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1.
Horm Metab Res ; 54(2): 76-83, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35130568

RESUMO

The aim of the study was to evaluate the effects of thyroperoxidase antibody (TPOAb) and thyroglobulin antibody (TgAb) on maternal and neonatal adverse outcomes in pregnant women. A total of 296 singleton pregnant women were classified into four groups according to the thyroid auto-antibody in the first trimester. Finally, there were 97 women in TPOAb positive group (TPOAb+/TgAb-), 35 in TgAb positive group (TPOAb-/TgAb+), 85 in TPOAb and TgAb positive group (TPOAb+/TgAb+), and 79 in TPOAb and TgAb negative group (TPOAb-/TgAb-). Thyroid function, TPOAb, and TgAb were checked during pregnancy and followed up at 6 weeks, 3 months, 6 months, 9 months, and 12 months postpartum. Levothyroxine sodium tablets could be taken to maintain euthyroid antepartum. Thyroid function of women with postpartum thyroiditis (PPT) were followed up at 2 and 3 years postpartum. We observed the incidence of PPT, premature rupture of membranes (PROM), placental abruption, placenta previa, polyhydramnios, oligohydramnios, postpartum hemorrhage, preterm birth, and low birth Weight in the four groups. 19.93% of the women had PPT. The incidence of PPT in TPOAb+/TgAb-, TPOAb-/TgAb+, TPOAb+/TgAb+groups was significantly higher than that in TPOAb-/TgAb- group, respectively (16.49 vs. 6.33%, 22.86 vs. 6.33%, 35.29 vs. 6.33%, p <0.05). The incidence of PPT in TPOAb+/TgAb+group was significantly higher than that in TPOAb+/TgAb- group (35.29 vs. 16.49%, p <0.01). PPT occurred as early as 6 weeks postpartum, but mainly at 3 and 6 months postpartum in the four groups (62.50%, 75.00%, 70.00%, 80.00%). All PPT in TPOAb-/TgAb- group occurred within 6 months postpartum, while it was found at 9 months or 12 months postpartum in other three groups. There was no classical form of PPT in TPOAb-/TgAb- group, while in the other three groups, all three types (classical form, isolated thyrotoxicosis, isolated hypothyroidism) existed. At 2 years postpartum of the women with PPT, the rate of euthyroidism in TPOAb+/TgAb+group was significantly lower than that in TPOAb-/TgAb- group (p <0.05). At 3 years postpartum of the women with PPT, the rate of euthyroidism in TPOAb+/TgAb-, TPOAb-/TgAb+, and TPOAb+/TgAb+groups were significantly lower than that in TPOAb-/TgAb- group (p <0.05). The values of TPOAb and TgAb postpartum were significantly higher than those during pregnancy (p <0.05). The incidence of PROM in TPOAb+/TgAb- group was significantly higher than that in TPOAb-/TgAb- group (32.99 vs. 17.72%, p <0.05). The binary logistic regression for PPT showed that the OR value of TPOAb was 2.263 (95% CI 1.142-4.483, p=0.019). The OR value of TgAb was 3.112 (95% CI 1.700-5.697, p=0.000). In conclusion, pregnant women with positive thyroid auto-antibodies had an increased risk of PPT and a reduced rate of euthyroidism at 2 and 3 years postpartum. TPOAb is associated with the incidence of PROM. Both of TPOAb and TgAb were independent risk factors for PPT. TgAb deserves more attention when studying autoimmune thyroid disease (AITD) combined with pregnancy.


Assuntos
Hipotireoidismo , Nascimento Prematuro , Autoanticorpos , Feminino , Humanos , Hipotireoidismo/epidemiologia , Recém-Nascido , Iodeto Peroxidase , Placenta , Gravidez , Gestantes , Tireoglobulina
2.
BMC Pediatr ; 22(1): 547, 2022 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-36104673

RESUMO

BACKGROUND: Preterm birth is serious public health worldwide, and early prediction of preterm birth in pregnant women may provide assistance for timely intervention and reduction of preterm birth. This study aimed to develop a preterm birth prediction model that is readily available and convenient for clinical application. METHODS: Data used in this case-control study were extracted from the National Vital Statistics System (NVSS) database between 2018 and 2019. Univariate and multivariate logistic regression analyses were utilized to find factors associated with preterm birth. Odds ratio (OR) and 95% confidence interval (CI) were used as effect measures. The area under the curve (AUC), accuracy, sensitivity, and specificity were utilized as model performance evaluation metrics. RESULTS: Data from 3,006,989 pregnant women in 2019 and 3,039,922 pregnant women in 2018 were used for the model establishment and external validation, respectively. Of these 3,006,989 pregnant women, 324,700 (10.8%) had a preterm birth. Higher education level of pregnant women [bachelor (OR = 0.82; 95%CI, 0.81-0.84); master or above (OR = 0.82; 95%CI, 0.81-0.83)], pre-pregnancy overweight (OR = 0.96; 95%CI, 0.95-0.98) and obesity (OR = 0.94; 95%CI, 0.93-0.96), and prenatal care (OR = 0.48; 95%CI, 0.47-0.50) were associated with a reduced risk of preterm birth, while age ≥ 35 years (OR = 1.27; 95%CI, 1.26-1.29), black race (OR = 1.26; 95%CI, 1.23-1.29), pre-pregnancy underweight (OR = 1.26; 95%CI, 1.22-1.30), pregnancy smoking (OR = 1.27; 95%CI, 1.24-1.30), pre-pregnancy diabetes (OR = 2.08; 95%CI, 1.99-2.16), pre-pregnancy hypertension (OR = 2.22; 95%CI, 2.16-2.29), previous preterm birth (OR = 2.95; 95%CI, 2.88-3.01), and plurality (OR = 12.99; 95%CI, 12.73-13.24) were related to an increased risk of preterm birth. The AUC and accuracy of the prediction model in the testing set were 0.688 (95%CI, 0.686-0.689) and 0.762 (95%CI, 0.762-0.763), respectively. In addition, a nomogram based on information on pregnant women and their spouses was established to predict the risk of preterm birth in pregnant women. CONCLUSIONS: The nomogram for predicting the risk of preterm birth in pregnant women had a good performance and the relevant predictors are readily available clinically, which may provide a simple tool for the prediction of preterm birth.


Assuntos
Nascimento Prematuro , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Recém-Nascido , Razão de Chances , Gravidez , Nascimento Prematuro/epidemiologia , Nascimento Prematuro/etiologia , Fatores de Risco , Magreza/complicações , Estados Unidos/epidemiologia
3.
Lancet Glob Health ; 10(10): e1523-e1533, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36113535

RESUMO

BACKGROUND: After considerable debate, there is now unequivocal evidence that use of antenatal corticosteroids improves outcomes in preterm neonates when used in women at risk of early preterm birth in reasonably equipped hospitals in low-resource countries. We aimed to evaluate the cost-effectiveness of dexamethasone administration in the management of preterm birth in a cohort of pregnant women from five low-resource countries. METHODS: We performed a cost-effectiveness analysis using data from 2828 women (and 3051 babies) who participated in the WHO ACTION-I trial, a multicentre, randomised, placebo-controlled trial that assessed the safety and efficacy of dexamethasone in pregnant women at risk of early preterm birth in 29 hospitals across Bangladesh, India, Kenya, Nigeria, and Pakistan. We used a decision tree model to assess the cost-effectiveness of dexamethasone treatment compared with no intervention from a health-care sector perspective. Outcome data were taken from the primary results of the trial and primary data on cost were collected in 28 hospitals. The primary cost-effectiveness outcome was cost per neonatal death or the cost per disability-adjusted life-years (DALYs) averted, or costs saved per 1000 woman-baby units if the intervention was found to be cost-saving. FINDINGS: Administration of dexamethasone averted 38 neonatal deaths per 1000 woman-baby units and 1132 DALYs per 1000 woman-baby units. Compared with no intervention, use of antenatal corticosteroids was cost-saving in all five countries, ranging from a saving of US$1778 per 1000 woman-baby units (95% uncertainty interval [UI] -13 878 to 9483) in Nigeria, to $20 531 per 1000 woman-baby units (-46 387 to 4897) in Pakistan, to $36 870 per 1000 woman-baby units (-61 569 to -15 672) in Bangladesh, to $38 303 per 1000 woman-baby units (-64 183 to -10 753) in India, and to $53 681 per 1000 woman-baby units (-113 822 to 2394) in Kenya. Findings remained consistent following sensitivity analyses. In all five countries, dexamethasone was more effective and cost less compared with no treatment. INTERPRETATION: Antenatal dexamethasone for early preterm birth was cost-saving when used in hospitals in low-resource countries. Decision makers in low-resource settings can be confident that use of antenatal dexamethasone for early preterm birth is cost-effective, and often cost-saving when used in reasonably equipped hospitals in low-resource countries. FUNDING: Bill & Melinda Gates Foundation and WHO.


Assuntos
Morte Perinatal , Nascimento Prematuro , Corticosteroides , Análise Custo-Benefício , Dexametasona/uso terapêutico , Feminino , Humanos , Lactente , Recém-Nascido , Gravidez , Nascimento Prematuro/prevenção & controle , Cuidado Pré-Natal/métodos , Organização Mundial da Saúde
4.
Clinics (Sao Paulo) ; 77: 100079, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36087567

RESUMO

Preterm birth is the leading cause of infant mortality. The mechanisms that instigate preterm birth remain elusive and this makes it difficult to predict or prevent preterm birth. In this study, the authors found that SP-A induced pathological damage to the placenta and promoted preterm birth. Through mechanism, SP-A promoted the expression of STOX1 which further promoted the oxidative stress in the placenta by inhibiting the activities of a series of antioxidant enzymes including SOD, CAT and GSH-Px. SP-A also induced dysregulation of arginine metabolism by inhibiting NOS2 and ARG2. Overexpression of STOX1 aggravated SP-A induced oxidative stress, pathological damage, and preterm birth, whereas knockdown of STOX1 alleviated SP-A induced oxidative stress, pathological damage and preterm birth. The present study uncovers that SP-A induces preterm birth by promoting oxidative stress via upregulating STOX1, which provides new targets for the prediction and prevention of preterm birth.


Assuntos
Nascimento Prematuro , Antioxidantes/metabolismo , Proteínas de Transporte/metabolismo , Feminino , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Estresse Oxidativo/fisiologia , Gravidez , Tensoativos
5.
J Infect Dev Ctries ; 16(8): 1243-1251, 2022 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-36099366

RESUMO

INTRODUCTION: Vulvovaginal candidiasis (VVC) is a yeast infection of the vulva, which is caused by Candida species and affects women worldwide. Pregnant women are more vulnerable to VVC due to certain risks. Moreover, their offspring are also exposed to the risk of preterm birth. In this context, ascertaining the burden of VVC is of paramount importance and this meta-analysis was conducted to estimate the occurrence of VVC among pregnant women in Africa. METHODOLOGY: Database search was carried out through PubMed, Scopus, Science-Direct, and Google Scholar from the date of inception until December 2020. All the studies on the prevalence of VVC among African pregnant women were included in the analysis. The pooled prevalence was estimated based on the Random-effect model DerSimonian-Laird approach with Freeman- Tukey double arcsine transformed proportion. Heterogeneity was assessed using I2 test and subsequently explored using subgroup and meta-regression analysis. RESULTS: A total of Sixteen records having a sample size 4,185 were included in this study. The overall prevalence of VVC was pooled at 29.2% (CI 95%: 23.4 - 33.0). Subgroup analysis revealed a higher prevalence in Eastern Africa, followed by Western Africa and North Africa (35%, 28%, and 15% respectively). Moderator analysis indicated that the studies that used advanced methods of detection had a higher prevalence (p = 0.048). In addition, the large sample size was associated with higher prevalence (p ≤ 0.001). No other moderators were found to be statistically significant. CONCLUSIONS: The overall prevalence of VVC among African pregnant women is comparable to other studies worldwide. However, appropriate identification techniques and larger sample size could likely be associated with an increased prevalence. Our findings necessitate the need for further investigations to determine the geographical distribution of VVC across African regions.


Assuntos
Candidíase Vulvovaginal , Nascimento Prematuro , África/epidemiologia , Candidíase Vulvovaginal/epidemiologia , Feminino , Humanos , Recém-Nascido , Gravidez , Gestantes , Prevalência
6.
J Infect Dev Ctries ; 16(8): 1372-1375, 2022 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-36099384

RESUMO

Tuberculosis remains a serious health problem in pregnant women. Tuberculosis during pregnancy is related to poor perinatal outcomes, including low birth weight, insufficient growth relative to gestational age, perinatal mortality, and maternal morbidity and mortality. Additionally, diabetes mellitus in pregnant women with tuberculosis is associated with a higher risk of maternal and fetal complications such as preeclampsia, preterm birth, hypoglycemia, and giant baby. We report two perinatal outcomes of (1) pregnancy during tuberculosis treatment and (2) tuberculosis in a pregnant woman with diabetes mellitus. Both women completed anti-tuberculosis treatments. This report emphasizes the importance of health promotion through family planning among women with tuberculosis. This case report also underscores the increased risk of developing tuberculosis in pregnant women with diabetes mellitus. Early diagnosis of tuberculosis in pregnant women is vital as it affects the health of both mother and child.


Assuntos
Nascimento Prematuro , Tuberculose Pulmonar , Tuberculose , Feminino , Promoção da Saúde , Humanos , Indonésia/epidemiologia , Lactente , Recém-Nascido , Gravidez , Resultado da Gravidez , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose Pulmonar/epidemiologia
7.
Clin Perinatol ; 49(3): 641-655, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36113927

RESUMO

According to the World Health Organization (WHO), 15 million babies are born preterm each year. Preterm infants are those born at less than 37 weeks, while extremely and very preterm neonates include those born at 22 to less than 32 weeks gestational age. Infants that fail to make it to term are missing a key part in neurodevelopment, as weeks 24 to 40 are a critical period of brain development. Neonatal brain injury is a crucial predictor for mortality and morbidity in premature and low birth weight (<1500 g) infants. Although the complications associated with preterm birth continue to be the number one cause of death in children under 5, the survival rates are increasing (Volpe, 2019). Despite this, the incidence of comorbidities, such as learning disabilities and visual and hearing problems, is still high. The functional deficits seen in these infants can be contributed to the white matter abnormalities (WMA) that have been found in 50% to 80% of extremely and very preterm neonates. While numerous, the etiology of the neonatal brain injury is essential for determining the mortality and morbidities of the infant, as there is an increased risk for both intraventricular hemorrhage (IVH) and periventricular leukomalacia (PVL), which can be attributed to their lack of cerebrovascular autoregulation and hypoxic events. Neuroimaging plays a key role in detecting and assessing these neurologic injuries that preterm infants are at risk for. It is essential to diagnose these events early on to assess neurologic damage, minimize disease progression, and provide supportive care. Brain MRI and cranial ultrasound (CUS) are both extensively used neuroimaging techniques to assess WMA, and it has become ever more important to determine the best imaging techniques and modalities with the increasing survival rates and high incidence of comorbidities among these infants.


Assuntos
Lesões Encefálicas , Doenças do Prematuro , Nascimento Prematuro , Criança , Feminino , Humanos , Lactente , Recém-Nascido de Baixo Peso , Recém-Nascido , Recém-Nascido Prematuro , Doenças do Prematuro/diagnóstico por imagem , Doenças do Prematuro/epidemiologia
8.
Int J Hyg Environ Health ; 245: 114029, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-36049361

RESUMO

Epidemiologic evidence on acute heat and cold stress and preterm birth (PTB) is inconsistent and based on ambient temperature rather than a thermophysiological index. The aim of this study was to use a spatiotemporal thermophysiological index (Universal Thermal Climate Index, UTCI) to investigate prenatal acute heat and cold stress exposures and spontaneous PTB. We conducted a space-time-stratified case-crossover analysis of 15,576 singleton live births with spontaneous PTB between January 1, 2000 and December 31, 2015 in Western Australia. The association between UTCI and spontaneous PTB was examined with distributed lag nonlinear models and conditional quasi-Poisson regression. Relative to the median UTCI, there was negligible evidence for associations at the lower range of exposures (1st to 25th percentiles). We found positive associations in the 95th and 99th percentiles, which increased with increasing days of heat stress in the first week of delivery. The relative risk (RR) and 95% confidence interval (CI) for the immediate (delivery day) and cumulative short-term (up to six preceding days) exposures to heat stress (99th percentile, 31.2 °C) relative to no thermal stress (median UTCI, 13.8 °C) were 1.01 (95% CI: 1.01, 1.02) and 1.05 (95% CI: 1.04, 1.06), respectively. Elevated effect estimates for heat stress were observed for the transition season, the year 2005-2009, male infants, women who smoked, unmarried, ≤ 19 years old, non-Caucasians, and high socioeconomic status. Effect estimates for cold stress (1st percentile, 0.7 °C) were highest in the transition season, during 2005-2009, and for married, non-Caucasian, and high socioeconomic status women. Acute heat stress was associated with an elevated risk of spontaneous PTB with sociodemographic vulnerability. Cold stress was associated with risk in a few vulnerable subgroups. Awareness and mitigation strategies such as hydration, reducing outdoor activities, affordable heating and cooling systems, and climate change governance may be beneficial. Further studies with the UTCI are required.


Assuntos
Transtornos de Estresse por Calor , Nascimento Prematuro , Adulto , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Gravidez , Nascimento Prematuro/epidemiologia , Risco , Estações do Ano , Austrália Ocidental/epidemiologia , Adulto Jovem
9.
Front Cell Infect Microbiol ; 12: 945851, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36061856

RESUMO

Background: The brain development of preterm infants is easily affected by various adverse extrauterine factors and complications, resulting in abnormal neurological and cognitive development. Recent studies have found that there is a significant correlation between intestinal microbial changes and cognitive behavior. Nevertheless, the correlation between the cognitive impairment and abnormal changes of intestinal microflora in the preterm newborn has been rarely elucidated. Aim: To analyze the differences of fecal intestinal flora, short chain fatty acids (SCFAs) and microbiota-gut-brain axis (MGBA)-related serum factors between preterm birth with and without cognitive impairment. Methods: Healthy female rats (body weight 410 ± 40 g) of 16-17 days of gestation were selected for the establishment of preterm cognitive impairment model and screened by Morris water maze navigation experiments. The pathological change of rat hippocampus was confirmed by HE staining. The abundance of fecal intestinal microflora was determined by 16sRNA sequencing, while the contents of fecal SCFAs were examined by gas chromatography. Results: Compared with the control group, the cognitive impairment group had decreased abundance and diversity of intestinal microflora and increased abundance of Proteobacteria at the level of phylum. While the abundances of Alistipes, Bacteroides, Prevotella, and Lactobacillus decreased significantly at the level of order, family, and genus, the abundances of Staphylococcaceae, Enterococci, Psychrobacter, and Oligella increased significantly. Moreover, the levels of total SCFAs and acetic acid in the disease group were significantly lower. The fecal abundance of acetic acid was positively correlated with that of Lactobacillaceae or Peptostreptococcaceae, and negatively correlated with that of Aerococcaceae, and Alcaligenaceae in disease rats. Furthermore, cognitive impairment caused significantly decreased levels of 5-HT, GABA, and BDNF, and increased levels of GR, CRH, IL-6, and TNF-α in rat blood. Conclusion: Alterations in intestinal microflora structure and the abundances of SCFAs contributed substantially to the cognitive impairment in preterm rats, which was associated with significant changes in MGBA-related soluble factors.


Assuntos
Disfunção Cognitiva , Microbioma Gastrointestinal , Nascimento Prematuro , Animais , Ácidos Graxos Voláteis , Feminino , Microbioma Gastrointestinal/genética , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Ratos
10.
Front Immunol ; 13: 971005, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36059524

RESUMO

Background: Thrombocytopenia is a common manifestation of antiphospholipid syndrome (APS), and is a main concern for bleeding on the standard treatment of low dose aspirin (LDA) and low molecular weight heparin (LMWH) in obstetric APS (OAPS). Objective: This study assesses the possible relationship between thrombocytopenia during the first trimester and adverse pregnancy outcomes (APOs) in OAPS patients. Methods: A case-control study was conducted at Peking University People's Hospital, Beijing, China. The clinical, immunologic, and pregnancy outcomes of the OAPS patients were collected. Univariate and multivariate logistic regression analyses were applied to assess the relationship between APOs and thrombocytopenia in the first trimester. Results: A total of 115 participants were included in the analysis. There were no difference on antepartum and postpartum hemorrhage between the two groups. The gestational age in the thrombocytopenia group was less than that in the control group (34.12 ± 8.44 vs. 37.44 ± 3.81 weeks, p = 0.002). Hypocomplementemia, double aPL positive, and high titers of anti-ß2 glycoprotein I were more frequent in APS patients with thrombocytopenia (p < 0.05). Compared to the control group, thrombocytopenia in the first trimester was correlated with SGA (12.12% vs. 31.25%, p = 0.043), premature birth <37 weeks (16.16% vs 43.75%, p = 0.010) and intrauterine fetal death (2.02% vs 12.50%, p = 0.033). Thrombocytopenia in first-trimester independently increased the risk of preterm birth <37 weeks (OR = 5.40, 95% CI: 1.35-21.53, p = 0.02) after adjusting for demographic and laboratory factors. After adding medication adjustments, these factors above become insignificant (p > 0.05). Of note, the number of platelets increased after delivery in 14 thrombocytopenia patients with live fetuses (p = 0.03). Conclusion: This study demonstrates that thrombocytopenia in the first trimester increases the risks of preterm birth in women with APS. The effective OAPS treatments may improve pregnancy outcomes and not increase the risk of antepartum and postpartum hemorrhage.


Assuntos
Síndrome Antifosfolipídica , Hemorragia Pós-Parto , Nascimento Prematuro , Trombocitopenia , Anticorpos Antifosfolipídeos , Síndrome Antifosfolipídica/complicações , Síndrome Antifosfolipídica/diagnóstico , Síndrome Antifosfolipídica/tratamento farmacológico , Estudos de Casos e Controles , Feminino , Heparina de Baixo Peso Molecular/uso terapêutico , Humanos , Recém-Nascido , Gravidez , Resultado da Gravidez , Primeiro Trimestre da Gravidez , Nascimento Prematuro/epidemiologia , Trombocitopenia/tratamento farmacológico , Trombocitopenia/epidemiologia , Trombocitopenia/etiologia
11.
Clin Transl Med ; 12(9): e1023, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36103557

RESUMO

BACKGROUND: Intrauterine infection and inflammation caused by microbial transfer from the vagina are believed to be important factors causing spontaneous preterm delivery (PTD). Multiple studies have examined the relationship between the cervicovaginal microbiome and spontaneous PTD with divergent results. Most studies have applied a DNA-based assessment, providing information on the microbial composition but not transcriptional activity. A transcriptomic approach was applied to investigate differences in the active vaginal microbiome and human transcriptome at midgestation between women delivering spontaneously preterm versus those delivering at term. METHODS: Vaginal swabs were collected in women with a singleton pregnancy at 18 + 0 to 20 + 6 gestational weeks. For each case of spontaneous PTD (delivery <37 + 0 weeks) two term controls were randomized (39 + 0 to 40 + 6 weeks). Vaginal specimens were subject to sequencing of both human and microbial RNA. Microbial reads were taxonomically classified using Kraken2 and RefSeq as a reference. Statistical analyses were performed using DESeq2. GSEA and HUMAnN3 were used for pathway analyses. RESULTS: We found 17 human genes to be differentially expressed (false discovery rate, FDR < 0.05) in the preterm group (n = 48) compared to the term group (n = 96). Gene expression of kallikrein-2 (KLK2), KLK3 and four isoforms of metallothioneins 1 (MT1s) was higher in the preterm group (FDR < 0.05). We found 11 individual bacterial species to be differentially expressed (FDR < 0.05), most with a low occurrence. No statistically significant differences in bacterial load, diversity or microbial community state types were found between the groups. CONCLUSIONS: In our mainly white population, primarily bacterial species of low occurrence were differentially expressed at midgestation in women who delivered preterm versus at term. However, the expression of specific human transcripts including KLK2, KLK3 and several isoforms of MT1s was higher in preterm cases. This is of interest, because these genes may be involved in critical inflammatory pathways associated with spontaneous PTD.


Assuntos
Líquidos Corporais , Nascimento Prematuro , Bactérias , Secreções Corporais , Feminino , Humanos , Recém-Nascido , Gravidez , Nascimento Prematuro/epidemiologia , Nascimento Prematuro/genética , Transcriptoma/genética , Vagina/microbiologia
12.
J Clin Pharmacol ; 62 Suppl 1: S79-S93, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36106783

RESUMO

Preterm birth (PTB; defined as delivery before 37 weeks of pregnancy) is the leading cause of morbidity and mortality in infants and children aged <5 years, conferring potentially devastating short- and long-term complications. Despite extensive research in the field, there is currently a paucity of medications available for PTB prevention and treatment. Over the past few decades, inflammation in gestational tissues has emerged at the forefront of PTB pathophysiology. Even in the absence of infection, inflammation alone can prematurely activate the main components of parturition resulting in uterine contractions, cervical ripening and dilatation, membrane rupture, and subsequent PTB. Mechanistic studies have identified critical elements of the complex inflammatory molecular pathways involved in PTB. Here, we discuss therapeutic options that target such key mediators with an aim to prevent, postpone, or treat PTB. We provide an overview of more traditional therapies that are currently used or being tested in humans, and we highlight recent advances in preclinical studies introducing novel approaches with therapeutic potential. We conclude that urgent collaborative action is required to address the unmet need of developing effective strategies to tackle the challenge of PTB and its complications.


Assuntos
Nascimento Prematuro , Criança , Feminino , Humanos , Recém-Nascido , Inflamação/tratamento farmacológico , Gravidez , Nascimento Prematuro/metabolismo , Nascimento Prematuro/prevenção & controle
13.
Sci Rep ; 12(1): 15345, 2022 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-36097276

RESUMO

We aimed to evaluate the changes in maternal and neonatal complications such as threatened preterm labor (TPL) and preterm birth before and during the coronavirus disease 2019 (COVID-19) pandemic using large-scale real-world data in Japan. We obtained data from the Japan Medical Data Center claims database and evaluated differences in maternal and neonatal complications, such as the prevalence of TPL and preterm birth before the COVID-19 pandemic (in the year 2018 or 2019) and during the COVID-19 pandemic (in 2020). We included 5533, 6257, and 5956 deliveries in the years 2018, 2019, and 2020, respectively. TPL prevalence and preterm birth had significantly decreased in 2020 (41.3%, 2.6%, respectively) compared with those reported in 2018 (45.3%, 3.9%, respectively) and 2019 (44.5%, 3.8%, respectively). Neonatal outcomes such as low-birth-weight infants and retinopathy of prematurity were also improved during the pandemic. There were no clear trends in the prevalence of maternal complications such as hypertensive disorders of pregnancy; hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome; and preeclampsia. Oral ritodrine hydrochloride usage in all participants had significantly decreased during the COVID-19 pandemic. In conclusion, our results suggest that the COVID-19 pandemic has ameliorated TPL and consequently reduced the number of preterm births.


Assuntos
COVID-19 , Trabalho de Parto Prematuro , Nascimento Prematuro , COVID-19/epidemiologia , Feminino , Humanos , Lactente , Recém-Nascido , Japão/epidemiologia , Trabalho de Parto Prematuro/epidemiologia , Pandemias/prevenção & controle , Gravidez , Nascimento Prematuro/epidemiologia , Nascimento Prematuro/prevenção & controle , Prevalência
14.
Sci Signal ; 15(751): eabi5453, 2022 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-36099339

RESUMO

The premature rupture of the amniotic sac, a condition referred to as a preterm prelabor rupture of membranes (pPROM), is a leading cause of preterm birth. In some cases, these ruptured membranes heal spontaneously. Here, we investigated repair mechanisms of the amnion, a layer of epithelial cells in the amniotic sac closest to the embryo. Macrophages migrated to and resided at rupture sites in both human and mouse amnion. A process called epithelial-mesenchymal transition (EMT), in which epithelial cells acquire a mesenchymal phenotype and which is implicated in tissue repair, was observed at rupture sites. In dams bearing macrophage-depleted fetuses, the repair of amnion ruptures was compromised, and EMT was rarely detected at rupture sites. The migration of cultured amnion epithelial cells in wound healing assays was mediated by EMT through transforming growth factor-ß (TGF-ß)-Smad signaling. These findings suggest that fetal macrophages are crucial in amnion repair because of their ability to induce EMT in amnion epithelial cells.


Assuntos
Ruptura Prematura de Membranas Fetais , Nascimento Prematuro , Âmnio , Animais , Transição Epitelial-Mesenquimal , Feminino , Feto , Humanos , Recém-Nascido , Macrófagos , Camundongos
15.
Front Immunol ; 13: 879487, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36072601

RESUMO

Background: Preterm birth (PTB) is a multifactorial syndrome that seriously threatens the health of pregnant women and babies worldwide. Recently, circular RNAs (circRNAs) have been understood as important regulators of various physiological and pathological processes. However, the expression pattern and potential roles of circRNAs in PTB are largely unclear. Methods: In this study, we extracted and analyzed the circRNA expression profiles in maternal and fetal samples of preterm and term pregnancies, including maternal plasma, maternal monocytes, myometrium, chorion, placenta, and cord blood. We identified the circRNAs which is associated with PTB in different tissues and explored their relationships from the perspective of the overall maternal-fetal system. Furthermore, co-expression analysis of circRNAs and mRNAs, target microRNAs (miRNAs), and RNA-binding proteins (RBPs), provided new clues about possible mechanisms of circRNA function in PTB. In the end, we investigated the potential special biofunctions of circRNAs in different tissues and their common features and communication in PTB. Results: Significant differences in circRNA types and expression levels between preterm and term groups have been proved, as well as between tissues. Nevertheless, there were still some PTB-related differentially expressed circRNAs (DECs) shared by these tissues. The functional enrichment analysis showed that the DECs putatively have important tissue-specific biofunctions through their target miRNA and co-expressed mRNAs, which contribute to the signature pathologic changes of each tissue within the maternal-fetal system in PTB (e.g., the contraction of the myometrium). Moreover, DECs in different tissues might have some common biological activities, which are mainly the activation of immune-inflammatory processes (e.g., interleukin1/6/8/17, chemokine, TLRs, and complement). Conclusions: In summary, our data provide a preliminary blueprint for the expression and possible roles of circRNAs in PTB, which lays the foundation for future research on the mechanisms of circRNAs in PTB.


Assuntos
MicroRNAs , Nascimento Prematuro , Feminino , Perfilação da Expressão Gênica , Humanos , Recém-Nascido , MicroRNAs/genética , MicroRNAs/metabolismo , Gravidez , Nascimento Prematuro/genética , RNA Circular/genética , RNA Mensageiro/genética
16.
PLoS One ; 17(9): e0272444, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36048848

RESUMO

BACKGROUND: Globally, complications due to preterm birth are the leading contributor to neonatal mortality, resulting in an estimated one million deaths annually. Kangaroo Mother Care (KMC) has been endorsed by the World Health Organisation as a low cost, safe, and effective intervention in reducing morbidity and mortality among preterm infants. The objective of this study was to describe the implementation of a KMC model among preterm infants and its impact on neonatal outcomes at a tertiary level hospital in Lusaka, Zambia. METHODS: We conducted a prospective descriptive study using data collected from the KMC room at the University Teaching Hospital between January 2016 and September 2017. Mothers and government nurses were trained in KMC. We monitored skin-to-skin and breastfeeding practices, weight at admission, discharge, and length of admission. RESULTS: We enrolled 573 neonates into the study. Thirteen extremely low weight infants admitted to the KMC room had graduated to Group A (1,000g-1,499g) at discharge, with a median weight gain of 500g. Of the 419 very low weight neonates at admission, 290 remained in Group A while 129 improved to Group B (1,500g-2,499g), with a median weight gain of 280g. Among the 89 low weight neonates, 1 regressed to Group A, 77 remained in Group B, and 11 improved to Group C (≥2,500g), individually gaining a median of 100g. Of the seven normal weight neonates, 6 remained in Group C individually gaining a median of 100g, and 1 regressed to Group B. Among all infants enrolled, two (0.35%) died in the KMC room. CONCLUSIONS: Based on the RE-AIM metrics, our results show that KMC is a feasible intervention that can improve neonatal outcomes among preterm infants in Zambia. The study findings show a promising, practical approach to scaling up KMC in Zambia. TRIAL REGISTRATION: The trial is registered under ClinicalTrials.gov under the following ID number: NCT03923023.


Assuntos
Método Canguru , Nascimento Prematuro , Feminino , Hospitais , Humanos , Recém-Nascido de Baixo Peso , Recém-Nascido , Recém-Nascido Prematuro , Método Canguru/métodos , Aumento de Peso , Zâmbia/epidemiologia
17.
Health Qual Life Outcomes ; 20(1): 136, 2022 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-36104723

RESUMO

BACKGROUND: Preterm birth with very low birth weight (VLBW, birth weight < 1500 g) is associated with health problems later in life. How VLBW individuals perceive their physical and mental health-related quality of life (HRQoL) is important to understand their putative burden of disease. Previous studies have shown mixed results, and longitudinal studies into adulthood have been requested. This study aimed to investigate differences in HRQoL between preterm VLBW and term born individuals at 32 years of age, and to study changes in HRQoL from 20 to 32 years. METHODS: In a geographically based longitudinal study, 45 VLBW and 68 term born control participants completed the Short Form 36 Health Survey (SF-36) at 32 years of age. Data from three previous timepoints was also available (20, 23 and 28 years of age). The SF-36 yields eight domain scores as well as a physical and a mental component summary. Between-group differences in these variables were investigated. We also performed subgroup analyses excluding individuals with disabilities, i.e., cerebral palsy and/or low estimated intelligence quotient. RESULTS: At 32 years of age, the physical component summary was 5.1 points lower (95% confidence interval (CI): 8.6 to 1.6), and the mental component summary 4.1 points lower (95% CI: 8.4 to - 0.3) in the VLBW group compared with the control group. For both physical and mental component summaries there was an overall decline in HRQoL from 20 to 32 years of age in the VLBW group. When we excluded individuals with disabilities (n = 10), group differences in domain scores at 32 years were reduced, but physical functioning, bodily pain, general health, and role-emotional scores remained lower in the VLBW subgroup without disabilities compared with the control group. CONCLUSION: We found that VLBW individuals reported lower HRQoL than term born controls at 32 years of age, and that HRQoL declined in the VLBW group from 20 to 32 years of age. This was in part, but not exclusively explained by VLBW individuals with disabilities.


Assuntos
Pessoas com Deficiência , Nascimento Prematuro , Adulto , Pessoas com Deficiência/psicologia , Feminino , Humanos , Recém-Nascido , Recém-Nascido de muito Baixo Peso/psicologia , Estudos Longitudinais , Qualidade de Vida/psicologia
18.
Int Breastfeed J ; 17(1): 69, 2022 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-36104819

RESUMO

BACKGROUND: Patient and Public Involvement (PPI) is a rich and valuable part of the process of planning, designing, carrying out and disseminating research. It is important to communicate PPI findings in detail so that the contributions of those involved are fully utilised and disseminated. The extended and iterative PPI process used within a neonatal randomised controlled trial related to the expression of breastmilk after very preterm birth is reported here. METHODS: Seven iterative stages of PPI were used. Stage 1 was informal PPI using historical interaction with parents and publicly available resources. Stage 2 was an online questionnaire open to parents of premature babies and advertised via a charity collaborator. Stage 3 was partnership with a charity collaborator. Stage 4 was a set of online panels focusing on study design and documents. Stage 5 was an interactive exercise to modify the trial intervention. Stage 6 is the presence of PPI contributors on the trial steering committee. Stage 7 is a dissemination panel. At each stage attention was paid to the diversity of participants involved, with strategies to increase the involvement of parents from under-reached groups. RESULTS: Six hundred and seventy-five participants responded at Stage 2, six parents were involved at Stage 4 and 12 parents at Stage 5. PPI contributed to the choice of study question, outcomes and produced a set of questions for future research. PPI impacted on the study design, with specific emphasis on reducing participant distress related to lactation, and reducing the burden of being involved in research at a time of significant stress. CONCLUSIONS: PPI had a far-reaching influence on this neonatal randomised controlled trial during the planning and design phase, which reinforces the importance of PPI at the earliest stages of the research cycle. The online questionnaire format elicited an unexpectedly deep and broad pool of transferable insights, which will have an impact on future research focus and design in the area of lactation and prematurity. Approaches to increasing PPI involvement from under-reached populations are important and can be successful despite resource constraints.


Assuntos
Neonatologia , Nascimento Prematuro , Aleitamento Materno , Feminino , Humanos , Lactente , Recém-Nascido , Lactação , Pais
19.
BMJ Paediatr Open ; 6(1)2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-36053580

RESUMO

INTRODUCTION: The WHO Nutrition Target aims to reduce the global prevalence of low birth weight by 30% by the year 2025. The Enhancing Nutrition and Antenatal Infection Treatment (ENAT) study will test the impact of packages of pregnancy interventions to enhance maternal nutrition and infection management on birth outcomes in rural Ethiopia. METHODS AND ANALYSIS: ENAT is a pragmatic, open-label, 2×2 factorial, randomised clinical effectiveness study implemented in 12 rural health centres in Amhara, Ethiopia. Eligible pregnant women presenting at antenatal care (ANC) visits at <24 weeks gestation are enrolled (n=2400). ANC quality is strengthened across all centres. Health centres are randomised to receive an enhanced nutrition package (ENP) or standard nutrition care, and within each health centre, individual women are randomised to receive an enhanced infection management package (EIMP) or standard infection care. At ENP centres, women receive a regular supply of adequately iodised salt and iron-folate (IFA), enhanced nutrition counselling and those with mid-upper arm circumference of <23 cm receive a micronutrient fortified balanced energy protein supplement (corn soya blend) until delivery. In standard nutrition centres, women receive routine counselling and IFA. EIMP women have additional screening/treatment for urinary and sexual/reproductive tract infections and intensive deworming. Non-EIMP women are managed syndromically per Ministry of Health Guidelines. Participants are followed until 1-month post partum, and a subset until 6 months. The primary study outcomes are newborn weight and length measured at <72 hours of age. Secondary outcomes include preterm birth, low birth weight and stillbirth rates; newborn head circumference; infant weight and length for age z-scores at birth; maternal anaemia; and weight gain during pregnancy. ETHICS AND DISSEMINATION: ENAT is approved by the Institutional Review Boards of Addis Continental Institute of Public Health (001-A1-2019) and Mass General Brigham (2018P002479). Results will be disseminated to local and international stakeholders. REGISTRATION NUMBER: ISRCTN15116516.


Assuntos
Nascimento Prematuro , Etiópia/epidemiologia , Feminino , Ácido Fólico/uso terapêutico , Humanos , Lactente , Recém-Nascido de Baixo Peso , Recém-Nascido , Ferro , Parto , Ensaios Clínicos Pragmáticos como Assunto , Gravidez , Nascimento Prematuro/epidemiologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
20.
Int J Mol Sci ; 23(17)2022 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-36077187

RESUMO

Intra-amniotic infection (IAI) is one major driver for preterm birth and has been demonstrated by clinical studies to exert both beneficial and injurious effects on the premature lung, possibly due to heterogeneity in the microbial type, timing, and severity of IAI. Due to the inaccessibility of the intra-amniotic cavity during pregnancies, preclinical animal models investigating pulmonary consequences of IAI are indispensable to elucidate the pathogenesis of bronchopulmonary dysplasia (BPD). It is postulated that on one hand imbalanced inflammation, orchestrated by lung immune cells such as macrophages, may impact on airway epithelium, vascular endothelium, and interstitial mesenchyme, resulting in abnormal lung development. On the other hand, excessive suppression of inflammation may as well cause pulmonary injury and a certain degree of inflammation is beneficial. So far, effective strategies to prevent and treat BPD are scarce. Therapeutic options targeting single mediators in signaling cascades and mesenchymal stromal cells (MSCs)-based therapies with global regulatory capacities have demonstrated efficacy in preclinical animal models and warrant further validation in patient populations. Ante-, peri- and postnatal exposome analysis and therapeutic investigations using multiple omics will fundamentally dissect the black box of IAI and its effect on the premature lung, contributing to precisely tailored and individualized therapies.


Assuntos
Displasia Broncopulmonar , Corioamnionite , Nascimento Prematuro , Líquido Amniótico , Animais , Feminino , Humanos , Recém-Nascido , Inflamação , Pulmão , Gravidez
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