Mild exercise plus levothyroxine ameliorate deficits of spatial navigation, anxiety profile, and hippocampal BDNF in hypothyroid male offspring rats.

PURPOSE: Levothyroxine (LEV) monotherapy cannot completely improve cognitive and behavioral impairments induced by hypothyroidism, whereas a combination therapy of exercise and LEV may ameliorate these deficits. This study aimed to determine the effects of mild-intensity forced exercise and LEV treatment on the anxiety profile and cognitive functions in male offspring of hypothyroid dams. METHOD: Twenty-four female rats (mothers) were randomly divided into sham (healthy) and hypothyroidism groups and then placed with male rats to mate. The presence of vaginal plaque confirmed pregnancy (gestational day, GD 0). 6-propyl-2-thiouracil (PTU, 100 ppm) was added to the drinking water of the hypothyroidism group from GD 6 to the 21st postnatal day (PND). The sham group received tap water. On PND 21, serum T4 levels of mothers, and 10 pups were measured to confirm hypothyroidism. Sixty-four male pups were left undisturbed for 30 days and then were divided into eight groups that received saline or LEV (50 µg/kg, i.p.) with or without forced mild-intensity exercise. After 14 days of interventions, anxiety-like behaviors, spatial learning and memory, and hippocampal brain-derived neurotrophic factor (BDNF) levels were evaluated. FINDING: A pre and postnatal PTU-induced model of hypothyroidism increased anxiety-like behaviors, impaired spatial learning and memory, and decreased hippocampal BDNF levels in male offspring rats. LEV alone increased BDNF levels and improved spatial learning. Exercise alone increased BDNF levels, improved spatial learning and memory, and decreased anxiety-like behaviors. Exercise plus LEV more effectively improved anxiety-like behaviors and spatial learning than exercise or LEV alone. CONCLUSION: Practically, these pre-clinical findings highlight the importance of the combination of exercise and LEV regimen in treating patients with hyperthyroidism.

Reversing valproic acid-induced autism-like behaviors through a combination of low-frequency repeated transcranial magnetic stimulation and superparamagnetic iron oxide nanoparticles.

Transcranial magnetic stimulation (TMS) is a neurostimulation device used to modulate brain cortex activity. Our objective was to enhance the therapeutic effectiveness of low-frequency repeated TMS (LF-rTMS) in a rat model of autism spectrum disorder (ASD) induced by prenatal valproic acid (VPA) exposure through the injection of superparamagnetic iron oxide nanoparticles (SPIONs). For the induction of ASD, we administered prenatal VPA (600 mg/kg, I.P.) on the 12.5th day of pregnancy. At postnatal day 30, SPIONs were injected directly into the lateral ventricle of the brain. Subsequently, LF-rTMS treatment was applied for 14 consecutive days. Following the treatment period, behavioral analyses were conducted. At postnatal day 60, brain tissue was extracted, and both biochemical and histological analyses were performed. Our data revealed that prenatal VPA exposure led to behavioral alterations, including changes in social interactions, increased anxiety, and repetitive behavior, along with dysfunction in stress coping strategies. Additionally, we observed reduced levels of SYN, MAP2, and BDNF. These changes were accompanied by a decrease in dendritic spine density in the hippocampal CA1 area. However, LF-rTMS treatment combined with SPIONs successfully reversed these dysfunctions at the behavioral, biochemical, and histological levels, introducing a successful approach for the treatment of ASD.

[Characterization of children born to mothers with Graves' disease]. / Caracterización de recién nacidos hijos de madres portadoras de enfermedad de Graves.

INTRODUCTION: Neonatal hyperthyroidism is a disease that can cause mortality and sequelae. To date, there is no clinical series of cases that allows us to know the local reality of this condition. OBJECTIVE: to charac terize the children of mothers with Graves' disease (GD) from a clinical and biochemical point of view. SUBJECTS AND METHOD: A prospective follow-up of all newborns (NB) of mothers with history of GD was performed in two public hospitals in Santiago, during 5 years. Clinical and laboratory variables of mother-child pairs and thyroid-stimulating hormone receptor antibodies (TRAbs) le vels were analyzed looking for associations between these variables and the development of neonatal hyperthyroidism. RESULTS: Seventy-six mother-child pairs were included (0.2% of all deliveries). Five neonates (6.6%) presented biochemical hyperthyroidism, and 3 of them developed clinical disease and required treatment. All 5 NBs who developed hyperthyroidism had mothers with positive or indeterminate TRAbs. No child of TRAbs-negative mothers developed the disease. TRAbs could be determined in only 65% of the mothers and 72% of the NBs. There was a significant correlation bet ween maternal TRAbs titers (p < 0.03), neonatal TRAbs titers (p < 0.008), and neonatal TSH between days 2-6 (p < 0.006), with the subsequent development of hyperthyroidism. All cases of neonatal hyperthyroidism were transient. There was no mortality in our series. CONCLUSIONS: This is the first national case series of children of mothers with GD. Maternal and neonatal TRAbs and TSH between days 2-6 of life were predictors of neonatal hyperthyroidism.

Intervenciones psicológicas del trastorno del espectro alcohólico fetal a lo largo del ciclo vital / Psychological interventions on fetal alcohol spectrum disorder across the life span

INTRODUCCIÓN: El trastorno del espectro alcohólico fetal (TEAF) es la principal causa conocida y prevenible de discapacidad intelectual en el mundo occidental y afecta hasta al 1-5% de la población. Se considera un trastorno infradiagnosticado e infratratado, y las intervenciones psicológicas con evidencia empírica son escasas. OBJETIVO: Revisar los estudios publicados hasta el momento sobre tratamiento psicológico del TEAF a lo largo de la vida. Se realizó una búsqueda bibliográfica mediante las bases de datos de Medline, PsychINFO, PubMed y Cochrane Library usando los términos fetal alcohol syndrome disorder AND cognitive behavioral intervention OR psychological intervention OR psychological treatment OR therapy OR psychotherapy. Se incluyeron los trabajos publicados que evaluaran la eficacia de tratamientos psicológicos para estos pacientes. DESARROLLO: Cumplieron los criterios de inclusión 20 estudios publicados. Los tratamientos se clasificaron en función del tipo de intervención: la regulación emocional y conductual, el entrenamiento en habilidades sociales y las intervenciones familiares. CONCLUSIONES: Los resultados indican que los tratamientos psicológicos dirigidos a trabajar la regulación emocional y conductual, el entrenamiento en habilidades sociales y las intervenciones familiares son los que tienen mayor evidencia en el tratamiento para el TEAF. La mayoría se basa en principios cognitivo-conductuales y a niños de edad escolar, y son escasas todavía las investigaciones de tratamientos para adultos con TEAF. A pesar del progreso en las intervenciones psicológicas para el TEAF, la investigación aún refleja marcadas limitaciones

INTRODUCTION. Fetal alcohol spectrum disorder (FASD) is the leading known and preventable cause of intellectual disability in the western world, affecting up to 1-5% of the population. It is considered an underdiagnosed and undertreated disorder, with few psychological interventions with empirical evidence. AIM. To review all the studies published to date on the psychological treatment of FASD throughout life. A bibliographic search was carried out using the MEDLINE, PsychINFO, PubMed and Cochrane Library databases using the terms fetal alcohol syndrome disorder AND cognitive behavioral intervention OR psychological intervention OR psychological treatment OR therapy OR psychotherapy. The review included published works which evaluate the efficacy of psychological treatments for these patients. DEVELOPMENT: Twenty published studies met the inclusion criteria. The treatments were classified according to the type of intervention: emotional and behavioral regulation, social skills training and family interventions for patients with FASD. CONCLUSIONS: The results indicate that psychological treatments focused on emotional and behavioral regulation, social skills training and family interventions are the most evidenced treatments for these patients. These treatments are based on cognitive-behavioral principles and include school-age children. However, more research is needed on psychological interventions for adults with FASD. Despite the progress in psychological interventions for FASD, the research still reflects highlighted limitations

Connecting People with People: Diagnosing Persons with Fetal Alcohol Spectrum Disorder Using Telehealth.

Fetal alcohol spectrum disorder (FASD) is a diagnostic term used to describe an array of structural, neurocognitive, and behavioral effects that result from prenatal alcohol exposure. While ongoing efforts have been made to increase the capacity of communities to provide early FASD diagnosis, there continues to be on-going challenges, particularly for remote and rural communities. Telehealth is the use of technology to connect communities at a distance and has been effectively used in medicine for several decades. This literature review describes the use of telehealth in FASD and other developmental disabilities and makes recommendations for how telehealth can be used to facilitate the assessment and diagnosis of FASD in rural and remote communities.

Sex-dependent metabolic effects of pregestational exercise on prenatally stressed mice.

Stressful events during the prenatal period have been related to hyperactive hypothalamic-pituitary-adrenal (HPA) axis responses as well as metabolic changes in adult life. Moreover, regular exercise may contribute to the improvement of the symptoms associated with stress and stress-related chronic diseases. Therefore, this study aims to investigate the effects of exercise, before the gestation period, on the metabolic changes induced by prenatal stress in adult mice. Female Balb/c mice were divided into three groups: control (CON), prenatal restraint stress (PNS) and exercise before the gestational period plus PNS (EX + PNS). When adults, the plasmatic biochemical analysis, oxidative stress, gene expression of metabolic-related receptors and sex differences were assessed in the offspring. Prenatal stress decreased neonatal and adult body weight when compared to the pregestational exercise group. Moreover, prenatal stress was associated with reduced body weight in adult males. PNS and EX + PNS females showed decreased hepatic catalase. Pregestational exercise prevented the stress-induced cholesterol increase in females but did not prevent the liver mRNA expression reduction on the peroxisome proliferator-activated receptors (PPARs) α and γ in PNS females. Conversely, PNS and EX + PNS males showed an increased PPARα mRNA expression. In conclusion, pregestational exercise prevented some effects of prenatal stress on metabolic markers in a sex-specific manner.

Environmental enrichment alters neurobehavioral development following maternal immune activation in mice offspring with epilepsy.

Epilepsy is a chronic brain disease affecting millions of people worldwide. Anxiety-related disorders and cognitive deficits are common in patients with epilepsy. Previous studies have shown that maternal infection/immune activation renders children more vulnerable to neurological disorders later in life. Environmental enrichment has been suggested to improve seizures, anxiety, and cognitive impairment in animal models. The present study aimed to explore the effects of environmental enrichment on seizure scores, anxiety-like behavior, and cognitive deficits following maternal immune activation in offspring with epilepsy. Pregnant mice were treated with lipopolysaccharides-(LPS) or vehicle, and offspring were housed in normal or enriched environments during early adolescence to adulthood. To induce epilepsy, adult male and female offspring were treated with Pentylenetetrazol-(PTZ), and then anxiety-like behavior and cognitive functions were assessed. Tumor-necrosis-factor (TNF)-α and interleukin (IL) 10 were measured in the hippocampus of offspring. Maternal immune activation sex-dependently increased seizure scores in PTZ-treated offspring. Significant increases in anxiety-like behavior, cognitive impairment, and hippocampal TNF-α and IL-10 were also found following maternal immune activation in PTZ-treated offspring. However, there was no sex difference in these behavioral abnormalities in offspring. Environmental enrichment reversed the effects of maternal immune activation on behavioral and inflammatory parameters in PTZ-treated offspring. Overall, the present findings highlight the adverse effects of prenatal maternal immune activation on seizure susceptibility and psychiatric comorbidities in offspring. This study suggests that environmental enrichment may be used as a potential treatment approach for behavioral abnormalities following maternal immune activation in PTZ-treated offspring.

Women with Mild Fasting Hyperglycemia in Early Pregnancy Have More Neonatal Intensive Care Admissions.

AIMS: To determine impact of mild fasting hyperglycemia in early pregnancy (fasting plasma glucose [FPG] 5.1-5.5 mmol/L) on pregnancy outcomes. METHODS: We measured FPG at 11.9 ± 1.8 weeks in 2006 women from a prospective cohort study. Women with FPG ≥5.6 mmol/L (19) received treatment and were excluded from further analyses. A total of 1838 women with FPG <5.6 mmol/L received a 75 g oral glucose tolerance test (OGTT) between 24 and 28 weeks of pregnancy. RESULTS: Of all participants, 78 (4.2%) had FPG 5.1 to 5.5 mmol/L in early pregnancy, of which 49 had a normal OGTT later in pregnancy (high fasting normal glucose tolerance [NGT] group). Compared with the NGT group with FPG <5.1 mmol/L in early pregnancy (low fasting NGT group, n = 1560), the high fasting NGT group had a higher body mass index (BMI), higher insulin resistance with more impaired insulin secretion and higher FPG and 30 minute glucose levels on the OGTT. The admission rate to neonatal intensive care unit (NICU) was significantly higher in the high fasting NGT group than in the low fasting NGT group (20.4% [10] vs 9.3% [143], P = .009), with no difference in duration (7.0 ± 8.6 vs 8.4 ± 14.3 days, P = .849) or indication for NICU admission between both groups. The admission rate to NICU remained significantly higher (odds ratio 2.47; 95% confidence interval 1.18-5.19, P = .017) after adjustment for age, BMI, and glucose levels at the OGTT. CONCLUSIONS: When provision of an OGTT is limited such as in the Covid-19 pandemic, using FPG in early pregnancy could be an easy alternative to determine who is at increased risk for adverse pregnancy outcomes.

A Systematic Review of Interventions to Improve Mental Health and Substance Use Outcomes for Individuals with Prenatal Alcohol Exposure and Fetal Alcohol Spectrum Disorder.

Individuals with fetal alcohol spectrum disorder (FASD) experience remarkably high rates of mental health and substance use challenges, beginning early in life and extending throughout adulthood. Proactive intervention can help to mitigate some of these negative experiences. Although the literature on FASD intervention is growing, there is currently a lack of consolidated evidence on interventions that may improve mental health and substance use outcomes in this population. Informed by a life course perspective, we undertook a systematic review of the literature to identify interventions that improve mental wellness through all developmental stages for people with prenatal alcohol exposure (PAE) and FASD. A total of 33 articles were identified, most of which were focused on building skills or strategies that underlie the well-being of children with PAE and FASD and their families. Other interventions were geared toward supporting child and family wellness and responding to risk or reducing harm. There was a notable lack of interventions that directly targeted mental health and substance use challenges, and a major gap was also noted in terms of interventions for adolescents and adults. Combined, these studies provide preliminary and emerging evidence for a range of intervention approaches that may support positive outcomes for individuals with FASD across the life course.

A Review of the Pathophysiology and Management of Diabetes in Pregnancy.

Diabetes is a common metabolic complication of pregnancy and affected women fall into two subgroups: women with pre-existing diabetes and those with gestational diabetes mellitus (GDM). When pregnancy is affected by diabetes, both mother and infant are at increased risk for multiple adverse outcomes. A multidisciplinary approach to care before, during, and after pregnancy is effective in reducing these risks. The PubMed database was searched for English language studies and guidelines relating to diabetes in pregnancy. The following search terms were used alone and in combination: diabetes, pregnancy, gestational diabetes, GDM, prepregnancy, and preconception. A date restriction was not applied. Results were reviewed by the authors and selected for inclusion based on relevance to the topic. Additional articles were identified by manually searching reference lists of included articles. Using data from this search we herein summarize the evidence relating to pathophysiology and management of diabetes in pregnancy. We discuss areas of controversy including the method and timing of diagnosis of GDM, and choice of pharmacologic agents to treat hyperglycemia during pregnancy. Therefore, this review is intended to serve as a practical guide for clinicians who are caring for women with diabetes and their infants.

Neonatal Hypocalcemia in the Infant of a Diabetic Mother.

Neonatal hypocalcemia (NHC) is one of the most common disorders of calcium metabolism in infants admitted to the NICU. Presentation can range from asymptomatic to generalized seizures or tetany. In this case study, an infant with NHC is presented along with an overview of the pathophysiology, prevalence, diagnosis, and management of NHC for neonatal clinicians.

Neonates Born to Mothers with Graves' Disease: 15 Year Experience of a Pediatric Endocrinology Department.

INTRODUCTION: Graves disease is characterized by the existence of autoantibodies directed to the thyrotropin receptor, which can have a stimulatory/inhibitory action, in women with the condition, their fetus or neonate. Our aim was to review the case series of these neonates in order to establish neonatal thyroid function predictors. MATERIAL AND METHODS: Retrospective cohort study of the database of the Department of Pediatric Endocrinology, including patients born to mothers with Graves' disease, between 2002 and 2017. Clinical and biochemical data were collected from mothers and offspring. RESULTS: Fifty newborns, from 46 women with a median of 3.5 years after diagnosis, were included. During all trimesters of pregnancy, more than half of women had positive autoantibodies directed to the thyrotropin receptor. Not every woman had a complete thyroid function evaluation every trimester. In 32 newborns, cord blood screening was done. During the neonatal period, there were three cases of hypothyroidism and two of hyperthyroidism. The mothers of these five newborns had higher levels of free thyroid hormones during the second trimester (p = 0.03). The level of antibodies directed to the thyrotropin receptor was significantly higher in the cord blood (p = 0.03) and in the first neonatal test (p = 0.03) of these dysthyroid newborns. DISCUSSION: Our results reinforce the need for every pregnant woman with Graves' disease to be subject to thyroid function and autoantibodies evaluation during every trimester, as well as the importance of evaluating these antibodies in cord blood. CONCLUSION: High levels of free thyroid hormones during the second trimester of pregnancy and antibodies directed to the thyrotropin receptor value in cord blood are predictors of dysthyroidism in neonates born from women with Grave's disease.

Introdução: A doença de Graves é caraterizada pela existência de autoanticorpos dirigidos ao recetor da tirotrofina, que podem ter uma ação estimuladora/inibitória, ao nível da mulher com a doença, bem como do seu feto ou recém-nascido. Quisemos rever a nossa série de casos de filhos de mães com doença de Graves de forma a estabelecer preditores da função tiroideia neonatal. Material e Métodos: Estudo retrospetivo de uma coorte da base de dados da Unidade de Endocrinologia Pediátrica, composta por filhos de mães com doença de Graves, seguidos entre 2002 e 2017. Foram recolhidos dados clínicos e laboratoriais dos processos clínicos das progenitoras e seus filhos. Resultados: Foram incluídos 50 recém-nascidos, de 46 mulheres com uma mediana de 3,5 anos de diagnóstico. Em todos os trimestres de gravidez, mais de metade das mulheres tinham autoanticorpos dirigidos ao recetor da tirotrofina positivos. Nem todas fizeram uma avaliação trimestral completa da função tiroideia. O rastreio no sangue do cordão foi realizado em trinta e dois recémnascidos. Durante o período neonatal houve três casos de hipotiroidismo e dois de hipertiroidismo. As mães destes recém-nascidos tinham valores mais elevados das frações livres das hormonas tiroideias no segundo trimestre (p = 0,03). O valor dos anticorpos dirigidos ao recetor da tirotrofina no sangue do cordão e na primeira avaliação neonatal foi significativamente mais elevado (p = 0,03 em ambos) nos recém-nascidos distiroideus. Discussão: Os nossos resultados sublinham a importância de todas as mulheres grávidas, com doença de Graves, fazerem a avaliação da função tiroideia e autoanticorpos dirigidos ao recetor da tirotrofina em cada trimestre, bem como da avaliação destes anticorpos no sangue do cordão. Conclusão: Valores elevados das frações livres das hormonas tiroideias no segundo trimestre de gravidez e de anticorpos dirigidos ao recetor da tirotrofina no sangue do cordão são preditores de distiroidismo nos recém-nascidos filhos de mães com doença de Graves.

Management of neonates born to mothers with thyroid dysfunction, and points for attention during pregnancy.

Thyroid hormone (TH) is indispensable for normal embryonic and fetal development. Throughout gestation TH is provided by the mother via the placenta, later in pregnancy the fetal thyroid gland makes an increasing contribution. Maternal thyroid dysfunction, resulting in lower or higher than normal (maternal) TH levels and transfer to the embryo/fetus, can disturb normal early development. (Maternal) thyroid dysfunction is mostly caused by autoimmune hypo- or hyperthyroidism, i.e. Hashimoto and Graves disease. Autoimmune hyperthyroidism is caused by stimulating TSH receptor antibodies (TSHR Ab), patients with autoimmune hypothyroidism may have blocking TSHR Ab. Maternal TSHR Ab cross the placenta from mid gestation and may cause fetal and transient neonatal hyper- or hypothyroidism. Anti-thyroid drugs taken for autoimmune hyperthyroidism cross the placenta throughout gestation, and may cause fetal and transient neonatal hypothyroidism. This review focusses on the consequences of maternal hypo- and hyperthyroidism for fetus and neonate, and provides a practical approach to clinical management of neonates born to mothers with thyroid dysfunction.

Red cell alloimmunization: A 2020 update.

Management of maternal red cell alloimmunization has been revolutionized over the last 60 years. Advances in the prevention, screening, diagnosis, and treatment of alloimmune-induced fetal anemia make this condition an exemplar for contemporary practice in fetal therapy. Since survival is now an expectation, attention has turned to optimization of long-term outcomes following an alloimmunized pregnancy. In this review, the current management of red cell alloimmunization is described. Current research and future directions are discussed with particular emphasis on later life outcomes after alloimmune fetal anemia.

Comparison of Protective Effects of Electroacupuncture at ST 36 and LU 5 on Pulmonary and Hypothalamic Pituitary Adrenal Axis Changes in Perinatal Nicotine-Exposed Rats.

BACKGROUND: Maternal smoking and/or exposure to environmental tobacco smoke continue to be significant factors in fetal and childhood morbidity and are a serious public health issue worldwide. Nicotine passes through the placenta easily with minimal biotransformation, entering fetal circulation, where it results in many harmful effects on the developing offspring, especially on the developing respiratory system. OBJECTIVES: Recently, in a rat model, electroacupuncture (EA) at maternal acupoints ST 36 has been shown to block perinatal nicotine-induced pulmonary damage; however, the underlying mechanism and the specificity of ST 36 acupoints for this effect are unknown. Here, we tested the hypothesis that compared with EA at ST 36, EA at LU 5 acupoints, which are on lung-specific meridian, will be equally or more effective in preventing perinatal nicotine-induced pulmonary changes. METHODS: Twenty-four pregnant rat dams were randomly divided into 4 groups: saline ("S"), nicotine ("N"), nicotine + ST 36 (N + ST 36), and nicotine + LU 5 (N + LU 5) groups. Nicotine (1 mg/kg, subcutaneously) and EA (at ST 36 or LU 5 acupoints, bilaterally) were administered from embryonic day 6 to postnatal day 21 once daily. The "S" group was injected saline. As needed, using ELISA, western analysis, q-RT-PCR, lung histopathology, maternal and offspring hypothalamic pituitary adrenal axes, offspring key lung developmental markers, and lung morphometry were determined. RESULTS: With nicotine exposure, alveolar count decreased, but mean linear intercept and septal thickness increased. It also led to a decrease in pulmonary function and PPARγ and an increase of ß-catenin and glucocorticoid receptor expression in lung tissue and corticosterone in the serum of offspring rats. Electroacupuncture at ST 36 normalized all of these changes, whereas EA at LU 5 had no obvious effect. CONCLUSION: Electroacupuncture applied to ST 36 acupoints provided effective protection against perinatal nicotine-induced lung changes, whereas EA applied at LU 5 acupoints was ineffective, suggesting mechanistic specificity and HPA axis' involvement in mediating EA at ST 36 acupoints' effects in mitigating perinatal nicotine-induced pulmonary phenotype. This opens the possibility that other acupoints, besides ST 36, can have similar or even more robust beneficial effects on the developing lung against the harmful effect of perinatal nicotine exposure. The approach proposed by us is simple, cheap, quick, easy to administer, and is devoid of any significant side effects.

Preeclampsia Emerging as a Novel Risk Factor for Cardiovascular Disease in the Offspring.

INTRODUCTION: Preeclampsia is a pregnancy specific disorder which affects 2%-8% of all gestations and is associated with high maternal, fetal and neonatal morbidity and mortality worldwide. There is no "cure" for the disease except for early delivery of the fetus and placenta, however leaving preeclampsia a long term health risk both for mothers and infants. AIM: The aim of the study is to review currently available information linking preclampsia to longterm cardiovascular complications in infants and children. RESULTS: Currently, there is evidence of predisposition to cardiovascular disease, and a higher incidence of cardiovascular risk factors among children born to preeclamptic mothers. Both in experimental models and human epidemiological studies it is now clear that the infants of pregnancies complicated by preeclampsia have an increased risk of developing high blood pressure and double the risk of stroke in later life. Preeclampsia is consistently associated with higher blood pressure and body mass index as early as 4-10 years of age. Also there is some evidence of higher cardiovascular risk in adults exposed to maternal hypertensive disorders of pregnancy. It seems that preeclampsia has an impact on the cardiovascular system independent of preterm birth and is associated with endothelial dysfunction, increased carotid intima media thickness and reductions in cardiac function that cannot be accounted for by prematurity alone. CONCLUSION: Taking into consideration the currently available evidence, it can now be suggested that preeclampsia is linked to adverse effects on the cardiometabolic health of the infant. Understanding the relationship between preeclampsia and cardiovascular disease will allow for implementation of early interventions to prevent or delay the onset of adverse events in this high risk population.

Prenatal Ethanol Exposure and Postnatal Environmental Intervention Alter Dopaminergic Neuron and Microglia Morphology in the Ventral Tegmental Area During Adulthood.

BACKGROUND: Prenatal ethanol exposure (PE) impairs midbrain dopaminergic (DA) neuron function, which might contribute to various cognitive and behavioral deficits, including attention deficits and increased addiction risk, often observed in individuals with fetal alcohol spectrum disorders. Currently, the underlying mechanisms for PE-induced deficits are unclear. PE could lead to neuroinflammation by activating microglia, which play an important role in synaptic function. In the present study, we investigated PE effects on microglial activation and DA neuron density and morphology in the ventral tegmental area (VTA). Since postnatal environmental enrichment can reduce neuroinflammation and ameliorate several PE-induced behavioral deficits, we examined if a postnatal environmental intervention strategy using neonatal handling and postweaning complex housing could reverse PE effects on VTA DA neurons and microglia. METHODS: Pregnant rats received 0 or 6 g/kg/d ethanol by 2 intragastric intubations on gestation days 8 to 20. After birth, rats were reared in the standard laboratory or enriched condition. Male adult rats (8 to 12 weeks old) were used for immunocytochemistry. RESULTS: The results showed that PE decreased VTA DA neuron body size in standardly housed rats. Moreover, there was a significant decrease in numbers of VTA microglial branches and junctions in PE rats, suggesting morphological activation of microglia and possible neuroinflammation. The PE effects on microglia were normalized by postnatal environmental intervention, which also decreased the numbers of microglial branches and junctions in control animals, possibly via reduced stress. CONCLUSIONS: Our findings show an association between PE-induced morphological activation of microglia and impaired DA neuron morphology in the VTA. Importantly, postnatal environmental intervention rescues possible PE-induced microglial activation. These data support that environmental intervention can be effective in ameliorating cognitive and behavioral deficits associated with VTA DA neuron dysfunctions, such as attention deficits and increased addiction risk.

Exposure to air pollution during the first 1000 days of life and subsequent health service and medication usage in children.

BACKGROUND: Evidence of health effects following early life exposure to short-to-medium duration of high pollution levels is extremely limited. OBJECTIVES: We aimed to evaluate the associations between: 1. intrauterine exposure to fine particulate matter (PM2.5) from coal mine fire emissions and the frequencies of general practitioner attendances and dispensations of prescribed asthma inhalers, steroid skin creams, and antibiotics during the first year of life; 2. infant exposure and those outcomes during the year following the fire. METHODS: All participants were recruited from the Latrobe Valley of Victoria, Australia. Participants' 24-h average and hourly peak mine fire-specific PM2.5 exposures from 09/02/2014 to 31/03/2014 were estimated using chemical transport modelling. Outcome data were obtained from the Australian Medicare Benefits Schedule and Pharmaceutical Benefits Scheme from each child's birth to 31/12/2016. We used negative binomial and logistic regression models to independently assess risks of the outcomes associated with every 10 and 100 µg m-3 increase in average or peak PM2.5 exposure, respectively, while adjusting for potential confounders. RESULTS: We included 286 of 311 children whose parents consented to be linked, comprising 77 with no exposure, 88 with intrauterine exposure and 121 with exposure in infancy. 10- and 100- µg m-3 increases in average and peak PM2.5 exposure during infancy were associated with greater incidence of antibiotics being dispensed during the year following the fire: the adjusted incidence rate ratios were 1.24 (95% CI 1.02, 1.50, p = 0.036) and 1.14 (1.00, 1.31, p = 0.048) respectively. No other significant associations were observed. CONCLUSION: Exposure to coal mine fire emissions during infancy was associated with increased dispensing of antibiotics. This could reflect increased childhood infections or increased prescriptions of antibiotics in the year following the fire.