RESUMO
INTRODUCTION: Pregnancy-induced hypertension (PIH) and preeclampsia (PE) are associated with disturbed maternal inflammatory response, oxidative stress and vascular endothelial cell dysfunction. Obesity is one of risk factors of PE. Leptin is elevated in obesity and its level correlates positively with the amount of adipose tissue. In contrast, adiponectin levels are decreased in obesity. Sirtuins are expressed in the placenta, however their role in pregnancy-related pathology in humans is not known. AIM OF THE STUDY: The aim of our study was to measure serum concentrations of selected sirtuins, adiponectin and leptin in healthy pregnancy and in women with PIH. MATERIALS AND METHODS: The study included 70 women: 38 healthy pregnant women and 32 women with PIH. Blood samples were obtained between the 20th and 40th week of gestation. Serum levels of sirtuins 1, 3, 6, leptin and adiponectin were measured with ELISA. RESULTS: Leptin levels were significantly higher in PIH group as compared to the controls and correlated positively with BMI. Highest leptin levels were observed in women who needed a cesarean section. Levels of sirtuins 1, 3 and 6 were similar in both groups and did not correlate with BMI. CONCLUSIONS: High leptin levels in PIH women during 3rd trimester might be helpful to predict the necessity for a caesarian section. Blood levels of sirtuins 1, 3 and 6 measured after the 20th week of gestation cannot be regarded as a single diagnostic test for PIH or preeclampsia. More studies to clarify significance of sirtuins in PIH and PE development and diagnosis are needed.
Assuntos
Adiponectina , Hipertensão Induzida pela Gravidez , Leptina , Sirtuínas , Humanos , Feminino , Adiponectina/sangue , Gravidez , Leptina/sangue , Adulto , Sirtuínas/sangue , Hipertensão Induzida pela Gravidez/sangue , Pré-Eclâmpsia/sangue , Índice de Massa Corporal , Sirtuína 3/sangue , Sirtuína 1/sangueRESUMO
Purpose: This study evaluated the association between maternal serum uric acid-to-creatinine ratio (SUA/SCr) in the first trimester and adverse maternal and neonatal outcomes. Methods: A prospective birth cohort study was conducted between 2018 and 2021. Logistic regression models and restricted cubic splines were utilized to estimate the associations between the SUA/SCr ratio and feto-maternal pregnancy outcomes. Women were stratified according to maternal age and pre-pregnancy body mass index. Results: This study included 33,030 pregnant women with live singleton pregnancies. The overall prevalence of gestational diabetes mellitus (GDM), pregnancy-induced hypertension (PIH), cesarean delivery, preterm birth, large-for-gestational age (LGA), small-for-gestational age, and low Apgar scores were 15.18%, 7.96%, 37.62%, 4.93%, 9.39%, 4.79% and 0.28%, respectively. The highest quartile of SUA/SCr was associated with the highest risk of GDM (odds ratio [OR] 2.14, 95% CI 1.93-2.36), PIH (OR 1.79, 95% CI 1.58-2.04), cesarean delivery (OR 1.24, 95% CI 1.16-1.33), and preterm birth (OR 1.30, 95% CI 1.12-1.51). The associations between SUA/SCr with adverse pregnancy outcomes showed linear relationships except for GDM (P < 0.001 for all, P < 0.001 for non-linearity). Subgroup analyses revealed that the associations between the SUA/SCr ratio and the risks of PIH and LGA were significantly stronger in younger pregnant women (P = 0.033 and 0.035, respectively). Conclusion: Maternal SUA/SCr levels were associated positively with the risk of adverse pregnancy outcomes. Timely monitoring of SUA and SCr levels during early pregnancy may help reduce the risk of adverse pregnancy outcomes and provide a basis for interventions.
Assuntos
Creatinina , Resultado da Gravidez , Ácido Úrico , Humanos , Gravidez , Feminino , Estudos Prospectivos , Adulto , Creatinina/sangue , Ácido Úrico/sangue , Resultado da Gravidez/epidemiologia , Recém-Nascido , Diabetes Gestacional/sangue , Diabetes Gestacional/epidemiologia , Nascimento Prematuro/sangue , Nascimento Prematuro/epidemiologia , Hipertensão Induzida pela Gravidez/sangue , Hipertensão Induzida pela Gravidez/epidemiologia , Primeiro Trimestre da Gravidez/sangue , Cesárea/estatística & dados numéricos , Fatores de Risco , Complicações na Gravidez/sangue , Complicações na Gravidez/epidemiologia , Idade Materna , China/epidemiologiaRESUMO
OBJECTIVIES: Pregnancy induced hypertension (PIH) syndrome is a disease that unique to pregnant women and is associated with elevated risk of offspring cardiovascular diseases (CVDs) and neurodevelopmental disorders in their kids. Previous research on cord blood utilizing the Human Methylation BeadChip or EPIC array revealed that PIH is associated with specific DNA methylation site. Here, we investigate the whole genome DNA methylation landscape of cord blood from newborns of PIH mother. METHODS: Whole-genome bisulfite sequencing (WGBS) was used to examine the changes in whole genome DNA methylation in the umbilical cord blood of three healthy (NC) and four PIH individuals. Using methylKit, we discovered Hypo- and hyper- differentially methylated probes (DMPs) or methylated regions (DMRs) in the PIH patients' cord blood DNA. Pathway enrichments were assessed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment assays. DMPs or DMRs relevant to the immunological, neurological, and circulatory systems were also employed for enrichment assay, Metascape analysis and PPI network analysis. RESULTS: 520 hyper- and 224 hypo-DMPs, and 374 hyper- and 186 hypo-DMRs between NC and PIH group, respectively. Both DMPs and DMRs have enhanced pathways for cardiovascular, neurological system, and immune system development. Further investigation of DMPs or DMRs related to immunological, neurological, and circulatory system development revealed that TBK1 served as a hub gene for all three developmental pathways. CONCLUSION: PIH-associated DMPs or DMRs in umbilical cord blood DNA may play a role in immunological, neurological, and circulatory system development. Abnormal DNA methylation in the immune system may also contribute to the development of CVDs and neurodevelopment disorders.
Assuntos
Metilação de DNA , Sangue Fetal , Hipertensão Induzida pela Gravidez , Humanos , Feminino , Gravidez , Sangue Fetal/química , Recém-Nascido , Hipertensão Induzida pela Gravidez/genética , Hipertensão Induzida pela Gravidez/sangue , Adulto , Epigenoma , Epigênese Genética , Estudos de Casos e Controles , Sequenciamento Completo do Genoma/métodosRESUMO
OBJECTIVES: To evaluate associations between serum analytes used for genetic screening and obstetric complications among twin pregnancies. METHODS: This cohort included twins delivered at a tertiary care hospital from 2009 to 2017. Abnormal levels of pregnancy associated plasma protein (PAPP-A), first and second trimester human chorionic gonadotropin (hCG), alpha fetoprotein (AFP), estriol, and inhibin, reported as multiples of the median (MoM), were defined as <5â¯%ile or >95â¯%ile for our cohort. Associations between abnormal analytes and preterm delivery, small for gestational age, and pregnancy-associated hypertension were calculated using Fisher's exact test. RESULTS: A total of 357 dichorionic/diamniotic and 123 monochorionic/diamniotic twins were included. Among dichorionic/diamniotic twins, elevated AFP (>3.70 MoM) was associated with increased preterm delivery <34 weeks (44.4 vs. 16.5â¯%, p=0.007), while elevated inhibin (>4.95 MoM) was associated with increased preterm delivery<37 weeks (94.1 vs. 58.8â¯%, p=0.004). For monochorionic/diamniotic twins, elevated inhibin (>6.34 MoM) was associated increased preterm delivery <34 weeks (66.7 vs. 24.8â¯%, p=0.04) and hypertension (66.7 vs. 21.4â¯%, p=0.03). CONCLUSIONS: Selected abnormal analyte levels were associated with increased rates of adverse outcomes in twin pregnancies, which differed by chorionicity. Our findings assist providers in interpreting abnormal analyte levels in twin pregnancies and may help to identify those at increased risk for adverse outcomes.
Assuntos
Aneuploidia , Inibinas , Gravidez de Gêmeos , Nascimento Prematuro , alfa-Fetoproteínas , Humanos , Feminino , Gravidez , Gravidez de Gêmeos/sangue , Adulto , Inibinas/sangue , Nascimento Prematuro/sangue , Nascimento Prematuro/diagnóstico , Nascimento Prematuro/epidemiologia , alfa-Fetoproteínas/análise , alfa-Fetoproteínas/metabolismo , Gonadotropina Coriônica/sangue , Proteína Plasmática A Associada à Gravidez/análise , Proteína Plasmática A Associada à Gravidez/metabolismo , Estriol/sangue , Resultado da Gravidez/epidemiologia , Recém-Nascido , Hipertensão Induzida pela Gravidez/sangue , Hipertensão Induzida pela Gravidez/diagnóstico , Hipertensão Induzida pela Gravidez/epidemiologia , Testes Genéticos/métodos , Estudos Retrospectivos , Recém-Nascido Pequeno para a Idade Gestacional , Estudos de CoortesRESUMO
AIMS: Hypertensive disorders of pregnancy (HDP) is a unique disease during gestational period, which is detrimental to pregnancy outcome. This study examined the clinical significance of long non-coding RNA GAS5 in gestational hypertension (GH) and preeclampsia (PE), aiming to explore potential biomarkers for the disease detection. METHODS: 180 pregnant women with HPD including 90 cases with GH and 90 cases with PE, and another 100 healthy pregnant women were enrolled. Serum GAS5 levels were measured by RT-qPCR method. The diagnostic performance of GAS5 was assessed in GH and PE through plotting receiver operating characteristic (ROC) curve. Logistic regression was applied for the identification of independent factors. RESULTS: Elevated serum GAS5 was identified in GH patients, and its diagnostic performance in discriminating GH cases from healthy people was determined by ROC curve. Serum GAS5 was positively associated with SBP, DBP, LDL-C and CRP values. Cases with PE had an increased serum GAS5 level relative to those with GH. Serum GAS5 was identified to be an independent predictor for PE, and can differentiate PE cases from GH ones. with a good diagnositc performance. Cases with high levels of serum GAS5 had a high risk of poor pregnancy outcomes. CONCLUSION: Elevated serum GAS5 could serve as an effective diagnostic biomarker in discriminating GH patients from healthy people by first trimester screening. Detection of serum GAS5 level has a certain predictive value for PE.
Assuntos
Biomarcadores , Hipertensão Induzida pela Gravidez , Pré-Eclâmpsia , Primeiro Trimestre da Gravidez , RNA Longo não Codificante , Humanos , Feminino , Gravidez , RNA Longo não Codificante/genética , RNA Longo não Codificante/sangue , Pré-Eclâmpsia/diagnóstico , Pré-Eclâmpsia/genética , Pré-Eclâmpsia/sangue , Hipertensão Induzida pela Gravidez/genética , Hipertensão Induzida pela Gravidez/diagnóstico , Hipertensão Induzida pela Gravidez/sangue , Adulto , Primeiro Trimestre da Gravidez/sangue , Primeiro Trimestre da Gravidez/genética , Biomarcadores/sangue , Curva ROC , Resultado da Gravidez/genética , Estudos de Casos e ControlesRESUMO
PURPOSE: Epidemiological studies examining the association between circulating micronutrients and the risk of hypertensive disorders during pregnancy (HDP) have produced inconsistent results. Therefore, we conducted a Mendelian randomization (MR) analysis to evaluate the potential causal relationship between micronutrients and HDP. METHODS: Nine micronutrients (beta-carotene, vitamin B6, vitamin B12, calcium, zinc, selenium, copper, folate, and phosphorus) were selected as the exposure factors. Summary data for gestational hypertension (14,727 cases and 196,143 controls) and preeclampsia/eclampsia (7212 cases and 174,266 controls) were extracted from the FinnGen consortium. The MR analysis employed the inverse variance weighted method and conducted a range of sensitivity analyses. RESULTS: The inverse variance weighted method indicated no significant causal relationship between nine genetically predicted micronutrient concentrations and gestational hypertension, as well as preeclampsia/eclampsia. Sensitivity analyses suggested the absence of pleiotropy. CONCLUSION: There is no strong evidence to support the causation between circulating micronutrients and hypertensive disorder during pregnancy.
Assuntos
Hipertensão Induzida pela Gravidez , Análise da Randomização Mendeliana , Micronutrientes , Humanos , Feminino , Gravidez , Micronutrientes/sangue , Hipertensão Induzida pela Gravidez/sangue , Hipertensão Induzida pela Gravidez/genética , Hipertensão Induzida pela Gravidez/epidemiologia , Pré-Eclâmpsia/sangue , Pré-Eclâmpsia/genética , Ácido Fólico/sangue , Selênio/sangue , beta Caroteno/sangue , Cobre/sangue , Vitamina B 12/sangue , Vitamina B 6/sangue , Zinco/sangue , Fatores de Risco , Fósforo/sangue , Cálcio/sangueRESUMO
PURPOSE: This study aimed to determine the association of first-trimester maternal serum biomarkers with preterm birth (PTB), fetal growth restriction (FGR) and hypertensive disorders of pregnancy (HDP) in twin pregnancies. METHODS: This is a retrospective cohort study of twin pregnancies followed at Maternidade Dr. Alfredo da Costa, Lisbon, Portugal, between January 2010 and December 2022. We included women who completed first-trimester screening in our unit and had ongoing pregnancies with two live fetuses, and delivered after 24 weeks. Maternal characteristics, pregnancy-associated plasma protein-A (PAPP-A) and ß-human chorionic gonadotropin (ß-hCG) levels were analyzed for different outcomes: small for gestational age (SGA), gestational hypertension (GH), early and late-onset pre-eclampsia (PE), as well as the composite outcome of PTB associated with FGR and/or HDP. Univariable, multivariable logistic regression analyses and receiver-operating characteristic curve were used. RESULTS: 466 twin pregnancies met the inclusion criteria. Overall, 185 (39.7%) pregnancies were affected by SGA < 5th percentile and/or HDP. PAPP-A demonstrated a linear association with gestational age at birth and mean birth weight. PAPP-A proved to be an independent risk factor for SGA and PTB (< 34 and < 36 weeks) related to FGR and/or HDP. None of the women with PAPP-A MoM > 90th percentile developed early-onset PE or PTB < 34 weeks. CONCLUSION: A high serum PAPP-A (> 90th percentile) ruled out early-onset PE and PTB < 34 weeks. Unless other major risk factors for hypertensive disorders are present, these women should not be considered candidates for aspirin prophylaxis. Nevertheless, close monitoring of all TwP for adverse obstetric outcomes is still recommended.
Assuntos
Biomarcadores , Gonadotropina Coriônica Humana Subunidade beta , Retardo do Crescimento Fetal , Hipertensão Induzida pela Gravidez , Primeiro Trimestre da Gravidez , Gravidez de Gêmeos , Proteína Plasmática A Associada à Gravidez , Nascimento Prematuro , Humanos , Feminino , Gravidez , Gravidez de Gêmeos/sangue , Adulto , Estudos Retrospectivos , Primeiro Trimestre da Gravidez/sangue , Biomarcadores/sangue , Retardo do Crescimento Fetal/sangue , Proteína Plasmática A Associada à Gravidez/análise , Proteína Plasmática A Associada à Gravidez/metabolismo , Nascimento Prematuro/sangue , Nascimento Prematuro/epidemiologia , Gonadotropina Coriônica Humana Subunidade beta/sangue , Hipertensão Induzida pela Gravidez/sangue , Hipertensão Induzida pela Gravidez/epidemiologia , Recém-Nascido Pequeno para a Idade Gestacional , Pré-Eclâmpsia/sangue , Pré-Eclâmpsia/diagnóstico , Pré-Eclâmpsia/epidemiologia , Resultado da Gravidez , Recém-Nascido , Estudos de Coortes , Portugal/epidemiologia , Idade GestacionalRESUMO
BACKGROUND AND AIM: Preeclampsia, a pregnancy complication associated with significant maternal and perinatal mortality and morbidity, has been found to be closely linked to dysfunction in the blood coagulation-fibrinolysis system. However, the relationship between hematologic data and severity and onset time of preeclampsia remains unclear. This study aimed to identify specific hematologic parameters in both preeclamptic and normotensive pregnant women and determine their potential significance in the pathogenesis of preeclampsia. MATERIALS AND METHODS: A total of 112 patients with gestational hypertension disease were divided into two groups: early-onset preeclampsia (32 cases) and late-onset preeclampsia (80 cases). A control group of 82 normotensive pregnant women matched for age and parity was also selected. Blood samples were collected from all participants to test for specific hematologic parameters. RESULTS: Mild and severe preeclampsia were associated with lower hemoglobin level (P = 0.01 and P = 0.03, respectively), higher mean platelet volume (P = 0.01 and P = 0.01, respectively) and fibrinogen (P = 0.01 and P = 0.01, respectively), and shorter prothrombin time (P = 0.02 and P = 0.01, respectively) and activated partial thromboplastin time (P = 0.01 and P = 0.02, respectively). CONCLUSION: These findings have provided evidence on the hematologic coagulative actors in the pathogenesis and severity of preeclampsia.
Assuntos
Pré-Eclâmpsia , Humanos , Feminino , Gravidez , Adulto , Pré-Eclâmpsia/sangue , Pré-Eclâmpsia/fisiopatologia , Pré-Eclâmpsia/diagnóstico , Estudos de Casos e Controles , Hipertensão Induzida pela Gravidez/sangue , Hipertensão Induzida pela Gravidez/fisiopatologia , Coagulação Sanguínea/fisiologia , Índice de Gravidade de Doença , Adulto Jovem , Fibrinogênio/metabolismo , Fibrinogênio/análise , Tempo de Protrombina , Volume Plaquetário Médio , Hemoglobinas/análise , Tempo de Tromboplastina ParcialRESUMO
This study aimed to establish in vitro hemodilution and resupplementation assays for obstetric hemorrhage in pregnancy-induced hypertension (PIH) and to monitor the coagulation function dynamically using a coagulation and platelet function analyzer. Forty-seven singleton pregnant women were divided into normal (n = 24) and PIH (n = 23) groups. Peripheral blood samples were used to construct the assays, and the activated clotting time (ACT), clotting rate (CR), and platelet function index (PF) were measured. The results showed that the baseline ACT was higher in the PIH group (p < 0.01). Hemodilution assays showed decreased ACT and increased CR and PF, with ACT changes significantly lower in the PIH group (p < 0.05). CR changed most in both groups at lower dilution ratios (35% to 50%), while ACT changed most at a higher dilution ratio (75%). In the resupplementation assay, ACT exhibited the most significant response. The analyzer effectively detected differences between pregnant women with and without PIH. Thus, we need to pay more attention to the changes of ACT in the actual clinical application to assess the coagulation status of parturients.
Assuntos
Coagulação Sanguínea , Hipertensão Induzida pela Gravidez , Testes de Função Plaquetária , Humanos , Feminino , Gravidez , Adulto , Hipertensão Induzida pela Gravidez/sangue , Hipertensão Induzida pela Gravidez/fisiopatologia , Coagulação Sanguínea/fisiologia , Testes de Coagulação Sanguínea , Hemorragia Pós-Parto/sangue , Adulto JovemRESUMO
BACKGROUND: Vitamin D deficiency is associated with several obstetric complications in singleton pregnancy. The aim of this study was to assess whether vitamin D levels affect the outcomes of twin pregnancy and if targeted supplementation can improve perinatal outcomes. METHODS: The serum vitamin D levels of 143 women with twin pregnancies were measured during their first trimester. Those with insufficient (10-30 ng/mL; IL group) or severely deficient (<10 ng/mL, DL group) vitamin D levels were supplemented. In the third trimester, vitamin D levels were reassessed. Perinatal outcomes of the IL and DL groups were compared with those of patients with sufficient levels (>30 ng/mL, SL group) since the beginning of pregnancy. RESULTS: Women in the IL and DL groups had a higher incidence of hypertensive disorders of pregnancy (HDP) compared to the SL group (24.8% and 27.8% vs. 12.5%, p = 0.045): OR = 1.58 for the IL group and 1.94 for the DL group compared to the SL group. In patients whose vitamin D levels were restored after supplementation, HDP incidence was lower than in patients who remained in the IL or DL groups (23.4% vs. 27.3%) but higher than those who were always in the SL group (12.5%). CONCLUSIONS: Insufficient or severely deficient levels of vitamin D in the first trimester are associated with an increased risk of HDP in twin pregnancy. The beneficial effect of targeted vitamin D supplementation in reducing HDP seems limited.
Assuntos
Suplementos Nutricionais , Resultado da Gravidez , Gravidez de Gêmeos , Deficiência de Vitamina D , Vitamina D , Humanos , Feminino , Gravidez , Vitamina D/sangue , Vitamina D/administração & dosagem , Vitamina D/análogos & derivados , Gravidez de Gêmeos/sangue , Adulto , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/epidemiologia , Hipertensão Induzida pela Gravidez/sangue , Hipertensão Induzida pela Gravidez/epidemiologia , Primeiro Trimestre da Gravidez/sangue , Complicações na Gravidez/sangueRESUMO
Hypertensive disorders of pregnancy (HDP) are among the major causes of high maternal and fetal/neonatal morbidity and mortality rates. Patients with HDP have significantly elevated N-terminal pro-brain natriuretic peptide (NT-proBNP) levels at diagnosis; however, the NT-proBNP levels during early pregnancy are largely unknown. This study aimed to validate the association between HDP and NT-proBNP levels. This retrospective study evaluated 103 pregnant women who developed HDP diagnosed after 35 weeks of gestation and 667 who did not. The HDP group had significantly lower early-pregnancy NT-proBNP levels than the without HDP group. However, the two groups did not significantly differ in terms of the late-pregnancy NT-proBNP levels. After adjusting for confounding factors such as age, body mass index, parity, and blood pressure levels, high early-pregnancy NT-proBNP levels were associated with a lower HDP risk. Early-pregnancy NT-proBNP levels ≥ 60.5 pg/mL had a negative predictive value of 97.0% for ruling out HDP, with a sensitivity of 87.4% and specificity of 62.5%. In conclusion, elevated early-pregnancy NT-proBNP levels were associated with a lower HDP risk. Moreover, a cutoff point of ≥ 60.5 pg/mL for early-pregnancy NT-proBNP levels had a high negative predictive value and sensitivity for ruling out HDP. These findings can provide new clinical implications.
Assuntos
Hipertensão Induzida pela Gravidez , Peptídeo Natriurético Encefálico , Fragmentos de Peptídeos , Humanos , Feminino , Gravidez , Peptídeo Natriurético Encefálico/sangue , Adulto , Fragmentos de Peptídeos/sangue , Hipertensão Induzida pela Gravidez/sangue , Hipertensão Induzida pela Gravidez/diagnóstico , Estudos Retrospectivos , Biomarcadores/sangue , Idade GestacionalRESUMO
BACKGROUND: Elevated maternal serum total bile acids (sTBA) level during pregnancy was associated with adverse fetal outcomes. Women with elevated sTBA could complicate with hepatic dysfunction or vascular disorders (hypertensive disorders of pregnancy, HDP), which aggravated adverse fetal outcomes. However, the relationships among sTBA level, hepatic dysfunction, HDP and adverse fetal outcomes were still illusive. OBJECTIVE: We aimed to explore whether hepatic dysfunction or vascular disorders (HDP) mediated the associations between elevated sTBA level and adverse fetal outcomes. METHODS: A large retrospective cohort study encompassing 117,789 Chinese pregnant women with singleton delivery between Jan 2014 and Dec 2022 was conducted. Causal mediation analysis was applied to assess the mediating role of hepatic dysfunction (alanine transaminase > 40 U/L) or HDP in explaining the relationship between high maternal sTBA level (≥10 µmol/L) and adverse fetal outcomes, including low birth weight (LBW), small for gestational age (SGA), and preterm birth (PTB). RESULTS: sTBA level were positively associated with LBW (adjusted odds ratio (aOR) = 1.40; [95 % confidence interval (CI): 1.24-1.59]), SGA (aOR=1.31; [95 % CI: 1.18-1.46]), and PTB (aOR=1.27; [95 % CI: 1.15-1.41]), respectively. The estimated proportions of the total associations mediated by HDP were 47 % [95 % CI: 31 %-63 %] for LBW, 24 % [95 % CI: 13 %-35 %] for SGA, and 34 % [95 % CI: 19 %-49 %] for PTB, excepting the direct effects of high sTBA level. The contribution of hepatic dysfunction as a mediator was weaker on the association between high sTBA level on fetal outcomes, as the proportions mediated and 95 % CI were 16 % [4 %-29 %], 4 % [-6%-14 %], 32 % [15 %-50 %] for LBW, SGA, and PTB, respectively. Moreover, the mediating effect of hepatic dysfunction was nearly eliminated after excluding cases of HDP in the sensitivity analysis. CONCLUSIONS: The substantial mediating effects through HDP highlighted its significant role in adverse fetal outcomes associated with elevated sTBA level. The findings also provoked new insights into understanding the mechanism and developing clinical management strategies (i.e. vascular protection) for adverse fetal outcomes associated with elevated sTBA level.
Assuntos
Ácidos e Sais Biliares , Hipertensão Induzida pela Gravidez , Resultado da Gravidez , Humanos , Gravidez , Feminino , Ácidos e Sais Biliares/sangue , Adulto , China/epidemiologia , Estudos Retrospectivos , Hipertensão Induzida pela Gravidez/sangue , Hipertensão Induzida pela Gravidez/epidemiologia , Estudos de Coortes , Recém-Nascido , Nascimento Prematuro/sangueRESUMO
In China, the implementation of 2-child policy since 2015 entitles increasing number of advanced maternal age. Recently, Chinese hypertensive disorders of pregnancy (HDP) in advanced-age women have attracted significant clinical and epidemiological research interest. Previous studies have shown an association between serum uric acid (SUA) levels and low birth weight (LBW) in children. Several studies have reported that advanced maternal age is a risk factor for many complications in pregnancy, including LBW. However, it remains unclear whether SUA affects LBW risk in advanced maternal age mothers with hypertensive diseases. The study was observational in nature. A total of 692 advanced maternal age with hypertension were enrolled in our study. A variety of demographic and vital sign data, laboratory test results, and pregnancy outcomes were collected. Children born with LBW served as the clinical endpoint. On admission, blood samples were taken, and women with advanced maternal ages were divided into 2 groups based on their SUA levels. In order to investigate the association between SUA and LBW, a logistic regression model was used. E-value analysis was used to determine the residual unmeasured confounding. The mean SUA level was increased in advanced maternal age patients with HDP. Of 692 newborns, 244 (35.26%) have LBW. With possible confounders adjusted, high SUA levels were independent risk factors for LBW (odds ratio [OR]2.88, 95% confidence intervals [CI]1.22-6.81), multivariate logistic regression analysis using SUA as a continuous variable recapitulated the pattern (OR 1.01, 95% CI 1.00-1.01). In addition, SUA levels in women with advanced maternal age and hypertension were linearly related to LBW incidence. According to this study, SUA levels in patients with advanced maternal age and HDP are associated with LBW incidence.
Assuntos
Recém-Nascido de Baixo Peso , Idade Materna , Ácido Úrico , Humanos , Feminino , Ácido Úrico/sangue , Adulto , Gravidez , Recém-Nascido , China/epidemiologia , Fatores de Risco , Hipertensão Induzida pela Gravidez/sangue , Hipertensão Induzida pela Gravidez/epidemiologia , Hipertensão/sangue , Hipertensão/epidemiologia , Modelos Logísticos , Resultado da Gravidez/epidemiologiaRESUMO
N-terminal prohormone of brain natriuretic peptide (NT-proBNP) is a non-active prohormone secreted by ventricular cardiomyocytes into the circulation in response to ventricle overload, mainly due to increased blood volume. The changes in NT-proBNP levels during pregnancy have been investigated in multiple studies. In the case of hypertensive disorders of pregnancy, increased vasoconstriction leads to increased blood pressure and afterload. Together with the volume overload of pregnancy, it leads to higher NT-proBNP secretion. As hypertensive disorders of pregnancy are among the leading causes of prematurity and perinatal mortality, early prediction and diagnosis of gestational hypertension, and preeclampsia are essential for improving maternal and infant prognosis. NT-proBNP has been regarded as a potential biomarker of hypertensive disorders of pregnancy. In this review, we have thoroughly summarized the current data on the prognostic and diagnostic utility of NT-proBNP in patients with gestational hypertension and preeclampsia. NT-proBNP values may help distinguish between non-preeclamptic and preeclamptic patients, even if there are no significant differences in blood pressure. Moreover, in pregnancies complicated by preeclampsia, the value of increased NT-proBNP level is related to the stage and the severity of the disease. Further improvement of our knowledge about NT-proBNP as a diagnostic biomarker and a putative predictor of adverse cardiac events in women with hypertensive disorders of pregnancy should lead to better management of these patients.
Assuntos
Biomarcadores , Hipertensão Induzida pela Gravidez , Peptídeo Natriurético Encefálico , Fragmentos de Peptídeos , Pré-Eclâmpsia , Humanos , Gravidez , Feminino , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Hipertensão Induzida pela Gravidez/sangue , Hipertensão Induzida pela Gravidez/diagnóstico , Pré-Eclâmpsia/sangue , Pré-Eclâmpsia/diagnóstico , Biomarcadores/sangue , PrognósticoRESUMO
OBJECTIVES: Maternal endothelial dysfunction in pregnancy hypertension is related to impairment of nitric oxide (NO) formation. However, NO levels and hemodynamic repercussions on the female offspring remain unclear. Therefore, this study hypothesized that maternal pregnancy hypertension reduces circulating NO metabolites and increases arterial blood pressure in first-generation offspring female rats. STUDY DESIGN: Descendant female rats were distributed in four groups as follows: virgin offspring of normotensive (VN) and hypertensive (VH) mothers and pregnant offspring of normotensive (PN) and hypertensive (PH) mothers. Hemodynamic and biochemical analyses were performed. MAIN OUTCOME MEASURES: The systolic (SBP) and diastolic (DBP) blood pressure, heart rate (HR), and body weight were measured. NO metabolites in plasma, NO formation in human umbilical vein endothelial cells (HUVECs) incubated with plasma, and endothelial NO synthase (eNOS) expression in aortas were determined. RESULTS: Increased SBP, DBP, and reduced HR were found on the 60 days of life in the VH group, whereas the PH group showed increased SBP and HR on pregnancy day 7. All groups showed no differences in body weight gain and eNOS expression. Plasma levels of NO metabolites were increased in the PN compared to the other groups. Increases in the NO formation were greater in HUVECs incubated with plasma from VN and PN groups compared to the VH and PH groups. CONCLUSIONS: Female virgin and pregnant first-generation offspring rats from hypertensive pregnant mothers may have negative cardiovascular repercussions featured by increases in SBP, and possibly impaired NO formation is involved.
Assuntos
Óxido Nítrico , Animais , Feminino , Gravidez , Óxido Nítrico/metabolismo , Óxido Nítrico/sangue , Ratos , Humanos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Hipertensão Induzida pela Gravidez/fisiopatologia , Hipertensão Induzida pela Gravidez/metabolismo , Hipertensão Induzida pela Gravidez/sangue , Efeitos Tardios da Exposição Pré-Natal , Pressão Arterial , Modelos Animais de Doenças , Pressão Sanguínea/fisiologia , Ratos Wistar , Frequência CardíacaRESUMO
This study aimed to evaluate the association between maternal liver biomarkers in early pregnancy and the risk of hypertensive disorders of pregnancy (HDP), as well as to evaluate interaction between liver enzymes and BMI on the development of HDP. Pregnant women in our study were recruited from the Zhoushan Pregnant Women Cohort. Participants who had their first prenatal follow-up and the blood pressure follow-up records, and measured liver biomarkers in the first trimester were eligible for inclusion in the study. A total of 10,610 pregnant women were included in the analysis, and 305 (2.87%) developed the HDP. There were positive associations between AST, GGT, ALP, HSI and SBP, as well as between ALT, GGT, ALP, HSI and DBP. In addition, AST/ALT level was negatively associated with DBP. The highest quartile of GGT, ALP, AST/ALT and HSI were significantly associated with 1.71-fold (95% Cl: 1.23-2.41), 1.53-fold (95% Cl: 1.10-2.14), 0.62-fold (95% Cl: 0.43-0.90) and 1.67-fold (95% Cl: 1.05-2.67) increased risk of HDP, respectively. There was no significant association between ALT, AST and HDP. These associations remained consistent in pregnant women with liver enzymes within the clinical reference range. Besides, we found an interaction between GGT and BMI (Pinteraction = 0.013) in the development of HDP. In summary, the level of GGT, ALP, AST/ALT and HSI were associated with the subsequent risk of HDP, even within the clinical reference range. And there was an interaction between liver biomarkers and BMI in the development of HDP. Our study showed the level of GGT, ALP, AST/ALT and HSI were associated with the subsequent risk of HDP. And there was an interaction between GGT and BMI in the risk of HDP.
Assuntos
Biomarcadores , Hipertensão Induzida pela Gravidez , Fígado , Primeiro Trimestre da Gravidez , Humanos , Feminino , Gravidez , Biomarcadores/sangue , Primeiro Trimestre da Gravidez/sangue , Adulto , Hipertensão Induzida pela Gravidez/sangue , Fígado/enzimologia , Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Índice de Massa Corporal , gama-Glutamiltransferase/sangue , Fatores de Risco , Fosfatase Alcalina/sangueRESUMO
OBJECTIVE: The objective of this study was to determine serum fibroblast growth factor-23 levels in preeclampsia, eclampsia, gestational hypertension, and the presence of fetal growth restriction subgroups. METHODS: A total of 55 pregnant women with planned cesarean section were included in this cross-sectional study. They were divided into two groups, namely, control (25) and gestational hypertensive disease (30). The gestational hypertensive disease group was evaluated by dividing it into three subgroups (preeclampsia, eclampsia, and gestational hypertension) according to the clinical and laboratory findings of the disease and two subgroups (presence of fetal growth restriction and absence of fetal growth restriction) according to the birth weight percentile. Demographic parameters, obstetric history, physical examination findings, and laboratory values were evaluated. RESULTS: Demographic parameters and obstetric history were similar between the two groups, while gestational week of delivery was lower in the gestational hypertensive disease group (p=0.002). Laboratory parameters and serum fibroblast growth factor-23 (pg/mL) values were similar between the two groups. In the subgroup analysis for gestational hypertension, preeclampsia, and eclampsia, there was no statistically significant difference in serum fibroblast growth factor-23 levels between gestational hypertension, preeclampsia, eclampsia, and control groups. In the subgroup analysis based on the presence of fetal growth restriction, serum fibroblast growth factor-23 levels were similar to the control group in the gestational hypertensive disease absence of fetal growth restriction, while serum fibroblast growth factor-23 levels and serum calcium levels were statistically significantly lower in the gestational hypertensive disease with the presence of fetal growth restriction (p=0.044 and p<0.001, respectively). CONCLUSION: Serum fibroblast growth factor-23 levels are similar between pregnancies complicated with gestational hypertensive disease and normotensive pregnancies. However, serum fibroblast growth factor-23 levels were found to be lower in pregnancies complicated with gestational hypertensive disease with the presence of fetal growth restriction.
Assuntos
Biomarcadores , Retardo do Crescimento Fetal , Fator de Crescimento de Fibroblastos 23 , Fatores de Crescimento de Fibroblastos , Hipertensão Induzida pela Gravidez , Pré-Eclâmpsia , Humanos , Feminino , Gravidez , Retardo do Crescimento Fetal/sangue , Estudos Transversais , Adulto , Hipertensão Induzida pela Gravidez/sangue , Fatores de Crescimento de Fibroblastos/sangue , Fator de Crescimento de Fibroblastos 23/sangue , Biomarcadores/sangue , Pré-Eclâmpsia/sangue , Estudos de Casos e Controles , Adulto Jovem , Idade Gestacional , Eclampsia/sangueRESUMO
BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are man-made chemicals that are slow to break down in the environment and widely detected in humans. Epidemiological evidence suggests that prenatal exposure to perfluorooctanoic acid (PFOA), a legacy PFAS, is linked to gestational hypertension and preeclampsia. However, the relationship between other PFAS, which are structurally similar, and these outcomes remains largely understudied, despite biologic plausibility. Here, we examined associations between serum PFAS mixtures in relation to hypertensive disorders of pregnancy within a birth cohort of African Americans. METHODS: Participants in the present study were enrolled in the Atlanta African American Maternal-Child cohort between 2014 and 2020 (n = 513). Serum samples collected between 8 and 14 weeks gestation were analyzed for four PFAS. Logistic regression was used to assess associations between individual natural log transformed PFAS and specific hypertensive disorders of pregnancy (preeclampsia, gestational hypertension), while quantile g-computation was used to estimate mixture effects. Preeclampsia and gestational hypertension were treated as separate outcomes in individual models. All models were adjusted for maternal education, maternal age, early pregnancy body mass index, parity, and any alcohol, tobacco, or marijuana use. RESULTS: The geometric mean of PFOS and PFHxS was slightly lower among those with preeclampsia relative to those without a hypertensive disorder (e.g., geometric mean for PFOS was 1.89 and 1.94, respectively). Serum concentrations of PFAS were not strongly associated with gestational hypertension or preeclampsia in single pollutant or mixture models. For example, using quantile g-computation, a simultaneous one quartile increase in all PFAS was not associated with odds of gestational hypertension (odds ratio = 0.86, 95% CI = 0.60, 1.23), relative to those without a hypertensive disorder of pregnancy. CONCLUSIONS: In this birth cohort of African Americans, there was no association between serum PFAS measured in early pregnancy and hypertensive disorders of pregnancy, which may be reflective of the fairly low PFAS levels in our study population.
Assuntos
Negro ou Afro-Americano , Poluentes Ambientais , Fluorocarbonos , Hipertensão Induzida pela Gravidez , Exposição Materna , Humanos , Feminino , Fluorocarbonos/sangue , Gravidez , Negro ou Afro-Americano/estatística & dados numéricos , Adulto , Hipertensão Induzida pela Gravidez/epidemiologia , Hipertensão Induzida pela Gravidez/sangue , Exposição Materna/estatística & dados numéricos , Poluentes Ambientais/sangue , Estudos de Coortes , Caprilatos/sangue , Georgia/epidemiologia , Adulto Jovem , Efeitos Tardios da Exposição Pré-Natal , Pré-Eclâmpsia/sangue , Pré-Eclâmpsia/epidemiologia , Ácidos Alcanossulfônicos/sangueRESUMO
Resumen Antecedentes: La preeclampsia se presenta en el 8% de los embarazos y genera el 25% de las muertes perinatales. Aunque su etiología es multifactorial, algunas alteraciones metabólicas se asocian a la disfunción endotelial presente en la enfermedad, y su estudio podría identificar marcadores tempranos de daño. Objetivo: Determinar la relación existente entre concentración plasmática de triglicéridos en las pacientes embarazadas con enfermedad hipertensiva inducida por el embarazo. Método: Estudio prospectivo que incluyó 147 pacientes gestantes sanas y 120 mujeres con enfermedad hipertensiva inducida por el embarazo y se determinaron colesterol total, lipoproteínas de baja densidad (LDL), lipoproteínas de alta densidad (HDL), hemoglobina glucosilada (HbA1c), biometría hemática (BH), química sanguínea (QS), electrolitos séricos, nitritos séricos y pruebas de función hepática. Resultados: Se encontró una diferencia significativa en la concentración de triglicéridos entre las pacientes normotensas y con preeclampsia (261.22 ± 80.27 vs. 361.46 ± 135.17 mg/dl; p < 0.0008). Además, se observó una menor concentración sérica de nitritos en las pacientes con preeclampsia, que contribuye a explicar la vasoconstricción. Conclusiones: Se encontró una asociación entre la hipertrigliceridemia y la presencia de DM II con el desarrollo de la enfermedad hipertensiva inducida por el embarazo.
Abstract Background: Preeclampsia occurs in 8% of pregnancies and generates 25% of perinatal deaths. Although its etiology is multifactorial, some metabolic alterations are associated with the endothelial dysfunction present in the disease, and its study could identify early markers of damage. Objective: To determine the relationship between plasma concentration of triglycerides in pregnant patients with hypertensive disease induced by pregnancy. Methods: Prospective study that included 147 healthy pregnant women and 120 women with hypertensive disease induced by pregnancy. Total cholesterol, low-density lipoprotein, high-density lipoprotein, Hemoglobin A1c, triglycerides, BH, QS, serum electrolytes, serum nitrites and liver function tests were determined. Results: A significant difference was found in the concentration of triglycerides between normotensive and patients with preeclampsia (261.22 ± 80.27 vs. 361.46 ± 135.17 mg/dl, p < 0.0008). In addition, a lower serum concentration of nitrites was observed in patients with preeclampsia, which helps explain vasoconstriction. Conclusions: We found an association between hypertriglyceridemia and the presence of diabetes mellitus II with the development of hypertensive disease induced by pregnancy.
Assuntos
Humanos , Feminino , Gravidez , Adulto , Hipertrigliceridemia/complicações , Hipertensão Induzida pela Gravidez/etiologia , Pré-Eclâmpsia/etiologia , Estudos Prospectivos , Hipertensão Induzida pela Gravidez/sangueRESUMO
ANTECEDENTES: La PAPP-A es una proteína utilizada en obstetricia de forma rutinaria para el cribado de aneuploidías de primer trimestre. En los últimos años se está conociendo más acerca de su papel en la función placentaria. Diversos estudios están mostrando una asociación entre un nivel bajo de PAPP-A y distintos eventos obstétricos. OBJETIVO: Establecer una asociación entre PAPP-A baja y eventos obstétricos adversos. MÉTODO: Estudio retrospectivo de casos y controles anidado en una cohorte. Se han recogido las gestaciones únicas con PAPP-A inferior a percentil 5 en primer trimestre durante 2 años. Se ha recogido de la misma cohorte un grupo control, en proporción 2:1. Se compara mediante análisis estadístico la incidencia de eventos obstétricos adversos de cada grupo. RESULTADOS: Se incluyó un total de 285 pacientes en el grupo de casos y 570 pacientes en el grupo control. Se observó un aumento significativo en el grupo de casos de la incidencia de prematuridad, restricción del crecimiento, hipertensión gestacional y diabetes gestacional. Se ha correlacionado la PAPP-A baja con varios eventos obstétricos adversos, incluyendo prematuridad (OR 4,27), diabetes gestacional (OR 2,40), restricción del crecimiento (OR 2,36) e hipertensión gestacional (OR 2,22). No se observó relación con el resto de eventos obstétricos adversos. CONCLUSIÓN: Un nivel de PAPP-A bajo se asocia con aumentos significativos de prematuridad, diabetes gestacional, restricción del crecimiento e hipertensión gestacional.
BACKGROUND: PAPP-A is a placental protein used in obstetrics as a first trimester marker in aneuploidy screening. In the last few years we are knowing more about its placental function. Some studies are showing a association between low PAPP-A and obstetrical adverse events. AIM: Establish an association between low PAPP-A an obstetrical adverse events. METHOD: This is a retrospective nested case-control study. We identified each singleton pregnancy with a normal phenotype and a low PAPP-A (under percentile 5) in the last 2 years, and match it with a control group of the same population in a 2:1 proportion. It was compared the incidence of each obstetrical adverse outcomes with statistical analysis. RESULTS: We found 285 patients in the case group and match it with 570 patients from control group. It was observed a significative increase in the incidence of prematurity, intrauterine growth restriction, gestational hypertension and gestational diabetes. A low PAPP-A level was correlated with some obstetrical adverse events, like prematurity (OR 4.27), gestational diabetes (OR 2.40), intrauterine growth restriction (OR 2.36) and gestational hypertension (OR 2.22). We observe no correlation with the rest of outcomes. CONCLUSIONS: A low PAPP-A level is related with significative increases of prematurity, gestational diabetes, intrauterine growth restriction and gestational hypertension.