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1.
Arch Endocrinol Metab ; 64(1): 89-95, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32187263

RESUMO

Clinical and subclinical hypothyroidism are the most common hormonal dysfunctions during pregnancy. Insufficient maternal thyroid hormones (THs) in the early stages of pregnancy can lead to severe impairments in the development of the central nervous system because THs are critical to central nervous system development. In the fetus and after birth, THs participate in neurogenic processes, cell differentiation, neuronal activation, axonal growth, dendritic arborization, synaptogenesis and myelination. Although treatment is simple and effective, approximately 30% of pregnant women in Brazil with access to prenatal care have their first consultation after the first trimester of pregnancy, and any delay in diagnosis and resulting treatment delay may lead to cognitive impairment in children. This review summarizes the effects of clinical and subclinical hypothyroidism on fetal neurodevelopment, behavior and cognition in humans and rodents. Arch Endocrinol Metab. 2020;64(1):89-95.


Assuntos
Encéfalo/embriologia , Disfunção Cognitiva/etiologia , Hipotireoidismo/complicações , Troca Materno-Fetal/fisiologia , Complicações na Gravidez/fisiopatologia , Animais , Encéfalo/fisiopatologia , Feminino , Humanos , Camundongos , Gravidez , Complicações na Gravidez/sangue , Resultado da Gravidez , Trimestres da Gravidez , Efeitos Tardios da Exposição Pré-Natal
2.
Life Sci ; 250: 117543, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32169518

RESUMO

AIMS: HMGB1 has been reported to play a crucial role in the physiological and pathophysiological responses during pregnancy. However, it is still unknown whether excessively expressed HMGB1 at the maternal-fetal interface related to Unexplained Recurrent Spontaneous Abortion (URSA). This study was designed to investigate the local capability of HMGB1 in the pathology of URSA, determined the distributions and characteristics of HMGB1, its receptors (RAGE/TLR2/TLR4) and important signaling molecule NF-κB p65 expression at the maternal-fetal interface,as well as compared the differences of HMGB1 expression between the URSA group, control group and aspirin treatment group. MATERIAL AND METHODS: H&E staining, Western blot analysis, immunofluorescence assay and immunohistochemical staining were applied to determine the effect of HMGB1 and its receptors at the maternal-fetal interface. ELISA was utilized to detect the concentration of HMGB1 in plasma. KEY FINDINGS: Our study demonstrated that the activation of the HMGB1-RAGE/TLR2/TLR4-NF-κB pathway at the maternal-fetal interface may have occurred in the URSA group. HMGB1 concentration in plasma was higher in the URSA group than the control group. Furthermore, the levels of HMGB1 of subjects with URSA could be reduced by administrating low doses of aspirin (ASPL). SIGNIFICANCE: This is the first report indicating the roles of HMGB1 at the maternal-fetal interface of URSA patients and broadening the horizons for clinical treatment of URSA. HMGB1-RAGE/TLR2/TLR4-NF-κB signaling pathway may be activated at the maternal-fetal interface in URSA and account for its pathogenesis. HMGB1 have the potential to be promising biomarkers in prevention and therapy of URSA.


Assuntos
Aborto Habitual/metabolismo , Aborto Espontâneo/metabolismo , Proteína HMGB1/metabolismo , Transdução de Sinais , Antígenos de Neoplasias/metabolismo , Aspirina/administração & dosagem , Feminino , Feto , Regulação da Expressão Gênica , Humanos , Antígenos Comuns de Leucócito/metabolismo , Troca Materno-Fetal , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Gravidez , Receptor 2 Toll-Like/metabolismo , Receptor 4 Toll-Like/metabolismo , Fator de Transcrição RelA/metabolismo , Regulação para Cima
4.
Zhonghua Yu Fang Yi Xue Za Zhi ; 54(3): 289-293, 2020 Mar 06.
Artigo em Chinês | MEDLINE | ID: mdl-32187934

RESUMO

Objective: To understand the levels of Pb, Cd, As, Hg, Mn, and Se in maternal and umbilical cord blood, and to explore the transplacental transfer efficiency (TTE). Methods: From September 2010 to December 2013, a total of 773 pregnant women and their newborns (Laizhou Bay Birth Cohort) were recruited from a second grade hospital in the south bank of Laizhou Bay, Bohai, Shandong Province. According to different detection methods, the six measured elements are classified into three groups including the Hg measurement group (595 mother-newborn pairs), the Pb measurement group (534 mother-newborn pairs), and the Cd, As, Mn and Se measurement group (244 mother-newborn pairs). The demographic characteristics of pregnant women and their newborns were obtained by the questionnaire. The concentrations of elements in maternal and umbilical cord blood were detected and the TTE of each element (elemental concentration in cord blood/elemental concentration in maternal blood) was calculated. The correlation of elements between maternal and cord blood was analyzed using Spearman's rank correlation coefficient. Results: The mean±SD of maternal age, gestational week and newborn birth weight of 773 mother-infant pairs were (28.34±4.50) years, (39.47±1.39) weeks and (3 419.47±497.39) g respectively. The median concentrations of Pb, Cd, As, Hg, Mn and As in maternal and cord blood were 31.12 and 30.02, 1.19 and 0.47, 8.05 and 6.03, 0.69 and 1.26, 100.70 and 105.55, 127.25 and 115.00 µg/L, respectively. The TTE of Pb, Cd, As, Hg, Mn, and Se was 0.98, 0.41, 0.73, 1.73, 0.96 and 0.91, respectively. Pb, Cd, Hg, Mn, and Se showed a significant positive correlation between maternal blood and cord blood, with Spearman correlation coefficients of 0.397, 0.298, 0.698, 0.555, and 0.285 (all P values<0.001). Conclusion: Each element was commonly detected in maternal blood and cord blood. The TTE of Hg was the highest.


Assuntos
Cádmio/sangue , Sangue Fetal/química , Sangue Fetal/metabolismo , Chumbo/sangue , Manganês/sangue , Troca Materno-Fetal , Mercúrio/sangue , Selênio/sangue , Cordão Umbilical/química , Biomarcadores/análise , Biomarcadores/sangue , Feminino , Humanos , Recém-Nascido , Gravidez , Oligoelementos/análise , Oligoelementos/sangue , Cordão Umbilical/irrigação sanguínea
5.
Pediatrics ; 145(3)2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32060140

RESUMO

BACKGROUND: Hepatitis C virus (HCV) prevalence doubled among pregnant women from 2009 to 2014, reaching 3.4 per 1000 births nationwide. Infants exposed to HCV may acquire HCV by vertical transmission. National guidelines recommend that infants exposed to HCV be tested; however, it is unclear if these recommendations are being followed. Our objectives were to determine if infants exposed to HCV were tested and to determine hospital- and patient-level factors associated with differences in testing. METHODS: In this retrospective cohort study of infants exposed to HCV who were enrolled in the Tennessee Medicaid program, we used vital statistics-linked administrative data for infants born between January 1, 2005, and December 31, 2014. Infants were followed until 2 years old. Multilevel logistic regression was used to assess the association of HCV testing and hospital- and patient-level characteristics. RESULTS: Only 23% of 4072 infants exposed to HCV were tested. Infants whose mothers were white versus African American (96.6% vs 3.1%; P <.001), used tobacco (78% vs 70%; P <.001), and had HIV (1.3% vs 0.4%; P = .002) were more likely to be tested. Infants exposed to HCV who had a higher median of well-child visits (7 vs 6; P <.001) were more likely to be tested. After accounting for maternal and infant characteristics and health care use patterns, African American infants were less likely to undergo general testing (adjusted odds ratio 0.32; 95% confidence interval, 0.13-0.78). CONCLUSIONS: Testing occurred in <1 in 4 infants exposed to HCV and less frequently among African American infants. Public health systems need to be bolstered to ensure that infants exposed to HCV are tested for seroconversion.


Assuntos
Hepatite C/diagnóstico , Hepatite C/transmissão , Transmissão Vertical de Doença Infecciosa , Triagem Neonatal , Complicações Infecciosas na Gravidez/epidemiologia , Adulto , Afro-Americanos/estatística & dados numéricos , Pré-Escolar , Estudos de Coortes , Grupo com Ancestrais do Continente Europeu/estatística & dados numéricos , Feminino , Infecções por HIV/epidemiologia , Humanos , Lactente , Recém-Nascido , Masculino , Troca Materno-Fetal , Medicaid , Visita a Consultório Médico/estatística & dados numéricos , Gravidez , Estudos Retrospectivos , Fumar/epidemiologia , Tennessee/epidemiologia , Estados Unidos , Adulto Jovem
6.
Sheng Li Xue Bao ; 72(1): 1-10, 2020 Feb 25.
Artigo em Chinês | MEDLINE | ID: mdl-32099979

RESUMO

The maintenance of human pregnancy and the initiation of parturition are closely related with the dynamic balance of the maternal-fetal immune microenvironment. Implantation of the blastocyst into the maternal decidua is the first step in pregnancy establishment, which is favored by the abundant blood flow and the immunotolerant microenvironment maintained by the balance of immune cells. The parturition resembles an inflammatory response that includes secretion of cytokines by resident and infiltrating immune cells into reproductive tissues and the maternal-fetal interface, which promotes the delivery of fetus from maternal organism. Therefore, the immune microenvironment in maternal-fetal interface regulates the critical steps of pregnancy and parturition. When the maternal-fetal immune microenvironment is imbalanced or impaired, miscarriage or preterm labor would happen. This article reviews the roles and mechanisms of several important immune cells in the maternal-fetal interface during the parturition and preterm labor.


Assuntos
Trabalho de Parto , Troca Materno-Fetal/imunologia , Trabalho de Parto Prematuro , Parto/imunologia , Citocinas/imunologia , Decídua , Feminino , Feto , Humanos , Recém-Nascido , Gravidez
7.
Sheng Li Xue Bao ; 72(1): 11-19, 2020 Feb 25.
Artigo em Chinês | MEDLINE | ID: mdl-32099980

RESUMO

Immune tolerance at maternal-fetal interface is the basis for establishment and maintenance of successful pregnancy. T cells are pivotal compositions of uterine decidual immune cells, which are required to mediate anti-infection immunity and protect embryos from external antigens attack. T cells also participate in the complex immune regulation process of maternal acceptance of semi-allogeneic embryos, and play an important role in regulating embryo implantation and maintaining pregnancy. Its dysfunction may lead to early pregnancy failures or mid-late pregnancy complications. This review summarizes the compositions, phenotypic characteristics and functions of decidual T cells at the maternal-fetal interface in recent years, and further describes the regulation of decidual CD4+ and CD8+ T cells in maternal-fetal immune tolerance as well as the molecular mechanisms of abnormal regulation leading to early pregnancy failures. Through the in-depth understanding the mechanism of maternal-fetal immune regulation, it supplies a novel concept on maternal-fetal immune tolerance and new clues for the immunotherapy of pregnancy-related diseases.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Decídua/imunologia , Tolerância Imunológica , Troca Materno-Fetal/imunologia , Feminino , Feto , Humanos , Gravidez
8.
Sheng Li Xue Bao ; 72(1): 115-124, 2020 Feb 25.
Artigo em Chinês | MEDLINE | ID: mdl-32099989

RESUMO

Placenta serves as a temporary fetal organ, which mediates maternal-fetal crosstalk and intrauterine fetal growth. Placental defensive barrier is a fundamental physiological function, which balances maternal immune tolerance to the fetus and resistance to pathogens. This review summarizes the latest research progress on the mechanisms of placental barrier formation from the view of placental development. Recent discoveries have shed light on the cellular and molecular properties of placental defensive mechanisms in syncytiotrophoblast, including autophagy, exosome mediated anti-pathogenic pathways, cell-cell junctions and cytoskeleton networks. We also present an overview of placental barrier dysfunction and its implications in intrauterine TORCH infections.


Assuntos
Troca Materno-Fetal , Placenta/fisiologia , Trofoblastos/fisiologia , Autofagia , Citoesqueleto , Exossomos , Feminino , Desenvolvimento Fetal , Feto , Humanos , Gravidez
9.
Environ Sci Technol ; 54(6): 3476-3486, 2020 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-32092248

RESUMO

In this study, a set of 15 bisphenols (BPs) and one emerging derivative (4-hydroxyphenyl 4-isoprooxyphenylsulfone, BPSIP) were analyzed in 60 pairs of maternal plasma, cord plasma, and placenta samples from pregnant women in South China. A total of 4 of the 15 target BPs, i.e., BPA, bisphenol S (BPS), bisphenol AF (BPAF), and bisphenol E (BPE), were frequently detected in the three human biological matrixes. The derivative BPSIP was identified in all maternal plasma samples at unexpectedly high levels, second only to BPA. The concentrations of bisphenols in maternal plasma were slightly higher than in cord plasma for BPA, BPS, and BPE but much higher for BPSIP and much lower for BPAF, indicating that the five frequently detected bisphenols have different placental transfer behaviors. The placental transfer efficiencies (PTEs) of BPA, BPS, and BPE were similar, which were significantly higher than the PTE of BPSIP. The PTE of BPAF was much higher than other BPs, indicating its strong maternal transfer and high fetal accumulation. The PTEs of bisphenols were structure-dependent, and passive diffusion was suggested as the potential mechanism of placental transfer. Significant concentration correlations of the five major bisphenols between maternal plasma and cord plasma were observed (p < 0.05). Meanwhile, significant associations of BPAF concentrations in maternal/cord plasma with some maternal characteristics and adverse birth outcomes were also identified (p < 0.05).


Assuntos
Compostos Benzidrílicos , Poluentes Ambientais , Feto , Troca Materno-Fetal , China , Feminino , Humanos , Placenta , Gravidez
10.
Mol Immunol ; 120: 32-42, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32045772

RESUMO

The pleiotropic cytokine leukemia inhibitory factor (LIF) is a key gestational factor known to establish dynamic cellular and molecular cross talk at the feto-maternal interface. Previously, we described the regulatory role of the LIF-trophoblast-IL10 axis in the process of macrophage deactivation in response to pro-inflammatory cytokines. However, the direct regulatory effects of LIF in macrophage and trophoblast cell function remains elusive. In this study, we aimed to examine whether and how LIF regulates the behavior of macrophages and trophoblast cells in response to pro-inflammatory stress factors. We found that LIF modulated the activating effects of interferon-gamma (IFNγ) and granulocyte-macrophage colony-stimulating factor (GM-CSF) in macrophages and trophoblast cells by reducing the phosphorylation levels of signal transducer and activator of transcription-1 (Stat1) and -5 (Stat5). Cell activation with IFNγ inhibited cell invasion and migration but this immobilizing effect was abrogated when macrophages and trophoblast cells were deactivated with LIF; macrophage cell motility restitution could in part be explained by the positive effects of LIF in Stat3 activation and matrix metalloproteinase 9 (MMP-9) expression. Pharmacological inhibition of Stat1 and Stat3 indicated that IFNγ-induced Stat1 activation mediated macrophage motility inhibition, and that cell motility in IFNγ-activated macrophages is restored via LIF-induced Stat3 activation and Stat1 inhibition. Moreover, IFNγ-induced TNFα gene expression was also abrogated by LIF through Stat1 inhibition and Stat3 activation. Finally, we have found that cell invasion of trophoblast cells is inhibited when they were cocultured with GM-CSF-differentiated, IFNγ-stimulated macrophages. This effect, however, was inhibited when macrophages were exposed to LIF. Overall, this in vitro study reveals for the first time the anti-inflammatory and pro-gestational activities of LIF by acting directly on macrophages and trophoblast cells.


Assuntos
Mediadores da Inflamação/imunologia , Fator Inibidor de Leucemia/imunologia , Macrófagos/imunologia , Trofoblastos/imunologia , Linhagem Celular , Movimento Celular/imunologia , Técnicas de Cocultura , Feminino , Expressão Gênica , Fator Estimulador de Colônias de Granulócitos e Macrófagos/imunologia , Humanos , Interferon gama/imunologia , Ativação de Macrófagos , Macrófagos/citologia , Macrófagos/metabolismo , Troca Materno-Fetal/imunologia , Metaloproteinase 9 da Matriz/metabolismo , Gravidez , Fator de Transcrição STAT1/metabolismo , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais/imunologia , Trofoblastos/citologia , Trofoblastos/metabolismo
11.
Ecotoxicol Environ Saf ; 191: 110235, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-31986458

RESUMO

Six parabens and their four metabolites were measured in paired maternal serum (MS) and cord serum (CS) samples collected from 95 pregnant women to elucidate placental transfer of this class of compounds. Matched maternal urine (MU) and amniotic fluid (AF) collected from 13 of 95 pregnant women were also analyzed to examine partition of these chemicals between maternal and fetal tissues. The placental transfer rates (PTRs; concentration ratio of parabens between CS and MS) of methyl- (MeP), ethyl- (EtP), propyl-parabens (PrP) were 0.81, 0.63, and 0.60, respectively. Furthermore, the PTRs of OH-MeP (0.93) and OH-EtP (1.8) were higher than those of their corresponding parent parabens, which suggested that hydroxylation increased placental transfer rates of parabens. Structure-dependent placental transfer mechanisms were observed. A significant negative correlation between molecular weights (or log Kow) of MeP, EtP, PrP, and p-hydroxy benzoic acid (4-HB) and PTRs suggested passive diffusion as a mechanism of placental transfer of these chemicals. Nevertheless, other hydroxylated metabolites (OH-EtP, OH-MeP, and 3,4-dihydroxy benzoic acid (3,4-DHB)) showed a positive correlation between molecular weight (or log Kow) and PTRs, which suggested that the placental transfer is mediated by protein binding of these metabolites. The MU to MS concentration ratios of MeP (MU/MSMeP) and PrP (MU/MSPrP) were 71 and 81, respectively, and MU/MSMeP was two orders of magnitude higher than that found for the metabolite (MU/MSOH-MeP: 0.35), suggesting that hydroxylation metabolite reduced urinary elimination of parabens. To our knowledge, this is the first time to report the occurrence and distribution of parabens and their metabolites in paired maternal-fetal serum, urine, and AF samples in China. Our results provide novel information on placental transfer of parabens and their metabolites.


Assuntos
Líquido Amniótico/química , Sangue Fetal/química , Exposição Materna , Troca Materno-Fetal , Parabenos/análise , Placenta/química , Líquido Amniótico/metabolismo , China , Cosméticos , Feminino , Sangue Fetal/metabolismo , Humanos , Parabenos/metabolismo , Placenta/metabolismo , Gravidez
12.
Toxicol Lett ; 322: 32-38, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31923464

RESUMO

Neonicotinoids (NNs), a widely used class of systemic pesticides, are regarded as exhibiting selective toxicity in insects. However, NNs are suspected of exerting adverse effects on mammals as well, including humans. To date, only adult male animal models have been subjected to general toxicity studies of NNs; fetuses have yet to be considered in this context. Here, we focused on the NN clothianidin (CLO) for the first quantitative LC-MS/MS analysis of maternal-to-fetal transfer and residual property of once-daily (single or multiple days), orally administered CLO and its metabolites in mice. The results revealed the presence of CLO and its five metabolites at approximately the same respective blood levels in both dams and fetuses. In the dams, CLO showed a peak value 1 h after administration, after which levels rapidly decreased at 3 and 6 h. In the fetuses of each group, levels of CLO were almost the same as those observed in the corresponding dams. The present results clearly demonstrated rapid passage of CLO through the placental barrier. However, metabolite-dependent differences observed in blood pharmacokinetics and residual levels. This is the first quantitative demonstration of the presence of CLO and its metabolites in fetal mouse blood.


Assuntos
Sangue Fetal/metabolismo , Guanidinas/sangue , Inseticidas/sangue , Troca Materno-Fetal , Neonicotinoides/sangue , Tiazóis/sangue , Animais , Biotransformação , Feminino , Guanidinas/administração & dosagem , Guanidinas/farmacocinética , Guanidinas/toxicidade , Inseticidas/administração & dosagem , Inseticidas/farmacocinética , Inseticidas/toxicidade , Exposição Materna , Camundongos Endogâmicos ICR , Neonicotinoides/administração & dosagem , Neonicotinoides/farmacocinética , Neonicotinoides/toxicidade , Gravidez , Medição de Risco , Tiazóis/administração & dosagem , Tiazóis/farmacocinética , Tiazóis/toxicidade , Toxicocinética
13.
Chemosphere ; 241: 124861, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31605998

RESUMO

Both arsenic (As) and fluorine (F) are toxic substances widely found in the environment, which threaten to various organs of both human and animals, especially the kidney. In this study, to investigate the individual and combined effects of arsenic (15 mg/L As2O3(III)) and fluoride (100 mg/L NaF), arsenic (15 mg/L As2O3(III)) and fluoride-arsenic (15 mg/L As2O3(III)+100 mg/L NaF) on the renal autophagy during early life, a mouse model of gestationally exposed to As and/or F was established. The results showed that the mRNA expression levels of LC3, LC3I, LC3II, Beclin-1, ULK1, Atg13 and Atg14 were significantly increased with a concomitant decrease in mTOR and Bcl-2 up on individual exposure to As and F rather than in combined (As + F) exposure. In addition, the protein expression levels of LC3-II/LC3-I, Beclin-1, and LAMP1 were significantly increased with a concomitant decrease in mTOR and Bcl-2 in the mice subjected to individual exposure than the combined exposure. Based on the results, it was observed that renal tissue of mice was highly sensitive to F than As. Moreover, the toxicity of the combined (As + F) exposure was significantly lower than that of the individual exposure, which could be attributed due to the antagonism between As and F.


Assuntos
Arsênico/toxicidade , Autofagia/efeitos dos fármacos , Exposição Ambiental , Fluoretos/toxicidade , Rim/fisiologia , Animais , Animais Recém-Nascidos , Interações Medicamentosas , Feminino , Humanos , Masculino , Troca Materno-Fetal , Camundongos , Gravidez , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Serina-Treonina Quinases TOR/metabolismo
14.
Gut ; 69(1): 42-51, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31036757

RESUMO

BACKGROUND AND AIMS: Prenatal and early life bacterial colonisation is thought to play a major role in shaping the immune system. Furthermore, accumulating evidence links early life exposures to the risk of developing IBD later in life. We aimed to assess the effect of maternal IBD on the composition of the microbiome during pregnancy and on the offspring's microbiome. METHODS: We prospectively examined the diversity and taxonomy of the microbiome of pregnant women with and without IBD and their babies at multiple time points. We evaluated the role of maternal IBD diagnosis, the mode of delivery, antibiotic use and feeding behaviour on the microbiome composition during early life. To assess the effects of IBD-associated maternal and infant microbiota on the enteric immune system, we inoculated germ-free mice (GFM) with the respective stool and profiled adaptive and innate immune cell populations in the murine intestines. RESULTS: Pregnant women with IBD and their offspring presented with lower bacterial diversity and altered bacterial composition compared with control women and their babies. Maternal IBD was the main predictor of the microbiota diversity in the infant gut at 7, 14, 30, 60 and 90 days of life. Babies born to mothers with IBD demonstrated enrichment in Gammaproteobacteria and depletion in Bifidobacteria. Finally, GFM inoculated with third trimester IBD mother and 90-day infant stools showed significantly reduced microbial diversity and fewer class-switched memory B cells and regulatory T cells in the colon. CONCLUSION: Aberrant gut microbiota composition persists during pregnancy with IBD and alters the bacterial diversity and abundance in the infant stool. The dysbiotic microbiota triggered abnormal imprinting of the intestinal immune system in GFM.


Assuntos
Microbioma Gastrointestinal/imunologia , Doenças Inflamatórias Intestinais/microbiologia , Complicações na Gravidez/microbiologia , Efeitos Tardios da Exposição Pré-Natal/microbiologia , Imunidade Adaptativa , Adulto , Animais , Bactérias/classificação , Bactérias/isolamento & purificação , Disbiose/imunologia , Disbiose/microbiologia , Transplante de Microbiota Fecal/métodos , Fezes/microbiologia , Feminino , Seguimentos , Trato Gastrointestinal/imunologia , Trato Gastrointestinal/microbiologia , Vida Livre de Germes , Humanos , Recém-Nascido , Doenças Inflamatórias Intestinais/imunologia , Masculino , Troca Materno-Fetal , Gravidez , Complicações na Gravidez/imunologia , Efeitos Tardios da Exposição Pré-Natal/imunologia , Estudos Prospectivos
15.
J Pharm Biomed Anal ; 177: 112838, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31525573

RESUMO

Raltegravir (RAL) is a HIV-integrase inhibitor recommended for treatment of HIV type 1 infection during pregnancy. The elimination of RAL to RAL glucuronide (RAL GLU) is mediated primarily by UDP glucuronosyltransferase 1A1 (UGT1A1). The present study shows the development and validation of 4 different methods for the analysis of RAL and RAL GLU in plasma and in urine samples. The methods were applied to evaluate the maternal-fetal pharmacokinetics of RAL and RAL GLU in a HIV-infected pregnant woman receiving RAL 400 mg twice daily. The sample preparation for RAL and RAL GLU analysis in 25 µL plasma and 100 µL diluted urine (10-fold with water containing 0.1% formic acid) were carried out by protein precipitation procedure. RAL and RAL GLU generate similar product mass fragments and require separation in the chromatographic system, so a suitable resolution was achieved for unchanged RAL and RAL GLU employing Ascentis Express C18 (75 × 4.6 mm, 2.7 µm) for both plasma and urine samples. The methods showed linearities at the ranges of 0.1-13.5 µg/mL RAL and 0.15-19.5 µg/mL RAL GLU in urine and 10-2000 ng/mL RAL and 2.5-800 RAL GLU in plasma. Precise and accurate evaluation showed coefficients of variation and relative errors ≤ 15%. The methods have been successfully applied in a maternal-fetal pharmacokinetic study.


Assuntos
Infecções por HIV/tratamento farmacológico , Inibidores de Integrase de HIV/análise , Troca Materno-Fetal , Complicações Infecciosas na Gravidez/tratamento farmacológico , Raltegravir Potássico/análise , Brasil , Cromatografia Líquida de Alta Pressão/métodos , Feminino , Glucuronídeos/administração & dosagem , Glucuronídeos/sangue , Glucuronídeos/química , Infecções por HIV/sangue , Infecções por HIV/urina , Inibidores de Integrase de HIV/administração & dosagem , Inibidores de Integrase de HIV/química , Inibidores de Integrase de HIV/farmacocinética , Humanos , Recém-Nascido , Permeabilidade , Placenta/metabolismo , Gravidez , Complicações Infecciosas na Gravidez/sangue , Complicações Infecciosas na Gravidez/urina , Terceiro Trimestre da Gravidez/metabolismo , Raltegravir Potássico/administração & dosagem , Raltegravir Potássico/química , Raltegravir Potássico/farmacocinética , Espectrometria de Massas em Tandem/métodos , Cordão Umbilical/química
17.
PLoS One ; 14(12): e0227120, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31887199

RESUMO

BACKGROUND: Interferon-beta (IFN-beta) is a commonly used treatment for multiple sclerosis (MS). Current guidelines recommend cessation of treatment during pregnancy, however the results of past studies on the safety of prenatal exposure to IFN-beta have been conflicting. A large scale study of a population of MS women is therefore warranted. OBJECTIVES: To assess whether, among those born to women with MS, infants prenatally exposed to IFN-beta show evidence of smaller size at birth relative to infants which were not prenatally exposed to any MS disease modifying drugs. METHODS: Swedish and Finnish register data was used. Births to women with MS in Sweden and Finland between 2005-2014 for which a birth measurement for weight, height, and head circumference was available were included. The exposure window was from 6 months prior to LMP to the end of pregnancy. RESULTS: In Sweden, 411 pregnancies were identified as exposed to IFN-beta during the exposure window, and 835 pregnancies were counted as unexposed to any MS DMD. The corresponding numbers for Finland were 232 and 331 respectively. Infants prenatally exposed to interferon-beta were on average 28 grams heavier (p = 0.17), 0.01 cm longer (p = 0.95), and had head circumferences 0.14 cm larger (p = 0.13) in Sweden. In Finland, infants were 50 grams lighter (p = 0.27), 0.02 cm shorter (p = 0.92) and had head circumferences 0.22 cm smaller (p = 0.15) relative to those unexposed. CONCLUSIONS: This study provides evidence that exposure to IFN-beta during pregnancy does not influence birth weight, length, or head circumference.


Assuntos
Peso ao Nascer/efeitos dos fármacos , Estatura/efeitos dos fármacos , Interferon beta/efeitos adversos , Esclerose Múltipla/tratamento farmacológico , Complicações na Gravidez/tratamento farmacológico , Adulto , Feminino , Finlândia , Humanos , Recém-Nascido , Troca Materno-Fetal , Esclerose Múltipla/imunologia , Gravidez , Complicações na Gravidez/imunologia , Sistema de Registros/estatística & dados numéricos , Suécia
18.
Isr Med Assoc J ; 21(11): 724-727, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31713359

RESUMO

BACKGROUND: The need for postnatal monitoring of infants exposed to intrauterine beta blockers (BBs) has not been clearly defined. OBJECTIVES: To evaluate infants exposed to intrauterine BBs in order to estimate the need for postnatal monitoring. METHODS: This retrospective case-control study comprised 153 term infants born to mothers who had been treated with BBs during pregnancy. Treatment indications included hypertension 76 mothers (49.7%), cardiac arrhythmias 48 (31.4%), rheumatic heart disease 14 (9.1%), cardiomyopathy 11 (7.2%) and migraine 4 (2.6%). The controls were infants of mothers with hypertension not exposed to BBs who were born at the same gestational age and born closest (before or after) to the matched infant in the study group. RESULTS: Compared to the control group, the infants in the study group had a higher prevalence of early asymptomatic hypoglycemia (study 30.7% vs. control 18.3%, P = 0.016), short symptomatic bradycardia events, other cardiac manifestations (P = 0.016), and longer hospitalization (P < 0.001). No life-threatening medical conditions were documented. The birth weight was significantly lower for the high-dose subgroup compared to the low-dose subgroup (P = 0.03), and the high-dose subgroup had a higher incidence of small-for-gestational-age (P = 0.02). CONCLUSIONS: No alarming or life-threatening medical conditions were observed among term infants born to BB treated mothers. These infants can be safely observed for 48 hours after birth close to their mothers in the maternity ward. Glucose follow-up is needed, especially in the first hours of life.


Assuntos
Antagonistas Adrenérgicos beta/efeitos adversos , Bradicardia/induzido quimicamente , Hipoglicemia/induzido quimicamente , Doenças do Recém-Nascido/induzido quimicamente , Troca Materno-Fetal , Resultado da Gravidez , Adulto , Peso ao Nascer , Estudos de Casos e Controles , Feminino , Humanos , Recém-Nascido , Tempo de Internação/estatística & dados numéricos , Masculino , Gravidez , Estudos Retrospectivos , Fatores de Risco
19.
Vet Clin North Am Food Anim Pract ; 35(3): 557-573, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31590902

RESUMO

A growing body of evidence has shown that calves can mount an immune response when vaccinated in the face of maternal antibodies (IFOMA), albeit inconsistently and often in ways that differ from seronegative calves or older cattle. Several previous reviews have endeavored to explain bovine neonatal immunology and have documented the issue of vaccinating young calves. However, as preweaning vaccination becomes more common in both beef and dairy production systems, so too has research on the impacts of such vaccination programs. This article aims to briefly review the challenges and opportunities for vaccinating calves IFOMA.


Assuntos
Imunidade Materno-Adquirida/imunologia , Vacinação/veterinária , Animais , Bovinos , Doenças dos Bovinos/prevenção & controle , Feminino , Troca Materno-Fetal/imunologia , Gravidez , Vacinação/métodos
20.
Drug Metab Rev ; 51(4): 524-532, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31595802

RESUMO

Fetal Alcohol Spectrum Disorder (FASD) describes the wide range of adverse physical, behavioral and cognitive effects resulting from ethanol exposure during embryonic and fetal development. Identification of children suffering from FASD is often difficult, as abuse of ethanol during pregnancy is a heavily stigmatized behavior that receives little prenatal screening attention in routine care. Over the last 3 decades, measurement of the ethanol metabolites fatty acid ethyl esters (FAEE) has emerged as a useful tool to detect in the neonatal period fetal alcohol exposure starting from mid gestation. This review aims at updating clinicians and researchers on the validity and utility of this biological marker in two aspects: The association with adverse fetal outcomes and in generating population estimates of fetal alcohol exposure.


Assuntos
Consumo de Bebidas Alcoólicas/metabolismo , Ácidos Graxos/metabolismo , Transtornos do Espectro Alcoólico Fetal/metabolismo , Mecônio/metabolismo , Efeitos Tardios da Exposição Pré-Natal , Consumo de Bebidas Alcoólicas/efeitos adversos , Animais , Ésteres/análise , Ésteres/metabolismo , Ácidos Graxos/análise , Feminino , Transtornos do Espectro Alcoólico Fetal/diagnóstico , Transtornos do Espectro Alcoólico Fetal/etiologia , Humanos , Recém-Nascido , Troca Materno-Fetal , Mecônio/química , Gravidez
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