Performance of the first-trimester Fetal Medicine Foundation competing risks model for preeclampsia prediction: an external validation study in Brazil.

BACKGROUND: The current version of the Fetal Medicine Foundation competing risks model for preeclampsia prediction has not been previously validated in Brazil. OBJECTIVE: This study aimed (1) to validate the Fetal Medicine Foundation combined algorithm for the prediction of preterm preeclampsia in the Brazilian population and (2) to describe the accuracy and calibration of the Fetal Medicine Foundation algorithm when considering the prophylactic use of aspirin by clinical criteria. STUDY DESIGN: This was a cohort study, including consecutive singleton pregnancies undergoing preeclampsia screening at 11 to 14 weeks of gestation, examining maternal characteristics, medical history, and biophysical markers between October 2010 and December 2018 in a university hospital in Brazil. Risks were calculated using the 2018 version of the algorithm available on the Fetal Medicine Foundation website, and cases were classified as low or high risk using a cutoff of 1/100 to evaluate predictive performance. Expected and observed cases with preeclampsia according to the Fetal Medicine Foundation-estimated risk range (≥1 in 10; 1 in 11 to 1 in 50; 1 in 51 to 1 in 100; 1 in 101 to 1 in 150; and <1 in 150) were compared. After identifying high-risk pregnant women who used aspirin, the treatment effect of 62% reduction in preterm preeclampsia identified in the Combined Multimarker Screening and Randomized Patient Treatment with Aspirin for Evidence-Based Preeclampsia Prevention trial was used to evaluate the predictive performance adjusted for the effect of aspirin. The number of potentially unpreventable cases in the group without aspirin use was estimated. RESULTS: Among 2749 pregnancies, preterm preeclampsia occurred in 84 (3.1%). With a risk cutoff of 1/100, the screen-positive rate was 25.8%. The detection rate was 71.4%, with a false positive rate of 24.4%. The area under the curve was 0.818 (95% confidence interval, 0.773-0.863). In the risk range ≥1/10, there is an agreement between the number of expected cases and the number of observed cases, and in the other ranges, the predicted risk was lower than the observed rates. Accounting for the effect of aspirin resulted in an increase in detection rate and positive predictive values and a slight decrease in the false positive rate. With 27 cases of preterm preeclampsia in the high-risk group without aspirin use, we estimated that 16 of these cases of preterm preeclampsia would have been avoided if this group had received prophylaxis. CONCLUSION: In a high-prevalence setting, the Fetal Medicine Foundation algorithm can identify women who are more likely to develop preterm preeclampsia. Not accounting for the effect of aspirin underestimates the screening performance.

Application of 4 birthweight curves and local reference range at a University Hospital of Rio de Janeiro, Brazil.

BACKGROUND: Numerous fetal growth curves have been developed from various subpopulations and geographic locations worldwide. OBJECTIVE: To determine the birthweight standard at the Maternity School and compare it to currently used standards in the clinical practice services. STUDY DESIGN: Cross-sectional, observational, and descriptive study. Data from infants born between 2011 and 2016 were collected from the Maternity School Hospital of the Federal University of Rio de Janeiro to define the 10th, 25th, 50th, 75th, and 90th percentiles of the birthweight by gestational age. It was determined the performance of the INTERGROWTH-21st, Fenton, Alexander, and Lubchenco for the Maternity School standards. RESULTS: After the 33rd week of pregnancy, the INTERGROWTH standard was similar to the local standard for small-for-gestational-age infants and Fenton for large-for-gestational-age infants at Maternity School Hospital. The INTERGROWTH standard was found to be inadequate to classify small-for-gestational-age infants, which are babies at major risk for morbidity and mortality at the onset of the 33rd week of pregnancy. CONCLUSION: It was possible to define reference values for birthweight for the maternal school hospital considering at least 33 weeks of pregnancy with a 95% confidence interval. The comparison of the INTERGROWTH, Fenton, Alexander, and Lubchenko standards to the maternal school hospital curve showed that the Fenton curve was the most suitable for the diagnosis of small for gestational age.

The prevalence and perinatal repercussions of preeclampsia after the implementation of a prophylaxis protocol with aspirin.

OBJECTIVES: To evaluate the prevalence and perinatal repercussions of preeclampsia (PE) after the implementation of a prophylaxis protocol with aspirin in singleton pregnancy at Maternity School of Federal University of Rio de Janeiro, Rio de Janeiro, Brazil (2015-2106). METHODOLOGY: PE prevalence according to gestational age (GA) and the prevalence ratio (PR) between PE and prematurity, small for gestational age (SGA), and fetal death were calculated in patients assisted during 2015 and 2016. RESULTS: PE occurred in 373(10.75%) of 3468 investigated cases, where PE < 37 weeks was of 2.79% and PE greater than 37 weeks was of 7.95%. A total of 413 (11.9%) prematurity cases, 320 SGA (9.22%), and 50 fetal deaths (1.44%) occurred. In the PE group, 97 premature newborns (PR 0.90) and 51 SGA (PR 1.16) were born, and two fetal deaths occurred (PR 7.46). Concerning PE < 37 weeks, 27 SGA cases (PR 1.42) and two fetal deaths (PR 2.62) were observed. Regarding PE greater than 37 weeks, 24 SGA (PR 1.09) were born, and no fetal deaths were observed. Our findings were compared to previously published results. CONCLUSIONS: PE was significantly associated with SGA newborns, especially premature PE. Prescribing aspirin for PE prophylaxis based only on clinical risk factors in a real-life scenario does not appear to be effective but resulted in a PE screening and prophylaxis protocol review and update at ME/UFRJ.

Risk of adverse outcomes in offspring with RT-PCR confirmed prenatal Zika virus exposure: An individual participant data meta-analysis of 13 cohorts in the Zika Brazilian Cohorts Consortium.

Background: Knowledge regarding the risks associated with Zika virus (ZIKV) infections in pregnancy has relied on individual studies with relatively small sample sizes and variable risk estimates of adverse outcomes, or on surveillance or routinely collected data. Using data from the Zika Brazilian Cohorts Consortium, this study aims, to estimate the risk of adverse outcomes among offspring of women with RT-PCR-confirmed ZIKV infection during pregnancy and to explore heterogeneity between studies. Methods: We performed an individual participant data meta-analysis of the offspring of 1548 pregnant women from 13 studies, using one and two-stage meta-analyses to estimate the absolute risks. Findings: Of the 1548 ZIKV-exposed pregnancies, the risk of miscarriage was 0.9%, while the risk of stillbirth was 0.3%. Among the pregnancies with liveborn children, the risk of prematurity was 10,5%, the risk of low birth weight was 7.7, and the risk of small for gestational age (SGA) was 16.2%. For other abnormalities, the absolute risks were: 2.6% for microcephaly at birth or first evaluation, 4.0% for microcephaly at any time during follow-up, 7.9% for neuroimaging abnormalities, 18.7% for functional neurological abnormalities, 4.0% for ophthalmic abnormalities, 6.4% for auditory abnormalities, 0.6% for arthrogryposis, and 1.5% for dysphagia. This risk was similar in all sites studied and in different socioeconomic conditions, indicating that there are not likely to be other factors modifying this association. Interpretation: This study based on prospectively collected data generates the most robust evidence to date on the risks of congenital ZIKV infections over the early life course. Overall, approximately one-third of liveborn children with prenatal ZIKV exposure presented with at least one abnormality compatible with congenital infection, while the risk to present with at least two abnormalities in combination was less than 1.0%.

External validation of first trimester combined screening for pre-eclampsia in Brazil: An observational study.

OBJECTIVE: To validate a combined algorithm for early prediction of pre-eclampsia (PE) in the Brazilian population. STUDY DESIGN: This is an unplanned secondary analysis of a cohort study. Consecutive singleton pregnancies undergoing first-trimester screening for PE involving examination of maternal characteristics, medical history, and biophysical markers were considered eligible. Women were classified as low-or high-risk using a cutoff of 1/200, but the individual risk was not used to dictate management, as aspirin prophylaxis was given to women based solely on clinical risk factors. Receiver-operating characteristics (ROC) curves for PE, preterm PE(PE < 37) and early 34(PE < 34) were constructed and detection rates(DR) and false-positive rates(FPR) were calculated, adjusting for the effect of aspirin. Propensity score analysis was utilized to account for possible confounding by indication. MAIN OUTCOME MEASURES: Screening performance and PE rates. RESULTS: Among 1695 women, 323(19.1%) were classified as high-risk for PE and 1372(80.9%) were considered low-risk. Aspirin use was registered in 62(3.7%) in the high-risk group and 33(1.9%) in the low-risk group. There were 164(9.7%) women who developed PE, including 41(2.4%) with PE < 37 and 18(1.1%) PE < 34.Subgroups with aspirin had higher incidence of PE, suggest confounding by indication. The algorithm had an AUC of 0.87, DR of 72% for PE < 34; an AUC of 0.8, DR of 59% for PE < 37, both with FPR of 18%. Accounting for effect of aspirin, we observed an improvement in DR of PE < 37 to 67%. CONCLUSION: Using combined predictive algorithm for preterm PE prediction is feasible in clinical practice in low/middle-income countries. Aspirin use needs to be accounted for when evaluating the performance of screening.

Case Report: SARS-CoV-2 Mother-to-Child Transmission and Fetal Death Associated With Severe Placental Thromboembolism.

SARS-CoV-2 infection during pregnancy is not usually associated with significant adverse effects. However, in this study, we report a fetal death associated with mild COVID-19 in a 34-week-pregnant woman. The virus was detected in the placenta and in an unprecedented way in several fetal tissues. Placental abnormalities (MRI and anatomopathological study) were consistent with intense vascular malperfusion, probably the cause of fetal death. Lung histopathology also showed signs of inflammation, which could have been a contributory factor. Monitoring inflammatory response and coagulation in high-risk pregnant women with COVID-19 may prevent unfavorable outcomes, as shown in this case.

Predictors for single-agent resistance in FIGO score 5 or 6 gestational trophoblastic neoplasia: a multicentre, retrospective, cohort study.

BACKGROUND: Patients with gestational trophoblastic neoplasia who have an International Federation of Gynaecology and Obstetrics (FIGO) risk score of 5 or 6 usually receive non-toxic single-agent chemotherapy as a first-line treatment. Previous studies suggest that only a third of patients have complete remission, with the remaining patients requiring toxic multiagent chemotherapy to attain remission. As stratification factors are unknown, some centres offer multiagent therapy upfront, resulting in overtreatment of many patients. We aimed to identify predictive factors for resistance to single-agent therapy to inform clinicians on which patients presenting with a FIGO score of 5 or 6 are likely to benefit from upfront multiagent chemotherapy. METHODS: We did a multicentre, retrospective, cohort study of patients with gestational trophoblastic neoplasia presenting with a FIGO score of 5 or 6, who received treatment at three gestational trophoblastic neoplasia reference centres in the UK, Brazil, and the USA between Jan 1, 1964, and Dec 31, 2018. All patients who had been followed up for at least 12 months after remission were included. Patients were excluded if they had received a non-standard single-agent treatment (eg, etoposide); had been given a previously established first-line multiagent chemotherapy regimen; or had incomplete data for our analyses. Patient data were retrieved from medical records. The primary outcome was the incidence of chemoresistance after first-line or second-line single-agent chemotherapy. Variables associated with chemoresistance to single-agent therapies were identified by logistic regression analysis. In patient subgroups defined by choriocarcinoma histology and metastatic disease status, we did bootstrap modelling to define thresholds of pretreatment human chorionic gonadotropin concentrations and identify groups of patients with a greater than 80% risk (ie, a positive predictive value [PPV] of 0·8) of resistance to single-agent chemotherapy. FINDINGS: Of 5025 patients with low-risk gestational trophoblastic neoplasia, we identified 431 patients with gestational trophoblastic neoplasia presenting with a FIGO risk score of 5 or 6. All patients were followed up for a minimum of 2 years. 141 (40%) of 351 patients developed resistance to single-agent treatments and required multiagent chemotherapy to achieve remission. Univariable and multivariable logistic regression revealed metastatic disease status (multivariable logistic regression analysis, odds ratio [OR] 1·9 [95% CI 1·1-3·2], p=0·018), choriocarcinoma histology (3·7 [1·9-7·4], p=0·0002), and pretreatment human chorionic gonadotropin concentration (2·8 [1·9-4·1], p<0·0001) as significant predictors of resistance to single-agent therapies. In patients with no metastatic disease and without choriocarcinoma, a pretreatment human chorionic gonadotropin concentration of 411 000 IU/L or higher yielded a PPV of 0·8, whereas in patients with either metastases or choriocarcinoma, a pretreatment human chorionic gonadotropin concentration of 149 000 IU/L or higher yielded the same PPV for resistance to single-agent therapy. INTERPRETATION: Approximately 60% of women with gestational trophoblastic neoplasia presenting with a FIGO risk score of 5 or 6 achieve remission with single-agent therapy; almost all remaining patients have complete remission with subsequent multiagent chemotherapy. Primary multiagent chemotherapy should only be given to patients with metastatic disease and choriocarcinoma, regardless of pretreatment human chorionic gonadotropin concentration, or to those defined by our new predictors. FUNDING: None. TRANSLATION: For the Portuguese translation of the abstract see Supplementary Materials section.

Performance of Fetal Medicine Foundation Software for Pre-Eclampsia Prediction Upon Marker Customization: Cross-Sectional Study.

BACKGROUND: FMF2012 is an algorithm developed by the Fetal Medicine Foundation (FMF) to predict pre-eclampsia on the basis of maternal characteristics combined with biophysical and biochemical markers. Afro-Caribbean ethnicity is the second risk factor, in magnitude, found in populations tested by FMF, which was not confirmed in a Brazilian setting. OBJECTIVE: This study aimed to analyze the performance of pre-eclampsia prediction software by customization of maternal ethnicity. METHODS: This was a cross-sectional observational study, with secondary evaluation of data from FMF first trimester screening tests of singleton pregnancies. Risk scores were calculated from maternal characteristics and biophysical markers, and they were presented as the risk for early pre-eclampsia (PE34) and preterm pre-eclampsia (PE37). The following steps were followed: (1) identification of women characterized as black ethnicity; (2) calculation of early and preterm pre-eclampsia risk, reclassifying them as white, which generated a new score; (3) comparison of the proportions of women categorized as high risk between the original and new scores; (4) construction of the receiver operator characteristic curve; (5) calculation of the area under the curve, sensitivity, and false positive rate; and (6) comparison of the area under the curve, sensitivity, and false positive rate of the original with the new risk by chi-square test. RESULTS: A total of 1531 cases were included in the final sample, with 219 out of 1531 cases (14.30; 95% CI 12.5-16.0) and 182 out of 1531 cases (11.88%; 95% CI 10.3-13.5) classified as high risk for pre-eclampsia development, originally and after recalculating the new risk, respectively. The comparison of FMF2012 predictive model performance between the originally estimated risks and the estimated new risks showed that the difference was not significant for sensitivity and area under the curve, but it was significant for false positive rate. CONCLUSIONS: We conclude that black ethnicity classification of Brazilian pregnant women by the FMF2012 algorithm increases the false positive rate. Suppressing ethnicity effect did not improve the test sensitivity. By modifying demographic characteristics, it is possible to improve some performance aspects of clinical prediction tests.

Cesarean section by maternal request.

Cesarean section by maternal request is the one performed on a pregnant woman without medical indication and without contraindication to vaginal delivery. There is great controversy over requested cesarean section. Potential risks include complications in subsequent pregnancies, such as uterine rupture, placenta previa and accreta. Potential benefits of requested cesareans include a lower risk of postpartum hemorrhage in the first cesarean and fewer surgical complications compared with vaginal delivery. Cesarean section by request should never be performed before 39 weeks. RESUMO A cesariana a pedido materno é aquela realizada em uma gestante sem indicações médicas e sem contraindicação para tentativa do parto vaginal. Existe grande controvérsia sobre a realização da cesariana a pedido. Riscos potenciais da cesariana a pedido incluem complicações em gravidezes subsequentes, tais como: rotura uterina, placenta prévia e acretismo. Potenciais benefícios da cesariana a pedido englobam um menor risco de hemorragia pós-parto na primeira cesariana e menos complicações cirúrgicas quando comparada ao parto vaginal. A cesariana a pedido jamais deve ser realizada antes de 39 semanas.