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Objective:  Early regulatory disorders (ERD) in infancy are typically associated with high parenting stress (PS). Theoretical and empirical literature suggests a wide range of factors that may contribute to PS related to ERD. The aim of this study was to identify key predictors of maternal PS within a large predictor data set in a sample of  N  = 135 mothers of infants diagnosed with ERD.   Methods:  We used machine learning to identify relevant predictors. Maternal PS was assessed with the Parenting Stress Index. The multivariate dataset assessed cross-sectionally consisted of 464 self-reported and clinically rated variables covering mother-reported psychological distress, maternal self-efficacy, parental reflective functioning, socio-demographics, each parent's history of illness, recent significant life events, former miscarriage/abortion, pregnancy, obstetric history, infants' medical history, development, and social environment. Variables were drawn from behavioral diaries on regulatory symptoms and parental co-regulative behavior as well as a clinical interview which was utilized to diagnose ERD and to assess clinically rated regulatory symptoms, quality of parent–infant relationship, organic/biological and psychosocial risks, and social–emotional functioning.   Results:  The final prediction model identified 11 important variables summing up to the areas maternal self-efficacy, psychological distress (particularly depression and anger-hostility), infant regulatory symptoms (particularly duration of fussing/crying), and age-appropriate physical development. The RMSE (i.e., prediction accuracy) of the final model applied to the test set was 21.72 ( R  2  = 0.58).   Conclusions:  This study suggests that among behavioral, environmental, developmental, parent–infant relationship, and mental health variables, a mother's higher self-efficacy, psychological distress symptoms particularly depression and anger symptoms, symptoms in the child particularly fussing/crying symptoms, and age-inappropriate physical development are associated with higher maternal PS. With these factors identified, clinicians may more efficiently assess a mother's PS related to ERD in a low-risk help-seeking sample.

Maternal Parenting Stress in the Face of Early Regulatory Disorders in Infancy: A Machine Learning Approach to Identify What Matters Most