Ultrasonographic scanning of placental thickness and the prenatal diagnosis of homozygous alpha-thalassaemia 1 in the second trimester

In order to evaluate the association between placental thickness (PT) and fetal homozygous alpha-thalassaemia 1 before the appearance of classic ultrasound findings of haemoglobin (Hb) Bart's hydrops fetalis, a total of 473 pregnancies were collected. The control group included 422 normal pregnancies with a gestational age from 14 to 23 weeks and the study group included 51 affected fetuses in the same gestational period. Fetal biparietal diameter (BPD) and PT were measured by high-resolution ultrasound. PT was evaluated against BPD. In the control group, the PT generally increased in parallel with the advancement of gestational age. All PT measurements in the study group were above the mean PT of their respective gestational week in the control group. Forty-six (90 per cent) of the pregnancies in the study group had PT larger than the mean plus two standard deviations of the control group. This study suggests that ultrasound measurement of PT may be a useful aid in the prenatal diagnosis of Hb Bart's hydrops fetalis before its classic findings become apparent in the late second trimester or third trimester.     

Fetal bradycardia in the first trimester: an unusual presentation of atrial extrasystoles

We report a fetus with fetal bradycardia at 13 weeks of gestation secondary to atrial extrasystoles. The fetus subsequently developed paroxysmal supraventricular tachycardia and hydrops fetalis. The cardiac arrhythmia recovered spontaneously without any medical intervention. This case illustrates that atrial ectopic beats can present in the first trimester with fetal bradycardia. Rapidly evolving hydrops fetalis secondary to supraventricular tachycardia can develop, warranting close monitoring with weekly heart rate assessment. Fetal bradycardia secondary to atrial extrasystole should be differentiated from first trimester sinus bradycardia and those associated with major structural cardiac abnormality, which have a high fetal loss rate. Copyright © 2002 John Wiley & Sons, Ltd.     

Transabdominal chorionic villus sampling in the second trimester of pregnancy: Feto-maternal transfusions in relation to pregnancy outcome

Volumes of feto-maternal transfusions (FMTs) in transabdominal chorionic villus sampling (TACVS) in the second trimester of pregnancy were calculated from the difference between maternal alpha-fetoprotein (AFP) concentrations before and 1 h after TACVS. In 50 pregnancies, there existed no correlation between FMT volume and the amount of villi collected or the number of TACVS attempts. The expected risk of fetal exsanguination due to very voluminous FMT could not be substantiated. In one case, immunization could have been the cause of hydrops fetalis, although only a volume of 0.15 ml could be calculated.     

Alkaline phosphatase activity in amniotic fluid in pregnancies with fetal disorders

Alkaline phosphatase (ALP) activity was determined in 255 amniotic fluid samples collected by amniocentesis between 15 and 39 weeks of gestation. The samples were originally used for chromosomal analysis and/or alpha-fetoprotein measurements. The mean ALP activity in early amniotic fluid from pregnancies with fetal trisomy 18 and 21 syndromes was half of that found in the controls. Highly elevated ALP activity (over 10 times the median level) was found in 14 samples. Two of these pregnancies had normal outcome. Three samples were from pregnancies with intrauterine fetal death. Fetal disorders, including abdominal wall defect (four cases), Meckel's syndrome (two), hydrops fetalis syndrome (two) and genital anomaly (one), were observed in nine cases. Moderately elevated ALP activity (over three times the median) was found in 10 cases, including five pregnancies with a preterm labour shortly after the sample collection. The results indicate that elevated ALP activity in the third trimester amniotic fluid is often associated with fetal disorders.     

Multiple marker screen positivity in the presence of hydrops fetalis

Three cases of hydrops fetalis presented in the second trimester as screen-positive for Down syndrome using multiple maternal serum markers. One case was a karyotypically normal female; one case was a monosomy X (Turner syndrome); and one case was a trisomy 21 (Down syndrome). In each case, the maternal serum human chorionic gonadotrophin (hCG) was disproportionately elevated. These cases support the contention that hydrops fetalis of any aetiology may present as screen-positive when using multiple maternal serum markers for Down syndrome. Further cases will be necessary before it can be determined whether a disproportionately elevated hCG is predictive of hydrops.     

Human parvovirus B19 infection and unbalanced translocation in a case of hydrops fetalis

In a case of hydrops fetalis, serological examination showed a recent maternal human parvovirus B19 infection. Amniocentesis revealed a unique unbalanced translocation between chromosomes 3 and 11 of the fetus. The mother proved to have a balanced reciprocal translocation between chromosomes 3 and 11. A grossly macerated hydropic male fetus was delivered with a flat nose and low implanted deformed ears. Histopathological examination revealed nuclear inclusion bodies in fetal erythroid cells, confirming human parvovirus B19 infection. Parvovirus B19 DNA was demonstrated by in situ hybridization in the nuclei of heart muscle cells. Our finding of two different disorders in one case illustrates the importance of a complete evaluation of every case of hydrops fetalis, especially concerning counselling on the outcome of future pregnancies. The human parvovirus B19 infection will not recur due to the acquired immunity of the mother, whereas the balanced reciprocal translocation will endanger future pregnancies.     

Prenatal diagnosis of chinese homozygous α-thalassaemia 1 and haemoglobin H disease by analysis of α- and φζ-globin genes in chorionic villi and amniocytes

Eighty-eight high-risk pregnancies, 81 for homozygous α-thalassaemia 1 and 7 for haemoglobin (Hb) H disease, were collected in this study. Chorionic villus sampling (CVS) was done in 63 cases and amniocentesis in 25 cases to obtain fetal cells. Southern blotting and DNA hybridization with α- and φζ-globin gene probes were used to determine the α-globin gene status. In two non-informative families with non-deletional mutations, DNA analysis failed to rule out the affected condition, and fetal blood sampling (FBS) and Hb electrophoresis were used for the final diagnosis. In the 81 fetuses at risk for homozygous α-thalassaemia 1, 17 (13 by CVS and 4 by amniocentesis) were afffected, 30 were α-thalassaemia 1 heterozygotes, 19 were normal, and the remaining 15 were either normal or heterozygous. In the seven fetuses at risk for Hb H disease, one was normal, three were α-thalassaemia 1 heterozygotes, two were α-thalassaemia 2 heterozygotes, and one was affected with Hb H disease and developed hydrops fetalis. DNA analysis on fetal cells enabled us to diagnose prenatally severe α-thalassaemias, to prevent the birth of infants with Hb H disease, and to minimize maternal obstetrical complications from harbouring a fetus with Hb Bart's hydrops fetalis.     

Radiographic,haematological, and biochemical findings in a fetus with Caffey disease

An early case of prenatal Caffey disease is reported. Ultrasound examination performed at 20 weeks showed major angulations of long bones, but both ultrasound scan and X-rays failed to make the differential diagnosis between Caffey disease and lethal osteogenesis imperfecta. A cordocentesis allowed us to find important biological abnormalities. The pregnancy was terminated after the rapid development of hydrops fetalis. The definitive diagnosis of Caffey disease was obtained by special X-ray and pathological study.     

In utero development of a mediastinal teratoma: A second-trimester event

Mediastinal teratomas have rarely been discovered during the prenatal period. When seen during the neonatal period, these tumours have caused respiratory distress or hydrops fetalis. We present the sonographic and pathological findings of a rapidly developing anterior mediastinal teratoma causing hydrops fetalis and in utero demise at 27 weeks' gestation.     

Prenatal diagnosis of mandibulofacial dysostosis

Four fetuses at risk of the autosomal dominant Treacher—Collins syndrome were examined by fetoscopy in the second trimester of pregnancy. Findings were normal in two cases and healthy babies were delivered after uneventful pregnancies. Mandibular hypoplasia and abnormalities of the palpebra and auricles were seen in the other two fetuses; one had an associated cleft palate. These pregnancies were terminated and the diagnoses confirmed by post-mortem examination.     

β-glucuronidase deficiency: Identification of an affected fetus with simultaneous sampling of chorionic villus and amniotic fluid

Four pregnancies at risk for mucopolysaccharidosis VII were monitored by chorionic villus sampling obtained in the first or second trimester of gestation. One fetus showed reduced β-glucuronidase activity following simultaneous sampling of chorionic villus and amniotic fluid at 17 weeks of gestation. The pregnancy was terminated. Subsequent assay of β-glucuronidase activity in the fetal tissues was consistent with a diagnosis of mucopolysaccharidosis VII, thus confirming that chorionic villus samples provide useful information for diagnosis of this condition.     

Likely pathogenic variant in the BICD2 gene in fetus presenting with non-immune hydrops

Trio exome sequencing was performed on a fetus presenting with severe hydrops fetalis at 21 + 0 weeks gestation. A novel de novo BICD2 missense variant was identified in the fetus. Pathogenic variants in the BICD2 gene are associated with lower extremity-predominant spinal muscular atrophy. The variant was initially classified as a variant of uncertain clinical significance (VUS) as at the time of analysis and initial report, pathogenic variants in the BICD2 gene specifically had not been associated with fetal hydrops and no other abnormalities had been detected. It was agreed in multidisciplinary team discussions to include the variant in the report as a VUS recommending phenotypic follow-up. The pregnancy was terminated and post-mortem findings were in keeping with a BICD2-pathogenic variant. In addition, a paper was published reporting another case with a pathogenic BICD2 variant presenting with fetal hydrops. The variant classification was then upgraded to class 4 likely pathogenic and reported as consistent with the diagnosis. This case demonstrates the importance of reporting these new gene/phenotypes in enabling others in the classification of variants, staying up-to-date with literature and following up phenotype for class 3 variants of interest.     

Prenatal diagnosis of the infantile type of neuronal ceroid lipofuscinosis by electron microscopic investigation of human chorionic villi

Chorionic villus biopsy specimens were studied electron microscopically in six pregnancies at risk of the infantile type of neuronal ceroid lipofuscinosis (INCL). The biopsy was performed in all cases in the first trimester of pregnancy (8–10 gestation weeks) by the transcervical route. In one case, the biopsy was repeated at 17 weeks by the transabdominal procedure. In two pregnancies, the endothelial cells and, to a lesser extent, the mesenchymal cells of the chorionic villi contained unit membrane-bound inclusions typical of INCL. In both cases, the pregnancy was terminated and in one of them identical inclusions were found in the brains and kidneys of the fetus at 20 weeks of gestational age. The children from the remaining four pregnancies are healthy and have shown no signs of the disease.     

Prenatal diagnosis of the pterygium syndrome

We report two second trimester pregnancy terminations in the same woman following intrauterine ultrasonic findings of hydrops fetalis, polyhydramnios, lack of fetal movements, and short, fixed malformed limbs. One fetus also showed a cystic mass at the back of the head. Radiographic and anatomic studies of the fetuses demonstrated multiple pterygia, flexion contracture of multiple joints, abnormal facial appearance, cleft palate, pulmonary hypoplasia, and gracile bones. The cystic mass of the back of the head was found to be a cystic hygroma. These findings are consistent with the lethal variant of multiple pterygium syndrome. Early prenatal diagnosis of this condition is possible using ultrasonography.     

Listeriosis: A cause of non-immune hydrops fetalis

A case of prenatally diagnosed non-immune hydrops fetalis, that was later shown to be caused by listeriosis, is presented, and the clinical course, as well as the appropriate diagnostic and therapeutic procedures are described. We conclude, that listeriosis should be excluded, whenever a non-immune hydrops fetalis is associated with septicemia, influenza-like illness and fever of unknown origin.     

β-Glucuronidase deficiency as a cause of prenatally diagnosed non-immune hydrops fetalis

We describe a case of β-glucuronidase deficiency presenting as a non-immune hydrops fetalis diagnosed at 26 weeks of gestation. The deficiency was disclosed on cultured amniotic fluid cells and in fetal plasma and was confirmed post-abortion. In a second pregnancy, a normal β-glucuronidase activity was found in extracts of chorionic villi obtained at 10 weeks of gestation. The pregnancy is continuing uneventfully. We conclude that it is of great importance to verify the presence of metabolic disease whenever the major causes of hydrops fetalis have been excluded.     

Non-immunological hydrops fetalis and intrapericardial teratoma: Case report and review

A large intrapericardial teratoma was found at necropsy in a 38−week stillborn fetus, in which prenatal diagnosis of hydrops fetalis and an ehogenic cardiac mass had been made. Clinical and pathological data are reported. In utero intrapericardial teratomata lead to different outcomes depending on whether fetal hydrops is associated. When generalized fetal hydrops is not present, the outcome is good, even in cases with large pericardial effusions. When generalized fetal hydrops occurs, it often results in a poor outcome. In our literature review, we have found eight perinatal deaths in nine similar cases reported.     

Intrauterine mediastinal teratoma associated with non-immune hydrops fetalis

We describe a rare case of non-immune hydrops fetalis caused by mediastinal teratoma. The sonographic appearance was that of a mixed cystic and solid mass in the antero-superior mediastinum. The teratoma, on post mortem, extended cranially to the upper part of the thyroid, exerting pressure and causing deviation of the trachea, oesophagus, and aortic arch. The pathogenesis of non-immune hydrops fetalis suggests obstruction of venous return caused by this tumour.     

Five years' experience of prenatal diagnosis of cystic fibrosis in the former U.S.S.R.

From a total of 490 cystic fibrosis (CF) high-risk families under supervision (mostly Russian Slavs from the European part of the country), DNA data including both direct screening for some CF gene(CFTR)mutations(deIF508, G551D and 1677delTA) and allelic polymorphism studies with tightly CF linked DNA markers were collected from 261 families. All full families (129) and 86 CF families with a deceased index child were found to be either fully (42 per cent) or partially (40 per cent) informative for DNA analysis. Prenatal diagnosis (PD) was carried out in 161 CF families. Microvillar enzyme (MVE) assay was applied to all 140 PD at the second trimester either as a single test (88) or in conjunction with DNA analysis (52). The frequency of false-negative results of the MVE assay was 1.3 percent and that of false-positive results, as judged by the albumin meconium test, was 5.0 per cent. Ambiguous results of MVE analysis were found in 30 cases, 12 of which were verified by DNA analysis. Molecular diagnosis of CF at the first trimester was carried out in 21 cases and four pregnancies were terminated. Altogether, 39 pregnancies with a predicted high risk of CF fetuses were terminated. The low average frequency of delF508 in CF chromosomes of Russian Slavs (50 per cent), its remarkable inter-population variation, and the significant proportion of at-risk families without an affected child determine the necessity of combined molecular and biochemical (MVE assay) approaches for efficient prenatal diagnosis of CF in the former U.S.S.R.     

Mesomelic campomelia,polydactyly and Dandy–Walker cyst in siblings

The present report describes two fetuses, one female and one male, with thus far undescribed skeletal malformations. The mother was a gravida 2, para 0. Both pregnancies were terminated in the second trimester because of multiple congenital anomalies diagnosed ultrasonographically resembling a short rib-polydactyly syndrome. Both fetuses were found to have postaxial hexadactyly of the hands and feet, marked bilateral campomelia of the forearm and shank bones, and a Dandy–Walker cyst. In addition, the fourth ventricle was dilated in the first sibling and the second sibling had an inverse intestinal malrotation. A literature search failed to reveal similar observations. Copyright © 2001 John Wiley & Sons, Ltd.