Fetal laser therapy: applications in the management of fetal pathologies

Fetoscopic coagulation of placental anastomoses is the treatment of choice for severe twin-to-twin transfusion syndrome. In the present day, fetal laser therapy is also used to treat amniotic bands, chorioangiomas, sacrococcygeal teratomas, lower urinary tract obstructions and chest masses, all of which will be reviewed in this article. Amniotic band syndrome can cause limb amputation by impairing downstream blood flow. Large chorioangiomas (>4 cm), sacrococcygeal teratomas or fetal hyperechoic lung lesions can lead to fetal compromise and hydrops by vascular steal phenomenon or compression. Renal damage, bladder dysfunction and lastly death because of pulmonary hypolasia may be the result of megacystis caused by a posterior urethral valve. The prognosis of these pathologies can be dismal, and therapy options are limited, which has brought fetal laser therapy to the forefront. Management options discussed here are laser release of amniotic bands, laser coagulation of the placental or fetal tumor feeding vessels and laser therapy by fetal cystoscopy. This review, largely based on case reports, does not intend to provide a level of evidence supporting laser therapy over other treatment options. Centralized evaluation by specialists using strict selection criteria and long-term follow-up of these rare cases are now needed to prove the value of endoscopic or ultrasound-guided laser therapy. © 2015 John Wiley & Sons, Ltd.     

Postnatal investigation of fetal renal disease

The antenatal ultrasound diagnosis of renal tract abnormalities is now firmly established. Postnatal imaging protocols are constantly evolving and still many questions remain unanswered. Most infants are asymptomatic at birth and aggressive imaging is unwarranted both for the infant and overburdened Radiology departments. The urgency with which to undertake imaging relates to the suspected antenatal diagnosis and clinical scenario, with bilateral hydronephrosis, posterior urethral valves and complicated duplex systems taking a high priority. The main imaging modality postnatally remains ultrasound, and together with nuclear medicine gives a powerful combination of both anatomy and function. Intravenous urography is never indicated in the neonate. Copyright © 2001 John Wiley & Sons, Ltd.     

Fetal surgery for severe lower urinary tract obstruction

Fetal interventions have been proposed for treatment of severe lower urinary tract obstruction (LUTO), as this condition is associated with high rates of perinatal mortality and postnatal renal impairment. The rationale for in utero treatment for those cases is based on the possibility of relieving the obstruction, improving the amniotic fluid volume, and preventing renal and bladder damage. Candidates for fetal intervention should be rigorously selected based on the confirmation of severe LUTO (dilated bladder and bilateral hydronephrosis), oligohydramnios or anyhydramnios and ‘favorable’ fetal urinalysis (dependent on gestational age). Nowadays there are two different therapeutic options with specific technical approaches. Vesico-amniotic shunting is an easier procedure, but with a higher frequency of related complications. Fetal cystoscopy can be used for diagnostic purpose and for treatment of posterior urethral valves, with suggestive advantage of allowing a more physiological release of the obstruction. According to the literature, estimated survival rates and postnatal normal renal function frequencies are approximately 40 and 50% after vesico-amniotic shunting and 75 and 65% after fetal cystoscopy, respectively. Copyright © 2011 John Wiley & Sons, Ltd.     

Non‒visualisations of the fetal bladder: aetiology and management

Failure to detect a normally filled fetal bladder on ultrasound scanning can imply the presence of a serious urogenital abnormality. Detailed scanning may elicit the underlying pathology, but there may be complex anomalies present, the full extent of which often has to await the results of postnatal investigations. Management in a combined paediatric urology:fetal medicine clinic is recommended. Copyright © 2001 John Wiley & Sons, Ltd.     

Fetal lower urinary tract obstruction: What should we tell the prospective parents?

Fetal lower urinary tract obstruction (LUTO), which often results in marked perinatal morbidity and mortality, is caused by a heterogeneous group of anatomical defects that lead to blockage of the urethra. The classic prenatal presentation of LUTO includes megacystis with hydronephrosis. While mild forms of the disease can be associated with favorable outcomes, more severe disease commonly leads to dysplastic changes in the fetal kidneys, and ultimately oligohydramnios, which can result in secondary pulmonary hypoplasia and renal failure at birth. The aim of this review is to provide practitioners with a general overview of the diagnosis and treatment of LUTO based on disease severity, along with some points to consider when counseling prospective parents of fetuses with this condition.     

Prenatal diagnosis of gall bladder anomalies—report of 17 cases

We describe here 17 cases of fetal gall bladder anomalies, detected as early as the 14th week of gestation, out of 10 016 fetal systemic examinations performed by us in the last 6 years (015 per cent). In seven cases, agenesis of the fetal gall bladder was detected. The diagnosis was confirmed by post-abortal examination in five cases and in two post-partum. In six other cases, a left-sided gall bladder and in one case, a ‘floating’ gall bladder were detected at 15 weeks' gestation. In two cases, a septated or bilobed gall bladder was visualized. None of these 15 cases was dyskaryotic, but in five cases, two with agenesis and three left-sided gall bladders were associated with other fetal malformations. In two other cases, the gall bladder appeared dysmorphic on sonographic examination and in both of them intrauterine growth retardation and other anomalies were detected. Trisomy 18 was diagnosed by amniocentesis in one of them. According to our experience, failure to visualize the fetal gall bladder by the 15th gestational week is diagnostic of its absence and should raise the differential diagnosis between gall bladder atresia, which has a good prognosis, and external biliary atresia, which has a poor prognosis. Further experience is needed to characterize the various gall bladder malformations and their prognosis.     

Failure to detect fetal obstructive uropathy by second trimester ultrasound

The prenatal diagnosis, management and outcome of an hereditary obstructive uropathy is presented. Serial ultrasonic assessment of the fetal urinary tract was carried out from the early second trimester onward. Slight bilateral hydronephrosis as a first sign of obstructive uropathy was only established as late as 30 weeks of gestation. On the basis of weekly ultrasound scans, a conservative approach was adopted. In view of fetal maturity, labour was induced at 36 weeks resulting in the vaginal delivery of a male infant with moderate bilateral hydronephrosis. Neonatally, anuria developed due to bilateral obstruction of the ureters as a result of increasing bladder wall hypertrophy due to urethral valves. A bilateral uretero-cutaneostomy was carried out. The infant so far develops normally, and renal function is normal for age. Women at risk for fetal obstructive uropathy should have ultrasonic monitoring throughout pregnancy.     

Dysplastic and polycystic kidneys: diagnosis,associations and management

Cystic and bright kidneys can pose a significant diagnostic dilemma when discovered as an incidental finding at the time of a routine fetal ultrasound scan. There are diverse aetiologies with equally variable implications for the prognosis in the affected fetus, and for future pregnancies. Accurate antenatal diagnosis in the absence of any positive family history is often not possible and a team approach to management (to include the fetal medicine specialist, paediatric nephrologist or urologist, geneticists and in some cases, pathologist) is essential. In this review we will attempt to describe the embryology and aetiology of these conditions and suggest an approach to management. Copyright © 2001 John Wiley & Sons, Ltd.     

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.     

Maternal genetic disorders and fetal development

With improvements in early diagnosis and management of genetic diseases, more women with genetic disorders are reaching reproductive age and becoming pregnant. While pregnancy can have a significant impact on a woman's health when there is an underlying genetic disorder, there can also be fetal effects, including embryopathy, fetal growth restriction, and brain injury. Some maternal genetic disorders are associated with adverse perinatal outcomes, including a high risk of perinatal loss and preterm birth. In this article, we review several maternal genetic disorders associated with fetal risk that are important for clinicians and patients to understand and manage appropriately. These include phenylalanine hydroxylase (PAH) deficiency and other inborn errors of metabolism, tuberous sclerosis complex, myotonic dystrophy, cystic fibrosis, Turner syndrome, sickle cell disease, and connective tissue disorders.     

Syndromic encephalocele in a fetal case with a 1p35-pter deletion and a 14q32-qter duplication inherited from a maternal balanced translocation

Occipital encephalocele belongs to the family of neural tube defects, which occur in one among 2000 to 5000 live births. Syndromic encephaloceles include Meckel–Gruber syndrome and various chromosomal abnormalities. We report on a fetal case (13 WG) with bilateral cleft lip and palate, choanal atresia, occipital encephalocele, bilateral club feet, bilateral multicystic kidneys, enlarged bladder and urethral atresia. The fetal chromosome analysis showed a maternally inherited unbalanced translocation between the short arm of chromosome 1 and the long arm of chromosome 14, resulting in 1p35-pter deletion and 14q32-qter duplication (46,XY,der(1),t(1;14)(p35;q32)). Since the chromosomal breakpoints have not previously been implicated in syndromic encephalocele, this observation is of interest for the identification of other genes responsible for occipital encephalocele. Copyright © 2007 John Wiley & Sons, Ltd.     

Discordant fetal sex on NIPT and ultrasound

Prenatal diagnosis of sex discordance is a relatively new phenomenon. Prior to cell-free DNA testing, the diagnosis of a disorder of sexual differentiation was serendipitous, either through identification of ambiguous genitalia at the midtrimester morphology ultrasound or discovery of genotype-phenotype discordance in cases where preimplantation genetic diagnosis or invasive prenatal testing had occurred. The widespread integration of cfDNA testing into modern antenatal screening has made sex chromosome assessment possible from 10 weeks of gestation, and discordant fetal sex is now more commonly diagnosed prenatally, with a prevalence of approximately 1 in 1500-2000 pregnancies. Early detection of phenotype-genotype sex discordance is important as it may indicate an underlying genetic, chromosomal or biochemical condition and it also allows for time-critical postnatal treatment. The aim of this article is to review cfDNA and ultrasound diagnosis of fetal sex, identify possible causes of phenotype-genotype discordance and provide a systematic approach for clinicians when counseling and managing couples in this circumstance.     

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.     

Prenatal diagnosis of pelvic kidney

A 30-year-old woman had serial ultrasound scans from 28 weeks' gestation which revealed the presence of a cystic area in the fetal pelvis. The ‘cyst’ remained unchanged until delivery at 41 weeks. Fetal growth and amniotic fluid volume were normal throughout. A pelvic kidney was confirmed at birth. The differential diagnosis and antenatal management of this ‘cyst’ are discussed.     

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.     

Klippel–Trenaunay–Weber (KTW) syndrome: the use of in utero magnetic resonance imaging (MRI) in a prospective diagnosis

The diagnosis of the Klippel–Trenaunay–Weber (KTW) syndrome is rarely made antenatally. We report the use of both ultrasound and in utero magnetic resonance imaging (MRI) in the prenatal diagnosis of this syndrome. This is the first report of the use of prenatal MRI in the diagnosis of this condition. There was concordance in the findings of both modalities, with limb hypertrophy, and multiple haemangiomata – both subcutaneous and internally – demonstrated with ultrasound and MRI. The patient elected to terminate the pregnancy because of associated oligohydramnios and a small fetal chest noted at 20 weeks. The postmortem examination confirmed the antenatal diagnosis. Copyright © 2001 John Wiley & Sons, Ltd.     

Detection of fetal structural abnormalities at the 11–14 week ultrasound scan

The aim of this study was to evaluate the detection of fetal structural abnormalities by the 11–14 week scan. 2853 pregnant women were submitted to a routine ultrasound scan between the 11th and 14th week and the fetal skull, brain, spine, abdominal wall, limbs, stomach and bladder were examined. Following the scans the patientes were examined in the second or third trimester of pregnancy. An isolated increased nuchal translucency was not considered an abnormality. However, these patients had an early echocardiography assessment. Fetal structural abnormalities were classified as major or minor and of early or late onset. A total of 130 (4.6%) defects were identified and 29 (22.3%) of these were diagnosed at the 11–14 week scan, including nine cardiac defects associated with increased nuchal translucency. The antenatal ultrasound detection rate was 71.5%, and 31.2% were detected in the first-trimester assessment. 78.8% of the major defects were diagnosed by the prenatal scan and 37.8% by the 11–14 week scan. Fetal structural abnormalities at the 11–14 week scan were detected in approximately 22.3% of the cases, therefore, a second-trimester anomaly scan is important in routine antenatal care to increase the prenatal detection of fetal defects. Copyright © 2002 John Wiley & Sons, Ltd.     

硼化物基超高温复合陶瓷超高速撞击作用下破坏模式研究

随着各国航天实验和航天器的增加,太空中存在微小碎片垃圾越来越多,对航天器正常运行有着极大的危害。研究弹丸超高速撞击硼化物基复合陶瓷产生的碎片云特性,采用非线性动力学分析软件AUTODYN,利用光滑质点动力学方法对圆柱形弹丸超高速撞击硼化物基超高温复合陶瓷单层板形成的碎片云进行数值模拟,分析相同质量不同速度弹丸撞击靶板的破坏模式,不同质量相同速度弹丸撞击靶板的破坏模式。结果表明在不同速度和质量弹丸撞击靶板的破坏模式中,穿孔半径变化规律为穿孔半径随着弹丸速度和质量的增大而增大。根据不同质量弹丸超高速撞击板靶的穿孔半径变化规律,得到弹丸撞击相同厚度靶板的击穿速度临界值。该结果可为航天器超高速撞击风险评估和防护设计提供了参考。     

Parvovirus B19 infection in pregnancy: new insights and management

In this article, we review the virology, pathology, epidemiology and clinical spectrum of intrauterine human parvovirus B19 (B19V) infection, including intrauterine fetal death, non-immune hydrops fetalis, thrombocytopenia and neurological manifestations such as pediatric stroke and perivascular calcifications. In addition, we discuss the new insights into the neurodevelopmental outcome of intrauterine B19V infection. Current diagnosis and management of B19V infection is summarized, including a diagnostic and follow-up flowchart for practical clinical use. Copyright © 2011 John Wiley & Sons, Ltd.