Pediatr Blood Cancer

REVIEW ARTICLE Weight and Height in Children Newly Diagnosed With Cancer Aeltsje Brinksma, PhD,1,2* Petrie F. Roodbol, PhD,1 Esther Sulkers, Msc,1,2 H. Louise Hooimeijer, MD,2 Pieter J.J. Sauer, MD, PhD,3 Eric van Sonderen, PhD,4 Eveline S.J.M. de Bont, MD, PhD,2 and Wim J.E. Tissing, MD, PhD2 Background. Although weight loss and lack of linear growth occur in children with cancer, growth history is not included in research that aims to determine nutritional status in children newly diagnosed with cancer. Therefore, this study aimed to determine weight loss and lack of linear growth in this patient group. Procedure. Weight and height were recorded in 95 children (ages 1.5–10 years) at diagnosis and compared with data predicted from growth curves. Age, gender, type of malignancy, extent of disease, and prior weight and height were tested for their potential relation to differences between actual and predicted data. Results. The incidence of undernutrition, based on z-scores for weight-for-age (WFA), heightfor-age (HFA), and weight-for-height (WFH), was 2%, 4%, and 7%, respectively. Actual z-scores were lower than predicted z-scores. Differences between actual and predicted z-scores of 5.0 years of age at the time of diagnosis. In case the two groups did not differ, further analyses were conducted for the whole group. Differences in weight and height z-score were evaluated in relation to age, gender, type of malignancy (hematological, solid, and brain), extent of disease, and weight and height prior to diagnosis. Extent of disease was divided into localized or advanced stage (defined as leucocytes >100  109/L in leukemia, metastasis in solid and brain malignancies, stage III and IV in lymphoma).

Statistical Analyses Weight and height z-scores at diagnosis were expected to be lower than predicted z-scores. Therefore, one-sided dependent t-tests were used to compare actual z-scores for WFA, HFA, and WFH with predicted z-scores for WFA, HFA, and WFH. Two-sided independent t-tests were performed to compare Dz-scores for children 5.0 years and children >5.0 years of age, and Pearson Chi-square was performed to compare percentage children with Dz < 0.5 SDS in both groups. The relationship between Dz and age, gender, and prior weight and height, was analyzed using the Pearson correlation coefficients and independent t-tests. Analysis of variance (ANOVA) was used to compare the Dz between the three types of malignancies. Odds ratio were calculated to determine the association between extent of disease and Dz. Significance of OR was tested by Pearson Chi-square. Given that the number of respondents was fixed at 95, statistical power was sufficient for an effect size of 0.25 (b ¼ 0.80; a ¼ 0.05). P-value 5 years did not differ (independent t-test all P values >0.05). Therefore, data of both groups were analyzed together. Actual z-scores for WFA, HFA, and WFH were lower than predicted z-scores (dependent t-test all P values 5.0 years (Pearson Chi-square all values >0.05).

Factors Related to Differences Between Actual and Predicted z-Scores Correlation coefficients revealed that differences in zWFA, zHFA, and zWFH were not related to age at diagnosis (Pearson r ¼ 0.024, 0.013, 0.031, respectively, all P values >0.05) or to nutritional status prior to diagnosis (Pearson r ¼ 0.126, 0.067, 0.124, respectively, all P values >0.05). No differences were found between

TABLE I. Characteristics of the Respondents (n ¼ 95) Characteristics Median age (range) Age 5.0 years Age >5.0 years Gender: female

Diagnosis Hematological Leukemia Lymphoma Solid tumors Neuroblastoma Wilms tumors Bone Solid other Brain tumors Medullo- and ependymoblastoma Astrocytoma/glioma Other

5.4 (1.7–10.8) n (%) 44 (46) 51 (54) 45 (47) Extent of disease, n (%)a n (%)b Localized (n ¼ 70)

Advanced (n ¼ 25)

43 (80) 40 3 14 (56) 2 4 5 3 13 (81) 2

11 (20) 5 6 11 (44) 7 2 1 1 3 (19) 2

5 6

0 1

a

Total 54 45 9 25 9 6 6 4 16 4

(57) (47) (10) (26) (10) (6) (6) (4) (17) (4)

5 (5) 7 (7)

% refers to percentage patients of the diagnosis group; b% refers to the total patient group. Pediatr Blood Cancer DOI 10.1002/pbc

Fig. 2. Percentage of patients (n ¼ 95) with z < 2 SDS, Dz < 0.5 SDS, and the total percentage of patients with actual low values for weight and height or significant differences. WFA, weight-for-age; HFA, height-for-age; WFH, weight-for-height; Dz-score: z-score diagnosis  predicted z-score; SDS, standard deviation score.

males and females (independent t-test: zWFA t ¼ 0.161, zHFA t ¼ 0.269, zWFH t ¼ 0.399, all P values >0.05). Patients with hematological and solid malignancies had lower z-scores for WFA, HFA, and WFH at diagnosis than predicted (Table II). In patients with brain malignancies zWFA remained stable, whereas zHFA at diagnosis was almost 0.5 SDS lower than the predicted zHFA (Table II). ANOVA analyses revealed that the three diagnosis groups did not differ with regard to the differences between actual and predicted z-scores (ANOVA(Welch statistic) WFA F ¼ 1.299, HFA F ¼ 1.121, WFH F ¼ 1.777, all P values >0.05). Differences in Dz-scores for WFA and WFH were greater in patients with advanced stage cancer compared with localized stage (independent t-test values P < 0.05, Table II). Advanced stage was associated with higher risk of significant weight loss (0.05).

DISCUSSION In this study, comparison of weight and height at diagnosis with data from growth curves indicated that, on average, children’s z-scores of weight and height at diagnosis were lower than predicted from their growth curves. Based on actual z-scores, 2%, 4%, and 7% of the children were undernourished at diagnosis for WFA, HFA, and WFH, respectively. However, compared with their growth curves another 20–24% of the children lost more than 0.5 SDS in WFA, HFA, and WFH z-score. In fact, more children were poorly nourished than weight and height at diagnosis indicated. A child with significant weight loss (for instance, >0.5 SDS in 1 month) may be more at risk of adverse health outcomes than a child who grows along the 2 SDS WFA curve. Therefore, growth history should be included when determining nutritional status in children newly diagnosed with cancer. The differences between actual and predicted z-scores of weight and height were the same for males and females and were independent of the child’s previous weight and height. Thus, children with low values for WFA on their growth curves were not more susceptible to weight loss than children with high values for WFA. Contrary to another study [25], which found higher risk of

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Brinksma et al.

TABLE II. Predicted Estimated z-Score, z-Score at Diagnosis and Difference in z-Score: Dz ¼ zP  zDx Predicted z-score growth curves Actual z-score at diagnosis All patients (n ¼ 95)

zWFA (SD) zHFA (SD) zWFH (SD)

Hematological (n ¼ 54)

zWFA (SD) zHFA (SD) zWFH (SD) zWFA (SD) zHFA (SD) zWFH (SD) zWFA (SD) zHFA (SD) zWFH (SD)

0.00 0.02 0.00 0.31 0.29 0.24 0.07 0.14 0.03

Localized stage (n ¼ 70) zWFA (SD) zHFA (SD) zWFH (SD) Advanced stage (n ¼ 25) zWFA (SD) zHFA (SD) zWFH (SD)

0.03 0.06 0.03 0.26 0.26 0.18

Solid (n ¼ 25) Brain (n ¼ 16)

Dz-score

P-valuea Effect sizeb

0.14 (1.03) 0.10 (1.20) 0.13 (1.12)

0.23 (0.55) 0.22 (0.61) 0.20 (0.85)

0.002 0.020 0.047

0.39 0.33 0.23

(0.88) (1.02) (0.81) (1.09) (1.26) (0.94) (0.93) (1.00) (0.79)

0.17 0.11 0.17 0.09 0.07 0.21 0.10 0.34 0.15

(0.95) (1.08) (1.02) (1.22) (1.39) (1.15) (1.06) (1.34) (1.37)

0.17 0.13 0.17 0.40 0.22 0.45 0.18 0.49 0.12

(0.40) (0.46) (0.74) (0.67) (0.60) (0.88) (0.74) (0.99) (1.06)

0.002 0.020 0.047 0.003 0.038 0.008 0.177 0.031 0.327

0.39 0.28 0.23 0.52 0.35 0.47 0.24 0.46 0.12

(0.93) (1.03) (0.83) (1.00) (1.21) (0.85)

0.11 0.12 0.07 0.21 0.07 0.31

(0.97) (1.21) (1.05) (1.21) (1.22) (1.28)

0.14 0.17 0.09 0.47 0.33 0.49

(0.48)† (0.60) (0.80)‡ (0.67)† (0.66) (0.93)‡

0.007 0.009 0.119 0.001 0.009 0.008

0.29 0.28 0.12 0.58 0.46 0.47

0.09 (0.94) 0.11 (1.08) 0.07 (0.84)

Mean (SD) are presented. y, years; SD, standard deviation; zWFA, z-score weight-for-age; zHFA, z-score height-for-age; zWFH, z-score weightfor-height. aP values based on one-sided Paired t-tests; bEffect size based on Cohen’s r; effect sizes are designated as small (0.10), medium (0.30), and large (0.50); †These values differ significantly according to independent t-test; ‡These values differ significantly according to independent t-test.

undernutrition in younger children after hospital admission, including children diagnosed for cancer, the current study found no relationship between age and weight loss, possibly because of the heterogeneity of the patient group. In patients with hematological and solid malignancies, significant losses in zWFA, zHFA, and zWFH were demonstrated. Next to loss in zHFA, loss in zWFH was significant as well. This means that, proportionally, loss in weight was more severe than lack of linear growth. In line with the literature [4,26], the current study demonstrated that children with an advanced stage of cancer experienced more severe weight loss. Their risk of 5% weight loss in 3 months compared with their weight at admission [22]. Rapid weight loss seems to make these children more vulnerable to bacterial infections. In the Pediatr Blood Cancer DOI 10.1002/pbc

literature [33], the most specific criteria define significant weight loss as >2% in 1 week, >5% in 1 month, >7.5% in 3 months, and >10% in 6 months. However, since z-scores do not change during normal growth, z-scores are better indicators to detect differences in weight and height over time and should therefore be preferred to % weight loss. Further research is needed to define clinical relevant cut-off values for changes in z-scores. An additional finding of this study was lack of linear growth in patients with hematological and solid malignancies. Weight loss is to be expected considering the acute nature of these malignancies. However, the lower than expected height at diagnosis reveals that some of these children may have suffered from poor health for a longer period of time, which suggests that the cancer process was present long before diagnosis. The model used in the current study to predict z-scores in each child is based on findings showing that children follow their own growth curve from approximately 1 to 1.5 years until puberty. Several studies demonstrated that in the period between infancy and puberty children kept their own growth curve; whereas in infancy and puberty z-scores deviated considerably [15–17]. Another study [34] found horizontal height tracks in a majority of prepubertal children, indicating that those children maintained their growth curve. The current study demonstrated that the inclusion of the normal growth pattern of the individual child resulted in the identification of nearly 25% more children with a poor nutritional status at diagnosis of cancer than a classification based on actual values alone. Children with advanced cancer had the highest risk of weight loss. Although the onset of cancer is considered to be acute and is associated with loss in weight, lack of linear growth was also found in this study. In conclusion, in addition to actual weight and height at diagnosis, comparison of weight and height with the child’s own growth history should be standard of care to ensure appropriate nutritional interventions and should be common practice in research

Weight and Height in Children With Cancer that aims to determine nutritional status in children newly diagnosed with cancer.

ACKNOWLEDGMENTS We are very grateful to all children and their parents for participating in the Pecannut study and Clep2 study. We wish to thank Sonja Hintzen of the University Medical Center Groningen for her constructive advice and editing service and we wish to thank Thijs de Bont of the University Medical Center Groningen for his graphical support.

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Weight and height in children newly diagnosed with cancer.

Although weight loss and lack of linear growth occur in children with cancer, growth history is not included in research that aims to determine nutrit...
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