Biomedical subjects

Jeffrey S Robinson

Publications and source records attributed to Jeffrey S Robinson.

At least 19 recordsLinked to original sources

PubMed2006

Gender differences in the relationship between leptin, insulin resistance and the autonomic nervous system.

OBJECTIVES: Leptin, an important hormonal regulator of body weight, has been shown to stimulate the sympathetic nervous system (SNS) in vitro although the physiological relevance remains unclear. Increased SNS activity has been implicated in the pathogenesis of insulin resistance and an increased cardiovascular risk. We have therefore investigated the relationship between leptin, insulin resistance and cardiac autonomic activity in healthy young adults. 130 healthy men and women age 20.9 years were studied. Insulin sensitivity was assessed using the IVGTT and minimal model with simultaneous measures of leptin. Cardiac autonomic activity was assessed using spectral analysis of heart rate variability. RESULTS: Women showed significantly higher fasting leptin, heart rate and cardiac sympathetic activity, and lower insulin sensitivity. Men showed inverse correlations between insulin resistance and heart rate, and between insulin resistance and cardiac sympatho-vagal ratio. Women, in contrast, showed no SNS relationship with insulin resistance, but rather an inverse correlation between leptin and the sympatho-vagal ratio, suggesting that leptin in women is associated with SNS activity. The correlation remained significant after adjustment for BMI and waist-to-hip ratio (beta=-0.33 and p=0.008). CONCLUSION: Insulin resistance and SNS activity appear to be linked, although the relationship showed marked gender differences, and the direction of causality was unclear from this cross-sectional study. Leptin appears to exert a greater effect on the SNS in women, possibly because of their greater fat mass.

Adult↗

PubMed2006

Placental restriction of fetal growth increases insulin action, growth, and adiposity in the young lamb.

Most children who are short or light at birth due to intrauterine growth restriction (IUGR) exhibit accelerated growth in infancy, termed "catch-up" growth, which together with IUGR, predicts increased risk of type 2 diabetes and obesity later in life. Placental restriction (PR) in sheep reduces size at birth, and also causes catch-up growth and increased adiposity at 6 wk of age. The physiological mechanisms responsible for catch-up growth after IUGR and its links to these adverse sequelae are unknown. Because insulin is a major anabolic hormone of infancy and its actions are commonly perturbed in these related disorders, we hypothesized that restriction of fetal growth would alter insulin secretion and sensitivity in the juvenile sheep at 1 month, which would be related to their altered growth and adiposity. We show that PR impairs glucose-stimulated insulin production, but not fasting insulin abundance or production in the young sheep. However, PR increases insulin sensitivity of circulating free fatty acids (FFAs), and insulin disposition indices for glucose and FFAs. Catch-up growth is predicted by the insulin disposition indices for amino acids and FFAs, and adiposity by that for FFAs. This suggests that catch-up growth and early-onset visceral obesity after IUGR may have a common underlying cause, that of increased insulin action due primarily to enhanced insulin sensitivity, which could account in part for their links to adverse metabolic and related outcomes in later life.

Adiposity↗

PubMed2006

Early treatment of the pregnant guinea pig with IGFs promotes placental transport and nutrient partitioning near term.

Appropriate partitioning of nutrients between the mother and conceptus is a major determinant of pregnancy success, with placental transfer playing a key role. Insulin-like growth factors (IGFs) increase in the maternal circulation during early pregnancy and are predictive of fetal and placental growth. We have previously shown in the guinea pig that increasing maternal IGF abundance in early to midpregnancy enhances fetal growth and viability near term. We now show that this treatment promotes placental transport to the fetus, fetal substrate utilization, and nutrient partitioning near term. Pregnant guinea pigs were infused with IGF-I, IGF-II (both 1 mg.kg-1.day-1) or vehicle subcutaneously from days 20-38 of pregnancy (term=69 days). Tissue uptake and placental transfer of the nonmetabolizable radio analogs [3H]methyl-D-glucose (MG) and [14C]aminoisobutyric acid (AIB) in vivo was measured on day 62. Early pregnancy exposure to elevated maternal IGF-I increased placental MG uptake by>70% (P=0.004), whereas each IGF increased fetal plasma MG concentrations by 40-50% (P<0.012). Both IGFs increased fetal tissue MG uptake (P<0.048), whereas IGF-I also increased AIB uptake by visceral organs (P=0.046). In the mother, earlier exposure to either IGF increased AIB uptake by visceral organs (P<0.014), whereas IGF-I also enhanced uptake of AIB by muscle (P=0.044) and MG uptake by visceral organs (P=0.016) and muscle (P=0.046). In conclusion, exogenous maternal IGFs in early pregnancy sustainedly increase maternal substrate utilization, placental transport of MG to the fetus, and fetal utilization of substrates near term. This was consistent with the previously observed increase in fetal growth and survival following IGF treatment.

Aminoisobutyric Acids↗

PubMed2006

Placental restriction of fetal growth reduces size at birth and alters postnatal growth, feeding activity, and adiposity in the young lamb.

Intrauterine growth restriction (IUGR) is associated with accelerated growth after birth. Together, IUGR and accelerated growth after birth predict reduced lean tissue mass and increased obesity in later life. Although placental insufficiency is a major cause of IUGR, whether it alters growth and adiposity in early postnatal life is not known. We hypothesized that placental restriction (PR) in the sheep would reduce size at birth and increase postnatal growth rate, fat mass, and feeding activity in the young lamb. PR reduced survival rate and size at birth, with soft tissues reduced to a greater extent than skeletal tissues and relative sparing of head width (P < 0.05 for all). PR did not alter absolute growth rates (i.e., the slope of the line of best fit for age vs. parameter size from birth to 45 days of age) but increased neonatal fractional growth rates (absolute growth rate relative to size at birth) for body weight (+24%), tibia (+15%) and metatarsal (+18%) lengths, hindlimb (+23%) and abdominal (+19%) circumferences, and fractional growth rates for current weight (P < 0.05) weekly throughout the first 45 days of life. PR and small size at birth reduced individual skeletal muscle weights and increased visceral adiposity in absolute and relative terms. PR also altered feeding activity, which increased with decreasing size at birth and was predictive of increased postnatal growth and adiposity. In conclusion, PR reduced size at birth and induced catch-up growth postnatally, normalizing weight and length but increasing adiposity in early postnatal life. Increased feeding activity may contribute to these alterations in growth and body composition following prenatal restraint and, if they persist, may lead to adverse metabolic and cardiovascular outcomes in later life.

Adiposity↗

PubMed2006

Neonatal respiratory distress syndrome after repeat exposure to antenatal corticosteroids: a randomised controlled trial.

BACKGROUND: The efficacy and safety of repeat doses of prenatal corticosteroids remains uncertain. Our aim was to establish whether repeat prenatal corticosteroids given to women at risk of preterm birth can reduce neonatal morbidity without harm. METHODS: In this hospital-based study, 982 women who remained at risk of preterm birth at less than 32 weeks' gestation, 7 or more days after receiving a first course of prenatal corticosteroids, were randomly assigned to receive a repeat intramuscular dose of either 11.4 mg betamethasone (as Celestone Chronodose), or saline placebo. This was repeated every week the woman remained undelivered, at less than 32 weeks' gestation, and at risk of preterm birth. Primary outcomes were occurrence and severity of neonatal respiratory distress syndrome, use and duration of oxygen and mechanical ventilation, and weight, length, and head circumference at birth and hospital discharge. Statistical analyses were on an intention to treat basis. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN48656428. FINDINGS: Fewer babies exposed to repeat corticosteroids had respiratory distress syndrome (33%vs 41%; relative risk 0.82, 95% CI 0.71-0.95, p=0.01) and fewer had severe lung disease (12%vs 20%; relative risk 0.60, 95% CI 0.46-0.79, p=0.0003) than those in the placebo group. In keeping with these benefits, babies exposed to repeat corticosteroids needed less oxygen therapy (p=0.03), and shorter duration of mechanical ventilation (p=0.01). Mean weight, length, and head circumference at birth and hospital discharge did not differ between treatment groups. Z-scores for weight (p=0.04) and head circumference (p=0.03) at birth were lower in the babies who received repeat corticosteroids although at the time of hospital discharge Z-scores did not differ between treatment groups (p=0.29 for weight, p=0.48 for head circumference). INTERPRETATION: Exposure to repeat doses of antenatal corticosteroids reduces neonatal morbidity. Pending long-term outcome results, the short-term benefits for the babies in our study support the use of repeat doses of corticosteroids in women who remain at risk of very preterm birth 7 or more days after an initial course.

Betamethasone↗

PubMed2006

Vitamins C and E and the risks of preeclampsia and perinatal complications.

BACKGROUND: Supplementation with antioxidant vitamins has been proposed to reduce the risk of preeclampsia and perinatal complications, but the effects of this intervention are uncertain. METHODS: We conducted a multicenter, randomized trial of nulliparous women between 14 and 22 weeks of gestation. Women were assigned to daily supplementation with 1000 mg of vitamin C and 400 IU of vitamin E or placebo (microcrystalline cellulose) until delivery. Primary outcomes were the risks of maternal preeclampsia, death or serious outcomes in the infants (on the basis of definitions used by the Australian and New Zealand Neonatal Network), and delivering an infant whose birth weight was below the 10th percentile for gestational age. RESULTS: Of the 1877 women enrolled in the study, 935 were randomly assigned to the vitamin group and 942 to the placebo group. Baseline characteristics of the two groups were similar. There were no significant differences between the vitamin and placebo groups in the risk of preeclampsia (6.0 percent and 5.0 percent, respectively; relative risk, 1.20; 95 percent confidence interval, 0.82 to 1.75), death or serious outcomes in the infant (9.5 percent and 12.1 percent; relative risk, 0.79; 95 percent confidence interval, 0.61 to 1.02), or having an infant with a birth weight below the 10th percentile for gestational age (8.7 percent and 9.9 percent; relative risk, 0.87; 95 percent confidence interval, 0.66 to 1.16). CONCLUSIONS: Supplementation with vitamins C and E during pregnancy does not reduce the risk of preeclampsia in nulliparous women, the risk of intrauterine growth restriction, or the risk of death or other serious outcomes in their infants. (Controlledtrials.com number, ISRCTN00416244.).

Adult↗

PubMed2006

Placental restriction alters circulating thyroid hormone in the young lamb postnatally.

Intrauterine growth restriction (IUGR) is associated with accelerated growth and increased adiposity in early life due to unknown mechanisms, which could include increased thyroid hormone (TH) action. We hypothesized that placental restriction (PR) of fetal growth would increase circulating TH concentrations and alter their response to fasting, and that these would relate to growth and body composition in the young lamb. PR reduced size at birth, increased fractional growth rates (FGRs) of soft and skeletal tissues up to 30 days of age, and slowed the ontogenic decrease in plasma total T3 and plasma total T3/T4. PR did not alter the abundance of plasma THs after short-term fasting. In general, plasma total T3 and total T3/T4 ratio correlated negatively, whereas plasma total T4 correlated positively with size at birth. Absolute growth rates of weight and crown-rump length correlated positively with plasma total T3 and total T4 between days 15 and 35. Current FGRs for weight and metatarsal length correlated positively with plasma total T3 between days 20 and 35. In conclusion, PR and small size at birth reduce plasma total T4 and increase plasma total T3 postnatally, whereas catch-up growth relates to increased abundance of the more bioactive forms of TH. Finally, greater soft tissue growth occurs in PR compared with control lambs at the same circulating TH concentrations. This suggests that PR and small size at birth may increase activation of T4 to T3 and sensitivity of soft tissues to TH, which may contribute to catch-up growth following IUGR.

Animals↗

PubMed2006

Maternal insulin-like growth factors-I and -II act via different pathways to promote fetal growth.

The placenta transports substrates and wastes between the maternal and fetal circulations. In mice, placental IGF-II is essential for normal placental development and function but, in other mammalian species, maternal circulating IGF-II is substantial and may contribute. Maternal circulating IGFs increase in early pregnancy, and early treatment of guinea pigs with either IGF-I or IGF-II increases placental and fetal weights by mid-gestation. We now show that these effects persist to enhance placental development and fetal growth and survival near term. Pregnant guinea pigs were infused with IGF-I, IGF-II (both 1 mg/kg.d), or vehicle sc from d 20-38 of pregnancy and killed on d 62 (term = 69 d). IGF-II, but not IGF-I, increased the mid-sagittal area and volume of placenta devoted to exchange by approximately 30%, the total volume of trophoblast and maternal blood spaces within the placental exchange region (+29% and +46%, respectively), and the total surface area of placenta for exchange by 39%. Both IGFs reduced resorptions, and IGF-II increased the number of viable fetuses by 26%. Both IGFs increased fetal weight by 11-17% and fetal circulating amino acid concentrations. IGF-I, but not IGF-II, reduced maternal adipose depot weights by approximately 30%. In conclusion, increased maternal IGF-II abundance in early pregnancy promotes fetal growth and viability near term by increasing placental structural and functional capacity, whereas IGF-I appears to divert nutrients from the mother to the conceptus. This suggests major and complementary roles in placental and fetal growth for increased circulating IGFs in early to mid-pregnancy.

Animals↗

PubMed2006

Hypnosis Antenatal Training for Childbirth (HATCh): a randomised controlled trial [NCT00282204].

BACKGROUND: Although medical interventions play an important role in preserving lives and maternal comfort they have become increasingly routine in normal childbirth. This may increase the risk of associated complications and a less satisfactory birth experience. Antenatal hypnosis is associated with a reduced need for pharmacological interventions during childbirth. This trial seeks to determine the efficacy or otherwise of antenatal group hypnosis preparation for childbirth in late pregnancy. METHODS/DESIGN: A single centre, randomised controlled trial using a 3 arm parallel group design in the largest tertiary maternity unit in South Australia. Group 1 participants receive antenatal hypnosis training in preparation for childbirth administered by a qualified hypnotherapist with the use of an audio compact disc on hypnosis for re-enforcement; Group 2 consists of antenatal hypnosis training in preparation for childbirth using an audio compact disc on hypnosis administered by a nurse with no training in hypnotherapy; Group 3 participants continue with their usual preparation for childbirth with no additional intervention. Women > 34 and < 39 weeks gestation, planning a vaginal birth, not in active labour, with a singleton, viable fetus of vertex presentation, are eligible to participate. Allocation concealment is achieved using telephone randomisation. Participants assigned to hypnosis groups commence hypnosis training as near as possible to 37 weeks gestation. Treatment allocations are concealed from treating obstetricians, anaesthetists, midwives and those personnel collecting and analysing data. Our sample size of 135 women/group gives the study 80% power to detect a clinically relevant fall of 20% in the number of women requiring pharmacological analgesia - the primary endpoint. We estimate that approximately 5-10% of women will deliver prior to receiving their allocated intervention. We plan to recruit 150 women/group and perform sequential interim analyses when 150 and 300 participants have been recruited. All participant data will be analysed, by a researcher blinded to treatment allocation, according to the "Intention to treat" principle with comprehensive pre-planned cost- benefit and subgroup analyses. DISCUSSION: If effective, hypnosis would be a simple, inexpensive way to improve the childbirth experience, reduce complications associated with pharmacological interventions, yield cost savings in maternity care, and this trial will provide evidence to guide clinical practice.

Journal Article↗

PubMed2006

Oral misoprostol for induction of labour at term: randomised controlled trial.

OBJECTIVE: To compare oral misoprostol solution with vaginal prostaglandin gel (dinoprostone) for induction of labour at term to determine whether misoprostol is superior. DESIGN: Randomised double blind placebo controlled trial. SETTING: Maternity departments in three hospitals in Australia. Population Pregnant women with a singleton cephalic presentation at > or = 36+6 weeks' gestation, with an indication for prostaglandin induction of labour. INTERVENTIONS: 20 mug oral misoprostol solution at ourly intervals and placebo vaginal gel or vaginal dinoprostone gel at six hourly intervals and placebo oral solution. MAIN OUTCOME MEASURES: Vaginal birth within 24 hours; uterine hyperstimulation with associated changes in fetal heart rate; caesarean section (all); and caesarean section for fetal distress. RESULTS: 741 women were randomised, 365 to the misoprostol group and 376 to the vaginal dinoprostone group. There were no significant differences between the two treatment groups in the primary outcomes: vaginal birth not achieved in 24 hours (misoprostol 168/365 (46.0%) v dinoprostone 155/376 (41.2%); relative risk 1.12, 95% confidence interval 0.95 to 1.32; P = 0.134), caesarean section (83/365 (22.7%) v 100/376 (26.6%); 0.82, 0.64 to 1.06; P = 0.127), caesarean section for fetal distress (32/365 (8.8%) v 35/376 (9.3%); 0.91, 0.57 to 1.44; P = 0.679), or uterine hyperstimulation with changes in fetal heart rate (3/365 (0.8%) v 6/376 (1.6%); 0.55, 0.14 to 2.21; P = 0.401). Although there were differences in the process of labour induction, there were no significant differences in adverse maternal or neonatal outcomes. CONCLUSIONS: This trial shows no evidence that oral misoprostol is superior to vaginal dinoprostone for induction of labour. However, it does not lead to poorer health outcomes for women or their infants, and oral treatment is preferred by women. TRIAL REGISTRATION: National Health and Medical Research Council, Perinatal Trials, PT0361.

Administration, Intravaginal↗

PubMed2006

Neonatal adrenal function after repeat dose prenatal corticosteroids: a randomized controlled trial.

OBJECTIVE: Do repeat prenatal corticosteroids suppress neonatal cortisol concentrations? STUDY DESIGN: Randomized controlled trial of women given weekly repeat corticosteroids or saline placebo, while at risk of preterm birth, until 32 weeks' gestation. RESULTS: Cord serum cortisol concentrations in infants exposed to repeat corticosteroids were similar compared with infants exposed to a single course of corticosteroids (mean difference -26 nmol/L (95% CI -57, 5 nmol/L, P = .10), as were prestress salivary cortisol concentrations on day 3 (median 16.5 vs 15.3 nmol/L, P = .96). The adrenal response to a stressor on day 3 was lower in the repeat corticosteroid group compared with the single course group (median 11.9 vs 21.4 nmol/L, P = .02). Cortisol concentrations were lower in the repeat corticosteroid group on day 7 (median 11.7 vs 18.2 nmol/L, P = .04), but not on days 14 and 21. CONCLUSION: The short- or long-term clinical impact, if any, of these changes in adrenal function needs to be determined.

Adrenal Glands↗

PubMed2006

Morning compared with evening induction of labor: a nested randomized controlled trial. A nested randomized controlled trial.

OBJECTIVE: To test the hypothesis that commencing induction of labor in the morning more closely reflects the physiologic timing of onset of labor and is associated with fewer women who remain undelivered 24 hours after cervical ripening and induction begins. METHODS: This was a nested randomized clinical trial, conducted between April 2001 and December 2004. Pregnant women at more than 36+6 weeks gestation with a cephalic presentation who were scheduled for prostaglandin induction of labor were eligible to participate. Women were randomly assigned to either admission in the morning (0800 hours) or admission in the evening (2,000 hours). The primary outcome measures were vaginal birth not achieved in 24 hours, uterine hyperstimulation with associated fetal heart rate changes, and cesarean delivery. RESULTS: A total of 620 women were entered in the trial, with 280 women in the morning admission group and 340 women in the evening admission group. There were no statistically significant differences between the timing of admission for induction and the primary trial outcomes. However, women admitted in the morning were less likely to require oxytocin infusion (morning admission 126 of 280 [45.0%] compared with evening admission 184 of 340 [54.1%]; relative risk 0.83, 95% confidence interval 0.70-0.97; P=.022). Nulliparous women admitted in the morning were less likely to require operative vaginal birth (morning admission 10 of 62 [16.1%] compared with evening admission 28 of 82 [34.2%]; relative risk 0.47, 95% confidence interval 0.25-0.90; P=.015). CONCLUSION: For women who require induction of labor, consideration should be given to admission in the morning rather than admission in the evening. CLINICAL TRIAL REGISTRATION: Australian Clinical Trials Registry, www.actr.org.au, 12606000156583.

Adult↗

PubMed2005

Effect of treatment of gestational diabetes mellitus on pregnancy outcomes.

BACKGROUND: We conducted a randomized clinical trial to determine whether treatment of women with gestational diabetes mellitus reduced the risk of perinatal complications. METHODS: We randomly assigned women between 24 and 34 weeks' gestation who had gestational diabetes to receive dietary advice, blood glucose monitoring, and insulin therapy as needed (the intervention group) or routine care. Primary outcomes included serious perinatal complications (defined as death, shoulder dystocia, bone fracture, and nerve palsy), admission to the neonatal nursery, jaundice requiring phototherapy, induction of labor, cesarean birth, and maternal anxiety, depression, and health status. RESULTS: The rate of serious perinatal complications was significantly lower among the infants of the 490 women in the intervention group than among the infants of the 510 women in the routine-care group (1 percent vs. 4 percent; relative risk adjusted for maternal age, race or ethnic group, and parity, 0.33; 95 percent confidence interval, 0.14 to 0.75; P=0.01). However, more infants of women in the intervention group were admitted to the neonatal nursery (71 percent vs. 61 percent; adjusted relative risk, 1.13; 95 percent confidence interval, 1.03 to 1.23; P=0.01). Women in the intervention group had a higher rate of induction of labor than the women in the routine-care group (39 percent vs. 29 percent; adjusted relative risk, 1.36; 95 percent confidence interval, 1.15 to 1.62; P<0.001), although the rates of cesarean delivery were similar (31 percent and 32 percent, respectively; adjusted relative risk, 0.97; 95 percent confidence interval, 0.81 to 1.16; P=0.73). At three months post partum, data on the women's mood and quality of life, available for 573 women, revealed lower rates of depression and higher scores, consistent with improved health status, in the intervention group. CONCLUSIONS: Treatment of gestational diabetes reduces serious perinatal morbidity and may also improve the woman's health-related quality of life.

Adult↗

PubMed2005

Polymorphisms in immunoregulatory genes and the risk of histologic chorioamnionitis in Caucasoid women: a case control study.

BACKGROUND: Chorioamnionitis is a common underlying cause of preterm birth (PTB). It is hypothesised that polymorphisms in immunoregulatory genes influence the host response to infection and subsequent preterm birth. The relationship between histologic chorioamnionitis and 22 single nucleotide polymorphisms in 11 immunoregulatory genes was examined in a case-control study. METHODS: Placentas of 181 Caucasoid women with spontaneous PTB prior to 35 weeks were examined for histologic chorioamnionitis. Polymorphisms in genes IL1A, IL1B, IL1RN, IL1R1, tumour necrosis factor (TNF), IL4, IL6, IL10, transforming growth factor beta-1 (TGFB1), Fas (TNFRSF6), and mannose-binding lectin (MBL2) were genotyped by polymerase chain reaction and sequence specific primers. Multivariable logistic regression including demographic and genetic variables and Kaplan-Meier survival analyses of genotype frequencies and pregnancy outcome were performed. RESULTS: Sixty-nine (34%) women had histologic evidence of acute chorioamnionitis. Carriage of the IL10-1082A/-819T/592A (ATA) haplotype [Multivariable Odds ratio (MOR) 1.9, P = 0.05] and MBL2 codon 54Asp allele (MOR 2.0, P = 0.04), were positively associated with chorioamnionitis, while the TNFRSF6-1377A/-670G (AG) haplotype (MOR 0.4, P = 0.03) and homozygosity for TGFB1-800G/509T (GT) haplotype (MOR 0.2, P = 0.04) were negatively associated. CONCLUSION: These findings demonstrate that polymorphisms in immunoregulatory genes IL10, MBL2, TNFRSF6 and TGFB1 may influence susceptibility to chorioamnionitis.

Journal Article↗

PubMed2005

Progesterone supplementation for preventing preterm birth: a systematic review and meta-analysis.

AIM: The aim of this study is to assess the role of progesterone in preterm birth prevention. METHODS: A MEDLINE search (from 1966 to the present; date of last search January 2005) was performed - using the key words progesterone, pregnancy, preterm birth, preterm labor, and randomized, controlled trial - in order to identify randomized, controlled trials in which progesterone (either intramuscular or vaginal administration) was compared with placebo or no treatment. Data were extracted and a meta-analysis was performed. RESULTS: Seven randomized, controlled trials were identified. Women who received progesterone were statistically significantly less likely to give birth before 37 weeks (seven studies, 1020 women, RR = 0.58, 95% CI = 0.48-0.70), to have an infant with birth weight of < or =2.5 kg (six studies, 872 infants, RR = 0.62, 95% CI = 0.49-0.78), or to have an infant diagnosed with intraventricular hemorrhage (one study, 458 infants, RR = 0.25, 95% CI = 0.08-0.82). CONCLUSIONS: For progesterone supplementation to be advocated for women at the risk of preterm birth, the prolongation of gestation demonstrated in this meta-analysis must translate into improved infant outcomes, including a reduction in mortality. There is currently insufficient information to allow recommendations regarding the optimal dose, route, and timing of administration of progesterone supplementation.

Administration, Intravaginal↗

PubMed2005

Developmental origins of the metabolic syndrome: prediction, plasticity, and programming.

The "fetal" or "early" origins of adult disease hypothesis was originally put forward by David Barker and colleagues and stated that environmental factors, particularly nutrition, act in early life to program the risks for adverse health outcomes in adult life. This hypothesis has been supported by a worldwide series of epidemiological studies that have provided evidence for the association between the perturbation of the early nutritional environment and the major risk factors (hypertension, insulin resistance, and obesity) for cardiovascular disease, diabetes, and the metabolic syndrome in adult life. It is also clear from experimental studies that a range of molecular, cellular, metabolic, neuroendocrine, and physiological adaptations to changes in the early nutritional environment result in a permanent alteration of the developmental pattern of cellular proliferation and differentiation in key tissue and organ systems that result in pathological consequences in adult life. This review focuses on those experimental studies that have investigated the critical windows during which perturbations of the intrauterine environment have major effects, the nature of the epigenetic, structural, and functional adaptive responses which result in a permanent programming of cardiovascular and metabolic function, and the role of the interaction between the pre- and postnatal environment in determining final health outcomes.

Aging↗

PubMed2004

Chronic maternal feed restriction impairs growth but increases adiposity of the fetal guinea pig.

Small size at birth has been associated with an increased risk of central obesity and reduced lean body mass in adult life. This study investigated the time of onset of prenatally induced obesity, which occurs after maternal feed restriction, in the guinea pig, a species that, like the human, develops substantial adipose tissue stores before birth. We examined the effect of maternal feed restriction [70% ad libitum intake from 4 wk before to midpregnancy, then 90% until day 60 gestation (term approximately 69 days)] on fetal growth and body composition in the guinea pig. Maternal feed restriction reduced fetal (-39%) and placental (-30%) weight at 60 days gestation and reduced liver, biceps muscle, spleen, and thymus weights, relative to fetal weight, while relative weights of brain, lungs, and interscapular and retroperitoneal fat pads were increased. In the interscapular depot, maternal feed restriction decreased the volume density of multilocular fat and increased that of unilocular fat, resulting in an increased relative weight of interscapular unilocular fat. Maternal feed restriction did not alter the relative weight of perirenal fat or the volume density of adipocyte populations within the depot but increased unilocular lipid locule size. Maternal feed restriction in the guinea pig is associated with decreased weight of major organs, including liver and skeletal muscle, but increased adiposity of the fetus, with relative sparing of unilocular adipose tissue. If this early-onset obesity persists, it may contribute to the metabolic and cardiovascular dysfunction that these offspring of feed-restricted mothers develop as adults.

Adipose Tissue↗

PubMed2004

Changing healthcare organisations to change clinical performance.

We propose the formation of evidence-based clinical practice support units in hospitals and clinical research implementation networks. The purpose of these initiatives will be to increase the uptake of beneficial forms of care and remove harmful or ineffective practices. They will bring together clinicians and other professionals to improve clinical care across the healthcare system.

Australia↗