Total uterine artery blood volume flow rate in nulliparous women is associated with birth weight and gestational age at delivery.

OBJECTIVES: To investigate the relationship between total uterine artery blood volume flow rate (TVFR) and birth weight and gestational age at delivery, and to establish normal ranges of TVFR throughout pregnancy. METHODS: This was a prospective cohort study of 334 nulliparous women booking antenatal care at University College London Hospital between August 2008 and September 2009. Women underwent a transabdominal ultrasound examination of uterine arteries for measurement of TVFR at 12, 20 and 24 weeks' gestation. Pregnancy outcomes were recorded and linear regression was used to study the relationship between TVFR and gestational age at delivery and birth weight. RESULTS: A total of 551 ultrasound scans were performed. There was a significant, positive correlation between TVFR at 11-13 weeks (TVFR1) and at 22-26 weeks (TVFR3) and birth weight. For every 100-mL/min increase in TVFR1 and TVFR3, there was an increase in birth weight of 45 g and 27 g, respectively. There was also a positive association between TVFR1 and gestational age at delivery, with a 1.4-day increase in gestational age for every 100-mL/min increase of TVFR1. CONCLUSION: Ultrasound measurement of TVFR in the first trimester is significantly associated with both birth weight and gestational age at delivery. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

The relationship between body mass index and mid-arm circumference in a pregnant population.

Our objective was to correlate body mass index (BMI) with mid-arm circumference (MAC) and also to ascertain whether maternal BMI could be calculated from MAC at booking. We approached all Caucasian women who met the inclusion criteria attending the University College Hospital, London between 1 April 1996 and 30 June 1997 and the Rotunda Hospital, Dublin, Ireland between 15 April 2003 and 19 May 2004. A total of 2,912 women agreed to participate in the research. The participants' maternal height and weight were measured. Their BMI was calculated using the formula: BMI = weight (kg) ÷ height (m(2)). The MAC was measured in cm. Statistical analysis was performed using SPSS for Windows version 11 with p < 0.05 as significant. We found that BMI is directly correlated with MAC (r = 0.836) and estimates of BMI may be calculated from the simple equation BMI = MAC ± 2. Alternatively, a MAC of ≥ 27 cm allowed for a detection rate for overweight patients of 75%, with a false positive rate of 15%.

Antenatal screening for Down's syndrome using the Integrated test at two London hospitals.

We carried out an audit of antenatal screening for Down's syndrome using the Integrated test (which provides a single screening result from information collected in the late first and early second trimesters of pregnancy) which was introduced into routine antenatal care at two London hospitals, University College Hospital (UCH) and St Mary's Hospital, in 2003-4. The audit was based on 15,888 women who accepted screening and booked in the first trimester. The Down's syndrome detection rate was 87% (95% confidence interval [CI], 74-95) consistent with an expected detection rate of 89% based on applying the estimates of screening performance of the Serum, Urine and Ultrasound Screening Study (SURUSS) to the maternal age distribution of women who were screened at UCH and St Mary's. The observed false-positive rate was 2.1% (95% CI, 1.9-2.3), compared with an expected of 2.5% for women of the same age. An audit trail (conducted at UCH) indicated that 98% (10,746/10,961) of women accepted integrated screening (2% having a first trimester test) and of these, 94% (10,116) completed both stages of the test. The audit demonstrated that it is feasible to conduct integrated screening within the NHS with a high acceptance rate and a screening performance consistent with that determined from previous research studies.

Local delivery of VEGF adenovirus to the uterine artery increases vasorelaxation and uterine blood flow in the pregnant sheep.

Impaired materno-placental perfusion causes two important obstetric complications, fetal growth restriction and preeclampsia. This study investigated whether adenoviral vector-mediated overexpression of vascular endothelial growth factor (VEGF) in the uterine arteries (UtAs) increases uterine artery blood flow (UBF). First-generation adenovirus vectors (5 x 10(11) particles) containing the VEGF gene (Ad.VEGF-A or -D) or the beta-galactosidase reporter gene (Ad.lacZ) were injected into the UtAs of pregnant sheep (n=6) at 88-102 days of gestation (term=145 days). UBF was measured using Doppler sonography before, and 4-7 days after injection. Mean UBF increased significantly from 233+/-156 (s.d.) ml min(-1) to 753+/-415 ml min(-1) following Ad.VEGF-A injection (P=0.005, n=5); Ad.lacZ infection had no significant effect. Organ bath experiments on uterine arterial sections 4-7 days after injection showed that, compared with Ad.lacZ vessels, Ad.VEGF-A-transduced vessels had a reduced contractile response to phenylephrine (E max 148+/-10.9 vs E max 228.2+/-27.5, P<0.05) but increased relaxation with bradykinin (pD2 (-log EC50) values 9.11+/-0.01 vs 8.65+/-0.11, P<0.05). Injection of Ad.VEGF-A into the UtAs increases UBF by enhancing vasodilatation. This may provide the basis for therapy in pregnancies complicated by uteroplacental insufficiency.

Association of isolated short femur in the mid-trimester fetus with perinatal outcome.

OBJECTIVES: To evaluate the prevalence of fetal isolated short femur in a cohort of women screened for Down syndrome by the integrated test, and to compare the outcome of fetuses with isolated short femur in the mid-trimester with that of fetuses with normal femur length (controls). METHODS: This was a retrospective cohort study of 1262 women booked for antenatal care and delivery at University College London Hospital. All women had integrated testing in the late first and early second trimesters and a detailed anomaly scan in the mid-trimester. All scan reports, screening results and neonatal data were analyzed statistically. RESULTS: The fetal femur was short (< 5(th) percentile) in 5.1% of patients and 4.7% had isolated short femur. In pregnancies with isolated short femur, the birth weight was significantly lower and there were higher rates of small-for-gestational age (SGA) and low birth weight (LBW) infants, compared with controls (P < 0.01). The odds ratios for SGA and LBW in pregnancies with isolated short femur were 3.0 (95% CI, 1.5-5.9) and 2.60 (95% CI, 1.1-6.2), respectively. Isolated short femur was associated significantly with low levels of pregnancy-associated plasma protein-A (P = 0.001). CONCLUSIONS: Isolated short femur in the mid-trimester fetus is associated with fetal growth restriction and SGA. In the context of normal Down syndrome screening and a normal anomaly scan, this marker should be regarded as a predictor for SGA, and fetal growth should be monitored during these pregnancies.

Urinary excretion of inositol phosphoglycan P-type in gestational diabetes mellitus.

OBJECTIVE: The mechanisms underlying insulin resistance during normal pregnancy, and its further exacerbation in pregnancies complicated by gestational diabetes mellitus (GDM), are generally unknown. Inositolphosphoglycan P-type (P-IPG), a putative second messenger of insulin, correlates with the degree of insulin resistance in diabetic subjects. An increase during normal pregnancy, in maternal and fetal compartments, has recently been reported. METHODS: A cross-sectional study was carried out in 48 women with GDM and 23 healthy pregnant women. Urinary levels of P-IPG were assessed spectrophotometrically by the activation of pyruvate dehydrogenase phosphatase in urinary specimens and correlated with clinical parameters. RESULTS: Urinary excretion of P-IPG was higher in GDM than in control women (312.1 +/- 151.0 vs. 210.6 +/- 82.7 nmol NADH/min/mg creatinine, P < 0.01) with values increasing throughout pregnancy in control subjects (r2 = 0.34, P < 0.01). P-IPG correlated with blood glucose levels (r(2) = 0.39, P < 0.01 for postprandial glycaemia and r2 = 0.18 P < 0.01 for mean glycaemia) and birthweight in the diabetic group (r2 = 0.14, P < 0.01). CONCLUSIONS: Increased P-IPG urinary excretion occurs in GDM and positively correlates with blood glucose levels. P-IPG may play a role in maternal glycaemic control and, possibly, fetal growth in GDM.

Polymorphisms in the angiotensin converting enzyme gene and growth in the first year of life.

Abnormal patterns of fetal and infant growth have been associated with an increased risk of cardiovascular disease in adulthood. Catch-up growth during the first year of life has been associated with a higher prevalence of type 2 diabetes mellitus, whereas a lack of catch-up growth tracks with a risk of hypertension. The role of genetic factors influencing both growth and blood pressure have not been explored. We genotyped cord blood samples from 530 singleton, Caucasian, uncomplicated pregnancies, drawn from a larger cohort of 1650 pregnancies, and related polymorphism in the angiotensin converting enzyme (ACE) gene (alleles insertion (I) or deletion (D)) with measures of size at birth and at age of 1 year. ACE genotype did not significantly influence size at birth, although there was a greater proportion of individuals with the D/D genotype born with a birth weight less than the 10th centile (P=0.004). The ACE I/I genotype was significantly associated with higher weight (p=0.001), body mass index (p=0.001) and mid arm circumference (p=0.001) at 1 year of age compared to the ACE D/D and I/D genotypes. Individuals with the I/I genotype displayed catch-up (gain from birth size of >or=0.6 Standard Deviation Score) in weight (p=0.04), body mass index (p=0.03) and mid arm circumference (p=0.03) compared to the D/D group, the majority of which showed no change or catch-down. The I/D genotype was distributed equally across the catch up/catch down/no change categories. The effect was more marked in males, but ACE genotype and sex of the infant contributed independently to mid arm circumference measurements and there was no interaction between the two. There was no effect of maternal or paternal ACE genotype on birth size. In a multiple linear regression model ACE genotype, socioeconomic status and sex of the infant explained 10.9% of the variance in body mass index SDS at 1 year of age. We conclude that the ACE I/I genotype is associated with a higher weight and body mass index SDS at 1 year of age, along with catch-up in terms of these measures from birth to 1 year. The D/D genotype is associated with a greater proportion of babies, born at term, that at small for gestational age. These results suggest that due consideration should be given to the underlying genotype of an individual when evaluating the association of early human growth with the development of risk factors for cardiovascular disease. The observation of independent effects of genotype, sex of the individual and socioeconomic status on postnatal growth suggests the need to develop methodologies for the integration of genetic and environmental factors in causality modelling.

Clinically applicable procedure for gene delivery to fetal gut by ultrasound-guided gastric injection: toward prenatal prevention of early-onset intestinal diseases.

Targeting gene therapy vectors to the fetal intestinal tract could provide a novel means toward prevention of the early postnatal intestinal pathology of cystic fibrosis and other conditions, such as congenital enteropathy, that cause intestinal failure. Among these conditions, cystic fibrosis is by far the most common lethal genetic disease. It is caused by a functional absence or deficiency of the cystic fibrosis transmembrane conductance regulator and manifests in the gut as meconium ileus. Prenatal treatment of genetic disease may avoid early-onset tissue damage and immune sensitization, and may target cells that are less accessible in the adult. We investigated gene transfer to the fetal gut, using a minimally invasive injection technique. First-generation replication-deficient adenoviral vectors encoding the beta-galactosidase gene and transduction-enhancing agents were injected into the stomach of early-gestation fetal sheep (n = 8, 60 days of gestation; term, 145 days) under ultrasound guidance. Reporter gene expression was observed 2 days after injection in the villi of the gastrointestinal epithelia after 5-bromo-4-chloro-3-indolyl-beta-D-galactopyranoside staining and beta-galactosidase immunohistochemistry of fetal tissues. Expression of beta-galactosidase, as measured by enzyme-linked immunosorbent assay, was enhanced after pretreatment of the fetal gut with sodium caprate, which opens tight junctions, and after adenovirus complexation with DEAE-dextran, which confers a positive charge to the virus. Instillation of the fluorocarbon perflubron after virus delivery resulted in tissue transduction from the fetal stomach to the colon. Using a clinically relevant technique, we have demonstrated widespread gene transfer to the fetal gastrointestinal epithelia.

Ultrasound-guided injection and occlusion of the trachea in fetal sheep.

OBJECTIVES: To access the fetal sheep trachea by ultrasound-guided transthoracic injection in order to deliver gene therapy vectors or occlude the trachea with a detachable balloon. METHODS: Fetal sheep were operated on at a mean gestational age of 102 (range, 81-116) days (term = 145 days). Under ultrasound guidance, either a 20-G spinal (for vector delivery) or a 16-G Kellett (for placement of an occlusive balloon) needle was inserted via the fetal thorax into the fetal trachea. RESULTS: Using the 20-G spinal needle the trachea was accessed successfully in 33/36 fetuses, with 97% survival. Failure to inject was related to fetal position and gestational age. Blood vessel damage causing significant morbidity occurred in two fetuses (6%). Tracheal occlusion was achieved by puncturing the trachea with the 16-G needle and advancing an endoluminal balloon in three out of five attempts in a mean time of 17 (range, 16-19) min, with 100% survival. In one case, the balloon became sited within the accessory lobe bronchus and was not inflated. At postmortem examination 21 days later, all balloons remained inflated and occluded the trachea, and the lung-to-body weight ratio and airways morphometric indices were consistent with relative pulmonary hyperplasia in the obstructed lungs. CONCLUSIONS: Ultrasound-guided transthoracic tracheal puncture is a reliable technique in fetal sheep, with low morbidity and mortality. Using this technique, a detachable endotracheal balloon can be placed to provoke pulmonary growth. Advances in needle design and balloon size may improve the success rate.

Prenatal diagnosis for severe inherited skin disorders: 25 years' experience.

BACKGROUND: Over the last 25 years there have been major advances in methods for prenatal testing of inherited skin disorders. Since 1979, our group at the St John's Institute of Dermatology has performed 269 prenatal diagnoses, using a variety of approaches, including fetal skin biopsy (FSB), chorionic villus sampling (CVS) and preimplantation genetic diagnosis (PGD). OBJECTIVES: This study was designed to review the clinical indications, testing procedures and laboratory analyses for all prenatal tests conducted at St John's over this period. METHODS: FSBs were examined for morphological and, when relevant or feasible, immunohistochemical abnormalities. The DNA-based tests involved screening by nucleotide sequencing, restriction enzyme digests or, in a few cases, by linkage analysis. Results Of the 269 tests, 191 were FSB, 76 were CVS and two were PGD. The major indications for FSB were epidermolysis bullosa (EB) (138 cases, including 88 junctional and 48 dystrophic), ichthyoses (37 cases, including 22 tests for harlequin ichthyosis) and oculocutaneous albinism (12 cases). Of the CVS procedures, 75 were for EB (40 junctional, 35 dystrophic) and one was for the EEC (ectrodactyly, ectodermal dysplasia, clefting) syndrome. Both of the PGD procedures were for the skin fragility-ectodermal dysplasia syndrome. All tests provided accurate diagnoses and the fetal loss rate was approximately 1% for both FSB and CVS. CONCLUSIONS: The development of prenatal testing has proved to be of great benefit for individuals or couples at risk of having children with severe inherited skin disorders and, in the absence of a cure, prenatal testing along with appropriate counselling has become an important translational benefit of basic research and an integral part of clinical management.

P-type inositol phosphoglycans in serum and amniotic fluid in active pre-eclampsia.

OBJECTIVES: Abnormal secretion of P-type inositol phosphoglycans (IPG-P) has been described in maternal urine of pre-eclamptic women. The aim of this study was to determine the origin of production of IPG-P. We examined the IPG-P content of maternal and fetal serum, maternal urine and amniotic fluid in both normal pregnancy and pre-eclampsia. DESIGN: Established extraction and bioactivity assay techniques were used to compare total IPG-P levels in serum samples, and a polyclonal-antibody-based ELISA to assay the amniotic fluid and urine samples in matched pairs of women. SUBJECTS: Eleven women with pre-eclampsia requiring caesarean section (subjects), 11 pregnant women requiring elective caesarean section for reasons other than pre-eclampsia (controls). RESULTS: Our data confirm the abnormal level of IPG-P in maternal urine during pre-eclampsia. Moreover, IPG-P levels were higher in umbilical sera than in maternal sera samples. Amniotic fluid as well as urine ELISA results were significantly higher in the pre-eclamptic group compared with normal controls. Total IPG-P bioactivity in serum did not vary between serum compartments in normal pregnancy. Uterine vein IPG-P levels were lower in pre-eclampsia when compared with normal pregnancy. A possible correlation was observed between urine and amniotic fluid levels in normal women. No correlation was observed between measured blood levels and those in urine and amniotic fluid. CONCLUSIONS: It is hypothesized that steady state equilibrium of IPG-P in serum in normal pregnancy is disrupted in pre-eclampsia. Additionally, an abnormal IPG-P sub-fraction, detectable in urine and amniotic fluid, may be present and involved in the pathophysiology of the syndrome, although sites of production of this abnormal form remain unclear.

In-vivo concentrations of inhibins, activin A and follistatin in human early pregnancy.

The aims of this study were to investigate the relationship between inhibins, activin A and follistatin in first trimester fetal fluids, maternal serum, placenta and decidua, and to investigate if these hormones are present in the circulation of the early second trimester human fetus. Amniotic and coelomic fluid, maternal serum, placental villi and decidual tissue were obtained from normal pregnancies at 8-12 weeks. Fetal blood by cardiocentesis and maternal blood were collected at 14-16 weeks gestation. Placental extracts had higher concentrations of inhibins, activin A and follistatin compared with decidual extracts. In the second trimester, inhibins and follistatin were detectable in fetal blood at 14-16 weeks gestation. Maternal serum concentrations of inhibin A (P < 0.001) and follistatin (P < 0.05) were significantly higher than fetal serum whereas inhibin B (P < 0.01) and pro-alpha C concentrations (P < 0.001) were higher in fetal serum. Inhibin B concentrations were also higher in male fetal serum samples that had higher concentrations of testosterone. The presence of all molecular forms of inhibins, activin A and follistatin in the first trimester fetal fluids, placental and decidual extracts in the first trimester confirms other reports. In the second trimester, high concentrations of inhibin B with testosterone in the fetal circulation indicate that these hormones may interact in the development of the male fetal gonads.

Screening for chromosomal anomalies: first or second trimester, biochemical or ultrasound?

Prenatal diagnosis pf chromosomal abnormalities can be accurately made by cytogenetic studies of samples obtained from invasive procedures, such as amniocentesis or chorionic villus sampling. Because these procedures are associated with a risk of miscarriage, the common approach is to perform non-invasive test to define an individual woman's risk of having a chromosomal abnormal pregnancy. Screening for chromosomal abnormalities has developed over the last decade. Prenatal screening can be performed in the late first trimester, the early second trimester or in both. Screening test can be carried out biochemically, ultrasonographically or by both modalities. A major goal of screening test is to achieve maximum accuracy and minimum harm at low cost. The integrated test currently meets best those criteria.

Percutaneous ultrasound-guided injection of the trachea in fetal sheep: a novel technique to target the fetal airways.

OBJECTIVE: To access the fetal airways percutaneously using ultrasound-guided injection of the fetal trachea in sheep. METHODS: Adenoviral gene therapy vectors and transduction-enhancing agents were delivered to the trachea via a needle inserted through the thorax or the neck of late-gestation (0.9 term, n = 3) or mid-gestation (0.5-0.8 term, n = 18) fetal sheep using ultrasound guidance. RESULTS: Injection of the trachea in the fetal thorax was successful in 16 out of 18 fetuses and achieved at the first attempt in 9 fetuses within 12 min [mean 7 min and 31 s +/- (SD) 3 min and 4 s]. Survival was 100%. Injecting the trachea in the neck was less successful. CONCLUSIONS: The fetal trachea of the sheep can be safely accessed by percutaneous ultrasound-guided injection to deliver vectors directly to the fetal airways for gene therapy. It may also enable tracheal occlusion for the antenatal treatment of congenital diaphragmatic hernia without the need for endoscopy or open surgery.

Preimplantation genetic diagnosis of chromosome abnormalities: implications from the outcome for couples with chromosomal rearrangements.

OBJECTIVES: Chromosomal rearrangements can lead to infertility or repeated spontaneous or induced abortions. The use of preimplantation genetic diagnosis (PGD) allows the selected transfer of chromosomally balanced embryos. The aim of this study was to carry out detailed analysis of the outcome of 11 PGD cycles for 8 patients carrying various chromosomal rearrangements. METHODS: Patients underwent routine in vitro fertilisation with biopsy of embryos on day 3. Specific fluorescent in situ hybridisation protocols were developed for each couple. Embryo transfer was possible in all 11 cycles. RESULTS: The outcome was four pregnancies, leading to three live births and one biochemical pregnancy. Post-zygotic mosaicism was detected in 75% of untransferred embryos, the majority of which were chaotic. Detailed follow-up and analysis provided evidence for the co-existence of chromosomally balanced and abnormal cells in six embryos. The mechanisms involved included chromosome breakage and loss of material. CONCLUSIONS: Biopsy and analysis of two blastomeres, where possible, reduced the risk of misdiagnosis in cases of balanced/aneuploid mosaics. The three live births achieved for the eight couples treated in this series, despite the poor history in almost all cases, is further proof that a policy of biopsying two cells from embryos consisting of six or more cells and a single cell from four- or five-cell embryos is compatible with a positive outcome.

Possible involvement of inositol phosphoglycan-P in human parturition.

Preterm labour is a major cause of neonatal morbidity and mortality but the pathophysiology that underlies preterm labour is unknown. Inositolphosphoglycans (IPGs) comprise a ubiquitous family of putative carbohydrate second messengers and they have been linked to the pathogenesis of various conditions, including diabetes and pre-eclampsia. Studying IPG-P levels in normal and pre-eclamptic pregnancies, we noticed a constant rise of urinary IPG-P levels in all women at the time of delivery. A prospective pilot study of urinary IPG-P levels in 23 non-labouring and labouring women with uncomplicated pregnancies has, therefore, been performed. Levels of urinary IPG-P were significantly higher in labour than in the non-labouring group (P<0.0001). These higher levels have been found in both spontaneous and induced labour. The clinical significance of this observation with particular reference to the onset of labour itself is discussed.

Cystic fibrosis: selecting the prenatal screening strategy of choice.

Cystic fibrosis is a serious disorder. Research into the treatment of affected individuals is in progress, but a cure is not expected in the near future. In this review, we demonstrate that prenatal screening for cystic fibrosis meets the requirements for a worthwhile screening programme. We explain the reasons that have led us to conclude that one approach ('couple screening') is the method of choice. The couple-based approach calls for reporting results to the couple as a unit. Only if both parents are found to be carriers is the result designated screen-positive and an amniocentesis or chorionic villus sampling offered. This offers a substantial reduction in the proportion of women with unaffected pregnancies with positive results (the false-positive rate) compared with other methods without reducing the detection of affected pregnancies. It also avoids creating a screen-positive group for which no definitive diagnosis is available. This is a problem with other screening methods. The couple method can achieve a 72% detection rate for a 0.1% false-positive rate. The screening method is simple, non-invasive, reliable, safe and reasonably cost effective. Existing programmes have shown that screening using this method is acceptable to health care professionals and patients. Setting up a national prenatal screening programme for cystic fibrosis is timely and should be implemented using the couple screening method.

Anti-HPA-1a-mediated platelet phagocytosis by monocytes in vitro and its inhibition by Fc gamma receptor (FcgammaR) reactive reagents.

The study was undertaken to delineate mechanisms of platelet destruction by phagocytosis during fetal/neonatal alloimmune thrombocytopenia (FAIT/NAIT) because of maternal antibodies against human platelet antigen 1a (HPA-1a). By employing a platelet phagocytosis assay based on the ORPEGEN flow cytometric bacterial phagocytosis test, we measured monocyte ingestion of platelets mediated by anti-HPA-1a antibodies. Moreover, we tested, as potential therapeutic agents, FcgammaR reactive reagents, for their inhibition of this process. Four of six anti-HPA-1a sera tested mediated phagocytosis of HPA-1a-positive platelets in a concentration-dependent manner. Monocyte ingestion of platelets was almost completely inhibited by cytochalasin D. No anti-HPA-1a-mediated phagocytosis was observed with anti-HPA-1a-negative platelets. The humanised anti-FcgammaRI monoclonal antibody H22 at concentrations 1-100 microg/ml, completely inhibited anti-HPA-1a-mediated phagocytosis as did similar concentrations of ivIg. By contrast, a mouse monoclonal anti-FcgammaRII (IV.3, Fab) at 10 microg/ml caused little or no suppression of platelet phagocytosis mediated by two anti-HPA-1 sera. Furthermore, the addition of anti-FcgammaRII (10 microg/ml) to sub-optimal concentrations of H22 did not significantly increase the inhibitory effect of the latter compound. Monomeric IgG (0.1-10 microg/ml) failed to suppress anti-HPA-1 mediated platelet ingestion by the phagocytes, as did anti-FcgammaRIII. To our knowledge this is a rare example of an assay that measures platelet phagocytosis in vitro. The results suggest that FcgammaRI plays a major role in anti-HPA-1a-mediated platelet phagocytosis by monocytes while FcgammaRIIa, is of little or minor importance only. Moreover, the findings indicate the use of H22 as an alternative to interavenous Ig (ivIg) in the management of FAIT/NAIT.

Dynamic three-dimensional color Doppler ultrasound of human fetal intracardiac flow.

OBJECTIVES: To develop dynamic three-dimensional ultrasound techniques for prenatal imaging of the intracardiovascular flow as well as the cardiovascular structure to address difficulties in assessing the spatially complex hemodynamics and morphology of the fetal heart. METHODS: Gray-scale and color (velocity) Doppler echocardiography were performed on 12 fetuses to provide serial anatomical and rheological tomograms which were spatially registered in three dimensions. Using a second ultrasound machine simultaneously, spectral Doppler ultrasound was performed to record umbilical arterial waveforms, thus providing the temporal (fourth) dimension in terms of the cardiac cycle and facilitating removal of motion artifacts. RESULTS: Acquisitions were successful in eight of 15 attempts. Imaging of the flow of blood in four dimensions was achieved in six of the eight datasets. In one case with complex cardiac malformations, three-dimensional reconstructions at systole and diastole offered dynamic diagnostic views not appreciated on the cross-sectional images. CONCLUSIONS: Our novel technique has made possible the prenatal visualization of the spatial distribution and true direction of intracardiac flow of blood in four dimensions in the absence of motion artifacts. The technique suggests that diagnosis of cardiac malformations can be made on the basis of morphological and hemodynamic changes throughout the entire cardiac cycle, offering unique and significant information complementary to conventional techniques. Further work to integrate the several non-purpose-built machines into a single system will improve the rate of acquisition of data, and may provide a new means of imaging and modeling structure and hemodynamics, not only for the fetal heart but for many other moving body parts.