RESUMO
BACKGROUND: Bisphenol A (BPA) and phthalates metabolites are linked to a variety of adverse health consequences but studies have not explored their association with growth trajectories. OBJECTIVE: Explore body mass index (BMI) trajectories for tertile exposures to BPA and phthalates metabolites in the third trimester of pregnancy. METHODS: We constructed BMI (kg/m2 ) trajectories from birth to 14 years in a birth cohort of 249 children from Mexico City using tertiles of third trimester maternal urinary concentrations of BPA and phthalates metabolites. Fractional age polynomials and mixed effects models were fit separately by sex. Predicted models were plotted for each metabolite tertile with the covariates mother's education and BMI centered at average values. RESULTS: Highest predicted BMI trajectories for female children were observed for third tertile exposure to the phthalate metabolite mono(2-ethyl-5-carboxypentyl) phthalate. In male children, first tertile exposure to mono-isobutyl phthalate and monobenzyl phthalate and second tertile exposure to mono(2-ethylhexyl) phthalate and mono(2-ethyl-5-hydroxyhexyl) phthalate predicted the highest BMI trajectory by adolescence. There was no relationshsip between BPA and child growth trajectory. CONCLUSIONS: These results suggest sex-specific differences in BMI trajectories by levels of metabolite exposure. Additional studies are needed to consider growth through adolescence in assessing the association of pregnancy exposures on child's BMI.
Assuntos
Compostos Benzidrílicos/urina , Índice de Massa Corporal , Exposição Ambiental/estatística & dados numéricos , Fenóis/urina , Ácidos Ftálicos/urina , Terceiro Trimestre da Gravidez/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Adolescente , Compostos Benzidrílicos/metabolismo , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Masculino , México/epidemiologia , Fenóis/metabolismo , Ácidos Ftálicos/metabolismo , Gravidez , Estudos ProspectivosRESUMO
Disruption of the maternal environment during pregnancy is a key contributor to offspring diseases that develop in adult life. To explore the impact of chronodisruption during pregnancy in primates, we exposed pregnant capuchin monkeys to constant light (eliminating the maternal melatonin rhythm) from the last third of gestation to term. Maternal temperature and activity circadian rhythms were assessed as well as the newborn temperature rhythm. Additionally we studied the effect of daily maternal melatonin replacement during pregnancy on these rhythms. Ten pregnant capuchin monkeys were exposed to constant light from 60% of gestation to term. Five received a daily oral dose of melatonin (250 µg kg/body weight) at 1800 h (LL+Mel) and the other five a placebo (LL). Six additional pregnant females were maintained in a 14â¶10 light:dark cycles and their newborns were used as controls (LD). Rhythms were recorded 96 h before delivery in the mother and at 4-6 days of age in the newborn. Exposure to constant light had no effect on the maternal body temperature rhythm however it delayed the acrophase of the activity rhythm. Neither rhythm was affected by melatonin replacement. In contrast, maternal exposure to constant light affected the newborn body temperature rhythm. This rhythm was entrained in control newborns whereas LL newborns showed a random distribution of the acrophases over 24-h. In addition, mean temperature was decreased (34.0±0.6 vs 36.1±0.2°C, in LL and control, respectively P<0.05). Maternal melatonin replacement during pregnancy re-synchronized the acrophases and restored mean temperature to the values in control newborns. Our findings demonstrate that prenatal melatonin is a Zeitgeber for the newborn temperature rhythm and supports normal body temperature maintenance. Altogether these prenatal melatonin effects highlight the physiological importance of the maternal melatonin rhythm during pregnancy for the newborn primate.
Assuntos
Ritmo Circadiano/efeitos da radiação , Luz , Mães , Temperatura , Animais , Animais Recém-Nascidos , Comportamento Animal/efeitos dos fármacos , Comportamento Animal/fisiologia , Comportamento Animal/efeitos da radiação , Cebus , Ritmo Circadiano/efeitos dos fármacos , Feminino , Masculino , Exposição Materna/efeitos adversos , Melatonina/farmacologia , Gravidez , Terceiro Trimestre da Gravidez/efeitos dos fármacos , Terceiro Trimestre da Gravidez/fisiologia , Terceiro Trimestre da Gravidez/efeitos da radiação , Fatores de TempoRESUMO
Because macrophage migration inhibitory factor (MIF) is a key cytokine in pregnancy and has a role in inflammatory response and pathogen defense, the objective of the present study was to investigate the effects of MIF in first- and third-trimester human placental explants infected with Toxoplasma gondii. Explants were treated with recombinant MIF, IL-12, interferon-γ, transforming growth factor-ß1, or IL-10, followed by infection with T. gondii RH strain tachyzoites. Supernatants of cultured explants were assessed for MIF production. Explants were processed for morphologic analysis, immunohistochemistry, and real-time PCR analysis. Comparison of infected and stimulated explants versus noninfected control explants demonstrated a significant increase in MIF release in first-trimester but not third-trimester explants. Tissue parasitism was higher in third- than in first-trimester explants. Moreover, T. gondii DNA content was lower in first-trimester explants treated with MIF compared with untreated explants. However, in third-trimester explants, MIF stimulus decreased T. gondii DNA content only at the highest concentration of the cytokine. In addition, high expression of MIF receptor was observed in first-trimester placental explants, whereas MIF receptor expression was low in third-trimester explants. In conclusion, MIF was up-regulated and demonstrated to be important for control of T. gondii infection in first-trimester explants, whereas lack of MIF up-regulation in third-trimester placentas may be involved in higher susceptibility to infection at this gestational age.
Assuntos
Idade Gestacional , Oxirredutases Intramoleculares/metabolismo , Fatores Inibidores da Migração de Macrófagos/metabolismo , Placenta/metabolismo , Placenta/parasitologia , Toxoplasma/fisiologia , Toxoplasmose/parasitologia , Antígenos de Diferenciação de Linfócitos B/genética , Antígenos de Diferenciação de Linfócitos B/metabolismo , Feminino , Regulação da Expressão Gênica , Antígenos de Histocompatibilidade Classe II/genética , Antígenos de Histocompatibilidade Classe II/metabolismo , Humanos , Oxirredutases Intramoleculares/biossíntese , Oxirredutases Intramoleculares/farmacologia , Fatores Inibidores da Migração de Macrófagos/biossíntese , Fatores Inibidores da Migração de Macrófagos/farmacologia , Modelos Biológicos , Nitritos/metabolismo , Placenta/efeitos dos fármacos , Placenta/patologia , Gravidez , Primeiro Trimestre da Gravidez/efeitos dos fármacos , Terceiro Trimestre da Gravidez/efeitos dos fármacos , Toxoplasma/citologia , Toxoplasma/efeitos dos fármacos , Toxoplasmose/patologia , Toxoplasmose/prevenção & controleRESUMO
BACKGROUND: The use of metformin throughout gestation by pregnant women with polycystic ovary syndrome (PCOS) significantly reduces the number of first trimester spontaneous abortions and the rate of occurrence of gestational diabetes. OBJECTIVE: The objective of this study was to investigate the pharmacokinetics and the placental transfer of metformin in pregnant women with PCOS. PATIENTS AND METHODS: Eight pregnant women with PCOS taking 850 mg metformin every 12 h during the third trimester of pregnancy were evaluated. Maternal blood samples were collected at steady state during the dose interval (0-12 h). Maternal and umbilical cord blood samples were also obtained at delivery. Metformin plasma concentrations were analyzed by high-performance liquid chromatography, and pharmacokinetic parameters were determined using a non-compartmental model. Data are reported as median and minimum and maximum values. RESULTS: Metformin pharmacokinetic parameters were: t(½), 3.8 (2.8-5.4) h; t(max), 2.0 (0.5-3.0) h; C(max), 1.4 (0.5-2.1) mg/L; C(mean), 0.5 (0.2-0.9) mg/L; AUC(0-12), 6.4 (1.1-9.2) mg h/L; Cl/f, 105 (60-274) L/h; Vd/f, 551 (385-1173) L; median fluctuation, 89 (79-95)%. Umbilical/maternal metformin plasma concentration ratios were 0.7 (0.4-1.3). CONCLUSION: Metformin oral clearance (Cl/f) had increased in our patients relative to nonpregnant healthy volunteers or diabetic patients. Therefore, lower plasma metformin concentrations were observed for nondiabetic pregnant women with PCOS. Future studies should be conducted to demonstrate the therapeutic efficacy of metformin during pregnancy. Caution is warranted as umbilical/maternal metformin plasma concentrations ratios of around 0.7 require metformin dosage adjustment.
Assuntos
Hipoglicemiantes/farmacocinética , Metformina/farmacocinética , Síndrome do Ovário Policístico/metabolismo , Complicações Neoplásicas na Gravidez/metabolismo , Adolescente , Adulto , Feminino , Sangue Fetal , Humanos , Hipoglicemiantes/efeitos adversos , Hipoglicemiantes/sangue , Hipoglicemiantes/uso terapêutico , Troca Materno-Fetal/efeitos dos fármacos , Metformina/efeitos adversos , Metformina/sangue , Metformina/uso terapêutico , Síndrome do Ovário Policístico/tratamento farmacológico , Gravidez , Complicações Neoplásicas na Gravidez/tratamento farmacológico , Terceiro Trimestre da Gravidez/efeitos dos fármacos , Adulto JovemRESUMO
BACKGROUND: Presence of Bisphenol A (BPA) has been documented worldwide in a variety of human biological samples. There is growing evidence that low level BPA exposure may impact placental tissue development and thyroid function in humans. The aim of this present pilot study was to determine urinary concentrations of BPA during the last trimester of pregnancy among a small subset of women in Mexico City, Mexico and relate these concentrations to risk of delivering prematurely. METHODS: A nested case-control subset of 60 participants in the Early Life Exposure in Mexico to ENvironmental Toxicants (ELEMENT) study in Mexico City, Mexico were selected based on delivering less than or equal to 37 weeks of gestation and greater than 37 weeks of gestation. Third trimester archived spot urine samples were analyzed by online solid phase extraction coupled with high performance liquid chromatography isotope dilution tandem mass spectrometry. RESULTS: BPA was detected in 80.0% (N = 48) of the urine samples; total concentrations ranged from < 0.4 µg/L to 6.7 µg/L; uncorrected geometric mean was 1.52 µg/L. The adjusted odds ratio of delivering less than or equal to 37 weeks in relation to specific gravity adjusted third trimester BPA concentration was 1.91 (95%CI 0.93, 3.91, p-value = 0.08). When cases were further restricted to births occurring prior to the 37th week (n = 12), the odds ratio for specific-gravity adjusted BPA was larger and statistically significant (p < 0.05). CONCLUSIONS: This is the first study to document measurable levels of BPA in the urine of a population of Mexican women. This study also provides preliminary evidence, based on a single spot urine sample collected during the third trimester, that pregnant women who delivered less than or equal to 37 weeks of gestation and prematurely (< 37 weeks) had higher urinary concentrations of BPA compared to women delivering after 37 weeks.
Assuntos
Exposição Ambiental/efeitos adversos , Poluentes Ambientais/intoxicação , Fenóis/intoxicação , Nascimento Prematuro/induzido quimicamente , Adulto , Compostos Benzidrílicos , Estudos de Casos e Controles , Feminino , Humanos , Modelos Logísticos , México/epidemiologia , Fenóis/urina , Projetos Piloto , Gravidez , Terceiro Trimestre da Gravidez/efeitos dos fármacos , Terceiro Trimestre da Gravidez/urina , Nascimento Prematuro/epidemiologia , Nascimento Prematuro/urinaRESUMO
Se diseñó un estudio prospectivo descriptivo de inducción de partos sobre 36 semanas, con el objetivo de certificar su seguridad y efectividad para obtener resulución vaginal del parto en pacientes con indicación de interrupción, pero con malas condiciones cervicales. A 207 pacientes del Hospital Regional de Puerto Montt, con feto único vivo sobre 36 semanas, en presentación cefálica y sin compromiso de la Unidad Fetoplacentaria (UFP) se les administró 100 mcg de Misoprostol intravaginal, obteniéndose un parto vaginal en el 81 por ciento de los casos, el 90,4 por ciento se produjo antes de las 24 horas. La complicación más frecuente fue la polisistolia y la principal causa de cesárea fue la sospecha clínica de compromiso de UFP, destacando sólo 5 casos con apgar < 7 a los 5 min. Se concluye que el Misoprostol intravaginal es un método eficaz, seguro, económico y de fácil uso en la inducción de parto en éste grupo de pacientes
Assuntos
Humanos , Feminino , Gravidez , Recém-Nascido , Adolescente , Adulto , Trabalho de Parto Induzido , Misoprostol/farmacologia , Administração Intravaginal , Cesárea , Hipertensão , Misoprostol/administração & dosagem , Complicações do Trabalho de Parto , Terceiro Trimestre da Gravidez/efeitos dos fármacos , Gravidez Prolongada/efeitos dos fármacosRESUMO
Este estudo teve como objetivo avaliar os aspectos técnicos da amnioinfusao transabdominal em pacientes com rotura prematura das membranas ovulares (RPM) e analisar seus efeitos sobre o período de latência, resoluçao da gestaçao, prognóstico neonatal e infecçao materna. Para cumprir estes objetivos foram arroladas 40 pacientes com RPM e idade gestacional entre 24 e 34 semanas. Destas, 20 formaram o grupo amnioinfundido (A) e as outras 20 constituíram o grupo controle nao infundido (NA). Estes grupos foram subdivididos quanto à idade gestacional, considerando gestantes entre 24 e 28 semanas de gestaçao e acima de 28 até 34 semanas. Para a infusao foi utilizado soluçao salina a 0,9 por cento, aquecida a 37 graus Celsius. Analisando os aspectos técnicos da amnioinfusao transabdominal, observou-se que esta deve iniciar com velocidade de infusao de 1 a 2 ml/min até se constatar a formaçao de bolsoes líquidos em regioes intra-amnióticas distantes da agulha, indicando sua localizaçao adequada na cavidade amniótica. A partir daí, passar à velocidade de infusao para 20 a 30 ml/min. O volume médio infundido foi de 408,5 ml + 108,6 ml, com intervalo médio entre as infusoes de 6,6 dias + 4,9 dias. Dentre os resultados deste trabalho, a única variável com diferença estatisticamente significativa foi o período de latência observado no grupo de mulheres infundidas (x= 20,5 dias) em relaçao ao grupo controle (X= 9,4 dias). As demais variáveis estudadas - resoluçao da gestaçao, prognóstico neonatal e infecçao materna - nao apresentaram diferenças estatisticamente significativas entre os dois grupos avaliados.