Plasma metabolomics signatures of developmental dysplasia of the hip in Tibet plateau

Developmental dysplasia of the hip (DDH) is a common childhood hip joint health complaint, including acetabular dysplasia, hip dislocation, and subluxation. A previous epidemiological investigation revealed a marked elevation in the incidence of DDH in the Tibetan region as compared to lowland areas, suggesting that altitude may play a significant role in the risk factors associated with DDH [1]. The pathogenesis of DDH is complex and involves multiple factors, including genetic and environmental factors. The most common risk factors for DDH include female gender, first birth, multiple births, family history of DDH, breech presentation, oligohydramnios, feet inward rotation deformity. The clinical manifestations of DDH vary with the age and severity of the dislocation. Children with unilateral dislocation may have limb length inequality, while children with bilateral hip dislocation may have a limping gait or duck-like gait. Additionally, children with DDH often have asymmetric thigh wrinkle.

The treatment for developmental dysplasia of the hip (DDH) varies depending on the age and severity of the condition. Generally, the goal is to achieve concentric reduction of the hip joint to provide a favorable environment for the development of the femoral head and acetabulum. For newborns and infants under 6 months of age, the most commonly used treatment method is the use of Pavlik’s splint. For Ortolani-positive hips, the recovery rate can reach 95%. After 6 months, the failure rate may exceed 50%. For the first 3 weeks of treatment, the splint should be reexamined and the ultrasound should be performed weekly. If the hip joint is reduced and stable, the follow-up interval can be extended until the ultrasound examination returns to normal.For patients between 6 months and 18 months of age, hip subluxation or dislocation should be treated by closed or open reduction as the preferred treatment method. For acetabular dysplasia, bracing can be used. For patients older than 18 months, surgical treatment is often required. The surgical approach will be individualized based on the patient’s age to achieve the best treatment outcome. For patients between 18 months and 8 years of age, open reduction and acetabular osteotomy are recommended. It is important to note that if DDH is not treated promptly, it can lead to serious complications and sequelae such as deformity, limited function, and pain. Therefore, early diagnosis and treatment are recommended to achieve a good prognosis. The early treatment of DDH is important to obtain a normal or near-normal hip [2, 3].

Finding abnormalities through early screening and timely correction by physical methods can effectively avoid the need for long-term hip replacement and reduce the long-term disability rate [4, 5]. The Standing Medical Advisory Committee (SMAC) was established by legislation in 1949 as source of relatively independent clinical advice for government of United Kingdom. The SMAC recommends that clinical screening for DDH should be conducted for all newborns, which emphasizes multiple examinations including on the day of birth, at discharge, 6 weeks, 6–9 months, and after starting to walk [6,7,8,9]. Magnetic resonance imaging (MRI) can be used to diagnose DDH in children with limited hip abduction, limb length inequality, limping, or duck-like gait. Ultrasound screening is an important method for early diagnosis, which can evaluate the shape of the hip joint, the position of the femoral head and the stability of the hip joint. Graf examination is the earliest ultrasound examination method to measure the coronal section of the hip joint, and it is also currently recognized as the most effective screening and diagnosis method. This method measures the α angle and β angle, which represent the acetabular angle and cartilage part angle, respectively. As age increases, the acetabular index decreases, and by 2 years of age it should be within 24° [10,11,12,13,14].

However, ultrasound screening requires high professional and technical capabilities, and there is a proportion of misdiagnosis and missed diagnosis [8, 9]. The early diagnosis is difficult due to the insidious clinical features and mild early symptoms of DDH, therefore, biomarkers are urgently needed for auxiliary diagnosis.

Metabolomics can achieve in-depth investigation of metabolites, and has been used to develop biomarkers for early disease diagnosis and monitoring therapy. An explorative study into the aetiology of DDH using targeted urine metabolomics showed that DDH is a systemic disease associated with altered uptake, formation, or handling of sulphate [15, 16]. There are no reports on metabolomics research using blood samples of DDH. Here, we performed integrated metabolomics profiling of patients with DDH.

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