Characterisation of the maternal response to chronic phase shifts during gestation in the rat: implications for fetal metabolic programming

Disrupting maternal circadian rhythms through exposure to chronic phase shifts of the photoperiod has lifelong consequences for the metabolic homeostasis of the fetus, such that offspring develop increased adiposity, hyperinsulinaemia and poor glucose and insulin tolerance. In an attempt to determine the mechanisms by which these poor metabolic outcomes arise, we investigated the impact of chronic phase shifts (CPS) on maternal and fetal hormonal, metabolic and circadian rhythms. We assessed weight gain and food consumption of dams exposed to either CPS or control lighting conditions throughout gestation. At day 20, dams were assessed for plasma hormone and metabolite concentrations and glucose and insulin tolerance. Additionally, the expression of a range of circadian and metabolic genes was assessed in maternal, placental and fetal tissue. Control and CPS dams consumed the same amount of food, yet CPS dams gained 70% less weight during the first week of gestation. At day 20, CPS dams had reduced retroperitoneal fat pad weight (−15%), and time-of-day dependent decreases in liver weight, whereas fetal and placental weight was not affected. Melatonin secretion was not altered, yet the timing of corticosterone, leptin, glucose, insulin, free fatty acids, triglycerides and cholesterol concentrations were profoundly disrupted. The expression of gluconeogenic and circadian clock genes in maternal and fetal liver became either arrhythmic or were in antiphase to the controls. These results demonstrate that disruptions of the photoperiod can severely disrupt normal circadian profiles of plasma hormones and metabolites, as well as gene expression in maternal and fetal tissues. Disruptions in the timing of food consumption and the downstream metabolic processes required to utilise that food, may lead to reduced efficiency of growth such that maternal weight gain is reduced during early embryonic development. It is these perturbations that may contribute to the programming of poor metabolic homeostasis in the offspring.Tamara J. Varcoe, Michael J. Boden, Athena Voultsios, Mark D. Salkeld, Leewen Rattanatray, David J. Kennawa

Chronic phase shifts of the photoperiod throughout pregnancy programs glucose intolerance and insulin resistance in the rat

Extent: 10p.Shift work during pregnancy is associated with an increased risk for preterm birth and low birth weight. However, the impact upon the long term health of the children is currently unknown. In this study, we used an animal model to determine the consequences of maternal shift work exposure on the health of the adult offspring. Pregnant rats were exposed to chronic phase shifts (CPS) in their photoperiod every 3–4 days throughout gestation and the first week after birth. Adult offspring were assessed for a range of metabolic, endocrine, circadian and neurobehavioural parameters. At 3 months of age, male pups exposed to the CPS schedule in utero had increased adiposity (+29%) and hyperleptinaemia (+99% at 0700h). By 12 months of age, both male and female rats displayed hyperleptinaemia (+26% and +41% respectively) and hyperinsulinaemia (+110% and +83% respectively). 12 month old female CPS rats displayed poor glucose tolerance (+18%) and increased insulin secretion (+29%) in response to an intraperitoneal glucose tolerance test. In CPS males the glucose response was unaltered, but the insulin response was reduced by 35%. The glucose response to an insulin tolerance test was decreased by 21% in CPS females but unaltered in males. Disruption of circadian rhythmicity during gestation resulted in gender dependent metabolic consequences for the adult offspring. These results highlight the need for a thorough analysis of shift work exposure in utero on the health of the adult offspring in humans.Tamara J. Varcoe, Nicole Wight, Athena Voultsios, Mark D. Salkeld and David J. Kennawa

Análise de custos da atenção hospitalar a recém-nascidos de risco: uma comparação entre Unidade Intermediária Convencional e Unidade Canguru

O objetivo deste estudo foi realizar uma análise comparativa entre o custo da Unidade Canguru e da Unidade Intermediária Convencional sob a perspectiva do SUS, no Município do Rio de Janeiro, Brasil. A população de referência é de recém-nascidos estáveis clinicamente, que podem receber assistência nas duas modalidades de cuidado. Um modelo de análise de decisão para uma coorte hipotética de mil recém-nascidos elegíveis foi elaborado para comparar os custos em cada estratégia avaliada. As probabilidades dos eventos e o consumo de recursos de saúde foram incorporados ao modelo com base na literatura e consulta a especialistas. O custo da diária foi de R$343,53 para a 2ª etapa da Unidade Canguru e de R$394,22 para a Unidade Intermediária Convencional. O custo para a coorte hipotética foi de R$5.710.281,66 para a assistência na 2ª e 3ª etapa da Unidade Canguru e de R$7.119.865,61 para a Unidade Intermediária Convencional. A Unidade Intermediária Convencional apresentou custos 25% superiores aos da Unidade Canguru. O estudo pode contribuir para a tomada de decisão na área da saúde, além de fornecer subsídios para pesquisas relacionadas à avaliação econômica na área neonatal.The aim of this study was to compare the direct costs of implementation of the Kangaroo Method and an Intermediate Neonatal Care Unit, from the perspective of the Brazilian Unified National Health System (SUS) in Rio de Janeiro, Brazil. Newborns were eligible for inclusion if they were clinically stable and were able to receive care in those two modalities. A decision tree model was developed that incorporated baseline variables and costs into a hypothetical cohort of 1,000 newborns, according to the literature and expert opinions. Daily cost was BR$343.53 for the second stage of the Kangaroo Unit and BR$394.22 for the Intermediate Neonatal Care Unit. The total cost for the hypothetical cohort was BR$5,710,281.66 for the second and third stages of the Kangaroo Unit and R$7,119,865.61 for the Intermediate Neonatal Care Unit. The Intermediate Neonatal Care Unit cost 25% more than the Kangaroo Unit. The study can contribute to decision-making in health, in addition to providing support for studies related to economic evaluation in neonatal health.El objetivo de este estudio fue realizar un análisis comparativo entre el coste de la Unidad Canguro y la Unidad Intermedia Convencional, dentro de la perspectiva del Sistema Único de Salud (SUS) en el municipio de Río de Janeiro, Brasil. La población de referencia son los recién nacidos clínicamente estables, que pueden recibir asistencia en ambas modalidades de atención. Se diseñó un modelo de análisis de decisión para una cohorte hipotética de 1.000 bebés elegibles, con el fin de comparar los costes de cada estrategia evaluada. Las probabilidades de ocurrencias y consumo de recursos sanitarios se incorporaron al modelo de la literatura y la consulta con expertos. El coste diario fue de R$343,53 en la 2ª etapa de la Unidad Canguro y R$394,22 en la Unidad Intermedia Convencional. El coste de la cohorte hipotética fue R$5,710,281.66 para la asistencia en la segunda y tercera etapa de la Unidad Canguro y R$7,119,865.61 para la Unidad Intermedia Convencional. La Unidad Intermedia Convencional tiene costes un 25% más altos que la Unidad Canguro. El presente estudio puede contribuir a la toma de decisiones en el cuidado de la salud