Publications by authors named "Julie A Owens"

79 Publications

Impact of maternal education on response to lifestyle interventions to reduce gestational weight gain: individual participant data meta-analysis.

BMJ Open 2019 08 1;9(8):e025620. Epub 2019 Aug 1.

Mother-Infant Department, University of Modena and Reggio Emilia, Modena, Italy.

Objectives: To identify if maternal educational attainment is a prognostic factor for gestational weight gain (GWG), and to determine the differential effects of lifestyle interventions (diet based, physical activity based or mixed approach) on GWG, stratified by educational attainment.

Design: Individual participant data meta-analysis using the previously established International Weight Management in Pregnancy (i-WIP) Collaborative Group database (https://iwipgroup.wixsite.com/collaboration). Preferred Reporting Items for Systematic reviews and Meta-Analysis of Individual Participant Data Statement guidelines were followed.

Data Sources: Major electronic databases, from inception to February 2017.

Eligibility Criteria: Randomised controlled trials on diet and physical activity-based interventions in pregnancy. Maternal educational attainment was required for inclusion and was categorised as higher education (≥tertiary) or lower education (≤secondary).

Risk Of Bias: Cochrane risk of bias tool was used.

Data Synthesis: Principle measures of effect were OR and regression coefficient.

Results: Of the 36 randomised controlled trials in the i-WIP database, 21 trials and 5183 pregnant women were included. Women with lower educational attainment had an increased risk of excessive (OR 1.182; 95% CI 1.008 to 1.385, p =0.039) and inadequate weight gain (OR 1.284; 95% CI 1.045 to 1.577, p =0.017). Among women with lower education, diet basedinterventions reduced risk of excessive weight gain (OR 0.515; 95% CI 0.339 to 0.785, p = 0.002) and inadequate weight gain (OR 0.504; 95% CI 0.288 to 0.884, p=0.017), and reduced kg/week gain (B -0.055; 95% CI -0.098 to -0.012, p=0.012). Mixed interventions reduced risk of excessive weight gain for women with lower education (OR 0.735; 95% CI 0.561 to 0.963, p=0.026). Among women with high education, diet based interventions reduced risk of excessive weight gain (OR 0.609; 95% CI 0.437 to 0.849, p=0.003), and mixed interventions reduced kg/week gain (B -0.053; 95% CI -0.069 to -0.037,p<0.001). Physical activity based interventions did not impact GWG when stratified by education.

Conclusions: Pregnant women with lower education are at an increased risk of excessive and inadequate GWG. Diet based interventions seem the most appropriate choice for these women, and additional support through mixed interventions may also be beneficial.
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http://dx.doi.org/10.1136/bmjopen-2018-025620DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6688690PMC
August 2019

Sex-specific programming of adult insulin resistance in guinea pigs by variable perinatal growth induced by spontaneous variation in litter size.

Am J Physiol Regul Integr Comp Physiol 2019 04 8;316(4):R352-R361. Epub 2019 Feb 8.

Robinson Research Institute, The University of Adelaide , Adelaide, South Australia , Australia.

Intrauterine growth restriction (IUGR) and subsequent neonatal catch-up growth are implicated in programming of insulin resistance later in life. Spontaneous IUGR in the guinea pig, due to natural variation in litter size, produces offspring with asymmetric IUGR and neonatal catch-up growth. We hypothesized that spontaneous IUGR and/or accelerated neonatal growth would impair insulin sensitivity in adult guinea pigs. Insulin sensitivity of glucose metabolism was determined by hyperinsulinemic-euglycemic clamp (HEC) in 38 (21 male, 17 female) young adult guinea pigs from litters of two-to-four pups. A subset (10 male, 8 female) were infused with d-[3-H]glucose before and during the HEC to determine rates of basal and insulin-stimulated glucose utilization, storage, glycolysis, and endogenous glucose production. n males, the insulin sensitivity of whole body glucose uptake ( r = 0.657, P = 0.002) and glucose utilization ( r = 0.884, P = 0.004) correlated positively and independently with birth weight, but not with neonatal fractional growth rate (FGR). In females, the insulin sensitivity of whole body and partitioned glucose metabolism was not related to birth weight, but that of endogenous glucose production correlated negatively and independently with FGR ( r = -0.815, P = 0.025). Thus, perinatal growth programs insulin sensitivity of glucose metabolism in the young adult guinea pig and in a sex-specific manner; impaired insulin sensitivity, including glucose utilization, occurs after IUGR in males and impaired hepatic insulin sensitivity after rapid neonatal growth in females.
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http://dx.doi.org/10.1152/ajpregu.00341.2018DOI Listing
April 2019

Prenatal Diet and Child Growth at 18 Months.

Pediatrics 2018 09 8;142(3). Epub 2018 Aug 8.

Discipline of Obstetrics and Gynaecology, Robinson Research Institute and.

Objective: Our objective was to evaluate the effect of an antenatal dietary and lifestyle intervention in pregnant women who are overweight or obese on child outcomes at age 18 months.

Methods: We conducted a follow-up study of children at 18 months of age who were born to women who participated in the Limiting Weight Gain in Overweight and Obese Women during Pregnancy to Improve Health Outcomes randomized trial. The primary follow-up study outcome was prevalence of child BMI scores >85th percentile. Secondary study outcomes included a range of anthropometric measures, neurodevelopment, general health, and child feeding. Intention to treat principles were used in analyses, according to the treatment group allocated at randomization.

Results: A total of 1602 children were assessed at age 18 months (lifestyle advice, = 816; standard care, = 786), representing 75.0% of the eligible sample ( = 2136). There were no statistically significant differences in the prevalence of child BMI scores >85th percentile for children born to women in the lifestyle advice group, compared with the standard care group (lifestyle advice, 505 [47.11%] versus standard care, 483 [45.36%]; adjusted relative risk: 1.04; 95% confidence interval: 0.94 to 1.16; = .45). There was no evidence of effects on child growth, adiposity, neurodevelopment, or dietary and physical activity patterns.

Conclusions: There is no evidence that providing pregnant women who were overweight or obese with an antenatal dietary and lifestyle intervention altered 18-month child growth and adiposity.
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http://dx.doi.org/10.1542/peds.2018-0035DOI Listing
September 2018

Effects of an antenatal dietary intervention in overweight and obese women on 6 month infant outcomes: follow-up from the LIMIT randomised trial.

Int J Obes (Lond) 2018 07 30;42(7):1326-1335. Epub 2018 Jan 30.

Discipline of Obstetrics & Gynaecology, and The Robinson Research Institute, The University of Adelaide, Adelaide, SA, Australia.

Background: The immediate impact of providing an antenatal dietary intervention during pregnancy has been extensively studied, but little is known of the effects beyond the neonatal period. Our objective was to evaluate the effect of an antenatal dietary intervention in overweight or obese women on infant outcomes 6 months after birth.

Methods: We conducted a follow up study of infants born to women who participated in the LIMIT trial during pregnancy. Live-born infants at 6-months of age, and whose mother provided consent to ongoing follow-up were eligible. The primary follow-up study endpoint was the incidence of infant BMI z-score ≥90th centile for infant sex and age. Secondary study outcomes included a range of infant anthropometric measures, neurodevelopment, general health, and infant feeding. Analyses used intention to treat principles according to the treatment group allocated in pregnancy. Missing data were imputed and analyses adjusted for maternal early pregnancy BMI, parity, study centre, socioeconomic status, age, and smoking status. Outcome assessors were blinded to the allocated treatment group.

Results: A total of 1754 infants were assessed at age 6 months (Lifestyle Advice n = 869; Standard Care n = 885), representing 82.1% of the eligible sample (n = 2136). There were no statistically significant differences in the incidence of infant BMI z-score ≥90th centile for infants born to women in the Lifestyle Advice group, compared with the Standard Care group (Lifestyle Advice 233 (21.71%) vs. Standard Care 233 (21.90%); adjusted relative risk (aRR) 0.99; 95% confidence interval 0.82 to 1.18; p = 0.88). There were no other effects on infant growth, adiposity, or neurodevelopment.

Conclusion: Providing pregnant women who were overweight or obese with an antenatal dietary and lifestyle intervention did not alter 6-month infant growth and adiposity.

Trial Registration: Australian and New Zealand Clinical Trials Registry (ACTRN12607000161426).
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http://dx.doi.org/10.1038/s41366-018-0019-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6054603PMC
July 2018

Late-gestation maternal dietary methyl donor and cofactor supplementation in sheep partially reverses protection against allergic sensitization by IUGR.

Am J Physiol Regul Integr Comp Physiol 2018 01 4;314(1):R22-R33. Epub 2017 Oct 4.

Robinson Research Institute, University of Adelaide , Adelaide, South Australia , Australia.

Perinatal exposures are associated with altered risks of childhood allergy. Human studies and our previous work suggest that restricted growth in utero (IUGR) is protective against allergic disease. The mechanisms are not clearly defined, but reduced fetal abundance and altered metabolism of methyl donors are hypothesized as possible underlying mechanisms. Therefore, we examined whether late-gestation maternal dietary methyl donor and cofactor supplementation of the placentally restricted (PR) sheep pregnancy would reverse allergic protection in progeny. Allergic outcomes were compared between progeny from control pregnancies (CON; n = 49), from PR pregnancies without intervention (PR; n = 28), and from PR pregnancies where the dam was fed a methyl donor plus cofactor supplement from day 120 of pregnancy until delivery (PR + Methyl; n = 25). Both PR and PR + Methyl progeny were smaller than CON; supplementation did not alter birth size. PR was protective against cutaneous hypersensitivity responses to ovalbumin (OVA; P < 0.01 in singletons). Cutaneous hypersensitivity responses to OVA in PR + Methyl progeny were intermediate to and not different from the responses of CON and PR sheep. Cutaneous hypersensitivity responses to house dust mites did not differ between treatments. In singleton progeny, upper dermal mast cell density was greater in PR + Methyl than in PR or CON (each P < 0.05). The differences in the cutaneous allergic response were not explained by treatment effects on circulating immune cells or antibodies. Our results suggest that mechanisms underlying in utero programming of allergic susceptibility by IUGR and methyl donor availability may differ and imply that late-gestation methyl donor supplementation may increase allergy risk.
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http://dx.doi.org/10.1152/ajpregu.00549.2016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5866368PMC
January 2018

Maternal methyl donor and cofactor supplementation in late pregnancy increases β-cell numbers at 16 days of life in growth-restricted twin lambs.

Am J Physiol Endocrinol Metab 2017 10 5;313(4):E381-E390. Epub 2017 Jul 5.

Robinson Research Institute and Adelaide Medical School, University of Adelaide, South Australia, Australia.

Restricted growth before birth (IUGR) increases adult risk of Type 2 diabetes by impairing insulin sensitivity and secretion. Altered fetal one-carbon metabolism is implicated in developmental programming of adult health and disease by IUGR. Therefore, we evaluated effects of maternal dietary supplementation with methyl donors and cofactors (MMDS), designed to increase fetal supply, on insulin action in the spontaneously IUGR twin lamb. In vivo glucose-stimulated insulin secretion and insulin sensitivity were measured at in singleton controls (CON, = 7 lambs from 7 ewes), twins (IUGR, = 8 lambs from 8 ewes), and twins from ewes that received MMDS (2 g rumen-protected methionine, 300 mg folic acid, 1.2 g sulfur, 0.7 mg cobalt) daily from 120 days after mating (~0.8 of term) until delivery (IUGR+MMDS, = 8 lambs from 4 ewes). Body composition and pancreas morphometry were assessed in lambs at IUGR reduced size at birth and increased neonatal fractional growth rate. MMDS normalized long bone lengths but not other body dimensions of IUGR lambs at birth. IUGR did not impair glucose control or insulin action at , compared with controls. MMDS increased metabolic clearance rate of insulin and increased β-cell numerical density and tended to improve insulin sensitivity, compared with untreated IUGR lambs. This demonstrates that effects of late-pregnancy methyl donor supplementation persist until at least the third week of life. Whether these effects of MMDS persist beyond early postnatal life and improve metabolic outcomes after IUGR in adults and the underlying mechanisms remain to be determined.
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http://dx.doi.org/10.1152/ajpendo.00033.2017DOI Listing
October 2017

Paternal obesity modifies the effect of an antenatal lifestyle intervention in women who are overweight or obese on newborn anthropometry.

Sci Rep 2017 05 8;7(1):1557. Epub 2017 May 8.

The University of Adelaide, Discipline of Obstetrics & Gynaecology, and Robinson Research Institute, Adelaide, South Australia, Australia.

The contribution of paternal obesity to pregnancy outcomes has been little described. Our aims were to determine whether the effect of an antenatal maternal dietary and lifestyle intervention among women who are overweight or obese on newborn adiposity, was modified by paternal obesity. We conducted a secondary analysis of a multicenter randomised trial. Pregnant women with BMI ≥25 kg/m received either Lifestyle Advice or Standard Care. Paternal anthropometric measures included height, weight, BMI; waist, hip, calf and mid-upper arm circumferences; biceps and calf skinfold thickness measurements (SFTM); and percentage body fat. Newborn anthropometric outcomes included length; weight; head, arm, abdominal, and chest circumferences; biceps, triceps, subscapular, suprailiac, thigh, and lateral abdominal wall SFTM; and percentage body fat. The effect of an antenatal maternal dietary and lifestyle intervention among women who were overweight or obese on neonatal anthropometric measures, was significantly modified by paternal BMI ≥35.0 kg/m, with a significantly smaller infant triceps, suprailiac, and thigh SFTM, and percent fat mass, compared with that observed in offspring of lean fathers. Further research is required to determine whether our observed associations are causal, and whether paternal weight loss prior to conception is a potential strategy to reduce the intergenerational effects of obesity.
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http://dx.doi.org/10.1038/s41598-017-01672-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5431557PMC
May 2017

Use of the hyperinsulinemic euglycemic clamp to assess insulin sensitivity in guinea pigs: dose response, partitioned glucose metabolism, and species comparisons.

Am J Physiol Regul Integr Comp Physiol 2017 07 24;313(1):R19-R28. Epub 2017 Apr 24.

Robinson Research Institute, The University of Adelaide, Adelaide, South Australia, Australia;

The guinea pig is an alternate small animal model for the study of metabolism, including insulin sensitivity. However, only one study to date has reported the use of the hyperinsulinemic euglycemic clamp in anesthetized animals in this species, and the dose response has not been reported. We therefore characterized the dose-response curve for whole body glucose uptake using recombinant human insulin in the adult guinea pig. Interspecies comparisons with published data showed species differences in maximal whole body responses (guinea pig ≈ human < rat < mouse) and the insulin concentrations at which half-maximal insulin responses occurred (guinea pig > human ≈ rat > mouse). In subsequent studies, we used concomitant d-[3-H]glucose infusion to characterize insulin sensitivities of whole body glucose uptake, utilization, production, storage, and glycolysis in young adult guinea pigs at human insulin doses that produced approximately half-maximal (7.5 mU·min·kg) and near-maximal whole body responses (30 mU·min·kg). Although human insulin infusion increased rates of glucose utilization (up to 68%) and storage and, at high concentrations, increased rates of glycolysis in females, glucose production was only partially suppressed (~23%), even at high insulin doses. Fasting glucose, metabolic clearance of insulin, and rates of glucose utilization, storage, and production during insulin stimulation were higher in female than in male guinea pigs ( < 0.05), but insulin sensitivity of these and whole body glucose uptake did not differ between sexes. This study establishes a method for measuring partitioned glucose metabolism in chronically catheterized conscious guinea pigs, allowing studies of regulation of insulin sensitivity in this species.
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http://dx.doi.org/10.1152/ajpregu.00028.2017DOI Listing
July 2017

The effects of dietary and lifestyle interventions among pregnant women who are overweight or obese on longer-term maternal and early childhood outcomes: protocol for an individual participant data (IPD) meta-analysis.

Syst Rev 2017 03 9;6(1):51. Epub 2017 Mar 9.

The University of Adelaide, Discipline of Obstetrics & Gynaecology, and Robinson Research Institute, Adelaide, South Australia, Australia.

Background: The aim of this individual participant data meta-analysis (IPDMA) is to evaluate the effects of dietary and lifestyle interventions among pregnant women who are overweight or obese on later maternal and early childhood outcomes at ages 3-5 years.

Methods/design: We will build on the established International Weight Management in Pregnancy (i-WIP) IPD Collaborative Network, having identified researchers who have conducted randomised dietary and lifestyle interventions among pregnant women who are overweight or obese, and where ongoing childhood follow-up of participants has been or is being undertaken. The primary maternal outcome is a diagnosis of maternal metabolic syndrome. The primary childhood outcome is BMI above 90%. We have identified 7 relevant trials, involving 5425 women who were overweight or obese during pregnancy, with approximately 3544 women and children with follow-up assessments available for inclusion in the meta-analysis.

Discussion: The proposed IPDMA provides an opportunity to evaluate the effect of dietary and lifestyle interventions among pregnant women who are overweight or obese on later maternal and early childhood health outcomes, including risk of obesity. This knowledge is essential to effectively translate research findings into clinical practice and public health policy.

Systematic Review Registration: This IPD has been prospectively registered (PROSPERO), ID number CRD42016047165 .
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http://dx.doi.org/10.1186/s13643-017-0442-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5343397PMC
March 2017

An Exercise-Only Intervention in Obese Fathers  Restores Glucose and Insulin Regulation in  Conjunction with the Rescue of Pancreatic Islet Cell  Morphology and MicroRNA Expression in Male  Offspring.

Nutrients 2017 Feb 9;9(2). Epub 2017 Feb 9.

Discipline of Obstetrics and Gynaecology, School of Paediatrics and Reproductive Health, University of Adelaide, Adelaide 5005, Australia.

Paternal obesity programs metabolic syndrome in offspring. Low-impact exercise in obese  males improves the metabolic health of female offspring, however whether this occurred in male  offspring remained unknown. C57BL/6NHsd (Harlan) mice were fed a control diet (CD; 6% fat, n =  7) or a high-fat diet (HFD; 21% fat, n = 16) for 18 weeks. After 9 weeks, HFD-fed mice either remained  sedentary (HH, n = 8) or undertook low-moderate exercise (HE, n = 8) for another 9 weeks. Male  offspring were assessed for glucose/insulin tolerance, body composition, plasma lipids, pancreatic  islet cell morphology and microRNA expression. Founder HH induced glucose intolerance, insulin  insensitivity, and hyperlipidaemia in male offspring (p < 0.05). Metabolic health was fully restored  in male offspring by founder exercise to control levels. Founder HH reduced pancreatic β-cell area  and islet cell size in male offspring, and altered the expression of 13 pancreatic microRNAs (p <  0.05). Founder HE led to partial restoration of pancreatic islet cell morphology and the expression  of two pancreatic microRNAs (let7d-5p, 194-5p) in male offspring. Founder HE reduced male  offspring adiposity, increased muscle mass, reduced plasma free fatty acids (FFAs), and further  altered pancreatic microRNAs (35 vs. HH; 32 vs. CD) (p < 0.05). Low-impact exercise in obese fathers  prior to conception, without dietary change, may be a viable intervention strategy to reduce the illeffects of obesity-induced paternal programming in male offspring.
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http://dx.doi.org/10.3390/nu9020122DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5331553PMC
February 2017

The effect of an antenatal lifestyle intervention in overweight and obese women on circulating cardiometabolic and inflammatory biomarkers: secondary analyses from the LIMIT randomised trial.

BMC Med 2017 Feb 14;15(1):32. Epub 2017 Feb 14.

The University of Adelaide, The Robinson Research Institute, and Discipline of Obstetrics & Gynaecology, Adelaide, South Australia, Australia.

Background: Maternal overweight and obesity during pregnancy is associated with insulin resistance, hyperglycaemia, hyperlipidaemia and a low-grade state of chronic inflammation. The aim of this pre-specified analysis of secondary outcome measures was to evaluate the effect of providing antenatal dietary and lifestyle advice on cardiometabolic and inflammatory biomarkers.

Methods: We conducted a multicentre trial in which pregnant women who were overweight or obese were randomised to receive either Lifestyle Advice or Standard Care. We report a range of pre-specified secondary maternal and newborn cardiometabolic and inflammatory biomarker outcomes. Maternal whole venous blood was collected at trial entry (mean 14 weeks gestation; non-fasting), at 28 weeks gestation (fasting), and at 36 weeks gestation (non-fasting). Cord blood was collected after birth and prior to the delivery of the placenta. A range of cardiometabolic and inflammatory markers were analysed (total cholesterol, triglycerides, non-esterified fatty acids, high-density lipoprotein cholesterol, insulin, glucose, leptin, adiponectin, C-reactive protein, granulocyte macrophage-colony stimulating factor, interferon gamma, TNF-α, and interleukins 1β, 2, 4, 5, 6, 8, and 10). Participants were analysed in the groups to which they were randomised, and were included in the analyses if they had a measure at any time point.

Results: One or more biological specimens were available from 1951 women (989 Lifestyle Advice and 962 Standard Care), with cord blood from 1174 infants (596 Lifestyle Advice and 578 Standard Care). There were no statistically significant differences in mean cardiometabolic and inflammatory marker concentrations across pregnancy and in infant cord blood between treatment groups. Estimated treatment group differences were close to zero, with 95% confidence intervals spanning a range of differences that were short of clinical relevance. There was no evidence to suggest that the intervention effect was modified by maternal BMI category.

Conclusions: Despite our findings, it will be worth considering potential relationships between cardiometabolic and inflammatory markers and clinical outcomes, including longer-term infant health and adiposity.

Trial Registration: Australian and New Zealand Clinical Trials Registry ( ACTRN12607000161426 ; Date Registered 09/03/2007).
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http://dx.doi.org/10.1186/s12916-017-0790-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5307888PMC
February 2017

Effects of induced placental and fetal growth restriction, size at birth and early neonatal growth on behavioural and brain structural lateralization in sheep.

Laterality 2017 Sep 19;22(5):560-589. Epub 2016 Oct 19.

a Robinson Research Institute , North Adelaide , Australia.

Poor perinatal growth in humans results in asymmetrical grey matter loss in fetuses and infants and increased functional and behavioural asymmetry, but specific contributions of pre- and postnatal growth are unclear. We therefore compared strength and direction of lateralization in obstacle avoidance and maze exit preference tasks in offspring of placentally restricted (PR: 10M, 13F) and control (CON: 23M, 17F) sheep pregnancies at 18 and 40 weeks of age, and examined gross brain structure of the prefrontal cortex at 52 weeks of age (PR: 14M, 18F; CON: 23M, 25F). PR did not affect lateralization direction, but 40-week-old PR females had greater lateralization strength than CON (P = .021). Behavioural lateralization measures were not correlated with perinatal growth. PR did not alter brain morphology. In males, cross-sectional areas of the prefrontal cortex and left hemisphere correlated positively with skull width at birth, and white matter area correlated positively with neonatal growth rate of the skull (all P < .05). These studies reinforce the need to include progeny of both sexes in future studies of neurodevelopmental programming, and suggest that restricting in utero growth has relatively mild effects on gross brain structural or behavioural lateralization in sheep.
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http://dx.doi.org/10.1080/1357650X.2016.1243552DOI Listing
September 2017

Programming the brain: Common outcomes and gaps in knowledge from animal studies of IUGR.

Physiol Behav 2016 10 7;164(Pt A):233-48. Epub 2016 Jun 7.

Robinson Research Institute, University of Adelaide, South Australia, Australia; Discipline of Obstetrics and Gynaecology, School of Medicine, University of Adelaide, South Australia, Australia. Electronic address:

IUGR in humans is associated with impaired pre- and postnatal neurodevelopment, and subsequent postnatal cognition, resulting in lower IQ, poorer memory, visuomotor and executive function skills, as well as behavioural and attentional problems. Experimental models of IUGR are needed to allow direct testing of causality and interventions, and have benefits in reducing both confounding by comorbidities such as prematurity, and variation due to environment and genetics. This review describes and discusses experimental models of IUGR in which neurodevelopmental and cognitive outcomes of IUGR have been reported. We consider the timing of neurodevelopment relative to birth and to the period of restriction, as well as the effects of each experimental perturbation on the fetal environment and development, before discussing neurodevelopmental and cognitive outcomes for progeny as fetuses, neonates and into adolescent and adult life. Experimental IUGR induces broadly similar outcomes to human IUGR, with altered brain morphology, in particular grey matter loss and discordant trajectory of white matter development, and poorer cognition and memory reported in various studies. Nevertheless, there remain gaps in knowledge of neurodevelopment in experimental models. We end the review with recommendations for the design of future studies to further investigate the mechanisms underlying adverse neurodevelopmental consequences of IUGR, and to evaluate interventions that may subsequently improve outcomes of IUGR in humans.
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http://dx.doi.org/10.1016/j.physbeh.2016.06.005DOI Listing
October 2016

Paternal under-nutrition programs metabolic syndrome in offspring which can be reversed by antioxidant/vitamin food fortification in fathers.

Sci Rep 2016 06 3;6:27010. Epub 2016 Jun 3.

Discipline of Obstetrics and Gynaecology, School of Medicine, Robinson Research Institute, University of Adelaide, South Australia, 5005, Australia.

There is an ever increasing body of evidence that demonstrates that paternal over-nutrition prior to conception programs impaired metabolic health in offspring. Here we examined whether paternal under-nutrition can also program impaired health in offspring and if any detrimental health outcomes in offspring could be prevented by micronutrient supplementation (vitamins and antioxidants). We discovered that restricting the food intake of male rodents reduced their body weight, fertility, increased sperm oxidative DNA lesions and reduced global sperm methylation. Under-nourished males then sired offspring with reduced postnatal weight and growth but somewhat paradoxically increased adiposity and dyslipidaemia, despite being fed standard chow. Paternal vitamin/antioxidant food fortification during under-nutrition not only normalised founder oxidative sperm DNA lesions but also prevented early growth restriction, fat accumulation and dyslipidaemia in offspring. This demonstrates that paternal under-nutrition reduces postnatal growth but increases the risk of obesity and metabolic disease in the next generation and that micronutrient supplementation during this period of under-nutrition is capable of restoring offspring metabolic health.
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http://dx.doi.org/10.1038/srep27010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4891691PMC
June 2016

The effect of antenatal dietary and lifestyle advice for women who are overweight or obese on emotional well-being: the LIMIT randomized trial.

Acta Obstet Gynecol Scand 2016 Mar 21;95(3):309-18. Epub 2015 Dec 21.

Discipline of Obstetrics and Gynaecology, The Robinson Research Institute, University of Adelaide, Adelaide, South Australia, Australia.

Introduction: Our aim was to evaluate the effect of dietary and lifestyle advice given to women who were overweight or obese during pregnancy on maternal quality of life, anxiety and risk of depression, and satisfaction with care.

Material And Methods: We conducted a randomized trial, involving pregnant women with body mass index ≥25 kg/m(2) , recruited from maternity units in South Australia. Women were randomized to Lifestyle Advice or Standard Care, and completed questionnaires assessing risk of depression (Edinburgh Postnatal Depression Scale), anxiety (Spielberger State-Trait Anxiety Inventory), and quality of life (SF-36) at trial entry, 28 and 36 weeks' gestation, and 4 months postpartum. Secondary trial outcomes assessed for this analysis were risk of depression, anxiety, maternal quality of life, and satisfaction with care.

Results: One or more questionnaires were completed by 976 of 1108 (90.8%) women receiving Lifestyle Advice and 957 of 1104 (89.7%) women receiving Standard Care. The risk of depression [adjusted risk ratio 1.01; 95% confidence interval (CI) 0.82-1.24; p = 0.95], anxiety (adjusted risk ratio 1.09; 95% CI 0.93-1.27; p = 0.31), and health-related quality of life were similar between the two groups. Women receiving Lifestyle Advice reported improved healthy food choice [Lifestyle Advice 404 (68.9%) vs. Standard Care 323 (51.8%); p < 0.0001], and exercise knowledge [Lifestyle Advice 444 (75.8%) vs. Standard Care 367 (58.8%); p < 0.0001], and reassurance about their health [Lifestyle Advice 499 (85.3%) vs. Standard Care 485 (77.9%); p = 0.0112], and health of their baby [Lifestyle Advice 527 (90.2%) vs. Standard Care 545 (87.6%); p = 0.0143].

Conclusion: Lifestyle advice in pregnancy improved knowledge and provided reassurance without negatively impacting well-being.
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http://dx.doi.org/10.1111/aogs.12832DOI Listing
March 2016

Paternal obesity negatively affects male fertility and assisted reproduction outcomes: a systematic review and meta-analysis.

Reprod Biomed Online 2015 Nov 10;31(5):593-604. Epub 2015 Aug 10.

Bump IVF, Mossman, Sydney, New South Wales 2088, Australia.

This systematic review investigated the effect of paternal obesity on reproductive potential. Databases searched were Pubmed, Ovid, Web of Science, Scopus, Cinahl and Embase. Papers were critically appraised by two reviewers, and data were extracted using a standardized tool. Outcomes were: likelihood of infertility, embryo development, clinical pregnancy, live birth, pregnancy viability, infant development, sperm; concentration, morphology, motility, volume, DNA fragmentation, chromatin condensation, mitochondrial membrane potential (MMP), and seminal plasma factors. Thirty papers were included, with a total participant number of 115,158. Obese men were more likely to experience infertility (OR = 1.66, 95% CI 1.53-1.79), their rate of live birth per cycle of assisted reproduction technology (ART) was reduced (OR = 0.65, 95% CI 0.44-0.97) and they had a 10% absolute risk increase of pregnancy non-viability. Additionally, obese men had an increased percentage of sperm with low MMP, DNA fragmentation, and abnormal morphology. Clinically significant differences were not found for conventional semen parameters. From these findings it can be concluded that male obesity is associated with reduced reproductive potential. Furthermore, it may be informative to incorporate DNA fragmentation analysis and MMP assessment into semen testing, especially for obese men whose results suggest they should have normal fertility.
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http://dx.doi.org/10.1016/j.rbmo.2015.07.012DOI Listing
November 2015

Placental and fetal growth restriction, size at birth and neonatal growth alter cognitive function and behaviour in sheep in an age- and sex-specific manner.

Physiol Behav 2015 Dec 5;152(Pt A):1-10. Epub 2015 Sep 5.

Robinson Research Institute, University of Adelaide, South Australia, Australia; School of Paediatrics and Reproductive Health, University of Adelaide, South Australia, Australia. Electronic address:

Intrauterine growth restriction and slow neonatal growth in humans are each associated with poorer learning, memory and cognitive flexibility in childhood and adulthood. The relative contributions of pre- and post-natal growth to cognitive outcomes are unclear, however. We therefore compared performance in learning, memory and reversal tasks using a modified Y-maze at 18 and 40 weeks of age in offspring of placentally-restricted (PR: 10 M, 13 F) and control (23 M, 17 F) ovine pregnancies. We also investigated relationships between size at birth, neonatal growth rates and cognitive outcomes. PR had limited effects on cognitive outcomes, with PR males requiring more trials to solve the initial learning task than controls (P=0.037) but faster completion of reversal tasks in both sexes at 18 weeks of age. In males, neonatal growth rate correlated inversely with numbers of trials and total time required to solve memory tasks at 40 weeks of age. In females, bleat frequency in the first reversal task at 18 weeks of age correlated positively with birth weight (r=0.734, P<0.05) and neonatal growth rate (r=0.563, P<0.05). We conclude that PR induces limited effects on cognitive outcomes in sheep, with some evidence of impaired learning in males, but little effect on memory or cognitive flexibility in either sex. Rapid neonatal growth predicted improved memory task performance in males, suggesting that strategies to optimize neonatal growth may have long-term cognitive benefits but that these may be sex-specific.
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http://dx.doi.org/10.1016/j.physbeh.2015.08.042DOI Listing
December 2015

Effect of placental restriction and neonatal exendin-4 treatment on postnatal growth, adult body composition, and in vivo glucose metabolism in the sheep.

Am J Physiol Endocrinol Metab 2015 Sep 28;309(6):E589-600. Epub 2015 Jul 28.

Robinson Research Institute and School of Paediatrics and Reproductive Health,

Intrauterine growth restriction (IUGR) increases the risk of adult type 2 diabetes (T2D) and obesity. Neonatal exendin-4 treatment can prevent diabetes in the IUGR rat, but whether this will be effective in a species where the pancreas is more mature at birth is unknown. Therefore, we evaluated the effects of neonatal exendin-4 administration after experimental restriction of placental and fetal growth on growth and adult metabolic outcomes in sheep. Body composition, glucose tolerance, and insulin secretion and sensitivity were assessed in singleton-born adult sheep from control (CON; n = 6 females and 4 males) and placentally restricted pregnancies (PR; n = 13 females and 7 males) and in sheep from PR pregnancies that were treated with exendin-4 as neonates (daily sc injections of 1 nmol/kg exendin-4; PR + exendin-4; n = 11 females and 7 males). Placental restriction reduced birth weight (by 29%) and impaired glucose tolerance in the adult but did not affect adult adiposity, insulin secretion, or insulin sensitivity. Neonatal exendin-4 suppressed growth during treatment, followed by delayed catchup growth and unchanged adult adiposity. Neonatal exendin-4 partially restored glucose tolerance in PR progeny but did not affect insulin secretion or sensitivity. Although the effects on glucose tolerance are promising, the lack of effects on adult body composition, insulin secretion, and insulin sensitivity suggest that the neonatal period may be too late to fully reprogram the metabolic consequences of IUGR in species that are more mature at birth than rodents.
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http://dx.doi.org/10.1152/ajpendo.00487.2014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4631533PMC
September 2015

The cost-effectiveness of providing antenatal lifestyle advice for women who are overweight or obese: the LIMIT randomised trial.

BMC Obes 2015 11;2:14. Epub 2015 Mar 11.

School of Paediatrics and Reproductive Health, and The Robinson Research Institute, The University of Adelaide, Adelaide, Australia.

Background: Overweight and obesity during pregnancy is common, although robust evidence about the economic implications of providing an antenatal dietary and lifestyle intervention for women who are overweight or obese is lacking. We conducted a health economic evaluation in parallel with the LIMIT randomised trial. Women with a singleton pregnancy, between 10(+0)-20(+0) weeks, and BMI ≥25 kg/m(2) were randomised to Lifestyle Advice (a comprehensive antenatal dietary and lifestyle intervention) or Standard Care. The economic evaluation took the perspective of the health care system and its patients, and compared costs encountered from the additional use of resources from time of randomisation until six weeks postpartum. Increments in health outcomes for both the woman and infant were considered in the cost-effectiveness analysis. Mean costs and effects in the treatment groups allocated at randomisation were compared, and incremental cost effectiveness ratios (ICERs) and confidence intervals (95%) calculated. Bootstrapping was used to confirm the estimated confidence intervals, and to generate acceptability curves representing the probability of the intervention being cost-effective at alternative monetary equivalent values for the outcomes avoiding high infant birth weight, and respiratory distress syndrome. Analyses utilised intention to treat principles.

Results: Overall, the increase in mean costs associated with providing the intervention was offset by savings associated with improved immediate neonatal outcomes, rendering the intervention cost neutral (Lifestyle Advice Group $11261.19±$14573.97 versus Standard Care Group $11306.70±$14562.02; p=0.094). Using a monetary value of $20,000 as a threshold value for avoiding an additional infant with birth weight above 4 kg, the probability that the antenatal intervention is cost-effective is 0.85, which increases to 0.95 when the threshold monetary value increases to $45,000.

Conclusions: Providing an antenatal dietary and lifestyle intervention for pregnant women who are overweight or obese is not associated with increased costs or cost savings, but is associated with a high probability of cost effectiveness. Ongoing participant follow-up into childhood is required to determine the medium to long-term impact of the observed, short-term endpoints, to more accurately estimate the value of the intervention on risk of obesity, and associated costs and health outcomes.

Trials Registration: Australian and New Zealand Clinical Trials Registry (ACTRN12607000161426).
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http://dx.doi.org/10.1186/s40608-015-0046-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4511432PMC
July 2015

Effects of an antenatal dietary intervention on maternal anthropometric measures in pregnant women with obesity.

Obesity (Silver Spring) 2015 Aug 14;23(8):1555-62. Epub 2015 Jul 14.

School of Paediatrics and Reproductive Health Discipline of Obstetrics and Gynaecology, The University of Adelaide, Adelaide, Australia.

Objective: The effect of providing antenatal dietary and lifestyle advice on secondary measures of maternal anthropometry was evaluated and their correlation with both gestational weight gain and infant birth weight was assessed.

Methods: In a multicenter, randomized controlled trial, pregnant women with BMI of ≥25 kg/m(2) received either Lifestyle Advice or Standard Care. Maternal anthropometric outcomes included arm circumference, biceps, triceps, and subscapular skinfold thickness measurements (SFTM), percentage body fat (BF), gestational weight gain, and infant birth weight. The intention to treat principles were utilized by the analyses.

Results: The measurements were obtained from 807 (74.7%) women in the Lifestyle Advice Group and 775 (72.3%) women in the Standard Care Group. There were no statistically significant differences identified between the treatment groups with regards to arm circumference, biceps, triceps, and subscapular SFTM, or percentage BF at 36-week gestation. Maternal anthropometric measurements were not significantly correlated with either gestational weight gain or infant birth weight.

Conclusions: Among pregnant women with a BMI of ≥25 kg/m(2) , maternal SFTM were not modified by an antenatal dietary and lifestyle intervention. Furthermore, maternal SFTM correlate poorly with both gestational weight gain and infant birth weight.
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http://dx.doi.org/10.1002/oby.21145DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5054850PMC
August 2015

Paternal obesity induces metabolic and sperm disturbances in male offspring that are exacerbated by their exposure to an "obesogenic" diet.

Physiol Rep 2015 Mar;3(3)

Discipline of Obstetrics & Gynaecology, Robinson Research Institute, Research Centre for Reproductive Health, School of Paediatrics and Reproductive Health, University of Adelaide, Adelaide, SA, Australia Monash IVF Group, Melbourne, Vic., Australia.

Obesity and related comorbidities are becoming increasingly prevalent globally. In mice preconception paternal exposure to a high fat diet (HFD) impairs the metabolic and reproductive health of male offspring, despite their control diet (CD) consumption. However, offspring share lifestyle, including diet, with parents. We assessed if male offspring from HFD fathers have a heightened susceptibility to HFD-induced metabolic and reproductive derangements. This 2 × 2 design saw founder males (F0) and their offspring (F1) fed either a HFD or a nutritionally matched CD. Regardless of paternal diet, HFD fed male offspring had greater total body weight and adiposity. Offspring sired by a HFD male and fed a HFD were the heaviest, had the greatest adiposity and had the greatest concentration of serum cholesterol, triglyceride, HDL, and NEFA compared with CD sired/fed littermates. A synergistic increase in serum insulin was unmasked by both father/son HFD consumption, concomitant with increased sera glucose. Either a paternal or offspring HFD was associated with similar reductions to offspring sperm motility. Whereas sperm ROS concentrations and sperm-oocyte binding saw detrimental effects of both F0 HFD and F1 HFD with an interaction evident between both, culminating in the most impaired sperm parameters in this group. This indicates that metabolic and fertility disturbances in male offspring sired by HFD fathers are exacerbated by a "second-hit" of exposure to the same obesogenic environment postnatally. If translatable to human health, this suggests that adverse reproductive and metabolic outcomes may be amplified across generations through a shared calorie dense diet, relevant to the current worldwide obesity epidemic.
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http://dx.doi.org/10.14814/phy2.12336DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4393169PMC
March 2015

Maternal insulin-like growth factor 1 and 2 differentially affect the renin-angiotensin system during pregnancy in the guinea pig.

Growth Horm IGF Res 2015 Jun 20;25(3):141-7. Epub 2015 Feb 20.

School of Paediatrics and Reproductive Health, Robinson Research Institute, University of Adelaide, Adelaide, South Australia, Australia. Electronic address:

Objective: Insulin-like growth factors (IGFs) are known to interact with the renin-angiotensin system (RAS). We previously demonstrated that administration of IGF1 to guinea pigs in early to mid pregnancy promotes placental function and fetal growth in mid to late gestation. Early administration of IGF2 had sustained, but not acute, effects on these parameters and also on placental structural differentiation. Here, we aimed to determine whether the IGFs interact with the placental RAS in early to mid gestation to modulate placental development and increase fetal growth and survival, and if IGF2 binding the IGF2R is implicated in the sustained effects of IGF2 treatment.

Design: At day 20 of pregnancy, guinea pigs were infused with 1m g/kg/day of IGF1, IGF2, (Leu27)IGF2 or vehicle for 18days and sacrificed on either day 62 (late pregnancy) or during the infusion period on day 35 (early-mid pregnancy). Placental structure at day 35 was analyzed using morphometric technique and expression of RAS genes in the placenta and placental and plasma renin activity were measured at both time points.

Results: Compared with vehicle at day 35 of gestation, IGF1 infusion reduced the total midsagittal cross-sectional area of the placenta (-17%, p = 0.02) and the labyrinth area (-22%, p = 0.014) but did not alter the labyrinth volume nor labyrinth:interlobium ratios. IGF2 treatment did not affect placental structure. IGF1 did not alter placental mRNA for any of the RAS genes quantified at day 35 (AGTR1, ACE, AGT, TGFB1) but increased TGFB1 expression by more than 16-fold (p = 0.005) at day 62. IGF2 increased placental expression of AGTR1 (+88%, p = 0.03) and decreased AGT (-73%, p = 0.01) compared with the vehicle-treated group at day 35, and both IGF2 and (Leu27)IGF2 increased expression of TGFB1 at day 62 by 9-fold (p = 0.016) and 6-fold (p = 0.019) respectively. Both IGFs increased the ratio of active:total placental renin protein (+22% p = 0.026 p = 0.038) compared to vehicle compared to vehicle at day 35 but not 62. At day 62, IGF2-treated mothers showed a marked increase in total plasma renin (+495%) and active renin (+359%) compared to vehicle but decreased the ratio of active to total renin by 41% (p = 0.042). (Leu27)IGF2-treated animals had higher levels of placental active renin (+73%, p = 0.001) and total renin (+71%, p = 0.001) compared with the vehicle control.

Conclusions: The data obtained in the current study suggest the potential for alternate roles for the induction of the RAS after IGF treatment. IGF1 and 2 treatments increase the activation of prorenin to renin in the placenta, possibly due to increased protease activity. In addition, IGF2 treatment in early pregnancy may enhance the maternal adaptation to pregnancy through stimulation of renin in the kidney. The sustained effects on placental differentiation and function after IGF2 treatment suggest therapeutic potential for exogenous administration of IGFs in improving pregnancy outcomes.
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http://dx.doi.org/10.1016/j.ghir.2015.02.001DOI Listing
June 2015

Preconception diet or exercise intervention in obese fathers normalizes sperm microRNA profile and metabolic syndrome in female offspring.

Am J Physiol Endocrinol Metab 2015 May 17;308(9):E805-21. Epub 2015 Feb 17.

School of Paediatrics and Reproductive Health, Discipline of Obstetrics and Gynaecology, Robinson Research Institute, University of Adelaide, Adelaide, South Australia, Australia; Freemasons Center for Men's Health, University of Adelaide, Adelaide, South Australia, Australia; and Monash IVF Group, Melbourne, Victoria, Australia.

Obesity and type 2 diabetes are increasingly prevalent across all demographics. Paternal obesity in humans and rodents can program obesity and impair insulin sensitivity in female offspring. It remains to be determined whether these perturbed offspring phenotypes can be improved through targeted lifestyle interventions in the obese father. Using a mouse model, we demonstrate that diet or exercise interventions for 8 wk (2 rounds of spermatogenesis) in obese founder males restores insulin sensitivity and normalized adiposity in female offspring. Founder diet and/or exercise also normalizes abundance of X-linked sperm microRNAs that target genes regulating cell cycle and apoptosis, pathways central to oocyte and early embryogenesis. Additionally, obesity-associated comorbidities, including inflammation, glucose intolerance, stress, and hypercholesterolemia, were good predictors for sperm microRNA abundance and offspring phenotypes. Interventions aimed at improving paternal metabolic health during specific windows prior to conception can partially normalize aberrant epigenetic signals in sperm and improve the metabolic health of female offspring.
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http://dx.doi.org/10.1152/ajpendo.00013.2015DOI Listing
May 2015

Do I turn left or right? Effects of sex, age, experience and exit route on maze test performance in sheep.

Physiol Behav 2015 Feb 18;139:244-53. Epub 2014 Nov 18.

Robinson Research Institute, University of Adelaide, South Australia 5005, Australia; School of Paediatrics and Reproductive Health, University of Adelaide, South Australia 5005, Australia. Electronic address:

Brain development and function are susceptible to perturbation by environmental factors. Sheep are increasingly being used as a neurodevelopmental model due to timing similarities with humans, but effects of age, experience and sex on cognition are not well characterised in this species. We therefore studied memory and reversal learning in sheep using a modified Y-maze at two ages: naive 18 weeks old (18N: 23 male, 17 female), experienced 40 week old sheep that had previously been tested at 18 weeks (40E: 22 male, 17 female), and naive 40 weeks old (40N: 4 male, 10 female). Younger naive animals (18N) required more trials and time to solve the first reversal task (task R1) than 40E (P=0.007 and P<0.001 respectively). Experience also improved outcomes, with 40N sheep requiring more time to solve tasks L (P=0.034) and R1 (P=0.002) than 40E. Increasing age (40N cf. 18N) decreased bleat frequency in tasks R1, M2 and R2 (each P<0.05). In 40N females, outcomes also differed by exit method in task R1, with those that exited via an indirect route taking less time to pass tasks R1 (P=0.009) and R2 (P=0.015) than those that used a direct route. Age plus experience improved learning outcomes, demonstrating knowledge retention for 22 weeks in this species, whilst age alone affected mostly behavioral responses. These results provide comparison data, and can be utilised to improve experimental design, for studies of neurodevelopment in the sheep.
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http://dx.doi.org/10.1016/j.physbeh.2014.11.037DOI Listing
February 2015

The effects of antenatal dietary and lifestyle advice for women who are overweight or obese on neonatal health outcomes: the LIMIT randomised trial.

BMC Med 2014 Oct 13;12:163. Epub 2014 Oct 13.

The University of Adelaide, School of Paediatrics and Reproductive Health, Robinson Research Institute, Adelaide, South Australia, Australia.

Background: Overweight and obesity during pregnancy represents a considerable health burden. While research has focused on interventions to limit gestational weight gain, there is little information describing their impact on neonatal health. Our aim was to investigate the effect on a range of pre-specified secondary neonatal outcomes of providing antenatal dietary and lifestyle advice to women who are overweight or obese.

Methods: We report a range of pre-specified secondary neonatal outcomes from a large randomised trial in which antenatal dietary and lifestyle advice was provided to women who were overweight or obese. Pregnant women were eligible for participation with a body mass index of 25 kg/m(2) or over, and singleton gestation between 10(+0) and 20(+0) weeks. Outcome measures included gestational age at birth; Apgar score below 7 at 5 minutes of age; need for resuscitation at birth; birth weight above 4.5 kg or below 2.5 kg; birth weight, length and head circumference (and Z-scores); admission to the nursery; respiratory distress syndrome; and postnatal length of stay. Data relating to the primary outcome (large for gestational age infants defined as birth weight above the 90th centile) and birth weight above 4 kg have been reported previously. Analyses used intention-to-treat principles.

Results: In total, 2,142 infants were included in the analyses. Infants born to women following lifestyle advice were significantly less likely to have birth weight above 4.5 kg (2.15% versus 3.69%; adjusted risk ratio (aRR)=0.59; 95% confidence interval (CI) 0.36 to 0.98; P=0.04), or respiratory distress syndrome (1.22% versus 2.57%; aRR=0.47; 95% CI 0.24 to 0.90; P=0.02), particularly moderate or severe disease, and had a shorter length of postnatal hospital stay (3.94±7.26 days versus 4.41±9.87 days; adjusted ratio of means 0.89; 95% CI 0.82 to 0.97; P=0.006) compared with infants born to women who received Standard Care.

Conclusions: For women who are overweight or obese, antenatal dietary and lifestyle advice has health benefits for infants, without an increase in the risk of harm. Continued follow-up into childhood will be important to assess the longer-term effects of a reduction in high infant birth weight on risk of child obesity. Please see related articles: http://www.biomedcentral.com/1741-7015/12/161 and http://www.biomedcentral.com/1741-7015/12/201 .

Clinical Trial Registration: Australian and New Zealand Clinical Trials Registry ( ACTRN12607000161426 ).
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http://dx.doi.org/10.1186/s12916-014-0163-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4194368PMC
October 2014

The effects of antenatal dietary and lifestyle advice for women who are overweight or obese on maternal diet and physical activity: the LIMIT randomised trial.

BMC Med 2014 Oct 13;12:161. Epub 2014 Oct 13.

School of Paediatrics and Reproductive Health, and The Robinson Research Institute, The University of Adelaide, Adelaide, Australia.

Background: Overweight and obesity is a significant health concern during pregnancy. Our aim was to investigate the effect of providing antenatal dietary and lifestyle advice to women who are overweight or obese on components of maternal diet and physical activity.

Methods: We conducted a randomised controlled trial, in which pregnant women with a body mass index≥25 kg/m2, and singleton gestation between 10(+0) to 20(+0) weeks were recruited and randomised to Lifestyle Advice (involving a comprehensive dietary and lifestyle intervention over their pregnancy) or Standard Care. Within the intervention group, we conducted a nested randomised trial in which a subgroup of women were further randomised to receive access to supervised group walking sessions in addition to the standard information presented during the intervention contacts (the Walking group) or standard information only. The outcome measures were maternal dietary intake, (including food groups, macronutrient and micronutrient intake, diet quality (using the Healthy Eating Index; HEI), dietary glycaemic load, and glycaemic index) and maternal physical activity. Women completed the Harvard Semi-Structured Food Frequency Questionnaire, and the Short Questionnaire to Assess Health-enhancing Physical Activity (SQUASH), at trial entry, 28 and 36 weeks' gestational age, and 4 months postpartum. Analyses were performed on an intention-to-treat basis, using linear mixed effects models with adjustment for the stratification variables.

Results: Women randomised to Lifestyle Advice demonstrated a statistically significant increase in the number of servings of fruit and vegetables consumed per day, as well as increased consumption of fibre, and reduced percentage energy intake from saturated fats (P<0.05 for all). Maternal HEI was significantly improved at both 28 (73.35±6.62 versus 71.86±7.01; adjusted difference in means 1.58; 95% CI 0.89 to 2.27; P<0.0001) and 36 (72.95±6.82 versus 71.17±7.69; adjusted difference in means 1.77; 95% CI 1.01 to 2.53; P<0.0001) weeks. There were no differences in dietary glycaemic index or glycaemic load. Women randomised to Lifestyle Advice also demonstrated greater total physical activity (adjusted difference in means 359.76 metabolic equivalent task units (MET) minutes/week; 95% CI 74.87 to 644.65; P=0.01) compared with women receiving Standard Care. The supervised walking group was poorly utilised.

Conclusions: For women who are overweight or obese, antenatal lifestyle advice improves maternal diet and physical activity during pregnancy. Please see related articles: http://www.biomedcentral.com/1741-7015/12/163 and http://www.biomedcentral.com/1741-7015/12/201.

Trial Registration: Australian and New Zealand Clinical Trials Registry ( ACTRN12607000161426).
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http://dx.doi.org/10.1186/s12916-014-0161-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4194375PMC
October 2014

Antenatal lifestyle advice for women who are overweight or obese: LIMIT randomised trial.

BMJ 2014 Feb 10;348:g1285. Epub 2014 Feb 10.

Robinson Institute and School of Paediatrics and Reproductive Health, University of Adelaide, 72 King William Road, North Adelaide, South Australia, Australia 5006.

Objective: To determine the effect of antenatal dietary and lifestyle interventions on health outcomes in overweight and obese pregnant women.

Design: Multicentre randomised trial. We utilised a central telephone randomisation server, with computer generated schedule, balanced variable blocks, and stratification for parity, body mass index (BMI) category, and hospital.

Setting: Three public maternity hospitals across South Australia.

Participants: 2212 women with a singleton pregnancy, between 10+0 and 20+0 weeks' gestation, and BMI ≥ 25.

Interventions: 1108 women were randomised to a comprehensive dietary and lifestyle intervention delivered by research staff; 1104 were randomised to standard care and received pregnancy care according to local guidelines, which did not include such information.

Main Outcome Measures: Incidence of infants born large for gestational age (birth weight ≥ 90th centile for gestation and sex). Prespecified secondary outcomes included birth weight >4000 g, hypertension, pre-eclampsia, and gestational diabetes. Analyses used intention to treat principles.

Results: 2152 women and 2142 liveborn infants were included in the analyses. The risk of the infant being large for gestational age was not significantly different in the two groups (lifestyle advice 203/1075 (19%) v standard care 224/1067 (21%); adjusted relative risk 0.90, 95% confidence interval 0.77 to 1.07; P=0.24). Infants born to women after lifestyle advice were significantly less likely to have birth weight above 4000 g (lifestyle advice 164/1075 (15%) v standard care 201/1067 (19%); 0.82, 0.68 to 0.99; number needed to treat (NNT) 28, 15 to 263; P=0.04). There were no differences in maternal pregnancy and birth outcomes between the two treatment groups.

Conclusions: For women who were overweight or obese, the antenatal lifestyle advice used in this study did not reduce the risk delivering a baby weighing above the 90th centile for gestational age and sex or improve maternal pregnancy and birth outcomes.

Trial Registration: Australian and New Zealand Clinical Trials Registry (ACTRN12607000161426).
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3919179PMC
http://dx.doi.org/10.1136/bmj.g1285DOI Listing
February 2014

Placental restriction of fetal growth reduces cutaneous responses to antigen after sensitization in sheep.

Am J Physiol Regul Integr Comp Physiol 2014 Apr 5;306(7):R441-6. Epub 2014 Feb 5.

Robinson Institute.

Prenatal and early childhood exposures are implicated as causes of allergy, but the effects of intrauterine growth restriction on immune function and allergy are poorly defined. We therefore evaluated effects of experimental restriction of fetal growth on immune function and allergic sensitization in adolescent sheep. Immune function (circulating total red and white blood cells, neutrophils, lymphocytes, monocytes, eosinophils, and basophils, and the antibody response to Clostridial vaccination) and responses to house dust mite (HDM) allergen and ovalbumin (OVA) antigen sensitization (specific total Ig, IgG1, and IgE antibodies, and cutaneous hypersensitivity) were investigated in adolescent sheep from placentally restricted (PR, n = 23) and control (n = 40) pregnancies. Increases in circulating HDM-specific IgE (P = 0.007) and OVA-specific IgE (P = 0.038) were greater in PR than control progeny. PR did not alter total Ig, IgG1, or IgM responses to either antigen. PR increased OVA-specific but not HDM-specific IgA responses in females only (P = 0.023). Multiple birth increased Ig responses to OVA in a sex-specific manner. PR decreased the proportion of positive cutaneous hypersensitivity responders to OVA at 24 h (P = 0.030) but had no effect on cutaneous responses to HDM. Acute wheal responses to intradermal histamine correlated positively with birth weight in singletons (P = 0.023). Intrauterine growth restriction may suppress inflammatory responses in skin downstream of IgE induction, without impairment in antibody responses to a nonpolysaccharide vaccine. Discord between cutaneous and IgE responses following sensitization suggests new mechanisms for prenatal allergy programming.
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http://dx.doi.org/10.1152/ajpregu.00432.2013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3962620PMC
April 2014

Paternal high-fat diet consumption induces common changes in the transcriptomes of retroperitoneal adipose and pancreatic islet tissues in female rat offspring.

FASEB J 2014 Apr 13;28(4):1830-41. Epub 2014 Jan 13.

1Department of Pharmacology, School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia, 2052.

We previously showed that paternal high-fat diet (HFD) consumption programs β-cell dysfunction in female rat offspring, together with transcriptome alterations in islets. Here we investigated the retroperitoneal white adipose tissue (RpWAT) transcriptome using gene and pathway enrichment and pathway analysis to determine whether commonly affected network topologies exist between these two metabolically related tissues. In RpWAT, 5108 genes were differentially expressed due to a paternal HFD; the top 5 significantly enriched networks identified by pathway analysis in offspring of HFD fathers compared with those of fathers fed control diet were: mitochondrial and cellular response to stress, telomerase signaling, cell death and survival, cell cycle, cellular growth and proliferation, and cancer. A total of 187 adipose olfactory receptor genes were down-regulated. Interrogation against the islet transcriptome identified specific gene networks and pathways, including olfactory receptor genes that were similarly affected in both tissues (411 common genes, P<0.05). In particular, we highlight a common molecular network, cell cycle and cancer, with the same hub gene, Myc, suggesting early onset developmental changes that persist, shared responses to programmed systemic factors, or crosstalk between tissues. Thus, paternal HFD consumption triggers unique gene signatures, consistent with premature aging and chronic degenerative disorders, in both RpWAT and pancreatic islets of daughters.
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http://dx.doi.org/10.1096/fj.13-244046DOI Listing
April 2014

Improving metabolic health in obese male mice via diet and exercise restores embryo development and fetal growth.

PLoS One 2013 19;8(8):e71459. Epub 2013 Aug 19.

School of Paediatrics and Reproductive Health, Discipline of Obstetrics and Gynaecology, University of Adelaide, South Australia, Australia.

Paternal obesity is now clearly associated with or causal of impaired embryo and fetal development and reduced pregnancy rates in humans and rodents. This appears to be a result of reduced blastocyst potential. Whether these adverse embryo and fetal outcomes can be ameliorated by interventions to reduce paternal obesity has not been established. Here, male mice fed a high fat diet (HFD) to induce obesity were used, to determine if early embryo and fetal development is improved by interventions of diet (CD) and/or exercise to reduce adiposity and improve metabolism. Exercise and to a lesser extent CD in obese males improved embryo development rates, with increased cell to cell contacts in the compacting embryo measured by E-cadherin in exercise interventions and subsequently, increased blastocyst trophectoderm (TE), inner cell mass (ICM) and epiblast cell numbers. Implantation rates and fetal development from resulting blastocysts were also improved by exercise in obese males. Additionally, all interventions to obese males increased fetal weight, with CD alone and exercise alone, also increasing fetal crown-rump length. Measures of embryo and fetal development correlated with paternal measures of glycaemia, insulin action and serum lipids regardless of paternal adiposity or intervention, suggesting a link between paternal metabolic health and subsequent embryo and fetal development. This is the first study to show that improvements to metabolic health of obese males through diet and exercise can improve embryo and fetal development, suggesting such interventions are likely to improve offspring health.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0071459PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3747240PMC
April 2014
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