Low folate in pregnancy leads to adverse outcomes, especially delivery of babies that are smaller than normal for gestational age (SGA), although the mechanism is as yet undefined (Tamura and Picciano 2006). A particularly vulnerable population, who have low folate status and an increased risk of delivering a SGA infant, are pregnant teenagers (Baker et al. 2009). Recent studies have shown impaired placental cell turnover and reduced nutrient transport in placentas from folate deficient teenagers. There is emerging evidence that microRNAs (miRs) regulate these processes in normal pregnancy and are altered in SGA placentas. We hypothesise that placental dysfunction associated with folate deficiency in teenagers is associated with altered miR expression. Expression of a panel of miRs including miR-143, miR-145, miR-22 and miR-222 was examined in placentas obtained from teenagers. Two groups were compared: teenagers with low folate (red blood cell folate 426nM, 324-500nM median + range, n=11)) and adequate folate status (red blood cell folate 927nM, 580-1178nM median + range, n=12; P< 0.001, Fishers exact test). Total RNA was isolated from villous tissue and expression of miRs assessed by quantitative RT-PCR using miR specific primers. Expression of the analysed miRs was normalised to 5s rRNA expression to correct for non-biological intersample variation. Of the miRs investigated, miR-143, miR-145, miR-22 and miR-222 were all expressed in the human placenta. Comparison of expression levels between teenagers with low and adequate folate status revealed that there was no significant difference in expression of miR-143, miR-145 or miR-22 in placental villous tissue. In contrast, miR-222 expression was significantly higher (30%) in placentas from teenagers with low folate status (relative expression 0.37, 0.28-0.71 median + range) compared to those with adequate folate status (relative expression 0.29, 0.15-0.54 median + range; Mann Whitney; P<0.05). Furthermore, miR-222 expression was negatively correlated with maternal folate status (Spearman rank: P<0.05, r = -0.3745). This study demonstrates that expression of miR-222 is elevated in placental tissue in teenage mothers with low folate status. Data from non-placental tissues suggest that miR-222 regulates components of cell cycle, proliferation and apoptotic signalling pathways. Ongoing studies are investigating the targets and functional role of miR-222 in the human placenta.