Maternal exposure to metals and time-to-pregnancy: The MIREC cohort study.

OBJECTIVE: To study the association between maternal exposure to arsenic, cadmium, lead, manganese and mercury, time-to-pregnancy (TTP) and infertility. DESIGN: Pregnancy-based retrospective TTP cohort study. SETTING: Hospitals and clinics from ten cities across Canada. POPULATION: A total of 1784 pregnant women. METHODS: Concentrations of arsenic, cadmium, lead, manganese and mercury were measured in maternal whole blood during the first trimester of pregnancy as a proxy of preconception exposure. Discrete-time Cox proportional hazards models generated fecundability odds ratios (FOR) for the association between metals and TTP. Logistic regression generated odds ratios (OR) for the association between metals and infertility. Models were adjusted for maternal age, pre-pregnancy body mass index, education, income, recruitment site and plasma lipids. MAIN OUTCOME MEASURES: TTP was self-reported as the number of months of unprotected intercourse to become pregnant. Infertility was defined as TTP longer than 12 months. RESULTS: A total of 1784 women were eligible for the analysis. Mean ± SD maternal age and gestational age at interview were 32.2 ± 5.0 years, and 11.6 ± 1.6 weeks, respectively. Exposure to arsenic, cadmium, manganese or mercury was not associated with TTP or infertility. Increments of one standard deviation of lead concentrations resulted in a shorter TTP (adjusted FOR 1.09, 95% CI 1.02-1.16); however, the association was not linear when exposure was modelled in tertiles. CONCLUSION: Blood concentrations of metals at typical levels of exposure among Canadian pregnant women were not associated with TTP or infertility. Further studies are needed to assess the role of lead, if any, on TTP.

Are Generative Pretrained Transformer 4 Responses to Developmental Dysplasia of the Hip Clinical Scenarios Universal? An International Review.

OBJECTIVE: There is increasing interest in applying artificial intelligence chatbots like generative pretrained transformer 4 (GPT-4) in the medical field. This study aimed to explore the universality of GPT-4 responses to simulated clinical scenarios of developmental dysplasia of the hip (DDH) across diverse global settings. METHODS: Seventeen international experts with more than 15 years of experience in pediatric orthopaedics were selected for the evaluation panel. Eight simulated DDH clinical scenarios were created, covering 4 key areas: (1) initial evaluation and diagnosis, (2) initial examination and treatment, (3) nursing care and follow-up, and (4) prognosis and rehabilitation planning. Each scenario was completed independently in a new GPT-4 session. Interrater reliability was assessed using Fleiss kappa, and the quality, relevance, and applicability of GPT-4 responses were analyzed using median scores and interquartile ranges. Following scoring, experts met in ZOOM sessions to generate Regional Consensus Assessment Scores, which were intended to represent a consistent regional assessment of the use of the GPT-4 in pediatric orthopaedic care. RESULTS: GPT-4's responses to the 8 clinical DDH scenarios received performance scores ranging from 44.3% to 98.9% of the 88-point maximum. The Fleiss kappa statistic of 0.113 ( P = 0.001) indicated low agreement among experts in their ratings. When assessing the responses' quality, relevance, and applicability, the median scores were 3, with interquartile ranges of 3 to 4, 3 to 4, and 2 to 3, respectively. Significant differences were noted in the prognosis and rehabilitation domain scores ( P < 0.05 for all). Regional consensus scores were 75 for Africa, 74 for Asia, 73 for India, 80 for Europe, and 65 for North America, with the Kruskal-Wallis test highlighting significant disparities between these regions ( P = 0.034). CONCLUSIONS: This study demonstrates the promise of GPT-4 in pediatric orthopaedic care, particularly in supporting preliminary DDH assessments and guiding treatment strategies for specialist care. However, effective integration of GPT-4 into clinical practice will require adaptation to specific regional health care contexts, highlighting the importance of a nuanced approach to health technology adaptation. LEVEL OF EVIDENCE: Level IV.

Routine ultrasound screening for hip dysplasia in children with clubfoot is not supported.

PURPOSE: Despite the existence of guidelines for screening for developmental dysplasia of the hip (DDH), there remains controversy regarding the need for routine ultrasound screening for DDH in patients with clubfoot due to an unclear correlation between the two conditions. The purpose of this study is to determine whether ultrasound screening for DDH in this population improved the diagnostic accuracy of DDH over standard assessment for patient risk factors and physical exam. METHODS: This is a retrospective cross-sectional review of infants diagnosed with idiopathic clubfoot who underwent hip ultrasounds to assess for DDH as identified by keyword search in an institutional radiological database at a tertiary care paediatric hospital. Patient demographics, risk factors for DDH, physical exam findings, and ultrasound results were recorded. RESULTS: Of the 120 patients who met the inclusion criteria between 2003 and 2018, 8 had hip dysplasia confirmed on ultrasound (6.7%). All these patients either had known risk factors for hip dysplasia or had an abnormal physical exam finding suggestive of hip instability or dislocation as performed by an orthopaedic surgeon on their initial consultation. CONCLUSION: A detailed history to determine risk factors and a thorough physical exam are adequate to determine the need for hip ultrasound in infants with idiopathic clubfoot. Routine ultrasound screening of all patients with clubfoot is likely unnecessary and may pose a significant burden on the health care system.

Comparing patient-reported outcomes of the Oxford Ankle and Foot Questionnaire in children with clubfoot from two different geographic and cultural environments: a cohort study in India and Canada.

PURPOSE: The purpose of this study is to compare the results of the Oxford Ankle and Foot Questionnaire (OxAFQ) in children with clubfoot in Canada and India to assess its ability to predict outcomes and capture patient experiences in different cultural contexts. METHODS: This is a retrospective study of children with clubfoot in India and Canada who completed the OxAFQ. Statistical analyses were implemented on registry-collected data to test for independent predictors of poor outcomes and compare scores between countries, among children and their parents, and in Canada where relapse data was collected and the effect of a relapse on scores. RESULTS: A total of 361 children were included. The mean Indian OxAFQ scores were higher (p < 0.001) in all domains. Pirani score, tenotomy, laterality, and age at presentation were found to be predictive of outcomes between the sites (p < 0.05). OxAFQ scores decreased after relapse for children in Canada (p < 0.05). Canadian children were found to generally have lower OxAFQ scores in all domains compared to their parents (n = 95; Z = -3.178, -3.493, -3.353, and -3.635 for physical, school and play, emotion, and footwear, respectively; p < 0.001). Indian parents and children showed no significant differences in their scores. CONCLUSIONS: A difference was observed in scores between both sites, suggesting there may be differences in how these populations assess personal health outcomes. These findings support the need for cultural validity of patient-reported outcome measures.

Cohort profile update: The Canadian Maternal-Infant Research on Environmental Chemicals Child Development study (MIREC-CD PLUS).

BACKGROUND: The pan-Canadian Maternal-Infant Research on Environmental Chemicals (MIREC) study was established to determine whether maternal environmental chemical exposures were associated with adverse pregnancy outcomes in 2001 pregnant women. OBJECTIVES: The MIREC-Child Development (CD PLUS) study followed this cohort with the goal of assessing the potential effects of prenatal exposures on anthropometry and neurodevelopment in early childhood. POPULATION: MIREC families with children between the ages of 15 months and 5 years who had agreed to be contacted for future research (n = 1459) were invited to participate in MIREC-CD PLUS which combines data collected from an online Maternal Self-Administered Questionnaire with biomonitoring and neurodevelopment data collected from two in-person visits. PRELIMINARY RESULTS: Between April 2013 and March 2015, 803 children participated in the Biomonitoring visit where we collected anthropometric measures, blood, and urine from the children. The Behavioural Assessment System for Children-2, Behaviour Rating Inventory of Executive Function, MacArthur-Bates Communicative Development Inventories and the Communication subscale of the Adaptive Behaviour Scale from the Bayley Scales of Infant and Toddler Development-III are available on close to 900 children. There were 610 singleton children who completed in-person visits for neurodevelopment assessments including the Social Responsiveness Scale, Wechsler Preschool Primary Scale of Intelligence-III and NEuroPSYchological assessments (NEPSY). Currently, we are following the cohort into early adolescence to measure the impact of early life exposures on endocrine and metabolic function (MIREC-ENDO). CONCLUSIONS: Data collection for the MIREC-CD PLUS study is complete and analysis of the data continues. We are now extending the follow-up of the cohort into adolescence to measure the impact of early life exposures on endocrine and metabolic function (MIREC-ENDO). MIREC-CD PLUS is limited by loss to follow-up and the fact that mothers are predominately of higher socioeconomic status and 'White' ethnicity, which limits our generalizability. However, the depth of biomonitoring and clinical measures in MIREC provides a platform to examine associations of prenatal, infancy and childhood exposures with child growth and development.

Urinary concentrations and determinants of glyphosate and glufosinate in pregnant Canadian participants in the MIREC study.

BACKGROUND: Glyphosate is the most widely applied herbicide in agriculture. Glufosinate is a broad spectrum herbicide used to manage glyphosate-resistant weeds. Despite the widespread use of these herbicides, biomonitoring data - which inform risk assessment and management - are sparse. OBJECTIVES: To identify determinants of urinary concentrations of these herbicides and their metabolites in pregnancy. METHODS: We measured urinary concentrations of glyphosate, glufosinate, and their primary metabolites aminomethylphosphonic acid (AMPA) and 3-methylphosphinicopropionic acid (3-MPPA) in a single spot urine specimen collected during the first trimester of pregnancy from the Maternal-Infant Research on Environmental Chemicals (MIREC) study. MIREC recruited about 2000 pregnant women from 10 Canadian cities between 2008 and 2011. We used UItra-Performance Liquid Chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) with sensitive limits of detection to quantify analyte concentrations. We examined urinary concentrations according to maternal sociodemographics, sample collection characteristics, reported pesticide use, and consumption of fruits, vegetables, legumes, and grain products. We used ANOVA models with specific gravity-standardized chemical concentrations as the dependent variable to determine associations with maternal and sample determinants. RESULTS: Among women with biobanked urine samples (n = 1829-1854), 74% and 72% had detectable concentrations of glyphosate and AMPA, respectively. In contrast, one and six percent of women had detectable concentrations of glufosinate and 3-MPPA, respectively. The specific gravity-standardized geometric mean (95% CI) concentrations of glyphosate and AMPA were 0.112 (0.099-0.127) µg/L and 0.159 (0.147-0.172) µg/L, respectively. We observed a dose-response relationship between consumption of whole grain bread and higher urinary glyphosate concentrations. Season of urine collection and self-reported pesticide use were not associated with increased concentrations of any analyte. CONCLUSIONS: We detected glyphosate and AMPA in the majority of pregnant women from this predominantly urban Canadian cohort. Diet was a probable route of exposure.

Prenatal and concurrent blood mercury concentrations and associations with IQ in canadian preschool children.

BACKGROUND: Prenatal and childhood mercury (Hg) exposures have been associated with negative impacts on child neurodevelopment. It is unclear if associations persist at the low Hg exposures typical in Western countries. OBJECTIVE: To examine associations between prenatal/childhood blood Hg concentrations and child IQ in Canadian male and female children while considering the potential modifying role of prenatal fish consumption. METHODS: We analyzed data from the Maternal-Infant Research on Environmental Chemicals study. Hg was measured in first trimester (n = 527), cord (n = 430), and child (at 3-4 years of age, n = 355) blood and examined sex-stratified associations between blood Hg and children's Full Scale IQ (FSIQ), Verbal IQ (VIQ), Performance IQ (PIQ), and General Language Composite (GLC) scores (assessed with WPPSI-III). Prenatal Hg analyses were further stratified by prenatal fish consumption (low: 0-2, moderate: 3-7, or high: ≥8 times/month). RESULTS: Higher cord blood Hg concentrations were associated with lower PIQ (ß = -3.27; 95%CI: 6.44, -0.09) in male children with the lowest prenatal fish consumption. Progressively stronger positive associations were observed with PIQ in male children for moderate (ß = 1.08; 95%CI: 0.10, 2.26) and high (ß = 3.07; 95%CI: 1.95, 4.19) prenatal fish consumption. Cord blood Hg concentrations were positively associated with female children's FSIQ (ß = 1.29; 95% CI: 0.77, 1.81) and PIQ (ß = 2.01; 95% CI: 1.19, 2.83); however, when stratified only in the highest fish consumption subgroup. Among female children, higher child blood Hg concentrations were associated with an approximately 1-point increase in FSIQ, VIQ, and GLC. CONCLUSIONS: Prenatal exposure to low levels of Hg was associated with lower PIQ scores in male children with low prenatal fish intake. Positive associations between cord and child blood Hg concentrations and IQ were primarily observed in female children and may be due to beneficial effects of prenatal fish intake.

Outcomes of paediatric septic arthritis patients: rates of re-admission, re-operation, and unplanned emergency room visits after discharge.

PURPOSE: This study is aimed at determining the rates and predictors of re-operation and re-admission in children with septic arthritis treated at an institution without routine clinical practice guidelines. METHODS: This is a retrospective cohort study of patients less than 18 years old who underwent surgery for septic arthritis between January 1, 2009, and January 1, 2019, at a single tertiary-care paediatric institution. Uni- and multivariate analysis was performed to identify any risk factors associated with re-operation or unplanned visits to the emergency department after hospital admission compared to patients who had an uncomplicated post-operative course. RESULTS: One hundred and forty-four patients were included. The mean age was five years (range 1 month-17 years), and the most commonly affected joint was the hip. The re-admission rate was 1% (n = 2), and the re-operation rate was 8% (n = 12). Twenty percent of patients (n = 29) had unplanned presentations to the emergency department (ED) after discharge. Discharge CRP level was not significantly higher in patients with unplanned presentations to the ED or re-operation. Positive joint fluid culture and infection of any other joint than the hip increased the likelihood of re-operation. Patients who had septic arthritis of the hip were more likely to have an unplanned ED presentation. CONCLUSIONS: Rates of re-admission and re-operation were similar to literature despite lack of a standardized treatment pathway or discharge protocol. Outcomes of pediatric septic arthritis did not correlate with discharge CRP level. There was a high rate of unplanned ED visits after discharge.

Enhancing Postoperative Pain Management and Decreasing Hospital Length of Stay on a Pediatric Orthopedic Unit: Implementation of an Ambulatory Continuous Peripheral Nerve Block Program.

PURPOSE: Pediatric Ambulatory Continuous Peripheral Nerve Block (ACPNB) programs are a safe and effective pain management modality that can reduce patient length of stay (LOS) while ensuring optimal, multimodal pain management at home after surgery. Our institution previously solely used electronic infusion pumps to deliver local anesthetic via peripheral nerve catheters, requiring postoperative inpatient admissions for pain management. We aimed to enhance postoperative pain management and decrease hospital LOS after orthopedic foot and ankle surgery through implementation of an ACPNB program. DESIGN: An ACPNB program was developed and implemented for pediatric patients undergoing foot and ankle reconstruction surgery. METHODS: We provide a detailed description of the multidepartment collaboration led by the acute pain service (APS) and orthopedics that resulted in the development and implementation of a pediatric ACPNB program using portable, elastomeric devices for patients undergoing reconstructive foot and ankle surgery. Implementation tools, including caregiver and nursing education resources, a data collection log, a process map, and staff surveys are shared. FINDINGS: Twenty-eight patients received elastomeric devices during the 12 months of data collection. All 28 patients who required a continuous peripheral nerve block (CPNB) for pain management following foot and ankle reconstruction surgery received their block via an elastomeric device rather than an electronic hospital infusion pump. All patients and caregivers expressed positive satisfaction with pain management after hospital discharge. No patient with an elastomeric device required scheduled opioids for pain management by the end of their hospital admission. LOS on the orthopedic inpatient unit for foot and ankle surgery decreased by 58%, representing an estimated 29 days and $27,557.88 saved. A majority (96.4%) of staff survey respondents reported feeling satisfied with their overall experience working with an elastomeric device. CONCLUSIONS: The successful implementation of a pediatric ACPNB program has led to positive patient outcomes, including a significant decrease in hospital LOS and health system cost savings for this patient population.

Hemiepiphysiodesis for juvenile hallux valgus deformity: A systematic review.

BACKGROUND: Among the numerous surgical interventions for correcting hallux valgus deformity in skeletally immature patients, hemiepiphysiodesis is a simple technique with a low complication rate yet its effectiveness remains unclear. This systematic review evaluates hemiepiphysiodesis of the first metatarsal for treating juvenile hallux valgus (JHV) deformities with respect to radiological outcomes, postoperative clinical outcomes, and postoperative complications. METHODS: EMBASE, MEDLINE, PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), and Cumulative Index to Nursing and Allied Health Literature (CINAHL) database were searched from inception to September 15th, 2022, for studies investigating hemiepephysiodesis for JHV and its effect on clinical and radiological outcomes. The search, data extraction and methodologic assessment were performed in duplicate for all included studies. RESULTS: Six studies out of 488 with a total of 147 feet in 85 patients were included in the final qualitative synthesis. The American Orthopaedic Foot & Ankle Society hallux metatarsophalangeal interphalangeal scale (AOFAS Hallux MTP-IP scale) was used in two studies. The mean pooled preoperative score was 62.2 ± 8.9 and improved to 88.6 ± 4.8 postoperatively in 33 patients. All six studies reported significant improvement in the hallux valgus angle (HVA) from mean preoperative angle of 29.2° ± 3.7-23.8° ± 4.5° postoperatively, while the intermetatarsal angle (IMA) preoperative and postoperative means corrected from 13.9° ± 1.1-11.4° ± 1.2°, respectively. Out of 147 feet, 21 (14.2%) had reported complications including recurrence and need for revision surgery. CONCLUSION: This systematic review confirms that hemiepiphysiodesis of the first metatarsal in patients with JHV has improved clinical and radiological outcomes. LEVEL OF EVIDENCE: Level IV, Systematic review.

Clinically Detected Leg Length Discrepancy in Patients With Idiopathic Clubfoot Deformity: Prevalence and Outcomes.

BACKGROUND: This study evaluates the prevalence and outcomes of patients with idiopathic clubfoot and clinically detected limb length discrepancy (LLD). METHODS: This is a retrospective cohort study of idiopathic clubfoot patients in a Research Ethics Board-approved clubfoot registry. Patients with LLD ≥0.5 cm (LLD+) were compared with those with no or <0.5 cm LLD (LLD-). LLD was determined by documented clinical examination. Exclusion criteria included nonidiopathic clubfoot deformity, <2-year follow-up, and incomplete records. RESULTS: Of the 300 patients included, 27 (9.0%) had an LLD, of whom 23 patients had a unilateral clubfoot deformity. The prevalence of LLD was 15.3% and 2.67% in unilateral and bilateral clubfoot patients, respectively. The mean LLD was 1.21 cm (0.5 to 3.5 cm, SD: 0.78 cm) in LLD+ patients, with a mean of 1.27 cm (SD: 0.79 cm) in unilateral clubfoot patients and 0.88 cm (SD: 0.75 cm) in bilateral patients. The total number of casts applied in LLD+ unilateral clubfoot patients was significantly higher than in LLD- unilateral patients (9.5 vs. 6.8 casts; P =0.015). The overall relapse rate in all patients was 30.3% and was significantly higher in the unilateral only LLD+ group [relative risk (RR)=2.89] and the total LLD+ patient cohort (RR=1.68). The risk of repeat casting for relapse was also higher in the unilateral LLD+ group (RR=2.45) and the total LLD+ group (RR=1.87). The risk of surgery for relapse was significantly higher in the unilateral LLD+ group for any surgery ( P =0.046), and most specifically for open tendo-Achilles tenotomy ( P =0.008) and tibialis anterior tendon transfer ( P =0.019). There was no correlation between the severity of LLD and Pirani score at presentation. CONCLUSIONS: LLD was present in 9% of idiopathic clubfoot patients, and most were <2 cm. There is a significantly higher risk of relapse in patients with unilateral clubfoot and LLD. The risk of surgery overall was higher in all patients with a unilateral LLD. Assessment of LLD should be routinely performed in clubfoot patients. LEVEL OF EVIDENCE: Level III.

Dynamic Supination in Congenital Clubfoot: A Modified Delphi Panel Approach to Standardizing Definitions and Indications for Treatment.

BACKGROUND: Dynamic supination is a well-recognized cause of congenital clubfoot deformity relapse. However, there is no consensus on how to diagnose it and there are varied approaches in its management. This study aims to define dynamic supination and indications for treatment by presenting consensus from an international panel of experts using a modified Delphi panel approach. METHODS: An international panel of 15 pediatric orthopaedic surgeons with clinical and research expertise in childhood foot disorders participated in a modified Delphi panel on dynamic supination in congenital clubfoot. Panelists voted on 51 statements using a 4-point Likert scale on dynamic supination, clinical indications for treatment, operative techniques, and postoperative casting and bracing. All panelists participated in 2 voting rounds with an interim meeting for discussion. Responses were classified as unanimous consensus (100%), consensus (80% or above), near-consensus (70% to 79%), and indeterminate (69% or less). RESULTS: Consensus was achieved for 34 of 51 statements. Panelists agreed dynamic supination is present when the forefoot is supinated during swing phase of gait with initial contact on the lateral border of the foot. There was also agreement that dynamic supination results from muscle imbalance between the tibialis anterior and the peroneus longus and brevis. There was no consensus on observation of hindfoot varus in dynamic supination, operative indications for posterior release of the ankle joint, or incisional approach for tibialis anterior tendon transfer. Reference to the calcaneopedal unit concept, planes of movement, and phases of gait were deemed important factors for consideration when evaluating dynamic supination. CONCLUSIONS: Consensus statements from the Delphi panel can guide diagnosis and treatment of dynamic supination in clubfoot deformity relapse, including clinical decision making regarding preoperative casting, surgical approach, and postoperative immobilization. Near-consensus and indeterminate statements may be used to direct future areas of investigation. LEVEL OF EVIDENCE: Level V.

Incidence of secondary interventions after early spica casting for diaphyseal femur fractures in young children.

BACKGROUND: Children aged 6 months to 5 years with diaphyseal femur fractures are typically treated with spica casting, as recommended by the American Association of Orthopaedic Surgeons clinical practice guideline. We aimed to determine the incidence of secondary interventions after early spica casting for femur fractures in children aged 6 years or less. METHODS: This was a retrospective cohort study of patients aged 6 years or less with diaphyseal femur fractures treated with early spica casting at a single Canadian tertiary care, level 1 trauma pediatric centre between January 2005 and May 2015. RESULTS: A total of 246 patients were included (190 boys [77.2%] and 56 girls [22.8%] with a mean age of 2.28 yr [standard deviation (SD) 1.35 yr]). Nine patients (3.7%) required early secondary interventions (cast wedging in 8 and flexible intramedullary nail fixation in 1). At last follow-up, 51 patients (20.7%) had clinically measurable limb length discrepancy (LLD) (mean 9.4 mm [SD 3-25 mm]), and 1 patient (0.4%) had mild clinical valgus deformity. Older, heavier patients with initial fracture shortening of 20 mm or more had a higher likelihood of developing a clinically measurable LLD. No patient required surgical intervention after fracture union to correct acquired LLD or angular deformity. CONCLUSION: Early spica casting for diaphyseal femoral fractures in children aged 6 years or younger had a low rate of complications and return to the operating room, Although 21% of patients had a clinically measurable LLD at last follow-up, no patient required secondary intervention after fracture union to correct acquired LLD or angular deformity. These findings have relevance for the Canadian health care system, especially during the COVID-19 pandemic.

[Epiphysiodesis and hemiepiphysiodesis : Physeal arrest and guided growth for the lower extremity]. / Epiphysiodesen und Hemiepiphysiodesen : Wachstumsstopp und Wachstumslenkung an der unteren Extremität.

The principals of growth arrest by epiphysiodesis and growth guidance by hemiepiphysiodesis are effective and powerful surgical techniques in pediatric orthopedics. These procedures can be used to correct leg length discrepancies as well as sagittal, coronal and oblique deformities. A differentiation is made between temporary and permanent techniques. The most significant advantage is that these techniques are minimally invasive and have low complication rates compared to acute osteotomy and gradual deformity correction. For optimal outcome an exact preoperative planning is needed to ensure accurate timing of the procedure, especially when permanent epiphysiodesis techniques are used. Although epiphysiodesis and hemiepiphysiodesis around the pediatric knee are most frequently used and can be considered the gold standard treatment of coronal plane deformities and leg length discrepancies, novel techniques for the hip and ankle are increasingly being performed. The successful clinical results with low complications support the broad use of hemiepiphysiodesis and epiphysiodesis for a variety of indications in the growing skeleton with deformities and leg length differences.

The Gait Outcomes Assessment List for Children With Lower Limb Difference (GOAL-LD): Assessment of Reliability and Validity.

BACKGROUND: The Gait Outcomes Assessment List for children with Lower Limb Difference (GOAL-LD) is a patient and parent-reported outcome measure that incorporates the framework of the International Classification of Functioning, Disability, and Health. This prospective multicenter cohort study evaluates the validity and reliability of the GOAL-LD and the differences between parent and adolescent report. METHOD: One hundred thirty-seven pediatric patients aged over 5 years attending limb reconstruction clinics at the participating sites were assessed at baseline, and a self-selected cohort also completed an assessment 2 to 6 weeks later. Construct and criterion validity were assessed by comparing GOAL-LD scores with a measure of limb deformity complexity (LLRS-AIM) and the Pediatric Outcomes Data Collection Instrument, using Spearman correlation coefficients. Face and content validity were determined through ratings of item importance. Test-retest reliability was reported as an intraclass correlation coefficient and internal consistency using Cronbach α. Adolescent reports were compared with their parents using paired t tests. RESULTS: The GOAL-LD demonstrated a moderate negative correlation with the LLRS-AIM (r=-0.40, P<0.001) and was able to discriminate between deformity complexity groups as defined by the LLRS-AIM (χ2=11.43, P=0.022). Internal consistency was high across all domains (α≥0.68 to 0.97). Like domains of the Pediatric Outcomes Data Collection Instrument and the GOAL-LD were well correlated. Parents reported a lower total GOAL-LD score when compared with adolescents (mean difference 3.04; SE 1.06; 95% confidence interval, 0.92-5.16; P<0.01); however this difference was only significant for body image and self-esteem (Domain F) and gait appearance (Domain D). Test-retest reliability remained high over the study period (intraclass correlation coefficient 0.85; SE 0.03; 95% confidence interval, 0.77-0.91). CONCLUSIONS: The GOAL-LD is a valid and reliable self and parent-reported outcome measure for children with lower limb difference. Parents report a lower level of function and attribute a higher importance to items when compared with their children. The GOAL-LD helps to communicate parent and child perspectives on their function and priorities and therefore has the capacity to facilitate family centered treatment planning and care. LEVEL OF EVIDENCE: Level II-diagnostic. Prospective cross-sectional and a longitudinal cohort design.

Organophosphate pesticides exposure during fetal development and IQ scores in 3 and 4-year old Canadian children.

BACKGROUND: Organophosphate pesticides are widely used in agriculture and for other purposes, leading to ubiquitous exposure in human populations. Some studies reported cognitive deficits in children exposed prenatally to organophosphate pesticides, but findings from recent studies were inconsistent. Furthermore, recent biomonitoring studies suggest exposure levels have decreased. Hence, the risks from current prenatal exposure to organophosphate pesticides for child neurodevelopment are uncertain. Furthermore, sex-differences also remain to be better documented in relation to potential neurodevelopmental effects. OBJECTIVE: To examine the association between prenatal exposure to organophosphate pesticides and IQ scores among boys and girls living in several major Canadian cities. METHODS: We used data from the MIREC cohort (Maternal-Infant Research on Environmental Chemicals). Women were recruited in 2008-2011 from 10 Canadian cities during their first trimester of pregnancy, and urine spot samples were collected for measurement of three dimethyl alkyl phosphate (DMAP) and three diethyl alkyl phosphate (DEAP) metabolites. When children were 3-4 years of age, we used the Wechsler Preschool and Primary Scales of Intelligence-III (WPPSI-III) to assess cognitive ability of children from 6 out of the 10 cities (Halifax, Hamilton, Kingston, Montreal, Toronto, and Vancouver). We analysed the association between maternal exposure to organophosphate pesticides (DMAP and DEAP urinary metabolites) and children's IQ scores with generalized estimating equations (GEEs) to take into account the clustered-data resulting from the six study sites. All analyses were sex-stratified (n = 296 boys and 311 girls). RESULTS: The participants were predominantly well-educated, white women, with a relatively high household income. Children had a mean age of 3.4 years at the moment of IQ assessment (range, 3.0-4.1 years). In girls, there was no association between IQ scores and DEAPs or DMAPs. Higher concentrations of DEAPs were significantly associated with poorer Verbal IQ scores (for a 10-fold increase in concentrations, -6.28; 95% CIs, -12.13, -0.43) in boys. The association for Performance IQ in boys also indicated poorer scores with higher DEAP concentrations, but the confidence intervals included the null value (-4.05; 95% CIs, -10.19, 2.10). The relation between DMAPs and IQ scores in boys was also negative, but association estimates were small and not significant. CONCLUSION: Urinary metabolites of organophosphate pesticides were not associated with IQ in girls, but we observed that higher maternal urinary DEAPs were associated with poorer Verbal IQ in boys. However, exposure misclassification may be an issue as only one urine sample per woman was analysed. The present study contributes to the accumulating evidence linking exposure to organophosphate pesticides during fetal development with poorer cognitive function in children, bringing data on the risks in a context of low exposure levels encountered in primarily urban populations from Canada.

Assessment and Management of the Pediatric Cavovarus Foot.

The cavovarus foot is challenging to treat. The deformity is typically progressive with an unpredictable natural history. There are concurrent deformities in the fore-, mid-, and hindfoot: the medial arch is elevated, the first ray is plantarflexed, and the heel is in varus. Muscle imbalance and joint contractures are common. Successful correction requires confirmation of the underlying diagnosis and the application of principles to select the appropriate surgical procedures.

Blood metal levels and early childhood anthropometric measures in a cohort of Canadian children.

Fetal exposure to some toxic metals has been associated with reduced fetal growth, but the impact of contemporary, low-level metals on anthropometric measures in childhood is not well understood. Our primary objective was to quantify associations between childhood levels of toxic metals and concurrently measured body mass index (BMI) in a population of Canadian preschool-aged children. We collected biomonitoring data and anthropometric measures on 480 children between the ages of two and five years in the Maternal-Infant Research on Environmental Chemicals (MIREC) Child Development Plus study. Concentrations of four toxic metals (lead, arsenic, cadmium, and mercury) were measured in whole blood collected from pregnant women and their children. Blood levels of key essential elements were also measured in children. Children's weight, height, and BMI z-scores were calculated using the World Health Organization growth standards. We used a series of linear regression models, adjusted for potential parental confounders, concurrently measured metals and elements, and prenatal blood metal levels, to evaluate associations between tertiles of each toxic metal and anthropometric measures. We tested for effect modification by sex. Of the 480 children, 449 (94%) were singleton births and had complete biomonitoring and anthropometric data. The majority of children had detectable concentrations of metals. In the adjusted models, girls with blood lead concentrations in the highest tertile (>0.82 µg/dL) had, on average, 0.26 (95% Cl: -0.55, 0.03) lower BMI z-scores than those in the referent category. In contrast, boys with lead levels in the highest tertile had, on average, 0.14 higher BMI z-scores (95% Cl: -0.14, 0.41) (p-value heterogeneity = 0.04). In this population of Canadian preschool-aged children with low-level blood lead concentrations, we observed effect modification by sex in the association between Pb and BMI but no statistically significant associations in the sex-specific strata. Child blood levels of As, Cd, and Hg were not associated with childhood BMI, weight, or height in boys or girls.

Novel phenotype of achondroplasia due to biallelic FGFR3 pathogenic variants.

Pathogenic variants in the fibroblast growth factor receptor 3 (FGFR3) gene are responsible for a broad spectrum of skeletal dysplasias, including achondroplasia (ACH). The classic phenotype of ACH is caused by two highly prevalent mutations, c.1138G > A and c.1138G > C (p.Gly380Arg). In the homozygous state, these variant results in a severe skeletal dysplasia, neurologic deficits, and early demise from respiratory insufficiency. Although homozygous biallelic mutations have been reported in patients with ACH in combination with hypochondroplasia or other dominant skeletal dysplasias, thus far, no cases of heterozygous biallelic pathogenic ACH-related variants in FGFR3 have been reported. We describe a novel phenotype of an infant with two ACH-related mutations in FGFR3, p.Gly380Arg and p.Ser344Cys. Discordant features from classic ACH include atypical radiographic findings, severe obstructive sleep apnea, and focal, migrating seizures. We also report the long-term clinical course of her father, who harbors the p.Ser344Cys mutation that has only been reported once previously in a Japanese patient. The phenotype of heterozygous biallelic mutations in FGFR3 associated with ACH is variable, underscoring the importance of recognition and accurate diagnosis to ensure appropriate management.

Associations between maternal triclosan concentrations in early pregnancy and gestational diabetes mellitus, impaired glucose tolerance, gestational weight gain and fetal markers of metabolic function.

BACKGROUND: Triclosan is a phenolic biocide used in a multitude of consumer products and in health care settings. It is widely detected in the American and Canadian populations and has been shown in animal models to act as an endocrine disrupting agent. However, there has been little examination to date of the effects of triclosan exposure in pregnancy on perinatal metabolic outcomes in human populations. METHODS: Using data from the Maternal-Infant Research on Environmental Chemicals (MIREC) Study, a Canadian pregnancy cohort, we measured associations of first-trimester urinary triclosan concentrations with total gestational weight gain, gestational diabetes mellitus and impaired glucose tolerance in pregnancy, and fetal markers of metabolic function. Leptin and adiponectin were measured in plasma from umbilical cord blood samples in term neonates and categorized into low (< 10th percentile), intermediate (10th-90th percentile) and high (> 90th percentile) levels. Triclosan concentrations were grouped into quartiles and associations with study outcomes were examined using logistic regression models with adjustment for maternal age, race/ethnicity, pre-pregnancy BMI, education and urinary specific gravity. Restricted cubic spline analysis was performed to help assess linearity and shape of any dose-response relationships. All analyses for leptin and adiponectin levels were performed on the entire cohort as well as stratified by fetal sex. RESULTS: Triclosan measures were available for 1795 MIREC participants with a live born singleton birth. Regression analyses showed a non-significant inverse association between triclosan concentrations and leptin levels above the 90th percentile that was restricted to female fetuses (OR for highest quartile of triclosan compared to lowest quartile = 0.4 (95% CI 0.2-1.1), p-value for trend across quartiles = 0.02). Triclosan concentrations in the second quartile were associated with elevated odds of adiponectin below the 10th percentile in male fetuses (OR for Q2 compared to Q1 = 2.5, 95% CI 1.1-5.9, p-value for trend across quartiles = 0.93). No significant linear associations between triclosan concentrations and leptin or adiponectin levels in overall or sex-specific analyses were observed from restricted cubic spline analyses. No significant associations were observed in adjusted analyses between triclosan concentrations and gestational diabetes mellitus, impaired glucose tolerance or gestational weight gain. CONCLUSIONS: This study does not support an association between triclosan concentrations in pregnancy and fetal metabolic markers, glucose disorders of pregnancy, or excessive gestational weight gain.