Visual complexity of egg patterns predicts egg rejection according to Weber's law.

Visual complexity is ubiquitous in nature. Drivers of complexity include selection in coevolutionary arms races between antagonists. However, the causes and consequences of biological complexity and its perception are largely understudied, partly because complexity is difficult to quantify. Here, we address this by studying egg pattern complexity and its perception in hosts (tawny-flanked prinia Prinia subflava), which visually recognize and reject mimetic eggs of their virulent brood parasite (cuckoo finch Anomalospiza imberbis). Using field data and an optimization algorithm, we compute a complexity metric which predicts rejection of experimentally placed conspecific eggs in prinia nests. Real cuckoo finch eggs exhibit significantly lower pattern complexity than prinia eggs, suggesting that high complexity benefits hosts because it distinguishes host eggs from parasitic eggs. We show that prinias perceive complexity differences according to Weber's law of proportional processing (i.e. relative, rather than absolute, differences between stimuli are processed in discrimination, such that two eggs with simple patterns are more easily discriminable than two with complex patterns). This may influence coevolutionary trajectories of hosts and parasites. The new methods presented for quantifying complexity and its perception can help us to understand selection pressures driving the evolution of complexity and its consequences for species interactions.

Thymic size is increased by infancy, but not pregnancy, nutritional supplementation in rural Gambian children: a randomized clinical trial.

BACKGROUND: Thymic size in early infancy predicts subsequent survival in low-income settings. The human thymus develops from early gestation, is most active in early life and is highly sensitive to malnutrition. Our objective was to test whether thymic size in infancy could be increased by maternal and/or infant nutritional supplementation. METHODS: The Early Nutrition and Immune Development (ENID) Trial was a randomized 2 × 2 × 2 factorial, partially blinded trial of nutritional supplementation conducted in rural Gambia, West Africa. Pregnant women (N = 875) were randomized to four intervention groups (iron-folate (standard care), multiple micronutrients, protein energy or protein energy + multiple micronutrients at 'booking' (mean gestational age at enrolment = 13.6 weeks, range 8-20 weeks) until delivery. The iron-folate and multiple micronutrient arms were administered in tablet form and the protein energy arms as a lipid-based nutritional supplement. All intervention arms contained 60 mg iron and 400 µg folic acid per daily dose. From 24 to 52 weeks of age, infants from all groups were randomized to receive a daily lipid-based nutritional supplement, with or without additional micronutrients. Thymic size was assessed by ultrasonography at 1, 8, 24 and 52 weeks of infant age, and a volume-related thymic index calculated. Detailed data on infant growth, feeding status and morbidity were collected. RESULTS: A total of 724 (82.7%) mother-infant pairs completed the trial to infant age 52 weeks. Thymic size in infancy was not significantly associated with maternal supplement group at any post-natal time point. Infants who received the daily LNS with additional micronutrients had a significantly larger thymic index at 52 weeks of age (equivalent to an 8.0% increase in thymic index [95% CI 2.89, 13.4], P = 0.002). No interaction was observed between maternal and infant supplement groups. CONCLUSIONS: A micronutrient-fortified lipid-based supplement given in the latter half of infancy increased thymic size, a key mediator of immune function. Improving the micronutrient status of infants from populations with marginal micronutrient status may improve immune development and survival. TRIAL REGISTRATION: ISRCTN registry (controlled-trials.com) Identifier: ISRCTN49285450.

Influence of intergenerational in utero parental energy and nutrient restriction on offspring growth in rural Gambia.

The prenatal environment can alter an individual's developmental trajectory with long-lasting effects on health. Animal models demonstrate that the impact of the early life environment extends to subsequent generations, but there is a paucity of data from human populations on intergenerational transmission of environmentally induced phenotypes. Here we investigated the association of parental exposure to energy and nutrient restriction in utero on their children's growth in rural Gambia. In a Gambian cohort with infants born between 1972 and 2011, we used multiple regression to test whether parental season of birth predicted offspring birth weight (n = 2097) or length (n = 1172), height-for-age z score (HAZ), weight-for-height z score (WHZ), and weight-for-age z score (WAZ) at 2 yr of age (n = 923). We found that maternal exposure to seasonal energy restriction in utero was associated with reduced offspring birth length (crude:-4.2 mm, P = 0.005; adjusted: -4.0 mm, P = 0.02). In contrast, paternal birth season predicted offspring HAZ at 24 mo (crude: -0.21, P = 0.005; adjusted: -0.22, P = 0.004) but had no discernible impact at birth. Our results indicate that periods of nutritional restriction in a parent's fetal life can have intergenerational consequences in human populations. Fetal growth appears to be under matriline influence, and postnatal growth appears to be under patriline intergenerational influences.-Eriksen, K. G., Radford, E. J., Silver, M. J., Fulford, A. J. C., Wegmüller, R., Prentice, A. M. Influence of intergenerational in utero parental energy and nutrient restriction on offspring growth in rural Gambia.

A double blind randomized controlled trial in neonates to determine the effect of vitamin A supplementation on immune responses: The Gambia protocol.

BACKGROUND: Vitamin A supplementation significantly reduces all-cause mortality when given between 6-59 months of age, but has a null or detrimental effect when given between 1-5 months. Studies of neonatal vitamin A supplementation conducted across Africa and South Asia have produced conflicting findings. These age-pattern variations might result from immunological interactions between vitamin A supplementation and vaccines. Knowledge on the potential immunological sequelae of human neonatal vitamin A supplementation is so scarce that the foremost aim of this study is to seek indicative data on aspects of immunity likely to be affected by neonatal vitamin A supplementation. The objective of this trial is to test whether human neonatal vitamin A supplementation modulates immune function including improved thymic maturation in infancy and improved systemic immune responses to routine immunization. METHODS/DESIGN: In an area of moderate vitamin A deficiency in a peri-urban area of The Gambia, 200 mother-infant pairs were enrolled in a double-blind randomised controlled trial. Within 48 hours of birth, neonates were randomised with stratification by birth weight and sex to receive either an oral dose of 50,000 IU vitamin A or placebo. Expanded Programme of Immunisation birth vaccinations were administered after supplementation, with subsequent vaccinations administered at 8, 12 and 16 weeks of age. A range of immunological outcomes were examined up to 17 weeks of age, with additional morbidity and anthropometry follow-up carried out throughout the first year of life. The primary endpoint of this trial is the frequency of circulating T regulatory (Treg) cells expressing gut homing receptors in infants at 17 week post-supplementation, with secondary outcomes including thymus maturation and B cell immune responses. DISCUSSION: Indicative immunological data from this trial (and its Bangladeshi counterpart), will complement the larger randomised controlled trials (conducted in India, Tanzania and Ghana), on the effectiveness and safety of neonatal vitamin A supplementation in improving infant survival. Combined these trials, in addition to the existing trials, will inform policy. TRIAL REGISTRATION: clinicaltrials.gov NCT01476358.

Combined food and micronutrient supplements during pregnancy have limited impact on child blood pressure and kidney function in rural Bangladesh.

Observational evidence suggests nutritional exposures during in utero development may have long-lasting consequences for health; data from interventions are scarce. Here, we present a trial follow-up study to assess the association between prenatal food and micronutrient supplementation and childhood blood pressure and kidney function. During the MINIMat Trial in rural Bangladesh, women were randomly assigned early in pregnancy to receive an early or later invitation to attend a food supplementation program and additionally to receive either iron and folate or multiple micronutrient tablets daily. The 3267 singleton birth individuals with measured anthropometry born during the trial were eligible for a follow-up study at 4.5 y old. A total of 77% of eligible individuals were recruited and blood pressure, kidney size by ultrasound, and glomerular filtration rate (GFR; calculated from plasma cystatin c) were assessed. In adjusted analysis, early invitation to food supplementation was associated with a 0.72-mm Hg [(95% CI: 0.16, 1.28); P = 0.01] lower childhood diastolic blood pressure and maternal MMS supplementation was associated with a marginally higher [0.87 mm Hg (95% CI: 0.18, 1.56); P = 0.01] childhood diastolic blood pressure. There was also some evidence that a supplement higher in iron was associated with a higher offspring GFR. No other effects of the food or micronutrient interventions were observed and there was no interaction between the interventions on the outcomes studied. These marginal associations and small effect sizes suggest limited public health importance in early childhood.

Chase-away evolution maintains imperfect mimicry in a brood parasite-host system despite rapid evolution of mimics.

We studied a brood parasite-host system (the cuckoo finch Anomalospiza imberbis and its host, the tawny-flanked prinia Prinia subflava) to test (1) the fundamental hypothesis that deceptive mimics evolve to resemble models, selecting in turn for models to evolve away from mimics ('chase-away evolution') and (2) whether such reciprocal evolution maintains imperfect mimicry over time. Over only 50 years, parasites evolved towards hosts and hosts evolved away from parasites, resulting in no detectible increase in mimetic fidelity. Our results reflect rapid adaptive evolution in wild populations of models and mimics and show that chase-away evolution in models can counteract even rapid evolution of mimics, resulting in the persistence of imperfect mimicry.

Intergenerational effects of maternal birth season on offspring size in rural Gambia.

Environmental conditions experienced in early life can influence an individual's growth and long-term health, and potentially also that of their offspring. However, such developmental effects on intergenerational outcomes have rarely been studied. Here we investigate intergenerational effects of early environment in humans using survey- and clinic-based data from rural Gambia, a population experiencing substantial seasonal stress that influences foetal growth and has long-term effects on first-generation survival. Using Fourier regression to model seasonality, we test whether (i) parental birth season has intergenerational consequences for offspring in utero growth (1982 neonates, born 1976-2009) and (ii) whether such effects have been reduced by improvements to population health in recent decades. Contrary to our predictions, we show effects of maternal birth season on offspring birth weight and head circumference only in recent maternal cohorts born after 1975. Offspring birth weight varied according to maternal birth season from 2.85 to 3.03 kg among women born during 1975-1984 and from 2.84 to 3.41 kg among those born after 1984, but the seasonality effect reversed between these cohorts. These results were not mediated by differences in maternal age or parity. Equivalent patterns were observed for offspring head circumference (statistically significant) and length (not significant), but not for ponderal index. No relationships were found between paternal birth season and offspring neonatal anthropometrics. Our results indicate that even in rural populations living under conditions of relative affluence, brief variation in environmental conditions during maternal early life may exert long-term intergenerational effects on offspring.

Twinning propensity and offspring in utero growth covary in rural African women.

In humans and other mammals, some females are more likely to experience twin pregnancies than others, but the reasons behind such individual variation are poorly understood. One hypothesis invokes variation in the dynamics of the insulin-like growth factor (IGF) system, which also regulates foetal growth. Using data from a rural African population living in a highly seasonal environment, we test a novel prediction generated by this hypothesis, that maternal twinning status predicts offspring birthweight. We found that among singleton offspring who experience a favourable in utero environment (born January-June), births before and after twins are, respectively, associated with a 134.07 g and 226.41 g increase in birthweight compared with those born to non-twinning mothers. These results were not mediated by maternal anthropometry. This is consistent with a role for the IGF system in individual variation in twinning propensity, a possibility with implications for understanding mechanisms of life-history variation in humans and other vertebrates.

Common polymorphic variation in the genetically diverse African insulin gene and its association with size at birth.

The insulin variable number of tandem repeats (INS VNTR) has been variably associated with size at birth in non-African populations. Small size at birth is a major determinant of neonatal mortality, so the INS VNTR may influence survival. We tested the hypothesis, therefore, that genetic variation around the INS VNTR in a rural Gambian population, who experience seasonal variation in nutrition and subsequently birth weight, may be associated with foetal and early growth. Six polymorphisms flanking the INS VNTR were genotyped in over 2,500 people. Significant associations were detected between the maternally inherited SNP 27 (rs689) allele and birth length [effect size 17.5 (5.2-29.8) mm; P = 0.004; n = 361]. Significant associations were also found between the maternally inherited African-specific SNP 28 (rs5506) allele and post-natal weight gain [effect size 0.19 (0.05-0.32) z score points/year; P = 0.005; n = 728). These results suggest that in the Gambian population studied there are associations between polymorphic variation in the genetically diverse INS gene and foetal and early growth characteristics, which contribute to overall polygenic associations with these traits.

Changes in malaria indices between 1999 and 2007 in The Gambia: a retrospective analysis.

BACKGROUND: Malaria is a major cause of morbidity and mortality in Africa. International effort and funding for control has been stepped up, with substantial increases from 2003 in the delivery of malaria interventions to pregnant women and children younger than 5 years in The Gambia. We investigated the changes in malaria indices in this country, and the causes and public-health significance of these changes. METHODS: We undertook a retrospective analysis of original records to establish numbers and proportions of malaria inpatients, deaths, and blood-slide examinations at one hospital over 9 years (January, 1999-December, 2007), and at four health facilities in three different administrative regions over 7 years (January, 2001-December, 2007). We obtained additional data from single sites for haemoglobin concentrations in paediatric admissions and for age distribution of malaria admissions. FINDINGS: From 2003 to 2007, at four sites with complete slide examination records, the proportions of malaria-positive slides decreased by 82% (3397/10861 in 2003 to 337/6142 in 2007), 85% (137/1259 to 6/368), 73% (3664/16932 to 666/11333), and 50% (1206/3304 to 336/1853). At three sites with complete admission records, the proportions of malaria admissions fell by 74% (435/2530 to 69/1531), 69% (797/2824 to 89/1032), and 27% (2204/4056 to 496/1251). Proportions of deaths attributed to malaria in two hospitals decreased by 100% (seven of 115 in 2003 to none of 117 in 2007) and 90% (22/122 in 2003 to one of 58 in 2007). Since 2004, mean haemoglobin concentrations for all-cause admissions increased by 12 g/L (85 g/L in 2000-04 to 97 g/L in 2005-07), and mean age of paediatric malaria admissions increased from 3.9 years (95% CI 3.7-4.0) to 5.6 years (5.0-6.2). INTERPRETATION: A large proportion of the malaria burden has been alleviated in The Gambia. Our results encourage consideration of a policy to eliminate malaria as a public-health problem, while emphasising the importance of accurate and continuous surveillance.

Dietary supplementation of rural Gambian women during pregnancy does not affect body composition in offspring at 11-17 years of age.

Fetal nutrition is thought to be an important determinant of later disease risk, although evidence from randomized-controlled trials in humans is lacking. We followed children born during a protein-energy supplementation trial to investigate to what extent this maternal supplement, which improved birth weight, influenced offspring body composition in adolescence. Subjects were 1270 Gambian children (659 boys, 611 girls) aged 11-17 y whose mothers had participated in the original cluster-randomized trial and had received the supplement during pregnancy (intervention) or postpartum (control). Basic anthropometry was measured using standard techniques and fatness was assessed by bioelectrical impedance analysis and population-specific prediction equations. For boys, mean body fat was 12.6% for both intervention and control groups. Mean trunk fat was 11.9% in the intervention group and 12.0% in the control. Intervention girls had a mean body fat of 19.5% and trunk fat of 15.2%; for control girls, it was 19.3 and 14.8%, respectively. BMI, body fat, trunk fat, fat mass index, and fat-free mass index did not differ for either sex when analyzed with generalized estimating equations adjusted for age, maternal height, maternal parity, location, season of birth, and menarche in females. Neither infant-attained size nor the onset of menarche were affected by maternal supplementation. These findings suggest that protein-energy supplements to pregnant women, compared with lactating women, do not affect offspring body composition during adolescence.

Haptoglobin genotype, anaemia and malaria in Gambian children.

OBJECTIVE: To retest our previous finding that the haptoglobin (Hp) 22 genotype is associated with seasonal anaemia, and to investigate the role of malaria in this effect. METHODS: Haemoglobin (Hb) and peripheral parasitaemia were assessed at pre- and post-malarial season cross-sectional surveys in rural Gambian children aged 10-72 months. Between the surveys, active longitudinal surveillance was conducted to detect febrile episodes. RESULTS: Unlike previously, no overall reduction in Hb was observed (Hb = 106.1 vs. 107.2 g/l, P = 0.13, n = 545). However, multi-variable linear regression revealed differences in Hb over the season by Hp and Hb-sickle (HbS) genotype (-2.20 g/l per copy of the Hp2 allele, P = 0.043; HbAS vs. HbAA + 3.13 g/l, P = 0.11, n = 536). There was no effect of malarial episodes during follow-up; this suggests that when effective treatment is given, Hb levels recover. The A61-C Hp promoter SNP, associated with the Hp2 allele, had no effect. CONCLUSION: The effect of the Hp2 allele appears to be independent of effects on malaria incidence but may affect Hb levels through increased oxidant stress and red cell turnover. This may be supported by our previous observations that the effect of Hp22 was independent of markers of iron status and zinc protoporphyrin measured at the cross-sectional surveys and therefore also of iron availability for erythropoiesis.

Changes in Women's Facial Skin Color over the Ovulatory Cycle are Not Detectable by the Human Visual System.

Human ovulation is not advertised, as it is in several primate species, by conspicuous sexual swellings. However, there is increasing evidence that the attractiveness of women's body odor, voice, and facial appearance peak during the fertile phase of their ovulatory cycle. Cycle effects on facial attractiveness may be underpinned by changes in facial skin color, but it is not clear if skin color varies cyclically in humans or if any changes are detectable. To test these questions we photographed women daily for at least one cycle. Changes in facial skin redness and luminance were then quantified by mapping the digital images to human long, medium, and shortwave visual receptors. We find cyclic variation in skin redness, but not luminance. Redness decreases rapidly after menstrual onset, increases in the days before ovulation, and remains high through the luteal phase. However, we also show that this variation is unlikely to be detectable by the human visual system. We conclude that changes in skin color are not responsible for the effects of the ovulatory cycle on women's attractiveness.

Comparative analysis of patterns of survival by season of birth in rural Bangladeshi and Gambian populations.

BACKGROUND: Analysis of data from rural Gambia has previously shown that being born during the annual hungry season strongly influences susceptibility to mortality from infectious disease in young adulthood, possibly through an influence on immune function. In rural Bangladesh pregnancies are exposed to similar seasonality. The current paper uses data from a large demographic survey in the Matlab region of Bangladesh to retest the Gambian-derived hypothesis that early life exposures correlated with season of birth predict later patterns of mortality. METHODS: Since 1966, a continuous demographic surveillance system has been in operation in the rural Matlab region of Bangladesh. The current analysis is based on 172 228 births and 24 697 deaths between 1974 and 2000. Season of birth was defined as 'harvest' (January-June) and 'hungry' (July-December), based on monthly variations in rates of conception and neonatal mortality within the same dataset. RESULTS: Birth during the hungry season resulted in excess mortality during the first year of life. However, for adult mortality (deaths >15 years), there was no excess in individuals born during the annual hungry season: ratio of hazard July-December versus January-June = 1.12; 95% CI: 0.87, 1.45. CONCLUSIONS: The current study found no excess mortality in young adults born during the 'hungry' season in rural Bangladesh. This differing pattern in survival when compared with The Gambia may be a consequence of the greatly reduced incidence of young adult deaths in Bangladesh (0.1%) compared with The Gambia (3%). Under such conditions possible differences in immune function may not be detectable with early adult death as the outcome. However, it also remains possible that our Gambian observation could be a highly discrete phenomenon localized in either time or place, and as such, will not be replicated in other populations.

Thymus development and infant and child mortality in rural Bangladesh.

BACKGROUND: Data from West Africa indicate that a small thymus at birth and at 6 months of age is a strong and independent risk factor for infection-related mortality up to 24 and 36 months of age, respectively. We investigated the association between thymus size (thymic index, TI) in infancy and subsequent infant and child survival in a contemporary South Asian population. METHODS: The study focused on the follow-up of a randomized trial of prenatal nutritional interventions in rural Bangladesh (ISRCTN16581394), with TI measured longitudinally in infancy (at birth and weeks 8, 24 and 52 of age) and accurate recording of mortality up to 5 years of age. RESULTS: A total of 3267 infants were born into the Maternal and Infant Nutrition Interventions, Matlab study; data on TI were available for 1168 infants at birth, increasing to 2094 infants by 52 weeks of age. TI in relation to body size was largest at birth, decreasing through infancy. For infants with at least one measure of TI available, there were a total of 99 deaths up to the age of 5 years. No association was observed between TI and subsequent mortality when TI was measured at birth. However, an association with mortality was observed with TI at 8 weeks of age [odds ratio (OR) for change in mortality risk associated with 1 standard deviation change in TI: all deaths: OR = 0.64, 95% confidence interval (CI) 0.41, 0.98; P = 0.038; and infection-related deaths only: OR = 0.32, 95% CI 0.14, 0.74; P = 0.008]. For TI when measured at 24 and 52 weeks of age, the numbers of infection-related deaths were too few (3 and 1, respectively) for any meaningful association to be observed. CONCLUSION: These results confirm that thymus size in early infancy predicts subsequent survival in a lower mortality setting than West Africa. The absence of an effect at birth and its appearance at 8 weeks of age suggests early postnatal influences such as breast milk trophic factors.

The demographic transition influences variance in fitness and selection on height and BMI in rural Gambia.

Recent human history is marked by demographic transitions characterized by declines in mortality and fertility. By influencing the variance in those fitness components, demographic transitions can affect selection on other traits. Parallel to changes in selection triggered by demography per se, relationships between fitness and anthropometric traits are also expected to change due to modification of the environment. Here we explore for the first time these two main evolutionary consequences of demographic transitions using a unique data set containing survival, fertility, and anthropometric data for thousands of women in rural Gambia from 1956-2010. We show how the demographic transition influenced directional selection on height and body mass index (BMI). We observed a change in selection for both traits mediated by variation in fertility: selection initially favored short females with high BMI values but shifted across the demographic transition to favor tall females with low BMI values. We demonstrate that these differences resulted both from changes in fitness variance that shape the strength of selection and from shifts in selective pressures triggered by environmental changes. These results suggest that demographic and environmental trends encountered by current human populations worldwide are likely to modify, but not stop, natural selection in humans.

Early exposure to toxic metals has a limited effect on blood pressure or kidney function in later childhood, rural Bangladesh.

BACKGROUND: Chronic exposure to toxic metals such as arsenic and cadmium has been implicated in the development of kidney and cardiovascular diseases but few studies have directly measured exposure during inutero and early child development. METHODS: We investigated the impact of exposure to arsenic (mainly in drinking water) and cadmium (mainly in rice) during pregnancy on blood pressure and kidney function at 4.5 years of age in rural Bangladesh. The effect of arsenic exposure in infancy was also assessed. RESULTS: Within a cohort of 1887 children recruited into the MINIMat study, exposure to arsenic (maternal urinary arsenic, U-As), but not cadmium, during in utero development was associated with a minimal increase in blood pressure at 4.5 years. Each 1 mg/l increase in pregnancy U-As was associated with 3.69 mmHg (95% CI: 0.74, 6.63; P: 0.01) increase in child systolic and a 2.91 mmHg (95% CI: 0.41, 5.42; P: 0.02) increase in child diastolic blood pressure. Similarly, a 1 mg/l increase in child U-As at 18 months of age was associated with a 8.25 mmHg (95% CI: 1.37, 15.1; P: 0.02) increase in systolic blood pressure at 4.5 years. There was also a marginal inverse association between infancy U-As and glomerular filtration rate at 4.5 years (-33.4 ml/min/1.72 m(2); 95% CI: -70.2, 3.34; P: 0.08). No association was observed between early arsenic or cadmium exposure and kidney volume at 4.5 years assessed by ultrasound. CONCLUSIONS: These modest effect sizes provide some evidence that arsenic exposure in early life has long-term consequences for blood pressure and maybe kidney function.

DNA methylation potential: dietary intake and blood concentrations of one-carbon metabolites and cofactors in rural African women.

BACKGROUND: Animal models show that periconceptional supplementation with folic acid, vitamin B-12, choline, and betaine can induce differences in offspring phenotype mediated by epigenetic changes in DNA. In humans, altered DNA methylation patterns have been observed in offspring whose mothers were exposed to famine or who conceived in the Gambian rainy season. OBJECTIVE: The objective was to understand the seasonality of DNA methylation patterns in rural Gambian women. We studied natural variations in dietary intake of nutrients involved in methyl-donor pathways and their effect on the respective metabolic biomarkers. DESIGN: In 30 women of reproductive age (18-45 y), we monitored diets monthly for 1 y by using 48-h weighed records to measure intakes of choline, betaine, folate, methionine, riboflavin, and vitamins B-6 and B-12. Blood biomarkers of these nutrients, S-adenosylhomocysteine (SAH), S-adenosylmethionine (SAM), homocysteine, cysteine, and dimethylglycine were also assessed monthly. RESULTS: Dietary intakes of riboflavin, folate, choline, and betaine varied significantly by season; the most dramatic variation was seen for betaine. All metabolic biomarkers showed significant seasonality, and vitamin B-6 and folate had the highest fluctuations. Correlations between dietary intakes and blood biomarkers were found for riboflavin, vitamin B-6, active vitamin B-12 (holotranscobalamin), and betaine. We observed a seasonal switch between the betaine and folate pathways and a probable limiting role of riboflavin in these processes and a higher SAM/SAH ratio during the rainy season. CONCLUSIONS: Naturally occurring seasonal variations in food-consumption patterns have a profound effect on methyl-donor biomarker status. The direction of these changes was consistent with previously reported differences in methylation of metastable epialleles. This trial was registered at www.clinicaltrials.gov as NCT01811641.

Nutritional supplementation during pregnancy and offspring cardiovascular disease risk in The Gambia.

BACKGROUND: Maternal nutritional intake during pregnancy may have important consequences for long-term health in offspring. OBJECTIVE: The objective was to follow up the offspring in 2 randomized trials of nutrient supplementation during pregnancy to investigate the effect on cardiovascular disease (CVD) risk in offspring. DESIGN: We recruited offspring born during 2 trials in The Gambia, West Africa. One trial provided protein-energy-dense food supplements (1015 kcal and 22 g protein/d) to pregnant (intervention, from 20 wk gestation until delivery) or lactating (control, for 20 wk from birth) women and was randomized at the village level. The second was a double-blind, individually randomized, placebo-controlled trial of calcium supplementation (1.5 g/d), which was also provided from 20 wk gestation until delivery. RESULTS: Sixty-two percent (n = 1267) of children (aged 11-17 y) born during the protein-energy trial were recruited and included in the analysis, and 64% (n = 350) of children (aged 5-10 y) born during the calcium trial were recruited and included in the analysis. Fasted plasma glucose was marginally lower in children born to mothers receiving protein-energy supplements during pregnancy than in those children of the lactating group (adjusted mean difference: -0.05 mmol/L; 95% CI: -0.10, -0.001 mmol/L). There were no other differences in CVD risk factors, including blood pressure, body composition, and cholesterol, between children born to intervention and control women from the protein-energy trial. Maternal calcium supplementation during pregnancy was unrelated to offspring blood pressure. CONCLUSION: These data suggest that providing supplements to pregnant women in the second half of pregnancy may have little effect on the CVD risk of their offspring, at least in this setting and at the ages studied here. This trial was registered at www.controlled-trials.com as ISRCTN96502494.

Analysis of complex patterns of human exposure and immunity to Schistosomiasis mansoni: the influence of age, sex, ethnicity and IgE.

BACKGROUND: Numerous factors may influence Schistosoma infection intensity and prevalence within endemic communities, including exposure-related factors such as local environment and behaviour, and factors relating to susceptibility to infection such as immunology and genetics. While animal studies performed in the laboratory can be tightly controlled, human populations are highly heterogeneous, varying according to demographic characteristics, genetic background and exposure to infection. The heterogeneous nature of human water contact behaviour in particular makes it difficult to distinguish between a lack of cercarial exposure and reduced susceptibility to infection as the cause for low levels of infection in the field. METHODS AND PRINCIPAL FINDINGS: In this study we investigate risk factors for Schistosoma mansoni infection in a rural Ugandan fishing community receiving treatment as part of a multi-disciplinary longitudinal reinfection study. More specifically, we examine the influence that age, sex and ethnic background have on susceptibility to reinfection after anti-helminth drug treatment, but use individual estimates of cercarial exposure and multivariable methods in an attempt to remove noise created by environmental and behavioural heterogeneities. We then investigate whether schistosome-specific IgE immune responses could account for any remaining variations in susceptibility to reinfection. Our findings suggest that observed ethnic- and sex-related variations in S. mansoni reinfection were due to variations in cercarial exposure, as opposed to biological differences in susceptibility to infection. Age-related differences in reinfection were not explained by exposure, however, and appeared linked to the balance of IgE and IgG(4) to the tegumental antigen SmTAL1 (formerly Sm22.6), which itself was significantly related to resistance to reinfection. CONCLUSIONS: This study highlights the benefit of taking a multidisciplinary approach in complex field settings; it allows the ecology of a population to be understood and thus more robust conclusions to be made.