To examine the roles of the placental and pituitary hormones in the control of maternal metabolism and fetal growth.
In addition to promoting growth of maternal tissues, placental growth hormone ...(GH-V) induces maternal insulin resistance and thereby facilitates the mobilization of maternal nutrients for fetal growth. Human placental lactogen (hPL) and prolactin increase maternal food intake by induction of central leptin resistance and promote maternal beta-cell expansion and insulin production to defend against the development of gestational diabetes mellitus. The effects of the lactogens are mediated by diverse signaling pathways and are potentiated by glucose. Pathologic conditions of pregnancy are associated with dysregulation of GH-V and hPL gene expression.
The somatogenic and lactogenic hormones of the placenta and maternal pituitary gland integrate the metabolic adaptations of pregnancy with the demands of fetal and neonatal development. Dysregulation of placental growth hormone and/or placental lactogen in pathologic conditions of pregnancy may adversely impact fetal growth and postnatal metabolic function.
Approximately 25% of the world's children aged <5 years have stunted growth, which is associated with increased mortality, cognitive dysfunction, and loss of productivity. Reducing by 40% the number ...of stunted children is a global target for 2030. The pathogenesis of stunting is poorly understood. Prenatal and postnatal nutritional deficits and enteric and systemic infections clearly contribute, but recent findings implicate a central role for environmental enteric dysfunction (EED), a generalized disturbance of small intestinal structure and function found at a high prevalence in children living under unsanitary conditions. Mechanisms contributing to growth failure in EED include intestinal leakiness and heightened permeability, gut inflammation, dysbiosis and bacterial translocation, systemic inflammation, and nutrient malabsorption. Because EED has multiple causal pathways, approaches to manage it need to be multifaceted. Potential interventions to tackle EED include: (1) reduction of exposure to feces and contact with animals through programs such as improved water, sanitation, and hygiene; (2) breastfeeding and enhanced dietary diversity; (3) probiotics and prebiotics; (4) nutrient supplements, including zinc, polyunsaturated fatty acids, and amino acids; (5) antiinflammatory agents such as 5-aminosalicyclic acid; and (6) antibiotics in the context of acute malnutrition and infection. Better understanding of the underlying causes of EED and development of noninvasive, practical, simple, and affordable point-of-care diagnostic tools remain key gaps. "Omics" technologies (genomics, epigenomics, transcriptomics, proteomics, and metabolomics) and stable isotope techniques (eg,
C breath tests) targeted at children and their intestinal microbiota will enhance our ability to successfully identify, manage, and prevent this disorder.
The factors controlling linear growth and weight gain in the human fetus and newborn infant are poorly understood. We review here the changes in linear growth, weight gain, lean body mass, and fat ...mass during mid- and late gestation and the early postnatal period in the context of changes in the secretion and action of maternal, placental, fetal, and neonatal hormones, growth factors, and adipocytokines. We assess the effects of hormonal determinants on placental nutrient delivery and the impact of preterm delivery on hormone expression and postnatal growth and metabolic function. We then discuss the effects of various maternal disorders and nutritional and pharmacologic interventions on fetal and perinatal hormone and growth factor production, growth, and fat deposition and consider important unresolved questions in the field.
Childhood obesity and its co-morbidities -- including type 2 diabetes, hypertension, dyslipidemia, sleep apnea, and fatty liver disease -- have seen striking increases in recent years. Despite a ...wealth of investigation, there is considerable controversy regarding the etiology of childhood obesity and the optimal approaches for prevention and treatment. Pediatric Obesity: Etiology, Pathogenesis, and Treatment addresses the controversy with a range of features that make it a unique resource for those who care for obese children and their families. Written from a perspective that is international in scope, the distinguished authors re-assess the roles of genetic and environmental factors in the pathogenesis of childhood obesity and critically review new studies of the effects of lifestyle, pharmacologic, and surgical interventions. The evidence-based approach of Pediatric Obesity: Etiology, Pathogenesis, and Treatment provides a comprehensive and invaluable guide for all healthcare providers concerned with the evaluation and care of children with nutritional and metabolic disease and with the societal implications of the obesity epidemic.
The body-fat content of a healthy full-term infant rises sharply from 10 to 14% at birth to 25 to 30% at 6 months of age,
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with a consequent 30% increase in the body-mass index (BMI). The accrual of ...body fat during infancy correlates with, and may be required for, normal linear growth, brain development, and cognitive function.
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After peaking at 6 to 12 months of age, the BMI normally declines to a nadir at 5 to 6 years of age and then “rebounds,” rising progressively throughout late childhood and adolescence. Numerous studies have shown that an early or exaggerated “adiposity . . .
Objective: Our objective was to formulate practice guidelines for the treatment and prevention of pediatric obesity.
Conclusions: We recommend defining overweight as body mass index (BMI) in at least ...the 85th percentile but < the 95th percentile and obesity as BMI in at least the 95th percentile against routine endocrine studies unless the height velocity is attenuated or inappropriate for the family background or stage of puberty; referring patients to a geneticist if there is evidence of a genetic syndrome; evaluating for obesity-associated comorbidities in children with BMI in at least the 85th percentile; and prescribing and supporting intensive lifestyle (dietary, physical activity, and behavioral) modification as the prerequisite for any treatment. We suggest that pharmacotherapy (in combination with lifestyle modification) be considered in: 1) obese children only after failure of a formal program of intensive lifestyle modification; and 2) overweight children only if severe comorbidities persist despite intensive lifestyle modification, particularly in children with a strong family history of type 2 diabetes or premature cardiovascular disease. Pharmacotherapy should be provided only by clinicians who are experienced in the use of antiobesity agents and aware of the potential for adverse reactions. We suggest bariatric surgery for adolescents with BMI above 50 kg/m2, or BMI above 40 kg/m2 with severe comorbidities in whom lifestyle modifications and/or pharmacotherapy have failed. Candidates for surgery and their families must be psychologically stable and capable of adhering to lifestyle modifications. Access to experienced surgeons and sophisticated multidisciplinary teams who assess the benefits and risks of surgery is obligatory. We emphasize the prevention of obesity by recommending breast-feeding of infants for at least 6 months and advocating that schools provide for 60 min of moderate to vigorous daily exercise in all grades. We suggest that clinicians educate children and parents through anticipatory guidance about healthy dietary and activity habits, and we advocate for restricting the availability of unhealthy food choices in schools, policies to ban advertising unhealthy food choices to children, and community redesign to maximize opportunities for safe walking and bike riding to school, athletic activities, and neighborhood shopping.
Pediatric obesity can lead to concurrent co-morbidities. Intensive lifestyle modification remains the primary treatment. Carefully selected patients with severe co-morbidities may benefit from the addition of pharmacotherapy and/or bariatric surgery. Because treatment is difficult, prevention is the ultimate goal.
Context: Insulin sensitivity is higher in patients with Prader-Willi syndrome (PWS) than in body mass index-matched obese controls (OCs). Factors contributing to the heightened insulin sensitivity of ...PWS remain obscure. We compared the fasting levels of various hormones, cytokines, lipids, and liver function tests in 14 PWS patients and 14 OCs with those in 14 age- and gender-matched lean children (LC). We hypothesized that metabolic profiles of children with PWS are comparable with those of LC, but different from those of OCs.
Results: Leptin levels were comparable in PWS patients and OCs, suggesting comparable degrees of adiposity. Glucose levels were comparable among groups. However, fasting insulin concentrations and homeostasis model assessment insulin resistance index were lower in PWS patients than in OCs (P < 0.05) and similar to LC. Moreover, high-density lipoprotein levels were lower and triglycerides higher in OCs (P < 0.05) but not PWS patients. Total adiponectin, high-molecular-weight (HMW) adiponectin and the HMW to total adiponectin ratio were higher in PWS patients (P < 0.05) than in OCs and similar to LC. High-sensitivity C-reactive protein and IL-6 levels were higher in OCs than in PWS patients or LC (P < 0.05). Nevertheless, PAI-1 levels were elevated in both OC and PWS patients. There were no group differences in glucagon-like peptide-1, macrophage chemoattractant protein-1, TNFα, IL-2, IL-8, IL-10, IL-12p40, IL-18, resistin, total or low-density lipoprotein cholesterol, aspartate aminotransferase, or alanine aminotransferase.
Conclusions: The heightened insulin sensitivity of PWS patients relative to OCs is associated with higher levels of adiponectin and lower levels of high-sensitivity C-reactive protein and IL-6. Future studies will determine whether PWS children are protected from obesity comorbidities such as type 2 diabetes, hyperlipidemia, and nonalcoholic fatty liver disease.
The heightened insulin sensitivity of Prader-Willi syndrome relative to obese controls is associated with higher levels of adiponectin and lower levels of pro-inflammatory cytokines, hsCRP, and IL-6.
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