Medication Use Among Pregnant Women With SARS-CoV-2 Infection and Risk of Hospitalization-A Study in Two Brazilian Hospitals.

There is limited evidence about the use of medications among pregnant women with COVID-19, as well as risk factors for hospitalization due to COVID-19 in pregnancy. We aimed to describe the use of medications among SARS-CoV-2-positive pregnant women at the time around infection and identify predictors for hospitalization due to COVID-19 in two hospitals in Brazil. This is a hospital record-based study among pregnant women with positive SARS-CoV-2 tests between March 2020 and August 2022 from two Brazilian hospitals. Characteristics of sociodemographic, obstetrical, and COVID-19 symptoms were extracted retrospectively. The prevalence use of medications was based on self-reported use, and this was administered at the hospital. Logistic regression was used to estimate predictors of hospitalization due to COVID-19. There were 278 pregnant women included in the study, of which 41 (14.7%) required hospitalization due to COVID-19. The remaining 237 (85.3%) had mild symptoms or were asymptomatic. Most of the women had the infection in the third trimester (n = 149; 53.6%). The most prevalent medications used across all trimesters were analgesics (2.4% to 20.0%), antibacterials (15.0% to 23.1%), and corticosteroids (7.2% to 10.4%). Pre- or gestational hypertensive disorder (odds ratio (OR) 4.94, 95% confidence interval (CI) 1.65, 14.87) and having at least one dose of vaccine against SARS-CoV-2 (OR 0.13, 95% CI 0.04, 0.39) were associated with hospitalization due to COVID-19. Analgesics, antibacterials, and corticosteroids were the most frequently used medications among pregnant women with COVID-19. Women with hypertensive disorders have almost a five-fold increased risk of hospitalization due to COVID-19. Vaccination was the strongest protective factor for severe COVID-19. The COVID-19 vaccination among pregnant women should be promoted, and pregnant women diagnosed with COVID-19 who have hypertensive disorders should be closely monitored.

Congenital diaphragmatic hernia treated via fetal endoscopic tracheal occlusion improves outcome in a middle-income country.

OBJECTIVES: A recent European randomized trial - Tracheal Occlusion To Accelerate Lung Growth - demonstrated that fetoscopic endoluminal tracheal occlusion (FETO) is associated with increased postnatal survival among infants with severe congenital diaphragmatic hernia (CDH). However, this differs in middle-income countries such as Brazil, where abortion is illegal and neonatal intensive care is inadequate. This study evaluated the effects of FETO on improving the survival of infants with moderate-to-severe CDH in isolated and non-isolated cases. METHODS: This retrospective cohort study selected 49 fetuses with CDH, a normal karyotype, and a lung-to-head ratio (LHR) of <1 from a single national referral center for fetal surgery in São Paulo, Brazil, between January 2016 and November 2019. FETO was performed between 26 and 29 weeks of gestation. The primary outcomes were infant survival until discharge from the neonatal intensive care unit and survival until six months of age. RESULTS: Forty-six women with singleton fetuses having severe CDH underwent prenatal intervention with FETO. Infant survival rates until discharge and at six months of age were both 38 %. The observed-to-expected LHR increased by 25 % after FETO in neonates who survived until discharge. Spontaneous intrauterine death occurred in four growth-restricted fetuses after FETO. Preterm birth in <37 weeks and preterm rupture of membranes in <34 weeks occurred in 56.5 % (26) and 26 % (12) cases, respectively. CONCLUSIONS: FETO may increase neonatal survival in fetuses with severe CDH, particularly in countries with limited neonatal intensive care.

Assessment of Human Fetuses Undergoing Acute Pain: Validation of the Fetal-7 Scale.

Improvements in fetal ultrasound have allowed for the diagnosis and treatment of fetal diseases in the uterus, often through surgery. However, little attention has been drawn to the assessment of fetal pain. To address this gap, a fetal pain scoring system, known as the Fetal-7 scale, was developed. The present study is a full validation of the Fetal-7 scale. The validation involved 2 steps: 1) 4 fetuses with the indication of surgery were evaluated in 3 conditions perioperatively: acute pain, rest, and under loud sound stimulation. Facial expressions were assessed by 30 raters using screenshots from 4D high-definition ultrasound films; 2) assessment of sensitivity and specificity of the Fetal-7 scale in 54 healthy fetuses and 2 fetuses undergoing acute pain after preoperative anesthetic intramuscular injection. There was high internal consistency with Cronbach's alpha (α) of .99. Intrarater reliability of the Fetal-7 scale (test-retest) calculated by intraclass correlation coefficient was .95, and inter-rater reliability was .99. The scale accurately differentiated between healthy fetuses at rest and those experiencing acute pain (sensitivity of 100% and specificity of 94.4%). The Fetal-7 scale is a valid tool for assessing acute pain-related behavior in third-trimester fetuses and may be of value in guiding analgesic procedures efficacy in these patients. Further research is warranted to explore the presence of postoperative pain in fetuses and its effects after birth. PERSPECTIVE: Recordings with 3-dimensional ultrasound of human fetuses undergoing preoperative anesthetic injections revealed complex facial expressions during acute pain, similar to those collected in newborns. This study presented the validation process and cut-off value of the Fetal-7 scale, paving the way for the study of pain before birth in humans.

Impact of SARS-CoV-2 Alpha and Gamma Variants among Symptomatic Pregnant Women: A Two-Center Retrospective Cohort Study between France and Brazil.

New variants of SARS-CoV-2 are a major source of concern, especially for pregnant women and in the perinatal context. The primary aim of this study was to compare the severity of COVID-19 infection in pregnant women depending on strain predominance between wild-type Alpha and Gamma variants. The secondary aim was to study the impact of these strains on obstetrical and neonatal outcomes. We conducted a two-center international retrospective cohort study, which included two type III maternity hospitals, one in France and one in Brazil, comparing the first period corresponding to the wild-type strain and the second period corresponding to the predominance of the Alpha variant in France and the Gamma variant in Brazil. We included 151 pregnant women with symptomatic SARS-CoV-2 infection confirmed by RT-PCR. The rate of severe-to-critical infection, according to the WHO definition, was seven-fold higher in patients infected during the "variant period" than in patients infected during the "wild-type period" (aOR = 7.07, 95CI [2.50−21.6], p < 0.001). There were no statistical differences concerning composite obstetrical and neonatal outcomes between the different periods. While analyzing each variant separately, it was found that, in France, the risk of developing a severe-to-critical infection was three times greater during the Alpha period than during the wild-type period (OR = 3.25, 95CI [0.70−15.6], p = 0.13) and, in Brazil, the risk was twelve times greater during the Gamma period than during the wild-type period (OR = 11.8, 95CI [2.46−72.3], p = 0.003). The Alpha and Gamma variants of SARS-CoV-2 seem to be more dangerous in the obstetrical context. With the rapid emergence of new variants, it is necessary to accelerate vaccination to protect women and newborn children.

Outcomes following medical termination versus prolonged pregnancy in women with severe preeclampsia before 26 weeks.

OBJECTIVE: To compare maternal complications and describe neonatal outcomes in women with severe preeclampsia at ≤ 26+0 weeks in two countries with different management policies: expectant management (Brazil) versus termination of pregnancy (France). METHODS: We conducted a retrospective comparative study by reviewing the medical records of women with severe preeclampsia at ≤ 26+0 weeks, from January 2010 to June 2018, in two centers: Hospital das Clínicas da Faculdade de Medicina, in Sao Paulo, Brazil (where medical abortion is forbidden in this indication) and Hôpital Antoine-Béclère, Clamart, France (where medical termination is accepted). We collected information on maternal characteristics, laboratory tests, maternal complications and fetal and newborn characteristics. We used Student's t-test and the Mann-Whitney U nonparametric test to compare quantitative variables, and Chi-square test or Fisher's exact test to evaluate the associations between the qualitative variables. RESULTS: There was no between-group difference in maternal complications during hospitalization (p = 0.846). In Brazil, the rate of cesarean section was 66.7%, and 20% of patients had vertical incision. The rate of spontaneous fetal death was 35.6% and among the live-born infants 26.6% were discharged from hospital. In France, one patient had a cesarean section with vertical incision. CONCLUSION: When comparing termination of pregnancy to expectant management in severe preeclampsia before 26 weeks, maternal complications were equivalent but maternal reproductive future might have been compromised in 20% of cases due to a higher risk of uterine rupture in subsequent pregnancies for patients having classic cesarean (vertical incision). 26.6% of children survived the neonatal period when pregnancy was pursued, however we lack information on their long-term follow-up.

Sorting pain out of salience: assessment of pain facial expressions in the human fetus.

INTRODUCTION: The question of whether the human fetus experiences pain has received substantial attention in recent times. With the advent of high-definition 4-dimensional ultrasound (4D-US), it is possible to record fetal body and facial expressions. OBJECTIVE: To determine whether human fetuses demonstrate discriminative acute behavioral responses to nociceptive input. METHODS: This cross-sectional study included 5 fetuses with diaphragmatic hernia with indication of intrauterine surgery (fetoscopic endoluminal tracheal occlusion) and 8 healthy fetuses, who were scanned with 4D-US in 1 of 3 conditions: (1) acute pain group: Fetuses undergoing intrauterine surgery were assessed in the preoperative period during the anesthetic injection into the thigh; (2) control group at rest: Facial expressions at rest were recorded during scheduled ultrasound examinations; and (3) control group acoustic startle: Fetal facial expressions were recorded during acoustic stimulus (500-4000 Hz; 60-115 dB). RESULTS: Raters blinded to the fetuses' groups scored 65 pictures of fetal facial expressions based on the presence of 12 items (facial movements). Analyses of redundancy and usefulness excluded 5 items for being of low discrimination capacity (P>0.2). The final version of the pain assessment tool consisted of a total of 7 items: brow lowering/eyes squeezed shut/deepening of the nasolabial furrow/open lips/horizontal mouth stretch/vertical mouth stretch/neck deflection. Odd ratios for a facial expression to be detected in acute pain compared with control conditions ranged from 11 (neck deflection) to 1,400 (horizontal mouth stretch). Using the seven-item final tool, we showed that 5 is the cutoff value discriminating pain from nonpainful startle and rest. CONCLUSIONS: This study inaugurates the possibility to study pain responses during the intrauterine life, which may have implications for the postoperative management of pain after intrauterine surgical interventions.

Associations of maternal personal exposure to air pollution on fetal weight and fetoplacental Doppler: A prospective cohort study.

We determined the influence of maternal air pollution exposure during each trimester of pregnancy on fetal and birth weight and fetoplacental hemodynamics. In total, 366 women with singleton pregnancies were prospectively followed in the city of São Paulo, Brazil. Nitrogen dioxide (NO2) and ozone (O3) were measured during each trimester using passive personal samplers. We evaluated fetal weight and Doppler velocimetry data from the umbilical, middle cerebral, and uterine arteries in the 3rd trimester, and birth weight. Multivariate analysis was performed, controlling for known determinants of fetal weight. Exposure to higher levels of O3 during the 2nd trimester was associated with higher umbilical artery pulsatility indices (PIs) [p=0.013; beta=0.017: standard error (SE)=0.007]. Exposure to higher levels of O3 during the 3rd trimester was associated with lower umbilical artery PIs (p=0.011; beta=-0.021; SE=0.008). Our results suggest that in the environment of São Paulo, O3 may affects placental vascular resistance.

Is Doppler ultrasound useful for evaluating gestational trophoblastic disease?

Doppler ultrasound is a non-invasive method for evaluating vascularization and is widely used in clinical practice. Gestational trophoblastic neoplasia includes a group of highly vascularized malignancies derived from placental cells. This review summarizes data found in the literature regarding the applications of Doppler ultrasound in managing patients with gestational trophoblastic neoplasia. The PubMed/Medline, Web of Science, Cochrane and LILACS databases were searched for articles published in English until 2014 using the following keywords: “Gestational trophoblastic disease AND Ultrasonography, Doppler.” Twenty-eight articles met the inclusion criteria and were separated into the 4 following groups according to the aim of the study. (1) Doppler ultrasound does not seem to be capable of differentiating partial from complete moles, but it might be useful when evaluating pregnancies in which a complete mole coexists with a normal fetus. (2) There is controversy in the role of uterine artery Doppler velocimetry in the prediction of development of gestational trophoblastic neoplasia. (3) Doppler ultrasound is a useful tool in the diagnosis of gestational trophoblastic neoplasia because abnormal myometrial vascularization and lower uterine artery Doppler indices seem to be correlated with invasive disease. (4) Lower uterine artery Doppler indices in the diagnosis of gestational trophoblastic neoplasia are associated with methotrexate resistance and might play a role in prognosis. CONCLUSION: Several studies support the importance of Doppler ultrasound in the management of patients with gestational trophoblastic neoplasia, particularly the role of Doppler velocimetry in the prediction of trophoblastic neoplasia and the chemoresistance of trophoblastic tumors. Doppler findings should be used as ancillary tools, along with human chorionic gonadotropin assessment, in the diagnosis of gestational trophoblastic neoplasia.

Is Doppler ultrasound useful for evaluating gestational trophoblastic disease?

UNLABELLED: Doppler ultrasound is a non-invasive method for evaluating vascularization and is widely used in clinical practice. Gestational trophoblastic neoplasia includes a group of highly vascularized malignancies derived from placental cells. This review summarizes data found in the literature regarding the applications of Doppler ultrasound in managing patients with gestational trophoblastic neoplasia. The PubMed/Medline, Web of Science, Cochrane and LILACS databases were searched for articles published in English until 2014 using the following keywords: "Gestational trophoblastic disease AND Ultrasonography, Doppler." Twenty-eight articles met the inclusion criteria and were separated into the 4 following groups according to the aim of the study. (1) Doppler ultrasound does not seem to be capable of differentiating partial from complete moles, but it might be useful when evaluating pregnancies in which a complete mole coexists with a normal fetus. (2) There is controversy in the role of uterine artery Doppler velocimetry in the prediction of development of gestational trophoblastic neoplasia. (3) Doppler ultrasound is a useful tool in the diagnosis of gestational trophoblastic neoplasia because abnormal myometrial vascularization and lower uterine artery Doppler indices seem to be correlated with invasive disease. (4) Lower uterine artery Doppler indices in the diagnosis of gestational trophoblastic neoplasia are associated with methotrexate resistance and might play a role in prognosis. CONCLUSION: Several studies support the importance of Doppler ultrasound in the management of patients with gestational trophoblastic neoplasia, particularly the role of Doppler velocimetry in the prediction of trophoblastic neoplasia and the chemoresistance of trophoblastic tumors. Doppler findings should be used as ancillary tools, along with human chorionic gonadotropin assessment, in the diagnosis of gestational trophoblastic neoplasia.