Iron status in early life and associations with developmental outcomes

Infants and young children are at particular risk of iron deficiency and its associated consequences for growth and development. The main objectives of this thesis were to quantify iron intakes, status and determinants of status in two year olds; explore determinants of neonatal iron stores; investigate associations between iron status at birth and two years with neurodevelopmental outcomes at two years and explore the influence of growth on iron status in early childhood, using data from the Cork BASELINE (Babies after SCOPE: Evaluating Longitudinal Impact using Neurological and Nutritional Endpoints) Birth Cohort Study (n=2137). Participants were followed prospectively with interviewer-led questionnaires and clinical assessments at day 2 and at 2, 6, 12 and 24 months. At two years, there was a low prevalence of iron deficiency and iron deficiency anaemia in this cohort, representing the largest study of iron status in toddlers in Europe, to date. The increased consumption of iron-fortified products and compliance with recommendations to limit unmodified cows’ milk intakes in toddlers has contributed to the observed improvements in status. Low serum ferritin concentrations at birth, which reflect neonatal iron stores, were shown to track through to two years of age; delivery by Caesarean section, being born small-for-gestational age and maternal obesity and smoking in pregnancy were all associated with significantly lower neonatal iron stores. Despite a low prevalence of iron deficiency in this cohort, both a mean corpuscular volume <74fl and ferritin concentrations <20μg/l were associated with lower neurodevelopmental outcomes at two years. An inverse association between growth in the second year of life and iron status at two years was also observed. This thesis has presented data from one of the largest, extensively-characterised cohorts of young children, to date, to explore iron and its associations with growth and development.

Seasonal changes in Vitamin D-effective UVB availability in Europe and associations with population serum 25-Hydroxyvitamin D

Low vitamin D status is common in Europe. The major source of vitamin D in humans is ultraviolet B (UVB)-induced dermal synthesis of cholecalciferol, whereas food sources are believed to play a lesser role. Our objectives were to assess UVB availability (Jm−2) across several European locations ranging from 35° N to 69° N, and compare these UVB data with representative population serum 25-hydroxyvitamin D (25(OH)D) data from Ireland (51–54° N), Iceland (64° N) and Norway (69° N), as exemplars. Vitamin D-effective UVB availability was modelled for nine European countries/regions using a validated UV irradiance model. Standardized serum 25(OH)D data was accessed from the EC-funded ODIN project. The results showed that UVB availability decreased with increasing latitude (from 35° N to 69° N), while all locations exhibited significant seasonal variation in UVB. The UVB data suggested that the duration of vitamin D winters ranged from none (at 35° N) to eight months (at 69° N). The large seasonal fluctuations in serum 25(OH)D in Irish adults was much dampened in Norwegian and Icelandic adults, despite considerably lower UVB availability at these northern latitudes but with much higher vitamin D intakes. In conclusion, increasing the vitamin D intake can ameliorate the impact of low UVB availability on serum 25(OH)D status in Europe.

Lack of effect of lowering LDL cholesterol on cancer: meta-analysis of individual data from 175,000 people in 27 randomised trials of statin therapy

Background: Statin therapy reduces the risk of occlusive vascular events, but uncertainty remains about potential effects on cancer. We sought to provide a detailed assessment of any effects on cancer of lowering LDL cholesterol (LDL-C) with a statin using individual patient records from 175,000 patients in 27 large-scale statin trials. Methods and Findings: Individual records of 134,537 participants in 22 randomised trials of statin versus control (median duration 4.8 years) and 39,612 participants in 5 trials of more intensive versus less intensive statin therapy (median duration 5.1 years) were obtained. Reducing LDL-C with a statin for about 5 years had no effect on newly diagnosed cancer or on death from such cancers in either the trials of statin versus control (cancer incidence: 3755 [1.4% per year [py]] versus 3738 [1.4% py], RR 1.00 [95% CI 0.96-1.05]; cancer mortality: 1365 [0.5% py] versus 1358 [0.5% py], RR 1.00 [95% CI 0.93-1.08]) or in the trials of more versus less statin (cancer incidence: 1466 [1.6% py] vs 1472 [1.6% py], RR 1.00 [95% CI 0.93-1.07]; cancer mortality: 447 [0.5% py] versus 481 [0.5% py], RR 0.93 [95% CI 0.82-1.06]). Moreover, there was no evidence of any effect of reducing LDL-C with statin therapy on cancer incidence or mortality at any of 23 individual categories of sites, with increasing years of treatment, for any individual statin, or in any given subgroup. In particular, among individuals with low baseline LDL-C (<2 mmol/L), there was no evidence that further LDL-C reduction (from about 1.7 to 1.3 mmol/L) increased cancer risk (381 [1.6% py] versus 408 [1.7% py]; RR 0.92 [99% CI 0.76-1.10]). Conclusions: In 27 randomised trials, a median of five years of statin therapy had no effect on the incidence of, or mortality from, any type of cancer (or the aggregate of all cancer).

Genome analysis and characterisation of the exopolysaccharide produced by Bifidobacterium longum subsp. longum 35624™

The Bifibobacterium longum subsp. longum 35624™ strain (formerly named Bifidobacterium longum subsp. infantis) is a well described probiotic with clinical efficacy in Irritable Bowel Syndrome clinical trials and induces immunoregulatory effects in mice and in humans. This paper presents (a) the genome sequence of the organism allowing the assignment to its correct subspeciation longum; (b) a comparative genome assessment with other B. longum strains and (c) the molecular structure of the 35624 exopolysaccharide (EPS624). Comparative genome analysis of the 35624 strain with other B. longum strains determined that the sub-speciation of the strain is longum and revealed the presence of a 35624-specific gene cluster, predicted to encode the biosynthetic machinery for EPS624. Following isolation and acid treatment of the EPS, its chemical structure was determined using gas and liquid chromatography for sugar constituent and linkage analysis, electrospray and matrix assisted laser desorption ionization mass spectrometry for sequencing and NMR. The EPS consists of a branched hexasaccharide repeating unit containing two galactose and two glucose moieties, galacturonic acid and the unusual sugar 6-deoxy-L-talose. These data demonstrate that the B. longum 35624 strain has specific genetic features, one of which leads to the generation of a characteristic exopolysaccharide.