RESUMO
OBJECTIVES: To perform a nationwide study of quadrichorionic quadriamniotic (QCQA) quadruplet pregnancies and to compare the pregnancy outcome in those undergoing fetal reduction with non-reduced quadruplets and dichorionic diamniotic (DCDA) twin pregnancies from the same time period. METHODS: This was a retrospective Danish national register-based study performed using data from the national Danish Fetal Medicine Database, which included all QCQA quadruplets and all non-reduced DCDA twin pregnancies with an estimated due date between 2008 and 2018. The primary outcome measure was a composite of adverse pregnancy outcomes, including pregnancy loss or intrauterine death of one or more fetuses. Secondary outcomes included gestational age at delivery, the number of liveborn children, preterm delivery before 28, 32 and 37 gestational weeks and birth weight. Data on pregnancy complications and baseline characteristics were also recorded. Outcomes were compared between reduced and non-reduced quadruplet pregnancies, and between DCDA pregnancies and quadruplet pregnancies reduced to twins. A systematic literature search was performed to describe and compare previous results with our findings. RESULTS: Included in the study were 33 QCQA quadruplet pregnancies, including three (9.1%) non-reduced pregnancies, 28 (84.8%) that were reduced to twin pregnancy and fewer than three (6.1%) that were reduced to singleton pregnancy, as well as 9563 DCDA twin pregnancies. Overall, the rate of adverse pregnancy outcome was highest in non-reduced quadruplets (66.7%); it was 50% in quadruplets reduced to singletons and 10.7% in quadruplets reduced to twins. The proportion of liveborn infants overall was 91.1% of the total number expected to be liveborn in quadruplet pregnancies reduced to twins. This was statistically significantly different from 97.6% in non-reduced dichorionic twins (P = 0.004), and considerably higher than 58.3% in non-reduced quadruplets. The rates of preterm delivery < 28, < 32 and < 37 weeks were decreased in quadruplets reduced to twins compared with those in non-reduced quadruplet pregnancies. Quadruplets reduced to twins did not achieve equivalent pregnancy outcomes to those of DCDA twins. CONCLUSION: This national study of QCQA quadruplets has shown that multifetal pregnancy reduction improves pregnancy outcome, including a decreased rate of preterm delivery and higher proportion of liveborn children. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.
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Gravidez de Quadrigêmeos , Nascimento Prematuro , Recém-Nascido , Feminino , Criança , Gravidez , Humanos , Resultado da Gravidez/epidemiologia , Redução de Gravidez Multifetal/métodos , Nascimento Prematuro/epidemiologia , Nascimento Prematuro/etiologia , Estudos Retrospectivos , Estudos de Coortes , Gêmeos Dizigóticos , Gravidez de Gêmeos , Idade Gestacional , Dinamarca/epidemiologiaRESUMO
OBJECTIVES: To describe the distributional properties and assess the performance of placental growth factor (PlGF) measured in blood samples collected before 11 weeks' gestation in the prediction of pre-eclampsia (PE). METHODS: The study population consisted of pregnant women included in the Pre-eclampsia Screening in Denmark (PRESIDE) study with a PlGF measurement from the routine combined first-trimester screening (cFTS) blood sample collected at 8-14 weeks' gestation. PRESIDE was a prospective multicenter study investigating the predictive performance of the Fetal Medicine Foundation (FMF) first-trimester screening algorithm for PE in a Danish population. In the current study, serum concentration of PlGF in the cFTS blood samples was analyzed in batches between January and June 2021. RESULTS: A total of 8386 pregnant women were included. The incidence of PE was 0.7% at < 37 weeks' gestation and 3.0% at ≥ 37 weeks. In blood samples collected at 10 weeks' gestation, PlGF multiples of the median (MoM) were significantly lower in pregnancies with preterm PE < 37 weeks compared to unaffected pregnancies. However, PlGF MoM did not differ significantly between pregnancies with PE and unaffected pregnancies in samples collected before 10 weeks' gestation. CONCLUSIONS: The gestational-age range for PlGF sampling may be expanded from 11-14 to 10-14 weeks when assessing the risk for PE using the FMF first-trimester screening model. There is little evidence to support the use of PlGF in blood samples collected before 10 weeks' gestation. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.
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Pré-Eclâmpsia , Gravidez , Recém-Nascido , Humanos , Feminino , Fator de Crescimento Placentário , Pré-Eclâmpsia/diagnóstico , Estudos Prospectivos , Algoritmos , Idade GestacionalRESUMO
OBJECTIVE: To investigate the national prevalence and prenatal detection rate (DR) of major congenital heart disease (mCHD) in twin pregnancies without twin-to-twin transfusion syndrome (TTTS)-associated CHD in a Danish population following a standardized prenatal screening program. METHODS: This was a national registry-based study of data collected prospectively over a 10-year period. In Denmark, all women with a twin pregnancy are offered standardized screening and surveillance programs in addition to first- and second-trimester screening for aneuploidies and malformation, respectively: monochorionic (MC) twins every 2 weeks from gestational week 15 and dichorionic (DC) twins every 4 weeks from week 18. The data were retrieved from the Danish Fetal Medicine Database and included all twin pregnancies from 2009-2018, in which at least one fetus had a pre- and/or postnatal mCHD diagnosis. mCHD was defined as CHD requiring surgery within the first year of life, excluding ventricular septal defects. All pregnancy data were pre- and postnatally validated in the local patient files at the four tertiary centers covering the entire country. RESULTS: A total of 60 cases from 59 twin pregnancies were included. The prevalence of mCHD was 4.6 (95% CI, 3.5-6.0) per 1000 twin pregnancies (1.9 (95% CI, 1.3-2.5) per 1000 live births). The prevalences for DC and MC were 3.6 (95% CI, 2.6-5.0) and 9.2 (95% CI, 5.8-13.7) per 1000 twin pregnancies, respectively. The national prenatal DR of mCHD in twin pregnancies for the entire period was 68.3%. The highest DRs were in cases with univentricular hearts (100%) and the lowest with aortopulmonary window, total anomalous pulmonary venous return, Ebstein's anomaly, aortic valve stenosis and coarctation of the aorta (0-25%). Mothers of children with prenatally undetected mCHD had a significantly higher body mass index (BMI) compared to mothers of children with a prenatally detected mCHD (median, 27 kg/m2 and 23 kg/m2 , respectively; P = 0.02). CONCLUSIONS: The prevalence of mCHD in twins was 4.6 per 1000 pregnancies and was higher in MC than DC pregnancies. The prenatal DR of mCHD in twin pregnancies was 68.3%. Maternal BMI was higher in cases of prenatally undetected mCHD. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.
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Cardiopatias Congênitas , Gravidez de Gêmeos , Gravidez , Criança , Humanos , Feminino , Prevalência , Idade Gestacional , Cardiopatias Congênitas/diagnóstico por imagem , Cardiopatias Congênitas/epidemiologia , Gêmeos Dizigóticos , Dinamarca/epidemiologia , Estudos RetrospectivosRESUMO
OBJECTIVES: To investigate the predictive performance of the Fetal Medicine Foundation (FMF) first-trimester screening algorithm for pre-eclampsia in a Danish population and compare screening performance with that of the current Danish strategy, which is based on maternal risk factors. METHODS: This was a prospective study of women with a singleton pregnancy attending for their first-trimester ultrasound scan and screening for aneuploidies at six Danish university hospitals between May 2019 and December 2020. Prenatal data on maternal characteristics and medical history were recorded, and measurements of mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI), serum pregnancy-associated plasma protein-A (PAPP-A) and serum placental growth factor (PlGF) were collected without performing a risk assessment for pre-eclampsia. Information on acetylsalicylic acid use was recorded. After delivery, pregnancy outcome, including gestational age at delivery and pre-eclampsia diagnosis, was recorded. Pre-eclampsia risk assessment for each woman was calculated blinded to outcome using the FMF screening algorithm following adjustment to the Danish population. Detection rates (DRs) of the FMF algorithm were calculated for a fixed screen-positive rate (SPR) of 10% and for the SPR achieved in the current Danish screening. RESULTS: A total of 8783 pregnant women were included, with a median age of 30.8 (interquartile range (IQR), 28.1-33.9) years. The majority were white (95%), naturally conceiving (90%), non-smokers (97%) and had no family history of pre-eclampsia (96%). The median body mass index was 23.4 (IQR, 21.2-26.6) kg/m2 . A complete risk assessment including maternal characteristics, MAP, UtA-PI, PlGF and PAPP-A was available for 8156 women (92.9%). In these women, UtA-PI was measured bilaterally with a median value of 1.58 (IQR, 1.27-1.94) and the median resting MAP of 80.5 (IQR, 76.1-85.4) mmHg in two consecutive measurements. Among these, 303 (3.7%) developed pre-eclampsia, including 55 (0.7%) cases of pre-eclampsia with delivery < 37 weeks of gestation and 16 (0.2%) cases of pre-eclampsia with delivery < 34 weeks. At a SPR of 10%, combined screening using the FMF algorithm based on maternal characteristics, MAP, UtA-PI, PlGF and PAPP-A had a DR of 77.4% (95% CI, 57.6-97.2%) for pre-eclampsia with delivery < 34 weeks, 66.8% (95% CI, 54.4-79.1%) for pre-eclampsia with delivery < 37 weeks and 44.1% (95% CI, 38.5-49.7%) for pre-eclampsia with delivery at any gestational age. The current Danish screening strategy using maternal risk factors detected 25.0% of women with pre-eclampsia with delivery < 34 weeks and 19.6% of women with pre-eclampsia with delivery < 37 weeks at a SPR of 3.4%. When applying the FMF algorithm including maternal characteristics, MAP, UtA-PI and PlGF at the fixed SPR of 3.4%, the DRs were 60.5% (95% CI, 36.9-84.1%) for PE with delivery < 34 weeks and 45.2% (95% CI, 32.0-58.5%) for PE with delivery < 37 weeks. CONCLUSION: In this large Danish multicenter study, the FMF algorithm based on maternal characteristics, MAP, UtA-PI, PlGF and PAPP-A predicted 77.4% of cases with pre-eclampsia with delivery < 34 weeks and 66.8% of cases with pre-eclampsia with delivery < 37 weeks of gestation at a SPR of 10%, suggesting that the performance of the algorithm in a Danish cohort matches that in other populations. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.
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Pré-Eclâmpsia , Diagnóstico Pré-Natal , Gravidez , Feminino , Humanos , Pré-Eclâmpsia/epidemiologia , Estudos Prospectivos , Proteína Plasmática A Associada à Gravidez , Fator de Crescimento Placentário , Pressão Arterial , Artéria Uterina/diagnóstico por imagem , Biomarcadores , Fluxo Pulsátil , Dinamarca/epidemiologiaRESUMO
OBJECTIVE: To estimate the prevalence of chromosomal conditions in all fetuses and children with major congenital heart defect (CHD) in Denmark between 2008 and 2018. METHODS: This was a national registry-based study including all singleton pregnancies with a prenatally or postnatally diagnosed major CHD usually requiring surgery within the first year after birth and a due date between July 2008 and December 2018 in Denmark. Data were retrieved from the Danish Fetal Medicine Database (DFMD) and the Danish Cytogenetic Central Register (DCCR) in October 2020. The DCCR contains information on all prenatal and postnatal genetic analyses, including karyotyping, chromosomal microarray, polymerase chain reaction, multiplex ligation-dependent probe amplification and fluorescence in-situ hybridization. All cases were reviewed by a clinical geneticist, and genetic changes were classified as pathogenic, likely pathogenic, variant of uncertain significance, likely benign or benign. Pathogenic and likely pathogenic variants were considered to be abnormal. Cases with CHD without any registered chromosomal analysis reported were considered genetically normal. Isolated CHD was defined as a case with major CHD without any other structural malformations detected prenatally or postnatally. Results are given as n (%). Comparisons between isolated and non-isolated cases were performed using logistic regression analysis, and data are presented as odds ratios (ORs) with 95% CIs. RESULTS: A total of 8482 cases with any cardiovascular diagnosis were retrieved from the DFMD. Twins (n = 112) and minor CHD cases (n = 6921) were excluded, resulting in 1449 cases with major CHD. Of the included cases, 918 (63.4%) underwent chromosomal analysis. An abnormal test result was found in 187 cases, giving a prevalence of a chromosomal condition of 12.9% (95% CI, 11.2-14.7%) among all cases with major CHD. The highest prevalence of a chromosomal condition was found in cases with pulmonary atresia with intact ventricular septum and those with truncus arteriosus (both 28.6%), while the lowest prevalence was found in cases with transposition of the great arteries (2.2%) and congenitally corrected transposition of the great arteries (0%). In isolated cases of transposition of the great arteries, the prevalence of a chromosomal condition was 0.6%. The overall OR for a chromosomal condition in non-isolated cases compared with isolated cases was 2.72 (95% CI, 1.90-3.88). CONCLUSIONS: We found an overall prevalence of a chromosomal condition of 12.9% among cases with major CHD in a national cohort with a high participation rate in first- and second-trimester screening, without employing whole genome and whole exome sequencing. The prevalence of a chromosomal condition varied considerably according to CHD diagnosis and presence of associated extracardiac malformations. These findings are important for prenatal counseling. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.
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Transtornos Cromossômicos , Cardiopatias Congênitas , Transposição dos Grandes Vasos , Gravidez , Feminino , Criança , Humanos , Prevalência , Cardiopatias Congênitas/epidemiologia , Cardiopatias Congênitas/genética , Cardiopatias Congênitas/diagnóstico , Sistema de Registros , Dinamarca/epidemiologia , Diagnóstico Pré-NatalRESUMO
OBJECTIVE: The aim of this national study was to examine the incidence of preterm pre-eclampsia (PE) and the proportion of women with risk factors for PE, according to the criteria suggested by the National Institute for Health and Care Excellence (NICE) and the American College of Obstetricians and Gynecologists (ACOG), during a 10-year period in Denmark. METHODS: Data from The Danish National Patient Registry and the Danish Medical Birth Registry were used to obtain the incidence of preterm PE with delivery < 37 weeks' gestation and risk factors for PE for all deliveries in Denmark from 1 January 2008 to 31 December 2017. The proportion of women with at least one high-risk factor and/or at least two moderate-risk factors for PE, according to the NICE and ACOG criteria, and the detection rate for preterm PE were examined. Race, socioeconomic status and the woman's weight at birth were not available from the registries used, and information on Type-2 diabetes was found to be invalid. RESULTS: Of the 597 492 deliveries during the study period, any PE was registered in 3.2%, preterm PE < 37 weeks in 0.7% and early-onset PE < 34 weeks' gestation in 0.3%. These proportions remained largely unchanged from 2008 to 2017. Overall, the NICE criteria were fulfilled in 7.5% of deliveries and the ACOG criteria in 17.3%. In the total population, the NICE criteria identified 47.6% of those with preterm PE and the ACOG criteria identified 60.5%. The current criteria for offering aspirin treatment in Denmark largely correspond to having at least one NICE high-risk factor. In 2017, a total of 3.5% of deliveries had at least one NICE high-risk factor, which identified 28.4% of cases that later developed preterm PE. CONCLUSIONS: The incidence of preterm PE remained largely unchanged in Denmark from 2008 to 2017. Prediction of PE according to high-risk maternal factors could be improved by addition of moderate-risk factors. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.
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Obstetrícia/normas , Pré-Eclâmpsia/diagnóstico , Nascimento Prematuro/diagnóstico , Diagnóstico Pré-Natal/estatística & dados numéricos , Medição de Risco/estatística & dados numéricos , Adulto , Aspirina/uso terapêutico , Dinamarca/epidemiologia , Feminino , Idade Gestacional , Humanos , Incidência , Recém-Nascido , Pré-Eclâmpsia/epidemiologia , Pré-Eclâmpsia/prevenção & controle , Valor Preditivo dos Testes , Gravidez , Nascimento Prematuro/epidemiologia , Nascimento Prematuro/prevenção & controle , Diagnóstico Pré-Natal/normas , Sistema de Registros , Medição de Risco/normas , Fatores de RiscoRESUMO
OBJECTIVE: To investigate prenatal changes in cardiac biometric and flow parameters in fetuses with bicuspid aortic valve (BAV) diagnosed neonatally compared with controls with normal cardiac anatomy. METHODS: This analysis was conducted as part of the Copenhagen Baby Heart Study, a multicenter cohort study of 25 556 neonates that underwent second-trimester anomaly scan at 18 + 0 to 22 + 6 weeks' gestation and neonatal echocardiography within 4 weeks after birth, in Copenhagen University Hospital Herlev, Hvidovre Hospital and Rigshospitalet in greater Copenhagen, between April 2016 and October 2018. From February 2017 (Rigshospitalet) and September 2017 (Herlev and Hvidovre hospitals), the protocol for second-trimester screening of the heart was extended to include evaluation of the four-chamber view, with assessment of flow across the atrioventricular valves, sagittal view of the aortic arch and midumbilical artery and ductus venosus pulsatility indices. All images were evaluated by two investigators, and cardiac biometric and flow parameters were measured and compared between cases with BAV and controls. All cases with neonatal BAV were assessed by a specialist. Maternal characteristics and first- and second-trimester biomarkers were also compared between the two groups. RESULTS: Fifty-five infants with BAV and 8316 controls with normal cardiac anatomy were identified during the study period and assessed using the extended prenatal cardiac imaging protocol. There were three times as many mothers who smoked before pregnancy in the group with BAV as in the control group (9.1% vs 2.7%; P = 0.003). All other baseline characteristics were similar between the two groups. Fetuses with BAV, compared with controls, had a significantly larger diameter of the aorta at the level of the aortic valve (3.1 mm vs 3.0 mm (mean difference, 0.12 mm (95% CI, 0.03-0.21 mm))) and the pulmonary artery at the level of the pulmonary valve (4.1 mm vs 3.9 mm (mean difference, 0.15 mm (95% CI, 0.03-0.28 mm))). Following conversion of the diameter measurements of the aorta and pulmonary artery to Z-scores and Bonferroni correction, the differences between the two groups were no longer statistically significant. Pregnancy-associated plasma protein-A (PAPP-A) multiples of the median (MoM) was significantly lower in the BAV group than in the control group (0.85 vs 1.03; P = 0.04). CONCLUSIONS: Our findings suggest that fetuses with BAV may have a larger aortic diameter at the level of the aortic valve, measured in the left-ventricular-outflow-tract view, and a larger pulmonary artery diameter at the level of the pulmonary valve, measured in the three-vessel view, at 20 weeks' gestation. Moreover, we found an association of maternal smoking and low PAPP-A MoM with BAV. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.
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Doença da Válvula Aórtica Bicúspide/diagnóstico , Biometria , Ecocardiografia , Coração Fetal/fisiopatologia , Ultrassonografia Pré-Natal , Adulto , Aorta/diagnóstico por imagem , Aorta/embriologia , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/embriologia , Doença da Válvula Aórtica Bicúspide/embriologia , Circulação Sanguínea , Estudos de Casos e Controles , Feminino , Coração Fetal/diagnóstico por imagem , Coração Fetal/embriologia , Feto/irrigação sanguínea , Feto/diagnóstico por imagem , Idade Gestacional , Humanos , Recém-Nascido , Masculino , Gravidez , Segundo Trimestre da Gravidez , Artéria Pulmonar/diagnóstico por imagem , Artéria Pulmonar/embriologia , Valva Pulmonar/diagnóstico por imagem , Valva Pulmonar/embriologiaRESUMO
OBJECTIVE: To evaluate the risk of inducing RhD immunisation in pregnancies of RhD-negative mothers with an RhD-positive fetus undergoing chorionic villus samplings (CVS) or amniocenteses (AC). DESIGN, SETTING AND POPULATION: Registry-based study in a Danish cohort which has not been given rhesus prophylaxis. METHODS: Data were retrieved from the Department of Clinical Immunology at Rigshospitalet. All RhD-negative women carrying an RhD-positive fetus with screen test results from weeks 8-12 and weeks 25-29 were linked to data from the Danish Fetal Medicine Database. Data were divided into cases where no invasive prenatal diagnostic procedure was performed, cases that had AC performed, and cases that had CVS performed. MAIN OUTCOME MEASURES: A comparison of the proportion of women who developed RhD immunisation between the two screen tests. RESULTS: The cohort consisted of 10 085 women: 9353 had no invasive procedures performed, 189 had AC and 543 had CVS performed. No women were immunised spontaneously or due to the procedure between the first and second screen test in the group with no procedure performed, or in the AC group. One woman was immunised in the CVS group. When comparing the proportion of women who was immunised in the CVS group with the no invasive test group a non-significant difference was found (P = 0.055). CONCLUSION: The RhD immunisation rate before gestational weeks 25-29 in RhD-negative women carrying an RhD-positive fetus is very low, even in women undergoing prenatal invasive testing without rhesus prophylaxis. TWEETABLE ABSTRACT: The RhD immunisation rate during pregnancy is very low even in women undergoing prenatal invasive testing.
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Complicações Hematológicas na Gravidez/diagnóstico , Diagnóstico Pré-Natal/efeitos adversos , Isoimunização Rh/etiologia , Imunoglobulina rho(D)/imunologia , Adulto , Amniocentese/efeitos adversos , Amostra da Vilosidade Coriônica/efeitos adversos , Estudos de Coortes , Bases de Dados Factuais , Dinamarca , Feminino , Idade Gestacional , Humanos , Gravidez , Estudos Retrospectivos , Risco , Adulto JovemAssuntos
Dispositivos Intrauterinos/normas , Derrame Pleural/complicações , Derrame Pleural/cirurgia , Anormalidades Múltiplas , Edema/complicações , Estudos de Viabilidade , Feminino , Doenças Fetais/epidemiologia , Doenças Fetais/mortalidade , Feto , Humanos , Pulmão/anormalidades , Pneumopatias/complicações , Derrame Pleural/diagnóstico por imagem , Derrame Pleural/epidemiologia , Pleurodese/métodos , Gravidez , Cuidado Pré-Natal , Prevalência , Taxa de Sobrevida , Toracentese/métodos , Ultrassonografia/métodosRESUMO
OBJECTIVE: To estimate the prevalence of specific neurodevelopmental disorders in children believed to have isolated mild ventriculomegaly (IMV) prenatally in the second trimester of pregnancy, in order to optimize the counseling process. METHODS: This was a nationwide registry-based study including all singleton pregnancies that had first- and second-trimester ultrasound scans in the period 1st January 2008 to 1st October 2014, identified in the Danish Fetal Medicine Database and local clinical databases in Denmark. All fetuses diagnosed prenatally with IMV (measurement of the atrium of the lateral ventricles, 10.0-15.0 mm) between 18 and 22 weeks' gestation were followed up in national patient registers until the age of 2-7 years. Information was obtained on the diagnoses of intellectual disability, cerebral palsy, autism spectrum disorder, epilepsy and impaired psychomotor development. Neurodevelopmental disorders were compared between those with postnatally confirmed IMV and a reference population of children in the same age range. RESULTS: Of a cohort of 292 046 fetuses, 133 were found to have apparent IMV on the second-trimester scan for fetal malformations. In 11 cases, long-term follow-up was not possible owing to termination of pregnancy, spontaneous miscarriage, neonatal death or loss to follow-up. Of the 122 liveborn children followed up until 2-7 years, 15 were identified as having an additional abnormality while 107 were confirmed postnatally to have IMV. Of these 107 children, the diagnosis of a neurodevelopmental disorder was registered in six (5.6%), corresponding to an odds ratio of 2.64 (95% CI, 1.16-6.02), as compared with the reference population. The diagnoses were autism spectrum disorder, epilepsy and impaired psychomotor development. None of these 107 children was diagnosed with intellectual disability or cerebral palsy. CONCLUSIONS: Our results show that a confirmed diagnosis of IMV was associated with an increased risk of a neurodevelopmental disorder, as compared with the reference population, but the absolute risk was low and there were no cases of intellectual disability or cerebral palsy. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.
Trastorno del desarrollo neurológico en fetos con sospecha de ventriculomegalia leve aislada prenatal OBJETIVO: Estimar la prevalencia de trastornos específicos del desarrollo neurológico en fetos con sospecha de ventriculomegalia leve aislada (IMV, por sus siglas en inglés) prenatal en el segundo trimestre del embarazo, a fin de optimizar el proceso de asesoramiento. MÉTODOS: Este estudio estuvo basado en un registro nacional que incluyó todos los embarazos con feto único a los que se les hizo ecografías en el primer y segundo trimestre entre el 1 de enero de 2008 y el 1 de octubre de 2014, identificados en la Base de Datos Danesa de Medicina Fetal y en las bases de datos clínicas locales en Dinamarca. Todos los fetos diagnosticados prenatalmente con IMV (por medición de la aurícula de los ventrículos laterales, 10,0-15,0 mm) entre las semanas de gestación 18 y 22 fueron monitoreados en los registros nacionales de pacientes hasta la edad de 2-7 años. Se obtuvo información sobre los diagnósticos de discapacidad intelectual, parálisis cerebral, trastornos del espectro autista, epilepsia y trastornos del desarrollo psicomotor. Se compararon los trastornos del desarrollo neurológico entre aquellos con IMV confirmada después del nacimiento y una población de referencia de niños en el mismo rango de edad. RESULTADOS: De una cohorte de 292 046 fetos, se encontró que 133 tenían IMV aparente en la ecografía del segundo trimestre realizada para detectar malformaciones fetales. El seguimiento a largo plazo no fue posible en 11 casos debido a la interrupción del embarazo, el aborto espontáneo, la muerte del recién nacido o el abandono del monitoreo. De los 122 niños nacidos vivos a los que se les dio seguimiento hasta los 2-7 años, se identificó a 15 con una anomalía adicional, mientras que a 107 se les confirmó postnatalmente que tenían IMV. De estos 107 niños, se registró el diagnóstico de un trastorno del desarrollo neurológico en seis (5,6%), lo que corresponde a una razón de momios de 2,64 (IC 95%: 1,16-6,02), en comparación con la población de referencia. Los diagnósticos fueron trastornos del espectro autista, epilepsia y trastornos del desarrollo psicomotor. Ninguno de estos 107 niños fue diagnosticado con discapacidad intelectual o parálisis cerebral. CONCLUSIONES: Nuestros resultados muestran que un diagnóstico confirmado de IMV se asoció con un mayor riesgo de trastorno del desarrollo neurológico, en comparación con la población de referencia, pero que el riesgo absoluto fue bajo y no hubo casos de discapacidad intelectual o parálisis cerebral.
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Doenças Fetais/diagnóstico por imagem , Hidrocefalia/diagnóstico por imagem , Transtornos do Neurodesenvolvimento/diagnóstico por imagem , Ultrassonografia Pré-Natal/métodos , Adulto , Criança , Pré-Escolar , Dinamarca/epidemiologia , Feminino , Doenças Fetais/mortalidade , Seguimentos , Idade Gestacional , Humanos , Hidrocefalia/mortalidade , Lactente , Recém-Nascido , Masculino , Transtornos do Neurodesenvolvimento/epidemiologia , Transtornos do Neurodesenvolvimento/mortalidade , Gravidez , Resultado da Gravidez , Segundo Trimestre da Gravidez , Diagnóstico Pré-Natal/métodos , PrevalênciaRESUMO
OBJECTIVES: The primary aim of this study was to compare the screening performance for trisomy 21 (T21) between combined first-trimester screening (cFTS) with referral for invasive testing at a T21 risk ≥ 1 in 300, and contingent screening consisting of referral for invasive testing at a cFTS-T21 risk ≥ 1 in 100 and referral for cell-free DNA (cfDNA) testing at a cFTS-T21 risk between 1 in 100 and 1 in 1000. Secondary aims were to compare the incidence of fetuses diagnosed with trisomy 18 (T18), trisomy 13 (T13) or sex chromosome aneuploidy, and examine the association between fetal fraction of cfDNA in maternal blood and maternal/fetal characteristics. METHODS: Women with a singleton pregnancy and a cFTS-T21 risk of ≥ 1 in 1000 were recruited consecutively from two Danish hospitals between August 2014 and May 2015. First-trimester combined screening was based on maternal age, nuchal translucency thickness and levels of pregnancy-associated plasma protein A (PAPP-A) and ß-human chorionic gonadotropin (ß-hCG). Blood samples for cfDNA testing were analyzed for risks of T21, T18, T13 and sex chromosomal aneuploidies. cfDNA analysis was conducted blinded to the cFTS assessment and karyotype results. Pregnancy outcomes and pre- and postnatal karyotypes were obtained from the Danish Fetal Medicine Database. RESULTS: Among 6449 women who underwent cFTS risk assessment, 869 (13.5%) had a T21 risk of ≥ 1 in 1000 and 597 were included for cfDNA testing. Among these, there were 15 cases of T21, one case of T18 and two cases of T13. The sensitivity for detection of T21 was 100% using both screening strategies, while specificity increased significantly (P < 0.0001) from 97.0% using the cFTS strategy to 98.8% using the contingent approach. The sensitivity for detection of T21, T18 and T13 increased from 94.4% using the cFTS strategy to 100% using the contingent approach, with overlapping CIs, while specificity increased significantly (P < 0.0001) from 97.1% for cFTS to 98.9% for the contingent strategy. Seven pregnancies were categorized as being at increased risk of a sex chromosomal aneuploidy by cfDNA testing but chromosome analysis was discordant, corresponding to a false-positive rate of 1.2%. The fetal fraction decreased significantly with increasing maternal weight and increased significantly with the level of ß-hCG and PAPP-A and among female fetuses, in both univariate and multivariate analyses. CONCLUSIONS: In a clinical setting with efficient cFTS, contingent screening offering women with a cFTS risk of ≥ 1 in 100 an invasive test and women with a risk from 1 in 100 to 1 in 1000 a cfDNA test had the same sensitivity for T21, T18 and T13, but significantly increased specificity, when compared with offering an invasive test to all women with a risk of ≥ 1 in 300. Implementing contingent screening would therefore reduce significantly the number of invasive tests performed at no loss of sensitivity. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.
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Ácidos Nucleicos Livres/sangue , Síndrome de Down/diagnóstico , Testes para Triagem do Soro Materno/estatística & dados numéricos , Medição da Translucência Nucal/estatística & dados numéricos , Adulto , Análise de Variância , Estudos de Coortes , Dinamarca/epidemiologia , Síndrome de Down/sangue , Síndrome de Down/epidemiologia , Síndrome de Down/genética , Feminino , Humanos , Idade Materna , Valor Preditivo dos Testes , Gravidez , Resultado da Gravidez/epidemiologia , Primeiro Trimestre da Gravidez , Medição de Risco , Síndrome da Trissomia do Cromossomo 13/sangue , Síndrome da Trissomia do Cromossomo 13/diagnóstico , Síndrome da Trissomia do Cromossomo 13/genética , Síndrome da Trissomía do Cromossomo 18/sangue , Síndrome da Trissomía do Cromossomo 18/diagnóstico , Síndrome da Trissomía do Cromossomo 18/genéticaRESUMO
OBJECTIVE: To investigate the association between fetal nuchal translucency (NT) thickness and neurodevelopmental disorders in euploid children. METHODS: This study included 222 505 euploid children who had undergone routine first-trimester screening during fetal life. Children were divided according to prenatal NT into three groups: NT < 95th percentile (n = 217 103 (97.6%)); NT 95th -99th percentile (n = 4760 (2.1%)); and NT > 99th percentile (n = 642 (0.3%)). All children were followed-up to a mean age of 4.4 years. Information on diagnoses of intellectual disability, autism spectrum disorders (ASD), cerebral palsy, epilepsy and febrile seizures was obtained from national patient registries. RESULTS: There was no excess risk of neurodevelopmental disorders among euploid children with first-trimester NT 95th -99th percentile. For children with NT > 99th percentile, there were increased risks of intellectual disability (odds ratio (OR), 6.16 (95% CI, 1.51-25.0), 0.31%) and ASD (OR, 2.48 (95% CI, 1.02-5.99), 0.78%) compared with children with NT < 95th percentile (incidence of 0.05% for intellectual disability and 0.32% for ASD), however, there was no detected increase in the risk of cerebral palsy (OR, 1.91 (95% CI, 0.61-5.95), 0.47%), epilepsy (OR, 1.51 (95% CI, 0.63-3.66), 0.78%) or febrile seizures (OR, 0.72 (95% CI, 0.44-1.16), 2.65%). CONCLUSIONS: In a large unselected cohort of euploid children, there was no increased risk of neurodevelopmental disorders among those with a first-trimester NT 95th -99th percentile. Among euploid children with first-trimester NT > 99th percentile, there were increased risks of intellectual disability and ASD, but the absolute risk was reassuringly low (< 1%). Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.
Assuntos
Aberrações Cromossômicas , Transtornos do Neurodesenvolvimento/epidemiologia , Medição da Translucência Nucal , Adulto , Pré-Escolar , Dinamarca/epidemiologia , Feminino , Seguimentos , Humanos , Lactente , Masculino , Transtornos do Neurodesenvolvimento/genética , Gravidez , Resultado da Gravidez , Primeiro Trimestre da Gravidez , Sistema de Registros , Fatores de RiscoRESUMO
OBJECTIVE: To assess prospectively the risk of fetal loss associated with chorionic villus sampling (CVS) and amniocentesis (AC) following combined first-trimester screening (cFTS) for Down syndrome. METHODS: This was a nationwide population-based study (Danish Fetal Medicine Database, 2008-2010) including 147,987 women with singleton pregnancy who underwent cFTS. Propensity score stratification was used to assess the risk of fetal loss with and without invasive testing. Analyses were performed between 3 and 21 days after cFTS for CVS and between 28 and 42 days after cFTS for AC. Results are reported as average risk differences with 95% CIs. RESULTS: The risks of miscarriage and stillbirth were not higher in women exposed to CVS or AC compared with unexposed women, independent of the analysis time-point. The average effect of CVS on risk of miscarriage was -0.08% (95% CI, -0.64; 0.47) at 3 days and -0.21% (95% CI, -0.58; 0.15) at 21 days after cFTS, while the effect on risk of stillbirth was -0.18% (95% CI, -0.50; 0.13) at 3 days and -0.27% (95% CI, -0.58; 0.04) at 21 days after cFTS. Regarding the effect of AC on risk of miscarriage, the analysis at 28 days after cFTS showed an average effect of 0.56% (95% CI, -0.21; 1.33), while the effect on risk of stillbirth was 0.09% (95% CI, -0.39; 0.58) at 42 days after cFTS. CONCLUSION: Neither CVS nor AC was associated with increased risk of miscarriage or stillbirth. These findings indicate that the procedure-related risk of CVS and AC is very low.
Assuntos
Aborto Espontâneo/epidemiologia , Amniocentese/estatística & dados numéricos , Amostra da Vilosidade Coriônica/estatística & dados numéricos , Síndrome de Down/diagnóstico , Natimorto/epidemiologia , Adulto , Estudos de Casos e Controles , Gonadotropina Coriônica Humana Subunidade beta/metabolismo , Estudos de Coortes , Dinamarca/epidemiologia , Feminino , Humanos , Medição da Translucência Nucal , Gravidez , Primeiro Trimestre da Gravidez , Proteína Plasmática A Associada à Gravidez/metabolismo , Pontuação de Propensão , Estudos Retrospectivos , Risco , Ultrassonografia Pré-Natal , Adulto JovemRESUMO
OBJECTIVE: To evaluate the influence of chorionicity on outcome in twin pregnancies with two live fetuses at the nuchal translucency scan in the first trimester. DESIGN: Population-based register study. SETTING: Denmark. POPULATION: A cohort of 3621 twin pregnancies, 84.3% dichorionic (DC) pregnancies and 15.7% monochorionic (MC) pregnancies (15% diamniotic [MCDA] and 0.7% monoamniotic [MCMA]). METHODS: A cohort study based on data collected from the Danish Fetal Medicine Database from July 2008 to July 2011. MAIN OUTCOME MEASURES: Fetal loss rate before week 22, intrauterine death rate from week 22 to birth, and neonatal mortality. RESULTS: Significantly more DC than MC pregnancies resulted in at least one live born infant-98.2% versus 92.3% in MCDA (P < 0.05) and 66.7% in MCMA pregnancies (P < 0.05). The rates of spontaneous loss of both fetuses before week 22 were 0.9, 2.4, and 20.8% for DC, MCDA and MCMA twins, respectively (P < 0.05). The rate of intrauterine death of one fetus after week 22 was higher in MCDA twins than DC twins 1.7% versus 0.6% (P < 0.05). We found no significant difference in the rate of neonatal death. CONCLUSIONS: The risk of spontaneous loss of both fetuses before week 22 of gestation was significantly higher in MCMA and MCDA pregnancies than in DC pregnancies, and significantly higher in MCMA pregnancies than in MCDA pregnancies. After week 22 the risk of loss of one fetus after week 22 was significantly higher in MCDA pregnancies than in DC pregnancies.
Assuntos
Córion , Morte Fetal/etiologia , Mortalidade Infantil , Gravidez de Gêmeos , Gêmeos Dizigóticos , Gêmeos Monozigóticos , Adulto , Estudos de Coortes , Feminino , Humanos , Lactente , Recém-Nascido , Gravidez , Primeiro Trimestre da Gravidez , Sistema de Registros , Estudos Retrospectivos , Medição de Risco , Fatores de RiscoRESUMO
OBJECTIVES: Targeted non-invasive prenatal testing (NIPT) tests for trisomies 21, 18 and 13 and sex chromosome aneuploidies and could be an alternative to traditional karyotyping. The aim of this study was to determine the risk of missing other abnormal karyotypes of probable phenotypic significance by NIPT. METHODS: This was a retrospective population-based analysis of all singleton pregnancies booked for combined first-trimester screening (cFTS) in Denmark over a 4-year period. Data concerning maternal demographics, cFTS and prenatal or postnatal karyotypes were collected from the Danish Fetal Medicine database. Karyotypes were classified according to whether the chromosomal anomaly would have been detected by NIPT and whether it was likely to affect phenotype. RESULTS: cFTS was completed in 193638 pregnancies. 10205 (5.3%) had cytogenetic or molecular analysis performed. Of these, 1122 (11.0%) had an abnormal karyotype, of which 262 (23.4%) would have been missed by NIPT, but would probably have been clinically significant. The prevalence of such 'atypical abnormal karyotypes' was increased in women above 45 years of age, in pregnancies with increased nuchal translucency (NT) thickness (≥ 3.5 mm), with abnormal levels of free ß-human chorionic gonadotropin (<0.2 or ≥ 5.0 multiples of the median (MoM)) or pregnancy-associated plasma protein-A<0.2 MoM. One or more of these factors was present in 3% of women, and the prevalence of atypical abnormal karyotypes in this high-risk cohort was 1.6%. CONCLUSIONS: A significant proportion of karyotypic abnormalities will be missed by targeted NIPT. Women of advanced maternal age, or with increased fetal NT or abnormal biochemistry, have a higher risk of having a fetus affected by an atypical abnormal karyotype and need to be counseled accordingly when considering NIPT.
Assuntos
Gonadotropina Coriônica Humana Subunidade beta/sangue , Transtornos Cromossômicos/diagnóstico , Idade Materna , Medição da Translucência Nucal , Proteína Plasmática A Associada à Gravidez/metabolismo , Diagnóstico Pré-Natal , Adulto , Biomarcadores/sangue , Transtornos Cromossômicos/sangue , Dinamarca , Feminino , Humanos , Recém-Nascido , Guias de Prática Clínica como Assunto , Gravidez , Primeiro Trimestre da Gravidez , Diagnóstico Pré-Natal/métodos , Diagnóstico Pré-Natal/normas , Estudos Retrospectivos , Fatores de RiscoRESUMO
OBJECTIVES: To assess the detection rate of triploidy at first-trimester screening for trisomy 21 and evaluate outcome in triploid pregnancies. METHODS: From 2008 to 2011, 198 427 women with singleton pregnancies underwent first-trimester screening between 11 + 2 and 14 + 0 weeks' gestation. Screening parameters included nuchal translucency, maternal serum free ß-human chorionic gonadotropin (ß-hCG) and pregnancy-associated plasma protein-A (PAPP-A). In all triploid fetuses, these parameters were re-evaluated. Karyotypes were established by invasive testing (chorionic villus sampling or amniocentesis) or postabortem and obtained from the Danish Cytogenetic Central Register and the Danish Fetal Medicine Database. RESULTS: A total of 30 triploid fetuses underwent first-trimester screening. Twenty-five were diagnosed as a result of abnormal first-trimester scan findings, a detection rate of 83.3%. Twenty-three fetuses were identified due to a high risk for trisomy 13, 18 or 21 and two fetuses due to structural abnormalities. The incidence of triploidy at first-trimester screening was 1:6614. A smaller crown-rump length than that estimated by date of last menstrual period was found in 95% of the fetuses with data available for evaluation. Eight fetuses had a larger biparietal diameter than expected for gestational age. Fetuses with a 69,XXX karyotype had significantly lower multiples of the median values for ß-hCG and PAPP-A than did 69,XXY fetuses (P = 0.045 and P = 0.02 forß-hCG and PAPP-A, respectively). No infants with triploidy were born in the study period. Among the triploid gestations detected on first-trimester screening, 20 (80.0%) women chose termination of pregnancy, four (16.0%) had spontaneous miscarriage and one (4.0%) was stillborn. CONCLUSION: First-trimester screening for trisomy 21 also provides a high detection rate for triploidy.
Assuntos
Síndrome de Down/diagnóstico , Doenças Fetais/diagnóstico , Triploidia , Adulto , Gonadotropina Coriônica Humana Subunidade beta/sangue , Estatura Cabeça-Cóccix , Dinamarca , Feminino , Idade Gestacional , Humanos , Cariotipagem , Medição da Translucência Nucal , Gravidez , Resultado da Gravidez , Primeiro Trimestre da Gravidez , Proteína Plasmática A Associada à Gravidez/análise , Adulto JovemRESUMO
OBJECTIVE: The aim of this study was to investigate gestational age-dependent effects of racial origin, smoking status and mode of conception on maternal serum levels of free ß-human chorionic gonadotropin (ß-hCG) and pregnancy-associated plasma protein-A (PAPP-A) at 7-14 weeks' gestation. METHODS: This was an analysis of data from prospective first-trimester combined screening for aneuploidies in singleton pregnancies, with ß-hCG and PAPP-A measured at 7 + 1 to 14 + 3 weeks' gestation. We included 27,908 pregnancies from three centers in the U.K. and 125,461 pregnancies from 22 centers in Denmark, all with known normal fetal karyotype or resulting in the birth of a phenotypically normal neonate. Multiple regression modelling of log10 -transformed marker concentrations was used to produce log10 multiple of the median (MoM) values for free ß-hCG and PAPP-A and to examine pregnancy characteristics that have significant effects on marker concentrations. RESULTS: Serum free ß-hCG and PAPP-A concentrations were significantly affected by gestational age, maternal weight, racial origin, parity, smoking and mode of conception. There were significant gestational age-dependent effects attributed to Afro-Caribbean race, smoking and conception through in-vitro fertilization (IVF) on PAPP-A and free ß-hCG levels. In women of Afro-Caribbean race there was a weekly increase in PAPP-A of 5.3% and in free ß-hCG of 1.8%. In smokers there was a weekly decrease in PAPP-A of 2.4% and in free ß-hCG of 1.6%. In cases of IVF conceptions there was a weekly increase in PAPP-A of 4.5% and in free ß-hCG of 4.6%. CONCLUSIONS: Serum free ß-hCG and PAPP-A concentrations at 7-14 weeks' gestation are affected by several pregnancy characteristics. The effects of Afro-Caribbean race, smoking and IVF conception change with gestational age.
Assuntos
Gonadotropina Coriônica Humana Subunidade beta/sangue , Idade Gestacional , Primeiro Trimestre da Gravidez/sangue , Proteína Plasmática A Associada à Gravidez/análise , Gravidez/sangue , Adulto , Etnicidade , Feminino , Humanos , Fatores de Risco , Fumar/epidemiologia , Fatores de TempoRESUMO
OBJECTIVE: To prospectively evaluate the performance of first-trimester combined screening for trisomy 21 using the biochemical markers pregnancy-associated plasma protein-A (PAPP-A) and free beta-human chorionic gonadotropin (free ß-hCG) obtained before and at the time of the nuchal translucency (NT) scan. METHODS: Three fetal medicine departments in Denmark participated in the study. Screening for trisomy 21 was set up as a two-step approach with blood sampling performed before the NT scan (early sample) and again at the time of the NT scan (late sample). PAPP-A and free ß-hCG were measured on both the early and late samples. Age-standardized detection and false-positive rates for different screening protocols were calculated. RESULTS: We collected two blood samples in 27 pregnancies affected by trisomy 21 and in 3891 control pregnancies. The early samples were taken between gestational ages 8 + 0 and 13 + 6 weeks, and the late samples between 11 + 3 and 14 + 6 weeks. The median interval between the samples was 17 (range, 1-40) days. We found a significantly better estimated screening performance when using early sampling vs late sampling (P < 0.05). With a risk cut-off of 1 in 100, at the time of the risk assessment the estimated detection and false-positive rates when using the early sample were 91% (95% CI, 81-98%) and 1.6% (95% CI, 1.3-2.0%), respectively. For fixed false-positive rates the highest detection rates were achieved using both blood samples. When comparing early sampling vs double sampling there was no significant difference in screening performance. CONCLUSION: In combined first-trimester screening for trisomy 21, use of early sampling with measurement of PAPP-A and free ß-hCG before the time of the NT scan can optimize screening performance. Using maternal serum markers obtained both before and at the time of the NT scan has the potential to further improve performance, but larger studies are needed to confirm this potential.
Assuntos
Gonadotropina Coriônica Humana Subunidade beta/sangue , Síndrome de Down/diagnóstico , Proteína Plasmática A Associada à Gravidez/análise , Diagnóstico Pré-Natal/métodos , Adulto , Biomarcadores/sangue , Dinamarca , Síndrome de Down/sangue , Síndrome de Down/diagnóstico por imagem , Feminino , Humanos , Medição da Translucência Nucal , Gravidez , Primeiro Trimestre da Gravidez , Estudos Prospectivos , Medição de Risco , Ultrassonografia Pré-NatalRESUMO
OBJECTIVE: To compare the standard first trimester combined risk assessment for trisomy 21 with a contingent screening protocol including tricuspid flow and ductus venosus flow. MATERIAL AND METHOD: Women with singleton pregnancies and a first trimester combined risk assessment>1:1000 were included. They all had additional assessment of the ductus venosus and the tricuspid flow. We compared screening performance in two screening strategies: (a) First trimester combined screening strategy based on the individual risk results from the routine screening test and (b) Contingent screening strategy based on a combination of the routine test results and additional ultrasound markers. RESULTS: We included 917 women in the study, 894 in the euploid group and 23 in the trisomy 21 group. Using a contingent screening strategy resulted in a significant decrease in screen positive rate from 48.3% to 17.7% (p<0.001) in the studied population. There was no statistical difference in detection rate between the two screening strategies. CONCLUSION: There is increasing evidence in favour of using additional ultrasound markers as part of contingent screening protocols in the first trimester. We do suggest performing further studies in routine clinical settings to provide validation of the available risk algorithms.