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Drug Exposure in Newborns: Effect of Selected Drugs Prescribed to Mothers During Pregnancy and Lactation.
Rentsch, KM
Therapeutic drug monitoring. 2020;(2):255-263
Abstract
The number of newborns exposed to therapeutic drugs during pregnancy is growing because of the increased use of drugs during pregnancy. In recent years, advances in our understanding of drug placental transfer have augmented the likelihood of a healthy baby in mothers with chronic diseases needing drug therapy. Globally, for example, more than 1.4 million pregnancies in 2015 have been burdened with antiretroviral drugs due to an increasing number of HIV-positive women treated with these drugs, particularly in low- and middle-income countries. In most cases, the fetus is exposed to much higher drug doses in utero than the newborn nursed by the mother. Drug transfer through the placenta takes place by passive diffusion, active transport, or facilitated transport, and drug concentrations in the fetal circulation may be comparable to that in the mother's blood concentration. The excretion of drugs into breastmilk predominantly occurs by passive diffusion, allowing only the non-protein-bound fraction of the blood drug concentration to penetrate. Drug agencies in the United States and Europe highly recommend performing clinical trials in pregnant or breastfeeding women. However, only a few drugs have reported statistically sound data in these patient groups. Most available results concerning pregnancy are obtained from observational studies after birth, assessing outcomes in the newborn or by measuring drug concentrations in the mother and umbilical cord blood. In the case of the lactation period, some studies have evaluated drug concentrations in breastmilk and blood of the mother and/or infant. In this review, exposure to antiretrovirals, immunosuppressants used after solid organ transplantation, and antiepileptics during pregnancy and lactation has been discussed in detail.
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Prevention of Gestational Diabetes Mellitus (GDM) and Probiotics: Mechanism of Action: A Review.
Homayouni, A, Bagheri, N, Mohammad-Alizadeh-Charandabi, S, Kashani, N, Mobaraki-Asl, N, Mirghafurvand, M, Asgharian, H, Ansari, F, Pourjafar, H
Current diabetes reviews. 2020;(6):538-545
Abstract
BACKGROUND Gestational Diabetes Mellitus (GDM) is a health problem that is increasing around the world. INTRODUCTION Prevention of GDM, rather than treatment, could have several benefits in terms of both health and economic cost. Even a slight reduction in maternal glucose in non-diabetic women, particularly in women at high risk for GDM, may have significant benefits for pregnancy results and the future health of off-springs. Probiotics are a relatively new intervention, which are assessed by mothers' metabolism, and can reduce blood sugar levels, prevent gestational diabetes and reduce the maternal and fetal complications resulting from it. The aim of this study was to review the studies on the prevention of gestational diabetes and assess the potential beneficial effects of probiotics on gestational diabetes and their possible mechanism of action. METHODS Articles compiled through clinical trials indexed in PubMed, Science Direct, Cochran, and Medlib between 2000 and 2017, with the keywords probiotics, prevention, and gestational diabetes mellitus were selected. RESULTS Considering the potential of probiotics in the modulation of gut microbiota, naturalization increases intestinal permeability, regulation of pro-inflammatory mediators' secretion and thereby controlling local and systemic inflammation results in decreasing intestinal permeability, enhancing the immune system. It likely has the ability to prevent or control diabetes during pregnancy although confirmatory studies are still needed. CONCLUSION Experimental and clinical evidence support the supposition that the modulation of the gut microbiota via probiotic microorganisms could be effective in the prevention of gestational diabetes mellitus.
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Interactions between nutrients in the maternal diet and the implications for the long-term health of the offspring.
Rees, WD
The Proceedings of the Nutrition Society. 2019;(1):88-96
Abstract
Nutritional science has traditionally used the reductionist approach to understand the roles of individual nutrients in growth and development. The macronutrient dense but micronutrient poor diets consumed by many in the Western world may not result in an overt deficiency; however, there may be situations where multiple mild deficiencies combine with excess energy to alter cellular metabolism. These interactions are especially important in pregnancy as changes in early development modify the risk of developing non-communicable diseases later in life. Nutrient interactions affect all stages of fetal development, influencing endocrine programming, organ development and the epigenetic programming of gene expression. The rapidly developing field of stem cell metabolism reveals new links between cellular metabolism and differentiation. This review will consider the interactions between nutrients in the maternal diet and their influence on fetal development, with particular reference to energy metabolism, amino acids and the vitamins in the B group.
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Bioactive food compounds, epigenetics and chronic disease prevention: Focus on early-life interventions with polyphenols.
Silva, LBAR, Pinheiro-Castro, N, Novaes, GM, Pascoal, GFL, Ong, TP
Food research international (Ottawa, Ont.). 2019;:108646
Abstract
Consumption of bioactive compounds such as polyphenols, isothiocyanates, sulfur-containing compounds and terpenoids, found in fruits and vegetables, is associated with prevention of chronic disease. These bioactive food compounds elicit their protective effects through complex mechanisms at the cellular and molecular, including epigenetic levels. According to the Developmental Origins of Health and Disease (DOHaD) paradigm, in utero exposure to stressors such as malnutrition through maternal diet would impair fetal development and epigenetically program increased risk of metabolic diseases and some cancers in adult life. In addition, a role for fathersĀ“ diet during preconception on their offspring health and chronic disease susceptibility has also emerged. This highlights early life as a promising window of opportunity for starting dietary interventions focusing on preventing chronic diseases. However, knowledge on the potential beneficial impact of early life exposure to bioactive food compounds is limited. Among the studies that have investigated bioactive food compounds in the context of DOHaD, most have focused on the impact of dietary polyphenols. Thus, in this review we discuss experimental evidence supporting a role for the dietary polyphenols resveratrol, genistein, epigallocatechin-3-gallate and anthocyanins in chronic disease prevention considering a perspective from early-life interventions through maternal and paternal diets and focusing on epigenetics as a potential underlying mechanism.
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Risk Factors Associated with the Occurrence of Neonatal Opioid Withdrawal Syndrome: A Review.
Kelty, E, Preen, DB
CNS drugs. 2019;(11):1113-1120
Abstract
In a number of countries, the prevalence of neonatal opioid withdrawal syndrome (NOWS) is increasing. While NOWS is ultimately the result of opioid exposure in utero, a wide range of risk factors have been associated with the prevalence of NOWS, extending beyond just drug exposure. This article reviews the available literature on factors associated with the incidence of NOWS in opioid-exposed neonates. A range of risk factors have been associated with NOWS, including features of neonatal drug exposure, maternal and neonatal characteristics, aspects of labor and delivery, and genetics. Increased length of gestation and higher birth weight were consistently associated with an increased risk of NOWS, while breast feeding and 'rooming-in' were associated with a reduced risk of NOWS. Additionally, several genetic factors have also been associated with NOWS severity. There is conflicting evidence on the association between NOWS and other risk factors including opioid dose, neonate sex, and the use of some medications during pregnancy. This may be in part attributable to differences in how NOWS is diagnosed and the variety of methodologies across studies. While a large number of risk factors associated with NOWS are non-modifiable, encouraging pregnant women to reduce other drug use (including smoking), breast feed their child, and the judicious use of medications during pregnancy may help reduce the prevalence of NOWS. The presence or absence of NOWS in an opioid-exposed neonate is associated with a wide range of factors. Some of these modifiable risk factors may be potential targets for the primary prevention of NOWS.
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The effect of iodine deficiency during pregnancy on child development.
Bath, SC
The Proceedings of the Nutrition Society. 2019;(2):150-160
Abstract
It is well known that severe iodine deficiency during pregnancy may cause impaired brain development in the child, with effects on cognitive and motor function, hearing and speech. Whether mild-to-moderate deficiency also affects neurological development is less well known, but in the past decade a number of observational studies have been conducted to answer this question and these studies are reviewed in this article. The picture is now emerging that even mild-to-moderate iodine deficiency during pregnancy may be associated with subtle impairments in cognition and school performance, although the evidence from randomised controlled trials is still lacking. As global efforts to eradicate iodine deficiency in populations continue, it is more likely that mild-to-moderate, rather than severe, iodine deficiency will be the issue of concern in pregnancy, and therefore further research in regions of mild-to-moderate deficiency is required to strengthen the research base and to inform public-health policy.
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Exposure to different intrauterine environments: implications for telomere attrition in early life.
Werlang, ICR, Hahn, MC, Bernardi, JR, Nast, M, Goldani, MZ, Michalowski, MB
The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians. 2019;(21):3675-3684
Abstract
Objective: Studies focusing on telomere attrition in newborns and what factors could be involved in this issue are sparse; most reports have been in adult populations. Thereby, the aim of this study was to present an overview of what is currently known about the relationship between environmental exposure of the fetus during pregnancy and telomere length outcomes in early life. Methods: The MEDLINE (via PubMed) and Bireme databases were searched for studies published until 1 June 2016. Studies that reported telomere length measurement from birth to age 1 year were included. Results: Fifteen articles were selected that evaluated possible relationships between maternal smoking, hyperglycemia, hypertension, sleep apnea, psychological stress, folate concentration in early pregnancy, and radiation, in addition to small-for-gestational-age status and preterm birth. We found that sleep apnea, psychological stress, and folate concentration in early pregnancy were associated with telomere shortening in the newborn. No association was found with radiation, small-for-gestational-age status, or preterm birth. Results for maternal smoking, hyperglycemia, and hypertension were conflicting, and further studies should be considered. Conclusion: The actual clinical implications of these findings have yet to be investigated.
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The Use of Non-insulin Agents in Gestational Diabetes: Clinical Considerations in Tailoring Therapy.
Blair, RA, Rosenberg, EA, Palermo, NE
Current diabetes reports. 2019;(12):158
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Abstract
PURPOSE OF REVIEW To assess evidence to date for use of non-insulin agents in treatment of gestational diabetes mellitus. RECENT FINDINGS There has been increasing interest in the use of non-insulin agents, primarily metformin and glyburide (which both cross the placenta). Metformin has been associated with less maternal weight gain; however, recent studies have shown a trend toward increased weight in offspring exposed to metformin in utero. Glyburide has been associated with increased neonatal hypoglycemia. Glycemic control during pregnancy is essential to optimize both maternal and fetal outcomes. There are a myriad of factors to consider when designing treatment programs including patient preference, phenotype, and glucose patterns. While insulin is typically recommended as first-line, some women refuse or cannot afford insulin and in those cases, non-insulin agents may be used. Further studies are needed to assess treatment in pregnancy, perinatal outcomes, and particularly long-term metabolic profiles in mothers and offspring.
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Environmental influences on health and development: nutrition, substance exposure, and adverse childhood experiences.
Gentner, MB, Leppert, MLO
Developmental medicine and child neurology. 2019;(9):1008-1014
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Scientific advances over the last century have generated compelling evidence of the primary and secondary effects of gestational, infant, and childhood conditions. These early environmental influences have the potential not only to impact an individual's health outcomes, such as heart disease, type 2 diabetes, and cancer, but also to confer various protections and risks to that individual's descendants. The immediate and extended ramifications of early environmental exposure bring an understanding of epidemiological impact on disease states and a hope for prevention. This review highlights the contributions of several key population studies and briefly explores specific environmental influences, including nutritional deficiencies, exposure to substances and infections, and adverse childhood experiences. Mechanisms of these influences (e.g. stress and epigenetics) are discussed, as well as possible means of mitigating their negative consequences. WHAT THIS PAPER ADDS Substance exposures in utero are associated with epigenetic changes and negative outcomes. Adverse childhood experiences in early childhood can induce HPA and epigenetic changes.
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Flooding: what is the impact on pregnancy and child health?
Mallett, LH, Etzel, RA
Disasters. 2018;(3):432-458
Abstract
Floods are the most common type of natural disaster in both developed and developing countries and have led to extensive morbidity and mortality throughout the world. Worldwide, over the past 30 years, flooding has claimed the lives of more than 200,000 people and affected more than 2.8 billion others. The impact of flooding on health varies among populations and depends primarily on vulnerability and the kind of event experienced. It severely disrupts livelihoods and has a significant impact on the health of pregnant women and children. In addition, it may exacerbate a range of negative psychological and physiological child and reproductive health outcomes. Awareness-raising, education, and the issuing of warnings appear to be key initiatives to mitigate or prevent flood morbidity and mortality, especially among people living in low- and middle-income countries. Agencies responding to emergencies also need to be more cognisant of the dangers, specifically those engaged in healthcare, nutrition, and water safety programmes.