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.     

DNA confirmation of congenital myotonic dystrophy in non-immune hydrops fetalis

We report on the prenatal diagnosis of congenital myotonic dystrophy in a case of nonimmune hydrops fetalis. DNA analysis of amniocytes revealed expansion of the trinucleotide (CTG) repeat within the myotonin PK gene, associated with myotonic dystrophy. The fetus was found to have approximately 1730 copies, while the normal population has between 5 and 27 copies, and minimally affected individuals have at least 50 copies.     

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.     

Antenatal diagnosis and palliative treatment of non-immune hydrops fetalis secondary to fetal parvovirus B19 infection

Hydrops fetalis was diagnosed at 22 weeks. An ultrasound examination demonstrated cardiomegaly and a fetal blood specimen obtained by cordocentesis revealed thrombocytopenia, anaemia, and neutropenia. Fetal paracentesis yielded straw-coloured fluid with electrolytes indicative of a transudate. Non-enveloped icosahedral viral particles approximately 23 mm in diameter were visualized in the ascitic fluid by electron microscopy. Immune electron microscopy confirmed human parvovirus B19. Direct fetal digitalization led to a reduction in umbilical artery resistance, a decline in the abdominal circumference from 20·3 to 17·8 cm, and resolution of the ascites within 72 h. Despite this dramatic response to therapy, fetal death occurred on day 5 of treatment. The initial maternal serum was positive for anti-B19 IgM and IgG antibodies. Electron microscopy of fetal cardiac tissue obtained post-mortem revealed intranuclear viral particles typical of B19, confirming the antenatal diagnosis of myocarditis. This case demonstrates that direct viral identification is applicable to prenatal diagnosis. To our knowledge, this is the first reported case of the antenatal diagnosis and palliative treatment of fetal viral infection.     

Fetal renal vein thrombosis,hydrops fetalis,and maternal lupus anticoagulant. A case report

Hydrops fetalis with fetal renal vein thrombosis in a mother with antiphospholipid antibody syndrome detected post-partum suggests an underlying pathogenetic association that may provide new strategies for treatment of a lethal disorder.     

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.     

Intrauterine hypercalcaemia and non-immune hydrops fetalis— relationship to the Williams syndrome

We describe a 28-week-old fetus with severe non-immune hydrpps. Intrauterine cord blood sampling revealed hypercalcaemia of 3–4mmol/l (n = 2·6±0·1). Subsequently, a postmortem examination revealed supravalvular aortic and pulmonary artery stenosis together with extensive arterial calcification. The maternal calcium, 25-hydroxyvitamin D₃, 1,25-dihydroxyvitamin D₃, and parathyroid hormone levels were normal at delivery. This is the first time that hypercalcaemia has been diagnosed in vitro. We speculate on the fact that the disorder resulted as a consequence of abnormal vitamin D metabolism in the fetoplacental unit, and that it might be related to the Williams syndrome.     

Ultrasound evaluation of pregnancies at risk for homozygous α-thalassaemia-1

Twenty-six pregnant Chinese women who were at risk of giving birth to a fetus affected with homozygous α-thalassaemia-1 were examined serially by ultrasound. Six of these 26 pregnancies were affected. In one third of the affected pregnancies progressive fetal ascites appeared before 24 weeks gestation and these pregnancies were terminated. In the remaining two thirds abnormal estimated fetal weight-placental volume (EFW-PV) ratio and fetal growth retardation as evidenced by a falling biparietal diameter (BPD), femur length (FL) but a normal abdominal circumference (AC) was apparent by 28 weeks gestation. Increased transverse cardiac (TC) diameter was another consistent finding but appeared late. All these features appeared before the onset of fetal ascites. A normal EFW-PV ratio and fetal growth until 28 weeks gestation was a reassuring sign of normality. Abnormal EFW-PV ratio was the earliest sign to appear in affected pregnancies and a normal ratio until 28 weeks gestation had a 100 per cent predictive value.     

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.     

A system-based approach to the genetic etiologies of non-immune hydrops fetalis

A wide spectrum of genetic causes may lead to nonimmune hydrops fetalis (NIHF), and a thorough phenotypic and genetic evaluation are essential to determine the underlying etiology, optimally manage these pregnancies, and inform discussions about anticipated prognosis. In this review, we outline the known genetic etiologies of NIHF by fetal organ system affected, and provide a systematic approach to the evaluation of NIHF. Some of the underlying genetic disorders are associated with characteristic phenotypic features that may be seen on prenatal ultrasound, such as hepatomegaly with lysosomal storage disorders, hyperechoic kidneys with congenital nephrosis, or pulmonary valve stenosis with RASopathies. However, this is not always the case, and the approach to evaluation must include prenatal ultrasound findings as well as genetic testing and many other factors. Genetic testing that has been utilized for NIHF ranges from standard chromosomal microarray or karyotype to gene panels and broad approaches such as whole exome sequencing. Family and obstetric history, as well as pathology examination, can yield additional clues that are helpful in establishing a diagnosis. A systematic approach to evaluation can guide a more targeted approach to genetic evaluation, diagnosis, and management of NIHF.     

Mid-trimester fetal ultrasound: Diagnostic dilemmas

Two cases are reported in which an unusual ultrasound finding preceded diagnostic amniocentesis and led to further work-up. In both cases a decision was made to terminate the pregnancy. One fetus in which a neck mass was detected by ultrasound was shown to be normal on post-mortem examination. The second fetus was aborted because of Rh sensitization and had the abnormality seen by ultrasound. However, this lesion, calcified intrahepatic plaques, had no presumed pathological significance. These cases suggest caution in the interpretation of results obtained with the new technologies used for prenatal diagnosis.     

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.     

Early prenatal diagnosis of A lethal syndrome of multiple congenital contractures

An ultrasonic diagnosis of a lethal, autosomally recessive syndrome of multiple congenital contractures was made in seven high-risk pregnancies on the 13rd to 17th gestational weeks. The diagnostic findings were the development of progressive subcutaneous oedema from the 13th gestational week on and the decrease of fetal limb movements.     

A large retinoblastoma detected in a fetus at 21 weeks of gestation

The facial tumour described here is the first reported case of a large retinoblastoma detected early in pregnancy and adds another item to the differential diagnosis of facial tumours visualized by prenatal ultrasound examination. Ultrasound examination of the fetal eyes can be offered in cases of retinoblastomas where prenatal DNA diagnosis is otherwise impossible.     

Attitudes toward abortion for fetal anomaly in the second vs. the third trimester: A survey of Parisian obstetricians

Cross-cultural differences exist in prenatal diagnosis and abortion for fetal anomaly, stemming from variations in laws, reimbursement policies, litigation, physicians' decision-making authority, and attitudes toward the prevention of handicaps. The first part of this paper discusses such differences in France and the U.S. The second part describes a survey of practising obstetricians in Paris, designed to assess (1) their attitudes toward pregnancy termination for various conditions, (2) their concern about fetal viability, (3) their desire for diagnostic certainty before justifying a late abortion, and (4) their perceived role in such decision-making. Among the 64.8 per cent (N = 217) who responded, the majority supported third-trimester termination (TTT) for diseases such as spina bifida, trisomy 21 , microcephaly, and Duchenne muscular dystrophy; 30–59 per cent supported TTT for cystic fibrosis and sickle cell disease; and 22–29 per cent supported TTT for haemophilia, tetralogy of Fallot, limb amputation, and Turner and Klinefelter syndromes. Obstetricians who approved of abortion across trimesters were less concerned with the certainty of diagnosis than its severity, more likely to think that abortion ought to be the parents' choice, but more likely to report making a recommendation to the parents about whether to abort a fetus. Such permissive abortion attitudes might imply more permissive prenatal diagnosis and abortion practice among Parisian obstetricians, which might lead to increased migration of patients from other E.C. countries. Cross-cultural variation in obstetric practice suggests that an international registry of pregnancies terminated for medical reasons, enabling further study of this issue, would be valuable.