A new polygenic score for refractive error improves detection of children at risk of high myopia but not the prediction of those at risk of myopic macular degeneration

BACKGROUND: High myopia (HM), defined as a spherical equivalent refractive error (SER) ≤ -6.00 diopters (D), is a leading cause of sight impairment, through myopic macular degeneration (MMD). We aimed to derive an improved polygenic score (PGS) for predicting children at risk of HM and to test if a PGS is predictive of MMD after accounting for SER. METHODS: The PGS was derived from genome-wide association studies in participants of UK Biobank, CREAM Consortium, and Genetic Epidemiology Research on Adult Health and Aging. MMD severity was quantified by a deep learning algorithm. Prediction of HM was quantified as the area under the receiver operating curve (AUROC). Prediction of severe MMD was assessed by logistic regression. FINDINGS: In independent samples of European, African, South Asian and East Asian ancestry, the PGS explained 19% (95% confidence interval 17-21%), 2% (1-3%), 8% (7-10%) and 6% (3-9%) of the variation in SER, respectively. The AUROC for HM in these samples was 0.78 (0.75-0.81), 0.58 (0.53-0.64), 0.71 (0.69-0.74) and 0.67 (0.62-0.72), respectively. The PGS was not associated with the risk of MMD after accounting for SER: OR = 1.07 (0.92-1.24). INTERPRETATION: Performance of the PGS approached the level required for clinical utility in Europeans but not in other ancestries. A PGS for refractive error was not predictive of MMD risk once SER was accounted for. FUNDING: Supported by the Welsh Government and Fight for Sight (24WG201)

Congenital Diaphragmatic Hernia: Long-term Risk of Gastroesophageal Reflux Disease

Objectives: Gastroesophageal reflux disease (GERD) is a well-recognized consequence of congenital diaphragmatic hernia (CDH). Results of studies examining predictive factors for early and late GERD are inconclusive. The aim of this study was to assess the incidence of early ( = 6 years) following CDH repair and to identify predictive variables. Patients and Methods: Of 183 patients born with high-risk CDH, 107 survived and 38 were excluded. Perinatal and postnatal data of 69 eligible patients were analysed to identify variables predictive for early GERD. For the follow-up study, 58 patients (84%) (ages 12.1 +/- 3.4 years; range 6-17) completed a standardised questionnaire. Results were compared with those from a healthy control group (n = 83). Patients who had a score indicating increased risk of GERD underwent further diagnostic assessment. Predictive factors for early and late GERD were identified using multivariate regression analysis. Results: Early GERD was demonstrated in 27 patients (39%). Patch closure and intrathoracic position of the stomach were independent predictive variables for early GERD. At the time of follow-up, 9 of 58 patients (16%) had symptoms suggestive of GERD. In 7 patients (12%), late GERD was confirmed. For late GERD, however, no perinatal or postnatal risk factors were identified. Conclusions: Early GERD is more common in CDH patients with patch closure or intrathoracic position of the stomach. Predictive factors for late GERD could not be identified and screening for early GERD does not protect for future GERD; therefore, long-term follow-up for GERD in CDH survivors is mandator

Is gluten challenge really necessary for the diagnosis of coeliac disease in children younger than age 2 years?

OBJECTIVE: In the diagnosis of coeliac disease (CD), gluten challenge is recommended for children under the age of 2 years at initial biopsy. The aim of the study was to investigate the diagnostic yield of gluten challenge in this group of children. PATIENTS AND METHODS: We included children aged 2 years or younger who were analysed for possible CD and who had villous atrophy at initial small bowel biopsy in the period 1993-2004. We subsequently identified all patients who underwent a complete gluten challenge. RESULTS: We identified 333 children with possible CD. In 100 children (30%), a gluten challenge was performed, with the diagnosis being confirmed in 97. Retrospectively, in 2 of the 3 children without mucosal relapse, data available before gluten challenge did not justify the initial diagnosis of CD. In the third patient, transient gluten intolerance could not be excluded. At first biopsy, the 2 children without mucosal relapse had negative serological parameters, whereas the third patient had IgA antigliadin antibodies, but no IgA anti-endomysium antibodies (EMA). Indeed, all of the patients with EMA at diagnosis had a relapse at gluten challenge. CONCLUSIONS: Routine gluten challenge in children younger than 2 years at initial diagnosis of CD has an extremely low diagnostic yield. We suggest that routine gluten challenge in this group of patients is not necessary when patients have villous atrophy in combination with EMA. Therefore, a revision of the current diagnostic criteria has to be considere