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2.
Obstet Gynecol ; 135(4): 812-820, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32168208

RESUMO

OBJECTIVE: To estimate the effect of antenatal treatment of subclinical hypothyroidism on maternal depressive symptoms. METHODS: We conducted an ancillary study to a multicenter trial in women with singleton pregnancies diagnosed with subclinical hypothyroidism randomized to antenatal thyroxine therapy or placebo. Treatment was discontinued at the end of pregnancy. Women with overt thyroid disease, diabetes, autoimmune disease, and those diagnosed with depression were excluded. Participants were assessed for depressive symptoms using the Center for Epidemiological Studies-Depression scale (CES-D) before starting the study drug (between 11 and 20 weeks of gestation), between 32 and 38 weeks of gestation, and at 1 year postpartum. The primary outcome was maternal depressive symptoms score as assessed using the CES-D. Secondary outcome was the percentage of women who scored 16 or higher on the CES-D, as such a score is considered screen-positive for depression. RESULTS: Two hundred forty-five (36.2% of parent trial) women with subclinical hypothyroidism were allocated to thyroxine (n=124) or placebo (n=121). Median CES-D scores and the proportion of participants with positive scores were similar at baseline between the two groups. Treatment with thyroxine was not associated with differences in CES-D scores (10 [5-15] vs 10 [5-17]; P=.46) or in odds of screening positive in the third trimester compared with placebo, even after adjusting for baseline scores (24.3% vs 30.1%, adjusted odds ratio 0.63, 95% CI 0.31-1.28, P=.20). At 1 year postpartum, CES-D scores were not different (6 [3-11] vs 6 [3-12]; P=.79), nor was the frequency of screen-positive CES-D scores in the treated compared with the placebo group (9.7% vs 15.8%; P=.19). Treatment with thyroxine during pregnancy was also not associated with differences in odds of screening positive at the postpartum visit compared with placebo even after adjusting for baseline scores. Sensitivity analysis including women who were diagnosed with depression by the postpartum visit did not change the results. CONCLUSIONS: This study did not achieve its planned sample size, thus our conclusions may be limited, but in this cohort of pregnant women with subclinical hypothyroidism, antenatal thyroxine replacement did not improve maternal depressive symptoms.

3.
Curr Hypertens Rep ; 22(2): 17, 2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-32052203

RESUMO

PURPOSE OF REVIEW: To review the rationale and biological plausibility and discuss the current research on novel interventions for the prevention of preeclampsia. RECENT FINDINGS: Preeclampsia affects up to 8% of pregnancies worldwide and remains a major cause of maternal and neonatal morbidity and mortality. Multiple medications have been investigated or repurposed as potential effective interventions for preeclampsia prevention. Aspirin is currently the only drug for which there is some evidence of benefit for preeclampsia prevention, and its use is recommended by professional societies for pregnancies at risk. Statins have shown promise for prevention of preeclampsia in animal models and human pilot studies, without any trend or concerns for safety signals or teratogenicity. The use of metformin has also gained popularity in experimental studies, but observations from randomized clinical trials were not consistent on its utility as a possible intervention for preeclampsia prevention. While initial studies evaluating esomeprazole were promising, randomized trials failed to show benefit. Contemporary research shows exciting new opportunities for prophylactic treatment for preeclampsia, to prevent this debilitating and life-threatening disease.

4.
Am J Perinatol ; 37(3): 281-290, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30731481

RESUMO

OBJECTIVE: To evaluate sex-specific genetic susceptibility to adverse neurodevelopmental outcome (ANO, defined as cerebral palsy [CP], mental, or psychomotor delay) at risk for early preterm birth (EPTB, < 32 weeks). STUDY DESIGN: Secondary case-control analysis of a trial of magnesium sulfate (MgSO4) before anticipated EPTB for CP prevention. Cases are infants who died by the age of 1 year or developed ANO. Controls, matched by maternal race and infant sex, were neurodevelopmentally normal survivors. Neonatal DNA was evaluated for 80 polymorphisms in inflammation, coagulation, vasoregulation, excitotoxicity, and oxidative stress pathways using Taqman assays. The primary outcome for this analysis was sex-specific ANO susceptibility. Conditional logistic regression estimated each polymorphism's odds ratio (OR) by sex stratum, adjusting for gestational age, maternal education, and MgSO4-corticosteroid exposures. Holm-Bonferroni corrections, adjusting for multiple comparisons (p < 7.3 × 10-4), accounted for linkage disequilibrium between markers. RESULTS: Analysis included 211 cases (134 males; 77 females) and 213 controls (130 males; 83 females). An interleukin-6 (IL6) polymorphism (rs2069840) was associated with ANO in females (OR: 2.6, 95% confidence interval [CI]: 1.5-4.7; p = 0.001), but not in males (OR: 0.8, 95% CI: 0.5-1.2; p = 0.33). The sex-specific effect difference was significant (p = 7.0 × 10-4) and was unaffected by MgSO4 exposure. No other gene-sex associations were significant. CONCLUSION: An IL6 gene locus may confer susceptibility to ANO in females, but not males, after EPTB.

6.
Am J Perinatol ; 36(13): 1351-1356, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30609428

RESUMO

OBJECTIVE: To assess whether distraction using music and/or video games influences timing of analgesia request and improves pain outcomes in women undergoing labor induction. STUDY DESIGN: A total of 219 pregnant women with singleton gestation undergoing labor induction with a Foley bulb (FB) at term were randomized to distraction with music and video games via iPod (n = 109) or no iPod (n = 110). The primary outcome was the time from FB placement to request for pain medication. Secondary outcomes included number of patients requesting pain medication within 6 and 12 hours, type of pain medication received, pain visual analog scale scores, and patient satisfaction. Mann-Whitney's, chi-square, Kaplan-Meier's curves, and Pearson's product moment correlation were used for statistical analysis (significance: p < 0.05). RESULTS: Baseline characteristics were similar between the two groups. There was no difference in the time from FB placement until pain medication request between the groups. There were no significant differences in secondary outcomes. Increased per cent time of iPod use correlated with a longer time until pain medication request (R 2 = 0.22, p = 0.03). CONCLUSION: We were not able to show that distraction using music and video games delays timing of analgesia request or improve pain outcomes in pregnant women undergoing mechanical labor induction at term.

7.
J Matern Fetal Neonatal Med ; 32(17): 2897-2904, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29534635

RESUMO

Objective: As anemia in pregnancy is associated with adverse perinatal outcomes, we sought to define the mean and the fifth percentile of Hb and Ht using a contemporary multiethnic large cohort of low-risk pregnancies, and assess potential racial differences. Methods: We conducted a retrospective cohort study on women who delivered between 1 January 2008 and 31 December 2013 in Reggio Emilia County, Italy. Linear mixed effects models were used to describe changes in mean Hb and Ht, while quantile regression with matrix-design bootstrap defined changes in the fifth percentile of Hb and Ht, controlling for race, maternal age, smoking, and pregnancy number. Results: We analyzed 23,657 hemograms from 7318 pregnancies and 6870 women. Multivariate analysis showed that when compared to Caucasians', African women's mean Hb and Ht were respectively 0.24 (95%CI 0.3-0.17) g/dl and 0.7 (95%CI 0.8-0.5) % lower, while Asian mothers' were 0.11 (95%CI 0.19-0.03) g/dl and 0.3 (95%CI 0.5-0.1) % inferior. Similarly, both African and Asian women had lower fifth Ht percentiles (-1, 95%CI -1.3 to -0.6, and -0.4, 95%CI -0.7 to -0.04) than Caucasians, while African mothers also had lower fifth Hb percentile (0.3, 95%CI 0.5-0.1). The fifth percentile for Hb and Ht were, respectively, 11.3 (95%CI 11-11.5) g/dl and 32.8 (95%CI 32.3-33.4) % in the first trimester, 10.4 (95%CI 10.1-10.6) g/dl and 30.2 (95%CI 29.6-30.8) % in the second trimester, 10.1 (95%CI 9.8-10.3) g/dl and 30.6 (95%CI 30-31.1) % in the third trimester. Conclusions: We provided contemporary references to define anemia in pregnancy, and we confirmed that even in pregnancy, African and Asian women have lower Hb and Ht than Caucasian. Racial and population-specific references may have significant clinical and public health implication for more accurate disease diagnosis and appropriate treatment.


Assuntos
Anemia/etnologia , Hematócrito , Hemoglobinas/metabolismo , Complicações Hematológicas na Gravidez/etnologia , Adulto , Grupo com Ancestrais do Continente Africano , Anemia/sangue , Grupo com Ancestrais do Continente Asiático , Grupo com Ancestrais do Continente Europeu , Feminino , Humanos , Itália/epidemiologia , Paridade , Gravidez , Complicações Hematológicas na Gravidez/sangue , Valores de Referência , Estudos Retrospectivos
8.
J Matern Fetal Neonatal Med ; 32(2): 271-278, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28936902

RESUMO

OBJECTIVE: To determine the association between maternal obesity and delivery due to chorioamnionitis prior to labor onset, among expectantly managed women with preterm premature rupture of membranes (pPROM). METHODS: This was a secondary analysis of a multicenter randomized trial of magnesium sulfate versus placebo to prevent cerebral palsy or death among offspring of women with anticipated delivery at 24-31-week gestation. After univariable analysis, Cox proportional hazard evaluated the association between maternal obesity and chorioamnionitis, while Laplace regression investigated how obesity affects the gestational age at delivery of the first 20% of women developing the outcome of interest. RESULTS: A total of 164 of the 1942 women with pPROM developed chorioamnionitis prior to labor onset. Obese women had a 60% increased hazard of developing such complication (adjusted HR 1.6, 95%CI 1.1-2.1, p = .008), prompting delivery 1.5 weeks earlier, as the 20th survival percentile was 27.2-week gestation (95%CI 26-28.6) among obese as opposed to 28.8 weeks (95%CI 27.4-30.1) (p = .002) among nonobese women. CONCLUSIONS: Maternal obesity is a risk factor for chorioamnionitis prior to labor onset. Future studies will determine if obesity is important enough to change the management of latency after pPROM according to maternal BMI.


Assuntos
Corioamnionite/epidemiologia , Ruptura Prematura de Membranas Fetais/epidemiologia , Ruptura Prematura de Membranas Fetais/terapia , Obesidade/epidemiologia , Complicações na Gravidez/epidemiologia , Nascimento Prematuro/epidemiologia , Adulto , Cesárea/estatística & dados numéricos , Corioamnionite/terapia , Feminino , Humanos , Recém-Nascido , Sulfato de Magnésio/uso terapêutico , Obesidade/complicações , Obesidade/terapia , Gravidez , Complicações na Gravidez/terapia , Resultado da Gravidez/epidemiologia , Nascimento Prematuro/terapia , Estudos Retrospectivos , Fatores de Tempo
9.
Br J Clin Pharmacol ; 84(2): 215-222, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28925019

RESUMO

Pregnant and breastfeeding women have been rendered therapeutic orphans as they have been historically excluded from clinical trials. Labelling for most approved drugs does not provide information about safety and efficacy during pregnancy. This lack of data is mainly due to ethico-legal challenges that have remained entrenched in the post-diethylstilbestrol and thalidomide era, and that have led to pregnancy being viewed in the clinical trial setting primarily through a pharmacovigilance lens. Policy considerations that encourage and/or require the inclusion of pregnant or lactating women in clinical trials may address the current lack of available information. However, there are additional pragmatic strategies, such the employment of pharmacometric tools and the introduction of innovative clinical trial designs, which could improve knowledge about the safety and efficacy of medication use during pregnancy and lactation. This paper provides a broad overview of the pharmacoepidemiology of drugs used during pregnancy and lactation, and offers recommendations for regulators and researchers in academia and industry to increase the available pharmacokinetic and -dynamic understanding of medication use in pregnancy.


Assuntos
Pesquisa Biomédica/métodos , Aleitamento Materno , Ensaios Clínicos como Assunto/métodos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Preparações Farmacêuticas/administração & dosagem , Complicações na Gravidez/tratamento farmacológico , Pesquisa Biomédica/legislação & jurisprudência , Ensaios Clínicos como Assunto/legislação & jurisprudência , Feminino , Regulamentação Governamental , Guias como Assunto , Humanos , Farmacoepidemiologia , Gravidez , Estados Unidos , United States Food and Drug Administration
10.
Obstet Gynecol ; 130(6): 1386-1387, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-29189684
11.
Obstet Gynecol ; 130(6): 1285-1294, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-29112649

RESUMO

OBJECTIVE: To examine whether racial and ethnic differences exist in the frequency of and indications for cesarean delivery and to assess whether application of labor management strategies intended to reduce cesarean delivery rates is associated with patient's race and ethnicity. METHODS: This is a secondary analysis of a multicenter observational obstetric cohort. Trained research personnel abstracted maternal and neonatal records of greater than 115,000 pregnant women from 25 hospitals (2008-2011). Women at term with singleton, nonanomalous, vertex, liveborn neonates were included in two cohorts: 1) nulliparous women (n=35,529); and 2) multiparous women with prior vaginal deliveries only (n=39,871). Women were grouped as non-Hispanic black, non-Hispanic white, Hispanic, and Asian. Multivariable logistic regression was used to evaluate the following outcomes: overall cesarean delivery frequency, indications for cesarean delivery, and utilization of labor management strategies intended to safely reduce cesarean delivery. RESULTS: A total of 75,400 women were eligible for inclusion, of whom 47% (n=35,529) were in the nulliparous cohort and 53% (n=39,871) were in the multiparous cohort. The frequencies of cesarean delivery were 25.8% among nulliparous women and 6.0% among multiparous women. For nulliparous women, the unadjusted cesarean delivery frequencies were 25.0%, 28.3%, 28.7%, and 24.0% for non-Hispanic white, non-Hispanic black, Asian, and Hispanic women, respectively. Among nulliparous women, the adjusted odds of cesarean delivery were higher in all racial and ethnic groups compared with non-Hispanic white women (non-Hispanic black adjusted odds ratio [OR] 1.47, 95% CI 1.36-1.59; Asian adjusted OR 1.26, 95% CI 1.14-1.40; Hispanic adjusted OR 1.17, 95% CI 1.07-1.27) as a result of greater odds of cesarean delivery both for nonreassuring fetal status and labor dystocia. Nonapplication of labor management strategies regarding failed induction, arrest of dilation, arrest of descent, or cervical ripening did not contribute to increased odds of cesarean delivery for non-Hispanic black and Hispanic women. Compared with non-Hispanic white women, Hispanic women were actually less likely to experience elective cesarean delivery (adjusted OR 0.60, 95% CI 0.42-0.87) or cesarean delivery for arrest of dilation before 4 hours (adjusted OR 0.67, 95% CI 0.49-0.92). Additionally, compared with non-Hispanic white women, Asian women were more likely to experience cesarean delivery for nonreassuring fetal status (adjusted OR 1.29, 95% CI 1.09-1.53) and to have had that cesarean delivery be performed in the setting of a 1-minute Apgar score 7 or greater (adjusted OR 1.79, 95% CI 1.07-3.00). A similar trend was seen among multiparous women with prior vaginal deliveries. CONCLUSION: Although racial and ethnic disparities exist in the frequency of cesarean delivery, differential use of labor management strategies intended to reduce the cesarean delivery rate does not appear to be associated with these racial and ethnic disparities.


Assuntos
Cesárea , Administração dos Cuidados ao Paciente/organização & administração , Gestantes , Serviços Preventivos de Saúde , Adulto , Cesárea/métodos , Cesárea/estatística & dados numéricos , Estudos de Coortes , Grupos Étnicos , Feminino , Disparidades em Assistência à Saúde/etnologia , Humanos , Preferência do Paciente/etnologia , Gravidez , Resultado da Gravidez/epidemiologia , Gestantes/etnologia , Gestantes/psicologia , Serviços Preventivos de Saúde/métodos , Serviços Preventivos de Saúde/estatística & dados numéricos , Estados Unidos/epidemiologia
12.
Obstet Gynecol ; 130(4): 765-769, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28885402

RESUMO

Obstetric hemorrhage remains the most common cause of maternal mortality worldwide. It is believed that increased fibrinolytic activity, secondary to release and activation of endothelial tissue plasminogen activator, is involved in its pathogenesis. Tranexamic acid (TXA), an antifibrinolytic agent, has been shown to be beneficial in trauma patients if used within 3 hours of injury. A recent large randomized controlled trial showed that TXA given to hemorrhaging women within 3 hours after delivery was associated with decreased risk of death resulting from bleeding with no increase in thromboembolic complications. Limited evidence suggests that prophylactic TXA reduces blood loss at the time of delivery and decreases transfusion rates in the obstetric population. Tranexamic acid appears to be a safe and effective option in the treatment of obstetric hemorrhage. In addition, the limited available evidence supports the need for a well-designed adequately powered clinical trial to test its benefit as a prophylactic agent.


Assuntos
Antifibrinolíticos/administração & dosagem , Hemorragia Pós-Parto/tratamento farmacológico , Ácido Tranexâmico/administração & dosagem , Feminino , Humanos , Hemorragia Pós-Parto/prevenção & controle , Gravidez , Resultado do Tratamento
14.
Clin Obstet Gynecol ; 60(1): 161-168, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-27906745

RESUMO

Preeclampsia is a multisystem disorder that affects 3% to 5% of pregnant women and remains a significant source of short-term and long-term maternal and neonatal mortality and morbidity. Many professional societies recommend the use of low-dose aspirin to prevent preeclampsia in high-risk women. Owing to the similarities in pathophysiology between preeclampsia and atherosclerotic cardiovascular disease, and the encouraging data from preclinical and pilot clinical studies, pravastatin has been proposed for preventing preeclampsia. However, before statin administration becomes part of routine clinical practice, a large, well-designed, and adequately powered randomized-controlled trial is needed.


Assuntos
Aspirina/administração & dosagem , Fibrinolíticos/administração & dosagem , Pravastatina/administração & dosagem , Pré-Eclâmpsia/prevenção & controle , Feminino , Humanos , Gravidez , Fatores de Risco
15.
J Physiol ; 594(23): 7015-7025, 2016 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-27506899

RESUMO

KEY POINTS: Nitric oxide is essential in the vascular adaptation to pregnancy, as knockout mice lacking nitric oxide synthase (NOS3) have abnormal utero-placental perfusion, hypertension and growth restriction. We previously showed with ex vivo studies on transgenic animals lacking NOS3 that adverse intrauterine environment alters fetal programming of vascular reactivity in adult offspring. The current research shows that altered vascular reactivity correlates with higher blood pressure in vivo. Our data suggest that higher blood pressure depends on both genetic background (NOS3 deficiency) and uterine environment, becomes more evident with age (> 7 postnatal weeks), activity and stress, is gender specific (preponderant among males), and can be affected by the sleep-awake cycle. In utero or early postnatal life (< 7 weeks), before onset of hypertension, may represent a potential window for intervention to prevent future cardiovascular disorders. ABSTRACT: Nitric oxide is involved in the vascular adaptation to pregnancy. Using transgenic animals, we previously showed that adverse intrauterine environment alters vascular reactivity in adult offspring. The aim of our study was to determine if altered vascular programming is associated with abnormal blood pressure (BP) profiles in vivo. Mice lacking a functional endothelial nitric oxide synthase (KO, NOS3-/- ) and wild-type mice (WT, NOS3+/+ ) were crossbred to generate homozygous NOS3-/- (KO), maternally derived heterozygous NOS3+/- (KOM: mother with adverse intrauterine environment from NOS3 deficiency), paternally derived heterozygous NOS3+/- (KOP: mother with normal in utero milieu) and NOS3+/+ (WT) litters. BP was measured in vivo at 7, 14 and 21 weeks of age. After univariate analysis, multivariate population-averaged linear regression models were used to identify factors affecting BP. When compared to WT offspring, systolic (SBP), diastolic (DBP) and mean (MAP) BP progressively increased from KOP, to KOM, and peaked among KO (P < 0.001), although significance was not reached for KOP. Higher BP was also associated with male gender, older age (> 7 postnatal weeks), higher locomotor activity, daytime recordings, and recent blood pressure transducer insertion (P < 0.001). Post hoc analysis showed that KOM had higher SBP than KOP (P < 0.05). Our study indicates that adverse intrauterine environment contributes, along with multiple other factors, to account for hypertension; moreover, in utero or early postnatal life may represent a possible therapeutic window for prevention of cardiovascular disease later in life.


Assuntos
Pressão Sanguínea , Desenvolvimento Fetal/fisiologia , Óxido Nítrico Sintase Tipo III/genética , Animais , Feminino , Frequência Cardíaca , Locomoção , Masculino , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Óxido Nítrico Sintase Tipo III/fisiologia , Telemetria , Útero
16.
J Clin Invest ; 126(8): 2792-4, 2016 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-27454294

RESUMO

Pregnant women with antiphospholipid syndrome (APS) are at a high risk of obstetrical complications. The current standard of care, including the use of low-dose aspirin and heparin, has not been shown to prevent preeclampsia or intrauterine growth restriction (IUGR). Due to the similarities in pathophysiology among preeclampsia, IUGR, and atherosclerotic cardiovascular disease, statins have been proposed for treating and/or preventing these obstetrical complications. In this issue of the JCI, Lefkou et al. report on a small, observational trial that showed a dramatic improvement in both maternal and fetal/neonatal outcomes in women with APS given pravastatin after the onset of preeclampsia and/or IUGR compared with women in the control group. These results, along with other recent clinical studies, support further evaluation of statins for prevention of preeclampsia in a large-scale randomized clinical trial.


Assuntos
Síndrome Antifosfolipídica , Pravastatina , Aspirina , Feminino , Humanos , Pré-Eclâmpsia , Gravidez , Complicações na Gravidez
18.
Reprod Sci ; 23(11): 1593-1599, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27170663

RESUMO

OBJECTIVE: Using an animal model of preeclampsia induced by overexpression of soluble fms-like tyrosine kinase 1 (sFlt-1), we previously showed that pravastatin prevents the development of a preeclampsia phenotype. Our objective is to determine whether pravastatin treatment may be explained by its effects on apoptotic/survival pathways in the placenta. METHODS: Pregnant CD1 mice at day 8 of gestation (length of gestation 19 days) were randomly allocated to injection via tail vein with either adenovirus carrying sFlt-1 or adenovirus carrying the murine immunoglobulin G2α Fc fragment (mFc virus control group). Mice from the sFlt group were randomly assigned to receive pravastatin (5 mg/kg/d) in their drinking water from day 9 until killing (sFlt-1 + Pravastatin) or water (sFlt-1). The mFc control received water only. Mice were killed on day 18, and the placentas were collected. Protein mitogen-activated protein kinase (MAPK) pathway substrates were assayed using Bioplex Multiplex Immunoassay (Bio-Rad, Hercules, California). Data are reported as mean ± standard error of the mean or median (interquartile range) when appropriate. One-way analysis of variance followed by post hoc analysis was performed. Two-sided P value < .05 was considered statistically significant. RESULTS: The sFlt-1 + Pravastatin mice had significantly higher placental protein concentrations of prosurvival/ antiapoptotic factors (activating transcription factor 2, pp38, phosphorylated c-jun N-terminal kinase, and phosphorylated extracellular signal-regulated kinase) and of heat-shock protein 27 and signal transducer and activator of transcription 3, 2 factors crucial for embryonic and placental development during oxidative stress, compared to sFlt-1 mice (P < .05) and similar to the mFc control group. No differences were noted in substrates of the proapoptotic pp53 pathway. CONCLUSION: Pravastatin ability to prevent preeclampsia phenotype may be mediated through pleiotropic mechanisms involving a prosurvival/ antiapoptotic MAPK pathway in the placenta. Our results further support continued research in the role for statins in the prevention of preeclampsia.


Assuntos
Apoptose/efeitos dos fármacos , Placenta/efeitos dos fármacos , Placenta/metabolismo , Pravastatina/administração & dosagem , Pré-Eclâmpsia/metabolismo , Animais , Modelos Animais de Doenças , Feminino , Proteínas de Choque Térmico HSP27/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Camundongos , Fosforilação , Pré-Eclâmpsia/prevenção & controle , Gravidez , Fator de Transcrição STAT3/metabolismo , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/metabolismo
19.
Am J Perinatol ; 33(14): 1357-1364, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27135955

RESUMO

Objective The objective of this study was to localize by neuroimaging the altered structural brain development of these offspring using an autism model of transgenic mice lacking contactin-associated protein-like 2 (Cntnap2). Materials and Methods Pregnant dams were randomly allocated to fructose solution (10% W/V) as only drinking fluid or water. Cntnap2 heterozygous (+/-) offspring from each group were euthanized at 6 months of age and their whole brains evaluated by magnetic resonance imaging. T2-weighted images were acquired to evaluate the volumes of 29 regions of interest involved in autism spectrum disorder (ASD) pathogenesis. Whole brains were washed and processed for Nissl staining. Mann-Whitney U test and one-way analysis of variance were used for statistical analysis (significance: p < 0.05). Results The corpus callosum, anterior commissure, and caudate putamen were significantly smaller in Cntnap2 (+/-) male offspring exposed to fructose. No brain alterations were found in the female counterparts. Nissl staining of the caudate putamen revealed higher neuronal cell count in the male fructose offspring. Female group revealed an increase in caudate putamen neuronal cell count. Conclusion Metabolic dysregulation in pregnancy alters fetal brain development in genetically predisposed offspring. This is consistent with findings in human studies and supports the role of intrauterine factors in the etiology of autism.


Assuntos
Transtorno do Espectro Autista/diagnóstico por imagem , Transtorno do Espectro Autista/patologia , Encéfalo/embriologia , Encéfalo/patologia , Frutose/administração & dosagem , Fenômenos Fisiológicos da Nutrição Materna , Animais , Transtorno do Espectro Autista/genética , Modelos Animais de Doenças , Feminino , Desenvolvimento Fetal , Imagem por Ressonância Magnética , Masculino , Proteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Proteínas do Tecido Nervoso/genética , Gravidez , Distribuição Aleatória , Fatores Sexuais
20.
Am J Obstet Gynecol ; 215(3): 378.e1-6, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27060421

RESUMO

BACKGROUND: Consumption of fructose-rich diets in the United States is on the rise and thought to be associated with obesity and cardiometabolic diseases. OBJECTIVE: We sought to determine the effects of antenatal exposure to high-fructose diet on offspring's development of metabolic syndrome-like phenotype and other cardiovascular disease risk factors later in life. STUDY DESIGN: Pregnant C57BL/6J dams were randomly allocated to fructose solution (10% wt/vol, n = 10) or water (n = 10) as the only drinking fluid from day 1 of pregnancy until delivery. After weaning, pups were started on regular chow, and evaluated at 1 year of life. We measured percent visceral adipose tissue and liver fat infiltrates using computed tomography, and blood pressure using CODA nonivasive monitor. Intraperitoneal glucose tolerance testing with corresponding insulin concentrations were obtained. Serum concentrations of glucose, insulin, triglycerides, total cholesterol, leptin, and adiponectin were measured in duplicate using standardized assays. Fasting homeostatic model assessment was also calculated to assess insulin resistance. P values <.05 were considered statistically significant. RESULTS: Maternal weight, pup number, and average weight at birth were similar between the 2 groups. Male and female fructose group offspring had higher peak glucose and area under the intraperitoneal glucose tolerance testing curve compared with control, and higher mean arterial pressure compared to control. Female fructose group offspring were heavier and had higher percent visceral adipose tissue, liver fat infiltrates, homeostatic model assessment of insulin resistance scores, insulin area under the intraperitoneal glucose tolerance testing curve, and serum concentrations of leptin, and lower concentrations of adiponectin compared to female control offspring. No significant differences in these parameters were noted in male offspring. Serum concentrations of triglycerides or total cholesterol were not different between the 2 groups for either gender. CONCLUSION: Maternal intake of high fructose leads to fetal programming of adult obesity, hypertension, and metabolic dysfunction, all risk factors for cardiovascular disease. This fetal programming is more pronounced in female offspring. Limiting intake of high fructose-enriched diets in pregnancy may have significant impact on long-term health.


Assuntos
Dieta , Frutose/administração & dosagem , Hipertensão/etiologia , Resistência à Insulina , Obesidade/etiologia , Efeitos Tardios da Exposição Pré-Natal , Animais , Glicemia/análise , Fígado Gorduroso/etiologia , Feminino , Frutose/efeitos adversos , Teste de Tolerância a Glucose , Gordura Intra-Abdominal/anatomia & histologia , Leptina/sangue , Camundongos Endogâmicos C57BL , Gravidez
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