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.

The effect of metabolic control on fetal nuchal translucency in women with insulin-dependent diabetes: a preliminary study.

OBJECTIVE: Diabetes could potentially alter fetal nuchal translucency (NT) measurements mainly by increasing microvascular permeability. The aim of this study was to test this hypothesis. METHODS: Sixty-five women with pre-pregnancy insulin-dependent diabetes mellitus undergoing NT screening were evaluated. The main outcome measure was the NT measurement, expressed as both absolute measurements and delta values (number of standard deviations by which the observed value differed from the normal mean for the same gestation). The relationships between NT and years of diabetes, insulin dose, glycosylated hemoglobin, and glycemic capillary profiles ('tight' glycemic control) were studied. RESULTS: There was no significant correlation between NT and any of the studied parameters. There were no differences in NT according to the result of either glycosylated hemoglobin or 'tight' control. CONCLUSIONS: Metabolic control does not affect the result of ultrasound-determined fetal NT measurement which, when available, seems to be the best option for screening for Down syndrome in women with diabetes mellitus.

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.

Women's attitudes towards management of breech presentation at term.

Current advice on the management of breech presentation at term is that all uncomplicated cases should be offered external cephalic version (ECV) or an elective caesarean section. Clinical experience suggests that ECV is currently not offered as widely as advised and that the majority are delivered electively by caesarean section. We present the results of a patient attitude survey of term breech deliveries in a university teaching hospital over 12 months. The results show that half of respondents were not offered ECV and that two-thirds of these women were not eligible for ECV, either having had a previous caesarean or breech presentation diagnosed in labour. One-third of women, potentially suitable for ECV, were not made aware of their options. The majority are offered elective caesarean section with a small minority (10%) opting for planned vaginal breech delivery.

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.

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).

Fetal protein loss in gastroschisis as an explanation of associated morbidity.

OBJECTIVE: Our purpose was to examine whether protein deficiency in utero develops in fetuses with gastroschisis. STUDY DESIGN: Twelve infants with prenatally diagnosed gastroschisis were compared with 29 control infants without gastroschisis and 2 infants with exomphalos who were delivered between 35 and 42 weeks of gestation. The groups were compared for birth weight, cord serum total protein and amniotic fluid total protein, and alpha-fetoprotein concentrations. The amniotic fluid samples were collected when the amniotic membranes were ruptured either during cesarean delivery or at artificial rupture of the membranes, and umbilical cord blood was obtained after delivery. RESULTS: In the 10 cases of gastroschisis in which cord serum total protein was measured, the median concentration was 51 g/L (range, 43-61 g/L) and was significantly lower than the median level of 62 g/L (range, 47-78 g/L) in the control group (P <.001). In the 8 cases of gastroschisis in which amniotic fluid total protein and alpha-fetoprotein concentrations were measured, the respective median levels were 5.1 g/L (range, 4.3-18.4 g/L) and 5.0 g/L (range, 2.4-13.2 g/L), which were significantly higher than the median levels of 2.0 g/L (range, 0.5-5.4 g/L) and 0.8 g/L (range, 0.5-1.7 g/L) in the control group (P <.0001). The ratio of amniotic fluid to cord serum total protein was significantly higher than that in the cases of exomphalos and in the control group (P <.001). The median birth weight in the neonates with gastroschisis was 2400 g (range, 1192-3155 g) and was significantly lower than the median value of 3535 g (range, 2520-4680 g) in the control group (P <.0001). CONCLUSIONS: Fetuses with gastroschisis have protein loss that could partly explain associated morbidity. However, whether this is a major contributor to poor fetal outcome remains to be shown.

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.

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.

Outcome of fetal talipes following in utero sonographic diagnosis.

OBJECTIVES: To examine the association between fetal talipes and other defects, and outcome in relation to postnatal surgery. METHODS: All cases of talipes presenting to the fetal medicine unit between 1993 and 1998 and cases of isolated talipes presenting to the ultrasound department between 1991 and 1998 were examined. The infants were followed-up to determine the number of cases that had structural or positional talipes and the number of cases requiring surgery. RESULTS: There were 76 cases, 59 of which attended the fetal medicine unit and 17 the ultrasound department. Postnatal follow-up details were available in 31 of the 40 live births. There were three neonates with unilateral talipes at birth who were thought to have bilateral talipes on prenatal ultrasound and one neonate had bilateral talipes at birth who had been thought to have unilateral talipes prenatally. In two (6.4%) neonates in whom talipes was not confirmed at birth the abnormality was diagnosed prenatally. Of the 29 neonates with confirmed talipes at birth, the defect was structural in 26 (90%) cases and positional in three. Surgery was necessary in 21 (72%) of the 29 cases and 18 (86%) of those undergoing surgery required only one operation. When live births with associated anomalies were excluded, there were 24 cases with confirmed isolated talipes and 18 (75%) required surgery. CONCLUSIONS: This study provides long-term outcome data which can be used to complement current prenatal counseling and shows that in cases of fetal talipes diagnosed prenatally, 90% have a structural rather than a positional deformity. For isolated talipes three quarters of children will require surgery and in the majority of cases only one operation on the foot is necessary. Parents should be made aware of the small possibility of a false-positive diagnosis and discrepancy between the ultrasound and postnatal diagnoses of laterality.

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.

The effect of fetal hydrops on the rate of fall of hemoglobin after fetal intravascular transfusion for red cell alloimmunization.

OBJECTIVE: We aimed to assess whether there is a difference between hydropic and nonhydropic fetuses in the rate of fall of hemoglobin (Hb) following intravascular transfusions. METHODS: Eighty-three intravascular transfusions in 34 fetuses were analyzed. The pretransfusion and posttransfusion Hb values, the gestational age, the volume of blood transfused, the number of days between transfusions and the rate of fall of Hb per day following a transfusion were assessed. Hb levels were expressed as multiples of standard deviation from the normal mean for gestational age. RESULTS: Eleven fetuses were hydropic at presentation and 23 were not. Twenty-three transfusions were undertaken in the 11 fetuses while they were hydropic and 60 transfusions were performed in nonhydropic fetuses. Comparisons of transfusion variables between the two groups were performed both for the first transfusion only and also for the total number of transfusions. The rate of Hb fall per day following a transfusion was similar in the two groups on both comparisons. The posttransfusion Hb level tended to be lower and the intervals between transfusions were a little shorter in the hydropic group, but these differences were not statistically significant. CONCLUSION: The posttransfusion Hb tended to be lower in the hydropic fetuses, but the fall in Hb was not faster in these cases. Therefore, with a similar rate of daily Hb decline in both groups, the hydropic fetuses are expected to become anemic again sooner than the nonhydropic fetuses only because of the lower posttransfusion Hb. The timing of the next transfusion should therefore be based on the posttransfusion Hb and the normal predicted drop per day irrespective of the presence or absence of hydrops.

An assessment of the use of interphase FISH with chromosome specific probes as an alternative to cytogenetics in prenatal diagnosis.

We have assessed the effects that would have been observed if we had changed from standard prenatal diagnosis to interphase fluorescence in situ hybridization (FISH) on our amniocentesis samples. We aimed to estimate the number of cases with aberrations other than chromosomes 13, 18, 21, X and Y, which would not have been detectable by FISH and to assess the potential clinical implications for these cases. In 1687 prenatal diagnoses, 111 cases had abnormal cytogenetic reports (6.5% aneuploidy rate). Out of those 111 cases, 14 had chromosomal abnormalities not detectable by FISH but four of these had major structural abnormalities diagnosed on ultrasound, which would have lead to counselling of a very poor prognosis anyway. In 10 cases without abnormal ultrasound findings, if FISH had been used rather than cytogenetics, it appears that there may have had no detrimental effects on the clinical outcomes of the cases studied. Out of those 10 cases, two pregnancies were terminated because of abnormal cytogenetic results (one was due to maternal age and the second one was due to abnormal biochemical screening) (mosaic 46,XY, /47,XY,+mar and 46,X,del(8)(p21) respectively) and their post-mortem results also did not show any abnormalities. One pregnancy was continued in spite of a de novo chromosomal rearrangement and resulted in an apparently normal live birth. Five cases (including a set of twins) with inherited balanced translocations resulted in four normal live births and one unexplained intrauterine death at 32 weeks' gestation and post-mortem was declined. One case with a paternally derived abnormal chromosome 21, decided to continue the pregnancy and resulted in a normal live birth. The last case in this group resulted in a rhesus related intrauterine death in the second trimester, and although an abnormal chromosome 13 insertion (paternally derived known aberration) there was no abnormality found at post-mortem. Therefore, we suggest that it is reasonable to use FISH as an alternative prenatal diagnosis for indications such as advanced maternal age and abnormal maternal serum biochemical screening when high quality ultrasound scanning is performed, but FISH should only be used as an additional test to conventional cytogenetics for the other indications, especially when abnormalities are found on ultrasound scan.

Fetal karyotyping by chorionic villus sampling after the first trimester.

OBJECTIVE: To evaluate chorionic villus sampling (CVS) as a technique for karyotyping after the first trimester by examining the incidence of result failure, confined placental mosaicism, and false positive or negative results at different gestational ages. METHODS: During a nine year period between 1989 and 1997, all results of CVS between 8 and 37 weeks of gestation provided by the Regional Cytogenetics Centre were analysed retrospectively by examining indications for CVS, weights of tissue received, gestational age at sampling and karyotype results. RESULTS: There were 2424 chorionic villus samples analysed by the direct method and/or cell culture. In 1548 cases CVS was performed before 14 weeks (Group 1), in 685 between 15 and 20 weeks (Group 2), in 160 between 21 and 28 weeks (Group 3) and in 31 cases after 29 weeks (Group 4). Although there was a trend for an increasing rate of failed direct preparation results from Groups 1 to 4 which were 3.8%, 4.7%, 5.6% and 6.6%, respectively; these results were not significantly different. There were 19 cases of confined placental mosaicism and the incidence was significantly greater in Group 3 compared with Group 1 (P < 0.05), and in Groups 3 and 4 combined compared with Group 1. There were six false positive and one false negative result following direct analysis with no significant differences between gestationar ages. CONCLUSIONS: CVS is a useful test after the first trimester, especially when a fast result is clinically required. However, after 20 weeks, when cordocentesis is available, the higher rate of cytogenetic discordancy between the placenta and the fetus means that cordocentesis may be preferable.

Amnioreduction: how much to drain?

OBJECTIVES: To assess the relationship between the volume of amniotic fluid removed and the change in amniotic fluid index (AFI) and calculate an equation describing this association. MATERIALS AND METHODS: A retrospective analysis of 19 amnioreduction procedures performed in our unit. Multiple regression analysis was used to assess the effect of gestational age and pre-procedure AFI on the change in AFI (DeltaAFI) after adjusting for the volume removed. RESULTS: As expected, a significant linear relationship was found between the change in AFI and the volume removed (r = 0.82, n = 19, p < 0.0001). DeltaAFI was not dependent on the gestational age or the pre-procedure AFI. The equation describing the association between the volume removed and DeltaAFI was: volume = (DeltaAFI - 2. 26)/0.008, which is close to 1 cm DeltaAFI for every 100 ml removed. DISCUSSION: Using the described equation, it is possible to predict the required volume to be removed in order to achieve a particular DeltaAFI, which may reduce the need to interrupt the procedure to measure the AFI. However, the limitation of AFI as a semiquantitative assessment of the liquor volume, together with its inter- and intra-observer variations mean this equation should be used only as a guide.

Maternal middle cerebral artery velocimetry in normal pregnancy and postpartum.

OBJECTIVE: To study changes throughout gestation and the puerperium of middle cerebral artery flow velocity waveforms obtained by transcranial Doppler ultrasound. DESIGN: Prospective, observational study. SETTING: John Radcliffe Maternity Hospital, Oxford, UK. PARTICIPANTS AND METHODS: Middle cerebral artery velocities were measured by transcranial Doppler ultrasound in 25 nonpregnant women, 22 women longitudinally followed throughout pregnancy and 21 women serially studied from delivery until the late puerperium. MAIN OUTCOME MEASURES: Transcranial Doppler changes in pregnancy and the puerperium. RESULTS: The transcranial Doppler ultrasound measurements showed good reproducibility. Signals from one middle cerebral artery could not be obtained in 4.6% of the examinations, but otherwise readings were similar on both sides. Women in the second half of pregnancy had lower middle cerebral artery mean velocities than nonpregnant women. Velocities decreased with advancing gestation but increased in the immediate puerperium to levels comparable to those found in nonpregnant women. CONCLUSIONS: Transcranial Doppler ultrasound is a noninvasive technique suitable for studying maternal cerebral haemodynamics in pregnancy and postpartum. Middle cerebral artery mean velocity decreased with advancing gestation and increased to nonpregnant values in the immediate puerperium. These physiological changes need to be considered when comparing data with measurements taken in abnormal pregnancy states.

The effect of nifedipine and methyldopa on maternal cerebral circulation.

OBJECTIVE: To study how the treatment of severe gestational hypertension affects maternal middle cerebral artery velocimetry. DESIGN: Prospective, clinical, descriptive study. SETTING: John Radcliffe Maternity Hospital, Oxford, England. PARTICIPANTS: Pregnant and puerperal women who required acute or chronic antihypertensive treatment with nifedipine (n = 46) or methyldopa (n = 26), respectively. METHODS: Transcranial Doppler ultrasound examinations of maternal middle cerebral arteries were performed before and 45 min after nifedipine; and before and 48 hours after the onset of methyldopa therapy. Blood pressure and heart rate were also recorded. MAIN OUTCOME MEASURES: Clinical and transcranial Doppler changes induced by the antihypertensive medication. RESULTS: Blood pressure and middle cerebral artery velocities decreased significantly following both short- and long-acting antihypertensive therapy. Nifedipine-induced changes were more pronounced and uniform than those found after methyldopa (16.7% and 6.4% decrease in middle cerebral artery mean velocity, respectively). The middle cerebral artery mean velocity decrease was independent of changes in the blood pressure or heart rate. CONCLUSIONS: Maternal cerebral haemodynamics are influenced by antihypertensive treatment. The reduction of middle cerebral artery flow velocities following administration of nifedipine and methyldopa may suggest that cerebral vasodilatation is occurring, which is consistent with the concept that cerebral vasospasm is present in women with pre-eclampsia. The cerebral vasodilatation could result from a direct effect of the medication on the arteries in question.

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.