Fetal biometry in the Brachmann-de Lange syndrome.

The Brachmann-de Lange syndrome (BDLS) is diagnosed in children on the basis of a distinctive clinical phenotype which includes retarded physical growth. Because there are no genetic or biochemical tests at present, the antenatal detection of the syndrome may depend upon identification of some aspect of the phenotype in the fetus using ultrasound imaging. We studied the growth of 23 subsequently diagnosed fetuses with the BDLS using standard biometric parameters defined by prenatal ultrasound imaging. Sonographic studies were obtained through a national parents' group, the Cornelia de Lange Syndrome Foundation. Assessment of fetal growth was made using four standardized measurements: the biparietal diameter, head circumference, femur length, and abdominal circumference. These values were compared to established tables of normal fetal growth and established ratios of fetal body proportions. The cross-sectional growth curve derived using all measurements collected as a composite group indicates that growth retardation would be first detected as early as 25 weeks. In five fetuses with measurements both before and after 25 weeks of gestation, longitudinal growth curves indicated that the diagnosis of "small for gestational age" would have been suggested between 20 and 25 weeks. The mean fetal weight estimates closely followed the fifth centile curve of normal fetuses both before and after 25 weeks. Cephalic indices in BDLS fetuses indicated either frank brachycephaly (25%), or were at the upper portion of the normal range. Femur lengths were relatively short (less than 90% of their expected length) ion 4 of the 11 fetuses where such information could be obtained.(ABSTRACT TRUNCATED AT 250 WORDS)

Fetal brain development of twins assessed in utero by ultrasound: implications for schizophrenia.

There is evidence that some forms of schizophrenia are due to alterations of in utero brain development. Given the concordance rate for schizophrenia in monozygotic twins is approx. 45%, it is not clear how a shared genetic predisposition for schizophrenia and a shared in utero environment might selectively lead to schizophrenia in one but not the other twin in a monozygotic twin pair. This study was undertaken to test the hypothesis that there is a difference in brain development between twins in a monozygotic twin pair that may contribute to the observed concordance rates for schizophrenia. Fetal ultrasound measures of brain (biparietal diameter, head circumference, ventricular width) and body size (femur length, abdominal circumference) obtained during the second trimester of fetal development were retrospectively analyzed in 41 monozygotic and 103 dizygotic twin pairs. In monozygotic twin pairs, there was a significant difference in measures of biparietal diameter, head circumference, and ventricular width, as well as in femur length and abdominal circumference, between twins. There was a similar difference in dizygotic twin pairs. These results indicate that in monozygotic twins, brain development is not identical. This difference in brain development may contribute to the observed concordance rates in monozygotic twins with schizophrenia.

Mild ventriculomegaly detected in utero with ultrasound: clinical associations and implications for schizophrenia.

The most consistent structural abnormality of the brain associated with schizophrenia is that of mild enlargement of the lateral cerebral ventricles. Mild ventriculomegaly (MVM) of the fetal brain detected in utero with ultrasound is associated with developmental delays similar to those described in children at high risk of schizophrenia. Fetal mild ventriculomegaly may be a marker for increased risk of schizophrenia and other neurodevelopmental abnormalities. Given the association between schizophrenia and obstetrical complications, pre- and perinatal complications and pregnancy outcomes were retrospectively reviewed in 51 pregnancies in which the fetus exhibited mild ventriculomegaly on routine ultrasonography and 49 control pregnancies. Mothers of children with MVM were older than controls and had shorter gestations. There were no significant between-group differences in numbers of pregnancy complications or pregnancy outcomes as reflected in gestational age at birth, birthweight, or Apgar scores. Children with isolated mild ventriculomegaly tended to be male. This study indicates that isolated mild ventriculomegaly detected in utero is not associated with pregnancy complications and suggests that isolated mild ventriculomegaly of the fetus is genetically determined or caused by environmental events not routinely considered pregnancy complications.

Outcome in children with fetal mild ventriculomegaly: a case series.

Mild enlargement of the lateral ventricles is associated with schizophrenia and other neurodevelopmental disorders. While it has been hypothesized that ventricle abnormalities associated with neurodevelopmental disorders arise during fetal brain development, there is little direct evidence to support this hypothesis. Using ultrasound, it is possible to image the fetal ventricles in utero. Fetal mild ventriculomegaly (MVM) has been associated with developmental delays in early childhood, though longer-term neurodevelopmental outcome has not been studied. Follow-up of five children (aged 4--9 years) with mild enlargement of the lateral ventricles on prenatal ultrasound and two unaffected co-twins is reported: one child had attention deficit hyperactivity disorder (ADHD), one had autism, and two had evidence of learning disorders. These cases suggest that the mild enlargement of the lateral ventricles associated with these neurodevelopmental disorders arises during fetal brain development and can be detected with prenatal ultrasound. In addition, the presence of mildly enlarged, asymmetric ventricles in two children on prenatal ultrasound and on follow-up MRI at age 6 years indicates that ventricle structure present in utero can persist well into childhood brain development. The study of fetal ventricle development with ultrasound may provide important insights into neurodevelopmental disorders and allow the identification of children at high risk.

A histopathologic study of 716 unselected eyes in patients with cancer at the time of death.

To determine the frequency of ocular metastases in the general population, we conducted a prospective histopathologic study of 716 eyes obtained from patients who had malignant neoplasms at the time of death. Fifty-two patients had ocular metastases; all of these individuals had widespread metastases that contributed to their deaths. The overall incidence of ocular metastases among all fatal cases of cancer was 9.3%. Thirty-three of the 117 patients with various types of leukemia and four of the 60 patients dying with lymphoma had ocular involvement. The total incidence of ocular metastases in patients dying of all types of carcinoma was 4.0%. In the nine patients dying of sarcoma, no ocular metastases were detected. We estimate that about 22,000 patients who will die of cancer in the United States during 1983 will have ocular metastases.

Value of sonography in the diagnosis of intracranial hemorrhage and periventricular leukomalacia: a postmortem study of 35 cases.

Periventricular leukomalacia and germinal matrix hemorrhages are major causes of neurodevelopmental abnormalities in the premature neonate. Although sonography is widely used to detect these abnormalities and is thought to be sensitive for hemorrhages and the later cystic stages of periventricular leukomalacia, its sensitivity for the more acute phase of periventricular leukomalacia remains to be determined. It has been difficult to study this issue because periventricular leukomalacia often is not lethal, and in postmortem studies there is usually a considerable interval between the time of in vivo imaging, if any, and the death of the patient. A "prospective" autopsy study was performed on brain specimens from infants who died at less than 1 year of age during a 10-month period. Thirty-five formalin-fixed brains were studied and sonographic images of these specimens were compared with histologic findings in whole brain sections to determine the sensitivity and specificity of sonography for the detection of germinal matrix hemorrhage and periventricular leukomalacia. Sonography identified germinal matrix hemorrhages as small as 5 mm, although smaller lesions were not visualized. Postmortem sonography had a sensitivity of 27% and specificity of 88% for all germinal matrix hemorrhages, but a sensitivity of 100% and specificity of 91% for hemorrhages larger than 5 mm. Periventricular leukomalacia, seen as hyperechoic areas in the periventricular white matter, was not detected as readily. For periventricular leukomalacia, the overall sensitivity and specificity were 50% and 87%, respectively. We conclude that sonography is useful for detecting the larger germinal matrix hemorrhages, but has more limited sensitivity in the early diagnosis of periventricular leukomalacia.

Fetal gastrointestinal abnormalities.

A wide range of abnormalities of the fetal gastrointestinal tract is currently detectable by antenatal sonography, but the sonographic appearance of normal fetal bowel is variable, with considerable overlap between normal and abnormal patterns. In examining the major gastrointestinal disorders that may be recognized by in utero sonography, this article emphasizes potential pitfalls due to confusion with normal anatomic variants and pathologic processes arising elsewhere in the fetus.

Infant cerebral ventricle volume: a comparison of 3-D ultrasound and magnetic resonance imaging.

Enlargement of the cerebral lateral ventricles is observed in several neuropsychiatric disorders with origins in early brain development. Lateral ventricle size is also predictive of poor neurodevelopmental outcome in premature infants. Three-dimensional (3-D) ultrasound (US) offers an improved methodology for the study of lateral ventricle volume in neonates and infants. To assess the validity of ventricle volume measures obtained with 3-D US, we compared the volumes obtained by 3-D US with magnetic resonance imaging (MRI) in seven infants. Ventricle volumes were determined using a computer-assisted image analysis program, IRIS. There was excellent correlation between ventricle volumes obtained with 3-D US and those obtained with MRI (intraclass correlation coefficient 0.92, F = 23.28, p = 0.00027), indicating that 3-D US provides valid measures of overall lateral ventricle volume compared to the "gold standard" of MRI. 3-D US can provide an economical and practical means of studying lateral ventricle volume in neonates, a neurostructural marker of abnormal brain development.

Sonography of the fetal gastrointestinal tract: anatomic variants, diagnostic pitfalls, and abnormalities.

Prenatal sonography has the potential to show a wide range of abnormalities in a fetus's gastrointestinal tract. Suspected fetal gastrointestinal abnormalities should be interpreted with caution, however, as the sonographic appearance of a healthy fetus's gastrointestinal tract is variable and there is considerable overlap in the appearances of normal and abnormal fetal bowel. Similarly, pathologic processes originating from organ systems other than the gastrointestinal tract can at times exhibit sonographic patterns remarkably similar to those of dilated bowel. This review examines the sonographic findings of gastrointestinal disorders seen in utero, emphasizing potential diagnostic pitfalls arising from confusion with normal anatomy, anatomic variants, and pathologic processes elsewhere in the fetus.

Ultrasound of the postpartum uterus. Prediction of retained placental tissue.

We reviewed ultrasound images an 53 postpartum patients referred for possible retained products of conception and correlated specific ultrasound patterns with clinical and pathologic follow-up. The most common finding in patients with retained placental tissue was an echogenic mass in the uterine cavity, seen in 9 of 11 patients with pathologically proven retained placental tissue. In the remaining 2 patients with pathologically confirmed retained placenta, a heterogeneous mass was seen in the uterine cavity at some point during the course of serial sonography. Retained placental tissue was unlikely when ultrasound demonstrated a normal uterine stripe (n = 18), endometrial fluid (n = 6), or hyperechoic foci in the uterine cavity without an associated mass (n = 17). The latter finding was often associated with recent uterine instrumentation. The sonographic appearance of retained placental tissue is variable, but detection of an echogenic mass in the uterus strongly supports the diagnosis. A heterogeneous mass is sometimes caused by retained placenta, but can also be secondary to blood clots or infected or necrotic material in the absence of placental tissue. Sonographic evaluation for retained products of conception is best done before uterine instrumentation to avoid confusion with iatrogenically introduced air.

Hyperechoic meconium in the third trimester fetus: an uncommon normal variant.

Fetal meconium is usually hypoechoic or isoechoic to adjacent abdominal structures on antenatal sonography. Hyperechoic meconium is associated with pathologic conditions, such as meconium ileus, meconium peritonitis, and anorectal malformations. The authors describe three third trimester fetuses with hyperechoic meconium and a normal outcome. Although a prospective study revealed that this finding is very uncommon, hyperechoic meconium can be a normal variant, particularly when it is seen as an isolated finding late in the third trimester.

Ectopic pregnancy: ultrasonographic diagnosis and interpretive pitfalls.

The ultrasonographic evaluation of ectopic pregnancy is fraught with potential pitfalls in image interpretation. Though recent advances in sonographic techniques have improved the precision and scope of the study, considerable expertise is still needed to perform and interpret the sonogram for a suspected ectopic gestation. In this article, we review the ultrasonic evaluation for ectopic pregnancy, emphasizing the difficulties in diagnosis.

Vasa previa: prenatal diagnosis by transperineal sonography with Doppler evaluation.

Antepartum diagnosis of vasa previa is of critical importance because of the high fetal mortality rate in unrecognized cases. This report describes the sonographic findings in 2 cases of vasa previa and demonstrates that transperineal sonography with Doppler evaluation can successfully establish the diagnosis of vasa previa prenatally.

Sonographic diagnosis of premature cervical dilatation. Potential pitfall due to lower uterine segment contractions.

Antenatal sonography is an accepted method of evaluating the cervix and lower uterine segment. Dilatation of the endocervical canal can be missed due to compression by an overdistended urinary bladder, intermittent changes in configuration of the cervix, and suboptimal visualization. However, the potential for overdiagnosis of this entity has not been previously emphasized. We present 14 cases demonstrating how contractions in the lower uterine segment can result in an appearance that falsely simulates preterm dilatation of the endocervical canal. The overdiagnosis of this entity can be avoided by distinguishing the following features typical of "pseudodilatation" due to a contraction: (1) apparent cervical length greater than 5 cm; (2) demonstration of normal-appearing cervical tissue distal to the apparently dilated region; and (3) rounding of the myometrium surrounding the apparently dilated area. If any of these features is detected in a patient with sonographic characteristics suggesting dilatation of the cervix, the possibility of pseudodilatation should be considered, and the lower uterine segment should be rescanned later in the examination.

Transperineal US: alternative technique to improve visualization of the presenting fetal part.

Transperineal ultrasound (TPU) was used as an alternative imaging technique to evaluate the anatomy of the presenting part in 27 second- and third-trimester fetuses when transabdominal ultrasound (US) images were suboptimal. Use of TPU improved visualization of the distal fetal spine in 20 of 21 breech cases, providing sufficient information regarding bone anatomy to rule out splaying of the posterior elements. In addition, the intact skin surface overlying the distal spine, not seen at transabdominal US, was well demonstrated at TPU in 18 of these fetuses. TPU was used to improve assessment of intracranial anatomy in six cases with a cephalic presentation in which the fetal head was located low in the maternal pelvis and could not be adequately visualized with the transabdominal technique. In one of these cases, TPU offered improved visualization of anencephaly. Use of TPU should be considered to optimize visualization of the presenting fetal part when results at transabdominal US are suboptimal and the poorly seen part overlies the maternal cervix.

First trimester fetal cardiac activity. Sonographic documentation of a progressive early rise in heart rate.

The heart rates of 124 first trimester fetuses were determined with real-time sonography and were analyzed with regard to gestational age. The mean embryonic heart rate increased from 101 beats per minute (bpm) at 5 to 5.95 menstrual weeks to 143 bpm at 8 to 8.95 weeks. After nine weeks, the rate reached a plateau, ranging from 137 to 144 bpm. Slower heart rates are normal early in the first trimester and should not be misinterpreted as an abnormal finding or mistaken for maternal pulsations.

Complications of cesarean section: role of transperineal US.

The pelvic area was prospectively examined with transabdominal and transperineal ultrasonography (US) in 22 patients referred for US evaluation for possible complications of cesarean section. The region of the uterine wound was seen with transabdominal US in all patients and with transperineal US in 20. The two in whom transperineal US did not reveal the lower uterus had undergone scanning with their bladders empty. Bladder flap hematomas were revealed with transabdominal US in 10 patients and with transperineal US in nine. Transabdominal and transperineal diagnoses regarding bladder flap hematoma were in agreement in all 19 patients who underwent transperineal US with a distended urinary bladder. With the transabdominal approach, subfascial hematomas were seen in nine patients, but none were revealed with the transperineal technique. In one patient, a hematoma in the space of Retzius was seen only with transperineal US. These findings indicate that transperineal US can complement transabdominal US in evaluation for complications of cesarean section.

Cerebellar vermian defects: antenatal sonographic appearance and clinical significance.

A partial or complete defect of the cerebellar vermis may occur sporadically or as a component of the Dandy-Walker syndrome, the Dandy-Walker variant, Down's syndrome, or Joubert-syndrome. We identified a defect of the cerebellar vermis in nine fetuses on routine antenatal sonographic studies. In five of the nine fetuses other abnormalities, including central nervous system and non-central nervous system lesions were identified. Three of these five fetuses died and two infants have remained well on follow-up. Four of nine fetuses (or infants) had no other abnormalities and have remained well on follow-up at 8 weeks to 4 years of age. Although cases of fatal and serious nonfatal outcomes have been reported by other investigators, in this small series the finding of an isolated inferior vermian defect was associated with a good prognosis.