Showing papers in "Journal of Developmental Origins of Health and Disease in 2016"

Impact of mode of delivery on the milk microbiota composition of healthy women

Abstract: Breast milk constitutes one of the most important sources of postnatal microbes. However, the influence of perinatal factors on the milk microbiome is still poorly understood. The aim of our study was to assess the impact of mode of delivery on the microbiome composition and diversity present in breast milk of healthy mothers. Mature milk samples (n=10) were taken from mothers after 1 month of exclusively breastfeeding. Microbiomes from milk samples were analyzed with 16S ribosomal RNA gene pyrosequencing and targeted quantitative polymerase chain reaction (PCR). Despite inter-individual variability in bacterial composition, The Principal Coordinates Analysis clearly separated milk microbiome from mothers with vaginal delivery (n=6) from those who undergo C-section (n=4). In addition, higher bacterial diversity and richness was found in milk samples from vaginal deliveries. Quantitative PCR data showed that higher levels of Bifidobacterium spp. were related significantly to lower levels of Staphylococcus spp. Despite the low sample size, our data suggest that mode of delivery has an important impact on milk microbiome composition. Further studies with larger sample sizes are needed to confirm these results and to understand the biological effects of C-section associated microbes on infant's health.

Hypertensive disorders during pregnancy and health outcomes in the offspring: a systematic review.

Abstract: UNLABELLED The hypertensive disorders of pregnancy complicate up to 10% of pregnancies worldwide and are a leading cause of maternal, foetal, and neonatal morbidity and mortality. The aim of this study was to present an overview of recent studies addressing offspring's medium and long-term health outcomes after intrauterine exposure to maternal hypertension. A search on PubMed/MEDLINE and Bireme databases was conducted to identify observational studies that reported any offspring outcome measured after the 6th month of life. The search was limited to studies published after May 2008. Forty-five articles were included and categorized into four groups of outcomes: cardiovascular, immune, metabolic and behavioural/neurological effects. According to our findings, hypertensive disorders of pregnancy had an overall negative impact on offspring's cardiovascular, immune and neurological health, although not all parameters analysed in each group had consistent results among studies. The most prominent and reliable associations were verified between gestational hypertension and higher offspring's blood pressure and between preeclampsia and offspring's lower cognitive functioning. In the metabolic outcomes, body composition had conflicting results among papers, while all studies that examined blood biomarkers showed no evidence that preeclampsia or gestational hypertension could be associated with an alteration of this metabolic outcomes. Most included studies were highly heterogeneous regarding the measure of outcomes and covariables used for adjustments. Future studies should consider using the same protocols and cut-off points already published so that results can be better compared and summarized. This review was registered in PROSPERO. REGISTRATION NUMBER CRD42015020838.

A review of fundamental principles for animal models of DOHaD research: An Australian perspective

Abstract: Epidemiology formed the basis of 'the Barker hypothesis', the concept of 'developmental programming' and today's discipline of the Developmental Origins of Health and Disease (DOHaD). Animal experimentation provided proof of the underlying concepts, and continues to generate knowledge of underlying mechanisms. Interventions in humans, based on DOHaD principles, will be informed by experiments in animals. As knowledge in this discipline has accumulated, from studies of humans and other animals, the complexity of interactions between genome, environment and epigenetics, has been revealed. The vast nature of programming stimuli and breadth of effects is becoming known. As a result of our accumulating knowledge we now appreciate the impact of many variables that contribute to programmed outcomes. To guide further animal research in this field, the Australia and New Zealand DOHaD society (ANZ DOHaD) Animals Models of DOHaD Research Working Group convened at the 2nd Annual ANZ DOHaD Congress in Melbourne, Australia in April 2015. This review summarizes the contributions of animal research to the understanding of DOHaD, and makes recommendations for the design and conduct of animal experiments to maximize relevance, reproducibility and translation of knowledge into improving health and well-being.

Early microbial contact, the breast milk microbiome and child health.

Abstract: The significance of contact with microbes in early life for subsequent health has been the subject of intense research during the last 2 decades. Disturbances in the establishment of the indigenous intestinal microbiome caused by cesarean section delivery or antibiotic exposure in early life have been linked to the risk of immune-mediated and inflammatory conditions such as atopic disorders, inflammatory bowel disease and obesity later in life. Distinct microbial populations have recently been discovered at maternal sites including the amniotic cavity and breast milk, as well as meconium, which have previously been thought to be sterile. Our understanding of the impact of fetal microbial contact on health outcomes is still rudimentary. Breast milk is known to modulate immune and metabolic programming. The breast milk microbiome is hypothesized to guide infant gut colonization and is affected by maternal health status and mode of delivery. Immunomodulatory factors in breast milk interact with the maternal and infant gut microbiome and may mediate some of the health benefits associated with breastfeeding. The intimate connection between the mother and the fetus or the infant is a potential target for microbial therapeutic interventions aiming to support healthy microbial contact and protect against disease.

Fetal programming of overweight through the microbiome: boys are disproportionately affected.

Abstract: Maternal and childhood obesity in pregnancy are worrisome public health issues facing our world today. New gene sequencing methods have advanced our knowledge of the disruptive effect of birth interventions and postnatal exposures on the maturation of gut microbiota and immunity during infancy. Yet, little is known about the impact of maternal pregnancy overweight on gut microbes and related processes, and how this may affect overweight risk in offspring. To address this gap in knowledge, we surveyed human studies for evidence in children, infants and pregnant women to piece together the limited literature and generate hypotheses for future investigation. From this literature, we learned that higher Lactobacillus yet lower Bacteroides spp. colonization of gut microbiota within 3 months of birth predicted risk for infant and child overweight. The abundance of bifidobacteria and staphylococci also appeared to play a role in the association with overweight, as did infant fecal immunoglobulin A levels, glycoproteins of the gut immune system that are acquired from breast milk and produced by the infant. We proposed that pregnancy overweight influences the compositional structure of gut microbiota in infants through vertical transfer of microbiota and/or their metabolites during pregnancy, delivery and breastfeeding. Finally, we brought forward emerging evidence on sex dimorphism, as well as ethnic and geographic variation, in reported associations between maternal overweight-induced gut microbiota dysbiosis and overweight risk.

Prenatal maternal mental health and fetal growth restriction: a systematic review.

Abstract: Maternal mental disorders during pregnancy are associated with a range of adverse health outcomes for offspring. This systematic review examines studies reporting on the relationship between maternal depression, anxiety or stress during pregnancy and fetal growth measured during pregnancy using ultrasound biometry. A systematic search of PsycINFO, Medline, Scopus, Web of Science and Embase was conducted and 1575 records were identified, with nine studies meeting inclusion criteria gathering data from over 7000 participants. All studies measured depression, six examined anxiety and depression, and five examined all three exposures. The majority measured symptoms rather than clinically diagnosable disorder. Studies consistently reported significant associations between maternal mental health, particularly anxiety symptoms, and reduced fetal head growth. Other fetal growth parameters showed inconsistent findings. A number of studies suggest that cortisol dysregulation associated with maternal mental health may play a role in fetal growth restriction. However, heterogeneity in the timing of growth measurement, assessment measures used for mental health and inconsistencies in adjustment for confounders, limits the synthesis and interpretation of findings. Future studies should consider differences in the timing, intensity and duration of mental health symptoms over pregnancy and should employ diagnostic assessment of mental disorders. Fetal growth should be repeatedly measured and further work is needed to establish the biological mechanisms involved.

Review of the importance of nutrition during the first 1000 days: maternal nutritional status and its associations with fetal growth and birth, neonatal and infant outcomes among African women.

Abstract: Maternal nutritional status (MNS) is a strong predictor of growth and development in the first 1000 days of life and may influence susceptibility to non-communicable diseases in adulthood. However, the role of nutrition during this window of developmental plasticity in Africa is unclear. This paper reviews published data to address whether maternal nutrition during the first 1000 days is important for Africa, with a focus on MNS and its associations with fetal growth and birth, neonatal and infant outcomes. A systematic approach was used to search the following databases: Medline, EMBASE, Web of Science, Google Scholar, ScienceDirect, SciSearch and Cochrane Library. In all, 26 studies met the inclusion criteria for the specific objectives. MNS in Africa showed features typical of the epidemiological transition: higher prevalences of maternal overweight and obesity and lower underweight, poor diet quality 1 and high anaemia prevalence. Maternal body mass index and greater gestational weight gain (GWG) were positively associated with birth weight; however, maternal overweight and obesity were associated with increased risk of macrosomia and intrauterine growth restriction. Maternal anaemia was associated with lower birth weight. Macro- and micronutrient supplementation during pregnancy were associated with improvements in GWG, birth weight and mortality risk. Data suggest poor MNS in Africa and confirms the importance of the first 1000 days as a critical period for nutritional intervention to improve growth, birth outcomes and potential future health risk. However, there is a lack of data beyond birth and a need for longitudinal data through infancy to 2 years of age.

High frequencies of antibiotic resistance genes in infants' meconium and early fecal samples.

Abstract: The gastrointestinal tract (GIT) microbiota has been identified as an important reservoir of antibiotic resistance genes (ARGs) that can be horizontally transferred to pathogenic species. Maternal GIT microbes can be transmitted to the offspring, and recent work indicates that such transfer starts before birth. We have used culture-independent genetic screenings to explore whether ARGs are already present in the meconium accumulated in the GIT during fetal life and in feces of 1-week-old infants. We have analyzed resistance to β-lactam antibiotics (BLr) and tetracycline (Tcr), screening for a variety of genes conferring each. To evaluate whether ARGs could have been inherited by maternal transmission, we have screened perinatal fecal samples of the 1-week-old babies' mothers, as well as a mother-infant series including meconium, fecal samples collected through the infant's 1st year, maternal fecal samples and colostrum. Our results reveal a high prevalence of BLr and Tcr in both meconium and early fecal samples, implying that the GIT resistance reservoir starts to accumulate even before birth. We show that ARGs present in the mother may reach the meconium and colostrum and establish in the infant GIT, but also that some ARGs were likely acquired from other sources. Alarmingly, we identified in both meconium and 1-week-olds' samples a particularly elevated prevalence of mecA (>45%), six-fold higher than that detected in the mothers. The mecA gene confers BLr to methicillin-resistant Staphylococcus aureus, and although its detection does not imply the presence of this pathogen, it does implicate the young infant's GIT as a noteworthy reservoir of this gene.

Recovery from stunting and cognitive outcomes in young children: evidence from the South African Birth to Twenty Cohort Study

Abstract: In this study we analyse the implications for cognitive function of recovery from stunting in early childhood. More specifically, we test whether children who met the definition for stunted at age 2, but not at age 5, perform better in cognitive tests than children who remain stunted over this period. The sample is drawn from the Birth to Twenty Cohort Study, a prospective data set of children born in 1990 in urban South Africa. The measure of cognitive function that we use is based on the Revised Denver Prescreening Developmental Questionnaire implemented when the children were age 5. We employ multivariate regression in the analysis to control for child-specific characteristics, socio-economic status, the home environment and caregiver inputs. We find that recovery from stunting is not uncommon among young children in our sample. However, children who recover from stunting by age 5 still perform significantly worse on cognitive tests than children who do not experience early malnutrition, and almost as poorly as children who remain stunted. These findings suggest that the timing of nutritional inputs in the early years is key in a child's cognitive development, with implications for school readiness and achievement.

Infant gut immunity: a preliminary study of IgA associations with breastfeeding.

Abstract: Secretory immunoglobulin A (IgA) plays a critical role in gut mucosal immune defense. Initially provided by breastmilk, IgA production by the infant gut is gradually stimulated by developing gut microbiota. This study reports associations between infant fecal IgA concentrations 4 months after birth, breastfeeding status and other pre/postnatal exposures in 47 infants in the Canadian Healthy Infant Longitudinal Development cohort. Breastfed infants and first-born infants had higher median fecal IgA concentrations (23.11 v. 9.34 µg/g protein, P<0.01 and 22.19 v. 8.23 µg/g protein, P=0.04). IgA levels increased successively with exclusivity of breastfeeding (β-coefficient, 0.37, P<0.05). This statistical association was independent of maternal parity and household pets. In the absence of breastfeeding, female sex and pet exposure elevated fecal IgA to levels found in breastfed infants. In addition to breastfeeding, infant fecal IgA associations with pre/postnatal exposures may affect gut immunity and risk of allergic disease.

Early life nutritional programming of health and disease in The Gambia

Abstract: Exposures during the early life (periconceptional, prenatal and early postnatal) period are increasingly recognized as playing an important role in the aetiology of chronic non-communicable diseases (NCD), including coronary heart disease, stroke, hypertension, Type 2 diabetes and osteoporosis. The 'Developmental Origins of Health and Disease' (DOHaD) hypothesis states that these disorders originate through unbalanced nutrition early in life and risk is highest when there is a 'mismatch' between the early- and later-life environments. Thus, the DOHaD hypothesis would predict highest risk in countries where an excess of infants are born with low birth weight and where there is a rapid transition to nutritional adequacy or excess in adulthood. Here, I will review data from work conducted in rural Gambia, West Africa. Using demographic data dating back to the 1940s, the follow-up of randomized controlled trials of nutritional supplementation in pregnancy and the 'experiment of nature' that seasonality in this region provides, we have investigated the DOHaD hypothesis in a population with high rates of maternal and infant under-nutrition, a high burden from infectious disease, and an emerging risk of NCDs.

Human fetal growth restriction: a cardiovascular journey through to adolescence.

Abstract: Intrauterine growth restriction has been noted to adversely impact morbidity and mortality in the neonatal period as well as cardiovascular well-being in adolescence and adulthood. Recent data based on a wide range of ultrasound parameters during fetal and neonatal life has noted early and persistent involvement of the cardiovascular system. Some of these measures are predictive of long-term morbidities. Assessment of vascular mechanics is a new and novel concept in this population, and opens up avenues for diagnosis, monitoring and evaluation of the likely effectiveness of interventions. Prevention of these adverse vascular and cardiac outcomes secondary to fetal growth restriction may be feasible and of clinical relevance. This review focuses on growth restriction in humans with respect to cardiovascular remodeling and dysfunction during fetal life, persistence of functional cardiac impairment during early childhood and adolescence, and possible preventive strategies.

The impact of early life gut colonization on metabolic and obesogenic outcomes: what have animal models shown us?

Abstract: The rise in the occurrence of obesity to epidemic proportions has made it a global concern. Great difficulty has been experienced in efforts to control this growing problem with lifestyle interventions. Thus, attention has been directed to understanding the events of one of the most critical periods of development, perinatal life. Early life adversity driven by maternal obesity has been associated with an increased risk of metabolic disease and obesity in the offspring later in life. Although a mechanistic link explaining the relationship between maternal and offspring obesity is still under investigation, the gut microbiota has come forth as a new factor that may play a role modulating metabolic function of both the mother and the offspring. Emerging evidence suggests that the gut microbiota plays a much larger role in mediating the risk of developing non-communicable disease, including obesity and metabolic dysfunction in adulthood. With the observation that the early life colonization of the neonatal and postnatal gut is mediated by the perinatal environment, the number of studies investigating early life gut microbial establishment continues to grow. This paper will review early life gut colonization in experimental animal models, concentrating on the role of the early life environment in offspring gut colonization and the ability of the gut microbiota to dictate risk of disease later in life.

Low birth weight, very low birth weight and extremely low birth weight in African children aged between 0 and 5 years old: a systematic review.

Abstract: Low birth weight (LBW<2500), very low birth weight (VLBW<1500), extremely low birth weight (ELBW<1500) infants are at high risk for growth failure that result in delayed development. Africa is a continent that presents high rates of children born with LBW, VLBW and ELBW particularly sub-Saharan Africa. To review the existing literature that explores the repercussions of LBW, VLBW and ELBW on growth, neurodevelopmental outcome and mortality in African children aged 0-5 years old. A systematic review of peer-reviewed articles using Academic Search Complete in the following databases: PubMed, Scopus and Scholar Google. Quantitatives studies that investigated the association between LBW, VLBW, ELBW with growth, neurodevelopmental outcome and mortality, published between 2008 and 2015 were included. African studies with humans were eligible for inclusion. From the total of 2205 articles, 12 articles were identified as relevant and were subsequently reviewed in full version. Significant associations were found between LBW, VLBW and ELBW with growth, neurodevelopmental outcome and mortality. Surviving VLBW and ELBW showed increased risk of death, growth retardation and delayed neurodevelopment. Post-neonatal interventions need to be carried out in order to minimize the short-term effects of VLBW and ELBW.

Early life nutrition and the opportunity to influence long-term health: an Australasian perspective

Abstract: There are now significant data to support the hypothesis that early life nutrition in the fetus, infant and young child can have profound effects on long-term health. This review considers some of this evidence with specific reference to the current burden of disease in Australia and New Zealand. As the findings of further research become available, recommendations on optimizing early life nutrition should be formulated and made widely available as part of the preventative health policy agenda in both Australia and New Zealand.

Maternal group B Streptococcus and the infant gut microbiota.

Abstract: Early patterns of gut colonization may predispose children to adult disease. Exposures in utero and during delivery are associated with the infant gut microbiome. Although ~35% of women carry group B strep (GBS; Streptococcus agalactiae) during pregnancy, it is unknown if GBS presence influences the infant gut microbiome. As part of a population-based, general risk birth cohort, stool specimens were collected from infant's diapers at research visits conducted at ~1 and 6 months of age. Using the Illumina MiSeq (San Diego, CA) platform, the V4 region of the bacterial 16S rRNA gene was sequenced. Infant gut bacterial community compositional differences by maternal GBS status were evaluated using permutational multivariate analysis of variance. Individual operational taxonomic units (OTUs) were tested using a zero-inflated negative binomial model. Data on maternal GBS and infant gut microbiota from either 1 (n=112) or 6-month-old stool (n=150) specimens was available on 262 maternal-child pairs. Eighty women (30.5%) were GBS+, of who 58 (72.5%) were given intrapartum antibiotics. After adjusting for maternal race, prenatal antifungal use and intrapartum antibiotics, maternal GBS status was statistically significantly associated with gut bacterial composition in the 6 month visit specimen (Canberra R 2=0.008, P=0.008; Unweighted UniFrac R 2=0.010, P=0.011). Individual OTU tests revealed that infants of GBS+ mothers were significantly enriched for specific members of the Clostridiaceae, Ruminococcoceae, and Enterococcaceae in the 6 month specimens compared with infants of GBS- mothers. Whether these taxonomic differences in infant gut microbiota at 6 months lead to differential predisposition for adult disease requires additional study.

A meta-analysis of neonatal health outcomes from oocyte donation.

Abstract: Donated oocytes are a treatment modality for female infertility which is also associated with increased risks of preeclampsia. Subsequently it is important to evaluate if there is concomitant increased risks for adverse neonatal events in donated oocyte neonates. A structured search of the literature using PubMed, EMBASE and Cochrane Reviews was performed to investigate the perinatal health outcomes of offspring conceived from donor oocytes compared with autologous oocytes. Meta-analysis was performed on comparable outcomes data. Twenty-eight studies were eligible and included in the review, and of these, 23 were included in a meta-analysis. Donor oocyte neonates are at increased risk of being born with low birth weight (<2500 g) [risk ratio (RR): 1.18, 95% confidence interval (CI): 1.14-1.22, P-value (P)<0.00001], very low birth weight (<1500 g) (RR: 1.24, CI: 1.15-1.35, P<0.00001), preterm (<37 weeks) (RR: 1.26, CI: 1.23-1.30, P<0.00001), of lower gestational age (mean difference -0.3 weeks, CI: -0.35 weeks to -0.25 weeks, P<0.00001), and preterm with low birth weight (RR: 1.24, CI: 1.19-1.29, P<0.00001), when compared with autologous oocyte neonates. Conversely, low birth weight outcomes were improved in term donor oocyte neonates (RR: 0.86, CI: 0.8-0.93, P=0.0003). These negative outcomes remained significant when controlling for multiple deliveries. The donor oocyte risk rates are higher than those found in general ART outcomes, are important considerations for the counselling of infertile patients and may also influence the long term health of the offspring.

Transgenerational transmission of pregestational and prenatal experience: maternal adversity, enrichment, and underlying epigenetic and environmental mechanisms.

Abstract: Transgenerational transmission refers to positive and negative adaptations in brain function and behavior that affect following generations. In this paper, empirical findings regarding the transgenerational transmission of maternal adversity during three critical periods - childhood, pregestational adulthood and pregnancy - will be reviewed in terms of pregnancy outcomes, maternal care, offspring behavior and development, and physiological functioning. Research on the transgenerational transmission of enrichment and the implications for interventions to ameliorate the consequences of adversity will also be presented. In the final section, underlying epigenetic and environmental mechanisms that have been proposed to explain how experience is transferred across generations through transgenerational transmission will be reviewed. Directions for future research are suggested throughout.

A cohort of Indigenous Australian women and their children through pregnancy and beyond: the Gomeroi gaaynggal study.

Abstract: Indigenous Australians have high rates of chronic diseases, the causes of which are complex and include social and environmental determinants. Early experiences in utero may also predispose to later-life disease development. The Gomeroi gaaynggal study was established to explore intrauterine origins of renal disease, diabetes and growth in order to inform the development of health programmes for Indigenous Australian women and children. Pregnant women are recruited from antenatal clinics in Tamworth, Newcastle and Walgett, New South Wales, Australia, by Indigenous research assistants. Measures are collected at three time points in pregnancy and from women and their children at up to eight time points in the child's first 5 years. Measures of fetal renal development and function include ultrasound and biochemical biomarkers. Dietary intake, infant feeding and anthropometric measurements are collected. Standardized procedures and validated tools are used where available. Since 2010 the study has recruited over 230 women, and retained 66 postpartum. Recruitment is ongoing, and Gomeroi gaaynggal is currently the largest Indigenous pregnancy-through-early-childhood cohort internationally. Baseline median gestational age was 39.1 weeks (31.5-43.2, n=110), median birth weight was 3180 g (910-5430 g, n=110). Over one third (39.3%) of infants were admitted to special care or neonatal nursery. Nearly half of mothers (47.5%) reported tobacco smoking during pregnancy. Results of the study will contribute to knowledge about origins of chronic disease in Indigenous Australians and nutrition and growth of women and their offspring during pregnancy and postpartum. Study strengths include employment and capacity-building of Indigenous staff and the complementary ArtsHealth programme.

Potential effectiveness of Community Health Strategy to promote exclusive breastfeeding in urban poor settings in Nairobi Kenya: a quasi-experimental study.

Abstract: Early nutrition is critical for later health and sustainable development. We determined potential effectiveness of the Kenyan Community Health Strategy in promoting exclusive breastfeeding (EBF) in urban poor settings in Nairobi, Kenya. We used a quasi-experimental study design, based on three studies [Pre-intervention (2007-2011; n=5824), Intervention (2012-2015; n=1110) and Comparison (2012-2014; n=487)], which followed mother-child pairs longitudinally to establish EBF rates from 0 to 6 months. The Maternal, Infant and Young Child Nutrition (MIYCN) study was a cluster randomized trial; the control arm (MIYCN-Control) received standard care involving community health workers (CHWs) visits for counselling on antenatal and postnatal care. The intervention arm (MIYCN-Intervention) received standard care and regular MIYCN counselling by trained CHWs. Both groups received MIYCN information materials. We tested differences in EBF rates from 0 to 6 months among four study groups (Pre-intervention, MIYCN-Intervention, MIYCN-Control and Comparison) using a χ(2) test and logistic regression. At 6 months, the prevalence of EBF was 2% in the Pre-intervention group compared with 55% in the MIYCN-Intervention group, 55% in the MIYCN-Control group and 3% in the Comparison group (P<0.05). After adjusting for baseline characteristics, the odds ratio for EBF from birth to 6 months was 66.9 (95% CI 45.4-96.4), 84.3 (95% CI 40.7-174.6) and 3.9 (95% CI 1.8-8.4) for the MIYCN-Intervention, MIYCN-Control and Comparison group, respectively, compared with the Pre-intervention group. There is potential effectiveness of the Kenya national Community Health Strategy in promoting EBF in urban poor settings where health care access is limited.

The fetal programming of food preferences: current clinical and experimental evidence.

Abstract: Increased energy consumption is one of the major factors implicated in the epidemic of obesity. There is compelling evidence, both clinical and experimental, that fetal paucity of nutrients may have programming effects on feeding preferences and behaviors that can contribute to the development of diseases. Clinical studies in different age groups show that individuals born small for their gestational age (SGA) have preferences towards highly caloric foods such as carbohydrates and fats. Some studies have also shown altered eating behaviors in SGA children. Despite an apparent discrepancy in different age groups, all studies seem to converge to an increased intake of palatable foods in SGA individuals. Small nutrient imbalances across lifespan increase the risk of noncommunicable diseases in adult life. Homeostatic factors such as altered responses to leptin and insulin and alterations in neuropeptides associated with appetite and satiety are likely involved. Imbalances between homeostatic and hedonic signaling are another proposed mechanism, with the mesocorticolimbic dopaminergic pathway having differential reward and pleasure responses when facing palatable foods. Early exposure to undernutrition also programs hypothalamic-pituitary-adrenal axis, with SGA having higher levels of cortisol in different ages, leading to chronic hyperactivity of this neuroendocrine axis. This review summarizes the clinical and experimental evidence related to fetal programming of feeding preferences by SGA.

Risk factors affecting child cognitive development: a summary of nutrition, environment, and maternal–child interaction indicators for sub-Saharan Africa

Abstract: An estimated 200 million children worldwide fail to meet their development potential due to poverty, poor health and unstimulating environments. Missing developmental milestones has lasting effects on adult human capital. Africa has a large burden of risk factors for poor child development. The objective of this paper is to identify scope for improvement at the country level in three domains--nutrition, environment, and mother-child interactions. We used nationally representative data from large-scale surveys, data repositories and country reports from 2000 to 2014. Overall, there was heterogeneity in performance across domains, suggesting that each country faces distinct challenges in addressing risk factors for poor child development. Data were lacking for many indicators, especially in the mother-child interaction domain. There is a clear need to improve routine collection of high-quality, country-level indicators relevant to child development to assess risk and track progress.

Just DO(HaD) It! Testing the clinical potential of the DOHaD hypothesis to prevent mental disorders using experimental study designs.

Abstract: Optimal early cognitive and emotional development are vital to reaching one's full potential and represent our best chance to improve the mental health of the population. The developmental origins of health and disease (DOHaD) hypothesis posits that adverse perinatal exposures can alter physiology and increase disease risk. As physiological plasticity decreases with age, interventions applied during gestation may hold the most promise for reducing the impact of mental disorders across the lifespan. However, this vast clinical potential remains largely unrealized as the majority of human DOHaD research is observational in nature. The application of more rigorous experimental designs [e.g. Randomized Controlled Trials (RCTs)] not only represents a major step toward unlocking this potential, but are required to fully test the scientific validity of the DOHaD hypothesis as it pertains to mental illness. Here, we argue that the optimization of maternal diet and exercise during pregnancy represents our best chance to improve offspring neurodevelopment and reduce the burden of mental disorders. Follow-up studies of the offspring of pregnant women enrolled in new and existing RCTs of maternal gestational nutrition+exercise interventions are required to determine if acting during pregnancy can prevent and/or meaningfully reduce the prevalence and severity of mental disorders in the population.

Phthalates in neonatal health: friend or foe?

Abstract: Exposure to environmental chemicals has adverse effects on the health and survival of humans. Emerging evidence supports the idea that exposure to endocrine-disrupting compounds (EDCs) can perturb an individual's physiological set point and as a result increase his/her propensity toward several diseases. The purpose of this review is to provide an update on di-(2-ethylhexyl) phthalate, the primary plasticizer found in plastic medical devices used in neonatal intensive care units, its effects on the fetus and newborn, epidemiological studies, pharmacokinetics, toxicity and epigenetic implications. We searched the PubMed databases to identify relevant studies. Phthalates are known EDCs that primarily are used to improve the flexibility of polyvinyl chloride plastic products and are called plasticizers in lay terms. Neonates and infants are particularly vulnerable to the effects of phthalates, beginning with maternal exposure and placental transfer during gestation and during infancy following birth. In line with the developmental origins of adult disease, a focus on the effects of environmental chemicals in utero or early childhood on the genesis of adult diseases through epigenome modulation is timely and important. The epigenetic effects of phthalates have not been fully elucidated, but accumulating evidence suggests that they may be associated with adverse health effects, some of which may be heritable. Phthalate exposure during pregnancy and the perinatal period is particularly worrisome in health-care settings. Although the clinical significance of phthalate exposure has been difficult to assess with epidemiologic studies, the evidence that physiological changes occur due to exposure to phthalates is growing and points toward the need for more investigation at a molecular, specifically epigenetic level.

Adolescent education: an opportunity to create a Developmental Origins of Health and Disease (DOHaD) circuit breaker.

Abstract: Health before conception, and periconceptional nutritional environments, contribute to conditioning of later-life health and disease. Health behaviors developed during adolescence continue into adulthood. Thus, even when the gap between pregnancy and adolescence is substantial, behaviors developed during adolescence influence later-life non-communicable disease (NCD) vulnerability in offspring. Consequently, adolescence is an important life phase where development of positive health behaviors can contribute to disruption of transgenerational cycles of NCD risk. Schooling is a core activity during adolescence. Modern curricula focus on development of capabilities associated with critical, engaged citizenship, empowering learning that supports action-based engagement in complex issues. Contexts relevant to adolescents and their communities, such as the NCD epidemic, are used to facilitate learning. Thus, engaging the education sector as participants in the work of the Developmental Origins of Health and Disease community offers an important strategy to capture the potential of adolescence as a life stage for transgenerational primary prevention of obesity and NCD risk.

Epicardial fat thickness, an emerging cardiometabolic risk factor, is increased in young adults born preterm

Abstract: Preterm birth and epicardial fat thickness (EFT) constitute novel risk factors for the onset of future adverse cardiovascular events. In total, 30 ex-extremely low birth weight (ex-ELBW) subjects (10 males, 20 females, aged 17-28) were enrolled and compared with 30 healthy peers. EFT was significantly higher (8.7±0.7 mm v. 5.6±0.9 mm; P<0.001) in ex-ELBW than in controls and was correlated with birth weight (r=-0.47, P=0.0009), gestational age (r=-0.39, P=0.03) and cardiac left ventricular mass (r=0.51, P=0.004). When excluding the influence of body mass index, birth weight was the sole remaining determinant of EFT, irrespective of gestational age (r=-0.37, P=0.04). The same findings when excluding the possible influence of blood pressure values on the cardiac structures (r=-0.40, P=0.028). In conclusion, EFT is significantly higher in former preterm subjects and is likewise associated with an increase in left ventricular mass. In view of the acknowledged correlation between the latter and an increased incidence of cardiovascular diseases, EFT appears to be an easy-to-measure tool capable of predicting the likely development of future adverse cardiovascular events in these subjects.

Exposures influencing total IgA level in colostrum

Abstract: Immunoglobulin A (IgA) is a predominant immunoglobulin present in human breast milk and is known to play an important role in infant gut immunity maturation. Breast milk composition varies between populations, but the environmental and maternal factors responsible for these variations are still unclear. We examined the relationship between different exposures and levels of IgA in colostrum. The objective of this study was to examine whether exposures analysed influence levels of IgA in colostrum. The present study used 294 colostrum samples from the MecMilk International cohort, collected from women residing in London, Moscow and Verona. Samples were analysed in automated Abbott Architect Analyser. We found an inverse correlation between time postpartum and colostrum total IgA level (r=-0.49, P<0.001). Adjusting for maternal parity, smoking, fresh fruit and fish consumption and allergen sensitization, multiple regression model showed that IgA levels were influenced by colostrum collection time (P<0.0001) and country of collection (P<0.01). Mode of delivery influence did not appear to be significant in univariate comparisons, once adjusted for the above maternal characteristics it showed a significant influence on total IgA (P=0.01). We conclude that the concentration of IgA in colostrum drops rapidly after birth and future studies should always consider this factor in analysis. IgA concentration varied significantly between countries, with the highest level detected in Moscow and lowest in Verona. Mode of delivery effect should be confirmed on larger cohorts. Further work is needed to determine ways to correct for IgA decline over time in colostrum, and to find the cause of variations in IgA levels between the countries.

Vitamin D fortification and seasonality of birth in type 1 diabetic cases: D-tect study.

Abstract: Fortification of margarine with vitamin D was mandatory in Denmark during 1961-1985. The aim of the study was to assess whether gestational and early infancy exposure to margarine fortification was associated with seasonality of birth in Danish type 1 diabetes (T1D) patients. The risks of T1D in Danes born during various exposure periods around margarine fortification termination in 1985 were analyzed. As expected, the T1D hazards in males unexposed to margarine fortification and born in spring were higher than in males born in autumn: relevant hazard ratios (95% confidence intervals) in various exposure groups ranged from 1.74 (1.112/2.708) to 37.43 (1.804/776.558). There were no indications of seasonality of birth in males exposed to fortification, nor in both exposed and unexposed females. The study suggests that early life exposure to low-dose vitamin D from fortified food eliminates seasonality of birth in T1D male patients. Further studies are required to investigate the identified gender differences.

Relationship between early growth and CVD risk factors in adolescents

Abstract: Low birth weight and a rapid weight gain in early childhood may lead to an increased risk for developing cardiovascular disease later in life, such as hypertension and dyslipidaemia. In this study, we examined the associations between size at birth, relative weight gain in infancy and childhood with specific cardiovascular disease risk factors in early adulthood. Adolescents (n=1935) from the Birth to Twenty plus (BT20+) cohort were included in the analysis. The following were treated as exposure variables: weight at birth, and relative conditional weight gain (CW), independent of height, between ages 0-24 months and 24-48 months. Outcomes were serum lipids and body composition variables at age 18 years. After adjusting for sex and other confounders, early life exposures were not associated with adolescent lipid profile. Following adjustment for sex and height (body size), birth weight [β=0.704 (0.40, 1.01)], CW 0-24 [β=1.918 (1.56, 2.28)] and CW24-48 [β=1.485 (1.14, 1.82)] accounted for 48% of the variance in fat mass. However, birth weight [β=0.773 (0.54, 1.01)], CW 0-24 [β=1.523 (1.24, 1.80)] and CW24-48 [β=1.226 (0.97, 1.49)] were also positively predicted and accounted for 71% of the variance in fat mass in adolescence (P<0.05). Our data suggests that birth weight and weight gain during infancy and early childhood independent of linear growth are related to adolescent body composition but not blood lipid profiles in an urban African population.

Vitamin D deficiency, behavioral atypicality, anxiety and depression in children with chromosome 22q11.2 deletion syndrome

Abstract: Chromosome 22q11.2 deletion syndrome (22q11.2DS) is a complex developmental disorder with serious medical, cognitive and emotional symptoms across the lifespan. This genetic deletion also imparts a lifetime risk for developing schizophrenia that is 25-30 times that of the general population. The origin of this risk is multifactorial and may include dysregulation of the stress response and immunological systems in relation to brain development. Vitamin D is involved in brain development and neuroprotection, gene transcription, immunological regulation and influences neuronal signal transduction. Low levels of vitamin D are associated with schizophrenia, depression and anxiety in the general population. Yet, little is known about how vitamin D levels in children with 22q11.2DS could mediate risk of psychosis in adulthood. Blood plasma levels of vitamin D were measured in children aged 7-16 years with (n=11) and without (n=16) 22q11.2DS in relation to parent reports of children's anxiety and atypicality. Anxiety and atypicality in childhood are risk indicators for the development of schizophrenia in those with 22q11.2DS and the general population. Children with 22q11.2DS had lower vitamin D levels, as well as elevated anxiety and atypicality compared with typical peers. Higher levels of anxiety, depression and internalizing problems but not atypicality were associated with lower levels of vitamin D. Vitamin D insufficiency may relate to higher levels of anxiety and depression, in turn contributing to the elevated risk of psychosis in this population. Further study is required to determine casual linkages between anxiety, stress, mood and vitamin D in children with 22q11.2DS.