Association of Assisted Reproductive Technology With Offspring Growth and Adiposity From Infancy to Early Adulthood.

Importance: People conceived using assisted reproductive technology (ART) make up an increasing proportion of the world's population. Objective: To investigate the association of ART conception with offspring growth and adiposity from infancy to early adulthood in a large multicohort study. Design, Setting, and Participants: This cohort study used a prespecified coordinated analysis across 26 European, Asia-Pacific, and North American population-based cohort studies that included people born between 1984 and 2018, with mean ages at assessment of growth and adiposity outcomes from 0.6 months to 27.4 years. Data were analyzed between November 2019 and February 2022. Exposures: Conception by ART (mostly in vitro fertilization, intracytoplasmic sperm injection, and embryo transfer) vs natural conception (NC; without any medically assisted reproduction). Main Outcomes and Measures: The main outcomes were length / height, weight, and body mass index (BMI; calculated as weight in kilograms divided by height in meters squared). Each cohort was analyzed separately with adjustment for maternal BMI, age, smoking, education, parity, and ethnicity and offspring sex and age. Results were combined in random effects meta-analysis for 13 age groups. Results: Up to 158 066 offspring (4329 conceived by ART) were included in each age-group meta-analysis, with between 47.6% to 60.6% females in each cohort. Compared with offspring who were NC, offspring conceived via ART were shorter, lighter, and thinner from infancy to early adolescence, with differences largest at the youngest ages and attenuating with older child age. For example, adjusted mean differences in offspring weight were -0.27 (95% CI, -0.39 to -0.16) SD units at age younger than 3 months, -0.16 (95% CI, -0.22 to -0.09) SD units at age 17 to 23 months, -0.07 (95% CI, -0.10 to -0.04) SD units at age 6 to 9 years, and -0.02 (95% CI, -0.15 to 0.12) SD units at age 14 to 17 years. Smaller offspring size was limited to individuals conceived by fresh but not frozen embryo transfer compared with those who were NC (eg, difference in weight at age 4 to 5 years was -0.14 [95% CI, -0.20 to -0.07] SD units for fresh embryo transfer vs NC and 0.00 [95% CI, -0.15 to 0.15] SD units for frozen embryo transfer vs NC). More marked differences were seen for body fat measurements, and there was imprecise evidence that offspring conceived by ART developed greater adiposity by early adulthood (eg, ART vs NC difference in fat mass index at age older than 17 years: 0.23 [95% CI, -0.04 to 0.50] SD units). Conclusions and Relevance: These findings suggest that people conceiving or conceived by ART can be reassured that differences in early growth and adiposity are small and no longer evident by late adolescence.

Prenatal determinants of depressive symptoms in childhood: Evidence from Growing Up in New Zealand.

BACKGROUND: Young people who experience depression are at an increased risk of adverse psychosocial and developmental outcomes that can persist over the lifecourse. Identifying maternal prenatal risk factors that may contribute to childhood depressive symptoms can be useful when considering mental health intervention. METHODS: The current study included 3,925 children from the Growing Up in New Zealand (GUiNZ) study who had complete data for self-reported depressive symptoms and mothers' antenatal information. Depressive symptoms were measured at age 8 using the Centre for Epidemiological Studies Depression Scale for Children (CESD-10) short form questionnaire. Hierarchical linear regression was used to determine the relationship between prenatal factors and depressive symptoms at age 8. RESULTS: When controlling for sociodemographic characteristics, our hierarchical linear regression revealed that the most significant maternal prenatal predictors of high depressive symptoms at age 8 were maternal perceived stress, smoking during pregnancy, body mass index (BMI) in the overweight/obese range, and paracetamol intake. LIMITATIONS: One limitation with the current study was a reduction in the sample due to attrition. This may have affected our statistical power, reflected in our modest effect sizes. The sample remained both socioeconomically and ethnically diverse, however our results should be interpreted with respect to the sample and not the whole New Zealand population. CONCLUSIONS: A combination of maternal mental health and lifestyle factors contribute to depressive symptoms for children, possibly through foetal programming. Our results emphasise the importance of mental and physical health support for expectant mothers.

The relationship between diet and sleep in 2-y-old children: Results from Growing Up in New Zealand.

OBJECTIVES: This study aimed to examine the relationship between dietary practices and sleep in young children. METHODS: In this study, 2-y-old children (n = 6327) and their mothers were enrolled at birth and during pregnancy, respectively. The study obtained maternal demographic, health, and lifestyle data during late pregnancy. Parents reported the 2-y-old child's dietary practices on a food frequency questionnaire, as well as sleep duration and night-waking frequency. Measures of dietary intake quantified servings per day for each food group (grouped as low/moderate/high intake). Sleep measures were as inadequate sleep when <11 h sleep in a 24-h period and increased night waking when waking ≥2 times per night. Multivariable logistic regression analyses examined associations between toddler diet and sleep, which were described using adjusted odds ratios (ORs) and 95% confidence intervals. RESULTS: In this study, 2-y-old children (n = 6288) slept for a mean of 12.3 hours (standard deviation: ±1.5 hours) over a 24-h period, with 734 children (12%) getting <11 h of sleep in 24 h. Increased night waking occurred in 1063 children (17%). Compared with low intake, high soft drink/snack/fast food intake was associated with inadequate sleep (OR: 1.37) and increased night waking (OR: 1.34). High milk/cheese/yoghurt intake (OR: 1.55) was associated with increased odds of night waking, but moderate (OR: 0.81) or high (OR: 0.78) vegetable intake was associated with decreased odds of night waking. Exposure to screens (OR: 1.28) and heavy maternal cigarette smoking (OR: 2.20) were also associated with inadequate sleep and increased night waking, respectively. CONCLUSIONS: At age 2 y, higher consumption of soft drinks/snacks/fast foods is associated with shorter, more disrupted sleep. Conversely, higher vegetable consumption is associated with less disrupted sleep. Dietary modifications may improve toddlers' sleep.

An index measuring adherence to New Zealand Infant Feeding Guidelines has convergent validity with maternal socio-demographic and health behaviours and with children's body size.

Using data from a nationally generalisable birth cohort, we aimed to: (i) describe the cohort's adherence to national evidence-based dietary guidelines using an Infant Feeding Index (IFI) and (ii) assess the IFI's convergent construct validity, by exploring associations with antenatal maternal socio-demographic and health behaviours and with child overweight/obesity and central adiposity at age 54 months. Data were from the Growing Up in New Zealand cohort (n 6343). The IFI scores ranged from zero to twelve points, with twelve representing full adherence to the guidelines. Overweight/obesity was defined by BMI-for-age (based on the WHO Growth Standards). Central adiposity was defined as waist-to-height ratio > 90th percentile. Associations were tested using multiple linear regression and Poisson regression with robust variance (risk ratios, 95 % CI). Mean IFI score was 8·2 (sd 2·1). Maternal characteristics explained 29·1 % of variation in the IFI score. Maternal age, education and smoking had the strongest independent relationships with IFI scores. Compared with children in the highest IFI tertile, girls in the lowest and middle tertiles were more likely to be overweight/obese (1·46, 1·03, 2·06 and 1·56, 1·09, 2·23, respectively) and boys in the lowest tertile were more likely to have central adiposity (1·53, 1·02, 2·30) at age 54 months. Most infants fell short of meeting national Infant Feeding Guidelines. The associations between IFI score and maternal characteristics, and children's overweight/obesity/central adiposity, were in the expected directions and confirm the IFI's convergent construct validity.

A prediction model for childhood obesity in New Zealand.

Several early childhood obesity prediction models have been developed, but none for New Zealand's diverse population. We aimed to develop and validate a model for predicting obesity in 4-5-year-old New Zealand children, using parental and infant data from the Growing Up in New Zealand (GUiNZ) cohort. Obesity was defined as body mass index (BMI) for age and sex ≥ 95th percentile. Data on GUiNZ children were used for derivation (n = 1731) and internal validation (n = 713). External validation was performed using data from the Prevention of Overweight in Infancy Study (POI, n = 383) and Pacific Islands Families Study (PIF, n = 135) cohorts. The final model included: birth weight, maternal smoking during pregnancy, maternal pre-pregnancy BMI, paternal BMI, and infant weight gain. Discrimination accuracy was adequate [AUROC = 0.74 (0.71-0.77)], remained so when validated internally [AUROC = 0.73 (0.68-0.78)] and externally on PIF [AUROC = 0.74 [0.66-0.82)] and POI [AUROC = 0.80 (0.71-0.90)]. Positive predictive values were variable but low across the risk threshold range (GUiNZ derivation 19-54%; GUiNZ validation 19-48%; and POI 8-24%), although more consistent in the PIF cohort (52-61%), all indicating high rates of false positives. Although this early childhood obesity prediction model could inform early obesity prevention, high rates of false positives might create unwarranted anxiety for families.

Kallikrein-1 Blockade Inhibits Aortic Expansion in a Mouse Model and Reduces Prostaglandin E2 Secretion From Human Aortic Aneurysm Explants.

Background Abdominal aortic aneurysm (AAA) is an important cause of mortality in older adults. The kinin B2 receptor agonist, bradykinin, has been implicated in AAA pathogenesis through promoting inflammation. Bradykinin is generated from high- and low-molecular-weight kininogen by the serine protease kallikrein-1. The aims of this study were first to examine the effect of neutralizing kallikrein-1 on AAA development in a mouse model and second to test how blocking kallikrein-1 affected cyclooxygenase-2 and prostaglandin E2 in human AAA explants. Methods and Results Neutralization of kallikrein-1 in apolipoprotein E-deficient (ApoE-/-) mice via administration of a blocking antibody inhibited suprarenal aorta expansion in response to angiotensin (Ang) II infusion. Kallikrein-1 neutralization decreased suprarenal aorta concentrations of bradykinin and prostaglandin E2 and reduced cyclooxygenase-2 activity. Kallikrein-1 neutralization also decreased protein kinase B and extracellular signal-regulated kinase 1/2 phosphorylation and reduced levels of active matrix metalloproteinase 2 and matrix metalloproteinase 9. Kallikrein-1 blocking antibody reduced levels of cyclooxygenase-2 and secretion of prostaglandin E2 and active matrix metalloproteinase 2 and matrix metalloproteinase 9 from human AAA explants and vascular smooth muscle cells exposed to activated neutrophils. Conclusions These findings suggest that kallikrein-1 neutralization could be a treatment target for AAA.

A Randomised Controlled Trial Assessing the Effects of Peri-operative Fenofibrate Administration on Abdominal Aortic Aneurysm Pathology: Outcomes From the FAME Trial.

OBJECTIVE: Experimental studies suggest that fenofibrate prevents abdominal aortic aneurysm (AAA) development by lowering aortic osteopontin (OPN) concentration and reducing the number of macrophages infiltrating the aortic wall. The current study examined the effects of a short course of fenofibrate on AAA pathology in people with large AAAs awaiting aortic repair. METHODS: This randomised double blind parallel trial included male and female participants aged ≥ 60 years who had an asymptomatic AAA measuring ≥ 50 mm and were scheduled to undergo open AAA repair. Participants were allocated to fenofibrate (145 mg/day) or matching placebo for at least two weeks before elective AAA repair. Blood samples were collected at recruitment and immediately prior to surgery. AAA biopsies were obtained during aortic surgery. The primary outcomes were (1) AAA OPN concentration; (2) serum OPN concentration; and (3) number of AAA macrophages. Exploratory outcomes included circulating and aortic concentrations of other proteins previously associated with AAA. Outcomes assessed at a single time point were compared using logistic regression. Longitudinal outcomes were compared using linear mixed effects models. RESULTS: Forty-three participants were randomised. After three withdrawals, 40 were followed until the time of surgery (21 allocated fenofibrate and 19 allocated placebo). As expected, serum triglycerides reduced significantly from recruitment to the time of surgery in participants allocated fenofibrate. No differences in any of the primary and exploratory outcomes were observed between groups. CONCLUSION: A short course of 145 mg of fenofibrate/day did not lower concentrations of OPN or aortic macrophage density in people with large AAAs.

Factor XII blockade inhibits aortic dilatation in angiotensin II-infused apolipoprotein E-deficient mice.

Abdominal aortic aneurysm (AAA) is an important cause of mortality in older adults. Chronic inflammation and excessive matrix remodelling are considered important in AAA pathogenesis. Kinins are bioactive peptides important in regulating inflammation. Stimulation of the kinin B2 receptor has been previously reported to promote AAA development and rupture in a mouse model. The endogenous B2 receptor agonist, bradykinin, is generated from the kallikrein-kinin system following activation of plasma kallikrein by Factor XII (FXII). In the current study whole-body FXII deletion, or neutralisation of activated FXII (FXIIa), inhibited expansion of the suprarenal aorta (SRA) of apolipoprotein E-deficient mice in response to angiotensin II (AngII) infusion. FXII deficiency or FXIIa neutralisation led to decreased aortic tumor necrosis factor-α-converting enzyme (TACE/a disintegrin and metalloproteinase-17 (aka tumor necrosis factor-α-converting enzyme) (ADAM-17)) activity, plasma kallikrein concentration, and epithelial growth factor receptor (EGFR) phosphorylation compared with controls. FXII deficiency or neutralisation also reduced Akt1 and Erk1/2 phosphorylation and decreased expression and levels of active matrix metalloproteinase (Mmp)-2 and Mmp-9. The findings suggest that FXII, kallikrein, ADAM-17, and EGFR are important molecular mediators by which AngII induces aneurysm in apolipoprotein E-deficient mice. This could be a novel pathway to target in the design of drugs to limit AAA progression.

Development of a two-stage limb ischemia model to better simulate human peripheral artery disease.

Peripheral arterial disease (PAD) develops due to the narrowing or blockage of arteries supplying blood to the lower limbs. Surgical and endovascular interventions are the main treatments for advanced PAD but alternative and adjunctive medical therapies are needed. Currently the main preclinical experimental model employed in PAD research is based on induction of acute hind limb ischemia (HLI) by a 1-stage procedure. Since there are concerns regarding the ability to translate findings from this animal model to patients, we aimed to develop a novel clinically relevant animal model of PAD. HLI was induced in male Apolipoprotein E (ApoE-/-) deficient mice by a 2-stage procedure of initial gradual femoral artery occlusion by ameroid constrictors for 14 days and subsequent excision of the femoral artery. This 2-stage HLI model was compared to the classical 1-stage HLI model and sham controls. Ischemia severity was assessed using Laser Doppler Perfusion Imaging (LDPI). Ambulatory ability was assessed using an open field test, a treadmill test and using established scoring scales. Molecular markers of angiogenesis and shear stress were assessed within gastrocnemius muscle tissue samples using quantitative polymerase chain reaction. HLI was more severe in mice receiving the 2-stage compared to the 1-stage ischemia induction procedure as assessed by LDPI (p = 0.014), and reflected in a higher ischemic score (p = 0.004) and lower average distance travelled on a treadmill test (p = 0.045). Mice undergoing the 2-stage HLI also had lower expression of angiogenesis markers (vascular endothelial growth factor, p = 0.004; vascular endothelial growth factor- receptor 2, p = 0.008) and shear stress response mechano-transducer transient receptor potential vanilloid 4 (p = 0.041) within gastrocnemius muscle samples, compared to animals having the 1-stage HLI procedure. Mice subjected to the 2-stage HLI receiving an exercise program showed significantly greater improvement in their ambulatory ability on a treadmill test than a sedentary control group. This study describes a novel model of HLI which leads to more severe and sustained ischemia than the conventionally used model. Exercise therapy, which has established efficacy in PAD patients, was also effective in this new model. This new model maybe useful in the evaluation of potential novel PAD therapies.

Multimorbidity in Early Childhood and Socioeconomic Disadvantage: Findings From a Large New Zealand Child Cohort.

OBJECTIVE: In contrast with multimorbidity during adulthood, the relationship of childhood multimorbidity with socioeconomic position (SEP) is poorly understood. We aimed to describe early childhood multimorbidity and investigate the relationship of this with SEP. METHODS: Within a diverse prospective child cohort study, we determined associations of SEP with multimorbidity (defined as the presence of 2 or more chronic conditions) at age 2 years. Maternal SEP was ranked into 5 categories using an index constructed from variables collected antenatally describing maternal education, employment, financial stress, beneficiary status, housing tenure, overcrowding, and residential mobility. Missing values were handled using multiple imputation with chained equations. Independent associations of SEP with multimorbidity were described using adjusted odds ratios (OR) and 95% confidence intervals (CI). RESULTS: Of the 6822 women and 6853 children who were enrolled into the cohort study, 5737 (84%) mother-child dyads had complete antenatal data and were interviewed at age 2 years. Of these 5737, for 3826 (67%) dyads, there were complete data for all variables. Multimorbidity was present in 374/3838 (9.7%) of the cohort children. After multiple imputation and adjustment for maternal ethnicity, smoking, poor health, depressive symptoms, and child gender, the odds of multimorbidity being present were increased for children of mothers in the most (OR 1.74, 95% CI 1.16-2.59) and second most (OR 1.43, 95% CI 1.00-2.04) versus the least disadvantaged group. CONCLUSION: The odds of multimorbidity are increased for children whose mothers have lower SEP. Cumulative socioeconomic disadvantage increases the potential for a chronic illness trajectory to develop in early childhood.

Antenatal determinants of early childhood talking delay and behavioural difficulties.

The determinants of talking delay alone or its comorbidity with behavioural difficulties was examined in 5768 two-year-old members of the Growing Up in New Zealand longitudinal study. Using the MacArthur-Bates Communicative Development inventories and the total difficulties score from the preschool Strengths and Difficulties Questionnaire, a composite measure was created so that children were categorised as showing no language or behavioural concerns (72.5%), behavioural only difficulties (6.1%), language only difficulties (18.1%), and comorbid language and behavioural difficulties (3.3%). Analyses revealed that antenatal factors such as maternal perceived stress, inadequate folate intake, vitamin intake, alcohol consumption during the first trimester and maternal smoking all had a significant effect on child outcomes. In particular, low multivitamin intake and perceived stress during pregnancy were associated with coexisting language and behavioural difficulties. These findings support international research in showing that maternal factors during pregnancy are associated with developmental outcomes in the early childhood period, and demonstrate these associations within a NZ context. Interventions which address maternal stress management and health behaviours during pregnancy could be beneficial to offspring development.

A longitudinal study of antenatal and perinatal risk factors in early childhood cognition: Evidence from Growing Up in New Zealand.

BACKGROUND: Poor maternal health, disadvantageous exposures during pregnancy and unfavourable perinatal events are associated with adverse trajectories in offspring cognitive development. AIM: To examine longitudinal associations between antenatal maternal, perinatal and maternal health characteristics and children's early cognitive development across executive control, motor ability and receptive language domains. STUDY DESIGN, SUBJECTS AND OUTCOME MEASURES: Analyses comprised interview and observational data from 4587 children and their mothers enrolled in the longitudinal Growing Up in New Zealand cohort study. Children's executive control (Luria hand clap task), motor skills (mothers' report) and receptive language ability (Peabody Picture Vocabulary Test) were assessed at age 4.5 years. Multivariate logistic regression analyses were conducted, controlling for sociodemographic factors. RESULTS: Smoking pre- and during pregnancy, no folate intake during first trimester and low birth weight were risk factors for poorer executive control. Perceived stress during pregnancy, no folate intake during first trimester and low birth weight were all risk factors for poorer motor ability. Smoking pre-pregnancy, antenatal anxiety and no folate intake during first trimester were risk factors for poorer receptive language ability. CONCLUSION: Adverse ante- and perinatal environments are associated with poorer executive control, motor and receptive language abilities in early childhood. Improving maternal education and support especially for more disadvantaged mothers during pregnancy may reduce the potential deleterious impact of adverse ante- and perinatal conditions on children's early cognition.

A diet enriched with tree nuts reduces severity of atherosclerosis but not abdominal aneurysm in angiotensin II-infused apolipoprotein E deficient mice.

BACKGROUND AND AIMS: Diets enriched with tree nuts have been demonstrated to reduce the risk of atherosclerosis-related cardiovascular events. Abdominal aortic aneurysm (AAA) shares common risk factors with atherosclerosis and AAA patients commonly have atherosclerosis related cardiovascular events. AAA has some distinct pathological and clinical characteristics to those of atherosclerosis. No previous study has examined the effect of a diet enriched with tree nuts on experimental or clinical AAA. This study investigated the effect of a diet enriched with tree nuts on the development and severity of AAA within an experimental rodent model. METHODS: Male apolipoprotein E deficient mice were allocated to a diet enriched with tree nuts or control diet for 56 days (n = 17 per group). After 28 days, all mice were infused with angiotensin II whilst being maintained on their respective diets. The primary outcome was AAA severity assessed by the supra-renal aortic diameter, measured by ultrasound and ex vivo morphometric analysis. The severity of atherosclerosis was assessed by computer-aided analysis of Sudan IV stained aortic arches and sections of brachiocephalic arteries prepared with Van Gieson's stain. RESULTS: The diet enriched with tree nuts did not influence aortic diameter or aortic rupture incidence. Mice receiving the diet enriched with tree nuts had significantly less atherosclerosis within the brachiocephalic artery (p = 0.033) but not in the aortic arch. CONCLUSIONS: This experimental study suggests that a diet enriched with tree nuts does not reduce the severity of AAA, but does reduce the severity of atherosclerosis within the brachiocephalic artery. The study was not powered to identify a moderate effect of the diet on the primary outcome and therefore this cannot be excluded.

Role of muscle spindle feedback in regulating muscle activity strength during walking at different speed in mice.

Terrestrial animals increase their walking speed by increasing the activity of the extensor muscles. However, the mechanism underlying how this speed-dependent amplitude modulation is achieved remains obscure. Previous studies have shown that group Ib afferent feedback from Golgi tendon organs that signal force is one of the major regulators of the strength of muscle activity during walking in cats and humans. In contrast, the contribution of group Ia/II afferent feedback from muscle spindle stretch receptors that signal angular displacement of leg joints is unclear. Some studies indicate that group II afferent feedback may be important for amplitude regulation in humans, but the role of muscle spindle feedback in regulation of muscle activity strength in quadrupedal animals is very poorly understood. To examine the role of feedback from muscle spindles, we combined in vivo electrophysiology and motion analysis with mouse genetics and gene delivery with adeno-associated virus. We provide evidence that proprioceptive sensory feedback from muscle spindles is important for the regulation of the muscle activity strength and speed-dependent amplitude modulation. Furthermore, our data suggest that feedback from the muscle spindles of the ankle extensor muscles, the triceps surae, is the main source for this mechanism. In contrast, muscle spindle feedback from the knee extensor muscles, the quadriceps femoris, has no influence on speed-dependent amplitude modulation. We provide evidence that proprioceptive feedback from ankle extensor muscles is critical for regulating muscle activity strength as gait speed increases. NEW & NOTEWORTHY Animals upregulate the activity of extensor muscles to increase their walking speed, but the mechanism behind this is not known. We show that this speed-dependent amplitude modulation requires proprioceptive sensory feedback from muscle spindles of ankle extensor muscle. In the absence of muscle spindle feedback, animals cannot walk at higher speeds as they can when muscle spindle feedback is present.

Determinants of folic acid supplement use outside national recommendations for pregnant women: results from the Growing Up in New Zealand cohort study.

OBJECTIVE: To evaluate the sociodemographic and lifestyle factors associated with insufficient and excessive use of folic acid supplements (FAS) among pregnant women. DESIGN: A pregnancy cohort to which multinomial logistic regression models were applied to identify factors associated with duration and dose of FAS use. SETTING: The Growing Up in New Zealand child study, which enrolled pregnant women whose children were born in 2009-2010. SUBJECTS: Pregnant women (n 6822) enrolled into a nationally generalizable cohort. RESULTS: Ninety-two per cent of pregnant women were not taking FAS according to the national recommendation (4 weeks before until 12 weeks after conception), with 69 % taking insufficient FAS and 57 % extending FAS use past 13 weeks' gestation. The factors associated with extended use differed from those associated with insufficient use. Consistent with published literature, the relative risks of insufficient use were increased for younger women, those with less education, of non-European ethnicities, unemployed, who smoked cigarettes, whose pregnancy was unplanned or who had older children, or were living in more deprived households. In contrast, the relative risks of extended use were increased for women of higher socio-economic status or for whom this was their first pregnancy and decreased for women of Pacific v. European ethnicity. CONCLUSIONS: In New Zealand, current use of FAS during pregnancy potentially exposes pregnant women and their unborn children to too little or too much folic acid. Further policy development is necessary to reduce current socio-economic inequities in the use of FAS.

Transitions in Smoking Across a Pregnancy: New Information from the Growing Up in New Zealand Longitudinal Study.

Introduction Maternal smoking remains a modifiable cause of adverse maternal and child health outcomes. This study investigated smoking transitions across pregnancy. Methods Data from the contemporary child cohort study Growing Up in New Zealand (n = 6822) were used to analyse smoking status across three points across a pregnancy: pre-pregnancy, during pregnancy and after pregnancy. Odds-ratios (OR) were calculated for maternal, socio-economic and pregnancy-related factors associated with each transition using multivariate logistic regression. Results The prevalence of smoking pre-pregnancy was 20.3%. The cessation rate during pregnancy was 48.5%, while the postpartum relapse rate was 36.0%. Heavy smokers were less likely to quit during pregnancy (OR 0.13, 95% CI 0.08-0.20), and more likely to relapse at 9 months (OR 2.63, CI 1.60-4.32), relative to light smokers. Women in households with another smoker were less likely to quit during pregnancy (OR 0.35, CI 0.25-0.48), and more likely to relapse postpartum (OR 2.00, CI 1.14-3.51), relative to women in a smoke-free household. Women without high school qualifications were less likely to quit during pregnancy than women with bachelor degrees (OR 0.21, CI 0.11-0.41) but no more likely to relapse. Maori women were less likely to quit during pregnancy than European women (OR 0.35, CI 0.25-0.49) but no more likely to relapse. Conclusion Heavy smokers and those with another smoker in the household are at high risk of smoking during pregnancy or relapsing after pregnancy. Decreasing smoking across a pregnancy therefore requires a focus on cessation in all households with heavy smokers of child-bearing age. The association between smoking and ethnicity may be confounded as it not consistent across the pregnancy.

Pre-school nutrition-related behaviours at home and early childhood education services: findings from the Growing Up in New Zealand longitudinal study.

OBJECTIVE: Pre-school nutrition-related behaviours influence diet and development of lifelong eating habits. We examined the prevalence and congruence of recommended nutrition-related behaviours (RNB) in home and early childhood education (ECE) services, exploring differences by child and ECE characteristics. DESIGN: Telephone interviews with mothers. Online survey of ECE managers/head teachers. SETTING: New Zealand. SUBJECTS: Children (n 1181) aged 45 months in the Growing Up in New Zealand longitudinal study. RESULTS: A mean 5·3 of 8 RNB were followed at home, with statistical differences by gender and ethnic group, but not socio-economic position. ECE services followed a mean 4·8 of 8 RNB, with differences by type of service and health-promotion programme participation. No congruence between adherence at home and in ECE services was found; half of children with high adherence at home attended a service with low adherence. A greater proportion of children in deprived communities attended a service with high adherence, compared with children living in the least deprived communities (20 and 12 %, respectively). CONCLUSIONS: Children, across all socio-economic positions, may not experience RNB at home. ECE settings provide an opportunity to improve or support behaviours learned at home. Targeting of health-promotion programmes in high-deprivation areas has resulted in higher adherence to RNB at these ECE services. The lack of congruence between home and ECE behaviours suggests health-promotion messages may not be effectively communicated to parents/family. Greater support is required across the ECE sector to adhere to RNB and promote wider change that can reach into homes.

Resveratrol Inhibits Growth of Experimental Abdominal Aortic Aneurysm Associated With Upregulation of Angiotensin-Converting Enzyme 2.

OBJECTIVE: Recent evidence suggests an important role for angiotensin-converting enzyme 2 (ACE2) in limiting abdominal aortic aneurysm (AAA). This study examined the effect of ACE2 deficiency on AAA development and the efficacy of resveratrol to upregulate ACE2 in experimental AAA. APPROACH AND RESULTS: Ace2 deletion in apolipoprotein-deficient mice (ApoE-/-Ace2-/y ) resulted in increased aortic diameter and spontaneous aneurysm of the suprarenal aorta associated with increased expression of inflammation and proteolytic enzyme markers. In humans, serum ACE2 activity was negatively associated with AAA diagnosis. ACE2 expression was lower in infrarenal biopsies of patients with AAA than organ donors. AAA was more severe in ApoE-/-Ace2-/y mice compared with controls in 2 experimental models. Resveratrol (0.05/100-g chow) inhibited growth of pre-established AAAs in ApoE-/- mice fed high-fat chow and infused with angiotensin II continuously for 56 days. Reduced suprarenal aorta dilatation in mice receiving resveratrol was associated with elevated serum ACE2 and increased suprarenal aorta tissue levels of ACE2 and sirtuin 1 activity. In addition, the relative phosphorylation of Akt and ERK (extracellular signal-regulated kinase) 1/2 within suprarenal aorta tissue and gene expression for nuclear factor of kappa light polypeptide gene enhancer in B cells 1, angiotensin type-1 receptor, and metallopeptidase 2 and 9 were significantly reduced. Upregulation of ACE2 in human aortic smooth muscle cells by resveratrol in vitro was sirtuin 1-dependent. CONCLUSIONS: This study provides experimental evidence of an important role for ACE2 in limiting AAA development and growth. Resveratrol upregulated ACE2 and inhibited AAA growth in a mouse model.

Do childcare menus meet nutrition guidelines? Quantity, variety and quality of food provided in New Zealand Early Childhood Education services.

OBJECTIVE: To describe food provision and evaluate menus in New Zealand childcare services, determining associations with service characteristics and/or cost of menu. METHODS: Licensed services in three regions of New Zealand participated in an online survey, uploading a weekly menu where applicable. Menus were scored for compliance with guidelines on quantity, variety and quality of foods served. Bivariate and multivariate associations between menu score and service characteristics were analysed. RESULTS: A total of 257 services participated (30% of 847 services invited). Food was provided daily in 56%, with 34% providing lunch and snacks daily. Of the 57 full menus analysed, only three (5%) met all 10 scoring criteria (mean score of 6.8/10). Higher menu scores were statistically associated with employing a cook, high and low (not medium) neighbourhood deprivation, the Heart Foundation's Healthy Heart Award program; there was no association with food costs. The Healthy Heart Award remained statistically associated with higher menu score after adjustment for other service characteristics. CONCLUSION: Most menus did not meet current nutrition guidelines for quantity, variety, and limiting 'sometimes' and 'occasional' foods. Implications for public health: This study provides a baseline for monitoring menu compliance in New Zealand and evidence for nutrition promotion and menu improvement programmes in early education.

Wnt Signaling Pathway Inhibitor Sclerostin Inhibits Angiotensin II-Induced Aortic Aneurysm and Atherosclerosis.

OBJECTIVE: Sclerostin (SOST) has been identified as an important regulator of bone formation; however, it has not been previously implicated in arterial disease. The aim of this study was to assess the role of SOST in aortic aneurysm (AA) and atherosclerosis using human samples, a mouse model, and in vitro investigations. APPROACH AND RESULTS: SOST protein was downregulated in human and mouse AA samples compared with controls. Transgenic introduction of human SOST in apolipoprotein E-deficient (ApoE-/-) mice (SOSTTg .ApoE-/-) and administration of recombinant mouse Sost inhibited angiotensin II-induced AA and atherosclerosis. Serum concentrations of several proinflammatory cytokines were significantly reduced in SOSTTg .ApoE-/- mice. Compared with controls, the aortas of mice receiving recombinant mouse Sost and SOSTTg .ApoE-/- mice showed reduced matrix degradation, reduced elastin breaks, and preserved collagen. Decreased inflammatory cell infiltration and a reduction in the expression of wingless-type mouse mammary virus integration site/ß-catenin responsive genes, including matrix metalloproteinase-9, osteoprotegerin, and osteopontin, were observed in the aortas of SOSTTg .ApoE-/- mice. SOST expression was downregulated and the wingless-type mouse mammary virus integration site/ß-catenin pathway was activated in human AA samples. The cytosine-phosphate-guanine islands in the SOST gene promoter showed significantly higher methylation in human AA samples compared with controls. Incubation of vascular smooth muscle cells with the demethylating agent 5-azacytidine resulted in upregulation of SOST, suggesting that SOST is epigenetically regulated. CONCLUSIONS: This study identifies that SOST is expressed in the aorta and downregulated in human AA possibly because of epigenetic silencing. Upregulating SOST inhibits AA and atherosclerosis development, with potential important implications for treating these vascular diseases.