BackgroundEarly-life adverse experiences can elevate the magnitude of the risk of developmental psychopathology, but the potential synergistic effects of multiple factors have not been well studied.AimsTo determine whether prenatal exposures to maternal stress (Superstorm Sandy) and maternal cannabis use synergistically alter the risk of developmental psychopathology.MethodThe study included 163 children (53.4% girls), longitudinally tracked (ages 2–5 years) in relation to the effects of two early-life adverse exposures (Superstorm Sandy and maternal cannabis use). Offspring were grouped by exposure status (neither, only maternal cannabis use, only Superstorm Sandy or both). DSM-IV disorders for offspring were derived from structured clinical interviews; caregiver-reported ratings of family stress and social support were also assessed.ResultsA total of 40.5% had been exposed to Superstorm Sandy and 24.5% to maternal cannabis use. Offspring exposed to both (n= 13, 8.0%), relative to those exposed to neither, had a 31-fold increased risk of disruptive behavioural disorders (DBDs) and a seven-fold increased risk of anxiety disorders. The synergy index demonstrated that offspring with two exposures had synergistic elevation in risk of DBDs (synergy index, 2.06,P= 0.03) and anxiety disorders (synergy index, 2.60,P= 0.004), compared with the sum of single risks. Offspring with two exposures had the highest parenting stress and lowest social support.ConclusionsOur findings are consistent with the double-hit model suggesting that offspring with multiple early-life adverse exposures (Superstorm Sandy and maternal cannabis use) have synergistically increased risks of mental health problems. Given the increasing frequency of major natural disasters and cannabis use, especially among women under stress, these findings have significant public health implications.