Refeeding Syndrome in Children Aged 6 to 59 Months with Severe Acute Malnutrition

By Abdul Salam Memon¹, Muhammad Rafique^1,2, Amanullah Lail^1,2, Kulsoom Abdul sattar¹, Zainab Khalid¹, Malik Sohail Danish¹

Affiliations

1. Department of Paediatric Medicine, Civil Hospital, Karachi, Pakistan
2. Department of Paediatrics, Dow University of Health and Science, Karachi, Pakistan

doi: 10.29271/jcpsp.2025.07.881

ABSTRACT
Objective: To assess the frequency and factors of refeeding syndrome in children aged 6 to 59 months with severe acute malnutrition (SAM).
Study Design: Descriptive, cross-sectional study.
Place and Duration of the Study: Department of Paediatric Medicine, Civil Hospital, Karachi, Pakistan, from April to September 2024.
Methodology: All children aged 6 to 59 months diagnosed with SAM, initially presenting with normal serum phosphate, potassium, and magnesium concentration and underwent nutritional rehabilitation within the initial 72 hours of hospital admission. Refeeding syndrome was defined as the sudden lowering of serum phosphate, potassium, and magnesium concentrations within 72 hours of initiating nutritional rehabilitation. Chi-square/Fisher’s exact test and paired t-test were applied to assess associations and mean differences, considering p ≤0.05 as significant.
Results: The study included 185 children, with mean age of 23.94 ± 12.64 months, comprising of 104 (56.2%) boys and 81 (43.8%) girls. Refeeding syndrome was observed in 23 (12.4%) children. Children with refeeding syndrome showed significant declines in serum phosphate (3.68 ± 1.17 vs. 1.53 ± 0.49 mg/dL, p <0.001), potassium (3.92 ± 0.72 vs. 2.81 ± 0.66 mg/dL, p <0.001), and magnesium (2.02 ± 0.27 vs. 0.93 ± 0.22 mg/dL, p <0.001) levels from the baseline. Refeeding syndrome was significantly associated with younger age (p = 0.009), shorter height (p = 0.009), and the use of nasogastric or intravenous nutritional support (p = 0.012). Cardiac irregularities were more frequent in children with refeeding syndrome (p = 0.039).
Conclusion: Refeeding syndrome occurred in 12.4% of SAM children and was linked to younger age, shorter height, and nasogastric or intravenous feeding.

Key Words: Refeeding syndrome, Severe acute malnutrition, Paediatrics, Electrolyte imbalance, Nutritional support.

INTRODUCTION

Severe acute malnutrition (SAM) is a significant health concern in developing countries and a major contributor to the global burden of childhood diseases.¹ Worldwide, an estimated 19 million children under the age of five years suffer from SAM, contributing to approximately. 400,000 child deaths each year.² Pakistan faces one of the highest rates of childhood malnutrition globally, with 2.14 million suffering from acute malnutrition (AM).³

SAM is associated with a wide array of complications, including hypothermia, hypoglycaemia, dehydration, electrolyte imbalances, sepsis, pneumonia, and micronutrient deficiencies (e.g., nutritional anaemia, dermatoses, mouth ulcers, conjunctival xerosis, and hair changes), and death.⁴

Management of SAM typically involves providing protein- and energy-rich foods.^5,6 However, while addressing nutritional deficits is essential, an abrupt initiation of high-protein, high- energy diets can lead to refeeding syndrome, a potentially life-threatening complication.^2,7

Refeeding syndrome occurs due to metabolic shifts resulting in fluid and electrolyte imbalances when caloric intake is suddenly increased. These imbalances can lead to severe clinical out- comes, with hypophosphataemia being the hallmark of biochemical disturbance, often accompanied by hypokalaemia, hypocalcaemia, and disruptions in fat and protein metabolism.⁸ Despite its potential severity, the true incidence of refeeding syndrome in children with SAM remains unclear, as research in this population is limited. Children with conditions such as Kwashiorkor, Marasmus, or significant recent weight loss (e.g., >10% of body weight in the past three months) are at heightened risk.^7,8

This study intended to investigate a critical yet underexplored aspect of paediatric nutrition. Despite its life-threatening potential, the treatment syndrome in children with SAM, particularly those aged 6 to 59 months, has not been adequately studied. By examining the frequency and associated factors of refeeding syndrome in this vulnerable population, this research seeks to address a vital knowledge gap. Understanding these patterns will contribute to optimising clinical management protocols for children with SAM. Moreover, by focusing on a unique age group with distinct physiological needs, this study may provide an opportunity to tailor interventions and develop more precise guidelines. The anticipated findings have the potential to enhance clinical decision-making and form public health strategies to combat SAM in similar resource-constrained settings. The aim of this study was to assess the frequency and factors of refeeding syndrome in children aged 6 to 59 months with SAM.

METHODOLOGY

A descriptive cross-sectional study was conducted at the Department of Paediatric Medicine, Civil Hospital, Karachi, Pakistan, from April to September 2024. Ethical approval was obtained from the Ethical Committee of the Dow University of Health Sciences, Karachi, Pakistan, prior to the commencement of the study (IRB No: IRB-3425/--/Approval/2024/100). Moreover, signed informed consent was obtained from the guardian/parents of study participants before enrolment in the study.

All children were enrolled in the study via non-probability consecutive sampling technique. The inclusion criteria were children aged 6 to 59 months diagnosed with SAM, initially presenting with normal serum phosphate, potassium, and magnesium concentrations and underwent nutritional rehabilitation within the initial 72 hours of hospital admission. Children with SAM who presented with abnormal electrolyte levels, those with underlying medical conditions that could affect nutritional status or complicate the assessment of refeeding syndrome, such as chronic renal failure, congenital heart disease, metabolic disorders, cystic fibrosis, severe respiratory conditions, neuromuscular disorders, or complex gastrointestinal disorders, or those who were immunocompromised, such as those undergoing chemotherapy for cancer, were excluded.

The Epi Info sample size calculator was used to calculate the sample size, keeping the expected incidence of refeeding syndrome in children as 14% with a marginal error of 5% and a 95% confidence interval.⁹ A total of 185 children with SAM were included.

SAM was defined as weight-for-height Z (WHZ) score <-3 or mid-upper arm circumference (MUAC) <115 millimetres or the presence of bilateral pitting oedema. A comprehensive baseline assessment was conducted, including information regarding demographic characteristics, medical histories such as previous hospitalisation, serum phosphate, potassium, and magnesium levels at the time of hospitalisation, and anthropometric measurements such as MUAC weight, and height were collected. Throughout the initial 72 hours of nutritional rehabilitation, close monitoring was performed to monitor serum electrolyte levels, along with the type of nutritional support and the early signs of refeeding syndrome. Cardiac and respiratory irregularities and neurological problems that occurred since the completion of the nutritional rehabilitation process were noted as early signs of refeeding syndrome. The presence of a rapid or irregular pulse was labelled as cardiac irregularity; rapid breathing, shortness of breath, or chest discomfort were labelled as respiratory distress; and neurological symptoms such as confusion, seizures, or unusual behaviour were labelled as neurological problems.

Refeeding syndrome was defined as the sudden lowering of serum phosphate, potassium, and magnesium concentrations within 72 hours of initiating nutritional rehabilitation in a child with SAM.¹⁰ The cut-off level for electrolyte imbalance was noted as follows: Hypokalaemia (serum potassium level <3.5mg/dL), hypomagnesaemia (serum magnesium level <1.8mg/dL), and hypophosphataemia (serum phosphate level <2.5mg/dL). All information was collected in a pre-designed proforma.

Data analysis was done using the SPSS version 21.0. Mean and standard deviation were calculated for quantitative variables such as age, weight, height / length, MUAC, and electrolyte levels at the baseline and during follow-up. Frequency and percentages were calculated for qualitative variables such as gender, previous hospitalisation, oedema, type of nutritional support, cardiac irregularities, respiratory distress, neurological symptoms, and refeeding syndrome. Chi-square/Fisher’s exact test was applied to see the relationship of refeeding syndrome with predictor variables. Moreover, a paired t-test was applied to see the mean difference of serum electrolyte levels at baseline and follow-up. A p-value of ≤0.05 was considered as significant.

RESULTS

The study included 185 children suffering from SAM with the mean age of 23.94 ± 12.64 months. There were 104 (56.2%) boys and 81 (43.8%) girls. The mean weight, height, and MUAC were 5.29 ± 2.13 kg, 59.68 ± 8.45 cm, and 106.64 ± 5.59 cm, respectively. Previous hospitalisation was reported by 55 (29.7%) and oedema by 173 (93.5%) children.

There were 84 (45.4%) children who were treated with oral nutritional support, 70 (37.8%) by nasogastric tube, and 31 (16.8%) by intravenous support. Cardiac irregularities since the completion of nutritional support were observed in 136 (73.5%), respiratory distress in 143 (77.3%), and neurological symptoms in 141 (76.2%) children.

The mean serum phosphate level was significantly higher at the baseline than at follow-up (p-value <0.001). Whereas serum potassium level was significantly higher at follow-up than at the baseline (p = 0.048). Similarly, serum magnesium level was significantly higher at follow-up than at the baseline (p <0.001, Table I). The frequency of refeeding syndrome was observed in 23 (12.4%) children.

Stratification of refeeding syndrome showed that in children with the refeeding syndrome, all three electrolytes were significantly higher at baseline than during follow-up (p <0.001), serum potassium (p <0.001), and serum magnesium (p <0.001, Table II).

Table I: Mean difference of electrolyte changes pre- and post-nutritional rehabilitation (n = 185).

Variables	Mean ± SD	Absolute mean difference	p-value	95% CI
Serum phosphate level at baseline, mg/dL	3.87 ± 1.09	0.71	<0.001	0.53 to 0.89
Serum phosphate level at follow-up, mg/dL	3.16 ± 0.84
Serum potassium level at baseline, mg/dL	3.85 ± 0.67	-0.13	0.048	-0.27 to -0.01
Serum potassium level at follow-up, mg/dL	3.98 ± 0.58
Serum magnesium level at baseline, mg/dL	1.33 ± 0.57	-0.64	<0.001	-0.76 to -0.52
Serum magnesium level at follow-up, mg/dL	1.98 ± 0.46
Paired t-test applied, p <0.05 considered as significant.

Table II: Mean difference of electrolyte changes pre- and post-nutritional rehabilitation stratified based on the presence and absence of refeeding syndrome (n = 185).

Variables	Mean ± SD	Mean difference	p-value	95% CI
Refeeding syndrome positive, (n = 23)
Serum phosphate level at baseline, mg/dL	3.68 ± 1.17	2.15	<0.001	1.61 to 2.71
Serum phosphate level at follow-up, mg/dL	1.53 ± 0.49
Serum potassium level at baseline, mg/dL	3.92 ± 0.72	1.12	<0.001	0.76 to 1.49
Serum potassium level at follow-up, mg/dL	2.81 ± 0.66
Serum magnesium level at baseline, mg/dL	2.02 ± 0.27	1.09	<0.001	0.96 to 1.22
Serum magnesium level at follow-up, mg/dL	0.93 ± 0.22
Refeeding syndrome negative, (n = 162)
Serum phosphate level at baseline, mg/dL	3.89 ± 1.08	0.50	<0.001	0.34 to 0.67
Serum phosphate level at follow-up, mg/dL	3.39 ± 0.57
Serum potassium level at baseline, mg/dL	3.84 ± 0.67	-0.31	<0.001	-0.43 to -0.19
Serum potassium level at follow-up, mg/dL	4.16 ± 0.31
Serum magnesium level at baseline, mg/dL	1.24 ± 0.54	-0.88	<0.001	-0.96 to -0.79
Serum magnesium level at follow-up, mg/dL	2.13 ± 0.24
Paired t-test applied, p <0.05 considered as significant.

Table III: Comparison of refeeding syndrome with demographic and clinical characteristics of the children (n = 185).

Variables	Total	Refeeding syndrome
		Yes (n = 23)	No (n = 162)	p-value
Age, months [mean ± SD]	23.94 ± 12.64	17.50 ± 6.91	24.86 ± 13.01	0.009¥
Weight, kg [mean ± SD]	5.29 ± 2.13	4.54 ± 1.91	5.39 ± 2.14	0.073 ¥
Height, cm [mean ± SD]	59.68 ± 8.45	55.38 ± 4.21	60.29 ± 8.73	0.009 ¥
Gender
Male	104	10 (9.6)	94 (90.4)	0.188α
Female	81	13 (16.0)	68 (84.0)
MUAC, cm [mean ± SD]	106.64 ± 5.59	105.64 ± 5.69	106.78 ± 5.58	0.363¥
Previous hospitalisation	55	11 (20.0)	44 (80.0)	0.042 α
Oedema	173	22 (12.7)	151 (87.3)	>0.999β
Type of nutritional support
Oral	84	4 (4.8)	80 (95.2)	0.012 α
NG Tube	70	12 (17.1)	58 (82.9)
Intravenous	31	7 (22.6)	24 (77.4)
Cardiac irregularities*	136	21 (15.4)	115 (84.6)	0.039 α
Respiratory distress*	143	21 (14.7)	122 (85.3)	0.087 α
Neurological symptoms*	143	21 (14.9)	120 (85.1)	0.069 α
*Since the completion of the nutritional rehabilitation process, αChi-square test applied, βFisher’s exact test applied, ¥Independent t-test applied.

A statistically significant difference was observed in the mean age and height of children diagnosed with refeeding syndrome compared to those without the condition (p = 0.009 for both variables). Moreover, refeeding syndrome was also present in those who received nutritional support by NG tube or intravenously (p = 0.012). Whereas cardiac irregularities since the completion of nutritional support were also significantly associated with refeeding syndrome (p = 0.039, Table III).

DISCUSSION

This study investigated the frequency and risk factors of refeeding syndrome in children with SAM and evaluated the biochemical and clinical parameters associated with refeeding syndrome. The findings revealed that 12.4% of children developed refeeding syndrome during nutritional rehabilitation. This aligns with the previously reported incidence of refeeding syndrome in malnourished paediatric populations, which varies between 8.7% and 34.8% depending on study settings and diagnostic criteria.^11-14 A study investigated the incidence of refeeding syndrome in the South African children hospitalised with SAM and found a frequency of 15%.¹¹ A study conducted in Kenya in 2018 found a 21% prevalence of refeeding syndrome among children with SAM. HIV infection was a significant risk factor, increasing the odds of refeeding syndrome sixfold.¹³ Though in the current study, all children with SAM initially presented with normal serum phosphate, potassium, and magnesium concentrations, previous studies have revealed significant associations to hypophosphataemia, hypokalaemia, and dehydration at admission.^11,14 Similarly, a case report from Pakistan highlighted the fatal consequences of refeeding syndrome in a 5-year child with SAM, emphasising the importance of monitoring serum phosphate levels during refeeding.¹⁵

According to the current study findings, a significant asso-ciation between younger age and refeeding syndrome was identified. Previous studies have also highlighted that younger children, particularly vulnerable children, are at a heightened risk of refeeding syndrome due to their limited metabolic reserves and higher vulnerability to rapid electrolyte shifts during refeeding.⁸

Electrolyte imbalances are hallmark features of refeeding syndrome, and in this study, serum phosphate, potassium, and magnesium levels were significantly lower during follow-up compared to baseline levels in children who developed refeeding syndrome. Notably, the baseline serum phosphate and magnesium levels were markedly higher than those observed during follow-up in children with refeeding synd-rome. This is consistent with existing evidence emphasising hypophosphataemia as a key biochemical marker of refeed-ing syndrome, often accompanied by hypomagnesaemia and hypokalaemia.^11,14 In a study, it was reported that hypophos-phataemia was a consistent finding, but the other abnorma-lities were not consistently identified.¹⁶

The mode of nutritional support also influenced the occurrence of refeeding syndrome, with children receiving nasogastric (NG) or intravenous (IV) nutritional support being significantly more likely to develop refeeding syndrome. This finding corroborates previous reports that aggressive or parenteral feeding is associated with a higher risk of refeed-ing syndrome due to rapid caloric intake overwhelming the body's metabolic and electrolyte regulation mechanisms.^8,17

Interestingly, cardiac irregularities were significantly asso-ciated with refeeding syndrome, reflecting the potential life-threatening consequences of untreated or poorly managed refeeding syndrome. Previous studies have reported arrhythmias and heart failure as critical complications of refeeding syndrome due to severe hypophosphataemia and associated electrolyte imbalances.^8,18,19

The biochemical findings from this study are noteworthy. While serum phosphate levels declined significantly from the baseline to follow-up, potassium and magnesium levels were observed to improve over time. These trends may reflect the efficacy of timely interventions and electrolyte monitoring during the nutritional rehabilitation process.²⁰ Similar to this study’s finding, Chanchal et al. observed that hypopho-sphataemia is a frequent biochemical abnormality in children with SAM.²¹ They emphasised the need for monitoring serum phosphate levels during treatment and refeeding, noting that while hypophosphataemia was not significantly linked to higher mortality, further research is warranted to clarify this association.²¹ A recent study from Pakistan demons-trated that introducing therapeutic feeds (F-75 and F-100) during the stabilisation and rehabilitation phases effectively improves phosphate levels in children with SAM who initially present with hypophosphataemia.²² Additionally, the current study highlights a significant gap in clinical management protocols for SAM-related refeeding syndrome in resource-constrained settings such as Pakistan. Despite established guidelines for the management of SAM, tailored strategies focusing on refeeding syndrome prevention, including cautious caloric advancement and rigorous electrolyte monitoring, remain under-implemented in many low- and middle-income countries.

The study’s strengths include the use of biochemical and clinical parameters to comprehensively evaluate refeeding syndrome in a high-risk paediatric population. However, limitations include its single-centre design and the lack of long-term follow-up, which might limit the generalisability of the findings. Future studies should explore multi-centre cohorts and evaluate the long-term outcomes of refeeding syndrome interventions.

CONCLUSION

This study found that refeeding syndrome affected 12.4% of children with SAM, with significant drops in phosphate, potassium, and magnesium levels during refeeding. Younger age, nasogastric or intravenous feeding, and cardiac irregu-larities were identified as key risk factors. The findings highlight the need for cautious refeeding protocols, close monitoring of electrolytes, and tailored nutritional strategies to prevent refeeding syndrome in this high-risk population.

ETHICAL  APPROVAL:
Ethical approval was obtained from the Ethical Committee of the Dow University of Health Sciences, Karachi, Pakistan (IRB No: IRB-3425/--/Approval/2024/100).

PATIENTS’ CONSENT:
Informed consent was obtained from the guardian/parents of the study participants before enrolment in the study.

COMPETING  INTEREST:
The authors declared no conflict of interest.

AUTHORS’ CONTRIBUTION:
ASM, MR: Concept, literature, and drafting of the manuscript.
ASM, AL: Design, analysis, interpretation, literature review, report writing, and data collection.
KAS, ZK, MSD: Acquisition and drafting of the manuscript.
All authors approved the final version of the manuscript to be published.

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