RESUMO
OBJECTIVE: To explore the association between the concentration of maternal serum biomarkers and the risk of fetal carrying chromosome copy number variants (CNVs). METHODS: Pregnant women identified as high risk in the second-trimester serological triple screening and underwent traditional amniotic fluid karyotype analysis, along with comparative genomic hybridization array (aCGH)/copy number variation sequencing (CNV-seq), were included in the study. We divided the concentration of serum biomarkers, free beta-human chorionic gonadotropin (fß-hCG), alpha fetoprotein (AFP) and unconjugated estriol (uE3), into three levels: abnormally low, normal and abnormally high. The prevalence of abnormally low, normal and abnormally high serum fß-hCG, AFP and uE3 levels in pregnant women with aberrant aCGH/CNV-seq results and normal controls was calculated. RESULTS: Among the 2877 cases with high risk in the second-trimester serological triple screening, there were 98 chromosome abnormalities revealed by karyotype analysis, while 209 abnormalities were detected by aCGH/CNVseq (Pï¼0.001) . The carrying rate of aberrant CNVs increased significantly when the maternal serum uE3 level was less than 0.4 multiple of median (MoM) of corresponding gestational weeks compared to normal controls, while the carrying rate of aberrant CNVs decreased significantly when the maternal serum fß-hCG level was greater than 2.5 MoM compared to normal controls. No significant difference was found in the AFP group. CONCLUSION: Low serum uE3 level (<0.4 MoM) was associated with an increased risk of aberrant CNVs.
Assuntos
Biomarcadores , Gonadotropina Coriônica Humana Subunidade beta , Variações do Número de Cópias de DNA , alfa-Fetoproteínas , Humanos , Feminino , Gravidez , Estudos Retrospectivos , Adulto , Biomarcadores/sangue , Gonadotropina Coriônica Humana Subunidade beta/sangue , alfa-Fetoproteínas/análise , alfa-Fetoproteínas/metabolismo , Segundo Trimestre da Gravidez/sangue , Estriol/sangue , Hibridização Genômica Comparativa , Aberrações Cromossômicas , Cariotipagem , Diagnóstico Pré-Natal/métodos , Testes para Triagem do Soro MaternoRESUMO
PURPOSE: Vaginal oestrogens can be used to treat genitourinary symptoms in women with early breast cancer. Studies evaluating vaginal oestrogens have commonly measured serum oestrogen levels as a surrogate marker of safety, but methods vary. We sought to summarise the data on serum oestrogen measurement in women with breast cancer using vaginal oestrogens to better understand the methods, levels and reliability. METHODS: We searched Medline, Embase, CENTRAL, SCOPUS and CINAHL from inception to October 2023 for clinical studies where serum oestrogen was measured in women with a history of early breast cancer using vaginal oestrogens. Studies with a reported testing methodology were included. RESULTS: Nine studies met the inclusion criteria for this systematic review. Methods used to measure oestradiol and oestriol in selected studies included mass spectrometry and immunoassays; several studies used more than one with variable concordance. Mass spectrometry detected oestradiol levels down to a lower limit between 1.0 pg/mL and 3.0 pg/mL. Immunoassays such as ELISA (enzyme-linked immunosorbent assay), ECLIA (enhanced chemiluminiscence immunoassay) and RIA (radioimmunoassay) had lower detection limits ranging between 0.8 pg/mL and 10 pg/mL. Studies were heterogeneous in testing techniques used, timing of testing, and the population including with subsequent varying results in the effect on oestrogens reported. CONCLUSIONS: Adopting consistent and standardised methods of measuring oestrogens in clinical trials involving women with early breast cancer on vaginal oestrogens is critical. Serum oestrogens are used as a surrogate marker of safety in this population, and good-quality data are necessary to enable clinicians and patients to feel confident in prescribing and taking vaginal oestrogens. Mass spectrometry, although more expensive, gives more reliable results when dealing with very low levels of oestrogens often found in women on aromatase inhibitors, compared to immunoassays.
Assuntos
Neoplasias da Mama , Sobreviventes de Câncer , Estrogênios , Feminino , Humanos , Administração Intravaginal , Neoplasias da Mama/sangue , Neoplasias da Mama/tratamento farmacológico , Estradiol/sangue , Estriol/sangue , Estrogênios/sangue , VaginaRESUMO
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
BACKGROUND: This study aimed to evaluate the predictive power of a model combining maternal risk factors and the Quadruple screen test for late-onset preeclampsia (PE). METHODS: All pregnant women that received the Quadruple test for Down syndrome at 15+ 0-20+ 6 weeks' gestation were recruited. Maternal serum α-fetoprotein, ß-human chorionic gonadotropin, unconjugated estriol, and inhibin A were measured as multiples of the median. A logistic regression model was used to identify predictors associated with late-onset PE with severe features. The receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to assess the model's predictive ability. RESULTS: Fifty-five of the 2,000 pregnant women had PE, and 31 of 55 women had late-onset PE. Multivariate analysis identified maternal age ≥ 35 years, inhibin A, history of previous PE, history of infertile, cardiac disease, chronic hypertension, and thyroid disease as significant risk factors. The area under the curve of the receiver operating characteristic curve was 0.78. The likelihood ratio to predict late-onset PE was 49.4 (total score > 60). CONCLUSIONS: Our model combining serum inhibin A with maternal risk factors was useful in predicting late-onset PE. Close monitoring of these patients is recommended.
Assuntos
Pré-Eclâmpsia , População do Sudeste Asiático , Adulto , Feminino , Humanos , Gravidez , Biomarcadores/sangue , Pré-Eclâmpsia/sangue , Pré-Eclâmpsia/diagnóstico , Fatores de Risco , Valor Preditivo dos Testes , Gonadotropina Coriônica Humana Subunidade beta/sangue , alfa-Fetoproteínas/análise , Estriol/sangue , Inibinas/sangueRESUMO
To evaluate second-trimester Down syndrome screening performance of the new ThermoFisher BRAHMS GOLD unconjugated estriol (uE3) and inhibin-A assays. Serum samples were analyzed for levels of uE3 and inhibin-A using the ThermoFisher BRAHMS GOLD immunoanalyzer and compared to other platforms. Levels were transformed to multiples of the median (MoM) in unaffected pregnancies. Log10 MoM distributions in unaffected and Down syndrome pregnancies were assessed for central tendency (mean) and dispersion (SD). Empirical and estimated screening performances were determined. Correlation between BRAHMS and AutoDELFIA® uE3 and inhibin-A were 0.63 and 0.97, respectively, the respective mean difference was 31.3% [95%CI 50.2% to -112.8%] and -23.3% [95%CI -41.9% to -4.7%]. Passing-Bablok indicated significant systematic (-2.78 [95%CI -3.57 to -2.04]) and proportional bias (1.30 [95%CI 1.15 to -1.47]) between uE3 assays and significant proportional bias (0.71[95%CI 0.65-0.78]) between inhibin-A assays. The uE3 and inhibin-A log10 MoM distribution mean [SD] in unaffected and Down syndrome pregnancies were 0.0024 [SD = 0.2341] and -0.0001 [SD = 0.2078], and -0.2028 [SD = 0.2495] and 0.3645 [SD = 0.2576], respectively. The new BRAHMS uE3 and inhibin-A assays had an 81-83% detection rate for Trisomy21 for a 5% false-positive rate. The new BRAHMS assays achieved the expected screening performance provided the risk estimation model is adjusted to account for the higher BRAHMS uE3 MoM measurement distribution variance.
Assuntos
Síndrome de Down/diagnóstico , Estriol/sangue , Imunoensaio/instrumentação , Inibinas/sangue , Diagnóstico Pré-Natal/métodos , Feminino , Humanos , Gravidez , Segundo Trimestre da Gravidez , Estudos Retrospectivos , alfa-Fetoproteínas/análiseRESUMO
OBJECTIVE: To evaluate the efficacy of the quadruple test for potential use as a Thai national policy for Down syndrome (DS) screening and establish an accurate equation for risk estimation of Down syndrome based on gestational age, weight and the ethnic-specific reference range of our population. METHODS: A prospective study was conducted on singleton pregnancies at 14 to 21 weeks of gestation to evaluate the efficacy of quadruple DS screening using the automatically calculated Western European descent factor (WF) in our population and the impact of screening using a specific Thai ethnic factor as well as to establish an equation for the risk estimation of DS based on gestational age, weight and a local Thai ethnic factor to correct for the impact of ethnic factor on the screening efficacy. RESULTS: Of a total of 5,515 women, 12 cases of DS and 8 cases of other aneuploidies were found. The detection rate, false positive rate and specificity were 75.0%, 9.1% and 90.9%, respectively, by automatic calculation with the widely used WF; the screening efficacy was lower when used in Asian populations than in other studies. The best-fitted regression equation of serum quadruple screening of AFP, free ß-hCG, uE3 and inhibin A was established by adjustment for gestational age (GA) in days, maternal weight and our Thai-specific ethnic reference range which was created for this study. Calculations with our Thai-specific ethnic model gave a better detection rate of 83.3%, a false positive rate of 9.6% and specificity of 90.4%. CONCLUSION: The serum quadruple test had a lower detection rate than expected when the risk estimation was based on the WF reference range. The serum quadruple test using WF had significantly different levels when corrected with our ethnic-specific factor. Using our local ethnic specific model could increase the detection rate of DS screening in Thailand with a minimal increase in false positive rates. Our findings indicate that DS screening should be adjusted with an appropriate individual ethnic factor when used for national screening.
Assuntos
Síndrome de Down/diagnóstico , Etnicidade/genética , Diagnóstico Pré-Natal/métodos , Povo Asiático/genética , Biomarcadores/sangue , Gonadotropina Coriônica Humana Subunidade beta/sangue , Países em Desenvolvimento , Síndrome de Down/sangue , Estriol/sangue , Feminino , Humanos , Inibinas/sangue , Gravidez , Segundo Trimestre da Gravidez , Gestantes , Diagnóstico Pré-Natal/estatística & dados numéricos , Valores de Referência , Tailândia , População Branca/genética , alfa-Fetoproteínas/análiseRESUMO
We aimed to assess whether the second-trimester maternal serum markers could be used for the prediction of labour induction success. This prospective study enrolled women planned labour induction at term. Women were assigned to one of two groups: vaginal prostaglandin or balloon dilatation. All patients were evaluated for Bishop score, maternal serum oestriol, human chorionic gonadotropin and progesterone at the time of second-aneuploidy screening. The total successful rate for induction of labour was 63.9% in both groups. Maternal serum oestriol multiple of median (MoM) values were significantly lower among the caesarean section group compared to the vaginal delivery group (p < .001). A MoM value of 0.74 for oestriol was associated with a sensitivity of 75.9%, specificity of 41.0%, a positive predictive value of 76.6% and a negative predictive value of 58.0% for a successful induction of labour. Oestriol had a good performance in the prediction of successful induction of labour at term.IMPACT STATEMENTWhat is already known on this subject? Induction of labour is a common procedure undertaken whenever the benefits of prompt delivery outweigh the risks of expectant management. Previous studies have reported that a decreased progesterone/oestradiol ratio and increased maternal plasma oestriol levels are associated with successful labour. What the results of this study add? The results of this study showed that second-trimester oestriol multiple of median (MoM) value provide a significant contribution to the efforts of the prediction of successful induction of labour in term pregnancy, having a sensitivity of 69.8%, specificity of 92.4%, positive predictive value of 83.3% and negative predictive value of 82.5%.What the implications are of these findings for clinical practice and/or further research? This finding can be used as an additional method for prediction of labour induction as well as multiparity and Bishop score. This adds new valuable data to the literature which could be used for systematic reviews and for implementing guidelines and protocols on labour induction.
Assuntos
Parto Obstétrico/estatística & dados numéricos , Trabalho de Parto Induzido/estatística & dados numéricos , Testes para Triagem do Soro Materno/estatística & dados numéricos , Segundo Trimestre da Gravidez/sangue , Nascimento a Termo/sangue , Administração Intravaginal , Adulto , Aneuploidia , Cesárea/estatística & dados numéricos , Gonadotropina Coriônica/sangue , Parto Obstétrico/métodos , Dilatação/métodos , Estriol/sangue , Feminino , Humanos , Trabalho de Parto Induzido/métodos , Valor Preditivo dos Testes , Gravidez , Progesterona/sangue , Estudos Prospectivos , Prostaglandinas/administração & dosagem , Resultado do TratamentoRESUMO
OBJECTIVE: This study aimed to examine whether prenatal biochemical screening analytes are associated with an increased risk of severe maternal morbidity (SMM) or maternal mortality. STUDY DESIGN: This population-based cohort study includes all women in Ontario, Canada, who underwent prenatal screening from 2001 to 2011. Increasing fifth percentiles of the multiple of the median (MoM) for alphafetoprotein (AFP), total human chorionic gonadotropin, unconjugated estriol (uE3), dimeric inhibin-A (DIA), and pregnancy-associated plasma protein A were evaluated. An abnormally high concentration (>95th percentile MoM) for each analyte, individually and combined, was also evaluated. The main outcome assessed was the adjusted relative risk (aRR) of SMM or maternal mortality from 20 weeks' gestation up to 26 weeks thereafter. RESULTS: Among 748,972 pregnancies, 11,177 resulted in SMM or maternal mortality (1.5%). Except for uE3, the aRR of SMM or maternal mortality increased in association with increasing fifth percentiles of the MoM for all analytes. AFP (aRR: 2.10; 95% confidence interval [CI]: 1.97-2.25) and DIA (aRR: 2.33; 95% CI: 1.98-2.74) > 95th versus ≤ 5th percentile of the MoM were especially associated with SMM or death. CONCLUSION: Women with abnormally high concentrations of certain prenatal biochemical analytes may be at a higher risk of SMM or death in pregnancy or postpartum.
Assuntos
Biomarcadores/sangue , Análise Química do Sangue , Mortalidade Materna , Complicações na Gravidez/sangue , Proteína Plasmática A Associada à Gravidez , Diagnóstico Pré-Natal , Transtornos Puerperais , Adolescente , Adulto , Gonadotropina Coriônica/sangue , Estudos de Coortes , Estriol/sangue , Feminino , Humanos , Inibinas/sangue , Idade Materna , Pessoa de Meia-Idade , Ontário , Gravidez , Resultado da Gravidez , Proteína Plasmática A Associada à Gravidez/análise , Transtornos Puerperais/sangue , Transtornos Puerperais/diagnóstico , Medição de Risco , Adulto Jovem , alfa-Fetoproteínas/análiseRESUMO
OBJECTIVES: Bovine alkaline phosphatase (BALP) mediated interference is a potential issue in the Beckman Access unconjugated estriol (uE3) assay. As the uE3 assay is a component of second trimester maternal serum screening characterizing this interference is essential for delivering accurate trisomy 18 and trisomy 21 risks. DESIGN AND METHODS: Residual serum samples (n = 517) were measured by two different lots of uE3 assay. Scavenger BALP (sBALP) was added to all samples to remove potential BALP dependent interference and assessed using both lots of uE3 reagent. RESULTS: BALP mediated interference was observed in similar frequency in both lots of reagent (~3%), although the patterns of positive and negative interference differed between the lots. Pretreatment with sBALP improved lot-to-lot comparison. The presence of BALP related interference was not related to the concentration of endogenous human alkaline phosphatase. The use of polyethylene glycol and sBALP treatment appeared to mitigate BALP mediated interference equally well, and resulted in concordance in measured uE3 concentrations between reagent lots. Additionally, heterophile antibody interference was observed in two samples affected with BALP interference, and the heterophile antibody interference was resolved by both PEG and heterophile antibody blocking reagent treatment, but not sBALP treatment. While the maternal screen numeric risk for affected samples changed, the risk classification changed from a negative to positive screen in two samples. CONCLUSIONS: Interference in the uE3 assay has the potential to affect maternal serum risk calculations in different reagent lots, and pretreatment of samples with scavenger BALP or PEG should be considered in cases of unexplained uE3 concentrations.
Assuntos
Fosfatase Alcalina/química , Biomarcadores/sangue , Testes Diagnósticos de Rotina/normas , Síndrome de Down/diagnóstico , Estriol/sangue , Testes para Triagem do Soro Materno/normas , Diagnóstico Pré-Natal/métodos , Fosfatase Alcalina/metabolismo , Animais , Bovinos , Síndrome de Down/sangue , Feminino , Humanos , Gravidez , Segundo Trimestre da GravidezRESUMO
BACKGROUND: To identify the relationship between quadruple test for aneuploidy screening (alpha-fetoprotein: AFP; free beta-human chorionic gonadotropin: b-hCG; unconjugated estriol: uE3 and inhibin-A: IHA) and fetal growth restriction and to construct predictive models for small-for-gestational-age (SGA) fetuses. METHODS: Women who underwent quadruple test for aneuploidy were followed-up for final outcomes. The multiples of the median (MoMs) of the four biochemical markers for the SGA group and those of normal fetuses were compared. The models for predicting SGA by the individual biomarkers and their combination were constructed using binary logistic regression analysis, and their diagnostic performances in predicting SGA were determined. RESULTS: Of 10,155 eligible pregnant women, 578 (5.7%) and 9577 (94.3%) had SGA and normal growth, respectively. High levels of AFP, b-hCG and IHA but low levels of uE3 significantly increased the risk of SGA. The constructed predictive equations had predictive performance for SGA, with areas under the receiver-operated characteristic curve of 0.724, 0.655, 0.597, 0.664 and 0.754 for AFP, b-hCG, uE3, IHA, and the combination, respectively. CONCLUSION: The quad test for aneuploidy screening could also be used as a predictor of SGA, without extra-effort and extra-cost.
Assuntos
Síndrome de Down/diagnóstico , Retardo do Crescimento Fetal/epidemiologia , Recém-Nascido Pequeno para a Idade Gestacional , Programas de Rastreamento/métodos , Adolescente , Adulto , Biomarcadores , Gonadotropina Coriônica Humana Subunidade beta/sangue , Síndrome de Down/sangue , Síndrome de Down/genética , Estriol/sangue , Feminino , Retardo do Crescimento Fetal/sangue , Retardo do Crescimento Fetal/genética , Seguimentos , Idade Gestacional , Humanos , Recém-Nascido , Inibinas/sangue , Modelos Genéticos , Valor Preditivo dos Testes , Gravidez , Segundo Trimestre da Gravidez/sangue , Medição de Risco/métodos , Tailândia/epidemiologia , Adulto Jovem , alfa-Fetoproteínas/análiseRESUMO
BACKGROUND: Gestational diabetes mellitus (GDM) is associated with adverse diabetic complications for both mother and child during pregnancy. The common Gold Standard (GS) for diagnosis of GDM is 75 g oral glucose tolerance test (OGTT) during 24-28 gestational weeks which seems a little late for any proper intervention. This study aimed to employ the Bayesian latent class models (LCMs) for estimating the early diagnostic power of combination of serum multiple marker in detecting GDM during 14-17 weeks of gestation. METHODS: Data from a sample of 523 pregnant women who participated in gestational diabetes screening tests at health centers affiliated to Shahid Beheshti University of Medical Sciences in Tehran, Iran from 2017 to 2018 were used. The beta-human chorionic gonadotropin (ß-hCG), unconjugated estriol (uE3), and alfa-fetoprotein (AFP) values were extracted from case records for all participants. The Bayesian LCMs were applied for estimating sensitivity, specificity, and area under receiver operating characteristic curve (AUC) of combining the three biomarkers' results in the absence of GS, adjusting for maternal age and body mass index. RESULTS: The mean (standard deviation) maternal age of the participants was 28.76 (±5.33) years. Additionally, the mean (standard deviation) BMI was 24.57 (±3.22) kg/m2. According to the Bayesian model, the cSensitivity, cSpecificity, and cAUC for the optimal composite diagnostic test were estimated as 94% (95% credible interval (CrI) [0.91-0.99]), 86% (95% CrI [0.80-0.92]), and 0.92 (95% CrI [0.87-0.98]), respectively. CONCLUSIONS: Overall, the findings revealed that the combination of uE3, AFP, and ß-hCG results might be considered as an acceptable predictor for detecting GDM with a rather high level of accuracy in the early second trimester of pregnancy without a GS.
Assuntos
Biomarcadores/sangue , Diabetes Gestacional/diagnóstico , Adulto , Teorema de Bayes , Gonadotropina Coriônica/sangue , Gonadotropina Coriônica Humana Subunidade beta/sangue , Testes Diagnósticos de Rotina , Diagnóstico Precoce , Estriol/sangue , Feminino , Idade Gestacional , Humanos , Irã (Geográfico) , Gravidez , Segundo Trimestre da Gravidez , Diagnóstico Pré-Natal/métodos , Curva ROC , Sensibilidade e Especificidade , Adulto Jovem , alfa-Fetoproteínas/análiseRESUMO
BACKGROUND: We aimed to determine whether inhibin A could be a reliable and accurate predictor of preterm birth, and discuss the possible pathogenic processes of inhibin A leading to preterm birth. METHODS: A retrospective cohort study was conducted on consecutive singleton pregnant women who underwent the second-trimester quad screen test at a gestational age of 15-20 weeks at Keelung Chang-Gung Memorial Hospital from March 2011 to May 2015. Data including maternal characteristics and pregnancy outcomes were collected from an electric medical record database. Data regarding pregnancy terminations before a gestational age of 24 weeks and regarding pregnancies that involved chromosomal or congenital anomalies were excluded from this analysis. One-way analysis of variance was used to compare second-trimester α-fetoprotein, human chorionic gonadotropin, unconjugated estriol, and inhibin A in women with preterm deliveries versus those with term deliveries. RESULTS: Although a total of 935 women with singleton pregnancies were enrolled, pregnancy outcome and complete maternal data were obtained from only 770 (82.3%)of them. In total, 687 (89.2%) women delivered at or after 37 weeks of gestation and 83 (10.8%) women delivered before 37 weeks of gestation. The results showed that the inhibin A level was significantly increased in the preterm labor group (p = 0.009). A cutoff inhibin A value above 2.25 was identified statistical significantly in the preterm labor group. CONCLUSIONS: From our results, an inhibin A level above 2.25 multiples of the median in the quad screen test may be associated with preterm labor afterward. Closely monitoring for uterine contractions or cervical length measurement in the second trimester may be indicated in patients with unexplained elevated inhibin A levels.
Assuntos
Gonadotropina Coriônica/sangue , Hospitais Comunitários/estatística & dados numéricos , Inibinas/sangue , Nascimento Prematuro/sangue , Adulto , Estriol/sangue , Feminino , Idade Gestacional , Humanos , Trabalho de Parto Prematuro/sangue , Trabalho de Parto Prematuro/diagnóstico , Gravidez , Resultado da Gravidez , Nascimento Prematuro/diagnóstico , TaiwanRESUMO
AIMS: To quantify estriol serum concentrations in "new" and "chronic users" of topical estriol cream using quantitative liquid chromatography tandem mass spectrometry. METHODS: In this singlecentre prospective observational study, postmenopausal women with urogynaecological complaints were enrolled: 40 had not used topical estriol previously ("new users") and 50 had been applying estriol cream for more than 12 weeks ("chronic users"). In "new users," serum estriol levels were measured at baseline and after 12 weeks use. Estriol cream 1 mg/g was used daily for 3 weeks, then twice weekly with applicator (group 1A) or digitally (group 1B) or three times per week digitally (group 1C). "Chronic users" applied the cream twice (n = 7) or three (n = 43) times per week. Serum samples were taken in the morning after using cream the previous night. The main outcome measures were estriol serum concentrations in "new" and "chronic users" of estriol cream. RESULTS: Baseline serum estriol concentrations were less than 5 pmol/L in all 40 "new users." At 12 weeks, the 12-hour serum estriol levels ranged from less than 5 to 494 pmol/L (median 22.8; Interquartile range [IQR] 9.2-108.5). Seven "new users" had levels more than 100 pmol/L. Most of the 50 "chronic users" also had 12-hour levels less than 100 pmol/L (median 15.1 pmol/L [IQR 2.7-33.9]: three had levels more than 100 pmol/L. CONCLUSIONS: This study reports serum estriol concentrations in a large number of "new" and "chronic users" of vaginal estriol cream, employing a novel highly sensitive and specific technique. Overall, the results are reassuring: 87% had 12-hour estriol levels less than 100 pmol/L.
Assuntos
Estriol/sangue , Pós-Menopausa/sangue , Cremes, Espumas e Géis Vaginais , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
OBJECTIVE: This study aimed to evaluate if maternal serum hormones along the maternal-fetal hypothalamic-pituitary-adrenal (HPA) axis, when drawn prior to labor induction, differed between women who delivered vaginally and those who underwent cesarean. STUDY DESIGN: This was a prospective observational study at a single perinatal center performed from August 2017 to May 2018. Nulliparous women with uncomplicated singleton pregnancies ≥39 weeks had maternal serum collected prior to induction. Corticotrophin-releasing hormone (CRH) was measured by ELISA; dehydroepiandrosterone sulfate (DHEA-S), cortisol, estriol (E3) estradiol (E2), and progesterone (P4) were measured by chemiluminescent reaction. Mean analyte concentrations as well as three ratios (E2/P4, E3/P4, and E2/E3) were compared between women who had a vaginal versus cesarean delivery. Logistic regression was used to model the relationship between CRH and the odds of vaginal birth. We estimated that a sample size of 66 would have 90% power to detect a 25% difference in mean CRH levels assuming a vaginal:cesarean ratio of 2:1 with a baseline CRH concentration of 140 (standard deviation = 36) pg/mL. RESULTS: Of the 88 women who had their serum analyzed, 27 (31%) underwent cesarean. Mean maternal serum CRH levels were similar between the vaginal delivery and cesarean groups (122.6 ± 95.2 vs. 112.3 ± 142.4, p = 0.73). Similarly, there were no significant differences in any other maternal serum analytes or ratios. Logistic regression showed a nonsignificant odds ratio for successful vaginal birth (p = 0.69) even when evaluating only the 16 women who had a cesarean for an arrest disorder (p = 0.08). CONCLUSION: In low-risk nulliparous women undergoing full-term labor induction, there were no differences noted in a broad array of other maternal-fetal HPA-axis hormones between women who had a vaginal or cesarean delivery.
Assuntos
Recém-Nascido/sangue , Sistema Hipófise-Suprarrenal/metabolismo , Gravidez/metabolismo , Adulto , Cesárea , Sulfato de Desidroepiandrosterona/sangue , Estradiol/sangue , Estriol/sangue , Feminino , Sangue Fetal/metabolismo , Humanos , Hidrocortisona/sangue , Sistema Hipotálamo-Hipofisário/metabolismo , Trabalho de Parto Induzido , Modelos Logísticos , Complicações na Gravidez/sangue , Progesterona/sangue , Estudos ProspectivosRESUMO
Abnormal sex hormone levels in utero have been associated with child behavioral problems, but it is unclear if normal variation in prenatal sex hormones is associated with subsequent behavior in childhood. We assessed maternal sex hormones, including serum estrone (E1), estradiol (E2), estriol (E3), free testosterone (FT), and total testosterone (TT), during early pregnancy (gestational week 6-21 (mean = 11.1)) and evaluated child behavior at ages 4-5 using the Behavioral Assessment System for Children (BASC-2) and Social Responsiveness Scale (SRS-2) in 404 mother/child pairs (211 girls, 193 boys) within The Infant Development and Environment Study, a multi-site pregnancy cohort study. Associations between hormones and composite scores were evaluated using multiple linear regressions in both sexes combined, and separate models assessed effect modification by sex with the addition of interaction terms. A 10-fold increase in maternal FT or TT was associated in both sexes with a 4.3-point (95 % CI: 0.5, 8.2) or 4.4-point (0.8, 8.0) higher BASC-2 internalizing composite T score, respectively. In addition, a 10-fold increase in FT or TT was associated with a 3.8-point (0.04, 7.5) or 4.0-point (0.5, 7.5) higher behavioral symptoms index composite score. In models evaluating effect modification by sex, a 10-fold increase in E1 was associated with a 4.3-point (1.2, 7.4) decrease in adaptive skills composite score in girls only (interaction p = 0.04). We observed associations between testosterone and internalizing behaviors and behavioral symptoms index in both sexes, as well as a female-specific association between E1 and adaptive skills. Sex hormones during pregnancy may play a key role in influencing later-life behavior, and additional studies should further examine different periods of susceptibility to hormonal signals.
Assuntos
Comportamento Infantil/fisiologia , Desenvolvimento Infantil/efeitos dos fármacos , Hormônios Esteroides Gonadais/efeitos adversos , Adulto , Comportamento Infantil/efeitos dos fármacos , Comportamento Infantil/psicologia , Pré-Escolar , Estudos de Coortes , Estradiol/análise , Estradiol/sangue , Estriol/análise , Estriol/sangue , Estrona/análise , Estrona/sangue , Feminino , Hormônios Esteroides Gonadais/sangue , Humanos , Masculino , Transtornos do Neurodesenvolvimento/etiologia , Transtornos do Neurodesenvolvimento/metabolismo , Gravidez , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Comportamento Problema/psicologia , Testosterona/análise , Testosterona/sangueRESUMO
Fetal adrenal-derived OH-DHEAS is the primary precursor for maternal estriol, an abundant, human, placental estrogen. We measured maternal pregnancy estriol as a marker of fetal adrenal functionâ¯+â¯placenta capacity to synthesize estriol. We hypothesized that maternal estriol is directly correlated with the adrenal hormone, DHEAS, in young adult women. We tested this hypothesis in a subset of women in the Child Health and Development Studies (351 of 470 eligible). 176 of these had serum samples collected at ages 27-30 for DHEAS assays, archived maternal pregnancy serum for estriol assays, and childhood growth data. In regression analyses, both maternal estriol and accelerated growth in middle childhood were independently, directly associated with DHEAS (+19% for quartile 4 versus quartile 1 of estriol, 95%CI=+ 2%, +36% and +12% for quartile 4 versus quartile 1 for middle childhood growth, 95%CI= +3%, +21%). Adrenal function may be programmed in utero and middle childhood with long-term consequences.
Assuntos
Desenvolvimento Infantil , Sulfato de Desidroepiandrosterona/sangue , Estriol/sangue , Estrogênios/sangue , Terceiro Trimestre da Gravidez/sangue , Adulto , California , Criança , Estudos de Coortes , Feminino , Humanos , Gravidez , Adulto JovemRESUMO
We previously reported that postmenopausal obese women exhibit increased levels of circulating adipocyte fatty acid binding protein (A-FABP), which is associated with breast cancer (BC) development. In postmenopause, increased oestrogen levels are reported to be associated with increased BC risk. Herein, we assessed if oestrogens, including oestrone (E1), oestradiol (E2) and oestriol (E3), are associated with A-FABP in the obesity-related BC development. We collected 249 serum samples from women with or without BC and measured serum levels of E1, E2, E3 and A-FABP. Considering all subjects, E1 and E2 but not E3 levels were significantly higher in pre- than in postmenopause individuals. E3 and E1 levels were higher in non-obese than in obese women. When samples were separated by BC status, E2 levels were significantly higher, while E1 and E3 levels were significantly lower in postmenopausal obese than non-obese women without BC. These differences based on body mass index (BMI) were not observed among women with BC. E3 levels were higher in obese women with BC than those without. A-FABP levels were significantly higher in postmenopausal obese women regardless of BC status. In addition, A-FABP was not associated with E1, E2 or E3. Altogether, our data suggest that A-FABP is independently regulated by obesity and menopausal status compared to oestrogens, thus playing a unique role in the development of BC.
Assuntos
Neoplasias da Mama/metabolismo , Estrogênios/sangue , Proteínas de Ligação a Ácido Graxo/metabolismo , Obesidade/metabolismo , Pós-Menopausa/metabolismo , Pré-Menopausa/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Método Duplo-Cego , Estradiol/sangue , Estriol/sangue , Estrona/sangue , Feminino , Humanos , Pessoa de Meia-Idade , Pós-Menopausa/sangue , Pré-Menopausa/sangue , Regulação para Cima , Adulto JovemRESUMO
The field of pediatric Surgery now encompasses fetal Surgery. The purpose of this article is to review aspects of antepartum care pertinent to the fetal and pediatric surgeon. We summarize antepartum screening, methods to assess the fetus, gestational disorders and variants of umbilical cord insertion sites and the placenta.
Assuntos
Testes Genéticos , Diagnóstico Pré-Natal , Aneuploidia , Gonadotropina Coriônica/sangue , Anormalidades Congênitas/diagnóstico , Estriol/sangue , Feminino , Desenvolvimento Fetal , Retardo do Crescimento Fetal/diagnóstico , Humanos , Oligo-Hidrâmnio/diagnóstico , Placenta/anormalidades , Poli-Hidrâmnios/diagnóstico , Gravidez , Trimestres da Gravidez , Proteína Plasmática A Associada à Gravidez/análise , Ultrassonografia Pré-Natal , Cordão Umbilical/anormalidades , alfa-Fetoproteínas/análiseRESUMO
OBJECTIVE: To determine the association between second-trimester serum Down syndrome screening (alpha-fetoprotein [AFP] free beta-human chorionic gonadotropin [b-hCG] unconjugated estriol [uE3]) and preterm birth and to create predictive models for preterm birth. METHODS: Secondary analysis on a prospective database of pregnancies undergoing second-trimester screen with complete follow-up. The multiples of medians (MoM) of the biomarkers were compared between the group of term, preterm (< 37 weeks), early preterm (< 34 weeks), and very early preterm (< 32 weeks) delivery. Predictive models were developed based on adjusted MoMs and logistic regression and diagnostic performances in predicting preterm birth were determined. RESULTS: Of 20,780 pregnancies, 1,554 (7.5), 363 (1.7), and 158 (0.8%) had preterm, early preterm, and very early preterm birth respectively. High levels of AFP and b-hCG but low levels of uE3 were significantly associated with higher rates of preterm, early preterm and very early preterm delivery. The predictive models had diagnostic performance in predicting preterm birth with the areas under the ROC curve of 0.688, 0.534, 0.599, and 0.718 for AFP, b-hCG, uE3, and combined biomarkers respectively. CONCLUSION: The second trimester Down syndrome screening could also be used as a tool of risk identification of preterm birth in the same test, without extra-effort and extra-cost.
Assuntos
Síndrome de Down/diagnóstico , Testes para Triagem do Soro Materno/estatística & dados numéricos , Segundo Trimestre da Gravidez/sangue , Nascimento Prematuro/diagnóstico , Adulto , Aneuploidia , Biomarcadores/sangue , Gonadotropina Coriônica Humana Subunidade beta/sangue , Síndrome de Down/embriologia , Estriol/sangue , Feminino , Humanos , Recém-Nascido , Modelos Logísticos , Valor Preditivo dos Testes , Gravidez , Nascimento Prematuro/etiologia , Estudos Prospectivos , Curva ROC , alfa-Fetoproteínas/análiseRESUMO
Objectives To identify factors predicting maternal sex steroid hormone concentrations in early pregnancy. Methods The Infant Development and the Environment Study recruited healthy pregnant women from academic medical centers in four US cities. Gold standard liquid chromatography-tandem mass spectrometry was used to measure maternal sex steroids concentrations (total testosterone [TT], free testosterone [FT], estrone [E1], estradiol [E2], and estriol [E3] concentrations) in serum samples from 548 women carrying singletons (median = 11.7 weeks gestation). Women completed questionnaires on demographic and lifestyle characteristics. Results In multivariable linear regression analyses, hormone concentrations varied in relation to maternal age, body mass index (BMI), race, and parity. Older mothers had significantly lower levels of most hormones; for every year increase in maternal age, there was a 1-2% decrease in E1, E2, TT, and FT. By contrast, each unit increase in maternal BMI was associated 1-2% lower estrogen (E1, E2, E3) levels, but 1-2% higher androgen (TT, FT) concentrations. Hormone concentrations were 4-18% lower among parous women, and for each year elapsed since last birth, TT and FT were 1-2% higher (no difference in estrogens). Androgen concentrations were 18-30% higher among Black women compared to women of other races. Fetal sex, maternal stress, and lifestyle factors (including alcohol and tobacco use) were not related to maternal steroid concentrations. Conclusions for Practice Maternal demographic factors predict sex steroid hormone concentrations during pregnancy, which is important given increasing evidence that the prenatal endocrine environment shapes future risk of chronic disease for both mother and offspring.