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Introduction The current study tests if mild perinatal adversities imply increased susceptibility to quality of instruction in early literacy skills. Method In a large-scale experiment ( N  = 981) preschool children were randomly assigned to a digital intervention condition offering guidance and continuous feedback ( Living Letters ) or to a digital control condition that did not contain these features. Effects of the program on short- and long–term literacy outcomes were assessed; for the group as a whole and for children with and without differential susceptibility markers. Results No main effects of the intervention program were found for the group as a whole. Previous findings of susceptibility of children with mild perinatal adversities to Living Letters were not replicated. Further exploration of the data revealed, however, increased susceptibility in children born late preterm. Both directly after the intervention and a year later, children born late preterm outperformed their full term born peers if they had received Living Letters in kindergarten, but fell behind if they had received the control program. Conclusion An extra program that typically provides continuous guidance and feedback can benefit children born late preterm, but does not benefit children born full term. An increased level of stress reactivity is proposed to be the mechanism underlying the susceptibility to the program found in children born late preterm. [ABSTRACT FROM AUTHOR]