RESUMO
OBJECTIVES: To compute a set of atypicality indices based on combined first-trimester screening (cFTS) markers and second-trimester estimated fetal weight (EFW), and to demonstrate their potential in identifying pregnancies at reduced or increased risk of chromosomal aberrations following a low-risk cFTS result. METHODS: The atypicality index quantifies the unusualness of an individual set of measurements relative to a reference distribution and can be computed from any variables or measurements available. A score of 0% on the atypicality index represents the most typical profiles, while a score of 100% indicates the highest level of atypicality. From the Danish Fetal Medicine Database, we retrieved data on all pregnant women seen for cFTS in the Central Denmark Region between January 2008 and December 2018. All pregnancies with a cytogenetic or molecular analysis obtained prenatally, postnatally or following pregnancy loss or termination were identified. A first-trimester atypicality index (AcFTS) was computed based on nuchal translucency (NT) thickness, maternal serum free ß-human chorionic gonadotropin (ß-hCG) and pregnancy-associated plasma protein-A (PAPP-A). Furthermore, a second-trimester index (AcFTS + EFW) was computed from cFTS markers and EFW from a routine second-trimester anomaly scan. All pregnancies were stratified into subgroups based on their atypicality levels and their cFTS risk estimates. The risk of chromosomal aberrations in each subgroup was then compared with the overall prevalence, and a graphical presentation of the multivariate measurement profiles was developed. RESULTS: We retrieved data on 145 955 singleton pregnancies, of which 9824 (6.7%) were genetically examined. Overall, 1 in 122 (0.82% (95% CI, 0.77-0.87%)) of all pregnancies seen for cFTS were affected by a fetal chromosomal aberration, and in screen-negative pregnancies (cFTS trisomy 21 risk < 1 in 100 and/or trisomy 18/13 risk < 1 in 50), 0.41% (95% CI, 0.38-0.44%) were affected. In screen-negative pregnancies with a typical first-trimester profile (AcFTS < 80%), the risk of chromosomal aberrations was significantly reduced (0.28%) compared with the overall risk. The risk of chromosomal aberrations increased with higher atypicality index to 0.49% (AcFTS [80-90%)), 1.52% (AcFTS [90-99%)) and 4.44% (AcFTS ≥ 99%) and was significantly increased in the two most atypical subgroups. The same applied for the second-trimester atypicality index, with risks of chromosomal aberrations of 0.76% and 4.16% in the two most atypical subgroups (AcFTS + EFW [90-99%) and AcFTS + EFW ≥ 99%, respectively). CONCLUSIONS: As an add-on to cFTS, the atypicality index identifies women with typical measurement profiles, which may provide reassurance, whereas atypical profiles may warrant specialist referral and further investigation. In pregnancies identified as low risk on cFTS but with a highly atypical distribution of NT, PAPP-A and ß-hCG, the risk of a chromosomal aberration is substantially increased. The atypicality index optimizes the interpretation of pre-existing prenatal screening profiles and is not limited to cFTS markers or EFW. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.
Assuntos
Gonadotropina Coriônica Humana Subunidade beta , Aberrações Cromossômicas , Medição da Translucência Nucal , Primeiro Trimestre da Gravidez , Proteína Plasmática A Associada à Gravidez , Humanos , Feminino , Gravidez , Gonadotropina Coriônica Humana Subunidade beta/sangue , Adulto , Aberrações Cromossômicas/embriologia , Aberrações Cromossômicas/estatística & dados numéricos , Dinamarca/epidemiologia , Proteína Plasmática A Associada à Gravidez/análise , Proteína Plasmática A Associada à Gravidez/metabolismo , Síndrome de Down/diagnóstico , Síndrome de Down/genética , Segundo Trimestre da Gravidez , Diagnóstico Pré-Natal/métodos , Peso Fetal , Biomarcadores/sangue , Síndrome da Trissomía do Cromossomo 18/diagnóstico , Síndrome da Trissomía do Cromossomo 18/embriologia , Transtornos Cromossômicos/diagnóstico , Transtornos Cromossômicos/embriologiaRESUMO
In this study, we aimed to examine the relationship between sleep quality, sleep apnoea and triple screen test results. This was an observational descriptive research study. The STOP questionnaire and the STOP-BANG questionnaire were performed to assess obstructive sleep apnoea risk and Pittsburgh Sleep Quality Index was used to evaluate sleep quality. The average Pittsburgh Sleep Quality Index score of the participants was 5.92 ± 3.26. According to the STOP test, 11.40% (87) of the pregnant women had a high risk of OSAS, and, according to the STOP-BANG test, 32 participants were under high risk of OSAS. An increased risk was detected in 1.30% of the participants in terms of Trisomy18 and in 1.60% in terms of neural tube defects. A direct and significant relationship was detected between Trisomy 21 risk and STOP-BANG score. This is the first study to show this relationship. Sufficient evidence needs to be collected on this issue. Testing in earlier weeks of pregnancy and in the conception period may allow more meaningful assessment of the relationship of OSAS with chromosomal abnormalities.IMPACT STATEMENTWhat is already known on this subject? There is a link between OSAS and epigenetic changes. Components of the triple screen test, levels of serum total ß-hCG and unconjugated oestriol are increased in OSAS.What do the results of this study add? An increase in Trisomy 21 risk is correlated with increased OSAS risk. Alpha Fetoprotein levels were higher in the low OSAS risk group.What are the implications of these findings for clinical practice and/or further research? This is the first study to show this relationship. Sufficient evidence needs to be collected on this issue. Treatment of OSAS may be necessary during pregnancy.
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Testes para Triagem do Soro Materno , Complicações na Gravidez/fisiopatologia , Apneia Obstrutiva do Sono/fisiopatologia , Qualidade do Sono , Adulto , Síndrome de Down/diagnóstico , Síndrome de Down/embriologia , Feminino , Humanos , Defeitos do Tubo Neural/diagnóstico , Defeitos do Tubo Neural/embriologia , Gravidez , Fatores de Risco , Inquéritos e Questionários , Síndrome da Trissomía do Cromossomo 18/diagnóstico , Síndrome da Trissomía do Cromossomo 18/embriologiaRESUMO
Clinical performance of the Momguard non-invasive prenatal test (NIPT) was evaluated in a cohort of Korean pregnant women. The foetal trisomies 21, 18 and 13 (T21, T18 and T13) were screened by low-coverage massive parallel sequencing in the maternal blood. Among the 1011 confirmed samples, 32 cases (3.2%) had positive NIPT results. Of these positive cases, 20 cases of T21, all cases of T18 and two cases of T13 had concordant karyotype findings. Only one case out of the remaining 979 negative NIPT samples showed a false negative result. The overall sensitivity and specificity of Momguard to detect the three chromosomal aneuploidies were 96.8% and 99.8%, respectively. Momguard is a clinically useful tool for the detection of T21, T18 and T13 in singleton pregnancy. However, as other NIPT tests, it carries the risk of false positive and false negative results. Hence, the genetic counsellors should provide these limitations to the examinees.Impact StatementWhat is already known on this subject? The NIPT approach using massive parallel sequencing (MPS) showed high sensitivity and specificity in various clinical studies. These results are based on analysis systems using their own bioinformatics algorithms.What the results of this study add? When this NIPT technology was introduced in Korea, the first biological specimens collected in Korea were transported overseas for processing in overseas laboratories and analysed by other country's analysis methods. We needed our own NIPT algorithm and developed Momguard NIPT for the first time in Korea. This study attempted to evaluate this Momguard NIPT protocol prospectively in a large number of samples obtained from three Korean hospitals.What the implications are of these findings for clinical practice and/or further research? The overall sensitivity and specificity to identify T13, T18 and T21 were 96.8% and 99.8%, respectively. These accuracy values were comparable to that of other studies. From this study, we found that Momguard is a clinically useful tool for the detection of three chromosomal aneuploidies. However, as other NIPT tests, it carries the risk of false positive and false negative results. Hence, the genetic counsellors should provide these limitations to the examinees.
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Síndrome de Down/diagnóstico , Teste Pré-Natal não Invasivo/estatística & dados numéricos , Síndrome da Trissomia do Cromossomo 13/diagnóstico , Síndrome da Trissomía do Cromossomo 18/diagnóstico , Adulto , Síndrome de Down/embriologia , Reações Falso-Negativas , Reações Falso-Positivas , Feminino , Humanos , Gravidez , Estudos Prospectivos , Reprodutibilidade dos Testes , República da Coreia , Sensibilidade e Especificidade , Síndrome da Trissomia do Cromossomo 13/embriologia , Síndrome da Trissomía do Cromossomo 18/embriologiaRESUMO
Objective To determine whether the measurement of inferior facial angle (IFA) and prefrontal space ratio (PFSR) in two-dimensional (2D) ultrasound images in the first trimester of pregnancy is reliable and to describe these markers in normal and aneuploid fetuses. Methods IFA and PFSR were measured in stored 2D midsagittal images of 200 normal and 140 aneuploid fetal profiles between 11 + 0 and 13 + 6 weeks of gestation. Limits of agreement (LOAs) and intraclass correlation coefficients (ICCs) for inter- and intraobserver differences were calculated. Results The mean IFA in normal fetuses was 76.5° ± 6.3. Between the two measurement rounds of the same observer, the LOAs were -5.4 to 7.1 (obs. 1) and 7.4 to 8.4 (obs. 2). For IFA measurements by the same observer the ICC was 0.88 (obs. 1) and for measurements by two different observers the ICC was 0.74. The mean PFSR was 0.76 ± 0.40 and the intraobserver LOAs were -0.372 to 0.395 (obs. 1) and -0.555 to 0.667 (obs. 2). For PFSR measurements by the same observer the ICC was 0.89 (obs. 1) and for measurements by two different observers the ICC was 0.65. Among aneuploid fetuses, IFA was below the normal range in one third of the cases with trisomy 18. PFSR was below the 95% prediction limit in 16.2% of fetuses with trisomy 21% and 17.9% of fetuses with trisomy 18. Conclusion IFA can be reliably measured in 2D ultrasound images in the first trimester of pregnancy with a high interobserver agreement and may provide information about retrognathia associated with various syndromes and aneuploidies at early stages of pregnancy.
Assuntos
Aneuploidia , Face/diagnóstico por imagem , Primeiro Trimestre da Gravidez , Retrognatismo/diagnóstico por imagem , Ultrassonografia Pré-Natal/métodos , Síndrome de Down/diagnóstico por imagem , Síndrome de Down/embriologia , Face/embriologia , Feminino , Humanos , Masculino , Variações Dependentes do Observador , Gravidez , Reprodutibilidade dos Testes , Retrognatismo/embriologia , Retrognatismo/genética , Estudos Retrospectivos , Síndrome da Trissomia do Cromossomo 13/diagnóstico por imagem , Síndrome da Trissomia do Cromossomo 13/embriologia , Síndrome da Trissomía do Cromossomo 18/diagnóstico por imagem , Síndrome da Trissomía do Cromossomo 18/embriologia , Síndrome de Turner/diagnóstico por imagem , Síndrome de Turner/embriologiaRESUMO
AIM: To explore the effectiveness of cavum septi pellucidi (CSP) width to anteroposterior cerebellar diameter (APCD) ratio as a diagnostic adjunct for prenatal diagnosis of trisomy 18. METHODS: Images of normal fetal brain within 15 and 35 weeks were stored in our center from 2016 to 2017. Images of aneuploid fetuses were retrospectively collected from 2004 to 2017. The transverse cerebellar diameter, APCD and CSP width were measured. CSP/APCD and APCD/transverse cerebellar diameter ratios were calculated and compared between euploid and aneuploid fetuses. RESULTS: One thousand and forty one fetuses were analyzed, including 817 euploid fetuses and 224 aneuploid fetuses (trisomy 21 117 cases, trisomy 18 82 cases, trisomy 13 9 cases, sex-linked 16 cases). No correlation had been found between both ratios and gestational weeks (P > 0.05). In aneuploid groups, means of ratios were both significantly different just between trisomy 18 group and euploid group (P < 0.05). The best area under the curve was shown by the CSP/APCD ratio. The cutoff value of CSP/APCD was 0.46 (sensitivity 87.0%, specificity 85.0%). CONCLUSION: A wide CSP or cerebellar hypoplasia warrants a more detailed ultrasound screening and genetic counseling. A larger CSP/APCD ratio alerts us to trisomy 18 syndrome, especially in cases with subtle anomalies.
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Cerebelo/embriologia , Feto/diagnóstico por imagem , Indicadores Básicos de Saúde , Septo Pelúcido/embriologia , Síndrome da Trissomía do Cromossomo 18/diagnóstico , Ultrassonografia Pré-Natal/estatística & dados numéricos , Adulto , Encéfalo/embriologia , Cerebelo/anormalidades , Cerebelo/diagnóstico por imagem , Deficiências do Desenvolvimento/diagnóstico por imagem , Feminino , Feto/patologia , Idade Gestacional , Humanos , Malformações do Sistema Nervoso/diagnóstico por imagem , Malformações do Sistema Nervoso/embriologia , Gravidez , Valores de Referência , Estudos Retrospectivos , Sensibilidade e Especificidade , Síndrome da Trissomía do Cromossomo 18/embriologiaRESUMO
OBJECTIVE: To analyze the results of contingent screening for common aneuploidies at our center from June 2017 to June 2019. MATERIALS AND METHODS: Traditional screening tests were performed using a combination of biochemical markers and ultrasound measurements in the first and second trimesters to assess the risk of trisomies 21 (T21), 18 (T18) and 13 (T13). Cell-free DNA (cf-DNA) testing was offered (Harmony test) to pregnant women at high risk (>1/280 for T21 and > 1/150 for T13 and T18) and a normal early morphology scan. In positive cases, prenatal sampling was strongly recommended to confirm the results by gold standard methods (QF-PCR and karyotyping). Newborns' phenotypes were corroborated after birth in all cases. RESULTS: In this prospective study, 8153 pregnant women were enrolled, resulting in 390 at high risk according to traditional screening tests. cfDNA testing was offered to 383 women. Traditional screening tests showed a false negative rate of 9.68% for T21. Traditional test sensitivity for T21 was 90.3%, for a false positive rate of 4.17% and a positive predictive value of 7.6%. The positive and negative predictive value for cfDNA testing was 100%. The approach used avoided invasive procedures in 91.3% of women at high risk. The prevalence of chromosomal abnormalities in the population analyzed was 1 in 164, and 1 in 210 for T21. CONCLUSIONS: Our results show that offering cf-DNA testing to women at high risk in traditional tests (including those with risks >1 in 50) significantly reduces false positives and, therefore, the number of invasive tests. Extending the use of cf-DNA testing to intermediate risk categories may be cost effective.
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Aneuploidia , Ácidos Nucleicos Livres/análise , Anormalidades Congênitas/diagnóstico , Testes Genéticos/métodos , Diagnóstico Pré-Natal/métodos , Adulto , Anormalidades Congênitas/embriologia , Análise Custo-Benefício , Síndrome de Down/diagnóstico , Síndrome de Down/embriologia , Feminino , Testes Genéticos/economia , Humanos , Valor Preditivo dos Testes , Gravidez , Diagnóstico Pré-Natal/economia , Estudos Prospectivos , Síndrome da Trissomia do Cromossomo 13/diagnóstico , Síndrome da Trissomia do Cromossomo 13/embriologia , Síndrome da Trissomía do Cromossomo 18/diagnóstico , Síndrome da Trissomía do Cromossomo 18/embriologia , Adulto JovemRESUMO
OBJECTIVE: We present rapid diagnosis of trisomy 18 of maternal origin by quantitative fluorescent polymerase chain reaction (QF-PCR) analysis following tissue culture failure for conventional cytogenetic analysis in a fetus with holoprosencephaly (HPE), ventricular septal defect (VSD), arthrogryposis of bilateral wrists and aplasia of the thumbs. CASE REPORT: A 22-year-old, primigravid woman was referred for first-trimester ultrasound screening at 13 weeks of gestation, and the fetus was found to have HPE and VSD. The pregnancy was subsequently terminated at 14 weeks of gestation, and a malformed fetus was delivered with cebocephaly, arthrogryposis of bilateral wrists and aplasia of the thumbs. The umbilical cord and placental tissues were collected for genetic analysis. However, tissue culture failure for conventional cytogenetic analysis occurred because of contamination. QF-PCR analysis using the polymorphic DNA markers of D18S1369 (18q12.2) and D18S1361 (18q22.3) confirmed trisomy 18 of maternal origin. CONCLUSION: QF-PCR analysis is useful for rapid confirmation of trisomy 18 and the parental origin when tissue culture failure for conventional cytogenetic analysis occurs in pregnancy suspicious of fetal trisomy 18.
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Artrogripose/diagnóstico , Comunicação Interventricular/diagnóstico , Holoprosencefalia/diagnóstico , Reação em Cadeia da Polimerase/métodos , Síndrome da Trissomía do Cromossomo 18/diagnóstico , Anormalidades Múltiplas/diagnóstico , Anormalidades Múltiplas/embriologia , Anormalidades Múltiplas/genética , Aborto Eugênico , Adulto , Artrogripose/embriologia , Artrogripose/genética , Análise Citogenética , Feminino , Testes Genéticos , Comunicação Interventricular/embriologia , Comunicação Interventricular/genética , Holoprosencefalia/embriologia , Holoprosencefalia/genética , Humanos , Gravidez , Polegar/anormalidades , Síndrome da Trissomía do Cromossomo 18/embriologia , Síndrome da Trissomía do Cromossomo 18/genética , Punho/anormalidadesRESUMO
OBJECTIVE: Advanced paternal age is related to poor sperm quality; however, little is known on its effect on aneuploidy embryo rates and, more importantly, on chromosomal abnormalities like trisomy 21, 18 and 13. The objective of this study was to evaluate the effect of advanced paternal age on the trisomy rates of the chromosomes 21, 18 or 13 in embryos obtained from donated oocytes. METHODS: A total of 378 embryos, obtained from 52 IVF/ICSI cycles with donated oocytes in conjunction with PGD, were allocated according to paternal age in three groups: Group A: ≤39 years (n=115 embryos), Group B: 40-49 years (n=157 embryos) and Group C: ≥50 year (n=106 embryos). Fertilization rates, embryo quality at day 3, blastocysts development, and aneuploidy embryo rates were then compared. RESULTS: There was no difference in seminal parameters (volume, concentration and motility) in the studied groups. Fertilization rate, percentages of zygotes that underwent cleavage, and good-quality embryos on Day 3 were similar between the three groups evaluated. The group of men ≥50 years had significantly more sperm with damaged DNA, higher global aneuploidy rates, and significantly more embryos with trisomy 21, 18 or 13 compared to the other two evaluated groups (p<0.05). CONCLUSIONS: Our data shows that advanced paternal age increases global chromosomal abnormalities, and percentages of trisomy 21, 18 or 13 in embryos, and such effect is significantly important as of the age of 50. Embryo genetic screening is highly recommended in patients in which paternal age is ≥50 years old.
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Envelhecimento/fisiologia , Fertilização in vitro/estatística & dados numéricos , Doação de Oócitos/estatística & dados numéricos , Idade Paterna , Diagnóstico Pré-Implantação/estatística & dados numéricos , Trissomia , Adulto , Síndrome de Down/diagnóstico , Síndrome de Down/embriologia , Síndrome de Down/epidemiologia , Feminino , Testes Genéticos/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Doação de Oócitos/métodos , Gravidez , Taxa de Gravidez , Diagnóstico Pré-Implantação/métodos , Estudos Retrospectivos , Injeções de Esperma Intracitoplásmicas/estatística & dados numéricos , Trissomia/diagnóstico , Trissomia/genética , Síndrome da Trissomia do Cromossomo 13/diagnóstico , Síndrome da Trissomia do Cromossomo 13/embriologia , Síndrome da Trissomia do Cromossomo 13/epidemiologia , Síndrome da Trissomía do Cromossomo 18/diagnóstico , Síndrome da Trissomía do Cromossomo 18/embriologia , Síndrome da Trissomía do Cromossomo 18/epidemiologiaRESUMO
OBJECTIVE: Trisomy 18 is one of the major numerical chromosomal disorders. The incidence of trisomy 18 is approximately one in 6000 live births. Dandy-Walker malformation (DWM) is the most common congenital malformation of the cerebellum, with an incidence of about one in 5000 live births. The incidence of trisomy 18 associated with DWM is rare and long-term survival rate is very low. CASE REPORT: A case involving a 39-year-old pregnant female with a case of trisomy 18 associated with DWM. CONCLUSION: The incidence of trisomy 18 associated with DWM is rare, and our report presents an unusual case that supplements our knowledge of this condition. We report a case involving a 39-year-old pregnant female with a case of trisomy 18 associated with Dandy-Walker malformation (DWM). Fetal ultrasonography showed hypoplasia of the cerebellar vermis and dilatation of the fourth ventricle and was characterized by an enlarged posterior fossa. Fetal magnetic resonance imaging showed inferior vermian hypoplasia and a large posterior fossa cyst communicating with the fourth ventricle causing high insertion of the torcular herophili, which was compatible with DWM. Furthermore, the karyotyping report revealed trisomy 18. The incidence of trisomy 18 associated with DWM is rare, and our report presents an unusual case that supplements our knowledge of this condition.