Maternal floor infarction (MFI) of the placenta has been associated with uteroplacental insufficiency and adverse perinatal outcomes including prematurity, intrauterine growth retardation and recurrent pregnancy loss. We reported that MFI was associated with an increased incidence of neonatal white matter injury (Ped Res 1997:41(4):190A). In the current study, we examined the neurodevelopmental (ND) outcome of surviving preterm infants born to mothers with MFI. Methods: Ten neonates with MFI were matched with 20 controls for gestational age, sex and nearest date of birth. ND outcome was assessed up to 36 months adjusted age (AA) using the Amiel-Tison Neurologic Screen and the Gesell Developmental Screening Inventory. Composite cognitive(MDI) and motor (PDI) scores were calculated from individual skill areas. All infants were seen at > 9 mo AA with the mean age at last exam being 19 mo AA. Results: The mean ± SD gestational age for both groups was 29± 3.4 wks. Compared to controls, MFI cases had lower mean birthweight (1045 ± 885 vs 1245 ± 471 grams, ns); were more likely to have birthweight less than the tenth centile (60% vs 45%, ns) and had a higher incidence (60% vs 15%, p=0.03) of neonatal white matter injury(echolucencies, persistent echodensities, or ventricular dilatation). MFI cases had lower mean MDI (75.4 ± 28 vs 95.2 ± 12, p=0.05) and PDI scores (77 ± 27 vs 97 ± 10, p=0.047). Other perinatal variables associated with lower ND scores by univariate analysis included lower birthweight, white matter injury, and Grade 3-4 IVH. Multivariate regression was performed using birthweight, gestational age, growth retardation, sex, white matter injury, IVH, and MFI as predictor variables. The MDI was independently predicted by cystic echolucencies (β -16, p=0.04) and ventricular dilatation (β -14, p=0.02) whereas the PDI was predicted by cystic echolucencies (β -19, p=0.001) and presence of MFI(β -14, p=0.025). Conclusion: Infants born to mothers with MFI are at higher risk for adverse neurodevelopmental outcome in early childhood, in large part due to an increased risk of neonatal white matter injury associated with maternal floor infarction of the placenta.