Objective: The purpose of this study was to determine the association between in utero exposure to acute inflammation and long-term major neurodevelopmental disability at age 6 years among children born prior to 32 weeks' gestation. Study Design: This was a follow-up investigation of a cohort of maternal-infant dyads delivered between 23 and < 32 weeks' gestation. Surviving infants (and their mothers or caregivers) underwent a battery of psychological and neurodevelopmental tests between 5 and 8 years of age. Pregnancy and neonatal data were analyzed among children with versus those without major neurodevelopmental disability (including IQ < 70 [n = 41], cerebral palsy [CP, n = 11], and a composite major disability [n = 52]). Results: A total of 261 (70%) of the 375 maternal-infant dyads with surviving children were successfully recruited and evaluated at 6.8 ± 0.7 years. Mean delivery gestational age (GA) and birthweight were 28.8 ± 2.2 weeks and 1163 ± 382 g, respectively. Neither surrogate indicators for nor direct markers of in utero exposure to acute inflammation were significantly associated with severe adverse outcomes. Delivery GA was significantly associated with outcome. Logistic regression indicated that each increasing gestational week was associated with a significantly decreased risk of an IQ < 70 (OR 0.75, 95% CI 0.6-0.9). An average 1.9 point increase in IQ at 6 years of age was observed per gestational week gained (23 to 32 weeks). Periventricular leukomalacia was associated with a 9.6 point mean deficit in IQ. The perceptive vocabulary scores (IQ proxy) of primary caregivers were significantly lower among children with an IQ < 70 vs ≥ 70 (87.5 ± 11.5 vs 92.1 ± 11.2, P = .016). Conclusion: Among children born between 23 and 32 weeks' gestation, neonatal complications, GA at delivery, and caregiver IQ, but not in utero exposure to acute inflammation, were associated with increased risk of severe adverse neurodevelopmental outcomes at age 6 years. © 2008 Mosby, Inc. All rights reserved.