Relationship between omega3 long-chain polyunsaturated fatty acid status during early infancy and neurodevelopmental status at 1 year of age.

OBJECTIVE: To determine the influence of alpha-linolenic acid (ALA; 18 : 3omega3) intake and, hence, the influence of plasma and/or erythrocyte phospholipid content of docosahexaenoic acid (DHA; 22 : 6omega3) during early infancy on neurodevelopmental outcome of term infants. METHODS: The Bayley Scales of Infant Development (second edition), the Clinical Adaptive Test/Clinical Linguistic and Auditory Milestone Scale (CAT/CLAMS) and the Gross Motor Scale of the Revised Gesell Developmental Inventory were administered at a mean age of 12.26 +/- 0.94 months to 44 normal term infants enrolled in a study evaluating the effects of infant formulas differing only in ALA content (0.4, 1.0, 1.7 and 3.2% of total fatty acids). RESULTS: As reported previously [Jensen et al., Lipids 13 (1996) 107; J. Pediatr. 131 (1997) 200], the group fed the formula with the lowest ALA content had the lowest mean plasma and erythrocyte phospholipid DHA contents at 4 months of age. This group also had the lowest mean score on every neurodevelopmental measure. The difference in mean gross motor developmental quotient of this group versus the group fed the formula with 1.0% ALA but not of the other groups was statistically significant (P < 0.05). Across the groups, motor indices correlated positively with each other and with the plasma phospholipid DHA content at 4 months of age (P=0.02-0.03). The CLAMS developmental quotient correlated with the erythrocyte phospholipid content of 20 : 5omega3 (P < 0.01) but not with DHA. CONCLUSIONS: These statistically significant correlations suggest that the omega3 fatty acid status during early infancy may be important with respect to neurodevelopmental status at 1 year of age and highlight the need for further studies of this possibility.

Early predictors of neurodevelopmental outcome in symptomatic congenital cytomegalovirus infection.

OBJECTIVE: To determine the ability of neonatal clinical, audiologic, and computed tomography (CT) findings to predict long-term neurodevelopmental outcome in children with symptomatic congenital cytomegalovirus (CMV) infection. METHODS: Longitudinal cohort study of children (n = 41) with symptomatic congenital CMV infection evaluated at birth and followed up with serial age-appropriate neurodevelopmental testing. The performance of birth characteristics as predictors of long-term outcome were determined, and clinical and CT scoring systems were developed and correlated with intellectual outcome. RESULTS: Microcephaly was the most specific predictor of mental retardation (100%; 95% CI 84.5-100) and major motor disability (92.3%; 95% CI 74.8-99). An abnormality detected by CT was the most sensitive predictor for mental retardation (100%; 95% CI 82.3-100) and motor disability (100%; 95% CI 78.2-100). A highly significant (P <.001) positive correlation was found between head size at birth and the intelligence/developmental quotient (IQ/DQ). Approximately 29% of children had an IQ/DQ >90. There was no association between sensorineural hearing loss at birth and cognitive outcome. However, children with sensorineural hearing loss on follow-up (congenital and late-onset) had a lower IQ/DQ (P =.006) than those with normal hearing. CONCLUSIONS: The presence of microcephaly at birth was the most specific predictor of poor cognitive outcome in children with symptomatic congenital CMV infection, whereas children with normal findings on head CT and head circumference proportional to weight exhibited a good cognitive outcome.

Effects of test administration order on children's neuropsychological performance: emerging one-word expressive and receptive language skills.

Differences in neuropsychological performance associated with specific test presentation sequences have been reported in adults. However, these effects have received little attention in children. The EOWPVT-R, a measure of one-word expressive language, and the PPVT-R, a measure of receptive language, were administered to 6- to 14-year-olds (control [n = 17] and experimental [n = 22] groups) in a counterbalanced fashion to investigate the potential effects of test presentation sequence on neuropsychological performance. Group findings were not evidenced subsequent to variation in test administration sequence. In contrast, order of test presentation revealed differences in performance. Administration of the PPVT-R prior to the EOWPVT-R resulted in enhanced EOWPVT-R expressive language scores in both groups of participants. Presentation of the PPVT-R after the EOWPVT-R did not affect performance. Applied and theoretical implications associated with these findings are discussed.

Replacement set mutagenesis of the four phosphate-binding arginine residues of thymidylate synthase.

Arginines R23, R178, R179 and R218 in thymidylate synthase (TS, EC 2. 1.1.45) are hydrogen bond donors to the phosphate moiety of the substrate, dUMP. In order to investigate how these arginines contribute to enzyme function, we prepared complete replacement sets of mutants at each of the four sites in Lactobacillus casei TS. Mutations of R23 increase K:(m) for dUMP 2-20-fold, increase K:(m) for cofactor 8-40-fold and decrease k(cat) 9-20-fold, reflecting the direct role of the R23 side chain in binding and orienting the cofactor in ternary complexes of the enzyme. Mutations of R178 increase K:(m) for dUMP 40-2000-fold, increase K:(m) for cofactor 3-20-fold and do not significantly affect k(cat). These results are consistent with the fact that this residue is an integral part of the dUMP-binding wall and contributes to the orientation and ordering of several other dUMP binding residues. Kinetic parameters for all R179 mutations except R179P were not significantly different from wild-type values, reflecting the fact that this external arginine does not directly contact the cofactor or other ligand-binding residues. R218 is essential for the structure of the catalytic site and all mutations of this arginine except R218K were inactive.

Survival of low-birth-weight infants with neonatal intraventricular hemorrhage. Outcome in the preschool years.

Twenty-nine low-birth-weight infants who survived neonatal intraventricular hemorrhage (IVH) were followed up prospectively and were last examined at a mean age of 3 1/2 years. The mean gestational age (+/- SD) of the group was 28.9 weeks (+/- 2.4 weeks), and the mean birth weight (+/- SD) was 1,167 g (+/- 292 g). Ten patients (34%) had normal neurologic outcome, and four (14%) had minimal abnormalities. Nine children (31%) were categorized as moderately abnormal, and six (21%) had severe abnormalities on neurologic examination. Intellectual performance was normal for 14 patients (48%), mildly delayed for seven (24%), and in the retarded range for eight (28%). Twelve children (41%), at 3 years of age, had handicapping conditions severe enough to warrant admission to special education programs in the public school. The grade of IVH was related significantly to neurologic outcome; both grade of hemorrhage and birth weight were correlated significantly with need for special education. Intellectual performance was related not only to grade of hemorrhage and birth weight, but also to paternal social class.