Fetal nuchal translucency: ultrasound screening for chromosomal defects in first trimester of pregnancy.

OBJECTIVE--To examine the significance of fetal nuchal translucency at 10-14 weeks'' gestation in the prediction of abnormal fetal karyotype. DESIGN--Prospective screening study. SETTING--The Harris Birthright Research Centre for Fetal Medicine, King''s College Hospital, London. SUBJECTS--827 fetuses undergoing first trimester karyotyping by amniocentesis or chorionic villus sampling. MAIN OUTCOME MEASURE--Incidence of chromosomal defects. RESULTS--The incidence of chromosomal defects was 3% (28 of 827 cases). In the 51 (6%) fetuses with nuchal translucency 3-8 mm thick the incidence of chromosomal defects was 35% (18 cases). In contrast, only 10 of the remaining 776 (1%) fetuses were chromosomally abnormal. CONCLUSION--Fetal nuchal translucency > or = 3 mm is a useful first trimester marker for fetal chromosomal abnormalities.     

Clastogen-induced chromosomal breakage as a marker for first trimester prenatal diagnosis of Fanconi anemia

Summary Using cultured trophoblast cells obtained by chorionic villus biopsy, we diagnosed Fanconi anemia (FA) in two pregnancies and excluded it in eight pregnancies at risk for the syndrome. Baseline chromosomal breakage and breakage induced by diepoxybutane (DEB) were analyzed. Increased breakage was used as a marker for the syndrome. Our results were unambiguous and provide a reliable method for prenatal detection of FA in the first trimester of pregnancy.     

Bayesian analysis for the meiosis I non-disjunction fraction in numerical chromosomal anomalies

The main causes of numerical chromosomal anomalies, including trisomies, arise from an error in the chromosomal segregation during the meiotic process, named a non-disjunction. One of the most used techniques to analyze chromosomal anomalies nowadays is the polymerase chain reaction (PCR), which counts the number of peaks or alleles in a polymorphic microsatellite locus. It was shown in previous works that the number of peaks has a multinomial distribution whose probabilities depend on the non-disjunction fraction F. In this work, we propose a Bayesian approach for estimating the meiosis I non-disjunction fraction F. in the absence of the parental information. Since samples of trisomic patients are, in general, small, the Bayesian approach can be a good alternative for solving this problem. We consider the sampling/importance resampling technique and the Simpson rule to extract information from the posterior distribution of F. Bayes and maximum likelihood estimators are compared through a Monte Carlo simulation, focusing on the influence of different sample sizes and prior specifications in the estimates. We apply the proposed method to estimate F. for patients with trisomy of chromosome 21 providing a sensitivity analysis for the method. The results obtained show that Bayes estimators are better in almost all situations.     

A metabolomics-based approach for non-invasive diagnosis of chromosomal anomalies

Introduction

Chromosomal anomalies (CA) are the most frequent fetal anomalies.

Objective

To evaluate the diagnostic performance of a machine learning ensemble model based on the maternal serum metabolomic fingerprint of fetal aneuploidies during the second trimester .

Methods

This is a case-control pilot study. Metabolomic profiles have been obtained on serum of 328 mothers (220 controls and 108 cases), using gas chromatography coupled to mass spectrometry. Eight machines learning and classification models were built and optimized. An ensemble model was built using a voting scheme. All samples were randomly divided into two sets. One was used as training set, the other one for diagnostic performance assessment.

Results

Ensemble machine learning model correctly classified all cases and controls. The accuracy was the same for trisomy 21 and 18; also, the other CA were correctly detected. Elaidic, stearic, linolenic, myristic, benzoic, citric and glyceric acid, mannose, 2-hydroxy butyrate, phenylalanine, proline, alanine and 3-methyl histidine were selected as the most relevant metabolites in class separation.

Conclusion

The proposed model, based on the maternal serum metabolomic fingerprint of fetal aneuploidies during the second trimester, correctly identifies all the cases of chromosomal abnormalities. Overall, this preliminary analysis appeared suggestive of a metabolic environment conductive to increased oxidative stress and a disturbance in the fetal central nervous system development. Maternal serum metabolomics can be a promising tool in the screening of chromosomal defects. Moreover, metabolomics allows to extend our knowledge about biochemical alterations caused by aneuploidies and responsible for the observed phenotypes.

     

The autoimmune process and chromosomal anomalies

Data available in literature on the role of immune system in the cytogenetic stability of the organism are presented. A direct relation is shown to exist between immunity disturbances and changes in the number and structure of chromosomes.     

Elevated ethnocentrism in the first trimester of pregnancy

Recent research employing a disease-threat model of the psychology of intergroup attitudes has provided preliminary support for a link between subjectively disease-salient emotional states and ethnocentric attitudes. Because the first trimester of pregnancy is a period of particular vulnerability to infection, pregnant women offer an opportunity to further test this association. We explored the expression of intergroup attitudes in a sample of pregnant women from the United States. Consistent with the predictions of the disease-threat model, results from our cross-sectional study indicate that favoritism toward the ingroup peaks during the first trimester of pregnancy and decreases during the second and third trimesters. We discuss this finding in light of the possible contributions of cultural and biological factors affecting ethnocentrism.     

妊娠初期妇女阴道微生态研究分析

目的 研究妊娠早期妇女阴道微生态状况,分析不同类型阴道炎在妊娠早期的发病率,比较Nugent评分和Claeys评级两种标准在诊断阴道炎方面的一致性。方法 选择2017年7月至2017年10月在上海市第一妇婴保健院产科门诊就诊的妊娠早期妇女726例（孕周≤12周）,采集阴道分泌物进行外阴阴道假丝酵母菌性阴道炎（vulvovaginal candidiasis,VVC）、滴虫性阴道炎（trichomonas vaginitis,TV）、需氧性阴道炎（aerobic vaginitis,AV）、细菌性阴道病（bacterial vaginosis,BV）检测,AV和（或）VVC阳性的分泌物进行培养鉴定;对革兰染色涂片进行Nugent评分和Claeys评级,以Nugent标准为金标准,评价Claeys评级在诊断阴道炎方面的性能。结果 726例标本中共检出异常标本153例（21.07%）,AV、BV、TV、VVC的发生率分别为5.23%、11.02%、0.13%、11.71%,混合感染占异常标本28.76%（44/153）,最常见的混合感染类型是BV合并VVC,AV最常见的致病菌是无乳链球菌、大肠杆菌、粪肠球菌。以Nugent方法为金标准,Claeys评级的敏感性、特异性、阳性预测值、阴性预测值、Kappa值分别为96.2%、88.1%、85.4%、97.1%、≥0.880。结论 妊娠早期阴道微生态失衡发生率较高且混合感染存在较高的比例,湿片和革兰染色结合分析可以提高阴道炎诊断的准确性。Claeys评级在阴道菌群分析上更全面、更简便,可作为Nugent标准的替代方法用于临床和科研。     

Anatomic and chromosomal anomalies in 639 spontaneous abortuses

Summary A total of 639 spontaneous abortuses collected in a maternity hospital were set up in culture. This sample included 565 unselected consecutive abortuses and 74 selected abortuses ascertained by morphology and/or clinical history. Among these, 339 were incomplete specimens with no recovered embryo or fetus, 110 were anatomically apparently normal and 190 were grossly abnormal. In the unselected series, 565 specimens were cultured and 402 were karyotyped; 215 (53.5%) were chromosomally abnormal. In the selected series, 74 specimens were set up in culture and 45 were karyotyped; 26 (57.7%) had an abnormal karyotype. In all, successful karyotyping was done on 447 abortuses (70%), of which 339 were studied with banding. One or more major chromosome abnormalities were detected in 241 (54%) of the karyotyped cases, 230 of which were numerical anomalies and 11 structural anomalies. Numerical anomalies included primary autosomal trisomies (31% of the total karyotyped), 45,X (10%), triploidy (6.5%), and tetraploidy (1.8%). Of the 22 types of autosomal trisomies possible, all except those for 1, 5, 17, and 19 were identified. An abortus with a 49,XX,+2,+5,+8 karyotype was detected. The excess autosomal material present in the triple trisomic abortus corresponded to 10% of the haploid autosomal complement. Of the 11 abortuses with structural abnormalities, seven were inherited while the other four were sporadic. The survival rate of 45,X conceptuses was estimated to be one in 300.     

Anatomic and chromosomal anomalies in 944 induced abortuses

Summary A total of 944 induced abortuses, 922 of which apparently were anatomically normal and 22 of which were anatomically abnormal, were set up in culture. Of these abortuses, 910 (96.4%) were successfully karyotyped. The study can be divided into two periods. In the initial period, specimens without recovered fetal tissues were excluded, and no chromosome anomalies were found among the 182 abortuses karyotyped. In the later period of sutdy, abortion specimens both with and without recovered fetal tissues were included, and 23 chromosomally abnormal abortuses, 9 of which were without recovered fetal tissues, were found among the 728 abortuses karyotyped. This gives a chromosome abnormality rate of 3.2%. The mean ovulation age for the 728 abortuses was 63.4 days (range 33–109 days). The mean maternal age was 28.4 years (range 15–48 years). The chromosomally abnormal abortuses included 13 (10 nonmosaic and 3 mosaic) trisomics, 7 triploids, 2 abortuses with balanced D/D translocations and an abortus with an XXq- karyotype. Among the 616 abortuses in which both amniotic and fetal tissues were karyotyped, there was complete karyotypic agreement between the two tissues. Among the 339 abortuses in which tissue samples from both sides of the body were analyzed, complete agreement was also found. Factors that may influence the prevalence of abnormal karyotypes in induced abortuses are discussed.     

Minor chromosomal variants and major chromosomal anomalies in couples with recurrent abortion.

One hundred three women with prior histories of recurrent spontaneous abortion and 81 of their mates were karyotyped with Q-banding during 1976-1980. Recurrent abortion was defined as two or more spontaneous pregnancy losses; no couple with a previous malformed fetus or child was included. These cases were reviewed in order to examine the possible contributions of minor polymorphic chromosomal variants and major chromosomal abnormalities to recurrent spontaneous pregnancy loss. Balanced translocations were detected in four women and two men in the study; mosaic X aneuploidy was noted in one woman. Quantitative (1 qh, 9qh, 16qh, Yqh) and qualitative (3c, 4c, 13p, 13s, 14p, 14s, 15p, 15s, 21p, 21s, 22p, 22s) heterochromatic polymorphisms were blindly assessed and compared with a control group. Cases and controls did not differ in the frequency of any qualitative polymorphisms or in the length of any quantitative polymorphism. Thus, while major parental cytogenetic aberrations are significantly associated with fetal wastage, these data suggest that minor polymorphic chromosomal variants do not play an important role in the etiology of recurrent spontaneous abortion.     

Fetal chromosome studies in the first trimester of pregnancy

The possibility of transcervical biopsy of chorion by the method of forceps and production of "direct" preparations of chromosomes in the first trimester of pregnancy has been studied. Satisfactory preparations are obtained during short-term incubation of villi for 24 and 48 hours. Portion of complete metaphases constitutes 0.23.