Asymmetric growth-limiting development of the female conceptus.

Introduction: Sex differences in prenatal growth may contribute to sex-dependent programming effects on postnatal phenotype. Methods: We integrated for the first time phenotypic, histomorphological, clinico-chemical, endocrine and gene expression analyses in a single species, the bovine conceptus at mid-gestation. Results: We demonstrate that by mid-gestation, before the onset of accelerated growth, the female conceptus displays asymmetric lower growth compared to males. Female fetuses were smaller with lower ponderal index and organ weights than males. However, their brain:body weight, brain:liver weight and heart:body weight ratios were higher than in males, indicating brain and heart 'sparing'. The female placenta weighed less and had lower volumes of trophoblast and fetal connective tissue than the male placenta. Female umbilical cord vessel diameters were smaller, and female-specific relationships of body weight and brain:liver weight ratios with cord vessel diameters indicated that the umbilico-placental vascular system creates a growth-limiting environment where blood flow is redistributed to protect brain and heart growth. Clinico-chemical indicators of liver perfusion support this female-specific growth-limiting phenotype, while lower insulin-like growth factor 2 (IGF2) gene expression in brain and heart, and lower circulating IGF2, implicate female-specific modulation of key endocrine mediators by nutrient supply. Conclusion: This mode of female development may increase resilience to environmental perturbations in utero and contribute to sex-bias in programming outcomes including susceptibility to non-communicable diseases.

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

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.

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

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-[3-3H]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 (FGR10-28). 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 FGR10-28 ( 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.

Prenatal Diet and Child Growth at 18 Months.

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 z 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, n = 816; standard care, n = 786), representing 75.0% of the eligible sample (n = 2136). There were no statistically significant differences in the prevalence of child BMI z 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; P = .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.

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

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).

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

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.

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

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 days 12-14 in singleton controls (CON, n = 7 lambs from 7 ewes), twins (IUGR, n = 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, n = 8 lambs from 4 ewes). Body composition and pancreas morphometry were assessed in lambs at day 16 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 days 12-14, compared with controls. MMDS increased metabolic clearance rate of insulin and increased ß-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.

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

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/m2 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/m2, 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.

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

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-[3-3H]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-1·kg-1) and near-maximal whole body responses (30 mU·min-1·kg-1). 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 (P < 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.

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.

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 .

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.

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 ß-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.

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.

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 1ß, 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).

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

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.

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

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.

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

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.

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

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.

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

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.

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.

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.

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

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.

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

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).