Prenatal diagnosis of gastrointestinal obstruction: A correlation between prenatal ultrasonic findings and postnatal operative findings

The impact of prenatal sonographic diagnosis of oesophageal and gastrointestinal obstructions has been analysed over a 10-year period. Three groups of patients were evaluated. The first group consisted of 46 newborns with abnormal prenatal sonogratns, 41 of which were confirmed to have intestinal obstruction postnatally. The second group consisted of 17 neonates with normal prenatal sonograms who had intestinal obstruction postnatally. The third group included 56 newborns who did not undergo a prenatal sonogram but who had intestinal obstruction confirmed at surgery. Polyhydramnios without the appearance of a stomach on ultrasound was diagnostic of pure oesophageal atresia. Polyhydramnios with intestinal dilation was diagnostic of intestinal obstruction. Although surgery was performed earlier in the infants diagnosed prenatally with ultrasound, mortality was no less than in the group that did not undergo a prenatal sonogram, probably because of the high incidence of associated anomalies.     

Prenatal diagnosis of thalassemia: The viewpoint of patients

Twenty-eight young people with thalassemia major expressed their opinion about prenatal diagnosis. All of them stated that they intended to marry and have children; thirteen of them (46 per cent) said that they would have also accepted a thalassemic carrier as a partner and that if married to a carrier they would have undergone prenatal diagnosis and selective abortion. All but one refused the prospect of an affected child. When asked if they would have preferred that before their birth their parents had undergone prenatal diagnosis and abortion, 19 patients (68 per cent) gave an affirmative answer. These results clearly indicate that even people affected by thalassemia major, who are the potential victims of prenatal diagnosis and selective abortion, largely accept prenatal diagnosis as a means of preventing their disease.     

Consequences of prenatal diagnosis of cystic fibrosis on the reproductive attitudes of parents of affected children

Three hundred and twenty-six French families with a cystic fibrosis-affected child who were referred for prenatal diagnosis were analysed by sibship size: 74.2 per cent of the couples had no further pregnancies to term after the affected child, who was deceased in 34.6 per cent of cases. These couples were followed prospectively after prenatal diagnosis and 77 had two or more consecutive pregnancies with prenatal diagnosis. The aim of these couples was to succeed in constituting a family with two normal children.     

Prenatal diagnosis of X-linked hydrocephalus in a Chinese family with four successive affected pregnancies

We report on a woman with four successive pregnancies affected with X-linked hydrocephalus (XLH). The first child had prenatal craniocentesis and died in utero. The second child had a postnatal shunting operation, but suffers from severe growth and mental retardation at 5 years of age. In the third pregnancy, prenatal ultrasound detected hydrocephalus at the 16th and 20th weeks of gestation and the pregnancy was terminated. In the fourth pregnancy, ultrasound scanning at the 17th and 20th weeks of gestation revealed no remarkable findings, but hydrocephalus was detected at the 24th week. Autopsy confirmed the prenatal diagnosis. DNA polymorphism analysis of the Bell site of exons 17–18 of factor VIII gene of the woman and her last two fetuses seemed to be compatible with a linkage between the XLH locus and factor VIII gene. Although XLH has a variable presentation of ventriculomegaly, ultrasound scanning is still a useful tool for prenatal diagnosis at present. Earlier and more accurate prenatal diagnosis will be feasible with molecular analysis of the XLH locus or its flanking regions.     

A sonographic approach to the prenatal diagnosis of skeletal dysplasias

Skeletal dysplasias are a heterogeneous group of conditions, many of which present unexpectedly in the prenatal period with a variety of ultrasound findings. Accurate prenatal diagnosis can now be facilitated using exome sequencing approaches, but in order to interpret results, accurate and detailed phenotyping is required. Here, we describe the sonographic approach to the prenatal diagnosis of skeletal abnormalities and illustrate how taking a systematic approach can facilitate diagnosis.     

Ethnic differences in determinants of participation and non-participation in prenatal screening for Down syndrome: A theoretical framework

Objective To develop a theoretical framework for analysing ethnic differences in determinants of participation and non-participation in prenatal screening for Down syndrome. Methods We applied Weinstein's Precaution Adoption Process (PAP) Model to the decision of whether or not to participate in prenatal screening for Down syndrome. The prenatal screening stage model was specified by reviewing the empirical literature and by data from seven focus group interviews with Dutch, Turkish and Surinamese pregnant women in the Netherlands. Results We identified 11 empirical studies on ethnic differences in determinants of participation and non-participation in prenatal screening for Down syndrome. The focus group interviews showed that almost all stages and determinants in the stage model were relevant in women's decision-making process. However, there were ethnic variations in the relevance of determinants, such as beliefs about personal consequences of having a child with Down syndrome or cultural and religious norms. Discussion The prenatal screening stage model can be applied as a framework to describe the decision-making process of pregnant women from different ethnic backgrounds. It provides scope for developing culturally sensitive, tailored methods to guide pregnant women towards informed decision-making on participation or non-participation in prenatal screening for Down syndrome. Copyright © 2007 John Wiley & Sons, Ltd.     

Fetal cardiac abnormalities: Genetic etiologies to be considered

Congenital heart diseases are a common prenatal finding. The prenatal identification of an associated genetic syndrome or a major extracardiac anomaly helps to understand the etiopathogenic diagnosis. Besides, it also assesses the prognosis, management, and familial recurrence risk while strongly influences parental decision to choose termination of pregnancy or postnatal care. This review article describes the most common genetic diagnoses associated with a prenatal finding of a congenital heart disease and a suggested diagnostic process.     

Prenatal diagnosis of Huntington's disease (HD): Experiences with six cases and PCR

In the course of a 2-year predictive testing programme for Huntington's disease (HD), six couples from a total of 52 applicants requested prenatal testing. In each case, the pregnancy was in the first or second trimester when the couples were referred for DNA diagnosis. In five cases, exclusion testing was offered; in one case, a person at risk with an increased risk of being a gene carrier requested prenatal diagnosis. In all cases, informative markers for prenatal testing could be determined. Whenever possible, the newer technique of polymerase chain reaction (PCR) for D4S125 was applied to perform rapid prenatal diagnosis. Two couples withdrew before chorionic villus sampling was undertaken; prenatal diagnosis was completed in the remaining four cases. After exclusion testing, two pregnancies were determined to have an increased risk and two fetuses to have a low risk of being HD gene carriers.     

Prenatal sonographic diagnosis of Malpuech syndrome

Malpuech syndrome (MS) is a rare autosomal recessive syndrome featuring pre- and post-natal growth deficiency, mental retardation, facial dysmorphism, cleft lip and palate (typically midline or bilateral), caudal appendage, renal malformations and male genital abnormalities. A prenatal diagnosis of MS was made in this fetus based on the family history and a combination of conventional and 3D prenatal ultrasound findings. The family were consanguineous with an affected first child. Prenatal ultrasound in the second pregnancy demonstrated bilateral cleft lip and palate in association with intrauterine growth retardation on serial prenatal ultrasound scans. Dysmorphic facial features and a small penis consistent with the diagnosis were confirmed on 3D scanning. Post-natal examination of the neonate confirmed the diagnosis of MS. To the best of our knowledge, this is the first prenatal diagnosis of this syndrome. Copyright © 2006 John Wiley & Sons, Ltd.     

Fetal cholecystomegaly: A prenatal marker of aneuploidy

The fetal gall bladder can now be easily identified during the second and third trimesters using high-resolution ultrasonography. In this report we present eight fetuses with an enlarged gall bladder detected on prenatal ultrasonography at a mean gestational age of 24.6 weeks (range 19–31 weeks). Additional ultrasonographic findings were present in four cases: fetal anomalies and intrauterine growth retardation in three and polyhydramnios in one. Of those cases associated with fetal anomalies, one woman underwent amniocentesis at 21 weeks revealing trisomy 18. The other two declined prenatal karyotyping; neonatal karyotyping revealed trisomy 13 in one and trisomy 18 in the other. Although an enlarged fetal gall bladder can be a normal variant in the second and third trimesters, the prenatal detection of cholecystomegaly should prompt a search for associated anomalies and other markers of aneuploidy. If found, prenatal karyotyping should be considered.     

Complex cardiac defect with hypoplastic right ventricle in a fetus with valproate exposure

We describe a fetus with a hypoplastic right ventricle detected by prenatal ultrasound examination. A possible causal relationship with prenatal valproate exposure is discussed. Copyright © 2005 John Wiley & Sons, Ltd.     

Prenatal diagnosis of a new syndrome: Holoprosencephaly with hypokinesia

Markedly decreased fetal activity (akinesia/hypokinesia) is usually readily apparent to experienced mothers, and frequently this concern leads to attempts at prenatal diagnosis. We report prenatal diagnosis of two fetuses with congenital contractures, markedly decreased fetal movement, and microcephaly due to severe holoprosencephaly. Such familial recurrence to phenotypically normal parents suggests a newly recognized autosomal recessive or X-linked syndrome that is readily detectable by prenatal ultrasonography.     

Prenatal diagnosis of trisomy 21 and X/XX sex chromosome mosaicism

Double aneuploidy involving Down syndrome and Turner syndrome is a rare chromosomal abnormality presumed to occur with a frequency of about 1 in 2 million births. Twenty-one cases of this combined anomaly have been reported and two infants were born with this anomaly after a mistake in prenatal diagnosis. We report the first prenatal diagnosis of Down syndrome combined with Turner mosaicism and suggest that this polysyndrome may be more common than previously estimated. We, therefore, wish to alert cytogenetic laboratories performing prenatal diagnoses of the potential risks of misdiagnosis of this polysyndrome if banding is not performed and if a sufficient number of mitotic cells are not analysed.     

State-wide increase in prenatal diagnosis of klinefelter syndrome on amniocentesis and chorionic villus sampling: Impact of non-invasive prenatal testing for sex chromosome conditions

Background

To analyze population-based trends in the prenatal diagnosis of sex chromosome aneuploidy (SCA) since the availability of non-invasive prenatal testing (NIPT).

Methods

Retrospective state-wide data for all prenatal diagnoses performed <25 weeks gestation from 2005 to 2020 in Victoria, Australia. Non-invasive prenatal testing became locally available from 2012. The prenatal diagnosis rates of SCA as proportions of all prenatal diagnostic tests and all births were calculated. Statistical significance was assessed with the χ² test for trend, with p < 0.05 considered significant.

Results

46,518 amniocentesis and chorionic villus sampling were performed during the study period, detecting 617 SCAs. There was a significant increase in the rate of prenatal SCAs from 5.8 per 10,000 births in 2005 to 8.7 per 10,000 births in 2020 (p < 0.0001). This increase was predominantly due to 47,XXY cases, 91% of which were ascertained via positive NIPT for this condition in 2020. The prenatal diagnosis rate of 47,XXY significantly increased from 0.8 per 10,000 births in 2005 to 4.3 per 10,000 births in 2020 (p < 0.0001).

Conclusion

Screening for SCAs using NIPT has directly led to an increase in their prenatal diagnosis on a population-wide basis, especially 47,XXY. This has implications for clinician education, genetic counselling, and pediatric services.     

Prenatal diagnosis of sex chromosome aneuploidy—What do we tell the prospective parents?

Sex chromosome aneuploidy (SCA) can be detected on prenatal diagnostic testing and cell free DNA screening (cfDNA). High risk cfDNA results should be confirmed with diagnostic testing. This summary article serves as an update for prenatal providers and assimilates data from neurodevelopmental, epidemiologic, and registry studies on the most common SCA. This information can be helpful for counseling after prenatal diagnosis of sex chromosome aneuploidy. Incidence estimates may be influenced by ascertainment bias and this article is not a substitute for interdisciplinary consultation and counseling.     

Women's opinions on the offer and use of prenatal diagnosis

We have studied the opinions and attitudes of women towards prenatal diagnosis (amnio-centesis/chorionic villus sampling/ultrasound/serum AFP testing). A questionnaire was sent to 185 women who had had their first baby a few months before. The respondents have a strong positive attitude towards the diagnostic procedures, especially if treatable abnormalities can be detected. Younger women and women with a high level of education were less inclined to make use of prenatal diagnosis. If tests were made more widely available, this might lead to a significant increase in the use of prenatal diagnosis.     

Prenatal findings on ultrasound and X-ray in a case of overgrowth syndrome associated with increased nuchal translucency

A case of prenatal diagnosis of an overgrowth syndrome at 30 weeks of gestation is reported. The diagnosis was suggested on the basis of increased fetal growth from 16 weeks onwards, advanced bone age, and characteristic facial features such as hypertelorism, broad forehead and small chin. The fetus presented at 12 weeks with a markedly increased nuchal translucency thickness and generalized skin edema, but normal karyotype. Serial ultrasound scans revealed brain abnormalities including mild unilateral ventriculomegaly and a cyst in the cavum septi pellucidi. The pregnancy was terminated at the parents' request at 32 weeks of gestation and postmortem examination confirmed the prenatal findings. This case demonstrates the possibility of prenatal diagnosis of early overgrowth syndromes and highlights the dilemma arising from the prenatal diagnosis of a non-lethal condition associated with an uncertain prognosis and poorly documented in utero. Copyright © 2001 John Wiley & Sons, Ltd.     

Promises,pitfalls and practicalities of prenatal whole exome sequencing

Prenatal genetic diagnosis provides information for pregnancy and perinatal decision-making and management. In several small series, prenatal whole exome sequencing (WES) approaches have identified genetic diagnoses when conventional tests (karyotype and microarray) were not diagnostic. Here, we review published prenatal WES studies and recent conference abstracts. Thirty-one studies were identified, with diagnostic rates in series of five or more fetuses varying between 6.2% and 80%. Differences in inclusion criteria and trio versus singleton approaches to sequencing largely account for the wide range of diagnostic rates. The data suggest that diagnostic yields will be greater in fetuses with multiple anomalies or in cases preselected following genetic review. Beyond its ability to improve diagnostic rates, we explore the potential of WES to improve understanding of prenatal presentations of genetic disorders and lethal fetal syndromes. We discuss prenatal phenotyping limitations, counselling challenges regarding variants of uncertain significance, incidental and secondary findings, and technical problems in WES. We review the practical, ethical, social and economic issues that must be considered before prenatal WES could become part of routine testing. Finally, we reflect upon the potential future of prenatal genetic diagnosis, including a move towards whole genome sequencing and non-invasive whole exome and whole genome testing. © 2017 John Wiley & Sons, Ltd.     

Prenatal diagnosis of inherited metabolic disorders by quantitation of characteristic metabolites in amniotic fluid: Facts and future

An attempt is made to summarize as completely as possible what is known about the prenatal diagnosis of amino– and organic acidurias by direct measurement of characteristic metabolites in amniotic fluid, and to indicate which disorders can potentially be diagnosed prenatally by direct quantitation of metabolites. Furthermore, the disorders are mentioned in which the prenatal diagnosis was proven to be unsuccessful by this approach. The prenatal diagnoses of a case of propionic acidemia and a case of tyrosinemia type I in the 11th and 12th week of gestational age, respectively, are reported and the prospects of performing amniocentesis in the first trimester for prenatal diagnosis are discussed.     

Severe bilateral renal disease: Correlation of antenatal and autopsy findings

We report 20 infants with severe bilateral renal disease examined by prenatal ultrasound and by autopsy. In 17, the prenatal and pathologic diagnoses correlated well. Although the prenatal and autopsy findings differed in the three remaining cases, the autopsy confirmed the presence of severe bilateral renal abnormalities. All 20 pregnancies were complicated by oligohydramnios, which was severe in 60 per cent. Most of these fetuses had malformation of other organ systems. This series supports the utility of prenatal ultrasound examinations, but emphasizes the need for postnatal evaluation of congenital renal disease including pathologic examination of tissue when possible for correct classification and genetic counselling.