RESUMEN
Developmental dysplasia of the hip (DDH) is the most prevalent congenital musculoskeletal disorder, yet its cause remains unknown. Adequate nutrient provision and coordinated electron exchange (redox) processes are critical for foetal growth and tissue development. This novel study sought to explore specific biochemical pathways in skeletal development for potential involvement in the aetiology of DDH. Spot urine samples were collected from infants, aged 13-61 days, with and without DDH. Ion chromatography-mass spectrometry was used to quantify thiosulphate, sulphate, nitrate, and phosphate, whilst nitrite was quantified using high-performance liquid chromato-graphy. Thiobarbituric acid reactive substances (TBARS) were measured as markers of lipid peroxidation. Creatinine and osmolality were determined by a 96-well plate assay and micro-osmometer to potentially normalise values for renal function, lean body mass, and hydration status. Urine samples were analysed from 99 babies: 30 with DDH and 69 age-matched non-DDH controls. Thiosulphate, TBARS, and creatinine concentrations differed between the DDH group and the controls (p = 0.025, 0.015, and 0.004 respectively). Urine osmolality was significantly lower in DDH compared to the controls (p = 0.036), indicative of the production of a more diluted urine in DDH infants. Following adjustment for osmolality, significant differences became apparent in urinary sulphate levels in DDH (p = 0.035) whereas all other parameters were similar between the groups. This is the first study to assess the potential role of these inorganic anions in DDH. The higher levels of sulphate found in infants with DDH suggests either enhanced intake from milk, increased endogenous formation, or impaired renal reabsorption. This investigation demonstrates the power of urine metabolomics and highlights the importance of normalisation for hydration status to disentangle developmental disorders. Our results strongly suggest that DDH is a systemic disease associated with altered uptake, formation, or handling of sulphate. There is potential for new opportunities in the prevention or treatment of DDH via nutritional intervention.
RESUMEN
BACKGROUND: The aim of this study was to assess the accuracy of clinical screening examination in newborns with dislocated hips compared with ultrasound scan (USS). METHODS: Newborns, up to 3 months of age, with confirmed hip dislocations on USS were prospectively enrolled in a multinational observational study. Data from 2010 to 2016 were reviewed to determine pretreatment clinical examination findings of the treating orthopaedic surgeon as well as baseline ultrasound indices of developmental dysplasia of the hip (DDH). All infants had been referred to specialist centres with expertise in DDH, due to abnormal birth examination or risk factor. RESULTS: The median age of the study population was 2.3 weeks and 84% of patients were female. Of the total 515 USS-confirmed dislocated hips included in the study, 71 (13.8%) were incorrectly felt to be reduced on clinical examination by the treating orthopaedist (P<0.001). Full hip abduction was documented in 106 hips. Of the hips correctly identified as dislocated, 322 hips were further analyzed based on clinical reducibility. Thirty-three of 322 (10.2%) were incorrectly thought to be reducible when in fact they were irreducible or vice versa. CONCLUSIONS: Expert examiners missed a significant number of frankly dislocated hips on clinical examination and their ability to classify hips based on clinical reducibility was only moderately accurate. This study provides evidence that, even in experienced hands, physical examination findings in DDH are often too subtle to elicit clinically in the first few months of life. This may explain the persistent and measurable rate of late presenting dislocations in countries with screening programmes reliant on clinical examination. LEVEL OF EVIDENCE: Level 1-testing of previously developed diagnostic criteria in series of consecutive patients (with universally applied reference "gold" standard).