The impact of sedation on the quality of initial skeletal surveys performed for suspected physical abuse in children: a comparative two-centre audit.

BACKGROUND: The impact of sedation on the quality of initial skeletal surveys performed for suspected physical abuse in children is not known. OBJECTIVE: To assess whether sedation influenced the number of, reason for and effective dose of repeat radiographs obtained as part of initial skeletal surveys, and their mean examination times. MATERIALS AND METHODS: One hundred consecutive antemortem initial skeletal survey examinations performed for suspected physical abuse in children <2 years were retrieved from two tertiary paediatric hospitals: Centre 1, where sedation is not used for initial skeletal survey imaging; and Centre 2, where sedation is used routinely. RESULTS: In total, 4055 radiographic projections were performed, of which 93 (2.3%) were repeats. Comparing centres, there was a significant difference in the total number of repeats (P=0.001) and the number of repeats in children aged <12 months (P=0.008). Mean examination times were significantly shorter in unsedated children (P=0.005), even after outliers were excluded (P=0.002). There was no significant difference between the number of routine projections (P=0.587), incompletely imaged body parts (P=0.254), rotation/suboptimal positioning (P=0.527), repeats in children aged >12 months (P=0.089), routine projections in children aged <12 months (P=0.642) or >12 months (P=0.979) or the effective doses of repeats (P=0.286). CONCLUSION: There were fewer repeat projections in sedated children and those aged <12 months but examination times were significantly longer. There was no difference in the effective doses of repeated projections. The routine use of sedation is not supported when performing skeletal survey imaging if the primary considerations are reducing radiation dose and examination time.

Diagnosis of metaphyseal fractures in infants and young children with suspected inflicted injury: a systematic review of cross-sectional imaging techniques.

AIM: To compare the diagnostic accuracy, advantages, and disadvantages of different medical imaging techniques for detecting metaphyseal fractures (also known as classic metaphyseal lesions [CMLs]) in infants and young children with suspected inflicted trauma. MATERIALS AND METHODS: This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) checklist and Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool criteria. Predefined keywords were used to search online databases for English articles published between 1 January 1980 and 31 March 2023. RESULTS: The initial search revealed 83 studies, only five of which met the inclusion criteria. The sensitivity and specificity of positron-emission tomography (PET) were 67% and 99%, respectively. The sensitivity and specificity of ultrasound were 55-61% and 96-97%, respectively. The sensitivity of magnetic resonance imaging (MRI) whole-body screening was 31%. The sensitivity of bone scintigraphy was 17% in one and 35% in a second study. Computed tomography was not used to detect CMLs in any diagnostic accuracy study. CONCLUSION: This systematic review has identified only a small number of relevant studies. In addition to the skeletal survey, PET and ultrasound may be helpful for the diagnosis of CMLs in infants and young children with suspected abuse; however, ultrasound has greater potential than PET due to its higher specificity, lack of radiation exposure, low cost, and wider availability.

Parathyroid hormone changes in infants investigated for inflicted injury; an observational retrospective single centre cohort study.

BACKGROUND: Biochemical and haematological testing is recommended in the United Kingdom when inflicted injury is suspected. We examined the associations of test results with radiologically-confirmed fracture(s), and between test results, in a large retrospective observational cohort. METHODS: Infants up to age two years presenting with suspected inflicted injury, without clinically or radiologically apparent bone disease, and where a skeletal survey was undertaken during the period 1st August 2013 to 31st December 2020, were included. Biochemical parameters: corrected calcium (cCa); phosphate (P); alkaline phosphatase (ALP); parathyroid hormone (PTH); 25-hydroxyvitamin D (25D); and haematological parameters: haemoglobin (Hb); mean corpuscular haemoglobin (MCH); mean corpuscular haemoglobin content (MCHC); mean corpuscular volume (MCV); platelet count were collated together with the results of the radiological assessments. FINDINGS: Of 332 eligible infants (190 male), 142 (84 male) had fracture(s) and/or intracranial injury. Mean PTH in the non-fracture group (n measured 50/190) was 27.3 ng/l; in those with intracranial injury alone (n measured 9/23) was 39.4 ng/l; in those with fracture alone (n measured 62/84) was 45.0 ng/l; and in those with fracture and intracranial injury (n measured 20/35) 51.8 ng/l. F-test of multiple means = 0.0369. There was no difference in 25D between the groups. INTERPRETATION: PTH was raised in infants who had fracture(s), intracranial injury or both. A single raised PTH may not necessarily be an indicator of prior disturbed skeletal health in these circumstances. The relevance of vitamin D status and interpretation of data from biochemical testing should be informed by the overall presentation in suspected inflicted injury cases. A single raised PTH may be a consequence of the child's injuries rather than prior disturbed bone health.

Monitoring Skull Base Abnormalities in Children with Osteogenesis Imperfecta - Review of Current Practice and a Suggested Clinical Pathway.

OBJECTIVES: In the context of a lack of national consensus on the benefits of skull base imaging in children with osteogenesis imperfecta (OI), this study aims to analyse and correlate the clinical symptoms and radiological images of children with severe OI. METHODS: A retrospective case notes and image analysis was carried out on children with complex OI between 2012 and 2018 at a specialist tertiary centre. Data were collected on patient demographic factors, clinical data, imaging findings (presence of Wormian bones, platybasia, basilar impression (McGregor's technique) and basilar invagination (McRae's technique)), and clinical features at the time of imaging. RESULTS: Of the 127 patients in the OI database, 94 were included. A total of 321 radiographs, 21 CT scans and 39 MRI scans were analysed. Average frequency of radiographs was 8 per 10 years. Of the 94 patients, 58 (62%), 10 (11%), 1 (1%) demonstrated platybasia, basilar impression, and basilar invagination, respectively. Of the radiographs analysed, platybasia, basilar impression, basilar invagination, and the presence of Wormian bones, could not be evaluated in 71 (22.3%), 48 (15.2%), 61 (19.5%) and 28 (9.4%) radiographs respectively (due to poor positioning, anatomical abnormalities, and poor image quality). Of the 140 radiographs with platybasia, 17 (12%) also demonstrated basilar impression compared to only 3 (2.9%) out of the 99 without platybasia (p = 0.03). No significant associations were seen between the presence of Wormian bones and basilar impression. Of the 39 MRIs, additional information on CSF flow rate, spinal cord signal and cerebellar morphology was reported in 14 (36%). There was a lack of concordance between MRI and matched radiographs in 7.1% (1/14) and 36% (5/14) for platybasia and basilar impression respectively, with full concordance for basilar invagination. Fewer than 5% had positive clinical symptoms/signs at the time of imaging; 2% (7/321) had macrocephaly, 0.6% (2/321) headache, all other neurological features were absent). Clinical features were not documented in >85% of patients. CONCLUSION: The apparent low prevalence of clinical symptoms and signs and of radiologically identified cranio-cervical abnormalities, suggests that current levels of serial imaging may be excessive. Until larger prospective studies clarify these issues, we suggest a clinical pathway for base of skull imaging which proposes a risk stratification approach to radiographic frequency and suggests parameters for proceeding to MRI.

High bone mass phenotype in a cohort of patients with Osteogenesis Imperfecta caused due to BMP1 and C-propeptide cleavage variants in COL1A1.

OBJECTIVES: Osteogenesis Imperfecta (OI) is a heterogeneous condition mainly characterised by bone fragility; extra-skeletal features in OI include blue sclerae, dentinogenesis imperfecta, skin laxity and joint hyper-extensibility. Most patients with OI are thought to have a low bone mass but contrary to expectations there are certain forms of OI with high bone mass which this study explores in further detail. METHOD: A cohort of n = 6 individuals with pathogenic variants in BMP1 and the C-propeptide cleavage variants in COL1A1 were included in this study. Detailed clinical and radiological phenotyping was done and correlated with genotype to identify patterns of clinical presentation and fracture history in this cohort of patients. This data was compared to previously reported literature in this group. RESULTS: 2 patients with BMP1 and 4 patients with pathogenic variants in C-propeptide region in COL1A1 were deep-phenotyped as part of this study and 1 patient with C-propeptide variant in COL1A1, showed low bone mineral density. In those with an elevated bone mineral density, this became even more apparent on bisphosphonate therapy. Patients in this cohort had variable clinical presentation ranging from antenatal presentation to more of an insidious course resulting in later confirmation of genetic diagnosis up to 19 years of age. CONCLUSIONS: Patients with pathogenic variants in the C-propeptide region of COL1A1/A2 and BMP1 appear to have a high bone mass phenotype with increased sensitivity to bisphosphonate therapy. It is important to closely monitor patients with these genotypes to assess their response to therapy and tailor their treatment regime accordingly.

Investigating rolling as mechanism for humeral fractures in non-ambulant infants: a preliminary finite element study.

AIM: To use personalised computed tomography (CT)-based finite element models to quantitatively investigate the likelihood of self-inflicted humeral fracture in non-ambulant infants secondary to rolling. MATERIALS AND METHODS: Three whole-body post-mortem CT examinations of children at the age of rolling (two 4-month-old and one 6-month-old) were used. The mechanical moment needed by each infant to perform a rolling manoeuvre was calculated and applied to the finite element model in order to simulate spontaneous rolling from the prone to the supine position. RESULTS: The maximum predicted strains were found to be substantially lower (with a difference of >80%) than the elastic limit of the bone. CONCLUSION: Results of this study challenge the plausibility of self-inflicted humeral fracture caused by rolling in non-ambulant infants and indicate that it is unlikely for a humeral fracture to result from this mechanism without the assistance of an external force.

Applicability of two bone age assessment methods to children from Saudi Arabia.

AIM: To assess the applicability of the Greulich & Pyle (G&P) and Tanner & Whitehouse (TW3) methods to children from Saudi Arabia using both subjective (manual) rating and BoneXpert software. MATERIALS AND METHODS: Bone age (BA) was assessed using the G&P and TW3 methods, firstly by independent manual rating of two observers, followed by a single observer using the BoneXpert software program. In total, 420 hand trauma radiographs for Saudi Arabians (220 males, 329 left, age range 1-18 years) performed in the period January 2012 to September 2016 were assessed. Paired sample t test was used to compare the difference between mean BA and mean chronological age (CA) and to compare the difference between manual and BoneXpert ratings. Statistical analysis was undertaken using SPSS v.25. RESULTS: A statistically significant difference was found between BA and CA in males when using the G&P (mean difference -0.36±1 years, p<0.01) and TW3 (mean difference -0.22±0.9 years, p=0.03) methods, but not in females for either G&P (mean difference 0.13±1.2 years) or TW3 (mean difference 0.08±1.1 years). In males, BoneXpert results conformed to the manual ratings for TW3, but not for G&P, for which the mean difference between manual and BoneXpert ratings was -0.27±0.5 years (p<0.01). DISCUSSION: The present results indicate that manual and BoneXpert-derived G&P and TW3 bone age assessment can be applied with no modification to Saudi Arabian females; however, only TW3 BoneXpert-derived BA can be applied without caution to Saudi Arabian males.

Finite element modelling of the developing infant femur using paired CT and MRI scans.

Bone finite element (FE) studies based on infant post-mortem computed tomography (CT) examinations are being developed to provide quantitative information to assist the differentiation between accidental and inflicted injury, and unsuspected underlying disease. As the growing skeleton contains non-ossified cartilaginous regions at the epiphyses, which are not well characterised on CT examinations, it is difficult to evaluate the mechanical behaviour of the developing whole bone. This study made use of paired paediatric post mortem femoral CT and magnetic resonance imaging (MRI) examinations at two different stages of development (4 and 7 months) to provide anatomical and constitutive information for both hard and soft tissues. The work aimed to evaluate the effect of epiphyseal ossification on the propensity to shaft fractures in infants. The outcomes suggest that the failure load of the femoral diaphysis in the models incorporating the non-ossified epiphysis is within the range of bone-only FE models. There may however be an effect on the metaphysis. Confirmation of these findings is required in a larger cohort of children.

Shortage of paediatric radiologists acting as an expert witness: position statement from the British Society of Paediatric Radiology (BSPR) National Working Group on Imaging in Suspected Physical Abuse (SPA).

One of the most challenging areas of radiological imaging in children is the diagnosis of physical abuse. There is a dearth of paediatric radiologists willing to act as expert witnesses, particularly in the family courts. There are a number of reasons why radiologists may not be interested or willing to put themselves forward to work as expert witnesses in this field. A group of imaging experts recently formed the "British Society of Paediatric Radiology (BSPR) Working Group on Imaging in Suspected Physical Abuse (SPA)". The group comprises radiologists and neuroradiologists with current or previous experience of providing expert witness reports to the court in cases of SPA. The group met in January 2019 to explore pragmatic solutions to the chronic inefficiencies in both medical and legal practices and the challenges that arise from working in a legal arena with different structures, goals, and assessment criteria. Key issues concerned organisational inefficiencies, variable support from National Health Service Trusts and the Royal College of Radiologists to conduct this work, and the risk/benefit of involvement. This work is important for the patient, parents, and society in general, and highly rewarding for clinical practitioners who are involved, but there are several issues with current practices that discourage active participation. With several members of the group either retired or close to retirement, the shortage of experts is becoming a pressing issue within the UK, which requires an engaged multidisciplinary group to come up with creative solutions. Here, the group provide a consensus opinion highlighting the current barriers and potential facilitators to increasing the number of radiologists willing to provide opinions to the court.

Evaluation of a semi-automated software program for the identification of vertebral fractures in children.

AIM: To assess observer reliability and diagnostic accuracy in children, of a semi-automated six-point technique developed for vertebral fracture (VF) diagnosis in adults, which records percentage loss of vertebral body height. MATERIALS AND METHODS: Using a semi-automated software program, five observers independently assessed T4 to L4 from the lateral spine radiographs of 137 children and adolescents for VF. A previous consensus read by three paediatric radiologists using a simplified algorithm-based qualitative technique (i.e., no software involved) served as the reference standard. RESULTS: Of a total of 1,781 vertebrae, 1,187 (67%) were adequately visualised according to three or more observers. Interobserver agreement in vertebral readability for each vertebral level for five observers ranged from 0.05 to 0.47 (95% CI: -0.19, 0.76). Intra-observer agreement using the intraclass correlation coefficient (ICC) ranged from 0.25 to 0.61. The overall sensitivity and specificity were 18% (95% CI: 14-22) and 97% (95% CI: 97-98), respectively. CONCLUSION: In contrast to adults, the six-point technique assessing anterior, middle, and posterior vertebral height ratios is neither satisfactorily reliable nor sensitive for VF diagnosis in children. Training of the software on paediatric images is required in order to develop a paediatric standard that incorporates not only specific vertebral body height ratios but also the age-related physiological changes in vertebral shape that occur throughout childhood.

Imaging and reporting considerations for suspected physical abuse (non-accidental injury) in infants and young children. Part 1: initial considerations and appendicular skeleton.

Recognising the skeletal manifestations of inflicted injury (II) in infants and young children is of crucial importance. There are specific fracture patterns which are highly suspicious of II in addition to common differential diagnoses with which radiologists should be familiar. Our objective is to provide a non-exhaustive review of the important factors relevant to the imaging and reporting of II as a platform for further learning. Part 1 encompasses important initial considerations and fracture patterns of the appendicular skeleton.

Imaging and reporting considerations for suspected physical abuse (non-accidental injury) in infants and young children. Part 2: axial skeleton and differential diagnoses.

Recognising the skeletal manifestations of inflicted injury (II) in infants and young children is of crucial importance. There are specific fracture patterns which are highly suspicious of II in addition to common differential diagnoses with which radiologists should be familiar. Our objective is to provide a non-exhaustive review of the important factors relevant to the imaging and reporting of II as a platform for further learning. Part 2 encompasses fracture patterns of the axial skeleton and important differential diagnoses.

Diagnostic accuracy of DXA compared to conventional spine radiographs for the detection of vertebral fractures in children.

OBJECTIVES: In children, radiography is performed to diagnose vertebral fractures and dual energy x-ray absorptiometry (DXA) to assess bone density. In adults, DXA assesses both. We aimed to establish whether DXA can replace spine radiographs in assessment of paediatric vertebral fractures. METHODS: Prospectively, lateral spine radiographs and lateral spine DXA of 250 children performed on the same day were independently scored by three radiologists using the simplified algorithm-based qualitative technique and blinded to results of the other modality. Consensus radiograph read and second read of 100 random images were performed. Diagnostic accuracy, inter/intraobserver and intermodality agreements, patient/carer experience and radiation dose were assessed. RESULTS: Average sensitivity and specificity (95 % confidence interval) in diagnosing one or more vertebral fractures requiring treatment was 70 % (58-82 %) and 97 % (94-100 %) respectively for DXA and 74 % (55-93 %) and 96 % (95-98 %) for radiographs. Fleiss' kappa for interobserver and average kappa for intraobserver reliability were 0.371 and 0.631 respectively for DXA and 0.418 and 0.621 for radiographs. Average effective dose was 41.9 µSv for DXA and 232.7 µSv for radiographs. Image quality was similar. CONCLUSION: Given comparable image quality and non-inferior diagnostic accuracy, lateral spine DXA should replace conventional radiographs for assessment of vertebral fractures in children. KEY POINTS: • Vertebral fracture diagnostic accuracy of lateral spine DXA is non-inferior to radiographs. • The rate of unreadable vertebrae for DXA is lower than for radiographs. • Effective dose of DXA is significantly lower than radiographs. • Children prefer DXA to radiographs. • Given the above, DXA should replace radiographs for paediatric vertebral fracture assessment.

Compound heterozygous variants in NBAS as a cause of atypical osteogenesis imperfecta.

BACKGROUND: Osteogenesis imperfecta (OI), the commonest inherited bone fragility disorder, affects 1 in 15,000 live births resulting in frequent fractures and reduced mobility, with significant impact on quality of life. Early diagnosis is important, as therapeutic advances can lead to improved clinical outcome and patient benefit. REPORT: Whole exome sequencing in patients with OI identified, in two patients with a multi-system phenotype, compound heterozygous variants in NBAS (neuroblastoma amplified sequence). Patient 1: NBAS c.5741G>A p.(Arg1914His); c.3010C>T p.(Arg1004*) in a 10-year old boy with significant short stature, bone fragility requiring treatment with bisphosphonates, developmental delay and immunodeficiency. Patient 2: NBAS c.5741G>A p.(Arg1914His); c.2032C>T p.(Gln678*) in a 5-year old boy with similar presenting features, bone fragility, mild developmental delay, abnormal liver function tests and immunodeficiency. DISCUSSION: Homozygous missense NBAS variants cause SOPH syndrome (short stature; optic atrophy; Pelger-Huet anomaly), the same missense variant was found in our patients on one allele and a nonsense variant in the other allele. Recent literature suggests a multi-system phenotype. In this study, patient fibroblasts have shown reduced collagen expression, compared to control cells and RNAseq studies, in bone cells show that NBAS is expressed in osteoblasts and osteocytes of rodents and primates. These findings provide proof-of-concept that NBAS mutations have mechanistic effects in bone, and that NBAS variants are a novel cause of bone fragility, which is distinguishable from 'Classical' OI. CONCLUSIONS: Here we report on variants in NBAS, as a cause of bone fragility in humans, and expand the phenotypic spectrum associated with NBAS. We explore the mechanism underlying NBAS and the striking skeletal phenotype in our patients.

The aetiology of rickets-like lower limb deformities in Malawian children.

UNLABELLED: Debilitating rickets-like lower limb deformities are common in children throughout the world, particularly in Malawi, Africa where the causes are unknown. We have identified that Blount disease and calcium deficiency rickets are the likely causes of these deformities and propose calcium supplementation as a potential treatment of Malawian rickets. INTRODUCTION: Surgical correction of rickets-like lower limb deformities is the most common paediatric operation performed at Beit Cure Orthopaedic Hospital, Malawi. The aim of this study was to investigate the aetiology of these deformities. METHODS: Children with a tibio-femoral angle of deformity >20° were enrolled (n = 42, 3.0-15.0 years). Anthropometric and early life and well-being data were collected. Early morning serum and urine samples were collected on the morning of the operation for markers of calcium and phosphate homeostasis. Knee radiographs were obtained, and the children were diagnosed with either Blount (BD, n = 22) or evidence of rickets disease (RD, n = 20). As BD is a mechanical rather than metabolic disease, BD were assumed to be biochemically representative of the local population and thus used as a local reference for RD. RESULTS: There were no differences in anthropometry or early life experiences between BD and RD. Parathyroid hormone (PTH), 1,25-dihydroxyvitamin D, total alkaline phosphatase and urinary phosphate were significantly higher and serum phosphate, 25-hydroxyvitamin D (25OHD) and tubular maximal reabsorption of phosphate significantly lower in RD than BD. There was no difference in serum calcium, fibroblast growth factor 23 or markers of iron status between groups. All children had 25OHD > 25 nmol/L. CONCLUSIONS: Vitamin D deficiency is not implicated in the aetiology of RD or BD in Malawian children. The cause of RD in Malawi is likely to be dietary calcium deficiency leading to elevated PTH resulting in increased losses of phosphate from the bone and glomerular filtrate. The causes of BD remain unclear; there was no evidence in support of previously suggested risk factors such as being overweight or starting to walk early. Prior to surgical intervention, supplementation with calcium should be considered for children with RD.