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1.
Neurological development of children who are HIV-exposed and uninfected.
Toledo, G, Côté, HCF, Adler, C, Thorne, C, Goetghebuer, T
Developmental medicine and child neurology. 2021;(10):1161-1170
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Abstract
Widespread use of antiretroviral drugs for pregnant/breastfeeding females with human immunodeficiency virus (HIV) has led to declining vertical transmission. Despite being HIV-uninfected, the increasing number of children who are HIV-exposed and uninfected (CHEU) often present with developmental alterations. We review seminal and recent evidence on the neurological development of CHEU and associations with early life HIV/antiretroviral exposure. Our conceptual model highlights the numerous exposures and universal risk factors for CHEU developmental disorders. Early studies suggest a significant association between HIV exposure and neurological abnormalities, varying according to the burden of HIV-specific exposures and other risk factors. More recent observations from the modern era are inconsistent, although some studies suggest specific antiretrovirals may adversely affect neurological development of CHEU. As the CHEU population continues to grow, alongside simultaneous increases in types and combinations of antiretrovirals used in pregnancy, long-term monitoring of CHEU is necessary for understanding the effects of HIV/antiretroviral exposure on CHEU developmental outcomes. What this paper adds Evidence on the neurological development of children who are human immunodeficiency virus (HIV)-exposed and uninfected (CHEU) is synthesized. Comparisons are made to children who are HIV-unexposed, across treatment eras and settings, and by antiretroviral drug regimens and drug classes. CHEU exposures are complex and include HIV-specific and universal risk factors which may affect development during the early years of life.
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Environmental and Genetic Risk Factors of Congenital Anomalies: an Umbrella Review of Systematic Reviews and Meta-Analyses.
Lee, KS, Choi, YJ, Cho, J, Lee, H, Lee, H, Park, SJ, Park, JS, Hong, YC
Journal of Korean medical science. 2021;(28):e183
Abstract
BACKGROUND The prevalence of congenital anomalies in newborns in South Korea was 272.9 per 100,000 in 2005, and 314.7 per 100,000 in 2006. In other studies, the prevalence of congenital anomalies in South Korea was equivalent to 286.9 per 10,000 livebirths in 2006, while it was estimated 446.3 per 10,000 births during the period from 2008 to 2014. Several systematic reviews and meta-analyses analyzing the factors contributing to congenital anomalies have been reported, but comprehensive umbrella reviews are lacking. METHODS We searched PubMed, Google Scholar, Cochrane, and EMBASE databases up to July 1, 2019, for systematic reviews and meta-analyses that investigated the effects of environmental and genetic factors on any type of congenital anomalies. We categorized 8 subgroups of congenital anomalies classified according to the 10th revision of the International Statistical Classification of Diseases (ICD-10). Two researchers independently searched the literature, retrieved the data, and evaluated the quality of each study. RESULTS We reviewed 66 systematic reviews and meta-analyses that investigated the association between non-genetic or genetic risk factors and congenital anomalies. Overall, 269 associations and 128 associations were considered for environmental and genetic risk factors, respectively. Congenital anomalies based on congenital heart diseases, cleft lip and palate, and others were associated with environmental risk factors based on maternal exposure to environmental exposures (air pollution, toxic chemicals), parental smoking, maternal history (infectious diseases during pregnancy, pregestational and gestational diabetes mellitus, and gestational diabetes mellitus), maternal obesity, maternal drug intake, pregnancy through artificial reproductive technologies, and socioeconomic factors. The association of maternal alcohol or coffee consumption with congenital anomalies was not significant, and maternal folic acid supplementation had a preventive effect on congenital heart defects. Genes or genetic loci associated with congenital anomalies included MTHFR, MTRR and MTR, GATA4, NKX2-5, SRD5A2, CFTR, and 1p22 and 20q12 anomalies. CONCLUSION This study provides a wide perspective on the distribution of environmental and genetic risk factors of congenital anomalies, thus suggesting future studies and providing health policy implications.
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Prenatal Immunity and Influences on Necrotizing Enterocolitis and Associated Neonatal Disorders.
Sampah, MES, Hackam, DJ
Frontiers in immunology. 2021;:650709
Abstract
Prior to birth, the neonate has limited exposure to pathogens. The transition from the intra-uterine to the postnatal environment initiates a series of complex interactions between the newborn host and a variety of potential pathogens that persist over the first few weeks of life. This transition is particularly complex in the case of the premature and very low birth weight infant, who may be susceptible to many disorders as a result of an immature and underdeveloped immune system. Chief amongst these disorders is necrotizing enterocolitis (NEC), an acute inflammatory disorder that leads to necrosis of the intestine, and which can affect multiple systems and have the potential to result in long term effects if the infant is to survive. Here, we examine what is known about the interplay of the immune system with the maternal uterine environment, microbes, nutritional and other factors in the pathogenesis of neonatal pathologies such as NEC, while also taking into consideration the effects on the long-term health of affected children.
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Maternal Nutrition and Neurodevelopment: A Scoping Review.
Cortés-Albornoz, MC, García-Guáqueta, DP, Velez-van-Meerbeke, A, Talero-Gutiérrez, C
Nutrients. 2021;(10)
Abstract
In this scoping review, we examined the association between maternal nutrition during pregnancy and neurodevelopment in offspring. We searched the Pubmed and ScienceDirect databases for articles published from 2000 to 2020 on inadequate intake of vitamins (B12, folate, vitamin D, vitamin A, vitamin E, vitamin K), micronutrients (cooper, iron, creatine, choline, zinc, iodine), macronutrients (fatty acids, proteins), high fat diets, ketogenic diets, hypercaloric diets, and maternal undernutrition. Some older relevant articles were included. The search produced a total of 3590 articles, and 84 studies were included in the qualitative synthesis. Data were extracted and analyzed using charts and the frequency of terms used. We concluded that inadequate nutrient intake during pregnancy was associated with brain defects (diminished cerebral volume, spina bifida, alteration of hypothalamic and hippocampal pathways), an increased risk of abnormal behavior, neuropsychiatric disorders (ASD, ADHD, schizophrenia, anxiety, depression), altered cognition, visual impairment, and motor deficits. Future studies should establish and quantify the benefits of maternal nutrition during pregnancy on neurodevelopment and recommend adequate supplementation.
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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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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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Abstract
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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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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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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10.
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.