Low Birthweight as a Risk Factor for Non-communicable Diseases in Adults

According to studies undertaken over the past 40 years, low birthweight (LBW) is not only a significant predictor of perinatal death and morbidity, but also increases the risk of chronic non-communicable diseases (NCDs) in adulthood. The purpose of this paper is to summarize the research on LBW as a risk factor for NCDs in adults. The Barker hypothesis was based on the finding that adults with an LBW or an unhealthy intrauterine environment, as well as a rapid catch-up, die due to NCDs. Over the last few decades, terminology such as thrifty genes, fetal programming, developmental origins of health and disease (DOHaD), and epigenetic factors have been coined. The most common NCDs include cardiovascular disease, diabetes mellitus type 2 (DMT2), hypertension (HT), dyslipidemia, proteinuria, and chronic kidney disease (CKD). Studies in mothers who experienced famine and those that solely reported birth weight as a risk factor for mortality support the concept. Although the etiology of NCD is unknown, Barry Brenner explained the notion of a low glomerular number (nGlom) in LBW children, followed by the progression to hyperfiltration as the physiopathologic etiology of HT and CKD in adults based on Guyton's renal physiology work. Autopsies of several ethnic groups have revealed anatomopathologic evidence in fetuses and adult kidneys. Because of the renal reserve, demonstrating renal function in proportion to renal volume in vivo is more difficult in adults. The greatest impact of these theories can be seen in pediatrics and obstetrics practice.

Epigenetic Issues. The Link Between Microbiota and Gestational Diabetes.

Gestational diabetes (GDM) is considered a significant and increasing problem worldwide. The growing body of evidence points out that a hostile intrauterine environment in mothers with GDM via epigenetic mechanisms induces "diabetogenic" and "obesogenic" changes in an offspring's DNA. This sets in motion a vicious intergenerational cycle of metabolic diseases gradually deteriorating the health of the human population. One of the most important players in this process seems to be altered microbiota/microbiome. There is a chance that the identification of specific epigenetic marks may provide a key for future diagnostic, prognostic and therapeutic solutions/measures in the field of person-alized medicine. Given the reversibility of most epigenetic changes, an opportunity arises to improve the long-term health of the human population/race. In this manuscript, we aim to summarize available data on epigenetic changes among women suffering from GDM and their progeny in association with changes in microbiome.

Ethanol consumption during gestation promotes placental alterations in IGF-1 deficient mice

Background: During pregnancy, the placenta is an extremely important organ as it secretes its own hormones, e.g. insulin-like growth factor 1 (IGF-1), to ensure proper intrauterine fetal growth and development. Ethanol, an addictive and widely used drug, has numerous adverse effects during pregnancy, including fetal growth restriction (FGR). To date, the molecular mechanisms by which ethanol triggers its toxic effects during pregnancy, particularly in the placenta, are not entirely known. For this reason, a murine model of partial IGF-1 deficiency was used to determine ethanol alterations in placental morphology and AAH expression. Methods: Heterozygous (HZ, Igf1+/-) female mice were given 10% ethanol during 14 days as an acclimation period and throughout pregnancy. HZ female mice given water were used as controls. At gestational day 19, pregnant dams were sacrificed, placentas were collected and genotyped for subsequent studies. Results: IGF-1 deficiency and ethanol consumption during pregnancy altered placental morphology, and decreased placental efficiency and aspartyl/asparaginyl β-hydroxylase (AAH) expression in placentas from all genotypes. No differences were found in Igf1, Igf2, Igf1r and Igf2r mRNA expression in placentas from all groups. Conclusions: IGF-1 deficiency and ethanol consumption throughout gestation altered placental development, suggesting the crucial role of IGF-1 in the establishment of an adequate intrauterine environment that allows fetal growth. However, more studies are needed to study the precise mechanism to stablish the relation between both insults.

The Role of Leptin in the Development of Energy Homeostatic Systems and the Maintenance of Body Weight

LEP is a pleiotropic gene and the actions of leptin extend well beyond simply acting as the signal of the size of adipose tissue stores originally proposed. This is a discussion of the multi-system interactions of leptin with the development of the neural systems regulating energy stores, and the subsequent maintenance of energy stores throughout the lifespan. The prenatal, perinatal, and later postnatal effects of leptin on systems regulating body energy stores and on the energy stores themselves are heavily influenced by the nutritional environment which leptin exposure occurs. This review discusses the prenatal and perinatal roles of leptin in establishing the neuronal circuitry and other systems relevant to the adiposity set-point (or “threshold”) and the role of leptin in maintaining weight homeostasis in adulthood. Therapeutic manipulation of the intrauterine environment, use of leptin sensitizing agents, and identification of specific cohorts who may be more responsive to leptin or other means of activating the leptin signaling pathway are ripe areas for future research.

Epigenetic: New Insight in Gestational Diabetes Mellitus

Gestational diabetes mellitus (GDM) is the more frequent metabolic complication of pregnancy with a prevalence that is significantly increased in the last decade accounting for 12–18% of all pregnancies. Recent evidences strongly suggests that epigenetic profile changes could be involved in the onset of GDM and its related maternal and fetal complications. In particular, the unfavorable intrauterine environment related to hyperglycemia, a feature of GDM, has been evidenced to exert a negative impact on the establishment of the epigenome of the offspring. Furthermore the adverse in utero environment could be one of the mechanisms engaged in the development of adult chronic diseases. The purpose of this article is to review a number of published studies to fill the gap in our understanding of how maternal lifestyle and intrauterine environment influence molecular modifications in the offspring, with an emphasis on epigenetic alterations.

Exposure to maternal hyperglycemia and high-fat diet consumption after weaning in rats: repercussions on periovarian adipose tissue

Clinical and epidemiological studies show that maternal hyperglycemia can change the programming of offspring leading to transgenerational effects. These changes may be related to environmental factors, such as high-fat diet (HFD) consumption, and contribute to the comorbidity onset at the adulthood of the offspring. The objective of this study was to evaluate the hyperglycemic intrauterine environment, associated or not with an HFD administered from weaning to adult life on the periovarian adipose tissue of rat offspring Maternal diabetes was chemically induced by Streptozotocin. Female offsprings were randomly distributed into four experimental groups (n = 5 animals/group): Female offspring from control or diabetic mothers and fed an HFD or standard diet. HFD was prepared with lard enrichment and given from weaning to adulthood. On day 120 of life, the rats were anesthetized and sacrificed to obtain adipose tissue samples. Then, the hyperglycemic intrauterine environment and HFD fed after weaning caused a higher body weight, total fat, and periovarian fat in adult offspring, which could compromise the future reproductive function of these females. These rats showed higher adiposity index and adipocyte area, contributing to hypertrophied adipose tissue. Therefore, maternal diabetes itself causes intergenerational changes and, in association with the HFD consumption after weaning, exacerbated the changes in the adipose tissue of adult female offspring.

Exploring Breastfeeding Influencers for obese mothers: The experiences and perceptions of five clinically obese women and their midwives

<p>What are the barriers and facilitators to exclusive breastfeeding for women with a BMI equalling or exceeding 35kg/m²? A qualitative interpretative inquiry. Breastfeeding is established as beneficial to both mothers and infants in terms of short-term and long-term health, or as normalising to the susceptibility of numerous conditions of poor health. Obesity is counted amongst these. A significant proportion of lactation research demonstrates exclusive breastfeeding as protective against obesity for the infant, and various explanations are put forward, such as; milk and gut microbiome species and diversity, comparative initial weight trajectories and impact on future BMI, and comparative satiety development. However, international and New Zealand trends of obesity prevalence are noted to be increasing; and obesity discourse, medical discourse and the World Health Organisation position on causes and consequences of obesity continue to be discordant, with the understanding of obesity as caused by energy in, versus energy out disequilibrium, being challenged. Current research continues to pursue directions which demonstrate obesity to be linked to infant experiences which influence infant gut microbiome, including mode of birth, feeding methods and skin-to-skin; and intrauterine environment – referring to the fetal inheritance/epigenetic inheritance theory. Notably, studies examining the influence of epigenetic heritance propose that infants born to obese mothers begin with a disadvantage in terms of health trajectories, considered to stem from the intrauterine environment and experiences; are at a higher risk of caesarean birth and of receiving breastmilk substitutes than infants born to non-obese mothers. This study aimed to examine the breastfeeding experiences of obese client participants, and breastfeeding support experiences of midwives who have cared for obese clients, to learn more about what were considered breastfeeding influencers, facilitators or barriers, within the maternity journey. A secondary aim of pursuing this research was to apply findings to the study site to see if a review of breastfeeding knowledge or support practices offered to obese women was indicated. The initial study design utilised Facebook as a means of contemporaneous data collection. Due to low recruitment, the design was modified to include one-to-one semi-structured interviews, and midwives were included as participants. Data was analysed using interpretative phenomenological analysis, and five themes were identified reflecting the participants’ experience of their maternity journey, and how breastfeeding was understood to interrelate with other maternity experiences. Five main themes emerged during data analysis. These included communication, normality and autonomy, the midwifery partnership, the experience of intervention, and how intervention was understood to affect lactation. Communication was interpreted as the core theme for all participants, and this underpinned experience of normality and autonomy (defining oneself as a normal woman, and the ability to make decisions regarding one’s maternity journey). How participants interpreted the themes of normality and autonomy, and their experience and interpretation of communication went on to influence their experience of the midwifery partnership and interventions in pregnancy, intrapartum and breastfeeding support. No theme in isolation was definable as either barrier or facilitator to exclusive breastfeeding, but developed as such, through the context of the experience. The ability to define oneself as a ‘normal woman’ and the ability to participate in one’s own care were either encouraged or discouraged through how communication was interpreted throughout the entirety of the maternity journey and hence were key findings of this research. Analysis of participant narratives revealed that it was through communication that these themes were interpreted. The midwife participants demonstrated awareness of these themes and related them further to the experience of the midwifery partnership, and how these factors, along with the social construct of obesity, underpinned communication with obese women, and the midwifery partnership. Through data analysis the researcher noted considerable disparity between emerging themes and the research reviewed in the literature review. As this study was heavily focussed on models of care delivery and organisation at the study site, I question whether the disparity is reflective of the gap between research and practice. The aim of this study has been to identify breastfeeding barriers and facilitators for obese women and their midwives, and the purpose of doing so was to glean whether current service warranted further examination. From the themes which emerged in this study, I suggest that the approach to the maternity care of obese women, including language and communication styles as an area worthy of further examination.</p>

Exploring Breastfeeding Influencers for obese mothers: The experiences and perceptions of five clinically obese women and their midwives

<p>What are the barriers and facilitators to exclusive breastfeeding for women with a BMI equalling or exceeding 35kg/m²? A qualitative interpretative inquiry. Breastfeeding is established as beneficial to both mothers and infants in terms of short-term and long-term health, or as normalising to the susceptibility of numerous conditions of poor health. Obesity is counted amongst these. A significant proportion of lactation research demonstrates exclusive breastfeeding as protective against obesity for the infant, and various explanations are put forward, such as; milk and gut microbiome species and diversity, comparative initial weight trajectories and impact on future BMI, and comparative satiety development. However, international and New Zealand trends of obesity prevalence are noted to be increasing; and obesity discourse, medical discourse and the World Health Organisation position on causes and consequences of obesity continue to be discordant, with the understanding of obesity as caused by energy in, versus energy out disequilibrium, being challenged. Current research continues to pursue directions which demonstrate obesity to be linked to infant experiences which influence infant gut microbiome, including mode of birth, feeding methods and skin-to-skin; and intrauterine environment – referring to the fetal inheritance/epigenetic inheritance theory. Notably, studies examining the influence of epigenetic heritance propose that infants born to obese mothers begin with a disadvantage in terms of health trajectories, considered to stem from the intrauterine environment and experiences; are at a higher risk of caesarean birth and of receiving breastmilk substitutes than infants born to non-obese mothers. This study aimed to examine the breastfeeding experiences of obese client participants, and breastfeeding support experiences of midwives who have cared for obese clients, to learn more about what were considered breastfeeding influencers, facilitators or barriers, within the maternity journey. A secondary aim of pursuing this research was to apply findings to the study site to see if a review of breastfeeding knowledge or support practices offered to obese women was indicated. The initial study design utilised Facebook as a means of contemporaneous data collection. Due to low recruitment, the design was modified to include one-to-one semi-structured interviews, and midwives were included as participants. Data was analysed using interpretative phenomenological analysis, and five themes were identified reflecting the participants’ experience of their maternity journey, and how breastfeeding was understood to interrelate with other maternity experiences. Five main themes emerged during data analysis. These included communication, normality and autonomy, the midwifery partnership, the experience of intervention, and how intervention was understood to affect lactation. Communication was interpreted as the core theme for all participants, and this underpinned experience of normality and autonomy (defining oneself as a normal woman, and the ability to make decisions regarding one’s maternity journey). How participants interpreted the themes of normality and autonomy, and their experience and interpretation of communication went on to influence their experience of the midwifery partnership and interventions in pregnancy, intrapartum and breastfeeding support. No theme in isolation was definable as either barrier or facilitator to exclusive breastfeeding, but developed as such, through the context of the experience. The ability to define oneself as a ‘normal woman’ and the ability to participate in one’s own care were either encouraged or discouraged through how communication was interpreted throughout the entirety of the maternity journey and hence were key findings of this research. Analysis of participant narratives revealed that it was through communication that these themes were interpreted. The midwife participants demonstrated awareness of these themes and related them further to the experience of the midwifery partnership, and how these factors, along with the social construct of obesity, underpinned communication with obese women, and the midwifery partnership. Through data analysis the researcher noted considerable disparity between emerging themes and the research reviewed in the literature review. As this study was heavily focussed on models of care delivery and organisation at the study site, I question whether the disparity is reflective of the gap between research and practice. The aim of this study has been to identify breastfeeding barriers and facilitators for obese women and their midwives, and the purpose of doing so was to glean whether current service warranted further examination. From the themes which emerged in this study, I suggest that the approach to the maternity care of obese women, including language and communication styles as an area worthy of further examination.</p>

Mid-gestation cytokine profiles in mothers of children affected by autism spectrum disorder: a case–control study

Autism Spectrum disorder is one of the commonest and most important neurodevelopmental conditions affecting children today. With an increasing prevalence and an unclear aetiology, it is imperative we find early markers of autism, which may facilitate early identification and intervention. Alterations of gestational cytokine profiles have been reported in mothers of autistic children. Increasing evidence suggests that the intrauterine environment is an important determinant of autism risk. This study aims to examine the mid-gestational serum cytokine profiles of the mothers of autistic children from a well-characterised birth cohort. A nested sub-cohort within a large mother–child birth cohort were identified based on a confirmed multi-disciplinary diagnosis of autism before the age 10 years and neuro-typical matched controls in a 2:1 ratio. IFN-γ, IL-1β, IL-4, IL-6, IL-8, IL-17A, GMCSF and TNFα were measured in archived maternal 20-week serum using MesoScale Diagnostics multiplex technology and validation of our IL-17A measurements was performed using an ultrasensitive assay. From a cohort of 2137 children, 25 had confirmed autism before 10 years and stored maternal serum from mid-gestation. We examined the sera of these 25 cases and 50 matched controls. The sex ratio was 4:1 males to females in each group, and the mean age at diagnosis was 5.09 years (SD 2.13). We found that concentrations of IL-4 were significantly altered between groups. The other analytes did not differ significantly using either multiplex or ultra-sensitive assays. In our well-characterised prospective cohort of autistic children, we confirmed mid-gestational alterations in maternal IL-4 concentrations in autism affected pregnancies versus matched controls. These findings add to promising evidence from animal models and retrospective screening programmes and adds to the knowledge in this field.