BACKGROUND No prospective cohort study of high-risk children has used rigorous exposure assessment and optimal diagnostic procedures to examine the perinatal antecedents of autism spectrum disorder (ASD), separately among those with and without cognitive impairment. OBJECTIVE To identify perinatal factors associated with increased risk for ASD with and without intellectual disability (ID: IQ < 70) in children born extremely preterm. STUDY DESIGN This prospective multi-center (14 institutions in 5 states) birth cohort study included children born at 23-27 weeks gestation in 2002-2004 who were evaluated for ASD and ID at age 10 years. Pregnancy information was obtained from medical records and by structured maternal interview. Cervical-vaginal ‘infection’ refers to maternal report of bacterial infection (n = 4), bacterial vaginosis (n = 30), yeast infection (n = 62), mixed infection (n = 4) or other/unspecified infection (n=43; e.g., chlamydia, trichomonas or herpes, etc.). We do not know the extent to which ‘infection’ per se was confirmed by microbial colonization. We use the terms ‘fetal growth restriction’ and ‘small for gestational age’ interchangeably in light of the ongoing challenge to discern pathologically from constitutionally small newborns. Severe fetal growth-restriction was defined as a birth weight Z-score for gestational age at delivery < - 2 (i.e., 2 standard deviations or more below the median birth weight in a referent sample that excluded pregnancies delivered for preeclampsia or fetal indications). Participants were classified into four groups based on whether or not they met rigorous diagnostic criteria for ASD and ID (ASD+/ID−, ASD+/ID+, ASD−/ID+ and ASD−/ID−). Temporally-ordered multinomial logistic regression models were used to examine the information conveyed by perinatal factors about increased risk for ASD and/or ID (ASD+/ID−, ASD+/ID+ and ASD−/ID+). RESULTS 889 of 966 (92%) children recruited were assessed at age 10 years, of whom 857 (96%) were assessed for ASD; of these, 840 (98%) children were assessed for ID. ASD+/ID− was diagnosed in 3.2% (27/840), ASD+/ID+ in 3.8% (32/840), and ASD−/ID+ in 8.5% (71/840). Maternal report of presumed cervical-vaginal ‘infection’ during pregnancy was associated with increased risk of ASD+/ID+ (odd ratio [OR], 2.7; 95% CI, 1.2-6.4). The lowest gestational age category (23-24 weeks) was associated with increased risk of ASD+/ID+ (OR, 2.9; 95% CI, 1.3-6.6) and ASD+/ID− (OR, 4.4; 95% CI, 1.7-11). Severe fetal growth restriction was strongly associated with increased risk for ASD+/ID− (OR, 9.9; 95% CI, 3.3-30), whereas peripartum maternal fever was uniquely associated with increased risk of ASD−/ID+ (OR, 2.9; 95% CI, 1.2-6.7). CONCLUSION Our study confirms that low gestational age is associated with increased risk for ASD irrespective of intellectual ability, whereas severe fetal growth restriction is strongly associated with ASD without ID. Maternal report of cervical-vaginal infection is associated with increased risk of ASD with ID, and per...

Objective To evaluate the difference in 10-year neurocognitive outcomes among extremely low gestational age newborns without bacteremia or with suspected or confirmed late-onset bacteremia. Study design Neurocognitive function was evaluated at 10 years of age in 889 children born at <28 weeks of gestation and followed from birth. Definite (culture positive) late-onset bacteremia during postnatal weeks 2–4 was identified in 223 children and 129 had suspected bacteremia. Results Infants with the lowest gestational age and birth weight Z-score had the highest prevalence of definite and suspected late-onset bacteremia. When compared with peers with no or suspected bacteremia, infants with definite bacteremia performed worse on tests of general cognitive ability, language, academic achievement, and executive function, even when adjusting for potential confounders. Adjustment for low IQ attenuated associations between bacteremia and all dysfunctions at 10 years. Children who had suspected bacteremia did not differ appreciably from children who did not have any evidence of bacteremia. The motor domain was unaffected. Conclusions Extremely low gestational age newborns who had definite late bacteremia during postnatal weeks 2–4 are at heightened risk of neurocognitive limitations at 10 years of age.

Objectives-To examine elevated neonatal inflammatory and neurotrophic proteins from children born extremely preterm in relation to later childhood brain Magnetic Resonance Imaging volumes and cognition.Study design-We measured circulating inflammation-related proteins and neurotrophic proteins on postnatal days 1, 7, and 14 in 166 children at 10 years of age (73 males; 93 females). Top quartile levels on ≥2 days for ≥3 inflammation-related proteins and for ≥4 neurotrophic

Three quarters of children had normal intellect at age ten years; nearly 70% were free of neurodevelopmental impairment. Forty percent of children with impairments had multiple diagnoses.

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