Associations between placental pathology and poor intrauterine growth among a cohort of mother-infant singleton pairs in Leyte, the Philippines.

OBJECTIVE: Poor intrauterine growth has negative impacts for child growth and development and disproportionately affects children living in low-resource settings. In the present study, we investigated relationships between placental pathologies and indicators of poor intrauterine growth. METHODS: We enrolled a longitudinal cohort of 279 mother-infant pairs from Leyte, the Philippines. Placental measures included characteristics, pathological findings, and immunohistochemistry. At birth, intrauterine growth was assessed using anthropometric measures, weight-for-gestational age, and the clinical assessment of nutritional status score (CANSCORE) for determining fetal malnutrition. Multivariate linear regression and log-binomial regression models were applied, controlling for potential confounding factors. RESULTS: Maternal vascular malperfusion (MVM) was related to reduced birthweight (P < 0.0001), birth length (P = 0.002), head circumference (P = 0.001), and weight-to-length ratio (P = 0.016). MVM increased the risk for preterm delivery (P = 0.0005) and small for gestational age (SGA) (P = 0.016). Acute chorioamnionitis (P = 0.013) and MVM (P = 0.021) both led to an increased risk for fetal malnutrition defined by CANSORE<25. Villous tissue activated caspase-3 was associated with lower birth length (P = 0.0006), higher weight-to-length ratio (P = 0.004), reduced risks for SGA (P = 0.011) and low weight-to-length ratio for gestational age (P = 0.004). CONCLUSION: The present study applied comprehensive measures for intrauterine growth and demonstrates that low placental weight and placental pathology, chiefly MVM, contribute to poor intrauterine growth. A better understanding of the mechanistic role of specific placental pathologies on adverse newborn outcomes will provide opportunities for reducing incidence of poor intrauterine growth and associated long-term morbidities.

Maternal and Placental Risk Factors for Small Gestational Age and Fetal Malnutrition.

AIMS: This case-control study was conducted to identify maternal and placental risk factors of small-for-gestational-age (SGA) and fetal malnutrition. METHODS: Cases comprised 104 consecutively delivered SGA neonates (determined as per INTERGROWTH- 21st standard). An equal number of next-born gestation and gender-matched appropriatefor- gestational age (AGA) neonates served as controls. Maternal risk factors were enquired, and placentae were evaluated by clinical and histopathological examination. Nutrition of the neonates was assessed by the clinical assessment of nutrition (CAN) score. Univariate and multivariate logistic regression analysis was done to identify the maternal and placental risk factors. RESULTS: The prevalence of SGA in the present study was 23.9%. Maternal fever [adjusted Odds Ratio (aOR), 95% confidence interval (CI), 16.3 (3.5-124.1); p = 0.001], presence of placental syncytial knots [aOR (95% CI), 2.9 (1.1-9.1); p = 0.04] and placental calcifications [aOR (95% CI), 3(1.1- 8.7); p = 0.03], were identified as independent predictors of SGA using multivariate logistic regression analysis. Malnutrition (SCORE <25) affected 64% of SGA and 16.3% of AGA neonates. The only risk factor significantly associated with malnourished SGA was prematurity, whereas malnourished AGA was significantly associated with prematurity and fetal distress. In-hospital morbidities significantly higher in SGA were perinatal asphyxia, respiratory distress, need for respiratory support, polycythemia, hypoglycemia, and feeding intolerance. Mortality before discharge was 4.8% and 3.8% in SGA and AGA population, respectively (p > 0.05). Neonatal outcomes were comparable among well-nourished, malnourished SGA and AGA groups. CONCLUSION: Maternal fever, placental syncytial knots, and calcifications were independent risk factors of SGA, whereas prematurity and fetal distress were responsible for malnutrition.

Fetal Undernutrition Modifies Vascular RAS Balance Enhancing Oxidative Damage and Contributing to Remodeling.

Fetal stress is known to increase susceptibility to cardiometabolic diseases and hypertension in adult age in a process known as fetal programming. This study investigated the relationship between vascular RAS, oxidative damage and remodeling in fetal programming. Six-month old Sprague-Dawley offspring from mothers that were fed ad libitum (CONTROL) or with 50% intake during the second half of gestation (maternal undernutrition, MUN) were used. qPCR or immunohistochemistry were used to obtain the expression of receptors and enzymes. Plasma levels of carbonyls were measured by spectrophotometry. In mesenteric arteries from MUN rats we detected an upregulation of ACE, ACE2, AT1 receptors and NADPH oxidase, and lower expression of AT2, Mas and MrgD receptors compared to CONTROL. Systolic and diastolic blood pressure and plasma levels of carbonyls were higher in MUN than in CONTROL. Vascular morphology evidenced an increased media/lumen ratio and adventitia/lumen ratio, and more connective tissue in MUN compared to CONTROL. In conclusion, fetal undernutrition indices RAS alterations and oxidative damage which may contribute to the remodeling of mesenteric arteries, and increase the risk of adverse cardiovascular events and hypertension.

Fetal malnutrition is associated with impairment of endogenous melatonin synthesis in pineal via hypermethylation of promoters of protein kinase C alpha and cAMP response element-binding.

This study investigated whether and how fetal malnutrition would influence endogenous melatonin synthesis, and whether such effect of fetal malnutrition would transmit to the next generation. We enrolled 2466 participants and 1313 of their offspring. The urine 6-hydroxymelatonin sulfate and serum melatonin rhythm were measured. Methylation microarray detection and bioinformatics analysis were performed to identify hub methylated sites. Additionally, rat experiment was performed to elucidate mechanisms. The participants with fetal malnutrition had lower 6-hydroxymelatonin sulfate (16.59 ± 10.12 µg/24 hours vs 24.29 ± 11.99 µg/24 hours, P < .001) and arear under curve of melatonin rhythm (67.11 ± 8.16 pg/mL vs 77.11 ± 8.04 pg/mL, P < .001). We identified 961 differentially methylated sites, in which the hub methylated sites were locating on protein kinase C alpha (PRKCA) and cAMP response element-binding protein (CREB1) promoters, mediating the association of fetal malnutrition with impaired melatonin secretion. However, such effects were not observed in the offspring (all P > .05). Impaired histomorphology of pineal, decreased melatonin in serum, pineal, and pinealocyte were also found in the in vivo and in vitro experiments (P < .05 for the differences of the indicators). Hypermethylation of 10 CpG sites on the PRKCA promoter and 8 CpG sites on the CREB1 promoter were identified (all P < .05), which down-regulated PRKCA and CREB1 expressions, leading to decreased expression of AANAT, and then resulting in the impaired melatonin synthesis. Collectively, fetal malnutrition can impair melatonin synthesis through hypermethylation of PRKCA and CREB1 promoters, and such effects cannot be transmitted to the next generation.

Sex-dependent vulnerability of fetal nonhuman primate cardiac mitochondria to moderate maternal nutrient reduction.

Poor maternal nutrition in pregnancy affects fetal development, predisposing offspring to cardiometabolic diseases. The role of mitochondria during fetal development on later-life cardiac dysfunction caused by maternal nutrient reduction (MNR) remains unexplored. We hypothesized that MNR during gestation causes fetal cardiac bioenergetic deficits, compromising cardiac mitochondrial metabolism and reserve capacity. To enable human translation, we developed a primate baboon model (Papio spp.) of moderate MNR in which mothers receive 70% of control nutrition during pregnancy, resulting in intrauterine growth restriction (IUGR) offspring and later exhibiting myocardial remodeling and heart failure at human equivalent ∼25 years. Term control and MNR baboon offspring were necropsied following cesarean-section, and left ventricle (LV) samples were collected. MNR adversely impacted fetal cardiac LV mitochondria in a sex-dependent fashion. Increased maternal plasma aspartate aminotransferase, creatine phosphokinase (CPK), and elevated cortisol levels in MNR concomitant with decreased blood insulin in male fetal MNR were measured. MNR resulted in a two-fold increase in fetal LV mitochondrial DNA (mtDNA). MNR resulted in increased transcripts for several respiratory chain (NDUFB8, UQCRC1, and cytochrome c) and adenosine triphosphate (ATP) synthase proteins. However, MNR fetal LV mitochondrial complex I and complex II/III activities were significantly decreased, possibly contributing to the 73% decreased ATP content and increased lipid peroxidation. MNR fetal LV showed mitochondria with sparse and disarranged cristae dysmorphology. Conclusion: MNR disruption of fetal cardiac mitochondrial fitness likely contributes to the documented developmental programming of adult cardiac dysfunction, indicating a programmed mitochondrial inability to deliver sufficient energy to cardiac tissues as a chronic mechanism for later-life heart failure.

Nutrition and Cardiovascular Diseases: Programming and Reprogramming

Abstract The Developmental Origin of Health and Disease (DOHaD) is an area of science dedicated to studying the processes by which insults during critical periods of mammals development leading to physiological changes resultig in diseases throughout life. Studies point to a complex interaction between nutritional status in early life and cardiovascular system homeostasis in which maternal malnutrition during gestation and/or lactation, as well as early weaning, are associated with development of cardiovascular diseases in adulthood. In this context, epigenetic changes, such as DNA methylation, histone acetylation, and change in microRNA expression have been considered molecular bases of cellular plasticity, which can also be gender-dependent. Experimental studies have demonstrated that interventions encompassing the consumption of functional food/bioactive compounds, as well as energetic and nutrients adjustments on the diet, may attenuate or even prevent consequences associated with plasticity of development, improving cardiovascular health. This review aimed to gather and discuss the findings within this context, published over the last ten years.

Kidney and epigenetic mechanisms of salt-sensitive hypertension.

Dietary salt intake increases blood pressure (BP) but the salt sensitivity of BP differs between individuals. The interplay of ageing, genetics and environmental factors, including malnutrition and stress, contributes to BP salt sensitivity. In adults, obesity is often associated with salt-sensitive hypertension. The children of women who experience malnutrition during pregnancy are at increased risk of developing obesity, diabetes and salt-sensitive hypertension as adults. Similarly, the offspring of mice that are fed a low-protein diet during pregnancy develop salt-sensitive hypertension in association with aberrant DNA methylation of the gene encoding type 1A angiotensin II receptor (AT1AR) in the hypothalamus, leading to upregulation of hypothalamic AT1AR and renal sympathetic overactivity. Ageing is also associated with salt-sensitive hypertension. In aged mice, promoter methylation leads to reduced kidney production of the anti-ageing factor Klotho and a decrease in circulating soluble Klotho. In the setting of Klotho deficiency, salt-induced activation of the vascular Wnt5a-RhoA pathway leads to ageing-associated salt-sensitive hypertension, potentially as a result of reduced renal blood flow and increased peripheral resistance. Thus, kidney mechanisms and aberrant DNA methylation of certain genes are involved in the development of salt-sensitive hypertension during fetal development and old age. Three distinct paradigms of epigenetic memory operate on different timescales in prenatal malnutrition, obesity and ageing.

Maternal Undernutrition Modulates Neonatal Rat Cerebrovascular Structure, Function, and Vulnerability to Mild Hypoxic-Ischemic Injury via Corticosteroid-Dependent and -Independent Mechanisms.

The present study explored the hypothesis that an adverse intrauterine environment caused by maternal undernutrition (MUN) acted through corticosteroid-dependent and -independent mechanisms to program lasting functional changes in the neonatal cerebrovasculature and vulnerability to mild hypoxic-ischemic (HI) injury. From day 10 of gestation until term, MUN and MUN-metyrapone (MUN-MET) group rats consumed a diet restricted to 50% of calories consumed by a pair-fed control; and on gestational day 11 through term, MUN-MET groups received drinking water containing MET (0.5 mg/mL), a corticosteroid synthesis inhibitor. P9/P10 pups underwent unilateral carotid ligation followed 24 h later by 1.5 h exposure to 8% oxygen (HI treatment). An ELISA quantified MUN-, MET-, and HI-induced changes in circulating levels of corticosterone. In P11/P12 pups, MUN programming promoted contractile differentiation in cerebrovascular smooth muscle as determined by confocal microscopy, modulated calcium-dependent contractility as revealed by cerebral artery myography, enhanced vasogenic edema formation as indicated by T2 MRI, and worsened neurobehavior MUN unmasked HI-induced improvements in open-field locomotion and in edema resolution, alterations in calcium-dependent contractility and promotion of contractile differentiation. Overall, MUN imposed multiple interdependent effects on cerebrovascular smooth muscle differentiation, contractility, edema formation, flow-metabolism coupling and neurobehavior through pathways that both required, and were independent of, gestational corticosteroids. In light of growing global patterns of food insecurity, the present study emphasizes that infants born from undernourished mothers may experience greater risk for developing neonatal cerebral edema and sensorimotor impairments possibly through programmed changes in neonatal cerebrovascular function.

[Fetal malnutrition assessment program].

OBJECTIVE: To study the application of ponderal index (PI), body mass index (BMI), mid-arm circumference/head circumference (MAC/HC), and Clinical Assessment of Nutritional Status (CANS) score in assessing the nutritional status of neonates at birth, and to find a simple and reliable scheme for the assessment of fetal nutritional status. METHODS: PI, BMI, MAC/HC, and CANS were used to assess the nutritional status of full-term infants and preterm infants shortly after birth. The assessment results of these methods were analyzed. RESULTS: Among the 678 full-term infants, 61, 102, 47, and 131 were diagnosed with malnutrition by PI, BMI, MAC/HC, and CANS respectively. Among the 140 preterm infants, 30, 87, 9, and 112 were diagnosed with malnutrition by PI, BMI, MAC/HC, and CANS respectively. The combination of BMI and CANS had a detection rate of 99.3% in full-term infants and 100% in preterm infants. Compared with the single method, the combination significantly improved the detection rate of malnutrition (P < 0.05), while there was no significant difference between the combination of BMI+CANS and the combination of PI+BMI+CANS (P > 0.05). CONCLUSIONS: The combination of BMI+CANS can reduce the rate of missed diagnosis of fetal malnutrition. It is therefore a simple and reliable method for the assessment of fetal malnutrition.

Behavioral Feeding Circuit: Dietary Fat-Induced Effects of Inflammatory Mediators in the Hypothalamus.

Excessive dietary fat intake has extensive impacts on several physiological systems and can lead to metabolic and nonmetabolic disease. In animal models of ingestion, exposure to a high fat diet during pregnancy predisposes offspring to increase intake of dietary fat and causes increase in weight gain that can lead to obesity, and without intervention, these physiological and behavioral consequences can persist for several generations. The hypothalamus is a region of the brain that responds to physiological hunger and fullness and contains orexigenic neuropeptide systems that have long been associated with dietary fat intake. The past fifteen years of research show that prenatal exposure to a high fat diet increases neurogenesis of these neuropeptide systems in offspring brain and are correlated to behavioral changes that induce a pro-consummatory and obesogenic phenotype. Current research has uncovered several potential molecular mechanisms by which excessive dietary fat alters the hypothalamus and involve dietary fatty acids, the immune system, gut microbiota, and transcriptional and epigenetic changes. This review will examine the current knowledge of dietary fat-associated changes in the hypothalamus and the potential pathways involved in modifying the development of orexigenic peptide neurons that lead to changes in ingestive behavior, with a special emphasis on inflammation by chemokines.

Oral exposure of pregnant rats to copper nanoparticles caused nutritional imbalance and liver dysfunction in fetus.

Copper nanoparticles (Cu NPs) are increasingly used as an animal feed additive in China. In previous studies, it was determined that Cu NPs can penetrate the placental barrier, however, its toxic effects on the fetus have not yet been elucidated. Therefore, in this study, we investigated the potential fetal toxic effects of Cu NPs. Cu NPs were orally administered to pregnant Sprague-Dawley rats from gestation days (GDs) 3-18 at a dose of 60, 120, and 180 mg/kg/day. Cesarean sections were conducted on GD 19. During fetal examination, no toxicities were observed regarding general clinical signs, however, Cu NPs significantly decreased fetal body weight, body length, and liver weights. Cu ions and Cu MPs exhibited similar effects on the fetal development. Cu NPs increased the liver concentration of Cu, and decreased protein levels and Fe in fetuses. Cu NPs also increased oxidative stress and inflammation in the fetus after pregnant rats were exposed to high doses of Cu NPs. Oral exposure to Cu NPs during pregnancy increased Cu concentrations in the fetus, which not only affected fetal development, but also significantly induced oxidative stress and inflammatory responses in fetal liver. Taken together, these findings are valuable to evaluate fetal risk assessment after oral exposure of Cu NPs during pregnancy. Additional comprehensive toxicity studies are deemed necessary to clarify the underlying mechanisms involved.

Programación fetal / Fetal programming

El término Origen Temprano de las Enfermedades del Adulto explica la aparición temprana de las condiciones anormales cardiovasculares y metabólicas en la vida adulta, mayor riesgo de morbilidad y muerte asociados a factores ambientales, especialmente nutricionales, que actúan en las primeras etapas de la vida. Estas respuestas programadas dependen de la naturaleza del estímulo o noxa, del tiempo de exposición y del momento de ocurrencia de la noxa, pudiendo un solo genotipo original varios fenotipos y estarían condicionadas por criterios críticos en los cuales se desarrollarían cambios a largo plazo pudiendo ser reversibles o no. La Programación Fetal explica que respuestas adaptativas embrionarias y fetales en un ambiente subóptimo genera consecuencias adversas permanentes. La desnutrición, así como la sobrenutrición fetal aumenta el riesgo de desarrollar alteraciones en el peso y composición corporal fetal, y posteriormente obesidad, síndrome metabólico, incremento en la adiposidad, alteración en el metabolismo de la glucosa y / o insulina, alteración del metabolismo lipídico, alteraciones hepáticas y de las cifras tensionales. La impronta genómica es esencial para el desarrollo y defectos en la misma puede originar alteraciones de la identidad parental transmisibles a las siguientes generaciones. Esta programación fetal puede ser explicada por la epigenética, definida como la serie de alteraciones hereditarias de la expresión genética a través de modificaciones del ADN y las histonas centrales sin cambios en la secuencia de ADN. Estas modificaciones epigenéticas alteran la estructura y condensación de la cromatina, afectando la expresión del genotipo y fenotipo. Este artículo desarrolla los aspectos involucrados en la Programación Fetal y los posibles mecanismos sobre la misma(AU)

The term Early Origin of Adult Diseases explains the early onset of abnormal cardiovascular and metabolic conditions in adult life, increased risk of morbidity and death associated with environmental factors, especially nutritional factors, that act in the early stages of life. These programmed responses depend on the nature of the stimulus or noxa, the time of exposure and the moment of occurrence of the noxa, with a single original genotype being able to have several phenotypes and would be conditioned by critical criteria in which long-term changes could develop, reversibles or not. Fetal Programming explains that embryonic and fetal adaptive responses in a suboptimal environment generate permanent adverse consequences. Fetal malnutrition as overnutrition increases the risk of developing alterations in fetal body weight and composition, and subsequently obesity, metabolic syndrome, increased adiposity, impaired glucose and / or insulin metabolism, impaired lipid metabolism, liver disorders and altered blood pressure. The genomic imprint is essential for development and defects in it can cause alterations of the parental identity and are transmitted to the following generations. This fetal programming can be explained by epigenetics, defined as the series of inherited alterations of genetic expression through modifications of DNA and central histones without changes in the DNA sequence. These epigenetic modifications alter the structure and condensation of chromatin, affecting the expression of the genotype and phenotype. This article develops the aspects involved in Fetal Programming and the possible mechanisms on it(AU)

Micro-anatomic alterations of the placenta in a non-human primate model of gestational protein-restriction.

OBJECTIVES: Maternal protein malnutrition is associated with impaired fetal growth, and lifetime consequences for the offspring. Our group has previously developed a model of protein-restriction in the non-human primate, which was associated with fetal growth restriction, stillbirth, decreased placental perfusion, and evidence of fetal hypoxia, suggesting perturbed vascular development. Our objective was to histologically characterize the micro-anatomic alterations associated with adverse pregnancy outcomes taking an approach that permits investigation of the 3D vascular structure and surrounding histology without the requirement for 3D vascular casting or relying on 2D stereology which both have methodological limitations. METHODS: Rhesus macaques were assigned in the pre-gestational period to a control diet that contained 26% protein, or study diet containing 13% protein (50% PR diet). Placental tissue was collected at delivery and processed using a clarification, immunohistochemistry, and confocal microscopy protocol published previously by our group. Three dimensional reconstructions and quantitative assessment of the vascular micro-anatomy was performed using analysis software (Imaris®) and statistical analysis accounted for maternal and fetal confounders. RESULTS: In unadjusted analysis, when comparing those pregnancies on a 50% PR diet (n = 4) with those on a control diet (n = 4), protein-restriction diet was associated with decreased maternal pre-pregnancy weight (difference of -1.975kg, 95% CI -3.267 to -0.6826). When controlling for maternal pre-pregnancy weight, fetal sex, and latency from tissue collection to imaging, a gestational protein-restriction diet was associated with decreases in total vascular length, total vascular surface area, total vascular volume, and vascular density. CONCLUSION: In this pilot study, a gestational protein-restriction diet altered the placental micro-vasculature with decreased vascular caliber and density, which may be related to the observed adverse pregnancy outcomes and perturbed placental perfusion previously demonstrated in this model.

Fetal Head Growth during Early to Mid-Gestation Associated with Weight Gain in Mothers with Hyperemesis Gravidarum: A Retrospective Cohort Study.

The epigenetic impact of malnutrition in mothers with hyperemesis gravidarum (HG) on their offspring has not been fully elucidated. Recently, several reports have demonstrated that children born to mothers with HG were small for gestational age and had low birth weight, reduced insulin sensitivity, and neurodevelopmental delays during childhood. Therefore, we examined the relationship between fetal growth and changes in the maternal body weight in HG cases. A total of 34 patients with HG were hospitalized and delivered at term between 2009 and 2012. The records of 69 cases of pregnant women without a history of HG were extracted after matching their maternal age, parity, pregestational body mass index (BMI), gestational age, and fetal sex ratio with those of the HG group for comparison. The maternal weight gain at term was less in the HG than in the control group. There was no statistical difference in birth weight, placental weight, and ultrasonic fetometric parameters expressed in standard deviation (SD) scores, including biparietal diameter, abdominal circumference, and femur length, between the HG and the control group. Whereas fetal head growth in the HG group was positively associated with maternal weight gain at 20 weeks of gestation only, this association was not observed in the control group. We herein demonstrate that maternal weight gain from the nadir is associated with fetal head growth at mid-gestation. Thus, maternal undernutrition in the first trimester of pregnancy could affect fetal brain growth and development, leading to an increased risk of neurodevelopmental delays in later life.

"INTERGROWTH21st vs customized fetal growth curves in the assessment of the neonatal nutritional status: a retrospective cohort study of gestational diabetes".

BACKGROUND: Gestational diabetes mellitus is associated with increased incidence of adverse perinatal outcomes including newborns large for gestational age, macrosomia, preeclampsia, polyhydramnios, stillbirth, and neonatal morbidity. Thus, fetal growth should be monitored by ultrasound to assess for fetal overnutrition, and thereby, its clinical consequence, macrosomia. However, it is not clear which reference curve to use to define the limits of normality. Our aim is to determine which method, INTERGROWTH21st or customized curves, better identifies the nutritional status of newborns of diabetic mothers. METHODS: This retrospective cohort study compared the risk of malnutrition in SGA newborns and the risk of overnutrition in LGA newborns using INTERGROWTH21st and customized birth weight references in gestational diabetes. The nutritional status of newborns was assessed using the ponderal index. Additionally, to determine the ability of both methods in the identification of neonatal malnutrition and overnutrition, we calculate sensitivity, specificity, positive predictive value, negative predictive value and likelihood ratios. RESULTS: Two hundred thirty-one pregnant women with GDM were included in the study. The rate of SGA indentified by INTERGROWTH21st was 4.7% vs 10.7% identified by the customized curves. The rate of LGA identified by INTERGROWTH21st was 25.6% vs 13.2% identified by the customized method. Newborns identified as SGA by the customized method showed a higher risk of malnutrition than those identified as SGA by INTERGROWTH21st. (RR 4.24 vs 2.5). LGA newborns according to the customized method also showed a higher risk of overnutrition than those classified as LGA according to INTERGROWTH21st. (RR 5.26 vs 3.57). In addition, the positive predictive value of the customized method was superior to that of INTERGROWTH21st in the identification of malnutrition (32% vs 27.27%), severe malnutrition (22.73% vs 20%), overnutrition (51.61% vs 32.20%) and severe overnutrition (28.57% vs 14.89%). CONCLUSIONS: In pregnant women with DMG, the ability of customized fetal growth curves to identify newborns with alterations in nutritional status appears to exceed that of INTERGROWTH21st.

Differential impacts of late gestational over-and undernutrition on adipose tissue traits and associated visceral obesity risk upon exposure to a postnatal high-fat diet in adolescent sheep.

We hypothesized that late gestation malnutrition differentially affects expandability of adipose tissues to predispose for early postnatal visceral adiposity. Twin-lambs born to dams fed HIGH (150%/110% of required energy/protein, respectively), NORM (100% of requirements) or LOW (50% of NORM) diets during the last trimester were used. Postnatally, lambs were raised on moderate (CONV) or high-carbohydrate-high-fat (HCHF) diets. Adipose tissues were sampled at autopsy at 6 months of age (~puberty) to characterize cellularity, adipocyte cross-sectional area and gene expression patterns. HIGH and LOW compared to NORM lambs had reduced intrinsic (under CONV diet) cellularity in subcutaneous and mesenteric (particularly LOW), and reduced obesity-induced (under HCHF diet) hyperplasia in subcutaneous, mesenteric and perirenal (particularly HIGH) adipose tissues. This corresponded with more pronounced HCHF diet-induced hypertrophy in mesenteric (particularly LOW), perirenal (particularly HIGH) and subcutaneous (particularly HIGH) adipose tissues, and tissue-specific reductions in mRNA expressions for lipid metabolism, angiogenesis and adipose development. Gene expression for inflammation and lipid metabolism markers were increased and decreased, respectively, in HCHF lambs (HCHF lambs became obese) in all tissues. Both prenatal over- and undernutrition predisposed for abdominal adiposity and extreme perirenal hypertrophy due to reduced intrinsic (observed under CONV diet) cellularity and impaired ability of subcutaneous, mesenteric and perirenal adipose tissues to expand by hyperplasia rather than hypertrophy on an obesogenic (HCHF) diet.

Fetal malnutrition-induced catch up failure is caused by elevated levels of miR-322 in rats.

If sufficient nutrition is not obtained during pregnancy, the fetus changes its endocrine system and metabolism to protect the brain, resulting in a loss of body size. The detailed mechanisms that determine the success or failure of growth catch-up are still unknown. Therefore, we investigated the mechanism by which catch-up growth failure occurs. The body weights of rat pups at birth from dams whose calorie intake during pregnancy was reduced by 40% were significantly lower than those of controls, and some offspring failed to catch up. Short-body-length and low-bodyweight rats showed blood IGF-1 levels and mRNA expression levels of IGF-1 and growth hormone receptor (GHR) in the liver that were lower than those in controls. The next generation offspring from low-bodyweight non-catch-up (LBW-NCG) rats had high expression of miR-322 and low expression of GHR and IGF-1. The expression of miR-322 showed a significant negative correlation with GHR expression and body length, and overexpression of miR-322 suppressed GHR expression. We found that insufficient intake of calories during pregnancy causes catch-up growth failure due to increased expression of miR-322 and decreased expression of GHR in the livers of offspring, and this effect is inherited by the next generation.

Female ponderal index at birth and idiopathic infertility.

Epidemiological studies have demonstrated an increased risk of developing non-transmittable diseases in adults subjected to adverse early developmental conditions. Metabolic and cardiovascular diseases have been the focus of most studies. Nevertheless, data from animal models also suggest early programming of fertility. In humans, it is difficult to assess the impact of the in utero environment retrospectively. Birthweight is commonly used as an indirect indicator of intrauterine development. This research is part of the ALIFERT study. We investigated a potential link between ponderal index at birth and female fertility in adulthood. Data from 51 infertile and 74 fertile women were analysed. BW was on average higher in infertile women, whereas birth length did not differ between the two groups; thus, resulting in a significantly higher ponderal index at birth in infertile women. Ponderal index at birth has been identified as a risk factor for infertility. These results suggest the importance of the intra-uterine environment, not only for long-term metabolic health but also for fertility.

Fetal malnutrition assessment program / 中国当代儿科杂志

OBJECTIVE@#To study the application of ponderal index (PI), body mass index (BMI), mid-arm circumference/head circumference (MAC/HC), and Clinical Assessment of Nutritional Status (CANS) score in assessing the nutritional status of neonates at birth, and to find a simple and reliable scheme for the assessment of fetal nutritional status.@*METHODS@#PI, BMI, MAC/HC, and CANS were used to assess the nutritional status of full-term infants and preterm infants shortly after birth. The assessment results of these methods were analyzed.@*RESULTS@#Among the 678 full-term infants, 61, 102, 47, and 131 were diagnosed with malnutrition by PI, BMI, MAC/HC, and CANS respectively. Among the 140 preterm infants, 30, 87, 9, and 112 were diagnosed with malnutrition by PI, BMI, MAC/HC, and CANS respectively. The combination of BMI and CANS had a detection rate of 99.3% in full-term infants and 100% in preterm infants. Compared with the single method, the combination significantly improved the detection rate of malnutrition (@*CONCLUSIONS@#The combination of BMI+CANS can reduce the rate of missed diagnosis of fetal malnutrition. It is therefore a simple and reliable method for the assessment of fetal malnutrition.