Early diagnosis of spina bifida: the value of cranial ultrasound markers

Ultrasonography plays an integral part in the prenatal diagnosis of neural tube defects. However, experienced sonographers with careful evaluation are successful in accurately diagnosing spina bifida only 80-90% of the time. This study was conducted to evaluate the accuracy and reliability of certain cranial ultrasound markers--the "lemon sign," cerebellar abnormalities, microcephaly, and ventriculomegaly--in facilitating the diagnosis of spina bifida in patients referred for prenatal diagnosis. Open spina bifida was diagnosed in 24 of 44 fetuses found to have neural tube defects. The lemon sign and cerebellar abnormalities were identified in all 16 fetuses in whom the diagnosis of spina bifida was made between 16-24 weeks' gestation. In four of these fetuses, the lemon sign and cerebellar abnormalities were noted 1-2 weeks before the spinal defect was identified. Microcephaly was present in 69% and ventriculomegaly in 63% of the cases. In the eight cases diagnosed after 24 weeks' gestation, the lemon sign was less reliable, being noted in only 25% of the fetuses. Ventriculomegaly increased in frequency to 75% and cerebellar abnormalities and microcephaly were present in all. Our findings indicate that these cranial ultrasound markers are extremely reliable for the early diagnosis of spina bifida; their identification should alert ultrasonographers at all skill levels to the possibility of open spina bifida.     

New ultrasonographic criteria for the prenatal diagnosis of Chiari type 2 malformation

BACKGROUND: During prenatal ultrasonography, characteristic malformations including the lemon sign, the banana sign, and obliteration of the cisterna magna are widely used for diagnosis of Chiari type 2 malformation (Arnold Chiari malformation). However, these signs are often obscured by 25 weeks' gestation. Here, we report an investigation of ultrasonographic markers of Chiari type 2 malformation for diagnosis after 24 weeks' gestation. METHODS: Twenty-two cases of 24-37 weeks' gestation referred as fetal ventriculomegaly were analyzed prospectively. Fetuses were examined with ultrasonography by axial section of the head to detect conventional signs, and then by coronary section of the posterior horn of the lateral ventricle to detect two prospective new signs: bilateral downward-triangle shape (triangle sign) and quadrilateral angular shape (square sign). RESULTS: From the axial sections, three cases were diagnosed with holoprosencephaly, but the remaining 19 cases did not show the lemon sign. In the coronary sections, the eight cases that showed the triangle sign were associated with open spina bifida at the lower vertebral site. The four cases that displayed the square sign showed upper spinal lesions. Chiari type 2 malformation was suspected in these 12 cases. Four of the other seven cases were suspected to be agenesis of the corpus callosum, and the remaining three were normal. All ultrasonographic findings were consistent with the subsequent MRI and postpartum definitive diagnoses. CONCLUSIONS: At 24 weeks' gestation or later, Chiari type 2 malformation can be precisely and efficiently diagnosed by two new characteristics detected during ultrasonography: triangular shape and quadrilateral angular shape.     

Comparison of six sonographic signs in the prenatal diagnosis of spina bifida

AIMS: To compare the diagnostic accuracy of sonographic signs that may be looked for in fetuses with spina bifida. METHODS: Forty-nine fetuses affected by spina bifida were enrolled, at a gestational age of 18-28 weeks. The following sonographic signs were looked for: "lemon" sign, small cerebellum, effaced cisterna magna, small posterior fossa, ventriculomegaly and direct visualization of a spinal defect. RESULTS: The "lemon" sign was present in 53%, a small cerebellum in 96%, an effaced cisterna magna in 93%, a small posterior fossa in 96%. Ventriculomegaly was present in 40/49 (81%) cases and was severe in 20 fetuses and borderline in the remaining 20. The spinal defect was missed in one fetus presenting the cerebellar and posterior fossa signs. In two fetuses, the myelomeningocele was present without cranial signs of Chiari II malformation and in both cases the defect was covered by intact skin. CONCLUSIONS: Our results confirm the usefulness of evaluation of the posterior fossa in the diagnosis of spina bifida, particularly in cases of small spinal defects that may be missed at ultrasound. Conversely, myelomeningocele covered by intact skin was not associated with the cranial signs of Chiari II malformation.     

Fetal lateral cerebral ventriculomegaly: associated malformations and chromosomal defects

In 267 consecutive cases of fetal lateral cerebral ventriculomegaly, additional fetal malformations were detected by ultrasonography in 209 (78%) of the cases. On the basis of the ultrasound findings, the patients were subdivided into three groups: (i) isolated ventriculomegaly (n = 58), (ii) ventriculomegaly and open spina bifida only (n = 172), and (iii) ventriculomegaly and other malformations (n = 37) with or without spina bifida. Antenatal karyotyping was performed in 64 cases from groups (i) and (iii), and 11 (18%) of the fetuses had chromosomal abnormalities. The incidence of chromosomal abnormalities was strongly related to the presence of multisystem malformations. Thus, only 3% of fetuses with isolated ventriculomegaly as opposed to 36% of those with additional malformations had chromosomal defects. Furthermore, the degree of ventriculomegaly in the chromosomally abnormal fetuses was relatively mild. In the chromosomally normal fetuses, mild, static ventriculomegaly was associated with apparently normal subsequent mental development.     

Spina bifida--retrospective analysis of fetuses diagnosed in the department of obstetrics & gynecology of the postgraduate center of medical education between 1997 & 2004

OBJECTIVES: Our objectives were to determine the kind and localisation of the spina bifida and if open neural tube defects are associated with other anomalies and ventriculomegaly. DESIGN: We retrospectively studied ultrasound reports of the fetuses with open neural tube defects. MATERIALS AND METHODS: We analyzed 178 cases diagnosed during the last seven years in our center. All fetuses underwent a detailed ultrasonographic survey. We also analyzed gestational age at the first examination. RESULTS: Associated anomalies were detected in 78 cases, in 100 cases spina bifida was the only anomaly. Lumbo-sacral and sacral localisation was presented in 88% of spina bifida not related with other anomalies and in 50% of cases with associated anomalies. In 94.4% of cases the malformation was myelomeningocoele. Ventriculomegaly was present in 89.1%. The median gestational age at the first examination was 26 weeks. Before 24 week only 34.3% of examinations was done. CONCLUSIONS: In fetuses with spina bifida detailed ultrasonographic survey should be performed. Measurement of the lateral ventricules should be done in each examination. Furthermore patient with fetus with spina bifida should be diagnosed as early as possible in the referral center.     

Maternal serum alpha-fetoprotein screening for open neural tube defects in twin pregnancies.

Data on maternal serum alpha-fetoprotein (AFP) levels at 13-24 weeks' gestation in 46 twin pregnancies with open neural tube defects (22 with anencephaly, 24 with open spina bifida) and 169 unaffected twins were used to estimate the detection and false-positive rates associated with different cut-off levels. Using the conventional cut-off level of 2.5 multiples of the median (MoM) for unaffected singleton pregnancies of the same gestation and laboratory, the detection rate in twins was 99 per cent for anencephaly and 89 per cent for open spina bifida, with a false-positive rate of 30 per cent. Using a 5.0 MoM cut-off level to maintain a similar false-positive rate to that found among singleton pregnancies at 16-18 weeks' gestation (about 3 per cent), the detection rate was 83 per cent for anencephaly and 39 per cent for open spina bifida. Estimates are provided of the odds of having an affected twin pregnancy given a positive AFP result as well as the odds for individual women with a raised AFP level.     

Ultrasonographic assessment of gestational age with the distal femoral and proximal tibial ossification centers in the third trimester

A prospective sonographic evaluation of the distal femoral and proximal tibial epiphyseal ossification centers in 228 normal pregnant women was carried out from 28 to 40 weeks' gestation. The mean gestational age at which the distal femoral epiphysis and proximal tibial epiphysis were imaged was 34 and 38 weeks, respectively. The distal femoral epiphysis was not identifiable before 28 weeks but was observed in 72% of fetuses at 33 weeks and in 94% of fetuses at 34 weeks' gestation. The presence of a distal femoral epiphysis measuring 1 or 2 mm was associated with a gestational age of greater than 33 weeks in 87.0% of fetuses, whereas a distal femoral epiphysis measuring greater than or equal to 3 mm was associated with a gestational age greater than 37 weeks in 85% of fetuses. The proximal tibial epiphysis, which was absent before 34 weeks' gestation, was observed in 56% of fetuses at 36 weeks, in 80% of fetuses at 37 weeks, and in 100% of fetuses at 39 weeks of gestation. The presence of a proximal tibial epiphysis of 1 or 2 mm was associated with a gestational age of greater than 36 weeks in 88% of fetuses, whereas a proximal tibial epiphysis greater than or equal to 3 mm was associated with a gestational age of greater than 38 weeks in 94% of fetuses. The sonographic evaluation of distal femoral epiphysis/proximal tibial epiphysis can be used as independent markers for estimation of gestational age during the third trimester, a period in which standard fetal biometric estimates of gestational age are least accurate.     

Second-trimester levels of maternal serum unconjugated oestriol and human chorionic gonadotropin in pregnancies affected by fetal anencephaly and open spina bifida

Unconjugated oestriol (uE3) and human chorionic gonadotropin (hCG) levels were determined in second-trimester maternal serum (MS) samples from 21 pregnancies associated with fetal anencephaly and 15 pregnancies associated with fetal open spina bifida. Each measurement was expressed as a multiple of the median (MoM) for unaffected pregnancies for each completed week of gestation. In pregnancies associated with anencephaly, the median value for MSuE3 was very low (0.17 MoM, range less than 0.12-0.33 MoM), suggesting a functional defect in the fetal adrenal prior to 20 weeks' gestation; the median value for MShCG was also low (0.73 MoM), although not to the same extent as for MSuE3. A biological explanation for the hCG result is not apparent. In pregnancies associated with open spina bifida, the MSuE3 and MShCG values were unremarkable, consistent with a lack of involvement of these open fetal defects in the synthesis and secretion of uE3 and hCG.     

Can prenatal ultrasound findings predict ambulatory status in fetuses with open spina bifida?

OBJECTIVE: To determine whether prenatal sonographic findings in fetuses with open spina bifida can predict ambulatory potential and the need for postnatal shunt placement. STUDY DESIGN: Ongoing pregnancies complicated by isolated open spina bifida from January 1996 to March 2000 were studied retrospectively. Static images and reports generated every 3-4 weeks from diagnosis until delivery were reviewed for lesion level and type, ventricular width, and lower extremity appearance. Operative summaries as well as neonatal and pediatric charts were reviewed. Ambulatory was defined in infants > or =2 years old as walking with or without appliances. In those <2 years of age, ambulatory was defined as at least 4/5 lower extremity muscle strength. RESULTS: Thirty-three cases of isolated open spina bifida were identified. Lower (more caudal) lesion levels and smaller ventricular size were associated with ambulatory status in univariate analyses (P <.001, P =.003, respectively). No infant with a thoracic lesion was ambulatory (n = 11); all had ventriculomegaly diagnosed prenatally and all required shunt placement. In contrast, all infants with L4-sacral lesions (n = 10) were ambulatory, and 60% had ventriculomegaly diagnosed prenatally. Of patients with L1-L3 lesions (n = 12), 50% were ambulatory. In this group, ambulatory potential could not be determined by the presence of ventriculomegaly, ventricular size, or the presence of club foot. In the entire cohort, no infant with a myeloschisis was ambulatory, and all infants except one with a sacral lesion required postnatal shunt placement. CONCLUSIONS: Sonographic determination of lesion level and type is useful in predicting the ambulatory potential of fetuses with open spina bifida.     

Amniotic fluid acetylcholinesterase measurement in the prenatal diagnosis of open neural tube defects. Second report of the Collaborative Acetylcholinesterase Study

Seventeen centres from Australia, Britain, France, and the United States collaborated in a study to compare amniotic fluid acetylcholinesterase (AChE) determination by gel electrophoresis and amniotic fluid alpha-fetoprotein (AFP) measurement as diagnostic tests for open neural tube defects. The study was based on 32,642 women with singleton pregnancies (including 428 with open spina bifida and 238 with anencephaly) who had an amniocentesis at 13-24 weeks' gestation. The AChE test yielded a detection rate for open spina bifida of 99 per cent (95 per cent confidence interval 98-100 per cent), 98 per cent for anencephaly (95 per cent confidence interval 96-100 per cent), and a false-positive rate of 0.34 per cent (95 per cent confidence interval 0.28-0.40 per cent) excluding miscarriages, intrauterine death, and serious fetal abnormalities. The false-positive rate was 0.30 per cent among the 13 centres that used a specific AChE inhibitor in the test. Comparable rates for the AFP test were less favourable. (For example, the open spina bifida detection rate was 90 per cent and the false-positive rate was 0.46 per cent using the cut-off levels specified in the U.K. Collaborative AFP Study.) The AChE false-positive rate was lower in samples that were not bloodstained (0.16 per cent) than in those that were (2.4 per cent). It was higher in women who had an amniocentesis on account of a raised maternal serum AFP level (0.56 per cent) than in those who had one for other reasons (0.29 per cent). The best results were obtained by a combination of the two tests, an effective and economical policy being to perform the AFP measurement on all amniotic fluid samples and an AChE test on samples with AFP levels greater than or equal to 2.0 multiples of the normal median (about 5 per cent of all samples). Using this policy, the open spina bifida detection rate was 96 per cent and the false-positive rate was 0.14 per cent (0.06 per cent for samples that were not bloodstained and 1.2 per cent for those that were; 0.40 per cent for women with raised serum AFP levels and 0.09 per cent for other women). This policy offers a useful improvement to the prenatal diagnosis of open spina bifida.     

Absent intracranial translucency--new ultrasound marker for spina bifida at 11-13+6 weeks of gestation

Spina bifida is the most common abnormality of the fetal central nervous system. Prenatal diagnosis is usually made by ultrasound in the second or third trimester of pregnancy. However, first trimester detection of spina bifida is still a challenge. A new indirect ultrasound sign of open spina bifida between 11-13 6 weeks of gestation (w.g.) has been recently described. The marker is associated with an absence of intracranial translucency (IT) in the mid-sagittal plane. We present a case report of an open spina bifida detected at 13+2 weeks of gestation with an absent IT. The main ultrasound characteristics of normal and absent IT are described. In addition, the diagnostic role of three-dimensional (3D) transvaginal ultrasound is also discussed.     

Second-trimester diagnosis of complete trisomy 9 associated with abnormal maternal serum screen results, open sacral spina bifida and congenital diaphragmatic hernia, and review of the literature

OBJECTIVES: To present the prenatal diagnosis of complete trisomy 9 and to review the literature CASE: A 25-year-old primigravida woman was referred for amniocentesis at 19 weeks' gestation because of abnormal maternal screen results showing an elevated maternal serum alpha-fetoprotein (MSAFP) level and a low maternal serum free beta-human chorionic gonadotrophin (MSfreebeta-hCG) level. RESULTS: Genetic amniocentesis revealed a karyotype of 47,XX,+9 in the amniocytes and an elevated amniotic fluid AFP level. Ultrasonography demonstrated intrauterine growth restriction, left congenital diaphragmatic hernia, fetal ascites, a sacral spina bifida, a horseshoe kidney, and absence of amniotic fluid. Ultrafast magnetic resonance imaging scans further depicted detailed anatomical configurations of the major congenital malformations. The pregnancy was terminated subsequently. The proband postnatally manifested characteristic facial dysmorphism, limb deformities, and an open sacral spina bifida with myelomeningocele. Cytogenetic analysis of the skin fibroblasts revealed a karyotype of 47,XX,+9. Molecular studies of various uncultured fetal tissues using microsatellite markers confirmed a diagnosis of complete trisomy 9 resulting from a meiotic I nondisjunction error of maternal origin. CONCLUSION: Complete trisomy 9 can be identified prenatally with advanced maternal age, sonographically detected fetal structural abnormalities, and abnormal maternal serum screen results. Fetuses with complete trisomy 9 may be associated with congenital diaphragmatic hernia, an open sacral spina bifida, elevated MSAFP, and low MSfreebeta-hCG. We suggest detailed prenatal imaging investigations and genetic analyses of multiple fetal tissues when a prenatal diagnosis of trisomy 9 is made.     

Ultrasonic evaluation of fetal body movements over twenty-four hours in the human fetus at twenty-four to twenty-eight weeks' gestation

Continuous 24-hour observations of fetal gross body movements were performed in 20 women between 24 and 28 weeks of gestation by means of real-time ultrasound examination. At 24 to 26 weeks, fetuses moved 13.1% +/- 0.3% of the time, which was not significantly different from the incidence of 12.4% +/- 0.8% at 26 to 28 weeks' gestation. An examination of the number of movements per hour demonstrated that fetuses at 24 to 26 weeks' gestation moved on the average 53.4 +/- 1.6 times/hr, which was significantly different from 26 to 28 weeks' gestation when fetuses made 46.2 +/- 1.4 movements/hr. When examined on an hourly basis, fetuses in both age groups demonstrated a significant increase in the number of movements overnight from 2300 to 0800 hours. Intermovement intervals were also examined. Ninety-nine percent of intervals less than 6 minutes in both age groups contained movement. The longest observed quiescent interval was 24 minutes in both age groups. These data suggest that the incidence of fetal body movements is different than that observed in fetuses during the last 10 weeks of gestation. Fetuses at 24 to 28 weeks' gestation exhibit a diurnal pattern of fetal movement and move more frequently than do older fetuses. However, these movements are of a sporadic nature and relatively short duration. Thus these fetuses do not appear to have well-defined periods of rest and activity.     

Maternal serum alpha-fetoprotein in fetal neural tube and abdominal wall defects at 10 to 14 weeks of gestation

Maternal serum alpha-fetoprotein concentration was determined in nine pregnancies with fetal anencephaly, seven with exomphalos containing liver, two with spina bifida and 100 normal controls at 10 to 14 weeks of gestation. The median alpha-fetoprotein in the group with fetal anencephaly and exomphalos was significantly higher than in normal fetuses but the sensitivity of this test is likely to be only about 30% for a false positive rate of 5%.     

Sonographically estimated fetal weight percentile as a predictor of preterm delivery

OBJECTIVE: To evaluate the association between relative growth restriction and preterm birth. STUDY METHODS: Pregnant women referred for sonographic fetal weight assessments between 24 and 34 weeks of gestation were studied for gestational age at delivery. If a patient underwent more than one study, only the last one was considered. Patients with delivery induced iatrogenically or with abnormal growth patterns due to known pathology, such as maternal diabetes or fetal congenital anomaly, were excluded. A gestational age of 37 weeks or less was considered preterm and a gestational age of more than 37 weeks at delivery was considered term. Fetal weight estimation was obtained by Hadlock's formula based on biparietal diameter, femur length, and head and abdominal circumferences. The estimated fetal weight percentile was computed according to William's tables. Mean gestational age and incidence of preterm delivery for each fetal weight percentile between 1 and 100, at increments of 10, were calculated. The mean estimated fetal weight percentile, biparietal diameter, femur length, head circumferences and abdominal circumferences of preterm and term patients were compared. RESULTS: Among the 419 patients who met the inclusion criteria, duration of gestation was significantly shorter in fetuses with low estimated fetal weight percentile. The risk of preterm birth was 49% in fetuses of less than the 40th birth-weight percentile compared with a risk of 20% in fetuses of more than the 40th birth-weight percentile, representing a relative risk of 2.3. Individual fetal measurements indicate a head-sparing effect in the preterm group. CONCLUSION: Sonographically estimated fetal weight percentile measured between 24 and 34 weeks' gestation may be used as an additional and individually pertinent predictor of preterm birth.     

Prenatal diagnosis in pregnancies at risk for Joubert syndrome by ultrasound and MRI

OBJECTIVES: To describe the prenatal imaging findings in fetuses at risk for Joubert syndrome (JS), review the literature and propose a protocol for prenatal diagnosis of JS using ultrasound and MRI. METHODS: We reviewed prenatal ultrasound and fetal MRI studies in two pregnancies at 25% recurrence risk for JS and correlated these findings with gross neuropathology in one affected fetus. RESULTS: While abnormalities such as occipital encephalocele or enlarged cisterna magna have been identified before mid-trimester, the definitive diagnosis of JS, based on core cerebellar findings, has only been possible after 17 weeks' gestation. CONCLUSIONS: With longitudinal monitoring, it is possible to diagnose JS in at-risk pregnancies before 24 weeks' gestation. On the basis of our data and review of the literature, we propose a protocol for monitoring pregnancies at risk for JS, utilizing serial ultrasounds combined with fetal MRI at 20-22 weeks' gestation to maximize the accuracy of prenatal diagnosis.     

Ratio of immunochemically determined amniotic fluid acetylcholinesterase to butyrylcholinesterase in the differential diagnosis of fetal abnormalities.

A total of 111 amniotic fluid samples, clear or blood stained, with elevated levels of alpha-fetoprotein and acetylcholinesterase was analysed by immunoassays specific for acetylcholinesterase and butyrylcholinesterase and the acetylcholinesterase/butyrylcholinesterase-ratios determined. Samples from 40 pregnancies associated with anencephaly, 47 pregnancies associated with open spina bifida or encephalocele and six pregnancies with fetal intrauterine death or miscarriage all had ratios of greater than 0.14. All 11 pregnancies with fetal ventral wall defects had ratios less than 0.14 as had four pregnancies with normal outcome and elevated levels of alpha-fetoprotein and acetylcholinesterase. Three fetuses with both open spina bifida and ventral wall defects were associated with ratios above 0.14. These results suggest that immunochemical determination of acetylcholinesterase and butyrylcholinesterase can be used to distinguish pregnancies complicated by anencephaly, open spina bifida, encephalocele and miscarriage from those with ventral wall defects and samples with false positive elevated levels of alpha-fetoprotein and acetylcholinesterase. The procedure is accurate and simple to carry out and well suited to routine use in a clinical chemistry laboratory.     

Preterm and term fetal cardiac and movement responses to vibratory acoustic stimulation

To assess fetal response to vibratory acoustic stimulation, 24 preterm (group A; less than 36 weeks' gestation) and 30 term (group B; greater than or equal to 36 weeks' gestation) pregnancies were studied. Study variables were perceived fetal movement, fetal heart rate, and fetal heart rate pattern. Observer- and patient-perceived fetal movement responses were noted in most cases but were slightly more common in term patients (group A: + fetal movement, patient 87.5%/observer 87.5%) group B: + fetal movement, patient 96.7%/observer 90%). Baseline changes in fetal heart rate (greater than or equal to 10 beats/min) were observed in 46% of preterm fetuses and 70% of term fetuses. Tachycardia (fetal heart rate greater than 160 beats/min) was a common finding in both groups. In group A, tachycardia after vibratory acoustic stimulation persisted more than 1 minute in 29.2% and more than 5 minutes in 12.5% of patients. In group B tachycardia beyond 1 and 5 minutes was noted in 73.3% and 50% of patients, respectively. A significant shift to "awake" fetal heart rate patterns occurred in both groups; 29% to 79% was noted in group A (p less than 0.001) and 46.7% to 90% in group B (p less than 0.001). When vibratory acoustic stimulation was used, the high occurrence of increased baseline, tachycardia, and emergence of unusual fetal heart rate patterns must be recognized to adequately interpret fetal heart rate tracings.     

Obstetrician-gynecologists' practice and knowledge regarding spina bifida

The purpose was to assess practicing obstetrician-gynecologists' knowledge about the prenatal diagnosis and postnatal prognosis of spina bifida. Written questionnaires designed to assess practicing obstetrician-gynecologists' knowledge of spina bifida were mailed to 1000 randomly selected American College of Obstetricians and Gynecologists Fellows. More than 50% did not identify many of the sonographic features indicative of an open neural tube defect in the fetus and more than one third overestimated the risks of stillbirth, whereas more than two thirds overestimated the risk for premature delivery in a pregnancy complicated by fetal spina bifida. Just more than 50% correctly estimated the 1-year survival rate and just less than 50% correctly estimated survival at 6 years. Sixty-six percent overestimated the incidence of mental retardation associated with spina bifida. Maternal-fetal medicine specialists returning the survey exhibited a much better understanding of the prenatal issues and prognostic and outcome factors related to spina bifida. There are gaps in obstetrician-gynecologists' knowledge about the diagnostic features of and prognosis for fetal spina bifida. It is important for them to take advantage of continuing medical education opportunities to learn more about the management of pregnancies complicated by fetal spina bifida and about the prognosis for affected individuals.     

S-100 protein in amniotic fluid of anencephalic fetuses

S-100 protein, which is found essentially in the astrocytes of the nervous system, was assayed in amniotic fluids by Particle Counting ImmunoAssay. It was present in 19 cases of anencephaly out of 26, in 1 case of open spina bifida out of 5 and in each of the 4 cases of fetal death, whereas it was not detected in the 48 control amniotic fluids collected between the 16th and the 35th week of gestation. Thirty-one amniotic fluids from fetuses with other congenital malformations were devoid of detectable S-100. The presence of S-100 in amniotic fluid of anencephalic fetuses can presumably be considered as a biological sign of necrosis of the exencephalic brain and seems specific to damage of the central nervous system accompanied by neural tube defect.