Background: The majority of women who have given birth will develop affection for their infants, however some have prolonged problems developing a loving attitude, leading to impaired mother-infant bonding. Some studies have found an association between postnatal depression and poor mother-infant bonding. On the other hand, little is known about the antenatal predictors of this problem. Aim: The aim of this study was to determine if it is possible to predict during pregnancy which women will develop impaired mother-infant bonding; and to assess whether having a high risk pregnancy could affect this bond. Method: A prospective cohort study was conducted with women who were recruited from one London Hospital between 2008 and 2012. Psychometric data were collected from 300 women in late pregnancy; 223 were followed up at six weeks postnatal using self-administered questionnaires. Sixty-six of these women had a high risk pregnancy. Saliva samples were collected from a subsample of participants (N=46) as part of a pilot study to physiologically measure cortisol and alpha-amylase (as biological markers of maternal stress and depression) embedded within the main study. Results: There was a lower risk of impaired mother-infant bonding at six weeks postnatal, if the woman had good fetal bonding in late pregnancy(OR=0.89, 95%CI=0.83-0.94, p<0.001), but a higher risk of impaired maternal bonding at this time, if the woman had symptoms of depression during pregnancy (OR=1.12, 95%CI=1.11-1.41, p<0.05). Another determinant of poor motherinfant bonding in the study was postnatal depressive symptoms and having an epidural analgesia during labour and birth, although reasons for this need further consideration. There were no significant differences in mother to infant bonding status between women who had a high or a low risk pregnancy. Conclusion: Maternal mental health and fetal bonding emerged as the strongest predictors of impaired maternal-infant bonding, together with the negative association with having an epidural analgesia. The findings from this study highlight the importance of training for clinicians to be aware that mother-infant bonding problem can develop during pregnancy. The negative effect of epidural analgesia on mother-infant bonding warrants further investigation.