Chemotherapy-related toxicities follow a typical pattern in children treated for acute lymphoblastic leukaemia.

AIM: Acute lymphoblastic leukaemia (ALL) therapy has been associated with a significant burden of toxicities. The aim of this study was to describe the full spectrum of toxic effects associated with childhood ALL. METHODS: Toxicity-related data were collected from the Nordic Society of Paediatric Haematology and Oncology (NOPHO) ALL-2008 toxicity registry, in which data on 19 clinically relevant toxicities were registered during ALL treatment, and from patient medical records. All patients treated according to the NOPHO ALL-2008 protocol in Oulu University Hospital between 2008 and 2020 were included in the study. RESULTS: The cohort consisted of 73 patients, 38 of whom were male. Mean age at diagnosis was 6.6 ± 4.2 (range 1.4-16.0) years. All but one of the patients developed at least one treatment-related toxicity and more than half had multiple toxicities. Female sex and older age were associated with a higher tendency towards toxicity. The most common toxicity was vincristine-induced peripheral neuropathy, which was observed in 70 patients. Most toxicities were moderate or severe, but even mild toxicities often affected leukaemia treatment. CONCLUSION: Moderate and severe treatment-related toxicities are common, and most toxicities occur in a typical pattern in relation to the treatment phases.

Parental Ability to Assess Pediatric Vital Signs.

OBJECTIVE: To evaluate parents' ability to accurately assess their child's heart and respiratory rates (RRs) in the context of potential utility for telehealth visits. STUDY DESIGN: In this controlled study of 203 child-parent pairs, parents measured their child's heart rate (HR) using 4 methods: palpation, auscultation, and 2 photoplethysmographic smartphone applications. Parents measured RR by inspecting the child and tapping the smartphone application. The gold standards were electrocardiogram for the HR and the child's breaths measured by a health care professional for 60 seconds for the RR. We plotted the measurements using a Bland-Altman plot with 95% limits of agreement. RESULTS: Parents underestimated HR by palpation with a calculated bias of -18 beats per minute (bpm) (SD, 19), with limits of agreement ranging from -56 to 19 bpm. Parents overestimated and underestimated HR by auscultation with limits of agreement ranging from -53 to 46 bpm. Smartphone applications did not improve the accuracy of measurements. The accuracy of parental RR measurements was low. For young children, bias was -0.8 breaths per minute (brpm) (SD, 9.8) with limits of agreement from -20 to 19 brpm, and for older children, bias was 0.9 brpm (SD 7.4) with limits of agreement from 6 to 15 brpm. The sensitivity of parental subjective opinion to recognize accelerated RR was 37% (95% CI, 25%-51%). CONCLUSION: Parents were not able to assess their child's RR or HR accurately. Digital remote assessment of children should not rely on parental measurements of vital signs.

A longitudinal study of facial asymmetry in a normal birth cohort up to 6 years of age and the predisposing factors.

OBJECTIVES: This prospective, population-based cohort study aimed to investigate the development of facial asymmetry up to 6 years of age using a three-dimensional (3D) soft tissue imaging method in a normal population. In addition, the study sought to identify potential predisposing factors to facial asymmetry. METHODS: A total of 102 newborns were enrolled in the study at birth. 3D stereophotogrammetric images of the head and face were analysed at the ages of 12 months (T1), 3 years (T2), and 6 years (T3). The surface-based analysis involved the calculation of the average distance (mm) and the symmetry percentage (%) between the original and mirrored surfaces. For landmark-based analysis, the distance of facial landmarks to the facial midline was examined. RESULTS: The final analysis included 70 (68.6%) subjects. Surface-based analysis showed a significant improvement of facial symmetry from T1 to T3 in all facial areas. Landmark-based analysis showed that upper facial landmarks were located, on average, slightly on the left and lower facial landmarks slightly on the right in relation to the facial midline (P < 0.001). LIMITATIONS: The size of the study population was limited. Facial posture may affect the reliability of the results, especially in younger children. CONCLUSION: Facial asymmetry is detectable in early childhood and tends to reduce with age in young children. The lower face deviates slightly to the right, and the upper face to the left in relation to the facial midline. Possible predisposing factors for facial asymmetry at the age of 6 years include deformational plagiocephaly, sleeping position, and previous facial asymmetry.

Reduced dose folinic acid rescue after rapid high-dose methotrexate clearance is not associated with increased toxicity in a pediatric cohort.

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.

Trends in age- and sex-adjusted body mass index and the prevalence of malnutrition in children with cancer over 42 months after diagnosis: a single-center cohort study.

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.

Analyzing infant head flatness and asymmetry using kernel density estimation of directional surface data from a craniofacial 3D model.

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.

The course of positional cranial deformation from 3 to 12 months of age and associated risk factors: a follow-up with 3D imaging.

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.

Preventing deformational plagiocephaly through parent guidance: a randomized, controlled trial.

Deformational plagiocephaly (DP) occurs frequently in otherwise healthy infants. Many infants with DP undergo physiotherapy or helmet therapy, and ample treatment-related research is available. However, the possibility of preventing DP has been left with little attention. We sought to evaluate the effectiveness of intervention in the newborn's environment, positioning, and handling on the prevalence of DP at 3 months and to investigate the causal relationship between DP and cervical imbalance. We carried out a randomized controlled trial, with healthy newborns randomized into two groups at birth. All families received standard positioning instructions to prevent SIDS. Additionally, the intervention group received detailed instructions regarding the infant's environment, positioning, and handling, with the goal of creating a nonrestrictive environment that promotes spontaneous physical movement and symmetrical motor development. Two- and three-dimensional photogrammetry served to assess cranial shape and goniometry to measure cervical motion. At 3 months, the prevalence of DP was lower in the intervention group in both 2D (11 vs 31 %) and 3D analyses (15 vs 33 %), and the asymmetry was milder in the intervention group. Infants with DP at follow-up had also developed more torticollis. CONCLUSION: An early educational intervention reduces the prevalence and severity of DP at 3 months. WHAT IS KNOWN: •Deformational plagiocephaly, often with associated torticollis, is common in healthy infants. •Parental education is frequently recommended for preventing deformational plagiocephaly, although information regarding the effectiveness of preventive strategies is scarce. WHAT IS NEW: •Early parent guidance effectively reduces the prevalence and severity of DP and improves the cervical range of motion at three months. •Educating both parents and professionals about proper infant positioning on a national scale could help minimize public healthcare costs.

Success and complications in lumbar punctures of pediatric patients with leukemia: a study protocol for a randomized clinical crossover trial of a bioimpedance needle system versus conventional procedure.

BACKGROUND: Acute lymphoblastic leukemia (ALL) is the most common malignancy diagnosed in children. At present, the long-term survival from pediatric ALL is well over 90%. However, the probability of event-free survival is reduced if the lumbar puncture (LP) procedures at the beginning of the patient's intrathecal therapy cause blood leakage into the spinal canal and blast cells contaminate the cerebrospinal fluid. According to the literature, such traumatic LP procedures concern one out of five pediatric patients with ALL. Recently, a novel medical device measuring the tissue bioimpedance at the tip of a spinal needle was found feasible in pediatric patients with ALL. The LP procedure was successful at the first attempt in 80% of procedures, and the incidence of traumatic LPs was then 11%. The purpose of the present study is to compare the bioimpedance spinal needle system with the standard clinical practice resting on a conventional spinal needle and investigate its efficacy in clinical practice. METHODS: The study is a multicenter, randomized, two-arm crossover noninferiority trial of pediatric hemato-oncology patients that will be conducted within the usual clinical workflow. Patients' LP procedures will be performed alternately either with the IQ-Tip system (study arm A) or a conventional Quincke-type 22G spinal needle (study arm B). For each enrolled patient, the order of procedures is randomly assigned either as ABAB or BABA. The total number of LP procedures will be at least 300, and the number of procedures per patient between two and four. After each study LP procedure, the performance will be recorded immediately, and 1-week diary-based and 4-week record-based follow-ups on symptoms, complications, and adverse events will be conducted thereafter. The main outcomes are the incidence of traumatic LP, first puncture success rate, and incidence of post-dural puncture headache. DISCUSSION: The present study will provide sound scientific evidence on the clinical benefit, performance, and safety of the novel bioimpedance spinal needle compared with the standard clinical practice of using conventional spinal needles in the LP procedures of pediatric patients with leukemia. TRIAL REGISTRATION: ISRCTN ISRCTN16161453. Registered on 8 July 2022.

Plagiocephaly after Neonatal Developmental Dysplasia of the Hip at School Age.

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.

Craniofacial Asymmetry from One to Three Years of Age: A Prospective Cohort Study with 3D Imaging.

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 < 0.05). As measured with the landmark-based methods, facial symmetry improved on the upper and lower jaw from T1 to T2 (p < 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.

A 3D Follow-Up Study of Cranial Asymmetry from Early Infancy to Toddler Age after Preterm versus Term Birth.

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 2-4 months (T1), 5-7 months (T2), 11-13 months (T3), and 2.5-3 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-T4 (p < 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.

Accuracy of measurements used to quantify cranial asymmetry in deformational plagiocephaly.

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.

Cranial shape, size and cervical motion in normal newborns.

BACKGROUND: Deformational plagiocephaly (DP) and torticollis are commonly seen in infants and they often co-occur, but little is known of the prevalence and relationship of these conditions in the immediate newborn period. No previous studies focusing on the relationship between cranial shape and cervical motion in newborns can be found. OBJECTIVES: Determining the incidence rates and characteristics of DP and torticollis and examining the relationship between cervical range of motion (ROM), cranial size and cranial shape in neonates. METHODS: A single-center, descriptive cross-sectional study including 155 healthy neonates was conducted. Participants were examined during their birth hospitalization. Oblique Cranial Length Ratio (OCLR) and Cephalic Index (CI), indicating cranial asymmetry and shape, were measured from standardized digital photographs with a computer-based cephalometric method. Cervical ROM was measured with goniometry. RESULTS: 7.7% of the newborns had DP and 3.9% had torticollis. 46.4% presented lesser cervical imbalances. DP was associated with gestational diabetes (adjusted OR 5.6; p<0.01) and vacuum assisted delivery (adjusted OR 6.8; p<0.01), but not at all with torticollis. CI correlated strongly with cervical ROM in all directions, while no definite association between cranial asymmetry and cervical motion could be found. CONCLUSIONS: DP and torticollis are common and minor cervical imbalances very common in normal newborns. Our results support the theory that in most cases neither DP nor torticollis is congenital, but rather develops and worsens synergistically in early infancy. Still, although no direct association between DP and torticollis was found, cranial shape is linked to cervical motion at birth.