Allergic disease has risen to epidemic proportions during recent years. It has become evident that prenatal events play a critical role in determining disease susceptibility via environmental influences on placental function and fetal programming. We hypothesize that childhood susceptibility to allergy is increased through significant alterations in placental function that exert a programming effect on the fetal immune system. We aim to identify the placental proteins associated with childhood allergy using placental tissue from two populations of women whose children have different risks of allergic disease susceptibility. Placental tissue were examined using a proteomic approach that involves quantitative label-free comparative MS and data analysis was performed using Mascot database and MaxQuant software. Placental tissue from children with no allergy were compared to children with allergic diseases (male n=8 and female n=8). 921 proteins were identified from the MaxLFQ analysis and three proteins were present in significant ratio in all placental sample associated with subsequent allergic disease in childhood. There were 19 proteins significantly altered in placentae of allergic males and 21 proteins altered in placentae of allergic female relative to non-allergic children. Many of these proteins could exert a programming effect on the fetal immune system. Out of these proteins, five candidate proteins associated with allergic diseases were chosen and further validated with Western Blots (n=55). These proteins include Chloride intracellular channel protein 3 (CLIC3) (ratio of >2 relative to non-allergic samples), Peroxiredoxin-2 (PRDX2), Haptoglobin (HPT) and Complement C3 (CO3) (ratio <0.5 fold change relative to non-allergic samples). Moreover, there is also 14-3-3 protein that had very high expression in allergic children and very low expression in control group. The current findings suggest protein expression varies in utero in children who subsequently develop allergy and the altered expression of these proteins vary in a sex specific manner.