Density-dependent winter survival of immatures in an irruptive raptor with pulsed breeding.

Highly mobile predators can show strong numerical responses to pulsed resources, sometimes resulting in irruptions where large numbers of young invade landscapes at a continental scale. High production of young in irruption years may have a strong influence on the population dynamics unless immature survival is reduced compared to non-irruption years. This could occur if subordinate individuals (mainly immatures) are forced into suboptimal habitats due to density-dependent effects in irruption years. To test whether irruptive individuals had lower survival than non-irruptive ones, we combined necropsy results (N = 365) with telemetry (N = 185) from more than 20 years to record timing and causes of mortality in snowy owls (Bubo scandiacus), which irrupt into eastern North America during winter following high breeding output caused by lemming peaks in the Arctic. Mortality was more than four times higher in irruption years than non-irruption years, but only for immatures, and occurred disproportionately in early winter for immatures, but not adults. Mortality was also higher in eastern North America, where owl abundance fluctuates considerably between years, compared to core winter regions of the Arctic and Prairies where populations are more stable. Most mortality was not due to starvation, but rather associated with human activity, especially vehicle collisions. We conclude that immature snowy owls that irrupt into eastern North America are limited by density-dependent factors, such as increased competition forcing individuals to occupy risky human-altered habitats. For highly mobile, irruptive animals, resource pulses may have a limited impact on population dynamics due to low subsequent survival of breeding output during the nonbreeding season.

Rethinking megafauna.

Concern for megafauna is increasing among scientists and non-scientists. Many studies have emphasized that megafauna play prominent ecological roles and provide important ecosystem services to humanity. But, what precisely are 'megafauna'? Here, we critically assess the concept of megafauna and propose a goal-oriented framework for megafaunal research. First, we review definitions of megafauna and analyse associated terminology in the scientific literature. Second, we conduct a survey among ecologists and palaeontologists to assess the species traits used to identify and define megafauna. Our review indicates that definitions are highly dependent on the study ecosystem and research question, and primarily rely on ad hoc size-related criteria. Our survey suggests that body size is crucial, but not necessarily sufficient, for addressing the different applications of the term megafauna. Thus, after discussing the pros and cons of existing definitions, we propose an additional approach by defining two function-oriented megafaunal concepts: 'keystone megafauna' and 'functional megafauna', with its variant 'apex megafauna'. Assessing megafauna from a functional perspective could challenge the perception that there may not be a unifying definition of megafauna that can be applied to all eco-evolutionary narratives. In addition, using functional definitions of megafauna could be especially conducive to cross-disciplinary understanding and cooperation, improvement of conservation policy and practice, and strengthening of public perception. As megafaunal research advances, we encourage scientists to unambiguously define how they use the term 'megafauna' and to present the logic underpinning their definition.

Development and application of sub-2-µm particle CO2 -based chromatography coupled to mass spectrometry for comprehensive analysis of lipids in cottonseed extracts.

RATIONALE: Refined cottonseed oil has widespread applications in the food and chemical industries. Although the major lipids comprising cottonseed oil (triacylglycerols) are well known, there are many diverse lipid species in cotton seeds that occur at much lower levels and have important nutritional or anti-nutritional properties. METHODS: The lipid technical samples were prepared in chloroform. The biological samples were extracted using a mixture of isopropanol/chloroform/H2 O (2:1:0.45). The data were collected using high and low collision energy with simultaneous data collection on a time-of-flight (TOF) mass spectrometer which allowed the characterization of lipids by precursor and product ion alignment. The supercritical fluid chromatography methodology is flexible and can be altered to provide greater retention and separation. The comprehensive method was used to screen seed lipid extracts from several cotton genotypes using multivariate statistical analysis. RESULTS: Method variables influencing the peak integrity and chromatographic separation for a mixture of lipids with different degrees of polarity were explored. The experiments were designed to understand the chromatographic behavior of lipids in a controlled setting using a variety of lipid extracts. Influences of acyl chain length and numbers of double bonds were investigated using single moiety standards. CONCLUSIONS: The methodology parameters were examined using single moiety lipid standards and standard mixtures. The method conditions were applied to biological lipid extracts, and adjustments were investigated to manipulate the chromatography. Insights from these method variable manipulations will help to frame the development of targeted lipid profiling and screening protocols. Copyright © 2017 John Wiley & Sons, Ltd.

An integrated ceramic, micro-fluidic device for the LC/MS/MS analysis of pharmaceuticals in plasma.

An integrated capillary scale (300 µm id) ceramic microfluidic LC system combined with MS/MS has been successfully employed for the quantitative analysis of pharmaceutical compounds in human plasma. The capillary ceramic microfluidic LC/MS/MS system showed an approximate 20-fold (range 11-38-fold) increase in sensitivity compared with a standard 2.1 mm scale UPLC/MS/MS system for a broad range of analytes. The loading capacity of the devices capillary separations channel allowed injection of 2 µL of an aqueous solution, and up to 1.2 µL of a typical protein-precipitated plasma sample, onto the reversed-phase chromatography system. The system also showed excellent chromatographic performance and robustness, with no deleterious effects on the chromatography observed over the course of 1000 injections of protein-precipitated plasma. The ability of the ceramic microfluidic LC/MS/MS system to deliver this level of sensitivity and performance enables the routine quantification of pharmaceutical compounds from small format samples, such as those obtained by dried blood spot or other blood microsampling approaches, to be performed.

Renewable sorbent material for solid phase extraction with direct coupling of sequential injection analysis-bead injection to liquid chromatography-electrospray ionization tandem mass spectrometry.

The use of small scale renewable sorbent material for automated solid phase extraction of multi-residue pharmaceuticals in environmental samples exploiting the sequential injection analysis-bead injection with direct coupling to liquid chromatography-electrospray ionization tandem mass spectrometry (SIA-BI-µSPE-LC-ESI-MS/MS) is presented to determine beta-blockers, namely atenolol, sotalol, pindolol, acebutolol, timolol, metoprolol, labetalol, carazolol, propranolol and betaxolol. These compounds yielded the same product ions, therefore were affected in terms of quantification when flow injection analysis-mass spectrometry (FIA-MS) was used. Thus, analytes and matrix present in the sample travel together into the ionization source which can seriously affect the ionization efficiency and analyte signals due to monitoring over a short time period. Graphical abstract A two-dimensional analysis involving a time dimension (retention time) and an m/z dimension (fragmentation ion) is promising for the various sample types. Using the developed method, absolute recoveries percentages of 10 mL of sample loading volume were >91% for all ß-blockers with enrichment factor of 62-74, limits of detection of 0.005-0.07 µg L(-1), limits of quantification of 0.01-0.23 µg L(-1), enrichment factor of 62-72 and repeatability within range 7-12%. This developed method is suggested to be used as quantitative screening technique for drugs of abuse or persistent contamination using different kinds of sorbent materials and complex matrix such as biological fluid sample as well.

Multidimensional LC-MS/MS enables simultaneous quantification of intact human insulin and five recombinant analogs in human plasma.

This work provides a multidimensional method for the simultaneous, direct quantification of intact human insulin and five insulin analogs in human plasma. This investigation solves both the selectivity and sensitivity problems encountered for accurate quantification of insulins in plasma since the former is not possible with conventional assays and the latter with conventional LC-MS/MS. The method uses a mixed-mode SPE and a multidimensional LC method including a solid-core particle column containing an anion exchange stationary phase. Matrix factors for all analogs were calculated in 6 sources of human plasma and CVs of the matrix factors were <15% in all cases supporting the selectivity of the method, while achieving LLOQs of 50-200 pg/mL (1.4-5.6 µIU/mL) for each insulin from 250 µL of human plasma. The average accuracy for the standard curve points in extracted human plasma was 99-100%. Average inter- and intraday accuracies for QC samples were 98% and 94%, respectively. Average inter- and intraday precisions for QC samples were 7.5 and 5.3%, respectively. Patient samples were analyzed in a blind study and results concurred with their diabetes multidosing regimes. The study also demonstrated that the presence of high levels of human insulin and bovine insulin does not interfere with quantification of any of the analyzed analogs. We propose this method for the accurate pharmacokinetic monitoring of diabetic patients, for sport antidoping and forensic toxicology analysis.

Genome-wide association study reveals a complex genetic architecture underpinning-induced CYP3A4 enzyme activity.

Atypical cytochrome P450 3A4 (CYP3A4) enzyme activity-induced and inhibited-is thought to be the driver of numerous poor or adverse therapeutic responses to up to 50 % of all commonly prescribed drugs. We carried out a genome-wide association study to identify common genetic variants associated with variation in induced CYP3A4 activity. A total of 310 twins were included in this study. Each participant had already completed a 14 days course of St John's Wort to induce CYP3A4, which was quantified through the metabolic ratio of exogenous 3-hydroxyquinine to quinine. We failed to detect any genome-wide significant associations (P < 1 × 10(-8)) with variation in induced CYP3A4 activity although several genomic regions were highlighted which may play minor roles. We report the first GWAS of variation in induced CYP3A4 activity and our preliminary results indicate a complex genetic architecture underpinning induced CYP3A4 enzyme activity.

Variation in herbivore space use: comparing two savanna ecosystems with different anthrax outbreak patterns in southern Africa.

BACKGROUND: The distribution of resources can affect animal range sizes, which in turn may alter infectious disease dynamics in heterogenous environments. The risk of pathogen exposure or the spatial extent of outbreaks may vary with host range size. This study examined the range sizes of herbivorous anthrax host species in two ecosystems and relationships between spatial movement behavior and patterns of disease outbreaks for a multi-host environmentally transmitted pathogen. METHODS: We examined range sizes for seven host species and the spatial extent of anthrax outbreaks in Etosha National Park, Namibia and Kruger National Park, South Africa, where the main host species and outbreak sizes differ. We evaluated host range sizes using the local convex hull method at different temporal scales, within-individual temporal range overlap, and relationships between ranging behavior and species contributions to anthrax cases in each park. We estimated the spatial extent of annual anthrax mortalities and evaluated whether the extent was correlated with case numbers of a given host species. RESULTS: Range size differences among species were not linearly related to anthrax case numbers. In Kruger the main host species had small range sizes and high range overlap, which may heighten exposure when outbreaks occur within their ranges. However, different patterns were observed in Etosha, where the main host species had large range sizes and relatively little overlap. The spatial extent of anthrax mortalities was similar between parks but less variable in Etosha than Kruger. In Kruger outbreaks varied from small local clusters to large areas and the spatial extent correlated with case numbers and species affected. Secondary host species contributed relatively few cases to outbreaks; however, for these species with large range sizes, case numbers positively correlated with outbreak extent. CONCLUSIONS: Our results provide new information on the spatiotemporal structuring of ranging movements of anthrax host species in two ecosystems. The results linking anthrax dynamics to host space use are correlative, yet suggest that, though partial and proximate, host range size and overlap may be contributing factors in outbreak characteristics for environmentally transmitted pathogens.

Probing gunshot residue, sweat and latent human fingerprints with capillary-scale ion chromatography and suppressed conductivity detection.

An investigation into capillary-scale ion chromatography with suppressed conductivity detection is presented for the identification of low molecular weight anions in samples of limited size. Both particle-packed and polymer monolith capillary ion exchange resins were compared with respect to their chromatographic efficiencies, operating back-pressures and thermal selectivities. Using a multistep hydroxide gradient, it was possible to separate a large selection of inorganic and organic anions in <23 mins using both phases with an injection volume of only 0.4 µL. Method performance was tested with respect to linearity, range, reproducibility and sensitivity and compared to a micro-bore (2 mm) IC method. Limits of mass sensitivity improved by factors up to 1,800-fold using the capillary IC system and lay in the range 0.3-26.2 pg. The finalised analytical method was applied to the determination of both endogenous and exogenous species in sweat and fingermark deposits. It was possible to determine presence of elevated levels of thiocyanate and benzoate in the sweat of three moderate smokers (5-10 cigarettes/day) in comparison to non-smokers. A controlled firing experiment was also conducted to assess the transfer of gunshot residue into fingerprints of a firer. Similarly, identification of direct contact with a black powder substitute is presented via analysis of latent fingermarks. To the best of our knowledge, this represents the first study of sweat and fingerprints using capillary-scale suppressed ion chromatography.

Determination of trace amount of enantiomeric impurity in therapeutic nicotine derivative using capillary electrophoresis with new imaging technology detection.

One of the many attempts to stop the danger of tobacco smoking is the development of an anti-smoking vaccine using nicotine butyric acid (NBA) linked to a carrier protein to produce anti-nicotine antibodies. NBA is a chiral molecule and there is a need to obtain a high degree of enantiomeric purity. The aim of this work is to develop a novel method for the enantioseparation of NBA and the determination of trace amounts of enantiomeric impurity required by regulatory authorities. This was achieved successfully using high-performance capillary electrophoresis combined with label-free intrinsic imaging as new imaging technology. A 50 µm id fused-silica capillary was used with UV detection at λ(214 ) nm and label-free intrinsic imaging. The background electrolyte consisted of highly sulphated ß-cyclodextrin 10% m/V as a chiral selector in 75 mM phosphoric acid-triethylamine at pH 7.0. Baseline separation and detection of 0.1% and possibly less of the unwanted impurity (R-enantiomer) were achieved. Also, the detection limits were calculated for both enantiomers. The use of label-free intrinsic imaging has improved the sensitivity, enabling us to detect trace amounts of enantiomeric impurities.

Black rhinoceros (Diceros bicornis) natural diets: comparing iron levels across seasons and geographical locations.

Although excessive iron storage in black rhinoceros (Diceros bicornis) has been a cause for continuous concern over the last four decades and differences in the iron content of diet items fed in captivity and in the wild have been documented, no reports exist on the iron content of the total diet ingested by free-ranging animals. Here, the results of field studies using backtracking to record the ingested diets of black rhinoceros from three habitats across three seasons are reported. Levels of iron and of condensed tannins, which might reduce iron availability, averaged at 91 +/- 41 ppm dry matter and 3.0 +/- 1.0% dry matter, respectively, across all habitats and seasons. Although geographic and seasonal variation was significant, these differences are of a much lower magnitude than differences between the averages of these diets and those fed to black rhinoceros in captivity. The results can provide guidelines for the iron content of diets designed for black rhinoceros and suggest that the effect of tannins in these species should be further investigated.

Prediction of variability in CYP3A4 induction using a combined 1H NMR metabonomics and targeted UPLC-MS approach.

The activity of Cytochrome P450 3A4 (CYP3A4) enzyme is associated with many adverse or poor therapeutic responses to drugs. We used (1)H NMR-based metabonomics to identify a metabolic signature associated with variation in induced CYP3A4 activity. A total of 301 female twins, aged 45--84, participated in this study. Each volunteer was administered a potent inducer of CYP3A4 (St. John's Wort) for 14 days and the activity of CYP3A4 was quantified through the metabolism of the exogenously administered probe drug quinine sulfate (300 mg). Pre- and postintervention fasting urine samples were used to obtain metabolite profiles, using (1)H NMR spectroscopy, and were analyzed using UPLC--MS to obtain a marker for CYP3A4 induction, via the ratio of 3-hydroxyquinine to quinine (3OH-Q:Q). Multiple linear regression was used to build a predictive model for 3OH-Q:Q values based on the preintervention metabolite profiles. A combination of seven metabolites and seven covariates showed a strong (r = 0.62) relationship with log(3OH-Q:Q). This regression model demonstrated significant (p < 0.00001) predictive ability when applied to an independent validation set. Our results highlight the promise of metabonomics for predicting CYP3A4-mediated drug response.

Genetic epidemiology of induced CYP3A4 activity.

AIM: The cytochrome P450 3A4 (CYP3A4) enzyme is implicated in the metabolism of more than 50% of all prescribed medications and its activity - including induced or inhibited activity - is deemed to be a crucial determinant of interindividual variability in drug disposition, poor therapeutic efficacy, and adverse response to medication. METHODS: We used the classical twin model in conjunction with an induction experiment to uncover the relative contribution of genetic and environmental factors to interindividual variation in induced CYP3A4 activity. A total of 367 healthy twins participated in the study. Each volunteer was administered a potent inducer of CYP3A4 (St John's Wort) for 14 days and the activity of CYP3A4 was quantified through the metabolism of the exogenously administered probe drug quinine sulfate. RESULTS: Baseline and induced CYP3A4 activity were highly variable with a seven-fold and 11-fold difference among our population, respectively. Alcohol consumption, BMI, and smoking were significantly associated with induced CYP3A4 activity, collectively explaining 20% of the variation (P<1×10(-4)). The narrow-sense heritability of induced CYP3A4 activity was estimated at 66%, whereas the remainder of the variation was attributed to unique environmental factors. CONCLUSION: To our knowledge, this is the first genetic epidemiological study of induced CYP3A4 activity. Our results motivate further research to identify common and rarer genetic variants that underpin the heritable component of variation in induced CYP3A4 activity.

Accommodating environmental variation in population models: metaphysiological biomass loss accounting.

1. There is a pressing need for population models that can reliably predict responses to changing environmental conditions and diagnose the causes of variation in abundance in space as well as through time. In this 'how to' article, it is outlined how standard population models can be modified to accommodate environmental variation in a heuristically conducive way. This approach is based on metaphysiological modelling concepts linking populations within food web contexts and underlying behaviour governing resource selection. Using population biomass as the currency, population changes can be considered at fine temporal scales taking into account seasonal variation. Density feedbacks are generated through the seasonal depression of resources even in the absence of interference competition. 2. Examples described include (i) metaphysiological modifications of Lotka-Volterra equations for coupled consumer-resource dynamics, accommodating seasonal variation in resource quality as well as availability, resource-dependent mortality and additive predation, (ii) spatial variation in habitat suitability evident from the population abundance attained, taking into account resource heterogeneity and consumer choice using empirical data, (iii) accommodating population structure through the variable sensitivity of life-history stages to resource deficiencies, affecting susceptibility to oscillatory dynamics and (iv) expansion of density-dependent equations to accommodate various biomass losses reducing population growth rate below its potential, including reductions in reproductive outputs. Supporting computational code and parameter values are provided. 3. The essential features of metaphysiological population models include (i) the biomass currency enabling within-year dynamics to be represented appropriately, (ii) distinguishing various processes reducing population growth below its potential, (iii) structural consistency in the representation of interacting populations and (iv) capacity to accommodate environmental variation in space as well as through time. Biomass dynamics provide a common currency linking behavioural, population and food web ecology. 4. Metaphysiological biomass loss accounting provides a conceptual framework more conducive for projecting and interpreting the population consequences of climatic shifts and human transformations of habitats than standard modelling approaches.

Systematic evaluation of acetone and acetonitrile for use in hydrophilic interaction liquid chromatography coupled with electrospray ionization mass spectrometry of basic small molecules.

Sub-2-µm particle size hydrophilic interaction liquid chromatography [HILIC] combined with mass spectrometry has been increasing in popularity as a complementary technique to reversed-phase LC for the analysis of polar analytes. The organic-rich mobile phase associated with HILIC techniques provides increases in compound ionization, due to increased desolvation efficiency during electrospray ionisation mass spectrometric (ESI-MS) analysis. Although recent publications illustrated selectivity and response comparisons between reversed-phase LC/MS and HILIC LC/MS, there are limited discussions evaluating the optimisation of the mass spectrometry parameters regarding analytes and alternative mobile phases. The use of acetone as an alternative organic modifier in HILIC has been investigated with respect to signal-to-noise in ESI-MS for a variety of polar analytes. Analyte reponses were measured based on a variety of cone and capillary voltages at low and high pH in both acetone and acetonitrile. In order to visualise compound behaviour in the ESI source, surface plots were constructed to assist in interpreting the observed results. The use of acetone in ESI is complicated at low m/z due to the formation of condensation products. Favourable responses were observed for certain analytes and we envisage offering an insight into the use of acetone as an alternative to acetonitrile under certain analytical conditions for particular compound classifications for small molecule analysis. We also highlight the importance of optimising source voltages in order to obtain the maximum signal stability and sensitivity, which are invariably, highly solvent composition dependent parameters.

Fluorinated monolithic column for CEC.

In order to overcome the drawbacks associated with particle-based fluorinated stationary phases, a fluorinated cationic monolith was successfully synthesized by the in situ copolymerization of a 45% monomer mixture and 55% porogens with thermal initiation using 0.1% initiator with respect to the monomer mixture. The monomer mixture was composed of perfluorododecyl acrylate (49.75%), ethylene dimethacrylate (49.75%), and 0.5% of the quaternary amine acrylic monomer supporting an anodal electroosmotic flow. A tertiary porogenic solvent system consisting of 40% 1-propanol, 40% 1-octanol, and 20% 1-dodecanol was used. The resulting monolith column showed good characteristics in terms of morphology, permeability (pressure drop was 4.8-25.7 MPa between 5 and 25 µL/min), and the electroosmotic mobility (3.68 (±0.05)×10(-4) cm(2) v(-1) s(-1)). The monolith was tested for the separation of four phenolic compounds, three aromatic hydrocarbons, and one fluorine-containing compound. Good efficiencies (up to 135,000 (±4000) plate/m and resolution up to 2.6 (±0.1)) with short analysis time (< 9 min for tau-fluvalinate, <7 min for four phenolic compounds, and <12 min for three aromatic hydrocarbons) and good stability (1.0-1.5% RSD for intraday, 1.2-1.6% RSD for interday, and 3.9-5.0% RSD for column-to-column) were obtained.

Evaluation of Chinese medicinal herbs fingerprinting by HPLC-DAD for the detection of toxic aristolochic acids.

Aristolochic acids are known to contribute to various renal disorders; therefore, expanding the availability of analytical methodology to detect these compounds is important in order to assess the quality of Chinese herbal medicines in which they can be found. Twelve medicinal herbal samples were procured from various sources and extracted in duplicate prior to a "fingerprint" analysis using conventional HPLC-DAD. Multivariate analysis was performed on the entire chromatographed fingerprints. The resulting output was a partial least-square discriminant analysis model, which was able to evaluate the potential presence of aristolochic acids I and II as well as providing an individual herbal "fingerprint". The results of this study provide evidence that the presence of aristolochic acids contained within certain herbal extractions could be detected using a simple method, although some limitations apply to this method for quality control, since newly detected samples for aristolochic acid (positives) will need further confirmation with purity checks or MS hyphenation.

Contrasting capabilities of two ungulate species to cope with extremes of aridity.

Southern Africa is expected to experience increased frequency and intensity of droughts through climate change, which will adversely affect mammalian herbivores. Using bio-loggers, we tested the expectation that wildebeest (Connochaetes taurinus), a grazer with high water-dependence, would be more sensitive to drought conditions than the arid-adapted gemsbok (Oryx gazella gazella). The study, conducted in the Kalahari, encompassed two hot-dry seasons with similar ambient temperatures but differing rainfall patterns during the preceding wet season. In the drier year both ungulates selected similar cooler microclimates, but wildebeest travelled larger distances than gemsbok, presumably in search of water. Body temperatures in both species reached lower daily minimums and higher daily maximums in the drier season but daily fluctuations were wider in wildebeest than in gemsbok. Lower daily minimum body temperatures displayed by wildebeest suggest that wildebeest were under greater nutritional stress than gemsbok. Moving large distances when water is scarce may have compromised the energy balance of the water dependent wildebeest, a trade-off likely to be exacerbated with future climate change.

First trimester maternal tobacco smoking habits and fetal growth.

RATIONALE: Maternal smoking in pregnancy is associated with reduced birth weight and childhood lung function. This study determined when maternal smoking first influences fetal growth and how this relates to childhood respiratory outcomes. METHODS: A longitudinal cohort of 1924 pregnant women was recruited. Fetal ultrasound measurements at 11 weeks (crown-rump length, CRL) and at 20 weeks gestation (femur length, FL, and biparietal diameter, BPD) and birth measurements were recorded. Childhood respiratory symptoms and spirometry were ascertained. RESULTS: Of the 1924 original study participants, fetal size was determined in 903 in the first trimester, 1544 in the second trimester and at term in 1737 infants. Maternal smoking when first pregnant was reported in 593 (31%) and was not associated with reduced CRL. There was an inverse exposure-response relationship between cigarette consumption and FL (mean reduction in lowest compared with highest tertile 0.91 cm, p=0.033). Birth weight and length of those born to mothers who did (n=331) and did not (n=56) reduce cigarette consumption were similar and reduced compared with 186 infants whose mothers quit during the first trimester (p < or = 0.020). Children of mothers who continued smoking had increased wheeze at age 2 years (OR 1.58, p=0.017) and GP visits with wheeze at age 5 years (OR 2.18, p=0.030) and mean reduction in forced expiratory volume in 1 s of 62 ml (p=0.014) compared with controls. CONCLUSIONS: Maternal smoking is associated with reduced fetal measurements in the second and third trimesters but not in the first trimester. Mothers who do not quit smoking during the first trimester deliver smaller infants who go on to have adverse respiratory outcomes in childhood.

Associations between fetal size, maternal {alpha}-tocopherol and childhood asthma.

BACKGROUND The origins of respiratory disease might be traced back to exposures during fetal life. The aim of the present study was to explore whether there was a relationship between fetal size and respiratory outcomes at 5 years of age in the context of fetal exposure to vitamin E. METHODS A longitudinal birth cohort study was recruited (n=1924). Antenatal ultrasound scan results were identified and the following recorded: crown-rump length (CRL) in the first trimester; femur length (FL) and biparietal diameter (BPD) in the second trimester. Maternal plasma alpha-tocopherol (vitamin E) was measured at the time of the first trimester scan. At 5 years, wheeze and asthma symptoms were reported by questionnaire, and spirometry was measured. RESULTS CRL, spirometry and questionnaire data at 5 years were available for 835, 579 and 1145 individuals, respectively. There were positive associations between CRL and forced expiratory volume in 1 s (FEV(1); 5 ml increase in FEV(1) per mm CRL, p=0.001, n=283), forced vital capacity (FVC; 6 ml increase in FVC per mm CRL, p=0.001) and forced expiratory flow between 25% and 75% of FVC (FEF(25-75); 0.008 ml/s increase in FEF(25-75) per mm CRL, p=0.023), and inverse relationships with CRL and current wheeze (OR 0.59 per CRL quartile, p=0.026, n=547) and asthma (OR 0.55 per CRL quartile p=0.011). CRL was positively associated with maternal plasma alpha-tocopherol (p=0.002). CONCLUSIONS These findings support the concept of very early fetal programming of respiratory disease. Maternal vitamin E status may be one determinant for growth of the fetus and fetal lungs during early pregnancy.