There are some drawbacks to this study. We could not follow the patients after discharge. We could not include subjects who had missing investigation profiles. There was no reassessment of the patients’ investigation reports. There were some limitations in investigations, such as the absence of an iron profile, peripheral blood film, and liver function test. The core temperature assessment was skipped because the patients had diarrhea, and the axillary temperature was instead taken. The MUAC was not used to select participants in this study. Despite its limitations, the study provided some key insights.
CONCLUSION
Children with different forms of malnutrition are vulnerable to different types of infection. In our study, children presented with diarrhea; in addition to biochemical changes, we observed significant hematological changes in laboratory findings. Along with symptomatic management of the acute illness of malnourishment, different management and follow-up guidelines for both severe acute malnutrition and severe stunting are needed to combat ramifications in this population.
ACKNOWLEDGMENTS
This research study was supported by core donors who provide unrestricted support to icddr,b for its operations and research. Current donors providing unrestricted support include the governments of Bangladesh and Canada. We thank our core donors for their support and commitment to icddr,b’s research efforts. The American Society of Tropical Medicine and Hygiene (ASTMH) assisted with publication expenses.
REFERENCES
- 1. UNICEF , 2022. Child Malnutrition. Available at: https://data.unicef.org/topic/nutrition/malnutrition/#:∼:text=In%202020*%20globally%2C%2045.4%20million,and%202.0%20per%20cent%2C%20respectively. Accessed January 12, 2023.
- 2. Black RE, Allen LH, Bhutta ZA, Caulfield LE, De Onis M, Ezzati M, Mathers C, Rivera J, Maternal and Child Undernutrition Study Group , 2008. Maternal and child undernutrition: global and regional exposures and health consequences. Lancet 371: 243–260. [DOI] [PubMed] [Google Scholar]
- 3. Black RE, Victora CG, Walker SP, Bhutta ZA, Christian P, De Onis M, Ezzati M, Grantham-McGregor S, Katz J, Martorell R, 2013. Maternal and child undernutrition and overweight in low-income and middle-income countries. Lancet 382: 427–451. [DOI] [PubMed] [Google Scholar]
- 4. Lenters L, Wazny K, Bhutta ZA, 2016. Management of Severe and Moderate Acute Malnutrition in Children. Reproductive, Maternal, Newborn, and Child Health: Disease Control Priorities. 3rd ed. Washington, DC: World Bank, 205–223. [PubMed] [Google Scholar]
- 5. Dipasquale V, Cucinotta U, Romano C, 2020. Acute malnutrition in children: pathophysiology, clinical effects and treatment. Nutrients 12: 2413. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6. World Health Organization , 2021. Levels and Trends in Child Malnutrition. Available at: https://www.who.int/publications/i/item/9789240025257. Accessed October 3, 2023.
- 7. National Institute of Population Research and Training (NIPORT) MEaFWD , Ministry of Health and Family Welfare, 2019. The Bangladesh Demographic and Health Survey. Available at: https://dhsprogram.com/pubs/pdf/PR104/PR104.pdf. Accessed October 3, 2023.
- 8. Services Directorate General of Health Services , 2020. Real Time Health Information Dashboard. Available at: https://dashboard.dghs.gov.bd/pages/index.php#wasting. Accessed January 12, 2013.
- 9. National Institute of Population Research and Training MEaFWD, Ministry of Health and Family Welfare, and The DHS Program, ICF , 2023. Bangladesh Demographic and Health Survey 2022: Key Indicators Report. Dhaka, Bangladesh and Rockville, MD: NIPORT and ICF. [Google Scholar]
- 10. Musa MK, Muhammad F, Lawal KM, Chowdhury A, Hossain A, 2017. Risk factors of severe acute malnutrition among under-five children: a hospital-based study in Bangladesh. J Med Sci Health 3: 13–21. [Google Scholar]
- 11. Chisti MJ, Hossain MI, Malek MA, Faruque AS, Ahmed T, Salam MA, 2007. Characteristics of severely malnourished under‐five children hospitalized with diarrhoea, and their policy implications. Acta Paediatr 96: 693–696. [DOI] [PubMed] [Google Scholar]
- 12. Olsen EM, Petersen J, Skovgaard AM, Weile B, Jørgensen T, Wright CM, 2007. Failure to thrive: the prevalence and concurrence of anthropometric criteria in a general infant population. Arch Dis Child 92: 109–114. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13. Talbert A, Thuo N, Karisa J, Chesaro C, Ohuma E, Ignas J, Berkley JA, Toromo C, Atkinson S, Maitland K, 2012. Diarrhoea complicating severe acute malnutrition in Kenyan children: a prospective descriptive study of risk factors and outcome. PLoS One 7: e38321. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14. Perignon M, Fiorentino M, Kuong K, Burja K, Parker M, Sisokhom S, Chamnan C, Berger J, Wieringa FT, 2014. Stunting, poor iron status and parasite infection are significant risk factors for lower cognitive performance in Cambodian school-aged children. PLoS One 9: e112605. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15. Getawa S, Getaneh Z, Melku M, 2020. Hematological abnormalities and associated factors among undernourished under-five children attending University of Gondar Specialized Referral Hospital, Northwest Ethiopia. J Blood Med 11: 465. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16. Laghari GS, Radhan AH, Shaikh SA, Khatti NUD, Ahmed Z, Qambrani KBK, 2021. Electrolyte imbalances in malnourished under-5 children with or without diarrhoea. Pak J Med Health Sci 15, doi: 10.53350/pjmhs2115102670. [DOI] [Google Scholar]
- 17. Nahani J, Nik-Aeen A, Rafii M, Mohagheghpour N, 1976. Effect of malnutrition on several parameters of the immune system of children. Ann Nutr Metab 20: 302–306. [DOI] [PubMed] [Google Scholar]
- 18. Cervantes-Ríos E, Ortiz-Muñiz R, Martínez-Hernández AL, Cabrera-Rojo L, Graniel-Guerrero J, Rodríguez-Cruz L, 2012. Malnutrition and infection influence the peripheral blood reticulocyte micronuclei frequency in children. Mutat Res Fundam Mol Mech Mutagen 731: 68–74. [DOI] [PubMed] [Google Scholar]
- 19. Basheir HM, Hamza KM, 2015. Hematological parameters of malnourished Sudanese children under 5 years–Khartoum state–2011. J Clin Med 1: 152–156. [Google Scholar]
- 20. Thakur N, Chandra J, Pemde H, Singh V, 2014. Anemia in severe acute malnutrition. Nutrition 30: 440–442. [DOI] [PubMed] [Google Scholar]
- 21. Ahmed T, Mahfuz M, Ireen S, Ahmed AS, Rahman S, Islam MM, Alam N, Hossain MI, Rahman SM, Ali MM, 2012. Nutrition of children and women in Bangladesh: trends and directions for the future. J Health Popul Nutr 30: 1. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22. Yasmeen M, Rehana M, Mohammad Hanif G, Salma S, 2007. Serum electrolytes changes in malnourished children with diarrhoea. Pak J Med Sci 23. [Google Scholar]
- 23. Shahrin L, Sarmin M, Rahman AS, Hasnat W, Mamun GM, Shaima SN, Shahid AS, Ahmed T, Chisti MJ, 2020. Clinical and laboratory characteristics of acute kidney injury in infants with diarrhea: a cross-sectional study in Bangladesh. J Int Med Res 48: 0300060519896913. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24. Bashir F, Tariful Islam Khan AKM , 2020. Annual Report 2020. Available at: https://www.icddrb.org/dmdocuments/icddr,b%20Annual%20Report%202020.pdf. Accessed October 3, 2023. [Google Scholar]
- 25. World Health Organization , 2013. Pocket Book of Hospital Care for Children: Guidelines for the Management of Common Childhood Illnesses. Geneva, Switzerland: World Health Organization. [PubMed] [Google Scholar]
- 26. World Health Organization , 2015. Stunting in a Nutshell. Available at: https://www.who.int/news/item/19-11-2015-stunting-in-a-nutshell#:∼:text=Stunting%20is%20the%20impaired%20growth,WHO%20Child%20Growth%20Standards%20median. Accessed October 7, 2022.
- 27. World Health Organization Malnutrition. Available at: https://www.who.int/health-topics/malnutrition#tab=tab_1. Accessed October 7, 2022.
- 28. Chisti MJ, Salam MA, Bardhan PK, Sharifuzzaman, Ahad R, La Vincente S, Duke T, 2010. Influences of dehydration on clinical features of radiological pneumonia in children attending an urban diarrhoea treatment centre in Bangladesh. Ann Trop Paediatr 30: 311–316. [DOI] [PubMed] [Google Scholar]
- 29. Nuzhat S, Hasan ST, Palit P, Afroze F, Amin R, Alam MA, Alam B, Chisti MJ, Ahmed T, 2022. Health and nutritional status of children hospitalized during the COVID-19 pandemic, Bangladesh. Bull World Health Organ 100: 98. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 30. Haque MA, Choudhury N, Ahmed ST, Farzana FD, Ali M, Naz F, Siddiqua TJ, Raihan MJ, Rahman SS, Faruque A, 2022. Enhanced women’s decision-making power after the Suchana intervention in north-eastern Bangladesh: a cluster randomised pre-post study. BMJ Open 12: e054148. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 31. Black RE, Brown KH, Becker S, 1984. Effects of diarrhea associated with specific enteropathogens on the growth of children in rural Bangladesh. Pediatrics 73: 799–805. [PubMed] [Google Scholar]
- 32. World Health Organization , 2009. Diarrhoea: Why Children are Still Dying and What Can be Done: UNICEF and WHO Launch Report on the Second Greatest Killer of Children. Available at: https://reliefweb.int/report/world/diarrhoea-why-children-are-still-dying-and-what-can-be-done-unicef-and-who-launch?gclid=Cj0KCQjwvL-oBhCxARIsAHkOiu1jScdrXhCyh5j72u1_To1CCsstYZ9nWegPcPBJjia6P4-cb-5mPFAaAj_9EALw_wcB. Accessed April 28, 2023.
- 33. Kotloff KL, Nataro JP, Blackwelder WC, Nasrin D, Farag TH, Panchalingam S, Wu Y, Sow SO, Sur D, Breiman RF, 2013. Burden and aetiology of diarrhoeal disease in infants and young children in developing countries (the Global Enteric Multicenter Study, GEMS): a prospective, case-control study. Lancet 382: 209–222. [DOI] [PubMed] [Google Scholar]
- 34. Tickell KD, Brander RL, Atlas HE, Pernica JM, Walson JL, Pavlinac PB, 2017. Identification and management of Shigella infection in children with diarrhoea: a systematic review and meta-analysis. Lancet Glob Health 5: e1235–e1248. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 35. Nuzhat S, Shahunja K, Shahid AS, Khan SH, Islam SB, Islam MR, Ahmed T, Chisti MJ, Hossain MI, Faruque A, 2020. Diarrhoeal children with concurrent severe wasting and stunting compared to severe wasting or severe stunting. Trop Med Int Health 25: 928–935. [DOI] [PubMed] [Google Scholar]
- 36. Wrotek S, LeGrand EK, Dzialuk A, Alcock J, 2021. Let fever do its job: the meaning of fever in the pandemic era. Evol Med Public Health 9: 26–35. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 37. Rytter MJH, Kolte L, Briend A, Friis H, Christensen VB, 2014. The immune system in children with malnutrition—a systematic review. PLoS One 9: e105017. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 38. Gangaraj S, Das G, Madhulata S, 2013. Electrolytes and blood sugar changes in severely acute malnourished children and its association with diarrhoea and vomiting. Int J Pharm Sci Invent 2: 33–36. [Google Scholar]
- 39. Sameen I, Moorani KN, 2014. Morbidity patterns of severely malnourished children at tertiary care hospital. Pak Pediatr J 38: 3–8. [Google Scholar]
- 40. Ahmad MS, Wahid A, Ahmad M, Mahboob N, Mehmood R, 2016. Prevalence of electrolyte disorders among cases of diarrhea with severe dehydration and correlation of electrolyte levels with age of the patients. J Coll Physicians Surg Pak 26: 394–398. [PubMed] [Google Scholar]
- 41. Zogg CK, Ahmed T, Faruque ASG, Das SK, Imran G, Chisti MJ, 2013. Predictive factors of hyponatremia in under-five severely malnourished children with pneumonia admitted to a large urban hospital in Dhaka, Bangladesh: a nested case-control design. Food Nutr Sci 4, doi: 10.4236/fns.2013.44051. [DOI] [Google Scholar]
- 42. Mohammed SH, Larijani B, Esmaillzadeh A, 2019. Concurrent anemia and stunting in young children: prevalence, dietary and non-dietary associated factors. Nutr J 18: 1–10. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 43. Getawa S, Getaneh Z, Melku M, 2020. Hematological abnormalities and associated factors among undernourished under-five children attending University of Gondar Specialized Referral Hospital, Northwest Ethiopia. J Blood Med 11: 465–478. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 44. Mohammed Mujib AS, Mohammad Mahmud AS, Halder M, Monirul Hasan CM, 2014. Study of hematological parameters in children suffering from iron deficiency anaemia in Chattagram Maa-o-Shishu General Hospital, Chittagong, Bangladesh. Anemia 2014: 503981. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 45. Liaqat A, Tufail N, Liaqat N, Zahra SHE, Iqbal T, Liaqat F, 2022. Frequency of thrombocytosis in iron deficiency anemia. Pak J Med Health Sci 16, doi: 10.53350/pjmhs22166122. [DOI] [Google Scholar]
- 46. Aspuru K, Villa C, Bermejo F, Herrero P, López SG, 2011. Optimal management of iron deficiency anemia due to poor dietary intake. Int J Gen Med 4: 741–750. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 47. Dalili H, Baghersalimi A, Dalili S, Pakdaman F, Rad AH, Kakroodi MA, Rezvany S, Koohmanaei S, 2015. Is there any relation between duration of breastfeeding and anemia? Iran J Ped Hematol Oncol 5: 218. [PMC free article] [PubMed] [Google Scholar]
- 48. Choudhury J, 2017. Thrombocytosis in under-five children with lower respiratory tract infection. Ann Med Health Sci Res 7:47–51. [Google Scholar]
- 49. Yaikhomba T, Poswal L, Goyal S, 2015. Assessment of iron, folate and vitamin B12 status in severe acute malnutrition. Indian J Pediatr 82: 511–514. [DOI] [PubMed] [Google Scholar]
- 50. Lakonawa KY, Sidiartha IGL, Pratiwi I, 2020. Anemia and metabolic acidosis as risk factor of mortality in children with severe acute malnutrition. Int J Health Sci 4: 60–68. [Google Scholar]
- 51. Üner A, Çalişkan Ü, Öner AF, Koç H, Kasap AF, 2001. Platelet functions in patients with protein-energy malnutrition. Clin Appl Thromb Hemost 7: 286–288. [DOI] [PubMed] [Google Scholar]

