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BACKGROUND: Extracellular vesicles (EVs) are membrane-enclosed structures containing lipids, proteins, and RNAs that play a crucial role in cell-to-cell communication. However, the precise mechanism through which circulating EVs disrupt hepatic glucose homeostasis in gestational diabetes mellitus (GDM) remains unclear. RESULTS: Circulating EVs isolated from human plasma were co-cultured with mammalian liver cells to investigate the potential induction of hepatic insulin resistance by GDM-EVs using glucose output assays, Seahorse assays, metabolomics, fluxomics, qRT-PCR, bioinformatics analyses, and luciferase assays. Our findings demonstrated that hepatocytes exposed to GDM-EVs exhibited increased gluconeogenesis, attenuated energy metabolism, and upregulated oxidative stress. Particularly noteworthy was the discovery of miR-1299 as the predominant miRNA in GDM-EVs, which directly targeting the 3'-untranslated regions (UTR) of STAT3. Our experiments involving loss- and gain-of-function revealed that miR-1299 inhibits the insulin signaling pathway by regulating the STAT3/FAM3A axis, resulting in increased insulin resistance through the modulation of mitochondrial function and oxidative stress in hepatocytes. Moreover, experiments conducted in vivo on mice inoculated with GDM-EVs confirmed the development of glucose intolerance, insulin resistance, and downregulation of STAT3 and FAM3A. CONCLUSIONS: These results provide insights into the role of miR-1299 derived from circulating GDM-EVs in the progression of insulin resistance in hepatic cells via the STAT3/FAM3A axis and downstream metabolic reprogramming.
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Diabetes Gestacional , Vesículas Extracelulares , Glucose , Hepatócitos , Homeostase , Resistência à Insulina , Fígado , MicroRNAs , Fator de Transcrição STAT3 , Diabetes Gestacional/metabolismo , Diabetes Gestacional/genética , MicroRNAs/metabolismo , MicroRNAs/genética , Humanos , Vesículas Extracelulares/metabolismo , Animais , Feminino , Gravidez , Fator de Transcrição STAT3/metabolismo , Fator de Transcrição STAT3/genética , Camundongos , Glucose/metabolismo , Fígado/metabolismo , Hepatócitos/metabolismo , Transdução de Sinais , Estresse Oxidativo , Camundongos Endogâmicos C57BL , Regiões 3' não Traduzidas , Células Hep G2RESUMO
Gut flora is considered to modulate lipid transport from the intestine into the bloodstream, and thus may potentially participate in the development of GDM. Although previous studies have shown that the intestinal microbiota influences lipid transport and metabolism in GDM, the precise mechanisms remain elusive. To address this, we used a high-fat diet (HFD)-induced GDM mouse model and conducted 16s rRNA sequencing and fecal metabolomics to assess gut microbial community shifts and associated metabolite changes. Western blot, ELISA, and chromatin immunoprecipitation (ChIP) were utilized to elucidate how gut microbiota affect intestinal lipid transport and the insulin sensitivity of hepatic, adipose, and skeletal muscle tissues. We found that HFD impaired the oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) in pregnant mice. 16s rRNA sequencing demonstrated profound compositional changes, especially in the relative abundances of Firmicutes and Bacteroidetes. Metabolomics analysis presented a decline in the concentration of short-chain fatty acids (SCFAs) in the GDM group. Western blot analyses showed an upregulation of HDAC3 and a concurrent reduction in H3K27 acetylation in the intestine. ChIP-qPCR showed that PPAR-γ was inhibited, which in turn activated lipid-transporter CD36. ELISA and insulin signaling pathway detection in insulin-target organs showed high concentrations of circulating fatty acids and triglycerides and insulin resistance in insulin-target organs. Our results suggest that gut microbiota is closely associated with the development of GDM, partly because decreased gut flora-associated SCFAs activate CD36 by suppressing the HDAC3-H3K27ac-PPAR-γ axis to transport excessive fatty acids and triglycerides into blood circulation, thereby dysregulating the insulin sensitivity of insulin target organs.
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OBJECTIVES: To investigate the associations of traffic-related air pollution exposures in early pregnancy with birth outcomes and infant neurocognitive development. DESIGN: Cohort study. SETTING: Eligible women attended six visits in the maternity clinics of two centres, the First Affiliated Hospital of Chongqing Medical University and Chongqing Health Centre for Women and Children. PARTICIPANTS: Women who were between 20 and 40 years of age and were at 11-14 weeks gestation with a singleton pregnancy were eligible for participation. Women were excluded if they had a history of premature delivery before 32 weeks of gestation, maternal milk allergy or aversion or severe lactose intolerance. 1273 pregnant women enrolled in 2015-2016 and 1174 live births were included in this analysis. EXPOSURES: Air pollution concentrations at their home addresses, including particulate matter with diameter ≤2.5 µm (PM2.5) and nitrogen dioxide (NO2), during pre-conception and each trimester period were estimated using land-use regression models. OUTCOME MEASURES: Birth outcomes (ie, birth weight, birth length, preterm birth, low birth weight, large for gestational age and small for gestational age (SGA) status) and neurodevelopment outcomes measured by the Chinese version of Bayley Scales of Infant Development. RESULTS: An association between SGA and per-IQR increases in NO2 was found in the first trimester (OR: 1.57, 95% CI: 1.06 to 2.32) and during the whole pregnancy (OR: 1.33, 99% CI: 1.01 to 1.75). Both PM2.5 and NO2 exposure in the 90 days prior to conception were associated with lower Psychomotor Development Index scores (ß: -6.15, 95% CI: -8.84 to -3.46; ß: -2.83, 95% CI: -4.27 to -1.39, respectively). Increased NO2 exposure was associated with an increased risk of psychomotor development delay during different trimesters of pregnancy. CONCLUSIONS: Increased exposures to NO2 during pregnancy were associated with increased risks of SGA and psychomotor development delay, while increased exposures to both PM2.5 and NO2 pre-conception were associated with adverse psychomotor development outcomes at 12 months of age. TRIAL REGISTRATION NUMBER: ChiCTR-IOR-16007700.
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Poluição do Ar , Desenvolvimento Infantil , Exposição Materna , Material Particulado , Humanos , Feminino , Gravidez , China/epidemiologia , Adulto , Recém-Nascido , Estudos Prospectivos , Material Particulado/efeitos adversos , Material Particulado/análise , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , Desenvolvimento Infantil/efeitos dos fármacos , Exposição Materna/efeitos adversos , Resultado da Gravidez/epidemiologia , Adulto Jovem , Dióxido de Nitrogênio/efeitos adversos , Dióxido de Nitrogênio/análise , Lactente , Peso ao Nascer , Poluentes Atmosféricos/efeitos adversos , Poluentes Atmosféricos/análise , Efeitos Tardios da Exposição Pré-Natal , Nascimento Prematuro/epidemiologia , MasculinoRESUMO
In order to slow the spread of COVID-19, on March 23, 2020, a strict lockdown was implemented in the UK. This was followed by alternating periods of less restrictive lockdowns until most public health restrictions were lifted in the summer of 2021. While these measures were necessary, they significantly affected people's daily activities, lifestyles, and mental well-being.This paper presents a longitudinal research study that focused on females aged 55 + in the UK, aiming to understand how COVID-19 and the subsequent 15-month period of lockdowns affected their lifestyles and emotions. The study collected data through online surveys, where respondents reported the frequency and mode of access to activities, and their positive and negative emotional experiences during distinct study phases that encompassed both lockdown and less strict periods.In contrast to previous studies highlighting vulnerabilities for females and the elderly during lockdowns, this research found that the studied group maintained an overall positive outlook throughout the study period and successfully adapted to the lockdowns by increasing their engagement in certain activities, in particular, activities like 'getting active'. In addition, our findings indicate rapid adaptive behaviour change towards many online activities, such as cultural activities. However, the study also revealed negative emotions and a decrease in some activities during the second lockdown in 2020 and the subsequent lockdowns in 2021, underscoring the challenges inherent in prolonged periods of confinement. In addition, the study found negative affect associated with some activities, including working and studying from home.The findings provide valuable insights into how females aged over 55 coped with stressful circumstances, which can inform the development of resilient and mental health-conscious public health policies and responses in preparation for future pandemics or other hazards.
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COVID-19 , Resiliência Psicológica , Humanos , Feminino , COVID-19/epidemiologia , COVID-19/psicologia , COVID-19/prevenção & controle , Estudos Longitudinais , Reino Unido/epidemiologia , Pessoa de Meia-Idade , Idoso , Quarentena/psicologia , Controle de Doenças Transmissíveis/métodos , Inquéritos e Questionários , Estilo de Vida , SARS-CoV-2 , Adaptação PsicológicaRESUMO
OBJECTIVE: Severe early-onset fetal growth restriction (FGR) causes stillbirth, neonatal death and neurodevelopmental impairment. Poor maternal spiral artery remodelling maintains vasoactive responsiveness but is susceptible to treatment with sildenafil, a phosphodiesterase type 5 (PDE5) inhibitor, which may improve perinatal outcomes. DESIGN: Superiority, double-blind randomised controlled trial. SETTING: A total of 20 UK fetal medicine units. POPULATION: Pregnancies affected by FGR, defined as an abdominal circumference below the tenth centile with absent end-diastolic flow in the umbilical artery between 22+0 and 29+6 weeks of gestation. METHODS: Treatment with sildenafil (25 mg three times/day) or placebo until delivery or 32 weeks of gestation. MAIN OUTCOME MEASURES: All infants alive at hospital discharge were assessed for cardiovascular function and cognitive, speech/language and neuromotor impairment at 2 years of age. The primary outcome was survival without cerebral palsy or neurosensory impairment, or a Bayley-III composite score of >85. RESULTS: In total, 135 women were randomised between November 2014 and July 2016 (70 to sildenafil and 65 to placebo). We previously published that there was no improvement in time to delivery or perinatal outcomes with sildenafil. In all, 75 babies (55.5%) were discharged alive, with 61 infants eligible for follow-up (32 sildenafil and 29 placebo). One infant died (placebo), three mothers declined and ten mothers were uncontactable. There was no difference in neurodevelopment or blood pressure following treatment with sildenafil. Infants who received sildenafil had a larger head circumference at 2 years of age (median difference 49.2 cm, IQR 46.4-50.3, vs 47.2 cm, 95% CI 44.7-48.9 cm). CONCLUSIONS: Sildenafil therapy did not prolong pregnancy or improve perinatal outcomes and did not improve infant neurodevelopment in FGR survivors. Therefore, sildenafil should not be prescribed for this condition.
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BACKGROUND: There has been a dramatic shift in food systems, and the consumption of commercially processed and packaged foods has grown globally, including among older infants and young children. Many of these products are ultraprocessed and contain additives, with concerning implications for the health and nutrition of children. OBJECTIVES: The study objectives were as follows: 1) to assess the levels of processing among different commercially produced complementary food product (CPCF) categories marketed in the Southeast Asia region, 2) to compare the nutrient content of CPCF products across levels of processing, and 3) to assess the types of additives present in different CPCF categories. METHODS: This cross-sectional study involved secondary analysis of a cross-sectional dataset of product label information from CPCF purchased in 2021 in Cambodia, Indonesia, Lao People's Democratic Republic, Malaysia, Philippines, Thailand, and Viet Nam. Ingredient lists were reviewed to determine the level of processing-based on the Nova classification-and the presence of additives. Nutrient declaration panels were reviewed to determine total sugar, sodium, and total fat. RESULTS: Nearly half of all CPCF were ultraprocessed, with total sugar and sodium content significantly higher among ultraprocessed CPCF than unprocessed/minimally processed products. Almost half of CPCF contained additives, with a median of 6 per product. More than 30% of all CPCF made use of cosmetic additives to enhance the products' appearance, flavor, or texture, with emulsifiers, colors, and thickeners the most prevalent. Almost one-third of products contained additives not permitted in Codex Alimentarius standards and guidelines for CPCF. CONCLUSIONS: Findings from this study should alert national governments to both adopt and ensure enforcement of Codex guidance on additives and regulations enacted to encourage lower levels of processing for CPCF.
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Aditivos Alimentares , Manipulação de Alimentos , Alimentos Infantis , Estudos Transversais , Humanos , Sudeste Asiático , Aditivos Alimentares/análise , Alimentos Infantis/análise , Alimentos Infantis/normas , Lactente , Valor Nutritivo , Rotulagem de Alimentos , População do Sudeste AsiáticoRESUMO
The COVID-19 pandemic has had a profound impact on society; it changed the way we work, learn, socialise, and move throughout the world. In the United Kingdom, policies such as business closures, travel restrictions, and social distance mandates were implemented to slow the spread of COVID-19 and implemented and relaxed intermittently throughout the response period. While negative emotions and feelings such as distress and anxiety during this time of crisis were to be expected, we also see the signs of human resilience, including positive feelings like determination, pride, and strength. A longitudinal study using online survey tools was conducted to assess people's changing moods during the pandemic in the UK. The Positive and Negative Affect Schedule (PANAS) was used to measure self-reported feelings and emotions throughout six periods (phases) of the study from March 2020 to July 2021. A total of 4,222 respondents participated in the survey, while a sub-group participated in each of the six study phases (n = 167). The results were analysed using a cross-sectional study design for the full group across each study phase, while prospective cohort analysis was used to assess the subset of participants who voluntarily answered the survey in each of the six study phases (n = 167). Gender, age and employment status were found to be most significant to PANAS score, with older people, retirees, and women generally reporting more positive moods, while young people and unemployed people generally reported lower positive scores and higher negative scores, indicating more negative emotions. Additionally, it was found that people generally reported higher positive feelings in the summer of 2021, which may be related to the relaxation of COVID-19-related policies in the UK as well as the introduction of vaccines for the general population. This study is an important investigation into what allows for positivity during a crisis and gives insights into periods or groups that may be vulnerable to increased negative states of emotions and feelings.
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COVID-19 , Pandemias , Humanos , Feminino , Idoso , Adolescente , Estudos Longitudinais , COVID-19/epidemiologia , Estudos Transversais , Estudos Prospectivos , Emoções , AutorrelatoRESUMO
Mounting evidence supports the beneficial role of breastfeeding in lowering obesity risk, but the enduring impact of breastfeeding on longitudinal changes in body mass index (BMI) (i.e., BMI trajectories) remains unclear. This systematic review summarized evidence on how breastfeeding influenced the longitudinal trajectories of BMI later in life. Literature searches were conducted in Medline, Embase, Web of Science, and ScienceDirect to identify studies that assessed how breastfeeding (versus other feeding types or duration) was associated with longitudinal trajectories of BMI or BMI z-score. Three randomized controlled trials (RCTs) and 24 longitudinal cohort studies were included. Two-thirds (18/27) of studies were rated as acceptable or high quality. Most cohort studies (9/11) showed that children who continued to breastfeed at 3 to 12 mo of age had a lower BMI trajectory or lower odds of following a high BMI trajectory than those who were formula-fed or mixed-fed. The BMI differences between breastfeeding and other feeding groups were evident from age 7 mo and remained up to 8 y, and the magnitude of between-group BMI differences increased with age. For breastfeeding duration, 12 out of 15 cohort studies found that longer breastfeeding duration was associated with lower BMI trajectories up to age 18 y. Moreover, beneficial associations were observed for both exclusive and any breastfeeding with BMI trajectory. In contrast, mixed findings were reported from 3 RCTs that compared BMI trajectories from birth to ages 12 to 24 mo between breastfeeding promotion versus control or breastfeeding versus formula-feeding groups. The current review provides further longitudinal evidence from cohort studies that breastfeeding versus formula/mixed feeding or longer breastfeeding duration was associated with lower BMI trajectories. Such associations initiated in early childhood became more apparent with age and were sustained into early adulthood. The existing evidence substantiates the importance of breastfeeding promotion and continuation to support obesity prevention.
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Aleitamento Materno , Obesidade , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Adolescente , Índice de Massa Corporal , Obesidade/prevenção & controle , Estudos de Coortes , Estudos Longitudinais , Redução de PesoRESUMO
PURPOSE: Saudi women have been deprived of equal access to and opportunities for an active lifestyle due to sociocultural restrictions. Using the theory of planned behaviour, this elicitation study aimed to explore the salient beliefs of young Saudi women aged 18-35 regarding physical activity (PA). METHODS: A descriptive qualitative methodology was utilized using a semi-structured interview. A total of 25 transcribed interviews were coded. Content analysis was used to identify the salient beliefs and to rank-order the beliefs using an adaptation of Burnard's model. FINDINGS: Thirty-five salient beliefs were identified as dominant factors in the decision to engage in PA. The salient beliefs about PA are classified as positive (related to advantages, social approval, and enabling) and negative (related to disadvantages, social disapproval, and barriers). These included behavioural beliefs (concerning physical/psychological well-being and social opportunities), normative beliefs (concerning family, community, international and local media influencers' expectations), and control beliefs (concerning personal, social, natural, and built environment enablers as well as constraints). CONCLUSIONS: Due to the elicited beliefs, young women may be able to adopt more active lifestyles and change their inactive behaviour. Addressing negative beliefs can help change their inactive behaviour. Strengthening positive beliefs and facilitators is also beneficial.
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Exercício Físico , Estilo de Vida , Humanos , Feminino , Arábia Saudita , Comportamento Social , Comportamento Sedentário , Pesquisa QualitativaRESUMO
AIMS: To determine whether different gestational diabetes mellitus (GDM) subtypes are associated with distinct perinatal outcomes in twin pregnancies. MATERIALS: This retrospective cohort study enrolled women with twin pregnancies who gave birth at a tertiary hospital between January 2017 and December 2022. GDM was diagnosed by the IADPSG diagnostic criteria. Three subtypes of GDM were defined as only abnormal fasting glucose (OAFG) values, only abnormal post-load glucose (OAPG) values and abnormal combined fasting and post-load glucose (ACFPG) values. Logistic regression or generalized estimation equation models were used to test the correlation of subtypes of GDM and perinatal outcomes. RESULTS: GDM with OAPG had a slightly higher risk for preterm delivery (PTD) at <37 gestational weeks (aOR 1.22, 95 %CI 1.01-1.47) and neonatalintensivecareunit (NICU) admission (aOR 1.31, 95 %CI 1.09-1.57). GDM with ACFPG were associated with PTD at <37 gestational weeks (aOR 1.42, 95 %CI 1.06-1.89) and PTD at <34 gestational weeks (aOR 1.65, 95 % CI 1.14-2.39). GDM with OAFG had a lower risk of being small-for-gestational age (SGA) (aOR 0.48, 95 % CI 0.26-0.92). CONCLUSIONS: Different subtypes of GDM are associated with distinct perinatal outcomes. Only abnormal fasting glucose levels may be responsible for reduced the risk of SGA neonates.
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Diabetes Gestacional , Doenças do Recém-Nascido , Nascimento Prematuro , Gravidez , Recém-Nascido , Feminino , Humanos , Diabetes Gestacional/diagnóstico , Diabetes Gestacional/epidemiologia , Gravidez de Gêmeos , Estudos Retrospectivos , Nascimento Prematuro/epidemiologia , Nascimento Prematuro/etiologia , Glucose , Resultado da GravidezRESUMO
OBJECTIVE: Syncytiotrophoblasts form via mononuclear cytotrophoblast fusion during placentation and play a critical role in maternal-fetal communication. Impaired syncytialization inevitably leads to pregnancy-associated complications, including preeclampsia. Endoplasmic reticulum stress (ERS) is reportedly linked with preeclampsia, but little is known about its association with syncytialization. High temperature requirement factor A4 (HtrA4), a placental-specific protease, is responsible for protein quality control and placental syncytialization. This study aimed to investigate the relationship among HtrA4, ERS, and trophoblast syncytialization in the development of early-onset preeclampsia (EO-PE). METHODS: HtrA4 expression and ERS in preeclamptic placentas and control placentas were analyzed by Western blotting and qRT-PCR. HtrA4 and ERS localization in placentas was determined by immunohistochemistry and immunofluorescence. BeWo cells were used to stimulate the effects of HtrA4 and ERS on syncytialization. RESULTS: HtrA4 expression was upregulated in EO-PE and positively correlated with ERS. HtrA4 activity was increased in preeclampsia. Under normoxia, HtrA4 overexpression in BeWo cells did not alter the ERS level. In addition, treatment with hypoxia/reoxygenation (H/R) or an ERS inducer increased HtrA4 expression. HtrA4 upregulation suppressed the levels of syncytin-2 and ß-HCG in the presence of forskolin (FSK), and this change was exaggerated after ERS activation. In addition, treatment with an ERS inhibitor markedly suppressed FSK-treated cell fusion in a manner related to downregulation of HtrA4 expression. CONCLUSION: Our results suggest that ERS enables syncytialization of placental development by upregulating HtrA4, but that excessive HtrA4 expression and preexisting ERS impair syncytialization and cause EO-PE.
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Pré-Eclâmpsia , Trofoblastos , Humanos , Gravidez , Feminino , Trofoblastos/metabolismo , Placenta/metabolismo , Pré-Eclâmpsia/metabolismo , Regulação para Cima , Ativação Transcricional , Colforsina/metabolismo , Serina Proteases/genética , Serina Proteases/metabolismoRESUMO
BACKGROUND & AIMS: Exposure to a range of elements, air pollution, and specific dietary components in pregnancy has variously been associated with gestational diabetes mellitus (GDM) risk or infant neurodevelopmental problems. We measured a range of pregnancy exposures in maternal hair and/or infant cord serum and tested their relationship to GDM and infant neurodevelopment. METHODS: A total of 843 pregnant women (GDM = 224, Non-GDM = 619) were selected from the Complex Lipids in Mothers and Babies cohort study. Forty-eight elements in hair and cord serum were quantified using inductively coupled plasma-mass spectrometry analysis. Binary logistic regression was used to estimate the associations between hair element concentrations and GDM risk, while multiple linear regression was performed to analyze the relationship between hair/cord serum elements and air pollutants, diet exposures, and Bayley Scales of infant neurodevelopment at 12 months of age. RESULTS: After adjusting for maternal age, BMI, and primiparity, we observed that fourteen elements in maternal hair were associated with a significantly increased risk of GDM, particularly Ta (OR = 9.49, 95% CI: 6.71, 13.42), Re (OR = 5.21, 95% CI: 3.84, 7.07), and Se (OR = 5.37, 95% CI: 3.48, 8.28). In the adjusted linear regression model, three elements (Rb, Er, and Tm) in maternal hair and infant cord serum were negatively associated with Mental Development Index scores. For dietary exposures, elements were positively associated with noodles (Nb), sweetened beverages (Rb), poultry (Cs), oils and condiments (Ca), and other seafood (Gd). In addition, air pollutants PM2.5 (LUR) and PM10 were negatively associated with Ta and Re in maternal hair. CONCLUSIONS: Our findings highlight the potential influence of maternal element exposure on GDM risk and infant neurodevelopment. We identified links between levels of these elements in both maternal hair and infant cord serum related to air pollutants and dietary factors.
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Poluentes Atmosféricos , Poluição do Ar , Diabetes Gestacional , Gravidez , Lactente , Feminino , Humanos , Diabetes Gestacional/epidemiologia , Estudos de Coortes , Sangue Fetal/química , Poluição do Ar/efeitos adversos , Poluentes Atmosféricos/análise , Ingestão de AlimentosRESUMO
BACKGROUND: Fetal growth restriction (FGR) is a condition of poor growth of the fetus in utero. One of the causes of FGR is placental insufficiency. Severe early-onset FGR at < 32 weeks of gestation occurs in an estimated 0.4% of pregnancies. This extreme phenotype is associated with a high risk of fetal death, neonatal mortality, and neonatal morbidity. Currently, there is no causal treatment, and management is focused on indicated preterm birth to prevent fetal death. Interest has risen in interventions that aim to improve placental function by administration of pharmacological agents affecting the nitric oxide pathway causing vasodilatation. OBJECTIVES: The objective of this systematic review and aggregate data meta-analysis is to assess the beneficial and harmful effects of interventions affecting the nitric oxide pathway compared with placebo, no therapy, or different drugs affecting this pathway against each other, in pregnant women with severe early-onset FGR. SEARCH METHODS: We searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (16 July 2022), and reference lists of retrieved studies. SELECTION CRITERIA: We considered all randomised controlled comparisons of interventions affecting the nitric oxide pathway compared with placebo, no therapy, or another drug affecting this pathway in pregnant women with severe early-onset FGR of placental origin, for inclusion in this review. DATA COLLECTION AND ANALYSIS: We used standard Cochrane Pregnancy and Childbirth methods for data collection and analysis. MAIN RESULTS: We included a total of eight studies (679 women) in this review, all of which contributed to the data and analysis. The identified studies report on five different comparisons: sildenafil compared with placebo or no therapy, tadalafil compared with placebo or no therapy, L-arginine compared with placebo or no therapy, nitroglycerin compared with placebo or no therapy and sildenafil compared with nitroglycerin. The risk of bias of included studies was judged as low or unclear. In two studies the intervention was not blinded. The certainty of evidence for our primary outcomes was judged as moderate for the intervention sildenafil and low for tadalafil and nitroglycerine (due to low number of participants and low number of events). For the intervention L-arginine, our primary outcomes were not reported. Sildenafil citrate compared to placebo or no therapy (5 studies, 516 women) Five studies (Canada, Australia and New Zealand, the Netherlands, the UK and Brazil) involving 516 pregnant women with FGR were included. We assessed the certainty of the evidence as moderate. Compared with placebo or no therapy, sildenafil probably has little or no effect on all-cause mortality (risk ratio (RR) 1.01, 95% confidence interval (CI) 0.80 to 1.27, 5 studies, 516 women); may reduce fetal mortality (RR 0.82, 95% CI 0.60 to 1.12, 5 studies, 516 women), and increase neonatal mortality (RR 1.45, 95% CI 0.90 to 2.33, 5 studies, 397 women), although the results are uncertain for fetal and neonatal mortality as 95% confidence intervals are wide crossing the line of no effect. Tadalafil compared with placebo or no therapy (1 study, 87 women) One study (Japan) involving 87 pregnant women with FGR was included. We assessed the certainty of the evidence as low. Compared with placebo or no therapy, tadalafil may have little or no effect on all-cause mortality (risk ratio 0.20, 95% CI 0.02 to 1.60, one study, 87 women); fetal mortality (RR 0.11, 95% CI 0.01 to 1.96, one study, 87 women); and neonatal mortality (RR 0.89, 95% CI 0.06 to 13.70, one study, 83 women). L-Arginine compared with placebo or no therapy (1 study, 43 women) One study (France) involving 43 pregnant women with FGR was included. This study did not assess our primary outcomes. Nitroglycerin compared to placebo or no therapy (1 studies, 23 women) One study (Brazil) involving 23 pregnant women with FGR was included. We assessed the certainty of the evidence as low. The effect on the primary outcomes is not estimable due to no events in women participating in both groups. Sildenafil citrate compared to nitroglycerin (1 study, 23 women) One study (Brazil) involving 23 pregnant women with FGR was included. We assessed the certainty of the evidence as low. The effect on the primary outcomes is not estimable due to no events in women participating in both groups. AUTHORS' CONCLUSIONS: Interventions affecting the nitric oxide pathway probably do not seem to influence all-cause (fetal and neonatal) mortality in pregnant women carrying a baby with FGR, although more evidence is needed. The certainty of this evidence is moderate for sildenafil and low for tadalafil and nitroglycerin. For sildenafil a fair amount of data are available from randomised clinical trials, but with low numbers of participants. Therefore, the certainty of evidence is moderate. For the other interventions investigated in this review there are insufficient data, meaning we do not know whether these interventions improve perinatal and maternal outcomes in pregnant women with FGR.
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Retardo do Crescimento Fetal , Nascimento Prematuro , Recém-Nascido , Gravidez , Feminino , Humanos , Retardo do Crescimento Fetal/tratamento farmacológico , Citrato de Sildenafila , Óxido Nítrico/uso terapêutico , Nascimento Prematuro/prevenção & controle , Nitroglicerina , Tadalafila , Placenta , Morte FetalRESUMO
BACKGROUND: Grass pollen is considered a major outdoor aeroallergen source worldwide. It is proposed as a mechanism for thunderstorm asthma that lightning during thunderstorms promotes electrical rupture of pollen grains that leads to allergic airway inflammation. However, most evidence of associations between grass pollen and asthma comes from temperate regions. The objective of this study was to investigate short-term associations between airborne grass pollen exposure and asthma emergency department presentations in a subtropical population. METHODS: Episode level public hospital presentations for asthma (2016-2020) were extracted for greater Brisbane, Australia, from Queensland Health's Emergency Data Collection. Concentrations of airborne pollen were determined prospectively using a continuous flow volumetric impaction sampler. Daily time series analysis using a generalised additive mixed model were applied to determine associations between airborne grass pollen concentrations, and lightning count data, with asthma presentations. RESULTS: Airborne grass pollen showed an association with asthma presentations in Brisbane; a significant association was detected from same day exposure to three days lag. Grass pollen exposure increased daily asthma presentations up to 48.5% (95% CI: 12%, 85.9%) in female children. Lightning did not modify the effect of grass pollen on asthma presentations, however a positive association was detected between cloud-to-cloud lightning strikes and asthma presentations (P = 0.048). CONCLUSION: Airborne grass pollen exposure may exacerbate symptoms of asthma requiring urgent medical care of children and adults in a subtropical climate. This knowledge indicates an opportunity for targeted management of respiratory allergic disease to reduce patient and health system burden. For the first time, an influence of lightning on asthma was detected in this context. The outcomes support a need for continued pollen monitoring and surveillance of thunderstorm asthma risk in subtropical regions.
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Asma , Poaceae , Adulto , Criança , Feminino , Humanos , Pólen , Asma/epidemiologia , Asma/etiologia , Alérgenos/análise , Serviço Hospitalar de EmergênciaRESUMO
Preeclampsia is a pregnancy-specific complication that is associated with an increased postpartum risk of cardiovascular disease (CVD) in both women and their offspring, although the underlying mechanisms have yet to be fully elucidated. Nevertheless, differential methylation of cytosine-phosphate-guanosine islands and alterations in the expression of microRNA, associated with an elevated risk of CVD, have been observed in women and their children following preeclampsia. Among this specific population, genetic and epigenetic factors play crucial roles in the development of CVD in later life. A series of biomolecules involved in inflammation, oxidative stress, and angiogenesis may link pregnancy vascular bed disorders in preeclampsia to the pathogenesis of future CVD and thus could be valuable for the prediction and intervention of long-term CVD in women with a history of preeclampsia and their offspring. Here, we present insights into the cardiovascular structure and functional changes of women with a history of preeclampsia and their offspring. With a focus on various underlying mechanisms, the conclusions from this review are expected to provide more potential diagnostics and treatment strategies for clinical practice.
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Doenças Cardiovasculares , Sistema Cardiovascular , Pré-Eclâmpsia , Gravidez , Criança , Feminino , Humanos , Pré-Eclâmpsia/metabolismo , Mães , Doenças Cardiovasculares/etiologia , Período Pós-PartoRESUMO
BACKGROUND: Being born with intrauterine growth restriction (IUGR) was associated with subsequent health issues later in life. However, the underlying role of adipokines in IUGR is unknown. OBJECTIVES: To measure the adiponectin and leptin concentrations in the cord blood of monochorionic (MC) twins with selective IUGR (sIUGR) and evaluate their associations with childhood growth trajectories. METHODS: Cord blood samples were collected from 22 pairs of MC twins with sIUGR and 20 pairs of normal MC twins. Adiponectin and leptin concentrations in cord blood were determined by ELISA. Data regarding perinatal outcomes and infantile growth trajectories from birth to 24 months were obtained. RESULTS: Only cord blood adiponectin concentrations were associated with IUGR (ß -1.51, 95% CI -2.45, -0.57, p = 0.002), and cord blood leptin concentrations were significantly lower in sIUGR twins compared to normal twins (2.8 ± 1.6 vs. 6.4 ± 3.0, p < 0.001). Adiponectin concentrations were negatively associated with height increments from birth to 6 months (ß -0.28, 95% CI -0.51, -0.06, p = 0.015). Leptin concentrations were negatively associated with weight at 6 and 24 months (ß -0.12 95% CI -0.22, -0.02, p = 0.002; ß -0.18 95% CI -0.33, -0.03, p = 0.019) and weight and height increments from birth to 6 months (ß -0.17 95% CI -0.29, -0.06, p = 0.020; ß -0.40 95% CI -0.81, -0.01, p = 0.037). CONCLUSION: Cord blood adiponectin concentrations were negatively associated with IUGR but did not predict childhood growth. Cord blood leptin concentrations were inversely associated with weight and height increments in the first 6 months.
Assuntos
Adiponectina , Retardo do Crescimento Fetal , Criança , Feminino , Humanos , Gravidez , Peso ao Nascer , Sangue Fetal , Leptina , GêmeosRESUMO
OBJECTIVE: This study aimed to determine the predictors of Knowledge, Attitude and Practice (KAP) towards Family Planning (FP) among pregnant Fijian women. METHODS: A cross-sectional study was conducted over two months in 2019 with adult pregnant women attending the Antenatal Clinic (ANC) at Ba Mission Hospital (BMH), Fiji. Data was collected using a self-administrated questionnaire. Statistical analysis included correlation tests and regression analysis in determining predictors of KAP. RESULTS: 240 pregnant women participated in this study with a mean age of 26.02 (± SD = 4.13). The results showed a moderate level of knowledge (mean 14.95, SD ± 3.15), positive attitude (mean 20.56, SD ± 5.68), and good practice (mean 4.97, SD ± 1.73). Linear regression identified that women with more than seven children had a knowledge score of 3.65, lower than null parity (t value = -2.577, p = 0.011). Women aged 20 to 24 had a 6.47 lower attitude score than women aged 18 to 19 (t value = -2.142, p = 0.033). Women in defacto relationships had a 2.12 lower attitude score compared to the married category (t value = -2.128, p = 0.034). Fijian women of Indian descent had a 1.98 lower attitude score than the I Taukei women (t value = -2.639, p = 0.009). Women aged 30-34 had 2.41 lower practice scores than those aged 18-19 (t value = -2.462, p = 0.015). CONCLUSION: This study found a medium knowledge of FP among pregnant women. These findings support a recommendation for further research to implement effective strategies.
Assuntos
Serviços de Planejamento Familiar , Gestantes , Adulto , Criança , Feminino , Gravidez , Humanos , Fiji , Estudos Transversais , Conhecimentos, Atitudes e Prática em Saúde , ParidadeRESUMO
OBJECTIVE: To determine whether a combined myo-inositol, probiotics and micronutrient nutritional supplement impacts time-to-natural-conception and clinical pregnancy rates. DESIGN: Secondary outcomes of a double-blind randomized controlled trial. SETTING: Community recruitment. PATIENTS: Women aged 18 to 38 years planning to conceive in the United Kingdom, Singapore, and New Zealand, excluding those with diabetes mellitus or receiving fertility treatment. INTERVENTION: A standard (control) supplement (folic acid, iron, calcium, iodine, ß-carotene), compared with an intervention additionally containing myo-inositol, probiotics, and other micronutrients (vitamins B2, B6, B12, D, zinc). MAIN OUTCOME MEASURES: Number of days between randomization and estimated date of natural conception of a clinical pregnancy, as well as cumulative pregnancy rates at 3, 6, and 12 months. RESULTS: Of 1729 women randomized, 1437 (83%; intervention, n=736; control, n=701) provided data. Kaplan-Meier curves of conception were similar between intervention and control groups; the time at which 20% achieved natural conception was 90.5 days (95% confidence interval: 80.7, 103.5) in the intervention group compared with 92.0 days (76.0, 105.1) in the control group. Cox's proportional hazard ratios (HRs) comparing intervention against control for cumulative achievement of pregnancy (adjusted for site, ethnicity, age, body mass index, and gravidity) were similar at 3, 6, and 12 months. Among both study groups combined, overall time-to-conception lengthened with higher preconception body mass index, and was longer in non-White than in White women. Among women who were overweight the intervention shortened time-to-conception compared with control regardless of ethnicity (12-month HR=1.47 [1.07, 2.02], P=.016; 20% conceived by 84.5 vs. 117.0 days) and improved it to that comparable to nonoverweight/nonobese women (20% conceived by 82.1 days). In contrast, among women with obesity, time-to-conception was lengthened with intervention compared with control (12-month HR=0.69 [0.47, 1.00]; P=.053; 20% conceived by 132.7 vs. 108.5 days); an effect predominantly observed in non-White women with obesity. CONCLUSIONS: Time-to-natural-conception and clinical pregnancy rates within a year were overall similar in women receiving the intervention supplement compared with control. Overweight women had a longer time-to-conception but there was suggestion that the supplement may shorten their time-to-conception to that comparable to the nonoverweight/nonobese women. Further studies are required to confirm this. CLINICAL TRIAL REGISTRATION NUMBER: clinicaltrials.gov (NCT02509988).
Assuntos
Sobrepeso , Probióticos , Gravidez , Humanos , Feminino , Taxa de Gravidez , Suplementos Nutricionais , Inositol/uso terapêutico , Probióticos/uso terapêutico , Micronutrientes , Método Duplo-Cego , ObesidadeRESUMO
In light of rapidly expanding road networks worldwide, there is increasing global awareness of the growing amount of mammalian roadkill. However, the ways in which road mortality affects the population dynamics of different species remains largely unclear. We aimed to categorise the demographic parameters in mammalian populations around the world that are directly or indirectly affected by road mortality, as well as identify the most effective study designs for quantifying population-level consequences of road mortality. We conducted a comprehensive systematic review to synthesise literature published between 2000 and 2021 and out of 11,238 unique studies returned, 83 studies were retained comprising 69 mammalian species and 150 populations. A bias towards research-intensive countries and larger mammals was apparent. Although searches were conducted in five languages, all studies meeting the inclusion criteria were in English. Relatively few studies (13.3%) provided relevant demographic context to roadkill figures, hampering understanding of the impacts on population persistence. We categorised five direct demographic parameters affected by road mortality: sex- and age-biased mortality, the percentage of a population killed on roads per year (values up to 50% were reported), the contribution of roadkill to total mortality rates (up to 80%), and roadkill during inter-patch or long-distance movements. Female-biased mortality may be more prevalent than previously recognised and is likely to be critical to population dynamics. Roadkill was the greatest source of mortality for 28% of studied populations and both additive and compensatory mechanisms to roadkill were found to occur, bringing varied challenges to conservation around roads. In addition, intra-specific population differences in demographic effects of road mortality were common. This highlights that the relative importance of road mortality is likely to be context specific as the road configuration and habitat quality surrounding a population can vary. Road ecology studies that collect data on key life parameters, such as age/stage/sex-specific survival and dispersal success, and that use a combination of methods are critical in understanding long-term impacts. Quantifying the demographic impacts of road mortality is an important yet complex consideration for proactive road management.
Assuntos
Ecossistema , Mamíferos , Animais , Feminino , Dinâmica Populacional , EcologiaRESUMO
BACKGROUND: Despite being essentially genetically identical, monozygotic (MZ) twins can be discordant for congenital heart disease (CHD), thus highlighting the importance of in utero environmental factors for CHD pathogenesis. This study aimed to identify the epigenetic variations between discordant MZ twin pairs that are associated with CHD at birth. METHODS: Cord blood of CHD-discordant MZ twins from the Chongqing Longitudinal Twin Study Cohort was subjected to whole-genome bisulfite sequencing, then validated by MeDIP-qPCR and qRT-PCR. RESULTS: 379 DMRs mapped to 175 differentially methylated genes (DMGs) were associated with CHD. Functional enrichment analysis identified these DMGs are involved in histone methylation, actin cytoskeleton organization, the regulation of cell differentiation, and adrenergic signaling in cardiomyocytes. Of note, SPESP1 and NOX5 were hypermethylated in CHD, and associated with lower gene expression levels. CONCLUSIONS: Specific DNA methy (DNAm) variations in cord blood were associated with CHD, thus illustrating new biomarkers and potential interventional targets for CHD. TRIAL REGISTRATION: ChiCTR-OOC-16008203, registered on 1 April 2016 at the Chinese Clinical Trial Registry.