Early nasogastric tube feeding in optimising treatment for hyperemesis gravidarum: The MOTHER randomised controlled trial (Maternal and Offspring outcomes after Treatment of HyperEmesis by Refeeding)

Background: Hyperemesis gravidarum (HG), or intractable vomiting during pregnancy, is the single most frequent cause of hospital admission in early pregnancy. HG has a major impact on maternal quality of life and has repeatedly been associated with poor pregnancy outcome such as low birth weight. Currently, women with HG are admitted to hospital for intravenous fluid replacement, without receiving specific nutritional attention. Nasogastric tube feeding is sometimes used as last resort treatment. At present no randomised trials on dietary or rehydration interventions have been performed. Small observational studies indicate that enteral tube feeding may have the ability to effectively treat dehydration and malnutrition and alleviate nausea and vomiting symptoms. We aim to evaluate the effectiveness of early enteral tube feeding in addition to standard care on nausea and vomiting symptoms and pregnancy outcomes in HG patients. Methods/Design: The MOTHER trial is a multicentre open label randomised controlled trial ( www.studies-obsgyn.nl/mother ). Women ≥ 18 years hospitalised for HG between 5 + 0 and 19 + 6 weeks gestation are eligible for participation. After informed consent participants are randomly allocated to standard care with intravenous rehydration or early enteral tube feeding in addition to standard care. All women keep a weekly diary to record symptoms and dietary intake until 20 weeks gestation. The primary outcome will be neonatal birth weight. Secondary outcomes will be the 24-h Pregnancy Unique Quantification of Emesis and nausea score (PUQE-24), maternal weight gain, dietary intake, duration of hospital stay, number of readmissions, quality of life and side-effects. Also gestational age at birth, placental weight, umbilical cord plasma lipid concentration and neonatal morbidity will be evaluated. Analysis will be according to the intention to treat principle. Discussion: With this trial we aim to clarify whether early enteral tube feeding is more effective in treating HG than intravenous rehydration alone and improves pregnancy outcome. Trial registration: Trial registration number: NTR4197. Date of registration: October 2nd 2013

The genetic architecture of the human cerebral cortex

INTRODUCTION The cerebral cortex underlies our complex cognitive capabilities. Variations in human cortical surface area and thickness are associated with neurological, psychological, and behavioral traits and can be measured in vivo by magnetic resonance imaging (MRI). Studies in model organisms have identified genes that influence cortical structure, but little is known about common genetic variants that affect human cortical structure. RATIONALE To identify genetic variants associated with human cortical structure at both global and regional levels, we conducted a genome-wide association meta-analysis of brain MRI data from 51,665 individuals across 60 cohorts. We analyzed the surface area and average thickness of the whole cortex and 34 cortical regions with known functional specializations. RESULTS We identified 306 nominally genome-wide significant loci (P < 5 × 10−8) associated with cortical structure in a discovery sample of 33,992 participants of European ancestry. Of the 299 loci for which replication data were available, 241 loci influencing surface area and 14 influencing thickness remained significant after replication, with 199 loci passing multiple testing correction (P < 8.3 × 10−10; 187 influencing surface area and 12 influencing thickness). Common genetic variants explained 34% (SE = 3%) of the variation in total surface area and 26% (SE = 2%) in average thickness; surface area and thickness showed a negative genetic correlation (rG = −0.32, SE = 0.05, P = 6.5 × 10−12), which suggests that genetic influences have opposing effects on surface area and thickness. Bioinformatic analyses showed that total surface area is influenced by genetic variants that alter gene regulatory activity in neural progenitor cells during fetal development. By contrast, average thickness is influenced by active regulatory elements in adult brain samples, which may reflect processes that occur after mid-fetal development, such as myelination, branching, or pruning. When considered together, these results support the radial unit hypothesis that different developmental mechanisms promote surface area expansion and increases in thickness. To identify specific genetic influences on individual cortical regions, we controlled for global measures (total surface area or average thickness) in the regional analyses. After multiple testing correction, we identified 175 loci that influence regional surface area and 10 that influence regional thickness. Loci that affect regional surface area cluster near genes involved in the Wnt signaling pathway, which is known to influence areal identity. We observed significant positive genetic correlations and evidence of bidirectional causation of total surface area with both general cognitive functioning and educational attainment. We found additional positive genetic correlations between total surface area and Parkinson’s disease but did not find evidence of causation. Negative genetic correlations were evident between total surface area and insomnia, attention deficit hyperactivity disorder, depressive symptoms, major depressive disorder, and neuroticism. CONCLUSION This large-scale collaborative work enhances our understanding of the genetic architecture of the human cerebral cortex and its regional patterning. The highly polygenic architecture of the cortex suggests that distinct genes are involved in the development of specific cortical areas. Moreover, we find evidence that brain structure is a key phenotype along the causal pathway that leads from genetic variation to differences in general cognitive function

Sexual orientation and gender identity after prenatal exposure to the Dutch famine.

Sexual differentiation of the human brain has been suggested to take place through exposure to sex steroids during intrauterine development. Animal experiments have shown that interference in this process by underfeeding of the mother can result in feminization of the male offspring. We explored the possible effects of prenatal exposure to famine on sexual orientation and gender identity in humans. We used the Klein Sexual Orientation Grid to assess sexual orientation and also assessed gender identity in a group of 380 men and 472 women who were born as term singletons around the time of the 1944-1945 Dutch famine. Prenatal exposure to famine did not affect sexual orientation in men or in women. Three people indicated having some gender identity problems: one woman born before the famine and one man and woman exposed to famine in late gestation. In men, a later birth order was associated with a non-exclusively heterosexual identification. In conclusion, we found no evidence for a significant association between exposure to famine in utero and altered sexual orientation and gender identity. The small sample size of participants with non-exclusively heterosexual identification (possibly due to underreporting of homosexuality) may have reduced our power to detect any difference

Prenatal exposure to the Dutch famine is associated with a preference for fatty foods and a more atherogenic lipid profile

Background: Evidence from animal models suggests that fetal undernutrition can predispose to hypercholesterolemia and metabolic disorders directly by programming cholesterol metabolism and may indirectly influence lifestyle choices. We have shown that persons who were exposed to the Dutch famine in early gestation have a more atherogenic lipid profile. Objective: We now investigate whether the excess in hypercholesterolemia may be a result of a more atherogenic diet or a reduction in physical activity. Design: We measured lipid profiles, dietary intake, and physical activity in 730 men and women (aged 58 y) born in the Wilhelmina Gasthuis in Amsterdam, Netherlands, around the time of the Dutch famine, whose birth records have been kept. Results: No differences were observed in mean intake of total energy or percentage of protein, carbohydrate, and fat in the diet between the different exposure groups. However, persons exposed to famine in early gestation were twice as likely (odds ratio: 2.1; 95% CI: 1.2, 3.9) to consume a high-fat diet (defined as the highest quartile of percentage of fat in the diet: >39% of energy from fat). They also tended to be less physically active (45% did sports compared with 52% in the unexposed group), although this did not reach statistical significance. Conclusions: This is the first direct evidence in humans that prenatal nutrition may affect dietary preferences and may contribute to more atherogenic lipid profiles in later life. \ua9 2008 American Society for Nutrition

Trophic ecology warrants multispecies management in a grassland setting: Proposed species interactions on black-tailed prairie dog colonies

Trophic cascades occur when flora and fauna directly and/or indirectly influence co-occurring species populations at different levels of the food chain, and North American temperate grasslands provide an interesting case study to research these relationships. We briefly define trophic cascades in terrestrial systems and explore the potential for a cascading trophic interaction among grassland-associated swift fox (Vulpes velox), western burrowing owl (Athene cunicularia hypugaea), and mountain plover (Charadrius montanus), three rangeland species of conservation concern, on black-tailed prairie dog (Cynomys ludovicianus) colonies using two US Forest Service data sets. Historic patterns of occurrence and co-occurrence suggest top-down control governs the spatiotemporal distribution patterns of the three species and may be influenced by habitat fragmentation and management actions. Managing for interactive, multitrophic communities requires the identification of species interactions and the mechanisms that drive them. Long-term multispecies occupancy research, combined with hypothesized driving mechanisms and the co-occurrence of associated grassland species, is recommended for addressing these complex interactions moving forward. The Society for Range ManagementThe Rangelands archives are made available by the Society for Range Management and the University of Arizona Libraries. Contact [email protected] for further information

Effects of famine on placental size and efficiency

Background: Placental growth responds to maternal influences including diet. We have examined placental size, shape and efficiency among babies born around the time of the 5-month wartime famine in Holland 1944-1945.Methods: We examined the birth records of 2414 term singleton babies born in Amsterdam during 1943–1947. The records included the size of the baby and the thickness of the placental surface, together with its length and breadth which we used to calculate its area and volume.Results: Compared to babies born before the famine babies who were in utero during the famine had smaller placental areas. Babies whose mothers conceived after the famine ended also had smaller placental areas. Famine was associated with a 19 cm2 decrease in area. Babies who were in mid-late gestation during the famine were 160 g lighter than would have been predicted from their placental area (p &lt; 0.001). Babies who were in early gestation during the famine, or who were conceived after it had ended were 102 g heavier than would have been predicted from their placental area (p &lt; 0.001). These latter babies were either longer or had larger head circumferences depending on when the mother experienced the famine. Among babies who were in early gestation during the famine the reduction in placental area was greater in boys than girls (p for interaction 0.03).Conclusion: Famine impaired the normal processes of placentation, even among babies who were conceived after it had ended. In babies who were in mid-late gestation during the famine, the placenta was less efficient. In babies who were in early gestation during the famine, or who were conceived after it had ended, the placenta was more efficient. The placentas of boys and girls responded differently to famine.<br/