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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. (Contains 2 tables and 1 figure.)

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 hemorrhage 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 less than 0.001, less than 0.002, and less than 0.042 respectively). In the subgroup of preterm infants, IMP scores were significantly affected by brain lesions on neonatal ultrasound (p less than 0.001) and by socio-economic status (p = 0.001). Interpretation: The findings support the construct validity of the IMP: IMP scores are clearly associated with relevant determinants of neuromotor function.

Objective: To evaluate whether including a test for faecal calprotectin, a sensitive marker of intestinal inflammation, in the investigation of suspected inflammatory bowel disease reduces the number of unnecessary endoscopic procedures., Design: Meta-analysis of diagnostic accuracy studies., Data Sources: Studies published in Medline and Embase up to October 2009. Interventions reviewed Measurement of faecal calprotectin level (index test) compared with endoscopy and histopathology of segmental biopsy samples (reference standard). Inclusion criteria Studies that had collected data prospectively in patients with suspected inflammatory bowel disease and allowed for construction of a two by two table. For each study, sensitivity and specificity of faecal calprotectin were analysed as bivariate data to account for a possible negative correlation within studies., Results: 13 studies were included: six in adults (n=670), seven in children and teenagers (n=371). Inflammatory bowel disease was confirmed by endoscopy in 32% (n=215) of the adults and 61% (n=226) of the children and teenagers. In the studies of adults, the pooled sensitivity and pooled specificity of calprotectin was 0.93 (95% confidence interval 0.85 to 0.97) and 0.96 (0.79 to 0.99) and in the studies of children and teenagers was 0.92 (0.84 to 0.96) and 0.76 (0.62 to 0.86). The lower specificity in the studies of children and teenagers was significantly different from that in the studies of adults (P=0.048). Screening by measuring faecal calprotectin levels would result in a 67% reduction in the number of adults requiring endoscopy. Three of 33 adults who undergo endoscopy will not have inflammatory bowel disease but may have a different condition for which endoscopy is inevitable. The downside of this screening strategy is delayed diagnosis in 6% of adults because of a false negative test result. In the population of children and teenagers, 65 instead of 100 would undergo endoscopy. Nine of them will not have inflammatory bowel disease, and diagnosis will be delayed in 8% of the affected children., Conclusion: Testing for faecal calprotectin is a useful screening tool for identifying patients who are most likely to need endoscopy for suspected inflammatory bowel disease. The discriminative power to safely exclude inflammatory bowel disease was significantly better in studies of adults than in studies of children.

Substantial improvements in long-term survival have been made with acute myeloid leukemia (AML). However, the overall success rate in treatment of AML is around 50%, despite intensive chemotherapeutic regimens. AML cell survival seems to be related to vascular endothelial growth factor (VEGF). The purpose of this study was to investigate whether VEGF production by AML cells is a prognostic factor for therapeutic outcome and whether this is independent of known prognostic factors such as WBC count, French-American-British (FAB) classification, and risk assessment in which the presence of t(8;21), t(15;17), and inv(16) or FAB M3 defines a low-risk group. Pretreatment levels were measured in the supernatant of AML cells obtained from 47 children with newly diagnosed AML treated between 1988 and 1998. All patients were treated with intensive chemotherapeutic protocols from the Dutch Childhood Leukemia Study Group [DCLSG (DCLSG-ANLL87, DCLSG-ANLL92/94, and DCLSG-ANLL97)]. VEGF was measured at the mRNA level with reverse transcription-PCR and at the protein level using a VEGF immunoassay. VEGF in the supernatant from AML cells was highly variable and in concordance with reverse transcription-PCR results. The low-risk group had significantly lower VEGF levels compared with all others (P = 0.002). VEGF levels were significantly increased in AML FAB M4/M5 versus AML patients with FAB M1/M2/M3/M4eo (P = 0.011), who are reported to have a longer remission duration. Subsequently, the influence of different variables on therapeutic outcome was analyzed. No differences were found in overall survival. But within the limits of the small patient population, VEGF levels as well as age at diagnosis had an independent significant effect on relapse-free survival (P = 0.032 and P = 0.029, respectively) in multivariate analysis.