Postmortem examination of human fetal hearts at or below 20 weeks' gestation: a comparison of high-field MRI at 9.4 T with lower-field MRI magnets and stereomicroscopic autopsy.

OBJECTIVES: To compare the diagnostic usefulness of high-field with low-field magnetic resonance imaging (MRI) and stereomicroscopic autopsy for examination of the heart in fetuses at or under 20 weeks' gestation. METHODS: Prior to invasive stereomicroscopic autopsy, MRI scans at 9.4, 3.0 and 1.5 T were performed on 24 fetuses between 11 and 20 weeks' gestation, including 10 fetuses with cardiac abnormalities. The ability to visualize different heart structures was evaluated according to the different field strength MRI magnets used and gestational age at examination. RESULTS: On 1.5- and 3.0-T MRI, only the heart situs and four-chamber view could be visualized consistently (in 75% or more of cases) when the fetus was beyond 16 weeks' gestation, but other heart structures could not be visualized for fetuses at any gestational age. In contrast, using high-field MRI at 9.4 T, the heart situs, four-chamber view and the outflow tracts could be visualized in all fetuses irrespective of gestational age. Using high-field MRI, the sensitivity for detecting an abnormality of the four-chamber view was 66.7% (95% CI, 30.1-92.1%) with a specificity of 80.0% (95% CI, 51.9-95.4%). For abnormalities of the outflow tracts, sensitivity was 75.0% (95% CI, 20.3-95.9%) and specificity 100.0% (95% CI, 83.3-100.0%). Eight fetuses out of 10 with congenital heart disease (CHD) were classified as having major CHD. High-field MRI at 9.4 T was able to identify seven out of the eight cases of major CHD. CONCLUSION: High-field MRI at 9.4 T seems to be an acceptable alternative approach to invasive stereomicroscopic autopsy for fetuses with CHD at or below 20 weeks' gestation.

Acceptance, reliability and confidence of diagnosis of fetal and neonatal virtuopsy compared with conventional autopsy: a prospective study.

OBJECTIVES: To compare prospectively maternal acceptance of fetal and neonatal virtuopsy with that of conventional autopsy and to determine the confidence with which magnetic resonance (MR) virtuopsy can be used to diagnose normality/abnormality of various fetal anatomical structures. METHODS: MR and/or computed tomography virtuopsy and conventional autopsy were offered to 96 women (102 fetuses/neonates) following termination of pregnancy (TOP), intrauterine fetal death (IUFD) or neonatal death. Multivariable logistic regression analysis was used to investigate the effect on maternal acceptance of virtuopsy and/or conventional autopsy of the age of the mother, gestational age at TOP or delivery after IUFD, order of pregnancy, parity, religion, type of caregiver obtaining consent and reason for death. When parents consented to both MR virtuopsy and conventional autopsy of fetuses ≥ 20 weeks of gestation or neonates, the confidence with which MR virtuopsy could be used to diagnose normality/abnormality of various anatomical structures was determined on a scale in which conventional autopsy was considered gold standard. On autopsy we classified fetuses/neonates as having either 'normal' or 'abnormal' anatomical structures; these groups were analyzed separately. At virtuopsy, we indicated confidence of diagnosis of normality/abnormality of every anatomical structure in each of these two groups defined at autopsy, using a scale from 0 (definitely abnormal) to 100 (definitely normal). RESULTS: Of the 96 women, 99% (n = 95) consented to virtuopsy and 61.5% (n = 59) to both conventional autopsy and virtuopsy; i.e. 36 (37.5%) consented to virtuopsy alone. Maternal acceptance of conventional autopsy was independently positively related to singleton pregnancy, non-Moslem mother, earlier gestation at TOP or delivery afer IUFD and a maternal-fetal medicine specialist obtaining consent. Thirty-three fetuses ≥ 20 weeks of gestation had both conventional autopsy and MR virtuopsy, of which 19 had a full autopsy including the brain. In fetuses with normal anatomical structures at conventional autopsy, MR virtuopsy was associated with high diagnostic confidence (scores > 80) for the brain, skeleton, thoracic organs except the heart, abdominal organs except the pancreas, ureters, bladder and genitals. In fetuses with abnormal anatomical structures at autopsy, MR virtuopsy detected the anomalies with high confidence (scores < 20) for these same anatomical structures. However, in three cases, virtuopsy diagnosed brain anomalies additional to those observed at conventional autopsy. CONCLUSION: MR virtuopsy is accepted by nearly all mothers while conventional autopsy is accepted by about two-thirds of mothers, in whom refusal depends mainly on factors over which we have no control. Although conventional autopsy remains the gold standard, the high acceptance of virtuopsy makes it an acceptable alternative when the former is declined.

Magnetic resonance imaging in the normal fetal heart and in congenital heart disease.

OBJECTIVE: To evaluate prospectively the feasibility of magnetic resonance imaging (MRI) for assessment of the fetal heart for congenital heart disease (CHD). METHODS: This was a cross-sectional study, including 66 fetuses with a normal heart and 40 with CHD. The fetal heart was examined on MRI using axial steady-state free precession (SSFP) sequences. Regression analysis was used to investigate the effect on the ability to visualize cardiac anatomy of gestational age at examination, maternal body mass index, presence of fetal cardiac abnormality, fetal movements, fetal lie and twinning. The sensitivity and specificity of detecting cardiac defects were calculated. RESULTS: The four-chamber view was visualized in 98.1% of fetuses. The sensitivity of detecting a cardiac defect on the four-chamber view was 88% and the specificity 96%. The ability to visualize the left and right outflow tracts was only influenced by the presence of fetal movements: for the left outflow tract 94.4 vs. 50.0% visualization and for the right outflow tract 92.6 vs. 53.8% visualization without and with fetal movements, respectively. The sensitivity of detecting a cardiac defect of the left outflow tract was 63% and the specificity 100%, while sensitivity and specificity were 59 and 97%, respectively, for the right outflow tract. CONCLUSIONS: Despite the use of SSFP sequences, MRI in the fetal heart remains of limited value. It can only be used as a second-line approach for abnormalities of the four-chamber view suspected at prenatal ultrasound.

Use of a high-frequency linear transducer and MTI filtered color flow mapping in the assessment of fetal heart anatomy at the routine 11 to 13 + 6-week scan: a randomized trial.

OBJECTIVE: To prospectively assess the contribution of a high-frequency linear transducer and of moving target indicator (MTI) filtered color flow mapping in the visualization of cardiac fetal anatomy at the routine 11 to 13 + 6-week scan. METHODS: This was a cross-sectional prospective study, including 300 singleton fetuses at 11 to 13 + 6 weeks' gestation. Patients were randomized into four groups and a detailed fetal cardiac examination was conducted transabdominally using either a conventional curvilinear transducer, a conventional curvilinear transducer and MTI filtered color flow mapping, a high-frequency linear transducer or a high-frequency linear transducer and MTI filtered color flow mapping. Regression analysis was used to investigate the effect on the ability to visualize different cardiac structures of the following parameters: gestational age at ultrasound examination; fetal crown-rump length (CRL); maternal body mass index (BMI); transducer-heart distance; the technique used at ultrasound; and the position of the placenta. RESULTS: The four-chamber view was visualized in 89.0% of fetuses and regression analysis showed this rate was correlated with CRL and the use of MTI filtered color flow mapping during ultrasonography, and inversely correlated with BMI and transducer-heart distance. Use of a conventional curvilinear transducer and MTI filtered color flow mapping allowed visualization of the four-chamber view in 97.3% of fetuses, while this was only possible in 84.0% of fetuses using a high-frequency linear transducer. The left and right outflow tracts were visualized in 62.3 and 57.7% of fetuses, respectively. Regression analysis showed that the ability to visualize the left or the right outflow tract was correlated with the use of MTI filtered color flow mapping during scanning and was inversely correlated with transducer-heart distance. The use of a conventional curvilinear transducer and MTI filtered color flow mapping allowed visualization of the left and right outflow tracts in 96.0 and 97.3% of fetuses, respectively, while this was only possible in 37.3 and 26.7% of fetuses using a high-frequency linear transducer. CONCLUSIONS: During the routine 11 to 13 + 6-week scan, the use of MTI filtered color flow mapping but not of a high-frequency linear transducer, improves visualization of cardiac anatomy.

Obstetric outcome after fetal reduction to singleton pregnancies.

OBJECTIVE: To study the outcome after fetal reduction or selective termination to singleton pregnancies for various indications. METHODS: Fetal reduction or selective feticide to singleton pregnancies was performed in 80 multiple gestations (congenital malformations, 17 cases; high-risk obstetric conditions, 25 cases; or social/psychological indications, 38 cases). RESULTS: The overall pregnancy loss rate was 10%; however, pregnancy failure was significantly higher in selective reductions performed for preterm prelabor rupture of membranes (PPROM) (4/8) compared with monochorionic twin and bad obstetric history. Fetal reduction to singletons for psychological reasons resulted in a pregnancy wastage of 5.3% (2/38). Procedures performed at < or =14 weeks showed a significantly lower fetal loss rate (2/61; 3.3%), a higher mean gestational age at delivery (38.3+/-2.2 weeks), and a decreased prematurity rate (p< or =0.001). The number of reduced fetuses, prenatal diagnosis by chorionic villus sampling before the reduction and maternal age did not interfere with pregnancy outcome. CONCLUSION: Fetal reduction to singleton pregnancies has a favorable outcome, especially when performed before 14 weeks of gestation.

Transient fetal hypothyroidism due to direct fetal administration of amiodarone for drug resistant fetal tachycardia.

Amiodarone, an anti-arrhythmic drug that contains 39% iodine, is rarely known to cause negative effects on fetal thyroid function after gestational exposure, when given orally to a pregnant woman. Two cases of fetal hypothyroidism after gestational exposure to amiodarone by direct fetal intravenous route are described here.

Prevention of congenital toxoplasmosis.

In utero infection with Toxoplasma gondii may result in congenital defects such as hydrocephalus, chorioretinitis and mental retardation; these defects may be present at birth or may develop later in life. Prevention of this disease can be achieved in different ways. The most effective measure is to prevent the acquisition of the disease during pregnancy by avoiding risk factors for Toxoplasma gondii infection. Health education may decrease the incidence of toxoplasmosis during pregnancy by 60%. A second preventive measure is based on serologic screening during pregnancy to identify infected women. Treatment during pregnancy results in a significant reduction in the incidence of sequelae including severe handicaps. A third possible intervention is treating infected neonates. Antibiotic treatment of infected children has a beneficial effect on the development of sequelae and the sooner therapy is started after birth, the better the outcome. This overview presents the potential benefits and harms of these different options available for the prevention of congenital toxoplasmosis.

Outcome of twin gestations after first trimester chorionic villus sampling.

OBJECTIVE: To tabulate genetic results and obstetric outcomes of twin pregnancies after first-trimester chorionic villus sampling (CVS). METHODS: The study included 262 consecutive women with twin pregnancies who had first-trimester CVS between 1988 and 1998. RESULTS: Major indications for prenatal diagnosis included maternal age (n = 82), pregnancies after intracytoplasmic sperm injection (n = 114), or both (n = 33). Among 524 fetuses, 519 were sampled adequately. Cytogenetic results were incorrect because of sampling the same fetus twice in two pregnancies. In three pregnancies, contamination caused by mixed sampling made cytogenetic results uncertain. Correct genetic diagnoses were obtained in 509 fetuses, 24 of which had chromosomal abnormalities on direct preparations and four of which had monogenetic conditions. Additional invasive procedures were done on five occasions. Fifteen fetuses were terminated selectively. The total fetal loss rate was 5.5% (28 of 509). The indication for the procedure did not significantly determine the fetal loss rate. The mean +/- standard deviation (SD) gestational age at birth was 35.9 +/- 2.9 weeks, and the mean +/- SD birth weights for twins A and B were 2429 +/- 589.1 g and 2378 +/- 588.5 g, respectively. CONCLUSION: First-trimester CVS is an accurate means of prenatal genetic diagnosis in twins, offering early selective termination in cases of abnormal genetic results in one of the fetuses.

Uterine artery pseudo-aneurysm: diagnosis and therapy during pregnancy.

Arterial aneurysms and pseudo-aneurysms are a rare but recognized cause of obstetric hemorrhage. Diagnosis during pregnancy, prior to rupture, is exceptional. We report the first case of diagnosis and treatment of an uterine artery pseudo-aneurysm during pregnancy.

Sources of toxoplasma infection in pregnant women: European multicentre case-control study. European Research Network on Congenital Toxoplasmosis.

OBJECTIVE: To determine the odds ratio and population attributable fraction associated with food and environmental risk factors for acute toxoplasmosis in pregnancy. DESIGN: Case-control study. SETTING: Six large European cities. PARTICIPANTS: Pregnant women with acute infection (cases) detected by seroconversion or positive for anti-Toxoplasma gondii IgM were compared with pregnant women seronegative for toxoplasma (controls). MAIN OUTCOME MEASURES: Odds ratios for acute infection adjusted for confounding variables; the population attributable fraction for risk factors. RESULTS: Risk factors most strongly predictive of acute infection in pregnant women were eating undercooked lamb, beef, or game, contact with soil, and travel outside Europe and the United States and Canada. Contact with cats was not a risk factor. Between 30% and 63% of infections in different centres were attributed to consumption of undercooked or cured meat products and 6% to 17% to soil contact. CONCLUSIONS: Inadequately cooked or cured meat is the main risk factor for infection with toxoplasma in all centres. Preventive strategies should aim to reduce prevalence of infection in meat, improve labelling of meat according to farming and processing methods, and improve the quality and consistency of health information given to pregnant women.

Diagnosis of congenital toxoplasmosis in the neonatal period: A multicenter evaluation.

OBJECTIVE: To evaluate different laboratory tests used to diagnose congenital toxoplasmosis in the neonatal period. STUDY DESIGN: A retrospective multicenter study of 294 pregnant women who experienced seroconversion for Toxoplasma gondii and subsequently delivered live-born infants. Fetal infection was assessed via specific IgM and IgA antibodies (cord and neonatal blood) and detection of T gondii in placenta and cord blood by mouse inoculation. RESULTS: Ninety-three (32%) of the 294 infants were congenitally infected. The sensitivity of IgA in cord blood and in neonatal blood was 64% and 66%; the sensitivity of IgM was 41% and 42%, respectively. Mouse inoculation of the placenta and cord blood had sensitivities of 45% and 16%. Positive results of the serologic tests in congenitally infected children correlated significantly with the gestational age at the time of maternal infection but was not significantly influenced by the administration of specific antiparasitic treatment during pregnancy. CONCLUSION: Specific T gondii IgA antibody is a more sensitive test than IgM for detecting congenital toxoplasmosis in the neonatal period. The overall specificity is better for serologic tests performed on neonatal blood than for those on cord blood. Neonatal screening with IgM or IgA antibodies will not detect the majority of children with congenital toxoplasmosis when the maternal infection occurred before the 20th week of pregnancy.

Prenatal diagnosis of congenital toxoplasmosis: a multicenter evaluation of different diagnostic parameters.

OBJECTIVE: Our purpose was to evaluate different methods of diagnosing congenital toxoplasmosis prenatally by amniocentesis and cordocentesis. STUDY DESIGN: In a retrospective multicenter study, we investigated consecutive women who had seroconversion for Toxoplasma gondii during pregnancy and who underwent either amniocentesis or cordocentesis or both to obtain a prenatal diagnosis of fetal toxoplasmosis. Data were obtained from 122 patients recruited in 6 different European Toxoplasma reference centers. Infants born to these mothers were followed up until 1 year of age to confirm or exclude congenital toxoplasmosis. Sensitivity, specificity, positive predictive value, and negative predictive value were measured for the following parameters: (1) detection of the parasite in amniotic fluid by mouse inoculation, (2) detection of the parasite in amniotic fluid by in vitro cell culture, (3) detection of Toxoplasma deoxyribonucleic acid in amniotic fluid by a polymerase chain reaction assay, (4) detection of the parasite in fetal blood by mouse inoculation, (5) detection of specific immunoglobulin M antibodies in fetal blood, and (6) detection of specific immunoglobulin A antibodies in fetal blood. RESULTS: The polymerase chain reaction test performed on amniotic fluid had the highest level of sensitivity (81%) and also a high level of specificity (96%). The combination of the polymerase chain reaction test and mouse inoculation of amniotic fluid increased sensitivity to 91%. The sensitivity of immunoglobulins M and A in fetal blood was 47% and 38%, respectively. In congenitally infected fetuses a negative correlation was observed between positive serologic parameters and gestational age at the time of maternal infection and at prenatal diagnosis. CONCLUSION: Congenital toxoplasmosis is best predicted by prenatal examination with the combination of T gondii polymerase chain reaction and mouse inoculation of amniotic fluid. The role of cordocentesis in the diagnosis of congenital toxoplasmosis is limited.

Neonatal screening for congenital cytomegalovirus infections.

We evaluated a screening program for the detection of congenital cytomegalovirus in 3075 unselected pregnant women. From each live-born child urine for CMV culture was collected within 7 days after birth. Each fetus expelled after a spontaneous second trimester abortion and each stillborn infant were also evaluated for a possible congenital CMV infection. For each congenital infection stored maternal sera were analysed to determine whether maternal infection was primary or recurrent. Fifteen out of the 3075 pregnancies studied resulted in a congenitally infected infant (0.49%). Nine maternal CMV infections were primary infections; five were recurrent infections, and in one case the type of infection could not be determined. Three congenital infections resulted in severe sequelae, leading to the termination of pregnancy in two instances and to neonatal death in one case. One of these severe fetal infections was due to a recurrent maternal infection. Follow-up of the other 12 neonates demonstrated hearing disorders in two children. One was born after a primary maternal infection and one after a recurrent maternal infection. We conclude that congenital CMV infections occurs in 0.49% of all pregnancies in the population studied. Twenty percent of the congenitally infected infants present severe sequelae at birth or during pregnancy, and an additional 17% have audiological deficits at 1 year of age. Severe sequelae may occur after both primary and recurrent maternal CMV infection.

Treatment of toxoplasmosis during pregnancy: a multicenter study of impact on fetal transmission and children's sequelae at age 1 year.

OBJECTIVE: Toxoplasmosis during pregnancy can cause fetal infection, with unpredictable sequelae in later life. We measured the effects of prenatal antibiotic therapy on the fetomaternal transmission of Toxoplasma gondii and on the appearance of sequelae in the congenitally infected child at age 1 year. STUDY DESIGN: In a multicenter study we investigated consecutive women with Toxoplasma seroconversion during pregnancy. Data were obtained from 144 women recruited in 5 different Toxoplasma reference centers. Through multivariate analysis we assessed the association between transmission and appearance of sequelae as a function of the following parameters: estimated gestational age at infection, administration of antibiotic therapy, duration of antibiotic therapy, and time lapse between infection and the start of antibiotic therapy. RESULTS: Sixty-four of the 144 women (44%) gave birth to a congenitally infected infant. Multivariate analysis showed that transmission was predicted neither by whether antibiotics had been administered nor by the time lapse between infection and the start of antibiotic therapy, but only by the gestational age at which maternal infection occurred (P <.0001). Sequelae were found in 19 children (13%), 9 of whom (6%) had severe sequelae. Administration of antibiotics was predictive of the absence of sequelae (P =.026, odds ratio 0.30, 95% confidence interval 0.104-0.863), in particular the absence of severe sequelae (P =.007, odds ratio 0.14, 95% confidence interval 0.036-0.584). The sooner antibiotics were given after the infection, the less frequently sequelae were seen (P =. 021). CONCLUSION: Prenatal antibiotic therapy after toxoplasmosis during pregnancy had no impact on the fetomaternal transmission rate but reduced the rate of sequelae among the infected infants. The early start of treatment resulted in a significant reduction in the number of severely affected infants.

Discordant prenatal diagnosis of congenital toxoplasmosis in a dizygotic pregnancy.

Prenatal diagnosis of toxoplasmosis gondii in twin pregnancies has been described twice. In both cases they were accomplished by prenatal blood sampling of the foetuses. We report the first prenatal diagnosis with a discordant result in a dizygotic pregnancy. One of the foetuses died in utero and the other was born unaffected at term.

Prenatal diagnosis by chorionic villus sampling in multiple pregnancies prior to fetal reduction.

Ovulation induction and assisted-reproduction techniques have dramatically increased the incidence of high-risk multiple pregnancies over the past 10 years. Perinatal outcome may be improved by the use of multifetal reduction. The fetus to be reduced used to be selected only on technical grounds. We report on the results of prenatal diagnosis by chorionic villus sampling (CVS) during the first trimester in 32 multifetal pregnancies in which fetal reduction was requested. The mean gestational age at CVS was 10.5 weeks. Chromosomal analyses were available for all sampled fetuses, three of which were chromosomally abnormal. In 24 couples, fetal reduction to twin pregnancies was successfully carried out within 1 week after the CVS. In seven cases, the couples elected not to proceed with fetal reduction after receiving information that the chromosomal analysis was normal in all fetuses. Mean gestational ages at delivery were, respectively, 34.6 and 31.8 weeks in the reduced and the nonreduced groups (p = 0.04). No fetal losses occurred in either group; one neonatal death was observed after a preterm delivery because of preeclampsia in a twin pregnancy. Prenatal cytogenetic diagnosis during the first trimester in multiple pregnancies prior to fetal reduction appears to be feasible, accurate, and safe. Abnormal chromosomal results indicate the fetus(es) to be reduced. The parents' decisions not to proceed with the fetal reduction procedure, where chromosomal results in all the fetuses were normal, were unexpected.

Circulating CD34+ cells in cord blood and mobilized blood have a different profile of adhesion molecules than bone marrow CD34+ cells.

The expression of adhesion molecules was studied on CD34+ hematopoietic precursors in cord blood, bone marrow and mobilized blood. The samples were labeled in a double immunofluorescence procedure with a CD34 monoclonal antibody and with antibodies against maturation and differentiation antigens and adhesion molecules. Myeloid precursors formed the majority of the CD34+ cells in all samples. In bone marrow a separate cluster of B-cell precursors with low forward scatter was present. Nearly all CD34+ cells in normal bone marrow expressed VLA-4 and VLA-5, PECAM-1, LFA-3 and HCAM. The majority of the CD34+ cells also had LFA -1 and L-selectin on the surface membrane. A small subset was VLA-2, VLA-3, ICAM-1 or Mac-1 positive. CD34+ cells expressing the vitronectin receptor or the CD11c antigen were rare. Cord blood and mobilized blood CD34+ cells had a lower expression of VLA-2, VLA-3 and VLA-5 and a higher expression of LFA-1, ICAM-1 and L-selectin than bone marrow CD34+ cells. Except for LFA-1, this was not due to the presence of more myeloid precursors in these samples. Low beta1 integrin expression may lead to less adhesion to the extracellular matrix. High expression of L-selectin may facilitate interaction with endothelial cells. Therefore, this phenotype may favour mobilization.

Anaesthetic management of a parturient with severe congenital factor XI deficiency undergoing caesarean section for triplet pregnancy.

The report describes the anaesthetic management of a Jewish patient of Ashkenazi descent with severe factor XI deficiency complicated by thrombocytopenia for caesarean section for triplets at the 35th week of gestation. Perioperative management consisted of sustained replacement therapy with fresh frozen plasma and platelets until the sixth postoperative day. General anaesthesia was used for the procedure. No other maternal or neonatal complications occurred.