Amniotic band syndrome in second trimester associated with fetal malformations

The Possibility of severe fetal malformations, including neural tube defects, secondary to early amniotic rupture followed by formation of fibrous bands (amniotic band syndrome) is a well-known entitity. The fact that these pregnancies are usually uneventful makes prenatal diagnosis difficult, but routine determination of serum alphafetoprotein, followed by ultrasound scanning, may detect some of the malformations. We present a case, where detection of a neural tube defect led to induced second trimester abortion of a fetus severely affected by this syndrome. There appeared to be a causal relationship between maternal trauma and the amniotic rupture.     

Development of the vertebrate central nervous system: formation of the neural tube

The developmental process of neurulation involves a series of coordinated morphological events, which result in conversion of the flat neural plate into the neural tube, the primordium of the entire central nervous system (CNS). Failure of neurulation results in neural tube defects (NTDs), severe abnormalities of the CNS, which are among the commonest of congenital malformations in humans. In order to gain insight into the embryological basis of NTDs, such as spina bifida and anencephaly, it is necessary to understand the morphogenetic processes and molecular mechanisms underlying neural tube closure. The mouse is the most extensively studied mammalian experimental model for studies of neurulation, while considerable insight into underlying developmental mechanisms has also arisen from studies in other model systems, particularly birds and amphibians. We describe the process of neural tube formation, discuss the cellular mechanisms involved and highlight recent findings that provide links between molecular signaling pathways and morphogenetic tissue movements. Copyright © 2009 John Wiley & Sons, Ltd.     

The synaptic membrane D2-protein in amniotic fluid from pregnancies with fetal neural tube defects

The D2-protein is a neuronal membrane protein which has an immunochemically detectable soluble derivative in cerebrospinal fluid. We used rocket-on-line immunoelectrophoresis with an antiserum against rat synaptosomal membranes for demonstration of the human D2-protein in fetal cerebrospinal fluid and in amniotic fluids from pregnancies with fetal neural tube defects. D2 was neither found in normal amniotic fluids nor in cases of amniotic fluids from pregnancies with other malformations. Analysis of D2 in amniotic fluids may thus have a future role in the antenatal diagnosis of fetal neural tube defects.     

Prenatal screening and diagnosis of neural tube defects

This review article discusses prenatal screening and diagnosis of neural tube defects (NTD). High detection rates occur in countries operating ultrasound screening programmes because classical two-dimensional ultrasound cranial signs (lemon shaped head, banana cerebellum, ventriculomegaly) are important diagnostic clues to the presence of spina bifida. Careful evaluation of both the spine and a search for other abnormalities is warranted. Important prognostic information for spina bifida relates to the lesion level, with a “watershed” between L3 and L4 marking a very high chance of being wheelchair bound with the higher lesions. Three-dimensional ultrasound using multiplanar views can achieve diagnostic accuracy within one vertebral body in around 80% of patients. There are high rates of pregnancy termination for spina bifida in many European countries, but the use of new imagining techniques allow better prediction of outcome, and consequently a refinement of prenatal counselling. Copyright © 2009 John Wiley & Sons, Ltd.     

S-100 protein and neuron-specific enolase in amniotic fluid as markers of abdominal wall and neural tube defects in the fetus

The aim of this study was to determine whether there is increased leakage of neuron-specific enolase (NSE) and S-100 protein into amniotic fluid in pregnancies with neural tube defects, since both these proteins are produced by neural tissue, and to compare the value of these substances for detecting such defects with that of the more conventional techniques of alpha-fetoprotein (AFP) and acetylcholinesterase (AChE) gel electrophoresis. Amniotic samples from 25 mid-pregnancies (15–17 weeks' gestation) with neural tube defects (14 with open spina bifida and 11 with anencephaly) and from seven mid-pregnancies with abdominal wall defects were compared with a control material consisting of 80 amniotic fluid samples from 80 consecutive mid-pregnancy amniocenteses, with normal karyotypes and AFP concentrations. All of the above cases of abnormalities were primarily detected through increased AFP levels in the amniotic fluid. Amniotic fluid samples from 13 pregnancies with fetuses with autosomal chromosomal abnormalities and seven amniotic fluid samples contaminated with blood were also included in the investigation. It is concluded from the results that the conventional AFP assay combined with AChE gel electrophoresis is the best method for screening amniotic fluid for neural tube defects and defects of the abdominal wall. Neither NSE nor S-100 assay alone proved to be superior for the detection of these cases in mid-trimester amniotic fluid. The S-100 assay, however, could give additional information in cases where AChE gel electrophoresis is not decisive; for example, in samples contaminated with blood.     

Prenatal screening for Down syndrome and neural tube defects in twin pregnancies

Prenatal screening and diagnosis in a twin pregnancy is not straightforward. Once a twin pregnancy has been identified, women and their partners need time to consider the implications and decide whether they wish the pregnancy to be screened for Down syndrome or neural tube defects. We discuss here how multiple marker screening for Down syndrome and alpha-fetoprotein screening for neural tube defects can be carried out, given that this is the parents' chosen option and that the health professionals involved are capable of performing a diagnosis and selective feticide, should this arise. Copyright © 2005 John Wiley & Sons, Ltd.     

Early prenatal sonographic appearance of rare thoraco-abdominal eventration

Fetal ventral wall malformations may be diagnosed prenatally with ultrasound. These include omphalocele, gastroschisis, or even thoracic defects with or without ectopia cordis. It is important whenever such a defect is found to carefully define the full extent of the lesion prior to parental counselling. Described and illustrated here is the prenatal diagnosis with real-time ultrasound at 17 weeks gestation of a rare thoraco-abdominal ventral wall defect including omphalocele, bifid sternum, diaphragmatic aplasia, and pericardial aplasia with incomplete ectopia cordis. The technique is described and the importance of the complete, accurate delineation of anatomic malformations is emphasized.     

Postnatal management and outcome for neural tube defects including spina bifida and encephalocoeles

The incidence of neural tube defects (NTDs) has declined in recent decades, however myelomeningocele and encephalocele still represent one of the commoner prenatally diagnosed congenital malformations. Improved perinatal and post natal care mean that the mortality associated with these conditions has also fallen. Advances in the multidisciplinary management of children with myelomeningocele have led to significant improvements in functional outcome for many with this condition. However, there remains a substantial population of patients born with NTDs whose life expectancy is substantially reduced and who suffer significant cognitive and physical disability remaining wholly or partially dependant on the care of others into adult life. This article aims to outline the contemporary early management of these conditions and examine the prospects for functional outcome where possible, attempting to show how early anatomical features of these conditions can help predict where, along the wide spectrum of outcome, a given individual may lie. Copyright © 2009 John Wiley & Sons, Ltd.     

Maternal environment and the expression of murine neural tube defects

The role that genetic and environmental factors play in triggering neural tube defects in the mouse mutant curly-tail (ct) were investigated by transplanting curly-tail blastocysts into the uterus of either curly-tail females or females of an unrelated A strain with a low natural incidence of abnormalities of the neural tube. The percentages of fetuses with neural tube defects were found to be similar in both groups. These results show that in curly-tail mice exencephaly and spina bifida are manifested independently of the maternal environment.     

Prenatally diagnosed developmental abnormalities of the central nervous system and genetic syndromes: A practical review

Developmental brain abnormalities are complex and can be difficult to diagnose by prenatal imaging because of the ongoing growth and development of the brain throughout pregnancy and the limitations of ultrasound, often requiring fetal magnetic resonance imaging as an additional tool. As for all major structural congenital anomalies, amniocentesis with chromosomal microarray and a karyotype is the first-line recommended test for the genetic work-up of prenatally diagnosed central nervous system (CNS) abnormalities. Many CNS defects, especially neuronal migration defects affecting the cerebral and cerebellar cortex, are caused by single-gene mutations in a large number of different genes. Early data suggest that prenatal diagnostic exome sequencing for fetal CNS defects will have a high diagnostic yield, but interpretation of sequencing results can be complex. Yet a genetic diagnosis is important for prognosis prediction and recurrence risk counseling. The evaluation and management of such patients is best done in a multidisciplinary team approach. Here, we review general principles of the genetic work-up for fetuses with CNS defects and review categories of genetic causes of prenatally diagnosed CNS phenotypes.     

Evaluation of prenatal diagnosis of limb reduction defects by a registry of congenital anomalies

Prenatal diagnosis performed by ultrasound scan is now a routine part of antenatal care in our region. How many fetal anomalies are actually detected by this procedure? We have used our registry of congenital malformations to answer this question regarding limb reduction defects (LRDs). The mean time of detection of LRDs was 26 weeks of pregnancy (range 16–32 weeks). The sensitivity of prenatal diagnosis of LRDs by ultrasonographic examination was much lower for isolated malformations (fetuses with only one anomaly) than for multiply malformed children with LRDs, 4·0 and 18·2 per cent, respectively. For all cases of LRDs, the percentage of prenatal detection was 11·5. Termination of pregnancy was performed in 6·7 per cent of the cases.     

Second trimester prenatal diagnosis of the Jarcho-Levin syndrome

The Jarche–Levin syndrome (spondylothoracic dysostosis) is a rare autosomal recessive disorder characterized by a short neck, short trunk and a constricted thorax due to multiple rib and vertebral defects; other visceral malformations are occasionally present. Most cases die in infancy due to respiratory failure. In this report we describe two cases in one family from the United Kingdom. Prenatal diagnosis by ultrasound examination during the second trimester was successfully accomplished in the second case.     

First-trimester sonographic diagnosis of distal urethral atresia with megalourethra in VACTERL association

Congenital megalourethra is a rare disorder. We present an early case diagnosed in the first trimester. Prenatal ultrasound showed a megalourethra with a normal fetal bladder, hyperechogenic cystic right kidney and single umbilical artery. After termination of pregnancy, necropsy confirmed all sonographic findings and revealed other malformations (spina bifida occulta, anal atresia, tracheo-oesophageal fistula, brachydactylia) resulting in the diagnosis of VACTERL association. The prenatal diagnostician should seek histological examination firstly to confirm his findings and secondly to avoid missing associations and inherited malformations. Copyright © 2002 John Wiley & Sons, Ltd.     

Post-natal investigations: management and prognosis for fetuses with CNS anomalies identified in utero excluding neurosurgical problems

The suspicion of an abnormality of the central nervous (CNS) system raises difficult questions for the clinician and the family and will inevitably lead to considerable anxiety. These questions include what it means for the child's future, whether it can be treated and whether it will happen again in subsequent pregnancies. For many disorders accurate prenatal diagnosis remains elusive, as even with fetal magnetic resonance imaging (MRI), early recognition and characterisation are simply not possible because of the immature state of brain development at that stage of pregnancy. The natural history of many prenatally diagnosed CNS disorders remains to be elucidated which means that an accurate prognosis cannot be given in all cases. We review the current state of knowledge regarding the investigation, management and prognosis of the most common and important CNS malformations. We also discuss the post-natal management of these conditions both in the neonate and subsequent pregnancies for the families. Copyright © 2009 John Wiley & Sons, Ltd.     

The impact of screening for open neural tube defects in England and Wales

Using information derived from the voluntary system of notification of congenital malformations in England and Wales, the birth prevalence of anencephaly and spina bifida was estimated to have declined by 80 per cent from 31.5 to 6.2 per 10 000 between 1964–1972 and 1985. Over the same period, notified terminations of pregnancy with a suspected fetal central nervous system abnormality increased from less than 1 per cent to 56 per cent of neural tube defect births and central nervous system terminations combined, accounting for 31 per cent of the decline in births. Routinely collected national statistics provide a method for monitoring the impact of screening for open neural tube defects. However because they are incomplete and lack detail an alternative method of monitoring is needed. This paper includes an outline of such a method, together with the results of a pilot study designed to assess the feasibility of monitoring screening in the Oxford Region.     

Fetal cardiac scanning today

The ability to examine the structure of the fetal heart in real-time started over 30 years ago now. The field has seen very great advances since then, both in terms of technical improvements in ultrasound equipment and in dissemination of operator skills. A great deal has been learnt about normal cardiac function in the human fetus throughout gestation and how it is affected by pathologies of pregnancy. There is increasing recognition of abnormal heart structure during routine obstetric scanning, allowing referral for specialist diagnosis and counselling. It is now possible to make accurate diagnosis of cardiac malformations as early as 12 weeks of gestation. Early diagnosis of a major cardiac malformation in the fetus can provide the parents with a comprehensive prognosis, enabling them to make the most informed choice about the management of the pregnancy. Copyright © 2010 John Wiley & Sons, Ltd.     

Neural tube defects in trisomy 18

In a retrospective survey, the incidence of neural tube defects in liveborn trimsomy 18 was found to be 6·2 per cent. Based on these data one would expect to find trisomy 18 in 1 of the 117 patients with myeloidysplasia; the incidence of trisomy 18 in dysraphic fetuses would be anticipated to be higher. These observations underscore the need for amniocentesis karyotyping of fetuses with neural tube defects, and the importance of careful examination of infants born with neural tube defects.     

Six years' experience with rapid karyotyping in prenatal diagnosis: Correlations between phenotype detected by ultrasound and fetal karyotype

From September 1985 to March 1992, 804 amniotic fluid samples from 64 different diagnostic centres of the Federal Republic of Germany were sent to our laboratory exclusively for rapid karyotyping. The average time needed for notification of the analysed karyotype was 4·65 days when the ‘pipette method’ was used for chromosome harvesting and 5·97 days when the ‘in situ’ technique was used. The overall incidence of chromosome aberrations was 15·3 per cent. Data are presented about the likelihood of abnormal ultrasound findings being caused by chromosome aberrations. These findings include polyhydramnios, oligohydramnios, growth retardation, fetal effusions, neural tube defects, craniofacial defects, heart defects, gastroschisis and omphalocele, gastrointestinal tract defects, urinogenital defects, and limb defects. In future, such data need to contain larger numbers of cases for each week of gestation. This will improve the risk evaluation for each case with abnormal ultrasound findings, which should lead to better management during pregnancy, delivery, and postnatal care for those who require rapid karyotyping.     

The early diagnosis of neural tube defects

The sonographic diagnosis of fetal neural tube defects (NTDs) has been enhanced by the recognition of associated brain and skull anomalies. Previous reports have found these anomalies to be accurate in predicting spina bifida after 16 weeks' gestation, and an inverse correlation was suggested between the presence of these sonographic markers and gestational age. Therefore, we assumed that early second-trimester sonography would be at least as accurate as that performed after 16 weeks' gestation. To examine this hypothesis, we looked for the presence of these cranial sonographic markers suggestive of open NTDs in 8011 low-risk cases, using transvaginal sonography (TVS), between the 12th and 17th week of gestation (menstrual age). Fetal NTDs were identified in ten cases (l.25%o). The NTDs were cervico-cranial in three, lumbo-sacral in six, and thoracal in one of the ten cases. None of the seven cases examined was dyskaryotic. Cerebellar dysmorphism, ‘banana’ sign, cerebellar absence, and hypoplasia were detected in all the low NTDs, usually before the detection of the spinal lesion. All the sonographically diagnosed malformations were confirmed by post-abortal examination except in one case, where the patient decided to continue the pregnancy and refused follow-up. We therefore conclude that transvaginal sonographic examination of the fetal skull before the 17th week of gestation is an accurate method for the detection of low NTDs.     

The value of sonographic diagnosis of fetal malformations: Different results between indication-based and screening-based investigations

The advantages of a routine screening or indication-based ultrasound investigation during pregnancy are still under debate. This is the first study where both methods are compared in two different time periods. More malformations were diagnosed before the 24th week of gestation by means of screening-based than indication-based investigation (18 per cent vs. 5 per cent, P<0·005), and before 28 weeks in 26 per cent compared with 15 per cent respectively (P<0·01). Twenty-six per cent of all malformations were detected by means of screening-based investigations as opposed to 15 per cent by means of indication-based scans. Primary fetal malformations were also diagnosed much earlier (25 weeks vs. 30 weeks). Except for the fetal head, the detection rate of malformations was higher in nearly all other body regions of the fetus in the screening-based investigation. The most important advantage of a screening-based ultrasound investigation during pregnancy is to detect the malformations early enough in pregnancy for possible intrauterine treatment or to offer safe termination of pregnancy for the woman, at least for those anomalies that are lethal or significantly handicapping.