SARS-CoV-2 and Pregnancy: A Review of the Facts.

OBJECTIVE: The present comprehensive review aims to show the full extent of what is known to date and provide a more thorough view on the effects of SARS-CoV2 in pregnancy. METHODS: Between March 29 and May, 2020, the words COVID-19, SARS-CoV2, COVID-19 and pregnancy, SARS-CoV2 and pregnancy, and SARS and pregnancy were searched in the PubMed and Google Scholar databases; the guidelines from well-known societies and institutions (Royal College of Obstetricians and Gynaecologists [RCOG], American College of Obstetricians and Gynecologists [ACOG], International Society of Ultrasound in Obstetrics & Gynecology [ISUOG], Centers for Disease Control and Prevention [CDC], International Federation of Gynecology and Obstetrics [FIGO]) were also included. CONCLUSION: The COVID-19 outbreak resulted in a pandemic with > 3.3 million cases and 230 thousand deaths until May 2nd. It is caused by the SARS-CoV2 virus and may lead to severe pulmonary infection and multi-organ failure. Past experiences show that unique characteristics in pregnancy make pregnant women more susceptible to complications from viral infections. Yet, this has not been reported with this new virus. There are risk factors that seem to increase morbidity in pregnancy, such as obesity (body mass index [BMI] > 35), asthma and cardiovascular disease. Current reports describe an increased rate of preterm birth and C-section. Vertical transmission is still a possibility, due to a few reported cases of neonatal positive real-time polymerase chain reaction (RT-PCR) in nasal swab, amniotic fluid, and positive immunoglobulin M (IgM) in neonatal blood. Treatments must be weighed in with caution due to the lack of quality trials that prove their effectiveness and safety during pregnancy. Medical staff must use personal protective equipment in handling SARS-CoV2 suspected or positive patients and be alert for respiratory decompensations.

OBJETIVO: A presente revisão detalhada busca fornecer dados objetivos para avaliar o que se sabe até o momento e possibilitar uma visão mais ampla dos efeitos do SARS-CoV2 na gravidez. MéTODOS: Entre 29 de março e 2 de maio de 2020, foi realizada uma busca nos bancos de dados PubMed e Google Scholar com as palavras COVID-19, SARS-CoV2, COVID-19 e gravidez, SARS-CoV2 e gravidez, e SARS e gravidez. As recomendações dos principais órgãos sobre o tema também foram acessadas. CONCLUSãO: O surto de COVID-19 resultou em uma pandemia com > 3.3 milhões de casos e 230 mil mortes até 2 de maio. É uma condição causada pelo vírus SARS-CoV2 e pode levar ao acometimento pulmonar difuso e à falência de múltiplos órgãos. Características únicas da gestante tornam essa população mais propensas a complicações de infecções virais. Até o momento, essa tendência não foi observada para esse novo vírus. Os fatores que parecem estar associados à maior morbidade materno-fetal são obesidade (índice de massa corporal [IMC] > 35), asma e doença cardiovascular. Há descrição de aumento de parto prematuro e parto cesáreo. Não se pode descartar a possibilidade de transmissão vertical da doença, devido a relatos de positividade de reação em cadeia de polimerase (RT-PCR) de swab nasal, RT-PCR de líquido amniótico e imunoglobulina M (IgM) de recém-nascidos. Tratamentos devem ser analisados caso a caso, dada a falta de qualidade de estudos que comprovem a sua eficácia e segurança na gravidez. O corpo clínico deve utilizar equipamentos de proteção individual (EPI) ao manusear pacientes suspeitos ou confirmados e ficar atento aos sinais de descompensação respiratória.

SARS-CoV-2 and pregnancy: A review of the facts / SARS-CoV-2 e gestação: uma revisão dos fatos

Abstract Objective The present comprehensive review aims to show the full extent of what is known to date and provide a more thorough view on the effects of SARS-CoV2 in pregnancy. Methods Between March 29 and May, 2020, the words COVID-19, SARS-CoV2, COVID- 19 and pregnancy, SARS-CoV2 and pregnancy, and SARS and pregnancy were searched in the PubMed and Google Scholar databases; the guidelines from well-known societies and institutions (Royal College of Obstetricians and Gynaecologists [RCOG], American College of Obstetricians and Gynecologists [ACOG], International Society of Ultrasound in Obstetrics & Gynecology [ISUOG], Centers for Disease Control and Prevention [CDC], International Federation of Gynecology and Obstetrics [FIGO]) were also included. Conclusion The COVID-19 outbreak resulted in a pandemic with > 3.3 million cases and 230 thousand deaths until May 2nd. It is caused by the SARS-CoV2 virus and may lead to severe pulmonary infection and multi-organ failure. Past experiences show that unique characteristics in pregnancy make pregnant women more susceptible to complications from viral infections. Yet, this has not been reported with this new virus. There are risk factors that seem to increase morbidity in pregnancy, such as obesity (body mass index [BMI] > 35), asthma and cardiovascular disease. Current reports describe an increased rate of pretermbirth and C-section. Vertical transmission

Resumo Objetivo A presente revisão detalhada busca fornecer dados objetivos para avaliar o que se sabe até o momento e possibilitar uma visãomais ampla dos efeitos do SARSCoV2 na gravidez. Métodos Entre 29 demarço e 2 de maio de 2020, foi realizada uma busca nos bancos de dados PubMed e Google Scholar com as palavras COVID-19, SARS-CoV2, COVID-19 e gravidez, SARS-CoV2 e gravidez, e SARS e gravidez. As recomendações dos principais órgãos sobre o tema também foram acessadas. Conclusão O surto de COVID-19 resultou em uma pandemia com> 3.3 milhões de casos e 230 mil mortes até 2 de maio. É uma condição causada pelo vírus SARS-CoV2 e pode levar ao acometimento pulmonar difuso e à falência de múltiplos órgãos. Características únicas da gestante tornam essa população mais propensas a complicações de infecções virais. Até o momento, essa tendência não foi observada para esse novo vírus. Os fatores que parecem estar associados à maior morbidade materno-fetal são obesidade (índice demassa corporal [IMC] > 35), asma e doença cardiovascular. Há descrição de aumento de parto prematuro e parto cesáreo. Não se pode descartar a possibilidade de transmissão vertical da doença, devido a relatos de positividade de reação em cadeia de polimerase (RT-PCR) de swab nasal, RT-PCR de líquido amniótico e imunoglobulina M (IgM) de recém-nascidos. Tratamentos devem ser analisados caso a caso, dada a falta de qualidade de estudos que comprovem a sua eficácia e segurança na gravidez. O corpo clínico deve utilizar equipamentos de proteção individual (EPI) ao manusear pacientes suspeitos ou confirmados e ficar atento aos sinais de descompensação respiratória.

Growth Patterns of Fetal Lung Volumes in Healthy Fetuses and Fetuses With Isolated Left-Sided Congenital Diaphragmatic Hernia.

OBJECTIVES: To evaluate fetal lung growth using 3-dimensional sonography in healthy fetuses and those with congenital diaphragmatic hernia (CDH). METHODS: Right and total lung volumes were serially evaluated by 3-dimensional sonography in 66 healthy fetuses and 52 fetuses with left-sided CDH between 20 and 37 weeks' menstrual age. Functions fitted to these parameters were compared for 2 groups: (1) healthy versus those with CDH; and (2) fetuses with CHD who survived versus those who died. RESULTS: Fetal right and total lung volumes as well as fetal observed-to-expected right and total lung volume ratios were significantly lower in fetuses with CDH than healthy fetuses (P< .001) and in those fetuses with CDH who died (P< .001). The observed-to-expected right and total lung volume ratios did not vary with menstrual age in healthy fetuses or in those with CDH (independent of outcome). CONCLUSIONS: Lung volume rates were lower in fetuses with left-sided CDH compared to healthy fetuses, as well as in fetuses with CDH who died compared to those who survived. The observed-to-expected right and total lung volume ratios were relatively constant throughout menstrual age in fetuses with left-sided CDH, suggesting that the origin of their lung growth abnormalities occurred before 20 weeks and did not progress. The observed-to-expected ratios may be useful in predicting the outcome in fetuses with CDH independent of menstrual age.

Prematurity and fetal lung response after tracheal occlusion in fetuses with severe congenital diaphragmatic hernia.

OBJECTIVE: To evaluate the independent association of fetal pulmonary response and prematurity to postnatal outcomes after fetal tracheal occlusion for congenital diaphragmatic hernia. METHODS: Fetal pulmonary response, prematurity (<37 weeks at delivery) and extreme prematurity (<32 weeks at delivery) were evaluated and compared between survivors and non-survivors at 6 months of life. Multivariable analysis was conducted with generalized linear mixed models for variables significantly associated with survival in univariate analysis. RESULTS: Eighty-four infants were included, of whom 40 survived (47.6%) and 44 died (52.4%). Univariate analysis demonstrated that survival was associated with greater lung response (p=0.006), and the absence of extreme preterm delivery (p=0.044). In multivariable analysis, greater pulmonary response after FETO was an independent predictor of survival (aOR 1.87, 95% CI 1.08-3.33, p=0.023), whereas the presence of extreme prematurity was not statistically associated with mortality after controlling for fetal pulmonary response (aOR 0.52, 95% CI 0.12-2.30, p=0.367). CONCLUSION: Fetal pulmonary response after FETO is the most important factor associated with survival, independently from the gestational age at delivery.

Standardization of Sonographic Lung-to-Head Ratio Measurements in Isolated Congenital Diaphragmatic Hernia: Impact on the Reproducibility and Efficacy to Predict Outcomes.

OBJECTIVES: The purpose of this study was to evaluate the impact of standardization of the lung-to-head ratio measurements in isolated congenital diaphragmatic hernia on prediction of neonatal outcomes and reproducibility. METHODS: We conducted a retrospective cohort study of 77 cases of isolated congenital diaphragmatic hernia managed in a single center between 2004 and 2012. We compared lung-to-head ratio measurements that were performed prospectively in our institution without standardization to standardized measurements performed according to a defined protocol. RESULTS: The standardized lung-to-head ratio measurements were statistically more accurate than the nonstandardized measurements for predicting neonatal mortality (area under the receiver operating characteristic curve, 0.85 versus 0.732; P = .003). After standardization, there were no statistical differences in accuracy between measurements regardless of whether we considered observed-to-expected values (P > .05). Standardization of the lung-to-head ratio did not improve prediction of the need for extracorporeal membrane oxygenation (P> .05). Both intraoperator and interoperator reproducibility were good for the standardized lung-to-head ratio (intraclass correlation coefficient, 0.98 [95% confidence interval, 0.97-0.99]; bias, 0.02 [limits of agreement, -0.11 to +0.15], respectively). CONCLUSIONS: Standardization of lung-to-head ratio measurements improves prediction of neonatal outcomes. Further studies are needed to confirm these results and to assess the utility of standardization of other prognostic parameters.

Prenatal diagnosis of a fetus with ring chromosomal 15 by two- and three-dimensional ultrasonography.

We report on a prenatal diagnosis of ring chromosome 15 in a fetus with left congenital diaphragmatic hernia (CDH) and severe intrauterine growth restriction (IUGR). A 31-year-old woman, gravida 2 para 1, was referred because of increased nuchal translucency at gestational age of 13 weeks. Comprehensive fetal ultrasound examination was performed at 19 weeks revealing an early onset IUGR, left CDH with liver herniation, and hypoplastic nasal bone. Three-dimensional ultrasound (rendering mode) showed low set ears and depressed nasal bridge. Amniocentesis was performed with a result of a 46,XX,r(15) fetus after a cytogenetic study. A 1,430 g infant (less than third percentile) was born at 36 weeks. The infant presented with respiratory failure and died at 2 h of life. Postnatal karyotype from the umbilical cord confirmed the diagnosis of 15-ring chromosome. We described the main prenatal 2D- and 3D-ultrasound findings associated with ring chromosome 15. The interest in reporting the present case is that CDH can be associated with the diagnosis of 15-ring chromosome because the critical location of the normal diaphragm development is at chromosome 15q26.1-q26.2.

Reference ranges for 2-dimensional sonographic lung measurements in healthy fetuses: a longitudinal study.

OBJECTIVES: The purpose of this study was to establish reference ranges for 2-dimensional sonographic measurements of fetal lungs from longitudinal data. METHODS: A total of 214 fetal lung measurements were longitudinally evaluated in 62 healthy fetuses between 20 and 36 weeks' menstrual age. Both right and left lung areas were measured in the heart 4-chamber view using lung area tracing and axis diameter methods. Multilevel modeling was used to evaluate the expected values and variability with respect to menstrual age and to generate reference ranges for the lung area, lung-to-head ratio, quantitative lung index, and observed-to-expected lung-to-head ratio for both lungs. RESULTS: The expected values varied with menstrual age for all parameters. Variance was menstrual age dependent for all parameters except the longest diameter area measurements and their lung-to-head ratios. CONCLUSIONS: Models are presented for expected 2-dimensional sonographic lung size parameters and their variance as a function of menstrual age. These data have been used to generate age-specific reference ranges for both measurements and indices.

New anatomical landmarks to study the relationship between fetal lung area and thoracic circumference by three-dimensional ultrasonography.

OBJECTIVE: To evaluate the relation between total lung area (TLA) and thoracic circumference (TC) ratio by three-dimensional (3D) ultrasonography applying new anatomical landmarks as the fetal aorta and inferior angle of the scapula. METHODS: A longitudinal prospective study was conducted with 56 uncomplicated pregnancies between 24 and 32 weeks of gestation. Polynomial regressions were used to evaluate the correlation between TC and gestational age (GA) as well as TC and estimated fetal weight (EFW). A simple linear regression was used to evaluate the correlation between TLA and Total thoracic area (TTA) and GA. The intraclass correlation coefficient (ICC) was used to assess the intra and interobserver variability. RESULTS: 127 examinations were performed. TC values ranged from 150 to 174 mm (mean 166 mm) at 24 weeks and 215-248 mm (mean 231 mm) at 32 weeks. The TLA/TC ratio ranged from a mean of 0.64 at 24 weeks (range 0.56-0.70) to 0.90 at 32 weeks gestation (range 0.79-1.01). The intraobserver variability using the ICC was of 0.919 for TC; 0.916 for TTA; 0.860 for right lung area (RLA) and 0.910 for left lung area (LLA). Interobserver reproducibility was with an ICC of 0.970 for TC; 0.984 for RLA and 0.910 for LLA. CONCLUSIONS: Measurement of fetal TC and the relationship between TLA and TC by 3D-ultrasonography applying new anatomical landmarks shows good reproducibility and allows a new assessment of thoracic and lung growth.

Reference range of fetal renal volume by three-dimensional ultrasonography using the VOCAL method.

OBJECTIVE: To establish reference values for fetal renal volume by three-dimensional sonography using the VOCAL (Virtual Organ Computer-Aided Analysis) method. METHODS: This prospective longitudinal study involved 57 healthy pregnant women who were examined between 24 and 34 weeks of pregnancy. Each fetal kidney was evaluated separately using the VOCAL method with a 30 degree rotation angle. For each gestational age, the following measures were obtained for the right and left kidneys: mean, standard deviation, minimum and maximum values, and the 5th, 10th, 25th, 50th, 75th and 90th percentiles. Polynomial regression models were constructed to assess the relationship between renal volume and gestational age, adjusted by the determination coefficient (R(2)). The Wilcoxon test was used to evaluate the concordance between the right and left renal volumes. Bland-Altman graphs were used to assess intra- and inter-observer variability. RESULTS: The right renal volume increased from 4.5 +/- 1.3 cm(3) at 24 weeks to 12.1 +/- 1.5 cm(3) at 34 weeks. The left renal volume increased from 4.6 +/- 0.8 cm(3) at 24 weeks to 11.9 +/- 1.1 cm(3) at 34 weeks. There was a strong correlation between both the right and left renal volumes and gestational age (R(2) = 0.975 and 0.970, respectively). There were no significant differences between the right and left renal volumes. The mean difference between repeated measures by the same examiner was -0.07 cm(3) (-0.88 to 0.75) for the right kidney and -0.21 cm(3) (-0.95 to 0.75) for the left kidney. The mean difference between repeated measures obtained by two different examiners was -0.07 cm(3) (-1.25 to 1.12) for the right kidney and 0 cm(3) (-1.53 to 1.53) for the left kidney. CONCLUSION: Reference values were generated for fetal renal volume assessed by three-dimensional ultrasonography using the VOCAL method.

Fetal lung volume: comparison by 2D- and 3D-sonography in normal fetuses.

PURPOSE: To compare two-dimensional ultrasonography (2D US) and three-dimensional ultrasonography (3D US) in the assessment of normal fetal lung volume. METHODS: A cross-sectional study was performed involving 50 normal pregnancies at 24-32 weeks' gestation. The following equations were used for lung volume calculation by 2D US: Eq(2D1) = 4.24 + {1.53 x [(area of base of both lungs) x 1/3 (height of right lung)]} and Eq(2D2) = [anteroposterior diameter (X) x transverse diameter (Y) x cranial-caudal diameter (Z) of the right lung x 0.152 + (X') x (Y') x (Z') of the left lung x 0.167]. For 3D US, the virtual organ computer-aided analysis (VOCAL) method was used with a 30 degrees rotation angle and the total lung volume (V3D) was obtained by summing the volumes of each lung. Regression models (R (2)) were devised to assess lung volume evolution over the course of the pregnancy. Pearson's correlation coefficient (r) was used to assess correlation among the techniques, while Friedman's test was used for means comparisons. RESULTS: Strong correlation was observed among the three techniques [V3D vs. Eq(2D2) r = 0.856; V3D vs. Eq(2D1) r = 0.838 and Eq(2D2) vs. Eq(2D1) r = 0.964; all with P < 0.001]. Mean lung volumes were 37.05 +/- 9.67, 29.79 +/- 8.79 and 12.67 +/- 4.12 ml for V3D, Eq(2D1) and Eq(2D2), respectively (P < 0.001). CONCLUSIONS: Strong correlation and significant difference was observed among the three techniques of fetal lung volume assessment in normal fetuses.

Prenatal diagnosis of Ebstein's anomaly using spatio-temporal image correlation (STIC) and inversion mode.

BACKGROUND: Ebstein's anomaly is a rare cardiac defect where the septal and posterior leaflets are displaced, towards the right ventricle. The leaflets are dysplastic and stuck to the ventricular wall. Its antenatal diagnosis is usually made through bidimensional echocardiography, which also has prognostic value. Recently, the technological breakthrough of three-dimensional ultrasound (3D-US) offered new diagnostic tools for congenital heart defects, less dependent on the ultrasonographer experience, when compared to two-dimensional ultrasound (2D-US). The spatio-temporal image correlation (STIC) technique allows the acquisition of the fetal heart volume and its structures as a 4D cineloop sequence showing the complete cardiac cycle. Inversion mode is a new image analysis tool for the examination of fluid-filled fetal structures that inverts the gray scale. CASE REPORT: We present a case of Ebstein's anomaly diagnosed at 26 weeks of pregnancy through bidimensional echocardiography. We emphasize its main findings in 3D-US using the STIC and inversion mode techniques.