Indian Pediatrics - Editorial

Brief Reports

Indian Pediatrics 2003; 40:976-984

Nutritional Parameters in Children with Malignancy

Vandana Jain, A.P. Dubey, S.K. Gupta*

Departments of Pediatrics and Biochemistry*, Maulana Azad Medical College, New Delhi 110 002, India.

Correspondence to: Dr. A.P. Dubey, Professor of Pediatrics & Incharge Division of Hemato-Oncology, Maulana Azad Medical College, New Delhi 110 002, India.

Manuscript received: July 30, 2002, Initial review completed: October 10, 2002; Revision accepted: April 2, 2003.

Abstract:

Nutritional status of 44 children with newly diagnosed malignancy was evaluated by anthropometric, hematological and biochemical parameters before initiating therapy and response to therapy was assessed during follow up. Malnutrition was seen in 56.8% children by weight for age criteria (WFA <–2z). Low hemoglobin was found in 82% children, 25% had low total proteins (<5.7g/dL), 20.5% low serum albumin (<3.2g/dL), 27.3% low serum transferrin (<210mg/dL) and 16.3% low serum iron (<60ug/dL). Mean anthropometric and biochemical parameters were higher among the survivors compared to non-survivors. Significant difference between the well nourished and the malnourished group was detected in the achievement of remission/response (69.5% vs 38.1%), delays in therapy (8.7% vs 38.1%) and mortality (30.5% vs 61.9%). Complications like febrile neutropenia and bleeding were more in the malnourished group. A statistically significant higher incidence of infection was seen in children with serum iron <60ug/dL than those with higher values of serum iron (42.8% vs 8%). Malnutrition is a major determining factor in treatment planning, complication rates, response to therapy and survival.

Key words: Childhood malignancies, Nutritional parameters.

Malnutrition is a major problem in children with cancer. The reported incidence varies from 6% to as high, as 50% depending upon the nature of the malignancy, the size, location and stage of the disease.

Malnutrition is closely related to late stage of malignancy and is a poor prognostic sign. In fact, it is a frequent cause of death in children with cancer. Compared with adults, children are at a greater risk for nutritional depletion since they have a more rapid metabolic rate and greater caloric needs for growth and development(l).

Till a few years ago, malnutrition in children with cancer was persistently ignored. The malnourished state was considered as part of the symptom complex of progressive and active cancer. Only recently has it been recognized as an isolated problem, quite apart from cancer, which must be identified and dealt with just like other complications like infection and thrombocytopenia.

Various factors have been implicated in the origin and progression of malnutrition in children with cancer(2). Malnutrition is one of the main problems in children with cancer and has been seen in some studies to adversely affect the tolerance to chemotherapy, perfor-mance status, immune status, disease free duration and survival(3).

It is, therefore, vital to pursue an active investigation of nutritional parameters in children with cancer and interrelationship of nutrition and response to treatment in order to assess whether integration of nutritional assessment and support into treatment proto-col improves the outcome.

Subjects and Methods

The study was conducted in the Departments of Pediatrics and Biochemistry, Maulana Azad Medical College and associated hospitals, New Delhi between January 1999 and April 2000. The study group comprised of 44 children (34 males and 10 females) aged between 10 months and 12 years with newly diagnosed malignancy.

An initial anthropometry was done in all cases prior to beginning therapy, that included measurements of weight (accuracy 0.1 kg), length/height (accuracy 0.5 cm), mid arm circumference (MAC) to the nearest 0.1 cm, and triceps skinfold (TSF) measured on the non-dominant arm using Holtain’s skinfold calipers, with an accuracy of 0.l mm. Mid arm muscle circumference (MAMC) was deter-mined using the formula MAMC = MAC-(3.14 × TSF)(4).

Weight For Age (WFA), Height For Age (HFA) and Weight For Height (WFH) values were compared with the NCHS standards for that age and sex(5). Z scores were calculated and values below –2Z were considered low. MAC, TSF and MAMC values were compared with the NHANES I data and values, below 5th percentile were considered low(6).

Hemoglobin was estimated by cyanmethe-moglobin method. Hemoglobin level of less than IIg/dL in children between 6 months and 5 years of age and less than 12 g/dL in the age group of 6 to 14 years was considered low(7). Total serum proteins were measured by Biuret method and values <5.7 g/dL were considered low(8,9). Serum albumin was measured by dye binding technique with bromo-cresol green. Serum albumin <3.2 g/dL was considered low(10,11). Serum iron was measured by the method of Peters et al using Bathophenanthroline reagent. Values below 60 µg/dL were considered low. Total iron binding capacity (TIBC) was also measured using the same method and 200-430 µg/dL was considered as normal range(12). Serum transferrin was calculated using the formula: Serum transferrin =TIBC/I.45. Values below 210 mg/dL were considered low(13).

All cases were followed up for a 6 month period during which response to therapy was assessed by (i) achievement of remission, (ii) tolerance to treatment, (iii) occurrence of relapse during follow up (iv) complications during treatment such as febrile neutropenia, infection and bleeding and (v) mortality during follow-up. Statistical analysis was done using Student t-test and chi-square test.

Results

The study group comprised of 44 patients(34 males and 10 females) in the age range of 10 months to 12 years. There were 14 children each in age group 0-4 years and 4-8 years and 16 in the 8-12 years age group. Various malignancies studied were hematological and lymphoreticular malig-nancies (n = 21), CNS tumors (n = 10), rhabdomyosarcoma (n = 4), retinoblastoma (n = 4), Wilms’ tumor (n = 3) and neuro-blastoma (n = 2). Of the hematological and lymphoreti-cular malignancies, 12 had acute lympho-blastic leukemia, 2 acute myeloid leukemia, 5 Hodgkin’s and 2 Non Hodgkin’s lymphoma.

A high prevalence of malnutrition was found by anthropometric criteria (Table I). The overall prevalence of malnutrition by conventional weight related parameters was found to be significantly lower as compared to arm anthropometry. The anthropometric para-meters of survivors were compared with those of non-survivors (Table II). The t-test detected a significant difference (p <0.05) in the mean weight for height value of survivors as compared to non-survivors. The mean weight for height was also found to be higher for survivors as compared to non-survivors in each of the malignancy groups. The mean MAC, TSF and MAMC were also higher in survivors than non-survivors in each of the individual malignancy groups, though not statistically significant.

TABLE I

Prevalence of Malnutrition by Anythropometric and Biochemical Criteria

Malignancy	No of PTS	WFA <–2Z N(%)	HFA <–2Z N(%)	WFH <–2Z N(%)	MAC <5th P N(%)	TSF <5th P PN(%)	MAMC <5th P N(%)	TP <5.7 g/dL N(%)	ALB <3.2 g/dL N(%)	TRANS <210 mg/dL N(%)	S IRON <60 ug/dL N(%)	TIBC >430 ug/dL N(%)
Hematological	21	14	5	11	18	19	15	8	6	9	4	3
		(66.7)	(23.8)	(52.4)	(87.5)	(90.5)	(71.4)	(38.1)	(28.5)	(42.9)	(19)	(14.3)
ALL	12	9	3	8	10	11	8	5	3	4	3	3
		(75)	(25)	(66.6)	(83.3)	(91.7)	(66.7)	(41.7)	(25)	(33.3)	(25)	(25)
HL	5	2	2	0	4	4	3	1	1	2	0	0
		(40)	(40)	(0)	(80)	(80)	(60)	(50)	(50)	(100)	(0)	(0)
NHL	2	2	0	2	2	2	2	0	0	1	0	0
		(100)		(100)	(100)	(100)	(100)	(0)	(0)	(20)	(0)	(0)
AML	2	1	0	1	2	2	2	2	2	2	1	0
		(50)		(50)	(100)	(100)	(100)	(100)	(100)	(100)	(50)	(0)
Solid Tumors	13	5	3	5	12	10	8	3	2	2	2	1
		(38.5)	(23.1)	(38.5)	(92.3)	(76.9)	(61.5)	(23.1)	(15.4)	(15.4)	(15.4)	(7.7)
CNS Tumors	10	6	2	5	8	8	8	0	1	1	1	1
		(60)	(20)	(50)	(80)	(80)	(80)	(0)	(10)	(10)	(10)	(10)
Total	44	25	10	21	38	37	31	11	9	12	7	5
Malignancies		(56.8)	(22.7)	(47.2)	(86.4)	(84.1)	(70.5)	(25)	(20.5)	(27.3)	(16.3)	(11.5)

WFA - Weight for age, HFA - Height for age, WFH - Weight for height, MAC - Mid arm
circumference, TSF - Triceps fold thickness, MAMC - Mid arm muscle circumference, 
TP - Total proteins, TIBC - Total iron binding capacity, ALL - Acute lymphatic leukemia,
HL - Hodgkins lymphoma, NHL - Non-Hodgkins lymphoma, AML - Acute myeloid leukemia.

TABLE II

Comparison of Anthropometric Parameters of Survivors and Non-survivors

Malignancy	No	HAZ mean (SD)	WHZ mean (SD)	WAZ mean (SD)	MAC mean (SD)	TSF mean (SD)	MAMC mean (SD)
Hematological
Survivors	10	–1.73 (0.88)	–1.54 (0.97)	–2.12 (0.79)	76.8 (9.01)	51.1 (14.15)	82.2 (9.26)
Non-Survivors	11	–1.33 (1.10)	–2.13 (0.81)	–2.21 (0.70)	73.5 (8.46)	46.3 (7.84)	78.9 (10.26)
CNS tumors
Survivors	6	–1.49 (0.42)	–1.67 (1.54)	–2.08 (1.34)	80.2 (12.3)	64.3 (26.07)	83.8 (10.06)
Non-survivors	4	–1.43 (1.57)	–3.04 (1.02)	–3.03 (1.70)	68.8 (12.7)	38.8 (17.3)	73.8 (10.9)
Solid tumors
Survivors	8	–1.48 (1.05)	–1.5 (0.90)	–2.12 (0.90)	76.4 (5.97)	48.1 (12.5)	83 (5.97)
Non-survivors	5	–0.9 (1.16)	–2.01 (0.79)	–1.96 (0.83)	70.6 (17.1)	45 (16.8)	77.9 (16.1)
Total
Survivors	24	–1.59 (0.93)	–1.56 (0.79)	–2.11 (0.96)	77.5 (8.84)	53.3 (17.8)	82.8 (8.18)
Non-survivors	20	–1.25 (1.13)	–2.28 (0.85)	–2.31 (1.00)	71.8 (11.3)	44.4 (12.19)	77.8 (11.55)

HAZ - Height for age z score, WHZ - Weight for height z score, WAZ - Weight for age z score,
MAC - Mid arm circumference, TSF = Triceps skinfold thickness, MAMC - Mid arm muscle 
circumference.
We also compared the outcome of children with malignancy between the well nourished and malnourished groups (Table III). Fisher’s exact and Chi-square tests were applied to test the significance of difference in these two groups. A significant difference (p <0.05) was found using WFH for remission/response, delay in therapy and mortality. Although no significant difference was found among any outcome variable in relation to any of the arm anthropometric parameters used, mortality was higher in malnourished (47.5%) as compared to well nourished group (33%) by MAMC and MAC. The well nourished group also tolerated therapy well in a higher proportion of cases.

TABLE III

Comparison of Outcome of Children with Malignancy Between Well nourished
and Malnourished groups

					Complications
Parameters		No. of patients	Remission/ response (%)	Treatment delay (%)	FN (%)	Infection (%)	Bleed (%)	Mortality (%)
HFA	wn	34	19(55)	7(20)	10(29)	5(15)	15(44)	15(44)
	mn	10	5(50)	3(30)	3(30)	0(0)	3(30)	5(50)
WFH	wn	23	16(69.5)	2(8.7)	6(26)	2(8.7)	7(30)	7(30)
	mn	21	8(38)	8(38)	7(33)	3(14)	11(52)	13(62)
WFA	wn	19	11(58)	3(15.8)	6(32)	2(10)	7(37)	8(42)
	mn	25	13(52)	7(28)	7(28)	3(12)	11(44)	12(48)
MAC	wn	6	4(66.7)	1(16.7)	2(33)	1(17)	3(50)	2(33)
	mn	38	20(52.6)	9(23.7)	11(29)	6(16)	15(39)	18(47)
TSF	wn	7	4(57)	2(28.5)	2(28)	1(14)	3(43)	3(43)
	mn	37	20(54)	8(21.6)	11(30)	6(16)	15(40)	17(46)
MAMC	wn	13	8(61.6)	2(15.4)	3(23)	1(7.7)	5(38)	5(38)
	mn	31	16(51.6)	8(25.8)	10(32)	6(19)	13(42)	15(48)

wn – well nourished, mn – malnourished, FN – febrile neutropenia.

Hemoglobin was low in 82% of children. The mean hemoglobin level among survivors of hematological malignancies was found to be significantly higher than that of non-survivors (8.3 vs 3.8 g/dL). Biochemical parameters detected a much lower prevalence of malnutrition as compared to anthro-pometric parameters, i.e., 25% by total proteins, 20.5% by serum albumin, 27.3% by serum transferrin, 16.3% by serum iron and 11.5% by TIBC (Table I). Prevalence of malnutrition by biochemical parameters was observed to be higher in children with hematological malignancies as compared to non-hematological malignancies.

The biochemical parameters were also compared between survivors and non survivors (Table IV). Serum albumin values were significantly lower (p <0.05) among the non-survivors. Although other biochemical parameters were also low in the non-survivor group, none of them achieved statistical significance. The incidence of infection was found to be significantly higher (p <0.05) in children with serum iron <60 µg/dL as compared to those having higher serum iron values (42.8% vs 8.1 %).
TABLE IV

Comparison of Biochemial Parameters of Survivors and Nonsurvivors
Group

No

Total protein Mean (SD) g/dL

S. Albumin Mean (SD) g/dL

S. Iron Mean (SD) µg/dL

TIBC Mean (SD) µg/dL

S. Transferrin Mean (SD) mg/dL

Survivors

24

6.5

3.8

101.8

336.6

244

(0.7)

(0.5)

(39.5)

(80.7)

(38.8)

Non-survivors

20

6.0

3.3

92.9

320.9

220.7

(0.8)

(0.5)

(33.8)

(63.1)

(43.4)

Discussion

In the past few years, there has been great improvement in the survival of children with cancer. Hence, the emphasis now is not just on the longevity but also on the quality of life of these children. Although the association of malnutrition with malignancy has been well known, only recently has it been recognized that the nutritional status of a child with malignancy has a bearing on the treatment and survival. Very few studies are available in Indian literature regarding the prevalence of malnutrition in childhood malignancies.

In the present study, the prevalence of malnutrition at the time of diagnosis in children with malignancies was studied using anthropometric, hematological and bio-chemical parameters. A comparison of the sensitivity for early detection of malnutrition by different parameters was made. An attempt was made to study the relationship if any between the various nutritional parameters at the time of diagnosis and the response to therapy and outcome. The overall prevalence of malnutrition was found to be very high in the present study. vanEys (14) found a 28.2% prevalence of malnutrition by weight for height at the time of diagnosis of cancer in children. Smith(15) in a similar study found that HFA and WFA were unaffected, but 20% of patients were malnourished by MAC and 23% by TSF. In another study WFH was unaffected but 27% patients were mal-nourished by MAC and TSF(16). Mukhopadhyay et al(17) in a retrospective study of ALL patients, found a prevalence of 16.9% by WFA and 10.3%by HFA. In a similar study of ALL patients(18), the prevalence of malnutrition at the time of diagnosis was found to be 52% by WFA which rose to 88% when arm anthropometric parameters were also evaluated.

The present study revealed that arm anthropometry detected a higher prevalence of malnutrition with all type of malignancies than the conventional weight and height based parameters. Similar findings have been reported in other studies(15,16,18). This can be explained by the fact that presence of a large tumor mass, ascites or edema can mask the effect of nutritional depletion on body weight and secondly, when faced with nutritional restrictions, the body first utilizes its nutritional reserves stored in the form of skeletal muscle protein and fat reflected by an early decline in MAC and TSF values(15).

When the mean values of different anthropometric parameters were compared between the survivor and non-survivors, the conventional as well as arm anthropometric parameters had higher mean values in the survivor group. However, WFH was the only parameter with which this difference in means achieved statistical significance (p <0.05). Many western studies(2,3,22-24) involving children with various malignancies have also inferred that malnutrition at the time of diagnosis had an adverse impact on the survival of these children whereas good nutritional status was associated with better survival. An interesting observation made was that in patients with solid tumors the WFA was higher for non-survivors than survivors. This was in consonance with the observations of other authors(19-21) as the tumor burden in association with ascites constitutes a major weight determining factor and hence is an unreliable indicator of nutritional status.

We also studied, the impact of nutritional status on the disease pattern i.e. incidence of relapse, treatment delays, dose reduction and complications (viz., febrile neutropenia, bleeding and infection). In the total study population, children malnourished by WFH were observed to have statistically significant (p <0.05) lower rates of achievement of remission, poor response to therapy and a greater incidence of delay in, treatment. Various other studies (11,20,22,25) have also found similar results.

Overall, 82% of children were seen to have low hemoglobin at diagnosis. The highest prevalence (85.7%) was seen with hemato-logical malignancies, which can be explained by the involvement of bone marrow in these cases. The mean hemoglobin level of survivors of hematological malignancies was found to be significantly higher in comparison to non-survivors. Carter et al(9) had found a mean hemoglobin of 9.5 g/dL in children with hematological malignancies and 12.2 g/dL in those with solid tumors. The much lower hemoglobin values in our cases could be explained by the low overall nutritional status of Indian children and their late presentation.

The prevalence of malnutrition by biochemical parameters was seen to be much lower in comparison to that detected by anthropometry. Similar observations were made by other authors as well (3,9,14,16). The mean values of total proteins and serum albumin were significantly higher for survivors (6.5 & 3.8 g/dL) compared to non-survivors (6 & 3.3 g/dL). A significantly higher infection rate (p <0.05) was found in children with serum iron <60 µg/dL (42.8%) as compared to those with higher values (8.1%). This was in consonance with the findings of other workers that iron defi- ciency leads to deranged immune function and increased susceptibility to infection (1,21,27).

In conclusion, malnutrition is widely prevalent in children with malignancy and is a major determining factor in treatment planning, complication rates and final outcome of the disease.

Contributors: VJ was responsible for data collection and drafting the paper. APD drafted the paper and was the guide, coordinator and main supervisor. He will act as the guarantor of the paper. SKG did the biochemical workup and was the co-guide for the study.

Funding: None stated.

Competing interests: None.

Key Messages

• Malnutrition is highly prevalent in children with malignancy at diagnosis.

• Malnourished children have lower rates of achievement of remission and higher incidence of delay in treatment.

• Higher incidence of febrile neutropenia, bleeding manifestations and infection is seen in malnourished children with malignancy.

• Iron deficiency is associated with a higher incidence of infection in children with malignancy.

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