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Purpose Low doses of folinic acid (FA) rescue after high-dose methotrexate (HD-MTX) have been associated with increased toxicity, whereas high doses may be related to a decreased antileukemic effect. The optimal dosage and duration of FA rescue remain controversial. This study was designed to investigate, whether a shorter duration of FA rescue in the setting of rapid HD-MTX clearance is associated with increased toxicity. Methods We reviewed the files of 44 children receiving a total of 350 HD-MTX courses during treatment for acute lymphoblastic leukemia according to the NOPHO ALL-2000 protocol. Following a 5 g/m2 HD-MTX infusion, pharmacokinetically guided FA rescue commenced at hour 42. As per local guidelines, the patients received only one or two 15 mg/m2 doses of FA in the case of rapid MTX clearance (serum MTX ≤ 0.2 μmol/L at hour 42 or hour 48, respectively). Data on MTX clearance, FA dosing, inpatient time, and toxicities were collected. Results Rapid MTX clearance was observed in 181 courses (51.7%). There was no difference in the steady-state MTX concentration, nephrotoxicity, hepatotoxicity, neutropenic fever, or neurotoxicity between courses followed by rapid MTX clearance and those without. One or two doses of FA after rapid MTX clearance resulted in a 7.8-h shorter inpatient time than if a minimum of three doses of FA would have been given. Conclusion A pharmacokinetically guided FA rescue of one or two 15 mg/m2 doses of FA following HD-MTX courses with rapid MTX clearance results in a shorter hospitalization without an increase in toxic effects.

The adequate nutritional status of pediatric cancer patients is particularly important to enable them to cope with the demands of the disease and its treatment and to maintain normal growth. Malnutrition and obesity have both been associated with reduced survival and increased drug toxicity. We investigated trends in the age- and sex-adjusted body mass index (ISO-BMI) and the prevalence of malnutrition in a Finnish cohort of 139 consecutive children receiving chemotherapy for cancer, with a follow-up period of 42 months after diagnosis. In total, 28% (39/139) of the patients experienced malnutrition (ISO-BMI < 17 or > 10% weight loss), and 12% (16/139) had a nasogastric tube or underwent gastrostomy. Patients with acute or chronic myeloid leukemia (5/10), central nervous system (CNS) tumors (5/13), or solid tumors (13/31) most frequently suffered from malnutrition. There was a significant increase in the ISO-BMI of patients with acute lymphoblastic leukemia (ALL) (+ 2.1 kg/m2) and lymphomas (+ 2.4 kg/m2) during the first 6 months, and the ISO-BMI of patients with ALL remained higher at 42 months compared to baseline (+ 1.9 kg/m2). Conclusion: The cumulative incidence of malnutrition in Finnish pediatric cancer patients is comparable to that reported in other populations. The nutritional status of patients with acute myeloid leukemia, CNS tumors, or solid tumors should be monitored with extra care to facilitate early intervention in the case of impending malnutrition.What is known:• Both malnutrition and obesity are associated with reduced survival and increased drug toxicity in pediatric cancer patients.What is new:• Overall, 28 % of Finnish children receiving chemotherapy for cancer suffer from malnutrition during the first 42 months following the initial cancer diagnosis. • ISO-BMI curves from initial diagnosis to 42 months after diagnosis are provided for patients with different types of cancer.

Infant skull deformation is analyzed using the distribution of head normal vector directions computed from a 3D image. Severity of flatness and asymmetry are quantified by functionals of the kernel estimate of the normal vector direction density. Using image data from 99 infants and clinical deformation ratings made by experts, our approach is compared with some recently suggested methods. The results show that the proposed method performs competitively. Copyright © 2016 John Wiley & Sons, Ltd.

Preterm infants are at higher risk for both symmetrical and asymmetrical head molding. This study involved 3D stereophotogrammetry to assess the cranial growth, molding, and incidence of deformational plagiocephaly (DP) in preterm children compared to term born children. Thirty-four preterm infants and 34 term born controls were enrolled in this study from Oulu University Hospital, Finland. Three-dimensional head images were obtained at the age of 2&ndash, 4 months (T1), 5&ndash, 7 months (T2), 11&ndash, 13 months (T3), and 2.5&ndash, 3 years (T4) from the term equivalent age (TEA). There was no statistically significant difference in oblique cranial length ratio (OCLR), cephalic index (CI), or weighted asymmetry score (wAS) between the two groups. Occipital flattening, defined by flatness score (FS) was statistically significantly greater in the preterm group than in the term group at T1&ndash, T4 (p &lt, 0.05). In both groups, OCLR improved gradually over time. There were no instances, in either group, of severe DP and no moderate DP after T2. Results indicate that DP affects preterm and full-term children almost equally during the first three years of life, and cranial asymmetry resolves at a similar rate in both preterm and term groups after three months of corrected age. Preterm infants present with more occipital flattening than full-term children.

Deformational plagiocephaly (DP) is considered a risk factor for facial asymmetry. This cohort-based, prospective, follow-up study used three-dimensional (3D) stereophotogrammetry to assess the development of facial asymmetry in a normal birth cohort and to investigate the impact of DP on facial asymmetry for the age range of one to three years. The study sample consisted of 75 children: 35 girls (47%) and 40 (53%) boys recruited from Oulu University Hospital. A total of 23 (31%) subjects had a history of DP in infancy. 3D facial images were obtained at the mean (SD) age of 1.01 (0.04) year old at T1 and 3.02 (0.14) years old at T2. To determine facial asymmetry, both landmark-based and surface-based facial symmetry methods were used. As measured with the surface-based methods, upper facial symmetry improved from T1 to T2 (p &lt, 0.05). As measured with the landmark-based methods, facial symmetry improved on the upper and lower jaw from T1 to T2 (p &lt, 0.05). The asymmetric effect of DP on the upper parts of the face tends to correct spontaneously during growth. Results indicate that previous DP does not seem to transfer to facial or occlusal asymmetry at the age of three years old.

Developmental dysplasia of the hip (DDH) may require early abduction treatment with infants sleeping on their back for the first few months of life. As sleeping on back is known to cause deformational plagiocephaly, we assessed school age children treated for dislocation or subluxation of the hip-joint in infancy. Plagiocephaly was analyzed by using cephalic index (CI) and oblique cranial length ratio (OCLR) as anthropometric measurements from 2D digital vertex view photographs. Six of the 58 (10.3%) DDH children and only one of the 62 (1.6%) control children had plagiocephaly (p = 0.041). Furthermore, cross bite was found in 14 (24.1%) of the DDH children and in 7 (10.3%) of the control children. Developmental dysplasia of the hip in infancy was associated with cranial asymmetries and malocclusions at school age. Preventive measures should be implemented.

Objective Various measurements are used to quantify cranial asymmetry in deformational plagiocephaly (DP), but studies validating cut-off values and comparing the accuracy of such measurements are lacking. In this study, we compared the accuracy of four different measurements in classifying children with and without DP diagnosed by visual assessment, and sought to determine their optimal cut-off values. Study design Two experts rated 407 3D craniofacial images of children aged between 3 and 36 months old using the Argenta classification. We then measured the following asymmetry-related variables from the images: Oblique Cranial Length Ratio (OCLR), Diagonal Difference (DD), Posterior Cranial Asymmetry Index (PCAI), and weighted Asymmetry Score (wAS). We created receiver operating characteristic curves to evaluate the accuracy of these variables. Results All variables performed well, but OCLR consistently provided the best discrimination in terms of area under the curve values. Subject's age had no clear effect on the cut-off values for OCLR, PCAI, and wAS; however, the cut-off for DD increased monotonically with age. When subjects with discrepant expert ratings were excluded, the optimal cut-off values for DP (Argenta class ≥ 1) across all age-groups were 104.0% for OCLR (83% sensitivity, 97% specificity), 10.5% for PCAI (90% sensitivity, 90% specificity), and 24.5 for wAS (88% sensitivity, 90% specificity). Conclusion We recommend using OCLR as the primary measurement, although PCAI and wAS may also be useful in monitoring cranial asymmetry. The threshold of relative asymmetry required for a deformation to appear clinically significant is not affected by the child's age, and DD has no additional utility in monitoring DP compared to using only OCLR.

Deformational plagiocephaly is reported in up to 46.6 % of healthy infants, with the highest point prevalence at around 3 months of age. Few prospective studies on the natural course of skull deformation have been conducted, and we know of no studies using 3D imaging starting from the highest point prevalence period. In this prospective, population-based cohort study, we describe the course of cranial asymmetry and shape in an unselected population using 3D stereophotogrammetry and investigate factors associated with late cranial deformation and failure to recover from previous deformation. We evaluated 99 infants at 3, 6, and 12 months of age. We acquired 3D craniofacial images and performed structured clinical examinations and parental interviews at each visit. Eight outcome variables, representing different aspects of cranial shape, were calculated from a total of 288 3D images. Scores of asymmetry-related variables improved throughout the observation period. However, the rate of correction for cranial asymmetry decreased as the infants grew older, also in relation to the rate of head growth, and a significant amount of asymmetry was still present at 12 months. Positional preference at 3 months predicted an unfavorable course of cranial asymmetry after 3 months, increasing the risk for DP persisting. What is known: • The prevalence of deformational plagiocephaly spontaneously decreases after the first months of life. • Limited neck range of motion and infant positional preference increase the risk of deformational plagiocephaly during the first months of life. What is new: • Positional preference at 3 months predicts an unfavorable spontaneous course of deformation also from three to 12 months of age, presenting a potential target for screening and treatment. • The spontaneous rate of correction for cranial asymmetry decreases after 6 months of age, also in relation to the rate of head growth.