Association of early and late maternal smoking during pregnancy with offspring body mass index at 4 to 5 years of age

The objective was to investigate the association between early and late maternal smoking during pregnancy on offspring body mass index (BMI). We undertook a retrospective cohort study using linked records from the Women's and Children's Health Network in South Australia. Among a cohort of women delivering a singleton, live-born infants between January 2000 and December 2005 (n=7658), 5961 reported not smoking during pregnancy, 297 reported quitting smoking during the first trimester of pregnancy, and 1400 reported continued smoking throughout pregnancy. Trained nurses measured the height and weight of the children at preschool visits in a state-wide surveillance programme. The main outcome measure was age- and sex-specific BMI z-score. At 4 to 5 years, mean (s.d.) BMI z-score was 0.40 (1.05), 0.60 (1.07) and 0.65 (1.18) in children of mothers who reported never smoking, quitting smoking and continued smoking during pregnancy, respectively. Compared with the group of non-smokers, both quitting smoking and continued smoking were associated with an increase in child BMI z-score of 0.15 (95% confidence interval: 0.01-0.29) and 0.21 (0.13-0.29), respectively. A significant dose-response relationship was also observed between the number of cigarettes smoked per day on average during the second half of pregnancy and the increase in offspring BMI z-score (P<0.001). In conclusion, any maternal smoking in pregnancy, even if mothers quit, is associated with an increase in offspring BMI at 4 to 5 years of age.L. E. Grzeskowiak, N. A. Hodyl, M. J. Stark, J. L. Morrison and V. L. Clifto

Novel insights, challenges and practical implications of DOHaD-omics research

Research investigating the developmental origins of health and disease (DOHaD) has never had the technology to investigate physiology in such a data-rich capacity and at such a microlevel as it does now.A symposium at the inaugural meeting of the DOHaD Society of Australia and New Zealand outlined the advantages and challenges of using "-omics" technologies in DOHaD research.DOHaD studies with -omics approaches to generate large, rich datasets were discussed.We discuss implications for policy and practice and make recommendations to facilitate successful translation of results of future DOHaD-omics studies.Nicolette A Hodyl and Beverly Muhlhausle

The important role for intravenous iron in perioperative patient blood management in major abdominal surgery: a randomized controlled trial

Objective: To determine if preoperative intravenous (IV) iron improves outcomes in abdominal surgery patients. Summary Background Data: Preoperative iron deficiency anemia (IDA) occurs frequently; however if left untreated, increases the risk of blood transfusion allogeneic blood transfusion (ABT). Limited evidence supports IDA treatment with preoperative IV iron. This randomized controlled trial aimed to determine whether perioperative IV iron reduced the need for ABT. Methods: Between August 2011 and November 2014, 72 patients with IDA were assigned to receive either IV iron or usual care. The primary endpoint was incidence of ABT. Secondary endpoints were various hemoglobin (Hb) levels, change in Hb between time points, length of stay, iron status, morbidity, mortality, and quality of life 4 weeks postsurgery. Results: A 60% reduction in ABT was observed in the IV iron group compared with the usual care group (31.25% vs 12.5%). Hb values, although similar at randomization, improved by 0.8 g/dL with IV iron compared with 0.1 g/dL with usual care (P = 0.01) by the day of admission. The IV iron group had higher Hb 4 weeks after discharge compared with the usual care group (1.9 vs 0.9 g/dL, P = 0.01), and a shorter length of stay (7.0 vs 9.7 d, P = 0.026). There was no difference in discharge Hb levels, morbidity, mortality, or quality of life. Conclusions: Administration of perioperative IV iron reduces the need for blood transfusion, and is associated with a shorter hospital stay, enhanced restoration of iron stores, and a higher mean Hb concentration 4 weeks after surgery.Bernd Froessler, Peter Palm, Ingo Weber, Nicolette A. Hodyl, Rajvinder Singh and Elizabeth M. Murph

MicroRNAs regulating Toll Like Receptor inflammatory pathways in preterm and term placenta and cord blood

Abstracts - P1.49Abstract not availableNatalie Aboustate, Vicki Clifton, Michael Stark, Nicolette Hody

Developmental perturbation induced by maternal asthma during pregnancy: The short- and long-term impacts on offspring

Extent: 8p.Maternal asthma is a common disease to complicate human pregnancy. Epidemiological studies have identified that asthma during pregnancy increases the risk of a number of poor outcomes for the neonate including growth restriction, lower birthweight, preterm delivery, neonatal resuscitation, and stillbirth. Asthma therefore represents a significant health burden to society and could have an impact on the lifelong health of the children of women with asthma. Our research has identified that maternal asthma in pregnancy induces placental dysfunction and developmental perturbation in the fetus in a sex specific manner. These alterations in development could increase the risk of metabolic disease in adulthood of children of asthmatic mothers, especially females. In this paper, we will discuss the evidence currently available that supports the hypothesis that children of mothers with asthma may be at risk of lifelong health complications which include diabetes and hypertension.Vicki L. Clifton, Michael Davies, Vivienne Moore, Ian M. R. Wright, Zainab Ali, and Nicolette A. Hody

Developmental perturbation induced by maternal asthma during pregnancy: The short- and long-term impacts on offspring

Extent: 8p.Maternal asthma is a common disease to complicate human pregnancy. Epidemiological studies have identified that asthma during pregnancy increases the risk of a number of poor outcomes for the neonate including growth restriction, lower birthweight, preterm delivery, neonatal resuscitation, and stillbirth. Asthma therefore represents a significant health burden to society and could have an impact on the lifelong health of the children of women with asthma. Our research has identified that maternal asthma in pregnancy induces placental dysfunction and developmental perturbation in the fetus in a sex specific manner. These alterations in development could increase the risk of metabolic disease in adulthood of children of asthmatic mothers, especially females. In this paper, we will discuss the evidence currently available that supports the hypothesis that children of mothers with asthma may be at risk of lifelong health complications which include diabetes and hypertension.Vicki L. Clifton, Michael Davies, Vivienne Moore, Ian M. R. Wright, Zainab Ali, and Nicolette A. Hody

Developmental perturbation induced by maternal asthma during pregnancy: The short- and long-term impacts on offspring

Extent: 8p.Maternal asthma is a common disease to complicate human pregnancy. Epidemiological studies have identified that asthma during pregnancy increases the risk of a number of poor outcomes for the neonate including growth restriction, lower birthweight, preterm delivery, neonatal resuscitation, and stillbirth. Asthma therefore represents a significant health burden to society and could have an impact on the lifelong health of the children of women with asthma. Our research has identified that maternal asthma in pregnancy induces placental dysfunction and developmental perturbation in the fetus in a sex specific manner. These alterations in development could increase the risk of metabolic disease in adulthood of children of asthmatic mothers, especially females. In this paper, we will discuss the evidence currently available that supports the hypothesis that children of mothers with asthma may be at risk of lifelong health complications which include diabetes and hypertension.Vicki L. Clifton, Michael Davies, Vivienne Moore, Ian M. R. Wright, Zainab Ali, and Nicolette A. Hody

Sex-specific associations between cortisol and birth weight in pregnancies complicated by asthma are not due to differential glucocorticoid receptor expression

Background: Fetal growth inhibition is a known sequelae of in utero glucocorticoid exposure and has long-term consequences for adult health. Sex-specific fetal growth patterns are observed in pregnancies with maternal asthma and may be due to differential sensitivity of the placenta to glucocorticoids. It is currently unknown whether expression of the placental glucocorticoid receptor (GR) becomes altered with asthma or the use of inhaled corticosteroids. Methods: Pregnant women with mild asthma (n¼52), moderate-severe asthma (n¼71) and without asthma (n¼51) were recruited at John Hunter Hospital, Newcastle, Australia. At delivery, placentae and cord blood were collected, and fetal sex and birth weight were recorded. Placental GR heterogeneous nuclear RNA (hnRNA), mRNA and protein were measured and cord blood cortisol concentrations were assessed. Results Placental GR gene activity increased with cortisol exposure but decreased with inhaled corticosteroid treatment (p¼0.05). With maternal asthma, female birth weight centiles were inversely associated with cortisol (r¼_0.286, p¼0.017) and, despite a decrease in placental GR mRNA (p¼0.003), placental GRa protein levels were unchanged. In males, no change to cortisol, birth weight or placental GR were evident in pregnancies with asthma. Together, these results indicate that in pregnancies complicated by asthma, placental GR gene activity, but not mRNA expression or protein levels, is dependent on cortisol and inhaled corticosteroid treatment. Conclusions The sex-specific associations between cortisol and birth weight observed in pregnancies with asthma are not due to altered GR expression; however, they may be due to differential glucocorticoid sensitivity via preferential transcription of GR isoforms or posttranslational modifications.Nicolette A Hodyl, Hayley Wyper, Annette Osei-Kumah, Naomi Scott, Vanessa E Murphy, Peter Gibson, Roger Smith and Vicki L Clifto

Salience versus magnitude in the measurement of the cortisol awakening response

Pulsatile ultradian secretion of cortisol, rarely studied in salivary data, has functional importance in hypothalamic pituitary adrenal (HPA) axis regulation. The first daily ultradian episode, the cortisol awakening response (CAR), was examined in healthy adults, in 5-min secretion rates of salivary cortisol from electronically monitored awakening time to 1.25 h. Aggregated rates revealed a cubic trend, with wave-length of almost exactly 1 h, as predicted from known ultradian periodicity. Peak secretion rate occurred 20-min post-awakening. Peak (20-min) to trough (59-min) amplitude (PTA) expressed a salient signal shape. Rates rose steeply to and from peak, and major secretion was packaged into a few 5-min intervals, inconsistent with normal or uniform distribution of 5-min rates, but consistent with known pulsatile cortisol delivery. Null hypotheses asserting normal or uniform distributions were rejected. Maximal rates overwhelmingly occurred before and minimal rates after 30-mins, with degree of extremity at each polarity significantly positively correlated. To demonstrate utility and reliability of PTA estimation in a clinically relevant domain, re- analyses of a previously published study were conducted. Data from only three saliva samples were used, given importance of cost considerations for many CAR researchers. Difference between mean rates before and after 30-min yielded a simple salience index, highly correlated with PTA derived from full 5-min interval data. CAR salience performed significantly better than traditional AUCi magnitude in discriminating control cases (higher inferred amplitude) and cases with Seasonal Affective Disorder (lower inferred amplitude). Evidence suggested that low AUCi may be more sensitive in identifying within-subject changes (e.g. more depressed mood in winter among SAD cases) and low CAR salience better at revealing enduring between-subjects associations (e.g. underlying disorder vulnerability). Since both PTA salience and AUCi magnitude can be analysed and compared using exactly the same data from the same commonly used saliva sampling points, further research is warranted into the importance of individual differences in patterns of cortisol delivery, not just how much is delivered

Day differences in the cortisol awakening response predict day differences in synaptic plasticity in the brain

The cortisol awakening response (CAR) is the most prominent, dynamic and variable part of the circadian pattern of cortisol secretion. Despite this its precise purpose is unknown. Aberrant patterns of the CAR are associated with impaired physical and mental health and reduced cognitive function, suggesting that it may have a pervasive role or roles. It has been suggested that the CAR primes the brain for the expected demands of the day but the mechanisms underlying this process are unknown. We examined temporal covariation of the CAR and rapid transcranial magnetic stimulation (rTMS)-induced long term depression (LTD)-like responses in the motor cortex. Plasticity was evaluated across 180 measures from 5 time points on 4 sessions across 9 researcher participants, mean age 25 ± 2.5 years. Plasticity estimates were obtained in the afternoon after measurement of the CAR on 4 days, at least 3 days apart. As both CAR magnitude and rTMS-induced responses are variable across days we hypothesised that days with larger than individual average CARs would be associated with a greater than individual average plasticity response. This was confirmed by mixed regression modelling where variation in the CAR predicted variation in rTMS-induced responses (Df: 1, 148.24; F: 10.41; p=0.002). As the magnitude of the CAR is regulated by the ‘master’ circadian CLOCK, and synaptic plasticity is known to be modulated by peripheral ‘slave’ CLOCK genes, we suggest that the CAR may be a mediator between the master and peripheral circadian systems to entrain daily levels of synaptic plasticity