The neglected role of insulin-like growth factors in the maternal circulation regulating fetal growth

Maternal insulin-like growth factors (IGFs) play a pivotal role in modulating fetal growth via their actions on both the mother and the placenta. Circulating IGFs influence maternal tissue growth and metabolism, thereby regulating nutrient availability for the growth of the conceptus. Maternal IGFs also regulate placental morphogenesis, substrate transport and hormone secretion, all of which influence fetal growth either via indirect effects on maternal substrate availability, or through direct effects on the placenta and its capacity to supply nutrients to the fetus. The extent to which IGFs influence the mother and/or placenta are dependent on the species and maternal factors, including age and nutrition. As altered fetal growth is associated with increased perinatal morbidity and mortality and a greater risk of developing degenerative diseases in adult life, understanding the role of maternal IGFs during pregnancy is essential in order to identify mechanisms underlying altered fetal growth and offspring programming

Post‐traumatic stress disorder, child abuse history, birthweight and gestational age: a prospective cohort study

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/87171/1/BJO_3071_sm_TableS1.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/87171/2/BJO_3071_sm_TableS4.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/87171/3/BJO_3071_sm_TableS3.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/87171/4/BJO_3071_sm_TableS2.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/87171/5/j.1471-0528.2011.03071.x.pd

Everyday legitimacy and international administration: global governance and local legitimacy in Kosovo

International administrations are a very specific form of statebuilding. This paper examines the limits illustrated by the experience in Kosovo. Here, the international administration faced the same requirements of any legitimate, Liberal government, but without the checks and balances normally associated with Liberal governance. Thus, the international administration was granted full authority and the power thereby associated, but without the legitimacy upon which the Liberal social contract rests. The state-building agenda put forth came to be seen as more exogenous, reinforcing the delegitimization process. This paper will specifically address the influence of the Weberian approach to legitimacy on the statebuilding literature, as well as its limits. It will then propose other possible avenues for statebuilding, more in line with a wider understanding of legitimacy and intervention

Body fat mass and the proportion of very large adipocytes in pregnant women are associated with gestational insulin resistance.

Pregnancy is accompanied by fat gain and insulin resistance. Changes in adipose tissue morphology and function during pregnancy and factors contributing to gestational insulin resistance are incompletely known. We sought to characterize adipose tissue in trimesters 1 and 3 (T1/T3) in normal weight (NW) and obese pregnant women, and identify adipose tissue-related factors associated with gestational insulin resistance

Study of Women, Infant feeding, and Type 2 diabetes mellitus after GDM pregnancy (SWIFT), a prospective cohort study: methodology and design

<p>Abstract</p> <p>Background</p> <p>Women with history of gestational diabetes mellitus (GDM) are at higher risk of developing type 2 diabetes within 5 years after delivery. Evidence that lactation duration influences incident type 2 diabetes after GDM pregnancy is based on one retrospective study reporting a null association. The Study of Women, Infant Feeding and Type 2 Diabetes after GDM pregnancy (SWIFT) is a prospective cohort study of postpartum women with recent GDM within the Kaiser Permanente Northern California (KPNC) integrated health care system. The primary goal of SWIFT is to assess whether prolonged, intensive lactation as compared to formula feeding reduces the 2-year incidence of type 2 diabetes mellitus among women with GDM. The study also examines whether lactation intensity and duration have persistent favorable effects on blood glucose, insulin resistance, and adiposity during the 2-year postpartum period. This report describes the design and methods implemented for this study to obtain the clinical, biochemical, anthropometric, and behavioral measurements during the recruitment and follow-up phases.</p> <p>Methods</p> <p>SWIFT is a prospective, observational cohort study enrolling and following over 1, 000 postpartum women diagnosed with GDM during pregnancy within KPNC. The study enrolled women at 6-9 weeks postpartum (baseline) who had been diagnosed by standard GDM criteria, aged 20-45 years, delivered a singleton, term (greater than or equal to 35 weeks gestation) live birth, were not using medications affecting glucose tolerance, and not planning another pregnancy or moving out of the area within the next 2 years. Participants who are free of type 2 diabetes and other serious medical conditions at baseline are screened for type 2 diabetes annually within the first 2 years after delivery. Recruitment began in September 2008 and ends in December 2011. Data are being collected through pregnancy and early postpartum telephone interviews, self-administered monthly mailed questionnaires (3-11 months postpartum), a telephone interview at 6 months, and annual in-person examinations at which a 75 g 2-hour OGTT is conducted, anthropometric measurements are obtained, and self- and interviewer-administered questionnaires are completed.</p> <p>Discussion</p> <p>This is the first, large prospective, community-based study involving a racially and ethnically diverse cohort of women with recent GDM that rigorously assesses lactation intensity and duration and examines their relationship to incident type 2 diabetes while accounting for numerous potential confounders not assessed previously.</p

Can We Modify the Intrauterine Environment to Halt the Intergenerational Cycle of Obesity?

Child obesity is a global epidemic whose development is rooted in complex and multi-factorial interactions. Once established, obesity is difficult to reverse and epidemiological, animal model, and experimental studies have provided strong evidence implicating the intrauterine environment in downstream obesity. This review focuses on the interplay between maternal obesity, gestational weight gain and lifestyle behaviours, which may act independently or in combination, to perpetuate the intergenerational cycle of obesity. The gestational period, is a crucial time of growth, development and physiological change in mother and child. This provides a window of opportunity for intervention via maternal nutrition and/or physical activity that may induce beneficial physiological alternations in the fetus that are mediated through favourable adaptations to in utero environmental stimuli. Evidence in the emerging field of epigenetics suggests that chronic, sub-clinical perturbations during pregnancy may affect fetal phenotype and long-term human data from ongoing randomized controlled trials will further aid in establishing the science behind ones predisposition to positive energy balance

Guinea pig models for translation of the developmental origins of health and disease hypothesis into the clinic

Over 30 years ago Professor David Barker first proposed the theory that events in early life could explain an individual\u27s risk of non-communicable disease in later life: the developmental origins of health and disease (DOHaD) hypothesis. During the 1990s the validity of the DOHaD hypothesis was extensively tested in a number of human populations and the mechanisms underpinning it characterised in a range of experimental animal models. Over the past decade, researchers have sought to use this mechanistic understanding of DOHaD to develop therapeutic interventions during pregnancy and early life to improve adult health. A variety of animal models have been used to develop and evaluate interventions, each with strengths and limitations. It is becoming apparent that effective translational research requires that the animal paradigm selected mirrors the tempo of human fetal growth and development as closely as possible so that the effect of a perinatal insult and/or therapeutic intervention can be fully assessed. The guinea pig is one such animal model that over the past two decades has demonstrated itself to be a very useful platform for these important reproductive studies. This review highlights similarities in the in utero development between humans and guinea pigs, the strengths and limitations of the guinea pig as an experimental model of DOHaD and the guinea pig\u27s potential to enhance clinical therapeutic innovation to improve human health. (Figure presented.)

Maternal nutrition affects the ability of treatment with IGF-I and IGF-II to increase growth of the placenta and fetus, in guinea pigs

The aim of this study was to investigate how administration of IGF-I and IGF-II, during early to mid pregnancy, affects maternal growth and body composition as well as fetal and placental growth, in ad libitum fed, and in moderately, chronically food restricted guinea pigs. From day 20 of gestation, mothers (3–4 months old) were infused with IGF-I, IGF-II (565 μg/day) or vehicle for 17 days and then killed on day 40 of gestation. Maternal organ weights, fetal and placental weights were assessed. Treatment with IGFs did not alter body weight gain and had small effects on body composition in the mothers. Both IGF-I and IGF-II increased fetal and placental weights in ad libitum fed dams and IGF-I increased placental weight in food restricted dams. In conclusion, treatment with IGF-I during the first half of pregnancy stimulates placental growth in both ad libitum fed and food restricted guinea pigs without affecting maternal growth while fetal growth is stimulated by IGF treatment only in ad libitum fed animals.A. Sohlström, P. Fernberg, J. A. Owens and P. C. Owenshttp://www.elsevier.com/wps/find/journaldescription.cws_home/623041/description#descriptio

Late pregnancy increases hepatic expression of insulin-like growth factor-I in well nourished guinea pigs

Abstract Blood IGF-I concentrations are persistently elevated throughout pregnancy in humans and guinea pigs and may regulate substrate partitioning between mother and conceptus. In the guinea pig, liver and adipose tissue have recently been suggested to contribute to the increased levels of circulating IGF-I in mid-pregnancy, but whether this persists in late pregnancy in undernutrition is not known. Therefore the effect of pregnancy and undernutrition on circulating IGF-I and hepatic expression of IGF-I in late gestation in the guinea pig was examined. Female guinea pigs (Cavia porcellus) were fed ad libitum throughout pregnancy or 70% of ad libitum intake for 28 days prior to and throughout pregnancy (term is 69 d). Non-pregnant animals were maintained for 88 days on the same diets. Plasma IGF-I was measured by RIA after molecular sieving chromatography at low pH. Abundances of IGF-I and β-actin mRNA in maternal liver were quantified by digoxigenin-ELISA after RT PCR. Late pregnancy increased both the concentration of IGF-I protein (p < 0.001) in plasma and the relative abundance of liver IGF-I mRNA (p < 0.001) in ad libitum fed, but not in feed restricted pregnant guinea pigs. The concentration of IGF-I protein in plasma correlated positively with the relative abundance of IGF-I mRNA in liver overall (p < 0.002), suggesting the liver as a major source of endocrine IGF-I in late pregnant guinea pigs. This study demonstrates that hepatic expression of IGF-I remains elevated during late pregnancy in the well fed guinea pig, which is in contrast to that observed in other non-human species.P.A. Grant, K.L. Kind, C.T. Roberts, A. Sohlstrom, P.C. Owens and J.A. Owenshttp://www.elsevier.com/wps/find/journaldescription.cws_home/623041/description#descriptio