Comparison of methods to identify significant proteinuria in pregnancy in the outpatient setting.

The efficacy of the albumin/creatinine ratio (ACR) measurement in detection of significant proteinuria when performed in a high-risk antenatal clinic was compared with automated dipstick, protein/creatinine ratio (PCR), and 24-hour urine protein measurements. Both the ACR (DCA 2000) and PCR were strongly predictive for the presence or absence of significant proteinuria, with positive likelihood ratios (LRs) of 27.4 and 31.6 and negative LRs of 0.0 and 0.1, respectively. Both the ACR (DCA 2000) and PCR are effective tests for both identifying and excluding significant proteinuria in the outpatient setting. The ACR (DCA 2000) has the advantage of providing an immediate result.

Flow cytometric detection of activated platelets in pregnant women prior to the development of pre-eclampsia.

Pre-eclampsia is a common complication of pregnancy, in which platelets may have an early pathogenetic role. In this prospective study a whole blood flow cytometric method has been used to detect circulating activated platelets in pregnant women prior to the development of pre-eclampsia. Activated platelets were identified by bound fibrinogen or by CD63 antigen expression. Of 121 healthy primiparous women studied at 28 weeks of pregnancy, 18 (15%) developed clinical pre-eclampsia six to thirteen weeks later. The platelets of these women showed increased fibrinogen binding ex vivo (5.1% platelets positive, compared with 3.4% in those who completed a normal pregnancy, p < 0.02), and increased CD63 antigen expression (0.73% positive compared to 0.45%, p = 0.01). In contrast, no differences between the women with different outcomes were detected at 28 weeks in platelet counts, or plasma beta-thromboglobulin levels. These findings confirm that whole blood flow cytometry is a sensitive technique for investigating platelet activation in a clinical setting and support the hypothesis that platelets have a critical role in the pathogenesis of pre-eclampsia.

Amniotic fluid culture failure: clinical significance and association with aneuploidy.

OBJECTIVE: To characterize clinical aspects associated with second-trimester amniotic fluid (AF) culture failure. METHODS: The reports of all amniocentesis samples received in our cytogenetic laboratory over a 9-year period were reviewed to identify cases in which culture failure of amniocytes occurred. Medical records were then reviewed for the prenatal ultrasonographic findings, karyotype when available, and clinical outcome. RESULTS: During the study period, 4134 second-trimester AF samples were processed, of which 42 (1%) failed to yield a result. Complete information was available in 41 pregnancies, which are the basis of this report. Karyotyping was done ultimately in 32 of the 41 cases (78%). The frequency of an abnormal karyotype was greater in those pregnancies in which AF culture failure occurred in comparison with those in which a cytogenetic result was obtained (six of 32 [19%] versus 149 of 4092 [4%], P < .001). There was also a greater prevalence of fetal abnormalities detected on prenatal ultrasonography, mainly oligohydramnios, hydrops, and fetal growth restriction, in the AF culture failure group compared with the successful AF culture group (17 of 41 [41%] versus 351 of 4092 [9%1, P < .001). All chromosomally abnormal fetuses had anomalies detected at ultrasonography. CONCLUSION: Our findings confirm the previously reported association between karyotype abnormality and AF culture failure, but suggest that this association is probably due to fetal anomalies, detectable on prenatal ultrasonography, that lead to decreased fetal cell shedding.

High failure rate of postmortem karyotyping after termination for fetal abnormality.

OBJECTIVE: To determine the failure rate of karyotyping from samples taken after termination of pregnancy for fetal abnormality. METHODS: Perinatal autopsy reports over a 12-month period were reviewed to identify those with cytogenetic studies performed after termination of pregnancy for fetal abnormality. RESULTS: During the audit period, there were 104 terminations for fetal abnormality. In 89 fetuses, fetal skin (n = 85), placenta (n = 62), or other samples (n = 8) were obtained for postmortem cytogenetic analysis. In 24 (27%) fetuses, postmortem tissues did not yield a karyotype result. The failure rate of post-termination karyotyping was significantly influenced by delivery-sampling interval, but not by gestational age, type of tissue sampled, use of potassium chloride, or aneuploidy. Of the 24 cases for which no post-termination karyotype was obtained, 16 had had successful pre-termination karyotyping, resulting in only eight of 89 (9%) cases in the overall series not having a final karyotype. CONCLUSION: The high failure rate for post-termination karyotyping suggests that a pre-termination procedure is necessary if parents wish to have almost 100% certainty that cytogenetic information will be available for later genetic counseling.

Comparative risk-benefit assessment of drugs used in the management of hypertension in pregnancy.

Antihypertensive treatment in pregnancy is needed to protect the mother from the dangers of severe hypertension (greater than or equal to 170/110mm Hg), particularly cerebral haemorrhage in the context of preeclampsia. There is no evidence that treatment of the hypertension confers any other benefit; the onset and progression of preeclampsia is neither prevented nor ameliorated. Therefore, there are no indications for treating mild-to-moderate hypertension (140 to 169/90 to 109mm Hg). Intravenous hydralazine and oral nifedipine are effective drugs to treat severe hypertension acutely, the latter having the advantage of ease of administration. For long term therapy, methyldopa is the only drug which has been fully assessed and shown to be safe for the neonate and infant. beta-Adrenoceptor antagonists are safe to use in the third trimester but cause significant intrauterine growth retardation when used for longer periods. ACE inhibitors are contraindicated and diuretics should be avoided. Although calcium antagonists appear to have much potential they require further assessment of their use in pregnancy.

Effect of intravitreal hyaluronidase on the clearance of tritiated water from the vitreous to the choroid.

The rate of transfer of intravitreally injected tritiated water from the mid vitreous to the choroid is significantly increased after depolymerization of vitreous hyaluronic acid by injected hyaluronidase. The significance of this finding is discussed in relation to such conditions as retinal detachment and reattachment.

Routes of clearance of radioactive water from the rabbit vitreous.

The movement of water to and from the vitreous across the retina and pigment epithelium is important in relation to an understanding of such conditions as retinal detachment and its surgical cure, central serous retinopathy, and retinal oedema. Experiments were carried out to determine the main routes for removal of water injected into the vitreous and to see if the removal could be explained on the basis of diffusion or whether bulk flow was also implicated. 25 microCi of 3H2O in 25 microliter were injected into a central position in the vitreous humour of living rabbits under general anaesthesia. For 9 animals blood was collected from one of the 4 vortex veins draining the choroid and the radioactivity in the samples measured. For another 6 rabbits similarly injected the radioactivity in samples of aqueous humour was determined. The percentage of injectate recovered from the vortex vein blood ranged between 13% and 38%, mean 25 +/- 3%. The percentage of injectate recovered from the aqueous humour ranged between 1.2% and 5.2%, mean 2.8 +/- 0.6%. Analysis of the time course of isotope activity in the samples revealed a mean transit time from the mid vitreous to the choroid of 32 +/- 2 minutes, and from the mid vitreous to the anterior chamber of 84 +/- 3 minutes. By means of a computer model it was calculated that diffusion alone could effect this transfer; if active transport were involved in the transport of 3H2O to the choroid, this was not a limiting factor under the conditions of the experiment.

Delayed ciliochoroidal detachment following intraocular lens implantation.

Three patients who had extracapsular cataract extractions with intraocular lens implants developed delayed ciliochoroidal detachments, which responded to systemic steroid therapy. This rare complication may have been due to ciliary sulcus fixation of the implant. The possible mechanism and treatment are discussed.

Middle cerebral artery Doppler for the prediction of fetal anaemia in cases without hydrops: a practical approach.

The aim of this study was to assess the value of the middle cerebral artery (MCA) Doppler time-averaged mean velocity (TAMV) for the prediction of fetal anaemia in at-risk cases without ultrasound evidence of hydrops. The study included 35 pregnant women with non-hydropic fetuses and with known red cell antibodies, referred either because of a rapid increase in antibody levels or because of a previous history of a severely anaemic fetus or neonate. After full ultrasound examination of the fetus, MCA Doppler TAMV was measured and, if severe anaemia was suspected, fetal blood sampling by cordocentesis was performed with blood ready for intrauterine transfusion if necessary. Of the 35 fetuses, 28 were anaemic and 7 had a haemoglobin (Hb) value within the normal range. There was a strong negative correlation between the MCA Doppler TAMV and the Hb values (correlation coefficient r=-0.65, p<0.0001). The mean MCA Doppler TAMV (z score) for fetuses with normal Hb was 1.55+/-1.68, while that for the anaemic fetuses was 4.06+/-1.38, (p<0.001). The sensitivity of the increased MCA Doppler TAMV to predict fetal anaemia in these cases was 96.4% and the specificity was 71.4%. These data confirm that MCA Doppler TAMV is significantly correlated to fetal Hb. This non-invasive investigation can be reliable in predicting anaemia in cases in which the need to sample fetal blood is not certain, therefore delaying invasive testing until treatment is likely to be required.

Intestinal complications associated with twin-twin transfusion syndrome after antenatal laser treatment: Report of two cases.

Two infants found to have ileal atresia after birth and who had intrauterine laser treatment to interupt twin to twin transfusion are presented. The donor twin in each pregnancy died in utero.

Long-term visual outcome following orbital decompression for dysthyroid eye disease.

The records of 33 patients who had undergone inferior and medial wall orbital decompressions for compressive optic neuropathy due to dysthyroid eye disease were reviewed. The indication for surgery in 32 patients was a reduction in Snellen visual acuity. The remaining patient had bilateral optic disc swelling but normal visual acuity. Twenty-nine patients (88%) were treated with systemic steroids pre-operatively, which resulted in an improvement in vision in all cases. In the immediate post-operative period visual acuity either improved or the steroid-induced visual improvement was maintained as the steroids were tailed off. Long-term visual outcome, however, varied. In 19 patients (58%) visual acuity was maintained with no requirement for additional treatment. In 12 patients (36%) there was a subsequent deterioration in vision which responded to additional treatment with either systemic steroids, orbital radiotherapy or further orbital surgery. In 2 patients (6%) vision continued to deteriorate despite further treatment. We conclude that although orbital decompression has resulted in the long-term preservation of visual acuity in 94% of our patients, there remains a small subgroup (6%) in whom visual function continues to deteriorate despite all forms of treatment.

Prenatal diagnosis of diastematomyelia: case reports and review of the literature.

Diastematomyelia is a rare malformation characterized by complete or incomplete division of the spinal cord by osseous or fibrocartilaginous septum. Most cases are seen in association with other anomalies of the vertebral column such as spina bifida, kyphoscoliosis, butterfly vertebra, and hemivertebra. In this report we describe two cases of isolated diastematomyelia detected at routine second-trimester detailed ultrasound scan, the most striking feature being the detection of an echogenic focus in the posterior aspect of the spine in association with widening of the interpedicular vertebral space. The prenatal literature is reviewed to assess the clinical significance of this finding.

Prenatal detection of congenital inherited cataracts.

In a high-risk pregnancy for ocular defects, routine second-trimester ultrasonography revealed a highly echogenic area within the fetal left eye with no other associated abnormalities. The diagnosis of congenital cataracts was confirmed after birth. Examination of the fetal face is an important part of prenatal ultrasonography, and visualization of the fetal eyes and lenses should be included in the routine assessment of facial anatomy. This is especially important in pregnancies at risk for congenital cataracts or for other anomalies affecting the fetal eye.

Correlation of prenatal ultrasound diagnosis and pathologic findings in fetal brain abnormalities.

OBJECTIVE: To determine the degree of agreement between prenatal ultrasound diagnosis of brain abnormalities and subsequent pathologic findings. METHODS: Between August 1993 and August 1999 there were 62 cases where a fetus with a prenatal ultrasound diagnosis of a brain abnormality other than neural tube defects underwent autopsy at the Regional Department of Pediatric Pathology. The cerebral diagnosis at ultrasound was compared with the findings at autopsy in all cases. RESULTS: In 47 of 61 (77%) cases the same defects were seen on ultrasound and at autopsy. The most common disparity was with the Dandy-Walker malformation or variant, where only six of the 14 (43%) cases prenatally diagnosed with this condition showed the same abnormality at autopsy. When fetuses with the Dandy-Walker malformation or variant were excluded, the scan findings correlated with autopsy in 41 of 47 (87%). In the main group with discordant findings, five of the seven cases where termination of pregnancy was undertaken had other fetal anomalies on ultrasound examination which were confirmed at autopsy. In the sixth case there was autolysis of brain tissue which affected detailed autopsy. CONCLUSIONS: A very high level of agreement between prenatal ultrasound and autopsy findings was found for all abnormalities of the fetal brain, except for the Dandy-Walker malformation or variant. Potential discrepancy in findings between ultrasound and autopsy should be explained to patients who are considering termination of pregnancy for the Dandy-Walker type of abnormality.

Management of anti-Rhesus-D antibodies in pregnancy: a review from 1994 to 1998.

OBJECTIVE: To review our management of anti-Rhesus-D antibodies in pregnancy over a 5-year period in order to assess possible changes in the management or prognosis which may have developed with time. METHOD: Retrospective analysis of prospectively collected data from 31 pregnancies with maternal anti-D levels >4 IU/ml and in which the fetus was Rhesus positive. RESULTS: There were a total of 30 amniocenteses, 8 cordocenteses, and 54 fetal blood transfusions performed. When undertaken as the first procedure, the mean gestational age at amniocentesis was 30 weeks as compared with 25 weeks for fetal blood sampling/transfusion (p < 0.05). The median anti-D level at the first procedure was 24 IU/ml for amniocentesis and 64 IU/ml for fetal blood sampling. Of the 54 blood transfusions, 43 were intravascular, 4 were intraperitoneal, and 7 transfusions were both intravascular and intraperitoneal. CONCLUSIONS: Intravascular as opposed to intraperitoneal transfusions were found to be the main method of transfusion in the later years in this study, a finding which was expected with improved sonographic equipment. Apart from this, management and prognosis of anti-D red cell isoimmunisation in pregnancy have remained relatively stable since the 1980s. Amniocentesis was useful in the management of such pregnancies, especially as an initial procedure in the cases with a lower initial anti-D level. In this series 90% of the fetuses requiring blood transfusion, but were without hydrops, survived, whereas this was about 70%, if they had become hydropic (this latter figure was reduced by 2 hydropic deaths before 20 weeks' gestation in the same very severely affected woman).

Noninvasive diagnosis of anemia in hydrops fetalis with the use of middle cerebral artery Doppler velocity.

OBJECTIVE: The purpose of this study was to assess the value of the middle cerebral artery time-averaged mean velocity for the detection of anemia as the cause of fetal hydrops. STUDY DESIGN: We examined 17 pregnant women with fetuses with hydrops (with ascites as the main component of hydrops) and who were considered at risk for anemia because there was no obvious explanation for the hydrops on the initial scan. Assessment included the measurement of the middle cerebral artery time-averaged mean velocity by color flow Doppler scan, followed by fetal blood sampling for investigations that included fetal hemoglobin. We investigated the correlation between increased middle cerebral artery time-averaged mean velocity (>2 SDs for gestational age) and fetal anemia (<2 SDs for gestational age). RESULTS: Eleven fetuses had anemia; 3 of the fetuses had red cell antibodies, and 6 of the fetuses had normal hemoglobin. There was a strong negative correlation between the middle cerebral artery time-averaged mean velocity and the hemoglobin values (r = -.9; P <.0001). The mean (z score) of middle cerebral artery time-averaged mean velocity for fetuses with normal hemoglobin was 1.1 +/- 0.81 and for the fetuses with anemia was 4.71 +/- 2.16 (P <.001). The sensitivity for the increased middle cerebral artery time-averaged mean velocity to predict fetal anemia was 91%, and the specificity was 100%. CONCLUSION: The middle cerebral artery time-averaged mean velocity is significantly increased in cases of hydrops caused by anemia, including cases other than red-cell alloimmunization. These findings can be useful for counseling and treatment and allow the investigation of the cause of hydrops without awaiting blood for intrauterine transfusion in patients who are very unlikely to be anemic and often avoids 2 procedures in those patients who require transfusion. Larger studies are required to further confirm these findings.

Vesicocentesis at 10-14 weeks of gestation for treatment of fetal megacystis.

This report of four cases shows that fetal vesicocentesis at 10-14 weeks of gestation is a useful treatment option in some cases with megacystis. Although megacystis at this gestation has been reported, there are few studies examining the role of early vesicocentesis. The natural history of the condition and outcome following treatment is reviewed with reference to the literature.