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.

Risk factors for shunting at 12 months following open fetal repair of spina bifida by mini-hysterotomy.

OBJECTIVES: Open spina bifida (OSB) is the most common neural tube defect. Prenatal repair reduces the need for ventriculoperitoneal shunting (VPS) due to hydrocephalus from 80-90% to 40-50%. We aimed to determine which variables work as risk factors for VPS at 12 months of age in our population. METHODS: Thirty-nine patients underwent prenatal repair of OSB by mini-hysterotomy. The main outcome was occurrence of VPS in the first 12 months of life. Logistic regression was used to estimate the odds ratios (OR) between prenatal variables and the need for shunting. RESULTS: VPS at 12 months occurred in 34.2% of the children. Larger ventricle size before surgery (62.5% ≥15 mm; 46.2% between 12 and 15 mm; 11.8% <12 mm; p=0.008), higher lesion level (80% >L2, vs. 17.9% ≤L3; p=0.002; OR, 18.4 [2.96-114.30]), and later gestational age at surgery (25.25 ± 1.18 vs. 24.37 ± 1.06 weeks; p=0.036; OR, 2.23 [1.05-4.74]) were related to increased need for shunting. In the multivariate analysis, larger ventricle size before surgery (≥15 mm vs. <12 mm; p=0.046; OR, 1.35 [1.01-1.82]) and higher lesion level (>L2 vs. ≤L3; p=0.004; OR, 39.52 [3.25-480.69]) were risk factors for shunting. CONCLUSIONS: Larger ventricle size before surgery (≥15 mm) and higher lesion level (>L2) are independent risk factors for VPS at 12 months of age in fetuses undergoing prenatal repair of OSB by mini-hysterotomy in the studied population.

Association between preterm births and socioeconomic development: analysis of national data.

BACKGROUND: The increasing prevalence of preterm birth, which is a global phenomenon, is attributable to the increased medical indications, artificial gestations, and some socioeconomic factors. This study was conducted to identify whether development and equality indices are associated with the incidence of preterm birth, specifically, spontaneous and elective preterm births. METHODS: This retrospective observational study comprised an analysis of data on live births from 2019 in Brazil and on socioeconomic indices that were derived from census information in 2017. Data were summarised using absolute and relative frequencies. Spearman's correlation was used to determine the correlation between socioeconomic factors and the preterm birth rate. Multiple beta regression analysis was performed to determine the best model of socioeconomic covariates and preterm birth rate. The significance level was set at 5%. RESULTS: In 2019 in Brazil, the preterm birth rate was 11.03%, of which 58% and 42% were spontaneous and elective deliveries, respectively. For all preterm births, Spearman's correlation varied from ρ = 0.4 for the Gini Index and ρ = - 0.24 for illiteracy. The best fit modelled the spontaneous preterm birth fraction as a negative function of the Human Development Index (HDI). The best-fit model considered the expected elective preterm birth fraction as a positive function of the HDI and as a negative function of the Gini Index, which was used as a precision parameter. CONCLUSIONS: We observed a reduction in the fraction of spontaneous preterm births; however, the distribution was not uniform in the territory: higher rates of spontaneous preterm birth were noticed in the north, northeast, and mid-west regions. Thus, areas with lower education levels and inequal income distribution have a higher proportion of spontaneous preterm birth. The fraction of elective preterm birth was positively associated with more advantaged indices of socioeconomic status.

Sonographic evaluation of umbilical cord thickness in monochorionic diamniotic twin pregnancies.

OBJECTIVE: To develop a nomogram of the thickness of the umbilical cord (UC) and its components in monochorionic diamniotic (MCDA) twin pregnancies. METHODS: This prospective longitudinal study involved 47 MCDA twin pregnancies (94 fetuses) between 18 and 33 weeks of gestation. Ultrasound assessments of UC cross-sections and measurements of the umbilical cord area (UCA), the umbilical vein area (UVA), the umbilical artery area (UAA), and the Wharton jelly area (WJA) were made. The UC measurements were correlated with gestational ages. Reference values for the gestational ages of MCDA pregnancies were determined and compared with those of dichorionic twins and singletons. The cases which developed selective intrauterine growth restriction were contrasted with normal cases. RESULTS: A positive correlation was found between all UC components and gestational age and fetal weight. The UCA of MCDA fetuses was significantly larger than that of DC fetuses (p < 0.001) at the expense of a larger WJA (p < 0.001) and similar to that of singleton pregnancies. The MCDA fetuses with an estimated fetal weight below the 10th percentile had a smaller UCA than fetuses with a normal estimated weight (p < 0.001). CONCLUSION: The MCDA twins exhibited a thicker UC than that of dichorionic twins.

Open fetal myelomeningocele repair at a university hospital: surgery and pregnancy outcomes.

PURPOSE: Myelomeningocele (MMC) is an open neural tube defect that causes great morbidity. Prenatal open repair is the standard treatment; however, there are many complications related to the procedure. This study reports preliminary findings of open in utero repair of MMC in a public tertiary hospital in Brazil and describes factors that could be associated with increased surgical morbidity. METHODS: Thirty-nine patients underwent open in utero repair of MMC from October 2015 to August 2019. The Clavien-Dindo classification of surgical complications and a classification system with the preterm definitions of the World Health Organization were used, respectively, for maternal and fetal complications. RESULTS: A total of 28 mothers (71.8%) and 31 fetuses (79.5%) experienced at least one minor to major complication. Three mothers (7.7%) had a severe grade 4 complication. Fetal complications grades 3 to 5 occurred in 13 fetuses (33.3%). Gestational age at surgery and at birth were 24.88 ± 1.16 weeks and 33.23 ± 3.68 weeks, respectively. Preterm delivery occurred in 30 patients (76.9%), membrane rupture in 18 patients (46.2%) and chorioamnionitis in 13 patients (33.3%). CONCLUSION: Open fetal surgery for MMC was performed at a Brazilian public tertiary care center, resulting in three grade 4 maternal complications. Relevant fetal complications were also present. The use of a standard classification system for complications renders studies more comparable and data more useful for counseling patients. Adjustments of perioperative procedures and long-term follow-up are needed to determine the real benefit of open in utero repair of MMC at our hospital.

Diagnostic power and clinical impact of exome sequencing in a cohort of 500 patients with rare diseases.

Rare diseases comprise a diverse group of conditions, most of which involve genetic causes. We describe the variable spectrum of findings and clinical impacts of exome sequencing (ES) in a cohort of 500 patients with rare diseases. In total, 164 primary findings were reported in 158 patients, representing an overall diagnostic yield of 31.6%. Most of the findings (61.6%) corresponded to autosomal dominant conditions, followed by autosomal recessive (25.6%) and X-linked (12.8%) conditions. These patients harbored 195 variants, among which 43.6% are novel in the literature. The rate of molecular diagnosis was considerably higher for prenatal samples (67%; 4/6), younger children (44%; 24/55), consanguinity (50%; 3/6), gastrointestinal/liver disease (44%; 16/36) and syndromic/malformative conditions (41%; 72/175). For 15.6% of the cohort patients, we observed a direct potential for the redirection of care with targeted therapy, tumor screening, medication adjustment and monitoring for disease-specific complications. Secondary findings were reported in 37 patients (7.4%). Based on cost-effectiveness studies in the literature, we speculate that the reports of secondary findings may influence an increase of 123.2 years in the life expectancy for our cohort, or 0.246 years/cohort patient. ES is a powerful method to identify the molecular bases of monogenic disorders and redirect clinical care.

Women's obstetric history and midtrimester cervical length measurements by 2d/3d and doppler ultrasound / História obstétrica e medida do comprimento do colo uterino de mulheres no segundo trimestre gestacional por ultrassonografia bi/tridimensional e Doppler

Abstract Objective The aim of the present study was to compare the obstetric history and both two- and tri-dimensional ultrasound parameters according to different cervical lengths. Methods The present cross-sectional study analyzed 248 midtrimester pregnant women according to cervical length and compared the data with the obstetric history and 2D/3D ultrasound parameters. Patients were divided into 3 groups according to cervical length: The Short Cervix group for cervical lengths ≥ 15mm and< 25mm(n= 68), the Very Short Cervix group for cervical lengths< 15mm (n = 18) and the Control group, composed of 162 pregnant women with uterine cervical lengths ≥ 25mm. Results When analyzing the obstetric history of only non-nulliparous patients, a significant association between the presence of a short cervix in the current pregnancy and at least one previous preterm birth was reported (p = 0.021). Cervical length and volume were positively correlated (Pearson coefficient = 0.587, p < 0.0001). The flow index (FI) parameter of cervical vascularization was significantly different between the Control and Very Short Cervix groups. However, after linear regression, in the presence of volume information, we found no association between the groups and FI. Uterine artery Doppler was also not related to cervical shortening. Conclusion The present study showed a significant association between the presence of a short cervix in the current pregnancy and at least one previous preterm birth. None of the vascularization indexes correlate with cervical length as an independent parameter. Uterine artery Doppler findings do not correlate with cervical length.

Resumo Objetivo O objetivo do presente estudo foi comparar a história obstétrica e os parâmetros bi- e tridimensionais ultrassonográficos de acordo com os diferentes comprimentos cervicais. Métodos O presente estudo transversal analisou 248 gestantes no segundo trimestre de acordo com o comprimento cervical e comparou os dados com a história obstétrica e os parâmetros ultrassonográficos 2D/3D. As pacientes foram divididas em 3 grupos de acordo com o comprimento do colo uterino: grupo Colo Curto para comprimentos cervicais ≥ 15mm e < 25mm (n = 68), grupo Colo Muito Curto para comprimentos cervicais < 15mm (n = 18) e grupo Controle, composto por 162 gestantes com comprimento cervical uterino ≥ 25 mm. Resultados Ao analisar a história obstétrica apenas de pacientes não nulíparas, foi relatadauma associação significativa entre a presença de colo uterino curto na gravidez atual e pelo menos um episódio de parto prematuro anterior (p = 0,021). Comprimento e volume do colo uterino foram correlacionados positivamente (coeficiente de Pearson = 0,587, p < 0,0001). O parâmetro índice de fluxo (IF) da vascularização cervical foi significativamente diferente entre os grupos Controle e Colo Muito Curto. Entretanto, após regressão linear, na presença de informações de volume, não encontramos associação entre os grupos e o parâmetro IF. Também não foi encontrada relação entre o Doppler da artéria uterina e o encurtamento cervical. Conclusão O presente estudo mostrou uma associação significativa entre a presença de colo uterino curto na gravidez atual e pelo menos um episódio de parto prematuro anterior. Nenhum dos índices de vascularização se correlaciona com o comprimento cervical como parâmetro independente, assim como o Doppler da artéria uterina também não está relacionado ao comprimento do colo uterino.

Women's Obstetric History and Midtrimester Cervical Length Measurements by 2D/3D and Doppler Ultrasound.

OBJECTIVE: The aim of the present study was to compare the obstetric history and both two- and tri-dimensional ultrasound parameters according to different cervical lengths. METHODS: The present cross-sectional study analyzed 248 midtrimester pregnant women according to cervical length and compared the data with the obstetric history and 2D/3D ultrasound parameters. Patients were divided into 3 groups according to cervical length: The Short Cervix group for cervical lengths ≥ 15 mm and < 25 mm (n = 68), the Very Short Cervix group for cervical lengths < 15 mm (n = 18) and the Control group, composed of 162 pregnant women with uterine cervical lengths ≥ 25 mm. RESULTS: When analyzing the obstetric history of only non-nulliparous patients, a significant association between the presence of a short cervix in the current pregnancy and at least one previous preterm birth was reported (p = 0.021). Cervical length and volume were positively correlated (Pearson coefficient = 0.587, p < 0.0001). The flow index (FI) parameter of cervical vascularization was significantly different between the Control and Very Short Cervix groups. However, after linear regression, in the presence of volume information, we found no association between the groups and FI. Uterine artery Doppler was also not related to cervical shortening. CONCLUSION: The present study showed a significant association between the presence of a short cervix in the current pregnancy and at least one previous preterm birth. None of the vascularization indexes correlate with cervical length as an independent parameter. Uterine artery Doppler findings do not correlate with cervical length.

OBJETIVO: O objetivo do presente estudo foi comparar a história obstétrica e os parâmetros bi- e tridimensionais ultrassonográficos de acordo com os diferentes comprimentos cervicais. MéTODOS: O presente estudo transversal analisou 248 gestantes no segundo trimestre de acordo com o comprimento cervical e comparou os dados com a história obstétrica e os parâmetros ultrassonográficos 2D/3D. As pacientes foram divididas em 3 grupos de acordo com o comprimento do colo uterino: grupo Colo Curto para comprimentos cervicais ≥ 15 mm e < 25 mm (n = 68), grupo Colo Muito Curto para comprimentos cervicais < 15 mm (n = 18) e grupo Controle, composto por 162 gestantes com comprimento cervical uterino ≥ 25 mm. RESULTADOS: Ao analisar a história obstétrica apenas de pacientes não nulíparas, foi relatada uma associação significativa entre a presença de colo uterino curto na gravidez atual e pelo menos um episódio de parto prematuro anterior (p = 0,021). Comprimento e volume do colo uterino foram correlacionados positivamente (coeficiente de Pearson = 0,587, p < 0,0001). O parâmetro índice de fluxo (IF) da vascularização cervical foi significativamente diferente entre os grupos Controle e Colo Muito Curto. Entretanto, após regressão linear, na presença de informações de volume, não encontramos associação entre os grupos e o parâmetro IF. Também não foi encontrada relação entre o Doppler da artéria uterina e o encurtamento cervical. CONCLUSãO: O presente estudo mostrou uma associação significativa entre a presença de colo uterino curto na gravidez atual e pelo menos um episódio de parto prematuro anterior. Nenhum dos índices de vascularização se correlaciona com o comprimento cervical como parâmetro independente, assim como o Doppler da artéria uterina também não está relacionado ao comprimento do colo uterino.

Emergency cerclage: gestational and neonatal outcomes.

BACKGROUND: The gestational and neonatal outcomes of women with early cervical dilatation undergoing emergency cerclage were evaluated and compared with women treated with expectant management and bed rest. METHODS: Retrospective analysis of pregnant women admitted between 2001 and 2017 with a diagnosis of early cervical dilatation and/or bulging membranes. Patients with a singleton pregnancy of a fetus without malformations, between 16 and 25 weeks and 6 days, with cervical dilatation of 1 to 3 cm were included; patients who delivered or miscarried within 2 days after admission were excluded. RESULTS: The study enrolled 30 patients: 19 in the cerclage group and 11 in the rest group. There was a significant difference, with the cerclage group showing better results concerning gestational age at delivery (28.7 vs. 23.3 weeks; p=0.031) and latency between hospital admission and delivery (48.6 vs. 16 days; p=0.016). The fetal death rate was lower in the cerclage group (5.3% vs. 54.5%, p=0.004). Considering gestational age at delivery of live newborns, no difference was observed between the cerclage and rest groups (29.13 vs. 27.4 weeks; p=0.857). CONCLUSIONS: Emergency cerclage was associated with longer latency, a significant impact on gestational age at delivery and reduction in the fetal death rate.

Emergency cerclage: gestational and neonatal outcomes

SUMMARY BACKGROUND: The gestational and neonatal outcomes of women with early cervical dilatation undergoing emergency cerclage were evaluated and compared with women treated with expectant management and bed rest. METHODS: Retrospective analysis of pregnant women admitted between 2001 and 2017 with a diagnosis of early cervical dilatation and/or bulging membranes. Patients with a singleton pregnancy of a fetus without malformations, between 16 and 25 weeks and 6 days, with cervical dilatation of 1 to 3 cm were included; patients who delivered or miscarried within 2 days after admission were excluded. RESULTS: The study enrolled 30 patients: 19 in the cerclage group and 11 in the rest group. There was a significant difference, with the cerclage group showing better results concerning gestational age at delivery (28.7 vs. 23.3 weeks; p=0.031) and latency between hospital admission and delivery (48.6 vs. 16 days; p=0.016). The fetal death rate was lower in the cerclage group (5.3% vs. 54.5%, p=0.004). Considering gestational age at delivery of live newborns, no difference was observed between the cerclage and rest groups (29.13 vs. 27.4 weeks; p=0.857). CONCLUSIONS: Emergency cerclage was associated with longer latency, a significant impact on gestational age at delivery and reduction in the fetal death rate.

RESUMO OBJETIVO: Os resultados gestacionais e neonatais de mulheres com cervicodilatação precoce submetidas à cerclagem de emergência foram avaliados e comparados com mulheres tratadas com manejo expectante com repouso no leito. MÉTODOS: Análise retrospectiva de gestantes admitidas entre 2001 e 2017 com diagnóstico de cervicodilatação precoce e/ou membranas protrusas. Foram incluídas pacientes com gestação única de feto sem malformações, entre 16 semanas e 25 semanas e 6 dias, com dilatação cervical de 1 a 3 cm; as pacientes que tiveram parto ou aborto dentro de 2 dias após admissão foram excluídas. RESULTADOS: O estudo envolveu 30 pacientes: 19 no grupo cerclagem e 11 no grupo repouso. Houve diferença significativa, com o grupo cerclagem apresentando melhores resultados em relação à idade gestacional no parto (28,7 vs. 23,3 semanas; p=0,031) e à latência entre a admissão hospitalar e o parto (48,6 vs. 16 dias; p=0,016). A taxa de mortalidade fetal foi menor no grupo cerclagem (5,3% vs. 54,5%, p=0,004). Considerando a idade gestacional no nascimento dos recém-nascidos vivos, não houve diferença entre os grupos cerclagem e expectante (29,13 vs. 27,4 semanas; p=0,857). CONCLUSÕES: A cerclagem de emergência foi associada a maior período de latência com impacto significativo na idade gestacional do parto e à redução da taxa de mortalidade fetal.

The role of three-dimensional ultrasound in pregnancies submitted to cerclage.

OBJECTIVE: Cervical cerclage is the standard treatment for cervical incompetence (CI); however, there is still a high risk of preterm birth for women who undergo this treatment. The aim of this study was to longitudinally evaluate findings on two-dimensional transvaginal ultrasonography (2DTVUS) and three-dimensional transvaginal ultrasonography (3DTVUS) that could be related to gestational age at birth. METHODS: A total of 68 pregnant women who were treated with cerclage were evaluated by 2DTVUS and 3DTVUS in the second and third trimesters of pregnancy. Log-rank tests and Cox regression analyses were used to identify significant findings related to gestational age at delivery. RESULTS: A cervical length lower than 281 mm (p= 0.0083), a proximal cervical length lower than 10 mm (p= 0.0151), a cervical volume lower than 18.17 cm3 (p= 0.0152), a vascularization index (VI) under 2.153 (p= 0.0044), and a vascularization-flow index (VFI) under 0.961 (p= 0.0059) in the second trimester were all related to earlier delivery. In the third trimester, a cervical length lower than 20.4 mm (p= 0.0009), a VI over 0.54 (p= 0.0327) and a VFI over 2.275 (p= 0.0479) were all related to earlier delivery. Cervical funnelling in the second and third trimesters and proximal cervical length in the third trimester were not related to gestational age at birth. The COX regression analyses showed that cervical volume in the second trimester; FI and VFI in the third trimester were significantly associated with gestational age at birth. CONCLUSION: In women treated with history-indicated cerclage or ultrasound-indicated cerclage, 2nd trimester cervical volume and 3rd trimester FI and VFI are independent significant sonographic findings associated with time to delivery.

The role of three-dimensional ultrasound in pregnancies submitted to cerclage

SUMMARY OBJECTIVE: Cervical cerclage is the standard treatment for cervical incompetence (CI); however, there is still a high risk of preterm birth for women who undergo this treatment. The aim of this study was to longitudinally evaluate findings on two-dimensional transvaginal ultrasonography (2DTVUS) and three-dimensional transvaginal ultrasonography (3DTVUS) that could be related to gestational age at birth. METHODS: A total of 68 pregnant women who were treated with cerclage were evaluated by 2DTVUS and 3DTVUS in the second and third trimesters of pregnancy. Log-rank tests and Cox regression analyses were used to identify significant findings related to gestational age at delivery. RESULTS: A cervical length lower than 281 mm (p= 0.0083), a proximal cervical length lower than 10 mm (p= 0.0151), a cervical volume lower than 18.17 cm3 (p= 0.0152), a vascularization index (VI) under 2.153 (p= 0.0044), and a vascularization-flow index (VFI) under 0.961 (p= 0.0059) in the second trimester were all related to earlier delivery. In the third trimester, a cervical length lower than 20.4 mm (p= 0.0009), a VI over 0.54 (p= 0.0327) and a VFI over 2.275 (p= 0.0479) were all related to earlier delivery. Cervical funnelling in the second and third trimesters and proximal cervical length in the third trimester were not related to gestational age at birth. The COX regression analyses showed that cervical volume in the second trimester; FI and VFI in the third trimester were significantly associated with gestational age at birth. CONCLUSION: In women treated with history-indicated cerclage or ultrasound-indicated cerclage, 2nd trimester cervical volume and 3rd trimester FI and VFI are independent significant sonographic findings associated with time to delivery.

RESUMO OBJETIVOS: Determinar quais características ultrassonográficas obtidas por meio da ultrassonografia transvaginal bidimensional (USG TV 2D) e tridimensional (USG TV 3D) associam-se ao parto prematuro em gestantes submetidas à cerclagem profilática e terapêutica. MÉTODOS: Sessenta e seis gestantes com feto único submetidas à cerclagem profilática ou terapêutica e acompanhadas no ambulatório de Aborto Habitual da Clínica Obstétrica do Hospital das Clínicas da Faculdade de Medicina da USP, entre 10 de juho de 2012 e 30 de outubro de 2015, foram avaliadas longitudinalmente, por meio das US TV 2D e US TV 3D associadas ao power Doppler para avaliação do VI, FI e VFI, nos três trimestres da gestação. Os resultados foram avaliados em relação ao parto em idade gestacional (IG) menor que 34 semanas e maior ou igual a 34 semanas, assim como em relação à idade do parto como variável contínua. RESULTADOS: O comprimento do colo uterino (CC) e a distância do ponto de cerclagem ao orifício interno do colo uterino (POI) diminuíram de forma significativa entre o segundo e terceiro trimestres da gestação. O CC, o POI e o afunilamento cervical no terceiro trimestre da gestação tiveram relação com a ocorrência de parto em IG<34 semanas. Na análise de regressão de COX, em que a variável de interesse foi o tempo até o parto, o volume do colo uterino no segundo trimestre e o FI e VFI no terceiro trimestre foram significativos. CONCLUSÃO: Foi possível identificar parâmetros ultrassonográficos do colo uterino bi e tridimensionais que se correlacionam com a idade gestacional do parto.

Isochromosome 21q is overrepresented among false-negative cell-free DNA prenatal screening results involving Down syndrome.

False-negative cell-free DNA (cfDNA) screening results involving Down syndrome are rare, but have high clinical impact on patients and their healthcare providers. Understanding the biology behind these results may allow for improved diagnostic follow-up and counseling. In 5 different centers offering cfDNA prenatal screening, 9 false-negative results were documented in 646 confirmed cases of trisomy 21; a false-negative rate of 1.4% (95% CI, 0.7-2.6). False-negative results included 4 cases of classical trisomy 21 and 5 cases with a de novo 21q;21q rearrangement. Two out of five rearrangements had molecular studies and were confirmed as isochromosomes. When combined with reports from the cfDNA screening literature, 8 out of 29 (28%) Down syndrome cases with a false-negative "non-invasive prenatal test" (NIPT) were associated with a 21q;21q rearrangement, compared with 2% reported in live born children with Down syndrome. In our laboratory series, evidence for placental or fetal mosaicism was present in 3 out of 3 true-positive cases involving a 21q;21q rearrangement and was confirmed in one false-negative case where placental material was available for study. Isochromosome 21q rearrangements are thus overrepresented among false-negative cfDNA screening results involving Down syndrome. Postzygotic isochromosome formation leading to placental mosaicism provides a biological cause for the increased prevalence of these rearrangements among false-negative cases. For clinical practice, a low trisomic fraction (z-score or equivalent measure) relative to the fetal fraction suggests placental mosaicism. Care should be taken as these cases may not reflect confined placental mosaicism, but rather full trisomy in the presence of a placenta containing normal cells.

Type II and III Selective Fetal Growth Restriction: Perinatal Outcomes of Expectant Management and Laser Ablation of Placental Vessels.

OBJECTIVES: To describe the perinatal outcomes of type II and III selective fetal growth restriction (sFGR) in monochorionic-diamniotic (MCDA) twin pregnancies treated with expectant management or laser ablation of placental vessels (LAPV). METHODS: Retrospective analysis of cases of sFGR that received expectant management (type II, n=6; type III, n=22) or LAPV (type II, n=30; type III, n=9). The main outcomes were gestational age at delivery and survival rate. RESULTS: The smaller fetus presented an absent/reversed "a" wave in the ductus venosus (arAWDV) in all LAPV cases, while none of the expectant management cases presented arAWDV. The median gestational age at delivery was within the 32nd week for expectant management (type II and III) and for type II LAPV, and the 30th week for type III LAPV. The rate of at least one twin alive at hospital discharge was 83.3% and 90.9% for expectant management type II and III, respectively, and 90% and 77.8% for LAPV type II and III, respectively. CONCLUSION: LAPV in type II and III sFGR twins with arAWDV in the smaller fetus seems to yield outcomes similar to those of less severe cases that received expectant management.

Spontaneous prematurity in fetuses with congenital diaphragmatic hernia: a retrospective cohort study about prenatal predictive factors.

BACKGROUND: To evaluate possible predictive factors of spontaneous prematurity in fetuses with congenital diaphragmatic hernia (CDH). METHODS: A retrospective cohort study was performed. Inclusion criteria were presence of CDH; absence of fetoscopy; absence of karyotype abnormality; maximum of one major malformation associated with diaphragmatic hernia; ultrasound monitoring at the Obstetrics Clinic of Clinicas Hospital at the University of São Paulo School of Medicine, from January 2001 to October 2014. The data were obtained through the electronic records and ultrasound system of our fetal medicine service. The following variables were analyzed: maternal age, primiparity, associated maternal diseases, smoking, previous spontaneous preterm birth, fetal malformation associated with hernia, polyhydramnios, fetal growth restriction, presence of intrathoracic liver, invasive procedures performed, side of hernia and observed-to- expected lung to head ratio (o/e LHR). On individual analysis, variables were assessed using the Chi-square test and the Mann-Whitney test. A multiple logistic regression model was applied to select variables independently influencing the prediction of preterm delivery. A ROC curve was constructed with the significant variable, identifying the values with best sensitivity and specificity to be suggested for use in clinical practice. RESULTS: Eighty fetuses were evaluated, of which, 21 (26.25%) were premature. O/e LHR was the only factor associated with prematurity (p = 0.020). The ROC curve showed 93% sensitivity with 48.4% specificity for the cutoff of 40%. CONCLUSION: O/e LHR was the only predictor of prematurity in this sample.

Type II and III selective fetal growth restriction: perinatal outcomes of expectant management and laser ablation of placental vessels

OBJECTIVES: To describe the perinatal outcomes of type II and III selective fetal growth restriction (sFGR) in monochorionic-diamniotic (MCDA) twin pregnancies treated with expectant management or laser ablation of placental vessels (LAPV). METHODS: Retrospective analysis of cases of sFGR that received expectant management (type II, n=6; type III, n=22) or LAPV (type II, n=30; type III, n=9). The main outcomes were gestational age at delivery and survival rate. RESULTS: The smaller fetus presented an absent/reversed "a" wave in the ductus venosus (arAWDV) in all LAPV cases, while none of the expectant management cases presented arAWDV. The median gestational age at delivery was within the 32nd week for expectant management (type II and III) and for type II LAPV, and the 30th week for type III LAPV. The rate of at least one twin alive at hospital discharge was 83.3% and 90.9% for expectant management type II and III, respectively, and 90% and 77.8% for LAPV type II and III, respectively. CONCLUSION: LAPV in type II and III sFGR twins with arAWDV in the smaller fetus seems to yield outcomes similar to those of less severe cases that received expectant management.

Validation of QF-PCR for prenatal diagnoses in a Brazilian population.

OBJECTIVES:: Quantitative fluorescence polymerase chain reaction (QF-PCR) is a rapid and reliable method for screening aneuploidies, but in Brazil, it is not used in public services. We investigated the accuracy of QF-PCR for the prenatal recognition of common aneuploidies and compared these results with cytogenetic results in our laboratory. METHOD:: A ChromoQuant QF-PCR kit containing 24 primer pairs targeting loci on chromosomes 21, 13, 18, X and Y was employed to identify aneuploidies of the referred chromosomes. RESULTS:: A total of 162 amniotic fluid samples analyzed using multiplex QF-PCR were compared with karyotyping analysis. The QF-PCR results were consistent with the results of cytogenetic analysis in 95.4% of all samples. CONCLUSION:: QF-PCR was demonstrated to be efficient and reliable for prenatal aneuploidy screening. This study suggests that QF-PCR can be used as a rapid diagnostic method. However, rearrangements and some mosaic samples cannot be detected with this test; thus, those exceptions must undergo cytogenetic analysis.

Validation of QF-PCR for prenatal diagnoses in a Brazilian population

OBJECTIVES: Quantitative fluorescence polymerase chain reaction (QF-PCR) is a rapid and reliable method for screening aneuploidies, but in Brazil, it is not used in public services. We investigated the accuracy of QF-PCR for the prenatal recognition of common aneuploidies and compared these results with cytogenetic results in our laboratory. METHOD: A ChromoQuant QF-PCR kit containing 24 primer pairs targeting loci on chromosomes 21, 13, 18, X and Y was employed to identify aneuploidies of the referred chromosomes. RESULTS: A total of 162 amniotic fluid samples analyzed using multiplex QF-PCR were compared with karyotyping analysis. The QF-PCR results were consistent with the results of cytogenetic analysis in 95.4% of all samples. CONCLUSION: QF-PCR was demonstrated to be efficient and reliable for prenatal aneuploidy screening. This study suggests that QF-PCR can be used as a rapid diagnostic method. However, rearrangements and some mosaic samples cannot be detected with this test; thus, those exceptions must undergo cytogenetic analysis.