Prediction of Childhood Obesity from Nationwide Health Records.

OBJECTIVE: To evaluate body mass index (BMI) acceleration patterns in children and to develop a prediction model targeted to identify children at high risk for obesity before the critical time window in which the largest increase in BMI percentile occurs. STUDY DESIGN: We analyzed electronic health records of children from Israel's largest healthcare provider from 2002 to 2018. Data included demographics, anthropometric measurements, medications, diagnoses, and laboratory tests of children and their families. Obesity was defined as BMI ≥95th percentile for age and sex. To identify the time window in which the largest annual increases in BMI z score occurs during early childhood, we first analyzed childhood BMI acceleration patterns among 417 915 adolescents. Next, we devised a model targeted to identify children at high risk before this time window, predicting obesity at 5-6 years of age based on data from the first 2 years of life of 132 262 children. RESULTS: Retrospective BMI analysis revealed that among adolescents with obesity, the greatest acceleration in BMI z score occurred between 2 and 4 years of age. Our model, validated temporally and geographically, accurately predicted obesity at 5-6 years old (area under the receiver operating characteristic curve of 0.803). Discrimination results on subpopulations demonstrated its robustness across the pediatric population. The model's most influential predictors included anthropometric measurements of the child and family. Other impactful predictors included ancestry and pregnancy glucose. CONCLUSIONS: Rapid rise in the prevalence of childhood obesity warrant the development of better prevention strategies. Our model may allow an accurate identification of children at high risk of obesity.

Estimating heritability of glycaemic response to metformin using nationwide electronic health records and population-sized pedigree.

Background: Variability of response to medication is a well-known phenomenon, determined by both environmental and genetic factors. Understanding the heritable component of the response to medication is of great interest but challenging due to several reasons, including small study cohorts and computational limitations. Methods: Here, we study the heritability of variation in the glycaemic response to metformin, first-line therapeutic agent for type 2 diabetes (T2D), by leveraging 18 years of electronic health records (EHR) data from Israel's largest healthcare service provider, consisting of over five million patients of diverse ethnicities and socio-economic background. Our cohort consists of 80,788 T2D patients treated with metformin, with an accumulated number of 1,611,591 HbA1C measurements and 4,581,097 metformin prescriptions. We estimate the explained variance of glycated hemoglobin (HbA1c%) reduction due to inheritance by constructing a six-generation population-size pedigree from national registries and linking it to medical health records. Results: Using Linear Mixed Model-based framework, a common-practice method for heritability estimation, we calculate a heritability measure of h 2 = 12.6 % (95% CI, 6.1 % - 19.1 % ) for absolute reduction of HbA1c% after metformin treatment in the entire cohort, h 2 = 21.0 % (95% CI, 7.8 % - 34.4 % ) for males and h 2 = 22.9 % (95% CI, 10.0 % - 35.7 % ) in females. Results remain unchanged after adjusting for pre-treatment HbA1c%, and in proportional reduction of HbA1c%. Conclusions: To the best of our knowledge, our work is the first to estimate heritability of drug response using solely EHR data combining a pedigree-based kinship matrix. We demonstrate that while response to metformin treatment has a heritable component, most of the variation is likely due to other factors, further motivating non-genetic analyses aimed at unraveling metformin's action mechanism.

Prediction of gestational diabetes based on nationwide electronic health records.

Gestational diabetes mellitus (GDM) poses increased risk of short- and long-term complications for mother and offspring1-4. GDM is typically diagnosed at 24-28 weeks of gestation, but earlier detection is desirable as this may prevent or considerably reduce the risk of adverse pregnancy outcomes5,6. Here we used a machine-learning approach to predict GDM on retrospective data of 588,622 pregnancies in Israel for which comprehensive electronic health records were available. Our models predict GDM with high accuracy even at pregnancy initiation (area under the receiver operating curve (auROC) = 0.85), substantially outperforming a baseline risk score (auROC = 0.68). We validated our results on both a future validation set and a geographical validation set from the most populated city in Israel, Jerusalem, thereby emulating real-world performance. Interrogating our model, we uncovered previously unreported risk factors, including results of previous pregnancy glucose challenge tests. Finally, we devised a simpler model based on just nine questions that a patient could answer, with only a modest reduction in accuracy (auROC = 0.80). Overall, our models may allow early-stage intervention in high-risk women, as well as a cost-effective screening approach that could avoid the need for glucose tolerance tests by identifying low-risk women. Future prospective studies and studies on additional populations are needed to assess the real-world clinical utility of the model.