Prenatal alcohol exposure results in cognitive, behavioral, and neurological deficits in offspring. There is an urgent need for safe and effective treatments to overcome these effects. Maternal choline supplementation has been identified as a potential intervention. Our objective was to review preclinical and clinical studies using choline supplementation in known cases of fetal alcohol exposure to determine its effectiveness in ameliorating deficits in offspring. A systematic search of 6 electronic databases was conducted and studies selected by reviewing titles/abstracts against specific inclusion/exclusion criteria. Study characteristics, population demographics, alcohol exposure, and intervention methods were tabulated, and quality of reporting was assessed. Data on cognitive, behavioral, and neurological outcomes were extracted and tabulated. Quantitative analysis was performed to determine treatment effects for individual study outcomes. A total of 189 studies were retrieved following duplicate removal. Of these, 22 studies (2 randomized controlled trials, 2 prospective cohort studies, and 18 preclinical studies) met the full inclusion/exclusion criteria. Choline interventions were administered at different times relative to alcohol exposure, impacting on their success to prevent deficits for specific outcomes. Only 1 clinical study showed significant improvements in information processing in 6-month-old infants from mothers treated with choline during pregnancy. Preclinical studies showed significant amelioration of deficits due to prenatal alcohol exposure across a wide variety of outcomes, including epigenetic/molecular changes, gross motor, memory, and executive function. This review suggests that choline supplementation has the potential to ameliorate specific behavioral, neurological, and cognitive deficits in offspring caused by fetal alcohol exposure, at least in preclinical studies. As only 1 clinical study has shown benefit, we recommend more clinical trials be undertaken to assess the effectiveness of choline in preventing deficits across a wider range of cognitive domains in children.

Background Premature infants are at high risk for acute kidney injury (AKI) and current diagnostic criteria are flawed. The objective of this study was to determine the diagnostic accuracy of urine and serum biomarkers not currently used in routine clinical practice to predict AKI in premature infants. Method A systematic review was performed that followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses of Diagnostic Test Accuracy Studies (PRISMA-DTA). Data were extracted on the diagnostic accuracy of AKI biomarkers using serum creatinine or urine output as the reference standard. Quality and validity were assessed using modified Standards for Reporting Diagnostic Accuracy (STARD) criteria. Results We identified 1024 articles, with 15 studies (791 infants) eligible for inclusion. Twenty-seven biomarkers were identified including serum cystatin C and urinary neutrophil gelatinase-associated lipocalin (uNGAL), osteopontin, kidney injury molecule-1, epidermal growth factor, and protein S100-P. However, many were only reported by one study each. A meta-analysis could only be conducted on uNGAL (288 infants from 6 studies) using a hierarchical, random-effects logistic-regression model. uNGAL had a summary sensitivity of 77% (95% CI 58–89%), specificity of 76% (95% CI 57–88%) and AUC-SROC of 0.83 (95% CI 0.80–0.86) for the diagnosis of AKI. By utilising uNGAL, the post-test probability of AKI increased to 52% (95% CI 37–66%) with a positive test and decreased to 9% (95% CI 5–16%) with a negative test if the pre-test probability was 25%. Conclusion uNGAL shows promise as a diagnostically accurate biomarker for AKI in premature infants. Graphical abstract