• Delphina Gomes, Lien Le, Sarah Perschbacher, Nikolaus A Haas, Heinrich Netz, Uwe Hasbargen, Maria Delius, Kristin Lange, Uta Nennstiel, Adelbert A Roscher, Ulrich Mansmann, and Regina Ensenauer.
• Institute for Medical Information Processing, Biometry, and Epidemiology (IBE), Faculty of Medicine, Ludwig-Maximilians-Universität München, Munich, Germany.
• Bmc Med. 2022 Apr 14; 20 (1): 156156.

BackgroundObesity in pregnancy and related early-life factors place the offspring at the highest risk of being overweight. Despite convincing evidence on these associations, there is an unmet public health need to identify "high-risk" offspring by predicting very early deviations in weight gain patterns as a subclinical stage towards overweight. However, data and methods for individual risk prediction are lacking. We aimed to identify those infants exposed to obesity in pregnancy at ages 3 months, 1 year, and 2 years who likely will follow a higher-than-normal body mass index (BMI) growth trajectory towards manifest overweight by developing an early-risk quantification system.MethodsThis study uses data from the prospective mother-child cohort study Programming of Enhanced Adiposity Risk in CHildhood-Early Screening (PEACHES) comprising 1671 mothers with pre-conception obesity and without (controls) and their offspring. Exposures were pre- and postnatal risks documented in patient-held maternal and child health records. The main outcome was a "higher-than-normal BMI growth pattern" preceding overweight, defined as BMI z-score >1 SD (i.e., World Health Organization [WHO] cut-off "at risk of overweight") at least twice during consecutive offspring growth periods between age 6 months and 5 years. The independent cohort PErinatal Prevention of Obesity (PEPO) comprising 11,730 mother-child pairs recruited close to school entry (around age 6 years) was available for data validation. Cluster analysis and sequential prediction modelling were performed.ResultsData of 1557 PEACHES mother-child pairs and the validation cohort were analyzed comprising more than 50,000 offspring BMI measurements. More than 1-in-5 offspring exposed to obesity in pregnancy belonged to an upper BMI z-score cluster as a distinct pattern of BMI development (above the cut-off of 1 SD) from the first months of life onwards resulting in preschool overweight/obesity (age 5 years: odds ratio [OR] 16.13; 95% confidence interval [CI] 9.98-26.05). Contributing early-life factors including excessive weight gain (OR 2.08; 95% CI 1.25-3.45) and smoking (OR 1.94; 95% CI 1.27-2.95) in pregnancy were instrumental in predicting a "higher-than-normal BMI growth pattern" at age 3 months and re-evaluating the risk at ages 1 year and 2 years (area under the receiver operating characteristic [AUROC] 0.69-0.79, sensitivity 70.7-76.0%, specificity 64.7-78.1%). External validation of prediction models demonstrated adequate predictive performances.ConclusionsWe devised a novel sequential strategy of individual prediction and re-evaluation of a higher-than-normal weight gain in "high-risk" infants well before developing overweight to guide decision-making. The strategy holds promise to elaborate interventions in an early preventive manner for integration in systems of well-child care.© 2022. The Author(s).

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