MARIA DE LOURDES BRIZOT
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Obstetrícia e Ginecologia, Faculdade de Medicina - Docente
LIM/57 - Laboratório de Fisiologia Obstétrica, Hospital das Clínicas, Faculdade de Medicina - Líder
LIM/57 - Laboratório de Fisiologia Obstétrica, Hospital das Clínicas, Faculdade de Medicina - Líder
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- Vaginal progesterone decreases preterm birth and neonatal morbidity and mortality in women with a twin gestation and a short cervix: an updated meta-analysis of individual patient data(2017) ROMERO, R.; CONDE-AGUDELO, A.; EL-REFAIE, W.; RODE, L.; BRIZOT, M. L.; CETINGOZ, E.; SERRA, V.; FONSECA, E. Da; ABDELHAFEZ, M. S.; TABOR, A.; PERALES, A.; HASSAN, S. S.; NICOLAIDES, K. H.ObjectiveTo assess the efficacy of vaginal progesterone for the prevention of preterm birth and neonatal morbidity and mortality in asymptomatic women with a twin gestation and a sonographic short cervix (cervical length 25 mm) in the mid-trimester. MethodsThis was an updated systematic review and meta-analysis of individual patient data (IPD) from randomized controlled trials comparing vaginal progesterone with placebo/no treatment in women with a twin gestation and a mid-trimester sonographic cervical length 25 mm. MEDLINE, EMBASE, POPLINE, CINAHL and LILACS (all from inception to 31 December 2016), the Cochrane Central Register of Controlled Trials, Research Registers of ongoing trials, Google Scholar, conference proceedings and reference lists of identified studies were searched. The primary outcome measure was preterm birth < 33 weeks' gestation. Two reviewers independently selected studies, assessed the risk of bias and extracted the data. Pooled relative risks (RRs) with 95% confidence intervals (CI) were calculated. ResultsIPD were available for 303 women (159 assigned to vaginal progesterone and 144 assigned to placebo/no treatment) and their 606 fetuses/infants from six randomized controlled trials. One study, which included women with a cervical length between 20 and 25 mm, provided 74% of the total sample size of the IPD meta-analysis. Vaginal progesterone, compared with placebo/no treatment, was associated with a statistically significant reduction in the risk of preterm birth < 33 weeks' gestation (31.4% vs 43.1%; RR, 0.69 (95% CI, 0.51-0.93); moderate-quality evidence). Moreover, vaginal progesterone administration was associated with a significant decrease in the risk of preterm birth < 35, < 34, < 32 and < 30 weeks' gestation (RRs ranging from 0.47 to 0.83), neonatal death (RR, 0.53 (95% CI, 0.35-0.81)), respiratory distress syndrome (RR, 0.70 (95% CI, 0.56-0.89)), composite neonatal morbidity and mortality (RR, 0.61 (95% CI, 0.34-0.98)), use of mechanical ventilation (RR, 0.54 (95% CI, 0.36-0.81)) and birth weight < 1500 g (RR, 0.53 (95% CI, 0.35-0.80)) (all moderate-quality evidence). There were no significant differences in neurodevelopmental outcomes at 4-5 years of age between the vaginal progesterone and placebo groups. ConclusionAdministration of vaginal progesterone to asymptomatic women with a twin gestation and a sonographic short cervix in the mid-trimester reduces the risk of preterm birth occurring at < 30 to < 35 gestational weeks, neonatal mortality and some measures of neonatal morbidity, without any demonstrable deleterious effects on childhood neurodevelopment. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.
- Vaginal progesterone for preventing preterm birth and adverse perinatal outcomes in twin gestations: a systematic review and meta-analysis(2023) CONDE-AGUDELO, Agustin; ROMERO, Roberto; REHAL, Anoop; BRIZOT, Maria L.; SERRA, Vicente; FONSECA, Eduardo Da; CETINGOZ, Elcin; SYNGELAKI, Argyro; PERALES, Alfredo; HASSAN, Sonia S.; NICOLAIDES, Kypros H.OBJECTIVE: To evaluate the efficacy of vaginal progesterone for the prevention of preterm birth and adverse perinatal outcomes in twin gestations.DATA SOURCES: MEDLINE, Embase, LILACS, and CINAHL (from their inception to January 31, 2023), Cochrane databases, Google Scholar, bibliographies, and conference proceedings.STUDY ELIGIBILITY CRITERIA: Randomized controlled trials that compared vaginal progesterone to placebo or no treatment in asymptomatic women with a twin gestation.METHODS: The systematic review was conducted according to the Cochrane Handbook for Systematic Reviews of Interventions. The primary outcome was preterm birth <34 weeks of gestation. Secondary outcomes included adverse perinatal outcomes. Pooled relative risks with 95% confidence intervals were calculated. We assessed the risk of bias in each included study, heterogeneity, publication bias, and quality of evidence, and performed subgroup and sensitivity analyses.RESULTS: Eleven studies (3401 women and 6802 fetuses/infants) fulfilled the inclusion criteria. Among all twin gestations, there were no significant differences between the vaginal progesterone and placebo or no treatment groups in the risk of preterm birth <34 weeks (relative risk, 0.99; 95% confidence interval, 0.84-1.17; high-quality evidence), <37 weeks (relative risk, 0.99; 95% confidence interval, 0.92-1.06; high-quality evidence), and <28 weeks (relative risk, 1.00; 95% confidence interval, 0.64-1.55; moderate-quality evidence), and spontaneous preterm birth <34 weeks of gestation (relative risk, 0.97; 95% confidence interval, 0.80-1.18; high-quality evidence). Vaginal progesterone had no significant effect on any of the perinatal outcomes evaluated. Subgroup analyses showed that there was no evidence of a different effect of vaginal progesterone on preterm birth <34 weeks of gestation related to chorionicity, type of conception, history of spontaneous preterm birth, daily dose of vaginal progesterone, and gestational age at initiation of treatment. The frequencies of preterm birth <37, <34, <32, <30, and <28 weeks of gestation and adverse perinatal outcomes did not significantly differ between the vaginal progesterone and placebo or no treatment groups in unselected twin gestations (8 studies; 3274 women and 6548 fetuses/infants). Among twin gestations with a transvaginal sonographic cervical length <30 mm (6 studies; 306 women and 612 fetuses/infants), vaginal progesterone was associated with a significant decrease in the risk of preterm birth occurring at <28 to <32 gestational weeks (relative risks, 0.48-0.65; moderate-to high-quality evidence), neonatal death (relative risk, 0.32; 95% confidence interval, 0.11-0.92; moderate-quality evidence), and birthweight <1500 g (relative risk, 0.60; 95% confidence interval, 0.39-0.88; high-quality evidence). Vaginal progesterone significantly reduced the risk of preterm birth occurring at <28 to <34 gestational weeks (relative risks, 0.41-0.68), composite neonatal morbidity and mortality (relative risk, 0.59; 95% confidence interval, 0.33-0.98), and birthweight <1500 g (relative risk, 0.55; 95% confidence interval, 0.33-0.94) in twin gestations with a transvaginal sonographic cervical length <= 25 mm (6 studies; 95 women and 190 fetuses/infants). The quality of evidence was moderate for all these outcomes. CONCLUSION: Vaginal progesterone does not prevent preterm birth, nor does it improve perinatal outcomes in unselected twin gestations, but it appears to reduce the risk of preterm birth occurring at early gestational ages and of neonatal morbidity and mortality in twin gestations with a sonographic short cervix. However, more evidence is needed before recommending this intervention to this subset of patients.
- Vaginal progesterone for the prevention of preterm birth and adverse perinatal outcomes in twin gestations with a short cervix: an updated individual patient data meta-analysis(2022) ROMERO, R.; CONDE-AGUDELO, A.; REHAL, A.; FONSECA, E. Da; BRIZOT, M. L.; RODE, L.; SERRA, V.; CETINGOZ, E.; SYNGELAKI, A.; TABOR, A.; PERALES, A.; HASSAN, S. S.; NICOLAIDES, K. H.
- Fetal intra-abdominal bowel dilation in prediction of complex gastroschisis(2019) ANDRADE, W. S.; BRIZOT, M. L.; V, R. P. Francisco; TANNURI, A. C.; SYNGELAKI, A.; AKOLEKAR, R.; NICOLAIDES, K. H.Objective To investigate intra-abdominal bowel dilation (IABD) in the prediction of complex gastroschisis. Methods This was a retrospective study of 174 singleton pregnancies with isolated fetal gastroschisis, resulting in live birth and with available ultrasound images from visits at both 20-22 and 30-32 weeks' gestation. IABD was measured as the greatest transverse diameter of the most dilated intra-abdominal bowel segment, by an operator blinded to postnatal outcome. The distribution of IABD measurements in those with complex and those with simple gastroschisis was determined and the best cut-off value to predict complex gastroschisis was selected using receiver-operating characteristics (ROC) curves. The area under the ROC curve (AUC), detection rate (DR), false-positive rate (FPR), positive predictive value (PPV) and negative predictive value (NPV) were determined. Results The study population included 39 (22.4%) cases of complex and 135 (77.6%) cases of simple gastroschisis. In the prediction of complex gastroschisis, the AUC at 20-22 weeks' gestation was 0.742 (95% CI, 0.628-0.856) and the respective value for 30-32 weeks was 0.820 (95% CI, 0.729-0.910). At the IABD cut-off of 7 mm at 20-22 weeks, DR, FPR, PPV and NPV for complex gastroschisis were 61.5%, 6.7%, 72.7% and 89.4%, respectively, and at IABD cut-off of 14 mm at 30-32 weeks, the respective values were 64.9%, 5.9%, 75.0% and 90.7%. Conclusion Measurement of IABD at 20-22 or at 30-32 weeks' gestation is useful in the prediction of complex gastroschisis.
- Post-Viral Fatigue Following SARS-CoV-2 Infection during Pregnancy: A Longitudinal Comparative Study(2022) OLIVEIRA, Ana Maria da Silva Sousa; CARVALHO, Mariana Azevedo; NACUL, Luis; CABAR, Fabio Roberto; FABRI, Amanda Wictky; PERES, Stela Verzinhasse; ZACCARA, Tatiana Assuncao; O'BOYLE, Shennae; ALEXANDER, Neal; TAKIUTI, Nilton Hideto; MAYAUD, Philippe; BRIZOT, Maria de Lourdes; FRANCISCO, Rossana Pulcineli VieiraStudies reported post-COVID-19 fatigue in the general population, but not among pregnant women. Our objectives were to determine prevalence, duration, and risk factors of post-viral fatigue among pregnant women with SARS-CoV-2. This study involved 588 pregnant women with SARS-CoV-2 during pregnancy or delivery in Brazil. Three groups were investigated: G1 (n = 259, symptomatic infection during pregnancy); G2 (n = 131, positive serology at delivery); G3 (n = 198, negative serology at delivery). We applied questionnaires investigating fatigue at determined timepoints after infection for G1, and after delivery for all groups; fatigue prevalence was then determined. Cox regression was used to estimate hazard ratio (HR) and 95% CI of the risk of remaining with fatigue in G1. Overall fatigue prevalence in G1 at six weeks, three months and six months were 40.6%, 33.6%, and 27.8%, respectively. Cumulative risk of remaining with fatigue increased over time, with HR of 1.69 (95% CI: 0.89-3.20) and 2.43 (95% CI: 1.49-3.95) for women with moderate and severe symptoms, respectively. Multivariate analysis showed cough and myalgia as independent risk factors in G1. Fatigue prevalence was significantly higher in G1 compared to G2 and G3. Post-viral fatigue prevalence is higher in women infected during pregnancy; fatigue's risk and duration increased with the severity of infection.
- Vertical transmission of SARS-CoV2 during pregnancy: A high-risk cohort(2021) MAEDA, Mariane de Fatima Yukie; BRIZOT, Maria de Lourdes; GIBELLI, Maria Augusta Bento Cicaroni; IBIDI, Silvia Maria; CARVALHO, Werther Brunow de; HOSHIDA, Mara Sandra; MACHADO, Clarisse Martins; SABINO, Ester Cerdeira; SILVA, Lea Campos de Oliveira da; JAENISCH, Thomas; MENDES-CORREA, Maria Cassia Jacintho; MAYAUD, Philippe; FRANCISCO, Rossana Pulcinelli VieiraObjective Identify the potential for and risk factors of SARS-CoV-2 vertical transmission. Methods Symptomatic pregnant women with COVID-19 diagnosis in whom PCR for SARS-CoV-2 was performed at delivery using maternal serum and at least one of the biological samples: cord blood (CB), amniotic fluid (AF), colostrum and/or oropharyngeal swab (OPS) of the neonate. The association of parameters with maternal, AF and/or CB positivity and the influence of SARS-CoV-2 positivity in AF and/or CB on neonatal outcomes were investigated. Results Overall 73.4% (80/109) were admitted in hospital due to COVID-19, 22.9% needed intensive care and there were four maternal deaths. Positive RT-PCR for SARS-CoV-2 was observed in 14.7% of maternal blood, 13.9% of AF, 6.7% of CB, 2.1% of colostrum and 3.7% of OPS samples. The interval between COVID-19 symptoms and delivery was inversely associated with SARS-CoV-2 positivity in the maternal blood (p = 0.002) and in the AF and/or CB (p = 0.049). Maternal viremia was associated with positivity for SARS-CoV-2 in AF and/or CB (p = 0.001). SARS-CoV-2 positivity in the compartments was not associated with neonatal outcomes. Conclusion Vertical transmission is possible in pregnant women with COVID-19 and a shorter interval between maternal symptoms and delivery is an influencing factor.
- Impact of SARS-CoV-2 on pregnancy and neonatal outcomes: An open prospective study of pregnant women in Brazil(2022) GOMEZ, Ursula Trovato; FRANCISCO, Rossana Pulcineli Vieira; BAPTISTA, Fernanda Spadotto; GIBELLI, Maria Augusta B. C.; IBIDI, Silvia Maria; CARVALHO, Werther Brunow de; PAGANOTI, Cristiane de Freitas; SABINO, Ester Cerdeira; SILVA, Lea Campos de Oliveira da; JAENISCH, Thomas; MAYAUD, Philippe; BRIZOT, Maria de LourdesObjectives: To determine the incidence and risk of adverse obstetric and neonatal outcomes according to SARSCoV-2 infection severity in pregnant women. Method: Open prospective study of pregnant women tested for SARS-CoV-2 by serological and molecular assays during pregnancy or delivery in two hospitals in Sao Paulo, Brazil from April 12, 2020, to February 28, 2021. Five groups were considered for analysis: C0, negative COVID-19 results and no COVID-19 symptoms; C1, positive COVID-19 results, and no symptoms; C2, positive COVID-19 results with mild symptoms; C3, positive COVID-19 results with moderate symptoms; and C4, positive COVID-19 results with severe symptoms. The association between obstetric and neonatal outcomes and COVID-19 severity was determined using multivariate analysis. Results: 734 eligible pregnant women were enrolled as follows: C0 (n = 357), C1 (n = 127), C2 (n = 174), C3 (n = 37), and C4 (n = 39). The following pregnancy and neonatal outcomes were associated with severe COVID19: oligohydramnios (adjusted Odds Ratio [aOR] = 6.18; 95% CI 1.87-20.39), fetal distress (aOR = 4.01; 95% Confidence Interval [CI] 1.84-8.75), preterm birth (aOR = 5.51; 95% CI 1.47-20.61), longer hospital stay (aOR = 1.66; 95% CI 1.36-2.02), and admission to the neonatal intensive care unit (aOR = 19.36; 95% CI, 5.8663.99). All maternal (n = 6, 15.4%, p < 0.001) and neonatal (n = 5, 12.5%, p < 0.001) deaths and most fetal deaths (n = 4, 9.8%, p < 0.001) occurred in C4 group. Moderate COVID-19 was associated with oligohydramnios (aOR = 6.23; 95% CI 1.93-20.13) , preterm birth (aOR = 3.60; 95% CI 1.45-9.27). Mild COVID-19 was asso-ciated with oligohydramnios (aOR = 3.77; 95% CI 1.56-9.07). Conclusion: Adverse pregnancy and neonatal outcomes were associated with maternal symptomatic COVID-19 sta-tus , risk increased with disease severity.
- Vaginal progesterone in twin gestation with a short cervix: revisiting an individual patient data systematic review and meta-analysis(2021) ROMERO, R.; CONDE-AGUDELO, A.; RODE, L.; BRIZOT, M. L.; CETINGOZ, E.; SERRA, V.; FONSECA, E. Da; TABOR, A.; PERALES, A.; HASSAN, S. S.; NICOLAIDES, K. H.
- Monitoring SARS-CoV-2 seroprevalence over time among pregnant women admitted to delivery units: Suitability for surveillance(2023) MIYADAHIRA, Mariana Yumi; BRIZOT, Maria de Lourdes; ALEXANDER, Neal; SABINO, Ester Cerdeira; SILVA, Lea Campos de Oliveira da; HOSHIDA, Mara Sandra; OLIVEIRA, Ana Maria da Silva Sousa; FARCHE, Ana Claudia Silva; FRANCISCO, Rossana Pulcineli Vieira; MAYAUD, PhilippeObjectivesTo determine SARS-CoV-2 seroprevalence over time and risk factors among pregnant women at delivery in Sao Paulo, Brazil; and to evaluate the suitability of pregnant women as a sentinel population for SARS-CoV-2 serosurveillance. MethodsUnselected consecutive pregnant women presenting at the labor ward of a single large hospital between July 20(th) 2020 to February 21(st) 2021 were enrolled and tested for SARS-CoV-2 serology using two assays: the rapid chromatic Wondfo One Step (for total IgA and IgG detection) and Roche Elecsys assay (detecting anti-nucleoprotein [N] IgG). SARS-CoV-2 seroprevalence was computed as smooth spline function over time with 95% confidence intervals (CI). Risk factors were evaluated for positivity by each assay. We compared timepoint seroprevalence by the two assays with four concomitant community household surveys (HHS), in which the Roche assay was used, to determine the sensitivity and relevance of the pregnant women population as sentinel population. ResultsOverall SARS-CoV-2 seroprevalence was 28.9% (221/763) by Roche and 17.9% (137/763) by Wondfo. Reported symptoms experienced during pregnancy were all significantly correlated with being SARS-CoV-2 seropositive at delivery with any assay (with odds-ratios ranging from 3.0 [95% CI: 2.1-4.3] for coryza to 22.8 [95% CI: 12.3-46.6] for ageusia). Seropositivity by either assay was high in women at delivery in the early period of the pandemic (June 2020), compared with seropositivity in women from the concomitant HHS: 44.1% (95% CI: 21.8-66.4) for Roche, 54.1% (30.9-78.5) for Wondfo, versus 11.4% (95% CI: 9.2-13.6) for HHS. For later periods (October 2020 and January 2021), the seropositivity in women at delivery measured by Roche corresponded well with the prevalence found among women in the HHS using the same assay, whilst prevalence measured by Wondfo dropped. ConclusionsWomen at delivery represent a highly exposed and readily accessible population for sentinel surveillance of emerging infections such as SARS-CoV-2.