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2B-1 Testicular function in newborn boys and fetal exposure to endocrine disrupters
Invited Lectures 1E-3 Perinatal factors influencing preterm brain development utilising advanced MRI techniques R.W. Hunt *. Consultant Neonatologist, The Royal Children’s Hospital, Melbourne, Australia Despite improvements in newborn intensive care, the preterm infant remains at significant risk of neurodevelopmental impairment. The VIBeS research group has been conducting a cohort study, in which preterm infants born less than 30 weeks’ gestation have been recruited, with early perinatal information collected, and then scanned with MRI at term corrected age. Post-acquisition analyses of these MR images have demonstrated significant differences in the structure of the preterm brain, compared to healthy term controls, with significant reductions in the volumes of tissue types such as cortical grey matter and unmyelinated white matter. This presentation will focus on the perinatal risk factors that contribute to differences in preterm brain structure, as well as the hormonal influences in the first six weeks of life that contribute to early postnatal brain development. Specifically, exposure to corticosteroids, both antenatally and postnatally, is significantly associated with fibre track development in the frontal white matter. Postnatal corticosteroid exposure is also associated with reductions in cortical grey matter volume. Postnatal endogenous levels of thyroxine, oestradiol and growth hormone all appear to play a role in different aspects of brain development in the preterm brain. Some of these effects may mediate the gender differences seen in neurodevelopmental outcomes in preterm infants.
Session 2A. Prenatal Nutrition 2A-2 Effects of periconceptional undernutrition on the mother and her offspring A.L. Jaquiery *. Liggins Institute, University of Auckland, New Zealand Undernutrition around the time of conception results in altered fetal growth, metabolism and endocrinology. The mechanisms underlying these changes are unclear. Possibilities include altered embryonic environment affecting development of fetal physiological systems, and altered maternal adaptation to pregnancy, affecting nutrient supply to the fetus later in gestation. In sheep, periconceptional undernutrition resulted in decreased maternal and fetal plasma concentrations of essential amino acids in early gestation. Rats fed a low protein diet between fertilisation and implantation had decreased cell number in the developing blastocyst, suggesting that the nutritional environment is important for normal embryonic growth. Maternal adaptation to pregnancy includes increased cardiac output, plasma volume, and uterine blood flow. Maximal plasma volume is positively associated with birth weight in humans. In sheep, periconceptional undernutrition results in increased uterine blood flow in late gestation, suggesting that nutritional status very early in pregnancy may affect cardiovascular adaptation later in gestation. Pregnancy related changes in metabolism include altered insulin action. Insulin resistance develops in mid to late gestation, to ensure adequate delivery of nutrients to the fetus. Maternal insulin sensitivity in late gestation is strongly inversely correlated with fetoplacental growth in humans. Sheep undernourished prior to conception failed to develop insulin resistance in mid pregnancy, suggesting that events early in gestation disrupt later metabolic adaptations, which in turn could affect fetal nutrient delivery and growth. Recent experiments aim to clarify the effects of periconceptional undernutrition on postnatal growth and metabolism. Results suggest altered growth regulation and carbohydrate metabolism persisting into post-pubertal life.
S35 2A-3 Maternal micronutrient deficiencies in the developing world do they influence birth outcomes? C. Parul *. Center for Human Nutrition, Department of International Health, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA Numerous physiologic, metabolic and behavioral changes of pregnancy facilitate adequate growth and development of the fetus. Hemorrhetic changes of pregnancy support preferential partitioning of nutrients to meet fetal demands. And yet, in malnourished settings, poor maternal nutritional status often leads to adverse birth outcomes and fetal growth restriction. This paper describes the burden of maternal micronutrient deficiencies in the developing world, examines the biological plausibility and possible mechanisms for the role of micronutrients in enhancing birth outcomes, reviews current knowledge and existing evidence for the impact of micronutrient supplementation on reproductive outcomes and identifies future research needs. Briefly, maternal deficiencies of micronutrients such as iron, vitamin A, iodine, zinc, folic acid and others have been associated with poor pregnancy outcomes. Current evidence exists to show that iron deficiency is causally associated with low birth weight, preterm delivery, and perinatal mortality. Such evidence is lacking for other single micronutrients including vitamin A and zinc. Numerous trials of multiple micronutrient supplementation during pregnancy have found no impact or modest improvements in birth weight. These trials have not been powered to examine effects on fetal or neonatal health and survival. A Cochrane meta-analysis of 9 published and unpublished trials has revealed insufficient evidence for replacing antenatal iron-folate with multiple micronutrients. Thus, more research is needed to test the efficacy of micronutrients beyond iron-folate for enhancing birth outcomes in the developing world.
Session 2B. Reproductive Health 2B-1 Testicular function in newborn boys and fetal exposure to endocrine disrupters K. Main *. University Department of Growth and Reproduction, Denmark The prevalence of congenital malformations such as hypospadias and cryptorchidism in boys has increased over the past decades, following time trends and geographic distribution of adult reproductive disorders such as testicular cancer and impaired semen quality. This suggests a common prenatal origin of a testicular dysgenesis syndrome. During the first postnatal months, the pituitary-gonadal axis is activated, which can be used as a diagnostic window of testicular function close to suspected adverse effects in utero. In our prospective, population-based cohort of 2562 newborn boys from Denmark and Finland, we found a higher prevalence of cryptorchidism and hypospadias in Danish than Finnish boys. Healthy Danish boys had smaller testes and showed less testicular growth during infancy, and their level of serum inhibin B was lower. In addition to low birth weight, being small for gestational age and prematurity, regular moderate maternal alcohol consumption and mild diabetes was found to be a risk factor for cryptorchidism. Environmental chemicals were measured in breast milk samples from mothers of cryptorchid and healthy boys. Positive associations were found between cryptorchidism and polybrominated diphenyl ethers (flame retardants) and polychlorinated pesticides. The content of phthalate monoesters (plastic emollients) was negatively correlated with serum testosterone levels. Our findings suggest, that perinatal exposure to some environmental chemicals may have adverse effects on testicular development in humans. This is of concern, as the foetus and infant will be persistently and simultaneously exposed to many chemicals.
Session 2A. Prenatal Nutrition 2A-2 Effects of periconceptional undernutrition on the mother and her offspring A.L. Jaquiery *. Liggins Institute, University of Auckland, New Zealand Undernutrition around the time of conception results in altered fetal growth, metabolism and endocrinology. The mechanisms underlying these changes are unclear. Possibilities include altered embryonic environment affecting development of fetal physiological systems, and altered maternal adaptation to pregnancy, affecting nutrient supply to the fetus later in gestation. In sheep, periconceptional undernutrition resulted in decreased maternal and fetal plasma concentrations of essential amino acids in early gestation. Rats fed a low protein diet between fertilisation and implantation had decreased cell number in the developing blastocyst, suggesting that the nutritional environment is important for normal embryonic growth. Maternal adaptation to pregnancy includes increased cardiac output, plasma volume, and uterine blood flow. Maximal plasma volume is positively associated with birth weight in humans. In sheep, periconceptional undernutrition results in increased uterine blood flow in late gestation, suggesting that nutritional status very early in pregnancy may affect cardiovascular adaptation later in gestation. Pregnancy related changes in metabolism include altered insulin action. Insulin resistance develops in mid to late gestation, to ensure adequate delivery of nutrients to the fetus. Maternal insulin sensitivity in late gestation is strongly inversely correlated with fetoplacental growth in humans. Sheep undernourished prior to conception failed to develop insulin resistance in mid pregnancy, suggesting that events early in gestation disrupt later metabolic adaptations, which in turn could affect fetal nutrient delivery and growth. Recent experiments aim to clarify the effects of periconceptional undernutrition on postnatal growth and metabolism. Results suggest altered growth regulation and carbohydrate metabolism persisting into post-pubertal life.
S35 2A-3 Maternal micronutrient deficiencies in the developing world do they influence birth outcomes? C. Parul *. Center for Human Nutrition, Department of International Health, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA Numerous physiologic, metabolic and behavioral changes of pregnancy facilitate adequate growth and development of the fetus. Hemorrhetic changes of pregnancy support preferential partitioning of nutrients to meet fetal demands. And yet, in malnourished settings, poor maternal nutritional status often leads to adverse birth outcomes and fetal growth restriction. This paper describes the burden of maternal micronutrient deficiencies in the developing world, examines the biological plausibility and possible mechanisms for the role of micronutrients in enhancing birth outcomes, reviews current knowledge and existing evidence for the impact of micronutrient supplementation on reproductive outcomes and identifies future research needs. Briefly, maternal deficiencies of micronutrients such as iron, vitamin A, iodine, zinc, folic acid and others have been associated with poor pregnancy outcomes. Current evidence exists to show that iron deficiency is causally associated with low birth weight, preterm delivery, and perinatal mortality. Such evidence is lacking for other single micronutrients including vitamin A and zinc. Numerous trials of multiple micronutrient supplementation during pregnancy have found no impact or modest improvements in birth weight. These trials have not been powered to examine effects on fetal or neonatal health and survival. A Cochrane meta-analysis of 9 published and unpublished trials has revealed insufficient evidence for replacing antenatal iron-folate with multiple micronutrients. Thus, more research is needed to test the efficacy of micronutrients beyond iron-folate for enhancing birth outcomes in the developing world.
Session 2B. Reproductive Health 2B-1 Testicular function in newborn boys and fetal exposure to endocrine disrupters K. Main *. University Department of Growth and Reproduction, Denmark The prevalence of congenital malformations such as hypospadias and cryptorchidism in boys has increased over the past decades, following time trends and geographic distribution of adult reproductive disorders such as testicular cancer and impaired semen quality. This suggests a common prenatal origin of a testicular dysgenesis syndrome. During the first postnatal months, the pituitary-gonadal axis is activated, which can be used as a diagnostic window of testicular function close to suspected adverse effects in utero. In our prospective, population-based cohort of 2562 newborn boys from Denmark and Finland, we found a higher prevalence of cryptorchidism and hypospadias in Danish than Finnish boys. Healthy Danish boys had smaller testes and showed less testicular growth during infancy, and their level of serum inhibin B was lower. In addition to low birth weight, being small for gestational age and prematurity, regular moderate maternal alcohol consumption and mild diabetes was found to be a risk factor for cryptorchidism. Environmental chemicals were measured in breast milk samples from mothers of cryptorchid and healthy boys. Positive associations were found between cryptorchidism and polybrominated diphenyl ethers (flame retardants) and polychlorinated pesticides. The content of phthalate monoesters (plastic emollients) was negatively correlated with serum testosterone levels. Our findings suggest, that perinatal exposure to some environmental chemicals may have adverse effects on testicular development in humans. This is of concern, as the foetus and infant will be persistently and simultaneously exposed to many chemicals.