[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to explore the relationships between nausea and vomiting in pregnancy and (a) fetal growth restriction; and (b) maternal caffeine metabolism and fetal growth restriction. A cohort of 2,643 pregnant women, aged 18-45 years, attending two UK maternity units between 8 and 12 weeks gestation, was recruited. A validated tool assessed caffeine intake at different stages of pregnancy and caffeine metabolism was assessed from a caffeine challenge test. Experience of nausea and vomiting of pregnancy was self-reported for each trimester. Adjustment was made for confounders, including salivary cotinine as a biomarker of current smoking status. There were no significant associations between fetal growth restriction and nausea and vomiting in pregnancy, even after adjustment for smoking and alcohol intake. There were no significant differences in the relationship between caffeine intake and fetal growth restriction between those experiencing symptoms of nausea and vomiting and those who did not, for either the first (p = 0.50) or second trimester (p = 0.61) after adjustment for smoking, alcohol intake and caffeine half-life. There were also no significant differences in the relationship between caffeine half-life and fetal growth restriction between those experiencing symptoms of nausea and vomiting and those who did not, for either the first trimester (p = 0.91) or the second trimester (p = 0.45) after adjusting for smoking, alcohol intake and caffeine intake. The results from this study show no evidence that the relationship between maternal caffeine intake and fetal growth restriction is modified by nausea and vomiting in pregnancy.
Maternal and Child Health Journal 05/2012; · 2.24 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Subsistence farming communities with low socio-economic status reliant on a mono cereal maize diet are exposed to fumonisin levels that exceed the provisional maximum tolerable daily intake of 2 μg kg−1 body weight day−1 recommended by the Joint FAO/WHO Expert Committee on Food Additives. In the rural Centane magisterial district, Eastern Cape Province, South Africa, it is customary during food preparation to sort visibly infected maize kernels from good maize kernels and to wash the good kernels prior to cooking. However, this customary practice seems not to sufficiently reduce the fumonisin levels. This is the first study to optimise the reduction of fumonisin mycotoxins in home-grown maize based on customary methods of a rural population under laboratory-controlled conditions. Maize obtained from subsistence farmers was analysed for the major naturally occurring fumonisins (FB1, FB2 and FB3) by fluorescence HPLC. Large variations were observed in the unsorted and the experimental maize batches attributable to the non-homogeneous distribution of fumonisin contamination in maize kernels. Optimised hand-sorting of maize kernels by removing the visibly infected/damaged kernels (fumonisins, 53.7 ± 15.0 mg kg−1, 2.5% by weight) reduced the mean fumonisins from 2.32 ± 1.16 mg kg−1 to 0.68 ± 0.42 mg kg−1. Hand washing of the sorted good maize kernels for a period of 10 min at 25 °C resulted in optimal reduction with no additional improvement for wash periods up to 15 h. The laboratory optimised sorting reduced the fumonisins by 71 ± 18% and an additional 13 ± 12% with the 10 min wash. Based on these results and on local practices and practicalities the protocol that would be recommended to subsistence farmers consists of the removal of the infected/damaged kernels from the maize followed by a 10 min ambient temperature water wash.
Food Control 03/2011; 22:396-400. · 2.74 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Deoxynivalenol (DON) is a ubiquitous contaminant of cereal crops in temperate regions of the world. It causes growth faltering and immune suppression in animals. Limited information is available on DON exposure in UK subpopulations. The objective of this study was to provide DON exposure assessment in a subset of pregnant women scheduled for an elective caesarean in a large multi-ethnic mother/infant birth cohort from Bradford, UK. Women aged 16-44 years (n = 85) provided a urine sample for DON analysis in the last trimester of pregnancy, and concurrently completed a food-frequency questionnaire (FFQ). The urinary DON biomarker was detected in all measured samples (geometric mean (GM) = 10.3 ng DON mg(-1) creatinine, range = 0.5-116.7 ng mg(-1)). Levels were higher in women classified as South Asian in origin (GM: 15.2 ng mg(-1); 95% CI = 10.7-21.5 ng mg(-1)) compared with non-South Asians (GM = 8.6 ng mg(-1); 95% CI = 6.6-11.8 ng mg(-1)), p = 0.02). Estimated DON intake from FFQ data and typical levels of DON contamination of food suggest that this was mainly due to higher levels of exposure from bread, particularly daily intake of DON from chapattis in South Asians (estimated mean = 2.4 µg day(-1); 95% CI = 1.2, 3.7 µg day(-1)) compared with non-South Asians (estimated mean = 0.2 µg day(-1); 95% CI = 0-0.4 µg day(-1)), p < 0.001. This is the first biomarker demonstration of DON exposure in pregnant women, and several urinary DON levels were the highest ever recorded in any study. A larger survey within this birth cohort is warranted to investigate any potential risk to mothers and their babies, from DON exposure during pregnancy.
Food Additives and Contaminants - Part A Chemistry, Analysis, Control, Exposure and Risk Assessment 01/2011; 29(2):269-76.
[Show abstract][Hide abstract] ABSTRACT: In the Centane magisterial area of South Africa, high rates of oesophageal cancer have been associated with home-grown maize contaminated with fumonisins. The aim of this study was to implement a simple intervention method to reduce fumonisin exposure in a subsistence-farming community. The hand-sorting and washing procedures, based on traditional maize-based food preparation practices, were previously customised under laboratory-controlled conditions. Home-grown maize and maize-based porridge collected at baseline were analysed for fumonisin B(1), B(2) and B(3). The geometric mean (95% confidence interval) of fumonisin contamination in the home-grown maize at baseline was 1.67 (1.21-2.32) mg kg(-1) and 1.24 (0.75-2.04) mg kg(-1) (dry weight) in the porridge. Fumonisin exposure was based on individual stiff porridge consumption and the specific fumonisin levels in the porridge (dry weight) consumed. Porridge (dry weight) consumption at baseline was 0.34 kg day(-1) and fumonisin exposure was 6.73 (3.90-11.6) µg kg(-1) body weight day(-1). Female participants (n = 22) were trained to recognise and remove visibly infected/damaged kernels and to wash the remaining maize kernels. The discarded kernels represented 3.9% by weight and the fumonisins varied from 17.1 to 76.9 mg kg(-1). The customised hand-sorting and washing procedures reduced fumonisin contamination in the maize and porridge by 84 and 65%, respectively. The intervention reduced fumonisin exposure by 62% to 2.55 (1.94-3.35) µg kg(-1) body weight day(-1). This simple intervention method has the potential to improve food safety and health in subsistence-farming communities consuming fumonisin-contaminated maize as their staple diet.
Food Additives & Contaminants: Part A 09/2010; 27(11):1582-1588. · 2.22 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Barrett's oesophagus (BO) carries an increased risk of progression to oesophageal adenocarcinoma. Chromoendoscopy with methylene blue (MB) can be used to facilitate identification of BO and target areas for biopsy. If photoexcited, MB can generate reactive oxygen species and genotoxic photodegradation products leading to DNA damage. We have previously demonstrated that levels of DNA damage are increased in BO following MB chromoendoscopy. The aim of this study was to investigate whether DNA damage, as measured by the comet assay, can be minimized during chromoendoscopy by varying MB concentration and light wavelength using an in vitro model. OE33 cells were treated with MB (0.015-15 mM) and exposed to white light (WL). Cells were also illuminated with WL fractions (580-700, 480-580, 350-480, <575, <610 and <688 nm) in the presence of MB. At clinically relevant concentrations, WL illumination of MB (15 mM) caused significant DNA damage in vitro (P < 0.001). Illumination of MB with red light (580-700 nm) also stimulated high levels of DNA damage in OE33 cells (P < 0.001). This effect was not observed with green or blue light. Filtering WL to remove red light wavelengths (>575 nm) reduced DNA damage and apoptosis to control levels in MB-treated cells. In addition, reducing the concentration of MB 10-fold markedly reduced the DNA-damaging effect of MB in vitro. The results show that photoactivation of MB by red light is responsible for the majority of DNA damage. Simple modifications to MB chromoendoscopy, such as filtering out red light from endoscopic WL or reducing MB concentration, are likely to limit DNA damage induced by the procedure.
[Show abstract][Hide abstract] ABSTRACT: Objective: To examine the association of maternal caffeine intake with fetal growth restriction.
Design Prospective longitudinal observational study.
Setting: Two large UK hospital maternity units.
Participants: 2635 low risk pregnant women recruited between 8-12 weeks of pregnancy.
Investigations: Quantification of total caffeine intake from 4 weeks before conception and throughout pregnancy was undertaken with a validated caffeine assessment tool. Caffeine half life (proxy for clearance) was determined by measuring caffeine in saliva after a caffeine challenge. Smoking and alcohol were assessed by self reported status and by measuring salivary cotinine concentrations.
Main outcome measures: Fetal growth restriction, as defined by customised birth weight centile, adjusted for alcohol intake and salivary cotinine concentrations.
Results: Caffeine consumption throughout pregnancy was associated with an increased risk of fetal growth restriction (odds ratios 1.2 (95% CI 0.9 to 1.6) for 100-199 mg/day, 1.5 (1.1 to 2.1) for 200-299 mg/day, and 1.4 (1.0 to 2.0) for >300 mg/day compared with <100 mg/day; test for trend P<0.001). Mean caffeine consumption decreased in the first trimester and increased in the third. The association between caffeine and fetal growth restriction was stronger in women with a faster compared to a slower caffeine clearance (test for interaction, P=0.06).
Conclusions: Caffeine consumption during pregnancy was associated with an increased risk of fetal growth restriction and this association continued throughout pregnancy. Sensible advice would be to reduce caffeine intake before conception and throughout pregnancy.
[Show abstract][Hide abstract] ABSTRACT: Mortality risks associated with Barrett's oesophagus SIRS, We read with interest the article by Moayyedi et al. 1 analysing cause-speci-fic mortality rates in a cohort of UK patients with Barrett's oesophagus (BO). We would like to bring to the authors' attention our recent article similarly analysing mortality rates in another BO cohort in the north of England. 2 In our analysis, we did not observe any increased risk of ischaemic heart disease [standardized mor-tality ratio (SMR) = 1.22, 95% CI = 0.79–1.80] or myocardial infarction (SMR = 1.15, 95% CI = 0.80–1.61), compared with the higher estimates of Moayyedi et al. for ischaemic heart disease compared with left ventricular failure (male SMR = 1.86, 95% CI = 0.97–2.75; female SMR = 2.05, 95% CI = 1.05–3.06). Regarding all-cause mortality, our study found only a small but statistically significant increased risk (SMR = 1.21, 95% CI = 1.06–1.37), which is in quantitative agreement with other estimates from the UK 3 (hazard ratio = 1.37, 95% CI = 1.12–1.66) and the Netherlands 4 (SMR = 1.46, 95% CI = 1.16–1.82). The much higher all-cause mortality estimates of Moayyedi et al. (male = 5.52, 95% CI = 4.66–6.38; female = 4.55, 95% CI = 3.57–5.52), are in further contrast to an Irish study which found the risk unaltered. 5 Although we prospectively followed fewer BO patients compared with Moa-yyedi et al., it is ultimately the number of deaths which determines the statisti-cal power of a SMR analysis, 6 for which our studies have approximately equal numbers. We also find that the conclusions of Moayyedi et al. require some clarification. They conclude that: 'Patients with Barrett's oesophagus die more commonly of bronchopneumonia and ischaemic heart disease compared with oesophageal adenocarcinoma'. Given the absolute numbers of deaths in these categories, this is true, as it would be for cohorts of almost every other pre-cancerous lesion; mortality risks associated specifically with BO are indicated by SMRs, while the absolute numbers of deaths merely reflect the underlying mortality risks of the general population. Whilst it is important to acknowledge the relatively low absolute risk of death from oesophageal adenocarcinoma in BO, we would emphasize that the overall evidence currently available suggests that BO has little, if any, effect on the risk of other specific causes of death when compared with the population.
[Show abstract][Hide abstract] ABSTRACT: Studies on the effects of caffeine on health, while numerous, have produced inconsistent results. One of the most uncertain and controversial effects is on pregnancy outcome. Studies have produced conflicting results due to a number of methodological variations. The major challenge is the accurate assessment of caffeine intake. The aim of the present study was to explore different methods of assessing caffeine exposure in pregnant women. Twenty-four healthy pregnant women from the UK city of Leeds completed both a detailed questionnaire, the caffeine assessment tool (CAT) designed specifically to assess caffeine intake and a prospective 3 d food and drink diary. The women also provided nine saliva samples over two consecutive days for estimation of caffeine and a metabolite (paraxanthine). Caffeine intakes from the CAT and diary showed adequate agreement (intra-class correlation coefficient of 0.5). For saliva caffeine and paraxanthine measures, the between-sample variation (within the same woman) was greater than between-woman and between-day variation. However, there was still adequate agreement between these measures and the CAT. The CAT is a valuable tool that is now being used in a large prospective study investigating caffeine's role in pregnancy outcome.
The British journal of nutrition 04/2008; 100(4):875-82. · 3.45 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Oesophageal adenocarcinoma frequently develops on a background of metaplastic Barrett's epithelium. The development of malignancy is accompanied by genetic alterations, which may be promising biomarkers of disease progression.
A case control study was conducted nested within a large unselected population based cohort of Barrett's patients. Incident oesophageal malignancies and high grade dysplasias were identified. For each case up to five controls were matched on age, sex, and year of diagnosis. Biopsies from the time of diagnosis of Barrett's epithelium were stained immunohistochemically for TP53, cyclin D1, cyclooxygenase 2 (COX-2), and beta-catenin proteins.
Twenty nine incident oesophageal malignancies and six cases of high grade dysplasia were identified. The odds of diffuse or intense TP53 staining were substantially elevated in biopsies from patients who developed oesophageal adenocarcinoma compared with controls (odds ratio (OR) 11.7 (95% confidence interval (CI) 1.93, 71.4)). This difference was also present when all cases were considered (OR 8.42 (95% CI 2.37, 30.0). Despite the association with TP53 staining, only 32.4% of cases had an initial biopsy showing diffuse/intense TP53 staining. There were no significant associations between cyclin D1, COX-2, or beta-catenin staining and case control status. The OR for positive staining for both TP53 and COX-2 was markedly increased in cases compared with controls (OR 27.3 (95% CI 2.89, 257.0)) although only 15% of cases had positive staining for both markers.
Immunohistochemical detection of TP53 expression is a biomarker of malignant progression in Barrett's oesophagus but sensitivity is too low to act as a criterion to inform endoscopic surveillance strategies. Additional biomarkers are required which when combined with TP53 will identify, with adequate sensitivity and specificity, Barrett's patients who are at risk of developing cancer.
[Show abstract][Hide abstract] ABSTRACT: Barrett's esophagus is associated with reflux disease and substantially increases the risk of esophageal adenocarcinoma. The authors undertook a systematic review and meta-analysis of the sex ratio for Barrett's esophagus, erosive reflux disease (ERD), and nonerosive reflux disease (non-ERD) to compare these results with the sex ratio for esophageal adenocarcinoma. MEDLINE (US National Library of Medicine, Bethesda, Maryland) (1966-2004) and EMBASE (Reed Elsevier PLC, Amsterdam, Netherlands) (1980-2004) were searched for relevant citations with a highly sensitive search strategy. Studies to be included required a sample size of 50 or more patients and consecutive recruitment at an institute accessible by all. Stata, version 8.2, software (StataCorp LP, College Station, Texas) was used to conduct random effects meta-analyses. Excess heterogeneity was investigated by meta-regression. The Barrett's esophagus meta-analysis gave an overall pooled male/female sex ratio of 1.96/1 (95% confidence interval (CI): 1.77, 2.17/1). For ERD, the pooled male/female sex ratio was 1.57/1 (95% CI: 1.40, 1.76/1) and, for non-ERD, 0.72/1 (95% CI: 0.62, 0.84/1). All of these estimates were associated with substantial heterogeneity (I2 = 81.1%, 92.7%, and 88.8%, respectively). The meta-analysis estimates for ERD and Barrett's esophagus, while showing an excess of males, are substantially lower than similar estimates for esophageal adenocarcinoma. It is important to establish why male Barrett's esophagus and ERD patients are at increased risk of malignancy compared with females.
American Journal of Epidemiology 01/2006; 162(11):1050-61. · 4.78 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Dys-regulation of the insulin-like growth factor (IGF) system increases the risk of a number of malignancies. The aim of this study was to investigate the role of members of the IGF binding protein (IGFBP) superfamily in the development of oesophageal adenocarcinoma (EAC) and their possible use as markers of disease risk. Expression of IGFBP-2, IGFBP-3, IGFBP-4, and IGFBP-10/CYR61 was assessed using Real-Time-polymerase chain reaction (PCR) and immunohistochemistry in oesophageal tissues from Barrett's oesophagus (BE) patients with and without associated EAC, and in control subjects. IGFBP-3, IGFBP-4, and IGFBP-10/CYR61 mRNA levels were up-regulated in Barrett's (n=17) and tumour tissue of EAC patients (n=18) compared with normal tissue of control subjects without BE or EAC (n=18) (p<0.001). Over-expression of IGFBP-3 and IGFBP-10/CYR61 proteins was observed in Barrett's, dysplastic and tumour tissue of EAC cases (n=47 for IGFBP-10; n=39 for IGFBP-3) compared with adjacent normal epithelium (p<0.050). Notably, IGFBP-3, IGFBP-4, and IGFBP-10/CYR61 expression in Barrett's tissue of EAC cases (n=17) was significantly (p<0.001) higher than in Barrett's tissue of BE patients with no sign of progression to cancer (n=15). Overall, the results suggest that members of the IGFBP superfamily are up-regulated during oesophageal carcinogenesis and merit further investigation as markers of EAC risk.