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AIM: Long-chain polyunsaturated fatty acid (LCPUFA) supplementation of infant formula may have a beneficial effect on cognitive development. This study aimed to investigate the effect of LCPUFA formula supplementation primarily on cognition and secondarily on behaviour at age 9 years. Special attention was paid to the potentially modifying effect of maternal smoking during pregnancy. METHOD: A double-blind, randomized control study was performed in two groups of healthy infants born at term: one group, constituting the control group, received standard formula (n=169) and another group received standard formula supplemented with LCPUFAs (n=146). A breastfed group (n=159) served as an additional reference. At 9 years of age, 72% of the children (control group: n=123; 71 males, 52 females; LCPUFA group: n=91; 42 males, 49 females; breastfed group: n=127, 64 males, 63 females) underwent extensive cognitive and behavioural testing. RESULTS: An interaction between infant nutrition and smoking during pregnancy was found. Among children exposed to smoking during pregnancy, LCPUFA supplementation was associated with higher mean verbal IQ scores (p=0.007) and learning and memory (p=0.006). Among children not exposed to smoking during pregnancy, LCPUFA supplementation was associated with lower mean verbal memory scores (p=0.003). Executive function scores were significantly lower in the LCPUFA-supplemented group than in the control group (p=0.001). Breastfeeding was associated with better performance on IQ (p=0.005). INTERPRETATION: No consistent beneficial effect of LCPUFA formula supplementation on cognitive development in term-born infants was found. The study confirmed that breastfeeding is associated with better cognition.

AIM The Infant Motor Profile (IMP) is a qualitative assessment of motor behaviour of infants aged 3 to 18 months. The aim of this study was to investigate construct validity of the IMP through the relation of IMP scores with prenatal, perinatal, and neonatal variables, including the presence of brain pathology indicated by neonatal ultrasound imaging of the brain. METHOD A longitudinal prospective study was performed in a group of 30 term infants (12 females, 18 males; median gestational age 40.1wks, range 37.6-42wks) and 59 preterm infants (25 females, 34 males; median gestational age 29.7wks, range 25-34.7wks). IMP assessments were performed at (corrected) ages of 4, 6, 10, 12, and 18 months. Socio-economic and perinatal data were collected, which, in the case of preterm infants, included information on periventricular leukomalacia and intraventricular haemorrhage based on neonatal cranial ultrasound. Data were analysed by fitting mixed-effects models. RESULTS Gestational age, socio-economic status, and 5-minute Apgar scores were significant determinants of IMP scores in the total group of infants (p INTERPRETATION The findings support the construct validity of the IMP: IMP scores are clearly associated with relevant determinants of neuromotor function.

Acute myeloid leukemia (AML) is a disease with a poor prognosis. It has been demonstrated that AML cells express the vascular endothelial growth factors, VEGFA and VEGFC, as well as kinase insert domain-containing receptor (VEGFR2), the main receptor for downstream effects, resulting in an autocrine pathway for cell survival. This study investigates the role of the VEGFR inhibitor PTK787/ZK 222584 in leukemic cell death, and the possibility of an additional effect on cell death by a chemotherapeutic drug, amsacrine. In three AML cell lines and 33 pediatric AML patient samples, we performed total cell-kill assays to determine the percentages of cell death achieved by PTK787/ZK 222584 and/or amsacrine. Both drugs induced AML cell death. Using a response surface analysis, we could show that, in cell lines as well as in primary AML blasts, an equal magnitude of leukemic cell death could be obtained when lower doses of the more toxic amsacrine were combined with low dosages of the less toxic VEGFR inhibitor. This study shows that PTK787/ ZK 222584 might have more clinical potential in AML when combined with a chemotherapeutic drug such as amsacrine. In future, it will be interesting to study whether the complications and the long-term effects of chemotherapy can be reduced by lowering the dosages of amsacrine, and by replacing it with other drugs with lower toxicity profiles, such as PTK787/ZK 222584.

Bile acid-induced lipid secretion was compared in unanesthetized normal control and Groningen Yellow Wistar rats during variations in endogenous bile acid output. Groningen Yellow rats express a genetic defect in the biliary secretion of various organic anions. During a 5-hr period after interruption of the enterohepatic circulation, bile acid secretion decreased from 36.4 +/- 1.8 to 1.9 +/- 0.3 mumol per 30 min in normal control rats and from 37.1 +/- 2.8 to 1.8 +/- 0.2 mumol per 30 min in Groningen Yellow rats, respectively (mean +/- S.E.M., n = 5). The relationship between bile acid secretion and bile flow showed similar slopes (normal control, 8.74 +/- 0.44 mul/mumol and Groningen Yellow rats, 7.71 +/- 0.42 mul/mumol) but different y-intercepts (normal control, 243 +/- 8 and Groningen Yellow, 127 +/- 4 mul per 30 min; p