Many lines of evidence, including epidemiologic data and extensive clinical and experimental studies, indicate that early life events play a powerful role in influencing later susceptibility to certain chronic diseases. This review synthesizes evidence from several disciplines to support the contention that environmental factors acting during development should be accorded greater weight in models of disease causation.

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Effect of In Utero and Early-Life Conditions on Adult Health and Disease

A scientific consensus is emerging that the origins of adult disease are often found among developmental and biological disruptions occurring during the early years of life. These early experiences can affect adult health in 2 ways—either by cumulative damage over time or by the biological embedding of adversities during sensitive developmental periods. In both cases, there can be a lag of many years, even decades, before early adverse experiences are expressed in the form of disease. From both basic research and policy perspectives, confronting the origins of disparities in physical and mental health early in life may produce greater effects than attempting to modify health-related behaviors or improve access to health care in adulthood.

https://jamanetwork.com/HttpHandlers/ArticlePdfHandler.ashx?journal=JAMA&articleId=184019&pdfFileName=jsc90003_2252_2259.pdf

Neuroscience, Molecular Biology, and the Childhood Roots of Health Disparities: Building a New Framework for Health Promotion and Disease Prevention

BACKGROUNDThese Guidelines for Paediatric Parenteral Nutrition have been developed as a mutual project of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN; www.espghan.org) and the European Society for Clinical Nutrition and Metabolism (ESPEN; www.espen.org). T

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1. Guidelines on Paediatric Parenteral Nutrition of the European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) and the European Society for Clinical Nutrition and Metabolism (ESPEN), Supported by the European Society of Paediatric Research (ESPR).

Summary: The apicomplexan parasite Toxoplasma gondii was discovered a little over 100 years ago, but knowledge of its biological life cycle and its medical importance has grown in the last 40 years. This obligate intracellular parasite was identified early as a pathogen responsible for congenital infection, but its clinical expression and the importance of reactivations of infections in immunocompromised patients were recognized later, in the era of organ transplantation and HIV infection. Recent knowledge of host cell-parasite interactions and of parasite virulence has brought new insights into the comprehension of the pathophysiology of infection. In this review, we focus on epidemiological and diagnostic aspects, putting them in perspective with current knowledge of parasite genotypes. In particular, we provide critical information on diagnostic methods according to the patient's background and discuss the implementation of screening tools for congenital toxoplasmosis according to health policies.

https://hal.archives-ouvertes.fr/hal-00696903/document

Epidemiology of and Diagnostic Strategies for Toxoplasmosis

The fetus and newborn face a complex set of immunological demands, including protection against infection, avoidance of harmful inflammatory immune responses that can lead to pre-term delivery, and balancing the transition from a sterile intra-uterine environment to a world that is rich in foreign antigens. These demands shape a distinct neonatal innate immune system that is biased against the production of pro-inflammatory cytokines. This bias renders newborns at risk of infection and impairs responses to many vaccines. This Review describes innate immunity in newborns and discusses how this knowledge might be used to prevent and treat infection in this vulnerable population.

Innate immunity of the newborn: basic mechanisms and clinical correlates

Fifth edition. Edited by Jack S. Remington and Jerome O. Klein. Philadelphia: W.B. Saunders Company, 2001. 1507 pages in one volume, illustrated

Infectious Diseases of the Fetus and Newborn Infant

Events during embryonic and fetal life as well as during early infancy may be a harbinger of disease in adulthood. Numerous examples can be cited to validate this contention. A fetus who fails to grow as a result of an adverse intrauterine environment may show a deficit of nephrons, predisposition of the nephrons to sclerosis from increased pressure in glomerular capillaries, and consequent development of hypertension in adult life. A fetus who has growth restriction with relative sparing of cranial growth may have an altered blood flow through the liver, possibly causing disruptions in cholesterol metabolism and coagulation, which may raise the risk of atherosclerosis and related cardiovascular disease in adult life. The same fetus may have a deficit of pancreatic b cells and be predisposed to insulin deficiency and type I diabetes mellitus as an adult. A low-birth-weight, small-for-gestational-age neonate whose nutrition is compromised may show metabolic adaptation by reducing dependence on glucose and using alternate fuels such as amino acids for survival, and in the process may develop insulin resistance and type II diabetes mellitus in adult life. A preterm neonate who has poor bone mineral content from deficient mineral intake and/or excessive mineral loss resulting from chronic use of diuretics may be at increased risk of osteoporosis as an adult. A preterm neonate with bronchopulmonary dysplasia may have alterations in alveolar number and size that may place the infant at risk for chronic obstructive pulmonary disease as an adult. The cases cited above raise an important hypothesis that many an adult disease may have its origin during development in periconceptional, embryonic, fetal and early neonatal life. Adult disease is probably a complex interplay of genotypic variation and environmental factors. One of the well-characterized adult diseases of developmental origin is termed metabolic syndrome, which comprises a pentad of hypertension, hyperinsulinism, dyslipidemia, obesity and cardiovascular disease. Insulin resistance, the hallmark of the metabolic syndrome, may be from genetic alterations such as angiotensin-converting enzyme gene-deletion polymorphism or from intrauterine and extrauterine environmental factors that lead to growth failure. If these concepts are important in our understanding of the management of a high-risk mother, fetus or neonate with regard to its consequences in adult life, we may be best served by reading a sentinel book entitled Developmental Origins of Health and Disease, edited by Peter Gluckman and Mark Hanson. With 84 authors from 12 countriesFamong them are maternal–fetal medicine specialists, neonatologists, epidemiologists, developmental biologists, nutritionists, endocrinologists, pathologists and physiologistsFthis book truly represents an international endeavor and a landmark contribution to the subject of human development in relation to its long-term effects. The in-depth coverage of many developmental perturbations causing adult disease introduces the reader to a unique lexicon relevant to the subject. For example, ‘critical window of developmental plasticity’ refers to a specific period during which an organ system may be most vulnerable to change, while being spared of an analogous effect of the genetic or the environmental factor during other times. The classic example of the window of plasticity is the development of a neural-tube defect attributed to folic acid deficiency, specifically during the periconceptional period. ‘Biologic adaptation’ is the adaptive response of a species to an environmental influence. The best example of the adaptive response is provided by observations in the desert locust. When the population density is high, the wing shape in the offspringFyielded by pheromonic signals from the mother at egg layingFis such that migration is possible, important for survival. Conversely, when the population is sparse, the wing shape is non-migratory, allowing the offspring to remain at the protective site of birth. ‘Thrifty genotype’ is an example of how low birth weight can promote genesFglucokinase as the probable candidate geneFthat protect the fetus from excess insulin during the intrauterine period of nutritional deprivation, but raising the specter of insulin resistance and type II diabetes mellitus during the period of surplus nutrition in later life. ‘Thrifty phenotype’ is an example of how low birth weight represents a phenotypic adaptation to a poor intrauterine environment in which a small size confers a survival benefit, but becomes deleterious in a postnatal environment of surplus energy. ‘Epigenetic’ is a term used to signify changes in gene expression in response to an environmental influence. Whether or not a gene is actively expressed within a particular cell is determined not only by the primary nucleotide sequence of the gene and its regulatory elements, but also by changes in the manner the DNA is modified and packaged within the nucleus. Epigenetic changes include Journal of Perinatology (2007) 27, 732–733 r 2007 Nature Publishing Group All rights reserved. 0743-8346/07 $30

Developmental origins of health and disease

Bronchopulmonary dysplasia (BPD) is the most prevalent form of chronic lung disease in infancy. Among the 3.9 million births in the United States in 1997, approximately 55 000 newborn infants weighed <1500 g at birth.1 Among these very low birth weight (VLBW) infants, 49 000 infants would be expected to be discharged alive at the end of their first hospitalization (Vanderbilt experience 1998). At an estimated incidence of 24% among the VLBW survivors (Vanderbilt experience 1998), 12 000 new cases of BPD would be expected to emerge annually, making BPD the leading cause of chronic lung disease in infancy.

The pathogenesis of BPD involves factors causing injury to an immature lung and factors inhibiting its healing.2,,3 The lung injury can result from such insults as hyaline membrane disease, barotrauma or volutrauma from mechanical ventilation, oxygen toxicity, and airway infection associated with prolonged tracheal intubation.4 The lung healing can be influenced by nutrients, antioxidants, inflammatory cells, eicosanoids, growth factors, peptide hormones, and components of extracellular matrix.5 The role of the essential micronutrient vitamin A (retinol) in the promotion of orderly growth and differentiation of regenerating epithelial tissues makes vitamin A an important nutrient during recovery from lung injury.6,,7 This review focuses on the pathophysiology of vitamin A deficiency in relation to BPD, examines the evidence for vitamin A deficiency in VLBW neonates, and provides guidelines for vitamin A supplementation as an approach toward amelioration of lung disease among the VLBW survivors.

Vitamin A promotes normal growth and differentiation of epithelial cells. Vitamin A deficiency, therefore, affects various organ systems, including the lung.6 The histopathologic changes in the respiratory system generally precede other consequences of vitamin A deficiency involving the genitourinary system, eye, and skin.6

Vitamin A deficiency results in a progressive sequence of …

Vitamin A supplementation in very low birth weight neonates: rationale and evidence.

We examined the ontogeny of vitamin A storage in fetal and neonatal lungs during perinatal development in the rat. High-performance liquid chromatography was used to measure concentrations of vitamin A and its esters, retinyl palmitate and stearate, in various fetal and neonatal tissues at times ranging from gestational day 14 through 21 and from postnatal day 1 through 21. The data show that significant vitamin A storage occurs in the fetal lung during the latter one-third of prenatal life. Depletion of these stores that begins before birth and continues into the early postnatal period suggests that the developing lung may be dependent on these local vitamin A stores during active growth and differentiation. The utilization of vitamin A stores in the developing lung appears to be independent of the liver stores of vitamin A.

Jayant P. Shenai

Papers

Infectious Diseases of the Fetus and Newborn Infant

Developmental origins of health and disease

Vitamin A supplementation in very low birth weight neonates: rationale and evidence.

Vitamin A storage in lungs during perinatal development in the rat.

Plasma retinol-binding protein response to vitamin A administration in infants susceptible to bronchopulmonary dysplasia.