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Highlights: [•] Perinatal growth restriction increases the risk of adult psychiatric disease. [•] Growth restriction decreases circulating leptin, a neurotrophic hormone. [•] Neonatal leptin deficiency decreases frontal lobe volume and programs hyperactivity. [•] Increased leptin receptor expression suggests a potential therapeutic intervention. [Copyright &y& Elsevier]

A rapidly expanding body of research indicates that early social environments characterized by adversity, subordination and stress, along with individual differences in susceptibility to such environments, create risks for lifelong chronic diseases, including declines in oral health. Emerging findings suggest that gene-environment interplay, resulting in epigenetically regulated differences in gene expression, underlie many such declines in health. The origins of these processes in early life reveal how many of the chronic morbidities of adulthood should be viewed as developmental disorders, with etiologic roots in childhood. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To determine the effect of gestational hypertension on the developmental origins of blood pressure (BP), altered kidney gene expression, salt-sensitivity and cardiac hypertrophy (CH) in adult offspring. Methods: Female mice lacking atrial natriuretic peptide (ANP−/−) were used as a model of gestational hypertension. Heterozygous ANP+/− offspring was bred from crossing either ANP+/+ females with ANP−/− males yielding ANP+/−WT offspring, or from ANP−/− females with ANP+/+ males yielding ANP+/−KO offspring. Maternal BP during pregnancy was measured using radiotelemetry. At 14weeks of age, offspring BP, gene and protein expression were measured in the kidney with real-time quantitative PCR, receptor binding assay and ELISA. Results: ANP+/−KO offspring exhibited normal BP at 14weeks of age, but displayed significant CH (P<0.001) as compared to ANP+/−WT offspring. ANP+/−KO offspring exhibited significantly increased gene expression of natriuretic peptide receptor A (NPR-A) (P<0.001) and radioligand binding studies demonstrated significantly reduced NPR-C binding (P=0.01) in the kidney. Treatment with high salt diet increased BP (P<0.01) and caused LV hypertrophy (P<0.001) and interstitial myocardial fibrosis only in ANP+/−WT and not ANP+/−KO offspring, suggesting gestational hypertension programs the offspring to show resistance to salt-induced hypertension and LV remodeling. Our data demonstrate that altered maternal environments can determine the salt-sensitive phenotype of offspring. [Copyright &y& Elsevier]

The growing field of epigenetics and human behavior affords an unprecedented opportunity to discover molecular underpinnings of mental health disorders and pave the way for the development of preventive intervention programs. Maternal depression during pregnancy is a serious public health issue and leads to a 4-fold increase in the likelihood that the child will develop depression. We describe how mood disorders, particularly depression, may be shaped by early life stress, programming, and epigenetic processes and pathways showing how these processes could lead to depression in childhood. Implications of this approach to the study of mental health disorders for preventive interventions are discussed. [ABSTRACT FROM AUTHOR]

Obesity and overnutrition during pregnancy affect fetal programming of adult disease. Children born after maternal bariatric gastrointestinal bypass surgery (AMS) are less obese and exhibit improved cardiometabolic risk profiles carried into adulthood compared with siblings born before maternal surgery (BMS). This study was designed to analyze the impact of maternal weight loss surgery on methylation levels of genes involved in cardiometabolic pathways in BMS and AMS offspring. Differential methylation analysis between a sibling cohort of 25 BMS and 25 AMS (2-25 y-old) offspring from 20 mothers was conducted to identify biological functions and pathways potentially involved in the improved cardiometabolic profile found in AMS compared with BMS offspring. Links between gene methylation and expression levels were assessed by correlating genomic findings with plasma markers of insulin resistance (fasting insulin and homeostatic model of insulin resistance). A total of 5,698 genes were differentially methylated between BMS and AMS siblings, exhibiting a preponderance of glucoregulatory, inflammatory, and vascular disease genes. Statistically significant correlations between gene methylation levels and gene expression and plasma markers of insulin resistance were consistent with metabolic improvements in AMS offspring, reflected in genes involved in diabetes-related cardiometabolic pathways. This unique clinical study demonstrates that effective treatment of a maternal phenotype is durably detectable in the methylome and transcriptome of subsequent offspring. [ABSTRACT FROM AUTHOR]

Clinical practice guidelines for elective cesarean section at early-term gestation (37-38 weeks) recommend antenatal corticosteroids to reduce neonatal respiratory morbidity. However, the long-term health implications for offspring exposed to corticosteroids at term are unknown and may differ from the effects of preterm corticosteroid exposure. We therefore randomized singleton-bearing ewes ( n = 64) to receive a clinically relevant dose of corticosteroids at term or no treatment. Body composition was assessed in adult offspring using dual-energy X-ray absorptiometry. Relative to skeletal size female, but not male, offspring of steroid-treated ewes had increased weight and a greater fat mass than controls (relative weight: 49.1 ± 1.1 vs. 52.9 ± 1.2 kg/m2, p = 0.02; relative fat mass: 5.4 ± 0.7 vs. 3.4 ± 0.7 kg/m2, p = 0.04). Whether corticosteroid exposure at early-term gestation increases adult adiposity in humans is unknown and needs further investigation. [ABSTRACT FROM AUTHOR]

Abstract: The association of socioeconomic status (SES) with a range of lifecourse outcomes is robust, but the causes of these associations are not well understood. Research on the developmental origins of health and disease has led to the hypothesis that early developmental disturbance might permanently affect the lifecourse, accounting for some of the burden of chronic diseases such as coronary heart disease. Here we assessed developmental disturbance using bodily and facial symmetry and examined its association with socioeconomic status (SES) in childhood, and attained status at midlife. Symmetry was measured at ages 83 (facial symmetry) and 87 (bodily symmetry) in a sample of 292 individuals from the Lothian Birth Cohort 1921 (LBC1921). Structural equation models indicated that poorer SES during early development was significantly associated with lower facial symmetry (standardized path coefficient −.25, p =.03). By contrast, midlife SES was not significantly associated with symmetry. The relationship was stronger in men (−.44, p =.03) than in women (−.12, p =.37), and the effect sizes were significantly different in magnitude (p =.004). These findings suggest that SES in early life (but not later in life) is associated with developmental disturbances. Facial symmetry appears to provide an effective record of early perturbations, whereas bodily symmetry seems relatively imperturbable. As bodily and facial symmetries were sensitive to different influences, they should not be treated as interchangeable. However, markers of childhood disturbance remain many decades later, suggesting that early development may account in part for associations between SES and health through the lifecourse. Future research should clarify which elements of the environment cause these perturbations. [Copyright &y& Elsevier]

The Peri/postnatal Epigenetic Twins Study (PETS) is a longitudinal cohort of 250 pairs of Australian twins and their mothers, who were recruited mid-way through pregnancy from January 2007 to September 2009. The study is centered on the developmental origins of health and disease paradigm (DOHaD) in which an adverse intrauterine environment predisposes the individual to complex disease in later life by reducing growth in utero and adversely altering developmental plasticity. Data concerning diet and lifestyle were collected from mothers during pregnancy, and samples of plasma and serum taken at 28 weeks’ gestation. We attended 75% of all births, at which time we collected multiple biological samples including placenta, cord blood, and neonatal cheek cells, the latter from 91% of pairs. Chorionicity was recorded and zygosity was determined by DNA testing where necessary. Approximately 40% of the twins are monozygotic, two-thirds of which are dichorionic. Twins were seen again at 18 months of age and repeat blood and cheek swabs taken where possible. Studies of gene expression and the epigenetic marks of DNA methylation have so far revealed that twins exhibit a wide range of epigenetic discordance at birth, that one-third of the epigenome changes significantly between birth and 18 months; shared (maternal) environment, genetic factors, and non-shared intrauterine environment contribute to an increasing proportion of epigenetic variation at birth, respectively, and affect tissues differently, and that within-pair birth weight discordance correlates with epigenetic discordance in genes associated with lipid metabolism, supporting an epigenetic mechanism for DOHaD. [ABSTRACT FROM AUTHOR]

Urochordates (ascidians) have recently supplanted cephalochordates (amphioxus) as the extant sister taxon of vertebrates. Given that urochordates possess migratory cells that have been classified as 'neural crest-like'- and that cephalochordates lack such cells - this phylogenetic hypothesis may have significant implications with respect to the origin of the neural crest and neural crest-derived skeletal tissues in vertebrates. We present an overview of the genes and gene regulatory network associated with specification of the neural crest in vertebrates. We then use these molecular data - alongside cell behaviour, cell fate and embryonic context - to assess putative antecedents (latent homologues) of the neural crest or neural crest cells in ascidians and cephalochordates. Ascidian migratory mesenchymal cells - non-pigment-forming trunk lateral line cells and pigment-forming 'neural crest-like cells' (NCLC) - are unlikely latent neural crest cell homologues. Rather, Snail-expressing cells at the neural plate of border of urochordates and cephalochordates likely represent the extent of neural crest elaboration in non-vertebrate chordates. We also review evidence for the evolutionary origin of two neural crest-derived skeletal tissues - cartilage and dentine. Dentine is a bona fide vertebrate novelty, and dentine-secreting odontoblasts represent a cell type that is exclusively derived from the neural crest. Cartilage, on the other hand, likely has a much deeper origin within the Metazoa. The mesodermally derived cellular cartilages of some protostome invertebrates are much more similar to vertebrate cartilage than is the acellular 'cartilage-like' tissue in cephalochordate pharyngeal arches. Cartilage, therefore, is not a vertebrate novelty, and a well-developed chondrogenic program was most likely co-opted from mesoderm to the neural crest along the vertebrate stem. We conclude that the neural crest is a vertebrate novelty, but that neural crest cells and their derivatives evolved and diversified in a step-wise fashion - first by elaboration of neural plate border cells, then by the innovation or co-option of new or ancient metazoan cell fates. [ABSTRACT FROM AUTHOR]

The article discusses if an association between infant growth and endothelial function is already present during discrete periods of growth during the first 5 months of life in healthy term infants. A cohort of 104 newborns was studied in the first week after birth and reexamined at the age of 6 months. Results show that growth in the first month of life is inversely associated with endothelium-dependent vasodilatation at the age of 6 months in healthy term infants, regardless of birth size.

The developmental origins of health and disease hypothesis is now strongly supported by both animal and human evidence, and as a consequence, obstetricians, neonatologists and paediatricians need to consider the impact that the in utero and early post-natal environment can have on later renal, cardiovascular and metabolic health. Four common clinical scenarios were provided along with animal and human evidence identifying long-term health implications. Suggestions as to how we should translate this growing body of evidence into practice are provided. [ABSTRACT FROM AUTHOR]

Summary: Background: Raised maternal anxiety during pregnancy is associated with increased risk of adverse neurodevelopmental outcomes for her child. The mechanisms underlying this are not known but animal studies suggest prenatal stress may alter the function of the placenta. Here we determined whether maternal prenatal anxiety was associated with a downregulation of placental 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2), the enzyme which metabolises cortisol. Methods: We recruited mothers the day before delivery by elective caesarean, and gave them the Spielberger Trait and State anxiety and Edinburgh Depression self-rating scales. Placentae were collected and aliquots stored for later analysis. Results: Prenatal Trait anxiety was negatively correlated with placental 11β-HSD2 mRNA expression (r =−0.40, p <0.01, n =56). Results were similar with male and female fetuses (r =−0.39, p =0.04, n =28; r =−0.40, p =0.03, n =28) respectively. Results were also significant with State anxiety (r =−0.27, p =0.05, n =56) but somewhat weaker for depression (r =−0.20, p =0.13, n =56). Preliminary analyses on a subset of cases (n =25) suggested parallel results for enzyme activity. Conclusions: These findings provide evidence for an association between prenatal maternal mood and downregulation of placental 11β-HSD2. Results are consistent with raised maternal anxiety being associated with increased fetal exposure to maternal cortisol, and support the hypothesis that this may be one mechanism underlying fetal programming by prenatal stress. [Copyright &y& Elsevier]

A fetal/neonatal neurology program should encompass interdisciplinary service, educational and research objectives, merging curricula concerning maternal, placental, fetal and neonatal contributions to brain health and disease. This approach is anchored by research in early life programming that demonstrates that prenatal and postnatal factors influence long-term neurologic health. This concept also supports the design of neuroprotective interventions during critical periods of brain development when brain circuitries more optimally adapt to maturational challenges. Preventive, rescue and repair protocols will transform pediatric medical practices, to promote improved childhood outcomes. Inclusion of life-course science and research will identify medical and socioeconomic factors that favorably or adversely affect quality of life into adulthood. Greater awareness of the convergence of developmental origins of brain health and disease and developmental aging theories will influence public health policies, to encourage financial support for programs that will improve the quality of life for the child and adult. [ABSTRACT FROM AUTHOR]

Osteoporosis is a major public health problem due to consequent fragility fractures; data from the UK suggest that up to 50% of women and 20% men aged 50 years will have an osteoporosis-related fracture in their remaining lifetime. Skeletal size and density increase from early embryogenesis through intrauterine, infant, childhood and adult life to reach a peak in the third to fourth decade. The peak bone mass achieved is a strong predictor of later osteoporosis risk. Epidemiological studies have demonstrated a positive relationship between early growth and later bone mass, both at peak and in later life, and also with reduced risk of hip fracture. Mother-offspring cohorts have allowed the elucidation of some of the specific factors in early life, such as maternal body build, lifestyle and 25(OH)-vitamin D status, which might be important. Most recently, the phenomenon of developmental plasticity, whereby a single genotype may give rise to different phenotypes depending on the prevailing environment, and the science of epigenetics have presented novel molecular mechanisms which may underlie previous observations. This review will give an overview of these latter developments in the context of the burden of osteoporosis and the wider data supporting the link between the early environment and bone health in later life. [ABSTRACT FROM AUTHOR]

The second part of this review of the developmental origins of cerebrovascular disease discusses prenatal gene-environment interactions concerning maternal, placental, and fetal conditions that culminate in specific injuries such as perinatal stroke, as well as complications of intrauterine growth restriction and congenital heart disease. A greater understanding of gene-environment influences on cerebrovascular health and disease in early life will contribute to the successful development of neuroprotective strategies throughout the lifespan. [ABSTRACT FROM AUTHOR]

Background: Iron deficiency is the most common micronutrient deficiency worldwide. Experimental animal studies suggest that mothers deficient in iron during pregnancy are more likely to have offspring who become obese with high blood pressure. C282Y mutation carriers are more likely to have higher iron stores. Methods: We undertook an instrumental variable (IV) analysis, using maternal C282Y as an indicator for the mother's iron status, to examine its association with offspring blood pressure (BP), waist circumference (WC), and body mass index (BMI), and compared the results to that of ordinary least squares (OLS) regression. Offspring of a sub-cohort of mothers from the UK Women's Cohort Study (UKWCS) were recruited in 2009-2010 (n = 348, mean age = 41 years). Their blood pressure, height, and weight were measured at their local general medical practice, and they were asked to self-measure their waist circumference. About half were offspring of C282Y carriers. Maternal ferritin was used as a biomarker of maternal iron status. Results: Maternal C282Y was strongly associated with maternal ferritin (mean difference per allele = 84 g/L, 95% confidence interval: 31-137, P = 0.002). Using IV analyses, maternal ferritin was not linked to offspring's BP, BMI, or WC. The first stage F-statistic for the strength of the instrument was 10 (Kleibergen-Paap rk LM P = 0.009). Maternal ferritin was linked to offspring diastolic BP, WC, and BMI in univariable, but not in multivariable OLS analysis. There was no difference between the OLS and the IV models coefficients for any of the outcomes considered. Conclusion: We found no association between maternal iron status and adult offspring's BP and adiposity using both multivariable OLS and IV modeling. To our knowledge, this is the first study examining this relationship. Further exploration in larger studies that have genetic variation assessed in both mother and offspring should be considered. [ABSTRACT FROM AUTHOR]

Abstract: Recent evidence has linked birth weight to later behaviour/mental disorders, yet studies have hitherto neglected to investigate the relationship between birth weight and adult anxiety disorders. Prospectively collected data from 2210 mother/offspring pairs of the Mater University Study of Pregnancy (MUSP) birth cohort was used to test for associations between birth weight z-score and four major groupings of DSM-IV anxiety disorders. Birth weight z-score was linearly and inversely associated with lifetime diagnosis of post-traumatic stress disorders at 21 years, with those falling within the smallest birth weight quintile group at almost two-fold increased odds (OR=1.96, 95% CI: 1.10, 3.52) of being diagnosed with the disorder compared to those falling within the largest group. The association remained when subsequent analysis restricted the sample to those exposed to trauma. This is the first study in which birth weight has been found to be associated with post-traumatic stress disorders in adults. [Copyright &y& Elsevier]

Most members of minority ethnic//racial groups in affluent western societies are recent immigrants or immediate descendants thereof. The health implications of ethnic groups also being migrant groups are important but often not fully explored. Research demonstrating developmental influences on the risk of type 2 diabetes and associated conditions suggests that migrants will differ in disease risk compared with the general population. It also leads us to expect intergenerational differences in disease risk within many minority ethnic//racial groups. Differences in health behaviors between ethnic//racial groups are also expected to change over time following migration, including across generations, but do not necessarily follow a simple model of acculturation. Understanding the ways in which the biosocial heritage of migrant groups interacts over the long term with migrants' new environments is central to understanding differences in disease risk that are identified as ethnic or racial and also highlights heterogeneity in risk within ethnic groups. [ABSTRACT FROM AUTHOR]

Evidence from previous studies suggests an association between prenatal exposure to famine and increased risk for depression. The aim of this study was to investigate whether prenatal exposure to the Dutch famine is associated with self-reported depression/anxiety and whether a potential association is mediated by the presence of cardio-metabolic disease. A total of 819 persons, born as term singletons around the 1944–1945 Dutch famine, filled out the Hospital Anxiety and Depression Scale (HADS) and were asked about their medical history. As indicators of cardio-metabolic disease we included type 2 diabetes (T2D), hypertension and coronary heart disease (CHD). In the total study population, exposure to famine during early gestation was associated with the presence of self-reported mild-to-severe anxiety. Evidence was found for several interactions between exposure in early gestation and sex. Subsequent analyses according to sex showed that men exposed to famine during early gestation scored higher on the HADS depression scale. Self-reported mild-to-severe anxiety symptoms were more prevalent among early exposed men. No such differences were found in women. T2D and hypertension were not correlated with any of the depression and anxiety measures. Adjusting for the presence of CHD did minimally attenuate the size of the reported associations. In conclusion, the present results do not match those previously reported in prenatally famine-exposed individuals. We found only weak evidence for an association between prenatal famine exposure and symptoms of depression and anxiety, which was shown exclusively in men exposed during early gestation. [ABSTRACT FROM PUBLISHER]

Summary: This systematic review and meta-analysis assessed the strength and magnitude of the association between birthweight and adult bone mass. Higher birthweight was associated with higher bone mineral content of the spine and hip in adult men and women at ages between 18 and 80 years across a range of settings. Introduction: The aim of this review was to assess the strength and magnitude of the association between early size and adult bone mass. Methods: Systematic review and meta-analysis of studies that assessed the association between birthweight or weight at 1 year, and bone mineral content (BMC) or bone mineral density (BMD) in adulthood. Results: Fourteen studies met inclusion criteria. Nine assessed the relationship between birthweight and lumbar spine BMC, most showing that higher birthweight was associated with greater adult BMC. Meta-analysis demonstrated that a 1 kg increase in birthweight was associated with a 1.49 g increase in lumbar spine BMC (95% CI 0.77-2.21). Birthweight was not associated with lumbar spine BMD in 11 studies. In six studies, considering the relationship between birthweight and hip BMC, most found that higher birthweight was associated with greater BMC. Meta-analysis demonstrated that a 1 kg increase in birthweight was associated with a 1.41 g increase in hip BMC (95% CI 0.91-1.91). Seven studies considered the relationship between birthweight and hip BMD and, in most, birthweight was not a significant predictor of hip BMD. Three studies assessing the relationship between weight at 1 year and adult bone mass all reported that higher weight at one was associated with greater BMC of the lumbar spine and hip. Conclusions: Higher birthweight is associated with greater BMC of the lumbar spine and hip in adulthood. The consistency of these associations, across a range of settings, provides compelling evidence for the intrauterine programming of skeletal development and tracking of skeletal size from infancy to adulthood. [ABSTRACT FROM AUTHOR]

We connect the recent medical and economic literatures on the long-run effects of early-life conditions by analyzing the effects of economic conditions on the individual cardiovascular (CV) mortality rate later in life, using individual data records from the Danish Twin Registry covering births since the 1870s and including the cause of death. To capture exogenous variation of conditions early in life, we use the state of the business cycle around birth. We find significant negative effects of economic conditions around birth on the individual CV mortality rate at higher ages. There is no effect on the cancer-specific mortality rate. From variation within and between monozygotic and dizygotic twin pairs born under different conditions, we conclude that the fate of an individual is more strongly determined by genetic and household-environmental factors if early-life conditions are poor. Individual-specific qualities come more to fruition if the starting position in life is better. [ABSTRACT FROM AUTHOR]

Background: Despite the perceived importance of early life nutrition for mental development, few studies have related gestational undernutrition to later-life cognitive functioning. We investigated the consequences of gestational exposure to the Dutch famine of 1944-45 for cognitive functioning at the age of 59 years.Methods: We recruited men and women who were (i) born in birth clinics in Amsterdam, Rotterdam and Leiden, between January 1945 and March 1946, whose mothers experienced famine during or immediately preceding pregnancy (n = 354); (ii) born in the same three institutions during 1943 and 1947, whose mothers did not experience famine during this pregnancy (n = 292); or (iii) same-sex siblings of those in the first two categories (n = 311). We assessed cognitive performance at the age of 59 years by means of a comprehensive test battery.Results: All cognitive functioning test scores were within normal ranges for this age group. There were no differences in cognitive performance at the age of 59 years between individuals exposed to gestational undernutrition and those without this exposure. For the general cognitive index, a summary measure across six functional domains (mean 100, standard deviation (SD) 15 points), famine exposure was associated with a decrease of 0.57 points [95% confidence interval (95% CI) -2.41 to 1.28] points. Individuals exposed to famine in gestational weeks 1-10 had a cognitive functioning index 4.36 (95% CI 8.04-0.67) points lower than those without this exposure. Within-sibling-pair analyses gave consistent results.Conclusion: We found no overall association between maternal exposure to acute famine in pregnancy and cognitive performance of the offspring at the age of 59 years, but cannot rule out an association specific to early pregnancy exposure. [ABSTRACT FROM AUTHOR]

Antenatal maternal hypoxia (AMH) can lead to intrauterine growth restriction (IUGR), as well as idiopathic pulmonary hypertension of newborn and adult, the latter of which may be a consequence of alterations in the local pulmonary renin-angiotensin system (RAS). Little is known of these adaptations, however. Thus, we tested the hypothesis that antenatal maternal hypoxia is associated with alterations in gene and protein expression of the pulmonary renin-angiotensin system, which may play an important role in pulmonary disorders in the offspring. In FVB/NJ mice, we studied messenger RNA (mRNA) and protein expression, as well as promoter DNA methylation and microRNA (miRNA) levels in response to 48 hours hypoxia (10.5% O2) at 15.5 day post coitum (DPC). In response to AMH, the pulmonary mRNA levels of angiotensin-converting enzyme (ACE) 1.2, ACE-2, and angiotensin II type 1b (AT-1b) receptors were increased significantly, as compared to controls (N = 4). In response to antenatal hypoxia, pulmonary protein levels of renin and ACE-2 also were increased significantly, whereas ACE-1 protein expression was reduced. In fetal lungs, we also observed reduced expression of the miRNAs: mmu-mir −199b, −27b, −200b, and −468 that putatively increase the translation of renin, ACE-1, ACE-2, and AT-1 receptors, respectively. In response to AMH, promoter methylation of ACE was unchanged. We conclude that AMH leads to changes in expression of pulmonary RAS of fetal mice. The possible implications of these changes for the regulation of pulmonary vascular contractility in later life remain to be explored. [ABSTRACT FROM PUBLISHER]

Summary: The incidence of hip fracture was estimated in 6,370 women born in Helsinki between 1934 and 1944. Women in the lowest quarter of adiposity gain had an 8.2-fold increase in hip fracture risk compared with those in the highest quarter ( p < 0.001). These data point to a relationship between childhood growth and fracture risk during later life. Introduction: Previous findings show that discordance between childhood increase in height and weight is associated with an increased risk of osteoporotic fractures during later life. Methods: We studied 6,370 women born in Helsinki between 1934 and 1944. Each woman's birth weight and length at birth was recorded, as well as her height and weight through childhood. We identified the occurrence of hip fracture through the National Finnish Hospital discharge register. Results: There were 49 hip fractures in the 6,370 women over 187,238 person-years of follow-up. Hip fracture was associated with increasing Z-scores for height between 1 and 12 years, not matched by a corresponding increase in weight. Therefore, reduction in the Z-score for body mass index was associated with increased risk of hip fracture. Women in the lowest quarter of change in Z-scores for body mass index had an 8.2-fold increase in hip fracture risk (95% CI 1.9 to 35), compared with those in the highest quarter ( p < 0.001). Conclusion: Thinness in childhood is a risk factor for hip fracture in later life. This could be a direct effect of low fat mass on bone mineralization, or represent the influence of altered timing of pubertal maturation. [ABSTRACT FROM AUTHOR]

Abstract: Little is known about the origins of the pointing gesture. We sought to gain insight into its emergence by investigating individual differences in the pointing of 12-month-old infants in two ways. First, we looked at differences in the communicative and interactional uses of pointing and asked how different hand shapes relate to point frequency, accompanying vocalizations, and mothers’ pointing. Second, we looked at differences in social-cognitive skills of point comprehension and imitation and tested whether these were related to infants’ own pointing. Infants’ and mothers’ spontaneous pointing correlated with one another, as did infants’ point production and comprehension. In particular, infants’ index-finger pointing had a profile different from simple whole-hand pointing. It was more frequent, it was more often accompanied by vocalizations, and it correlated more strongly with comprehension of pointing (especially to occluded referents). We conclude that whole-hand and index-finger pointing differ qualitatively and suggest that it is index-finger pointing that first embodies infants’ understanding of communicative intentions. [Copyright &y& Elsevier]

Background Although increased morbidity and mortality associated with pre-term birth and restricted fetal growth have been extensively studied, relatively little is known about variations in health outcomes among term births, because they are often assumed to be homogeneous.Methods We examined variations in height, body mass index (BMI), systolic and diastolic blood pressure (SBP and DBP), and intellectual performance by gestational age and fetal ‘growth’ (birth weight for gestational age) among young Swedish men born at term (37–41 weeks of gestation). We also compared the magnitude of associations among 314 642 men from different families and among 72 212 full brothers from 35 215 families to assess whether the associations are explained by familial factors shared by siblings.Results Gestational age in completed weeks was positively associated with height [0.11 cm, 95% confidence interval (CI): 0.09–0.13] and intellectual performance (0.01, 95% CI: 0.00–0.02) and negatively associated with SBP (−0.28 mmHg, 95% CI: −0.33 to −0.24), after controlling for birth weight, maternal age at the men’s birth, parity, family socio-economic position and family structure. The associations with height and SBP were observed also among brothers within families, suggesting that they are not explained by shared family characteristics. However, the positive association between gestational age and intellectual performance was no longer present within families. Birth weight for gestational age (z-score) was positively associated with height, BMI and intellectual performance and negatively associated with SBP. These associations were robust within families.Conclusions Among young men born at term, fetal growth and even gestational age are independently associated with adult size, BP and cognitive ability. The extent to which shared family characteristics explain the associations varies across outcomes. [ABSTRACT FROM PUBLISHER]

This paper reviews publications on developmental trajectories of disruptive behaviour (DB) problems (aggression, opposition-defiance, rule breaking, and stealing-vandalism) over the past decade. Prior to these studies two theoretical models had strongly influenced research on DB: social learning and disease onset. According to these developmental perspectives, children learn DB from their environment and onset of the disease is triggered by accumulated exposition to disruptive models in the environment, including the media. Most of the evidence came from studies of school age children and adolescents. Longitudinal studies tracing developmental trajectories of DB from early childhood onwards suggest an inversed developmental process. DB are universal during early childhood. With age, children learn socially acceptable behaviours from interactions with their environment. A ‘disease’ status is given to children who fail to learn the socially acceptable behaviours. The mechanisms that lead to deficits in using socially accepted behaviours are strongly intergenerational, based on complex genetic and environmental contributions, including epigenetic mechanisms. Prevention of these deficits requires early, intensive and long-term support to parents and child. Newly discovered epigenetic mechanisms suggest that intensive perinatal interventions will have impacts on numerous aspects of physical and mental health, including DB. This review also concludes that: a) subtypes of disruptive behaviours should not be aggregated because they have different developmental trajectories and require specific corrective interventions; b) the overt–covert and destructive–nondestructive dimensions appear the most useful to create DB subtypes; c) overt DB onset before covert DB because the latter require more brain maturation; d) DB subtype taxonomies are more useful for clinicians than developmental taxonomies because the latter are post mortem diagnoses and clinicians’ retrospective information is unreliable; e) we need large-scale collaborative preventive experimental interventions starting during early pregnancy to advance knowledge on causes and prevention of DB problems. [ABSTRACT FROM AUTHOR]

The article discusses the result of a study which investigated prenatal influences on bone health. The findings suggest that intrauterine growth may influence postnatal volumetric density and skeletal size and that the tracking of skeletal development originates in the prenatal period. It also indicates that the factors affecting late intrauterine growth may have lasting effects on postnatal skeletal development. It concludes that the velocity of femur growth from 19 to 34 weeks predicts childhood skeletal size at four years.

Objective: Maternal protein malnutrition during pregnancy can lead to significant alterations in the systemic renin-angiotensin system (RAS) in the fetus. All components of the RAS are present in brain and may be altered in many disease states. Importantly, these disorders are reported to be of higher incidence in prenatally malnourished individuals. In the current study, we tested the hypothesis that antenatal maternal low protein diet (MLPD) leads to epigenetic changes and alterations in gene expression of brain RAS of the mouse fetus. Methods: Mice dams were given control and 50% MLPD during second half of the gestation. We analyzed messenger RNA (mRNA), microRNA (miRNA), promoter DNA methylation, and protein expression of various RAS genes in the fetal offspring. Results: As a consequence of 50% MLPD, fetal brains showed increased mRNA expression of angiotensinogen and angiotensin converting enzyme-1 (ACE-1), with a decrease in mRNA levels of angiotensin II type-2 (AT2) receptors. In contrast, while angiotensinogen protein expression was unaltered, the protein levels of ACE-1 and AT2 receptor genes were significantly reduced in the fetal brain from the MLPD dams. Our results also demonstrated hypomethylation of the CpG islands in the promoter regions of ACE-1 gene, and upregulation of the miRNAs, mmu-mir-27a and 27b, which regulate ACE-1 mRNA translation. Furthermore, our study showed reduced expression of the miRNA mmu-mir-330, which putatively regulates AT2 translation. Conclusion: For the developing fetal brain RAS, MLPD leads to significant alterations in the mRNA and protein expression, with changes in DNA methylation and miRNA, key regulators of hypertension in adults. [ABSTRACT FROM AUTHOR]

The article presents a study which suggests that maternal vitamin D insufficiency can influence fetal femoral development as early as 19 weeks' gestation. To determine whether maternal vitamin D insufficiency affects fetal femur growth, the researchers looked at 424 pregnant within a prospective longitudinal study of maternal nutrition and lifestyle before and during pregnancy. They found that lower maternal 25-hydroxyvitamin vitamin D concentration was associated with greater femoral metaphyseal cross-sectional area and higher femoral splaying index.

In this study we examined the short- and long-term impact of early life dietary sodium (Na) on prenatally programmed hypertension. Hypertension was induced in rat offspring by a maternal low protein (LP) diet. Control and LP offspring were randomized to a high (HS), standard (SS), or low (LS) Na diet after weaning. On the SS diet, the LP pups developed hypertension by 6 weeks of age. The development of hypertension was prevented by the LS diet and exacerbated by the HS diet. Kidney nitrotyrosine content, a measure of oxidative stress, was reduced by the LS diet compared with the HS diet. The modified diets had no effect on control pups. A group of animals on the SS diet was followed up to 51 weeks of age after an early life 3-week exposure to the HS or LS diet. This brief early exposure of LP animals to the LS diet prevented the later development of hypertension and ameliorated the nephrosclerosis observed after early exposure to the HS diet. The LP offspring with early exposure to LS diet had lost their salt-sensitivity when challenged with the HS diet at the age of 43–49 weeks. No effect of early life dietary Na was observed in control animals. These results show that hypertension in this model is salt sensitive and may, in part, be mediated by salt-induced renal oxidative stress and that there may exist a developmental window which allows postnatal “reprogramming” of the hypertension. [ABSTRACT FROM AUTHOR]

Summary: The nephron endowment begins with the complex process of nephrogenesis, which is controlled through genetic and environmental influences from preconception up until approximately 36 weeks of gestation. The total number of nephrons in human beings averages about 1 million per kidney but varies up to 10-fold, from approximately 200,000 to more than 2 million. Low nephron mass is associated with the development of hypertension and, in some ethnic populations, the concurrence of cardiovascular and renal disease risks in later life. Kidney size and nephron number also are related directly to birth weight with persons born preterm or with evidence of intrauterine growth restriction more likely to develop certain diseases in later life. [ABSTRACT FROM AUTHOR]

Abstract: Background: Rapid postnatal weight gain is associated with obesity and type 2 diabetes in later life. The influence of rapid weight gain on body composition in early infancy is still unknown and the critical periods of weight gain for later disease are debated. Aims: To investigate the effect of birth weight and rapid weight gain on body composition in the first 6 months of life. Study design: The Generation R Study, a population-based prospective cohort study from fetal life onwards. Subjects and outcome measures: We measured body fat and fat distribution by skinfold thickness at the age of 6 weeks and 6 months in 909 Dutch term infants. Analyses were adjusted for current body mass index, sex and maternal socioeconomic status, pre-pregnancy body mass index, height and duration of breastfeeding. Results: Upward postnatal weight percentile change was associated with increased skinfold thickness, percentage body fat at 6 weeks and 6 months and a larger truncal/peripheral fat ratio at 6 months (p <0.01 for all). Birth weight was inversely associated with truncal/peripheral fat ratio (p <0.01) but not with relative body fat at 6 months. Conclusion: During early postnatal rapid weight gain infants do not grow in all body tissues in equal measure. Instead, they acquire relatively large amounts of fat, which is preferentially distributed to the truncal region. Long term observational studies have to assess if such changes in body composition persist into adulthood. [Copyright &y& Elsevier]

We analyze causal effects of conditions early in life on the individual mortality rate later in life. Conditions early in life are captured by transitory features of the macro-environment around birth, notably the state of the business cycle around birth, but also food price deviations, weather indicators, and demographic indicators. We argue that these features can only affect high-age mortality by way of the individual early-life conditions. Moreover, they are exogenous from the individual point of view, which is a methodological advantage compared to the use of unique characteristics of the newborn individual or his or her family or household as early-life indicators. We collected national annual time-series data on the above-mentioned indicators, and we combine these to the individual data records from the Danish Twin Registry covering births in 1873–1906. The empirical analyses (mostly based on the estimation of duration models) indicate a significant negative causal effect of economic conditions early in life on individual mortality rates at higher ages. If the national economic performance in the year of birth exceeds its trend value (i.e., if the business cycle is favorable) then the mortality rate later in life is lower. The implied effect on the median lifetime of those who survive until age 35 is about 10 months. A systematic empirical exploration of all macro-indicators reveals that economic conditions in the first years after birth also affect mortality rates later in life. [Copyright &y& Elsevier]

The purpose of this article is to define the concept of developmental origins of health and disease (DOHaD) as an emerging paradigm for relating evolutionary biology to contemporary health issues. As illustrated, several paradoxes emerge related to adaptations initiated in utero and in early life. Epigenetics is a concept that must be incorporated in order to understand plasticity adaptations, such as programming. The public health consequence of DOHaD challenges the one-size-fits-all norm and shows the need for prescreening prior to some interventions and for the eventuality of individualized, rather than collectively applied, preventive or remedial measures as the safest option. [ABSTRACT FROM AUTHOR]