Automated quantitative evaluation of fetal atrioventricular annular plane systolic excursion.

OBJECTIVES: The primary aim of this study was to evaluate the feasibility of automated measurement of fetal atrioventricular (AV) plane displacement (AVPD) over several cardiac cycles using myocardial velocity traces obtained by color tissue Doppler imaging (cTDI). The secondary objectives were to establish reference ranges for AVPD during the second half of normal pregnancy, to assess fetal AVPD in prolonged pregnancy in relation to adverse perinatal outcome and to evaluate AVPD in fetuses with a suspicion of intrauterine growth restriction (IUGR). METHODS: The population used to develop the reference ranges consisted of women with an uncomplicated singleton pregnancy at 18-42 weeks of gestation (n = 201). The prolonged-pregnancy group comprised women with an uncomplicated singleton pregnancy at ≥ 41 + 0 weeks of gestation (n = 107). The third study cohort comprised women with a singleton pregnancy and suspicion of IUGR, defined as an estimated fetal weight < 2.5th centile or an estimated fetal weight < 10th centile and umbilical artery pulsatility index > 97.5th centile (n = 35). Cineloops of the four-chamber view of the fetal heart were recorded using cTDI. Regions of interest were placed at the AV plane in the left and right ventricular walls and the interventricular septum, and myocardial velocity traces were integrated and analyzed using an automated algorithm developed in-house to obtain mitral (MAPSE), tricuspid (TAPSE) and septal (SAPSE) annular plane systolic excursion. Gestational-age specific reference ranges were constructed and normalized for cardiac size. The correlation between AVPD measurements obtained using cTDI and those obtained by anatomic M-mode were evaluated, and agreement between these two methods was assessed using Bland-Altman analysis. The mean Z-scores of fetal AVPD in the cohort of prolonged pregnancies were compared between cases with normal and those with adverse outcome using Mann-Whitney U-test. The mean Z-scores of fetal AVPD in IUGR fetuses were compared with those in the normal reference population using Mann-Whitney U-test. Inter- and intraobserver variability for acquisition of cTDI recordings and offline analysis was assessed by calculating coefficients of variation (CV) using the root mean square method. RESULTS: Fetal MAPSE, SAPSE and TAPSE increased with gestational age but did not change significantly when normalized for cardiac size. The fitted mean was highest for TAPSE throughout the second half of gestation, followed by SAPSE and MAPSE. There was a significant correlation between MAPSE (r = 0.64; P < 0.001), SAPSE (r = 0.72; P < 0.001) and TAPSE (r = 0.84; P < 0.001) measurements obtained by M-mode and those obtained by cTDI. The geometric means of ratios between AVPD measured by cTDI and by M-mode were 1.38 (95% limits of agreement (LoA), 0.84-2.25) for MAPSE, 1.00 (95% LoA, 0.72-1.40) for SAPSE and 1.20 (95% LoA, 0.92-1.57) for TAPSE. In the prolonged-pregnancy group, the mean ± SD Z-scores for MAPSE (0.14 ± 0.97), SAPSE (0.09 ± 1.02) and TAPSE (0.15 ± 0.90) did not show any significant difference compared to the reference ranges. Twenty-one of the 107 (19.6%) prolonged pregnancies had adverse perinatal outcome. The AVPD Z-scores were not significantly different between pregnancies with normal and those with adverse outcome in the prolonged-pregnancy cohort. The mean ± SD Z-scores for SAPSE (-0.62 ± 1.07; P = 0.006) and TAPSE (-0.60 ± 0.89; P = 0.002) were significantly lower in the IUGR group compared to those in the normal reference population, but the differences were not significant when the values were corrected for cardiac size. The interobserver CVs for the automated measurement of MAPSE, SAPSE and TAPSE were 28.1%, 17.7% and 15.3%, respectively, and the respective intraobserver CVs were 33.5%, 15.0% and 17.9%. CONCLUSIONS: This study showed that fetal AVPD can be measured automatically by integrating cTDI velocities over several cardiac cycles. Automated analysis of AVPD could potentially help gather larger datasets to facilitate use of machine-learning models to study fetal cardiac function. The gestational-age associated increase in AVPD is most likely a result of increasing cardiac size, as the AVPD normalized for cardiac size did not change significantly between 18 and 42 weeks. A decrease was seen in TAPSE and SAPSE in IUGR fetuses, but not after correction for cardiac size. © 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Massive blood transfusion in relation to delivery: incidence, trends and risk factors: a population-based cohort study.

OBJECTIVE: To estimate incidence, trends over time, and risk factors for massive blood transfusions in obstetric patients. A secondary aim was to evaluate transfusion ratios in relation to massive transfusion. DESIGN: Population-based cohort. SETTING: Five hospitals, in the Stockholm County, Sweden, from 1990 to 2011. POPULATION: All women that gave birth in Stockholm county, Sweden, and who received blood transfusions postpartum between 1990 and 2011. METHODS: Data on pregnancies and deliveries from the Swedish National Medical Birth Registry was cross-linked to the Stockholm transfusion database. Massive blood transfusion was defined as the transfusion of ≥10 units of red blood cells from partus through the next day. MAIN OUTCOME MEASURES: Main primary outcome was massive blood transfusion postpartum. RESULTS: Our cohort comprised 517 874 deliveries. Massive blood transfusion occurred in 277 women, for an incidence of 5.3 per 10 000 deliveries, and increased by 30% (P < 0.001) between the first and the second half of the study period. Major risk factors apparent before delivery were abnormal placentation (odds ratio [OR] 41; 95% CI 29.3-58.1), pre-eclampsia/placental abruption (OR 4; 95% CI 2.8-5.6), and previous caesarean delivery (OR 4; 95% CI 3.1-6.0). Risk factors at time of delivery were uterine rupture, atonic uterus, and caesarean delivery (OR 38, 17, and 3, respectively). CONCLUSION: We found an increasing trend in the postpartum rate of massive transfusion. Women with abnormal placentation were found to have the highest increased risk. Improved antenatal awareness of these women at risk might improve management and reduce the rate of massive transfusion. TWEETABLE ABSTRACT: Risk of massive blood transfusion in obstetric patients increases with placental complications and prior caesarean section.

Automated analysis of fetal cardiac function using color tissue Doppler imaging in second half of normal pregnancy.

OBJECTIVES: Color tissue Doppler imaging (cTDI) is a promising tool for the assessment of fetal cardiac function. However, the analysis of myocardial velocity traces is cumbersome and time-consuming, limiting its application in clinical practice. The aim of this study was to evaluate fetal cardiac function during the second half of pregnancy and to develop reference ranges using an automated method to analyze cTDI recordings from a cardiac four-chamber view. METHODS: This was a cross-sectional study including 201 normal singleton pregnancies between 18 and 42 weeks of gestation. During fetal echocardiography, a four-chamber view of the heart was visualized and cTDI was performed. Regions of interest were positioned at the level of the atrioventricular plane in the left ventricular (LV), right ventricular (RV) and septal walls of the fetal heart, to obtain myocardial velocity traces that were analyzed offline using the automated algorithm. Peak myocardial velocities during atrial contraction (Am), ventricular ejection (Sm) and rapid ventricular filling, i.e. early diastole (Em), as well as the Em/Am ratio, mechanical cardiac time intervals and myocardial performance index (cMPI) were evaluated, and gestational age-specific reference ranges were constructed. RESULTS: At 18 weeks of gestation, the peak myocardial velocities, presented as fitted mean with 95% CI, were: LV Am, 3.39 (3.09-3.70) cm/s; LV Sm, 1.62 (1.46-1.79) cm/s; LV Em, 1.95 (1.75-2.15) cm/s; septal Am, 3.07 (2.80-3.36) cm/s; septal Sm, 1.93 (1.81-2.06) cm/s; septal Em, 2.57 (2.32-2.84) cm/s; RV Am, 4.89 (4.59-5.20) cm/s; RV Sm, 2.31 (2.16-2.46) cm/s; and RV Em, 2.94 (2.69-3.21) cm/s. At 42 weeks of gestation, the peak myocardial velocities had increased to: LV Am, 4.25 (3.87-4.65) cm/s; LV Sm, 3.53 (3.19-3.89) cm/s; LV Em, 4.55 (4.18-4.94) cm/s; septal Am, 4.49 (4.17-4.82) cm/s; septal Sm, 3.36 (3.17-3.55) cm/s; septal Em, 3.76 (3.51-4.03) cm/s; RV Am, 6.52 (6.09-6.96) cm/s; RV Sm, 4.95 (4.59-5.32) cm/s; and RV Em, 5.42 (4.99-5.88) cm/s. The mechanical cardiac time intervals generally remained more stable throughout the second half of pregnancy, although, with increased gestational age, there was an increase in duration of septal and RV atrial contraction, LV pre-ejection and septal and RV ventricular ejection, while there was a decrease in duration of septal postejection. Regression equations used for the construction of gestational age-specific reference ranges for peak myocardial velocities, Em/Am ratios, mechanical cardiac time intervals and cMPI are presented. CONCLUSION: Peak myocardial velocities increase with gestational age, while the mechanical time intervals remain more stable throughout the second half of pregnancy. Using an automated method to analyze cTDI-derived myocardial velocity traces, it was possible to construct reference ranges, which could be used in distinguishing between normal and abnormal fetal cardiac function. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Prediction of stillbirth in women with overweight or obesity-A register-based cohort study.

OBJECTIVE: To develop a model for prediction of stillbirth after the 28th gestational week in singleton pregnancies of women with overweight or obesity. METHOD: This is a register-based cohort study. The first trimester screening database including data from 2006 until 2015 was cross-linked with the Swedish Medical Birth Register and the Swedish Register of Total Population. The final study cohort comprised 145,319 pregnancies, out of which 45,859 pregnancies were complicated by overweight or obesity and without pre-gestational diabetes. There were in total 282 stillbirths. Prediction models for stillbirth in pregnancies with overweight or obesity were constructed based on maternal characteristics, pregnancy complications and biochemical markers. Receiver Operating Characteristic (ROC) and area under curve (AUC) were calculated, based on logistic regression analyses. RESULTS: The prevalence of stillbirth was 1.6/1000 births and 2.6/1000 births in normal weight and overweight/obese women, respectively. The final predictive model had an AUC of 0.69 (95% CI: 0.64-0.74) with a sensitivity of 28% at a 90% fixed specificity. CONCLUSIONS: It is possible to predict 28% of stillbirths in overweight or obese women, at a false positive rate of 10%. In particular, growth-restricted fetuses are at increased risk of stillbirth.

Automated analysis of fetal cardiac function using color tissue Doppler imaging.

OBJECTIVE: To evaluate the feasibility of automated analysis of fetal myocardial velocity recordings obtained by color tissue Doppler imaging (cTDI). METHODS: This was a prospective cross-sectional observational study of 107 singleton pregnancies ≥ 41 weeks of gestation. Myocardial velocity recordings were obtained by cTDI in a long-axis four-chamber view of the fetal heart. Regions of interest were placed in the septum and the right (RV) and left (LV) ventricular walls at the level of the atrioventricular plane. Peak myocardial velocities and mechanical cardiac time intervals were measured both manually and by an automated algorithm and agreement between the two methods was evaluated. RESULTS: In total, 321 myocardial velocity traces were analyzed using each method. It was possible to analyze all velocity traces obtained from the LV, RV and septal walls with the automated algorithm, and myocardial velocities and cardiac mechanical time intervals could be measured in 96% of all traces. The same results were obtained when the algorithm was run repeatedly. The myocardial velocities measured using the automated method correlated significantly with those measured manually. The agreement between methods was not consistent and some cTDI parameters had considerable bias and poor precision. CONCLUSIONS: Automated analysis of myocardial velocity recordings obtained by cTDI was feasible, suggesting that this technique could simplify and facilitate the use of cTDI in the evaluation of fetal cardiac function, both in research and in clinical practice. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Do adverse pregnancy outcomes contribute to accelerated cardiovascular events seen in young women with systemic lupus erythematosus?

Cardiovascular events (CVEs) are prevalent in patients with systemic lupus erythematosus (SLE), and it is the young women who are disproportionately at risk. The risk factors for accelerated cardiovascular disease remain unclear, with multiple studies producing conflicting results. In this paper, we aim to address both traditional and SLE-specific risk factors postulated to drive the accelerated vascular disease in this cohort. We also discuss the more recent hypothesis that adverse pregnancy outcomes in the form of maternal-placental syndrome and resultant preterm delivery could potentially contribute to the CVEs seen in young women with SLE who have fewer traditional cardiovascular risk factors. The pathophysiology of how placental-mediated vascular insufficiency and hypoxia (with the secretion of placenta-like growth factor (PlGF) and soluble fms-tyrosine-like kinase-1 (sFlt-1), soluble endoglin (sEng) and other placental factors) work synergistically to damage the vascular endothelium is discussed. Adverse pregnancy outcomes ultimately are a small contributing factor to the complex pathophysiological process of cardiovascular disease in patients with SLE. Future collaborative studies between cardiologists, obstetricians, obstetric physicians and rheumatologists may pave the way for a better understanding of a likely multifactorial aetiological process.

Composition and dynamics of the uterine NK cell KIR repertoire in menstrual blood.

Uterine natural killer (NK) cells are abundantly present in endometrium and decidua. Their function is governed by interactions between killer cell immunoglobulin-like receptors (KIRs) and cognate human leukocyte antigen (HLA) class I ligands. These interactions have implications for reproductive success. Whereas most uterine NK cells are known to express KIRs, little information is available about KIR repertoire formation and stability over time. This is primarily due to inherent difficulties in gaining access to human uterine tissue. As endometrial immune cells are shed during menstruation, menstrual blood may serve as a source for studies of KIRs on uterine NK cells. Here, we performed a combined assessment of six inhibitory and activating KIRs on uterine NK cells from paired menstrual and peripheral blood. Menstrual blood contained a high frequency of uterine NK cells expressing KIRs. The uterine NK cell KIR repertoires were markedly different from those in peripheral blood NK cells, biased toward KIR2D-receptor expression, and formed independently of selection conferred by cognate HLA class I molecules. Moreover, uterine NKG2C+self-KIR+ NK cell expansions were detected. Finally, the distinct KIR repertoires of uterine NK cells were stable over multiple menstrual cycles. Our results provide novel insight into KIR repertoire formation on human uterine NK cells.

Characterisation of maternal human leukocyte antigen class I antibodies in suspected foetal and neonatal alloimmune thrombocytopenia.

OBJECTIVES: To investigate the specificities and level of HLA class I antibodies in selected cases referred for suspected foetal and neonatal alloimmune thrombocytopenia (FNAIT). BACKGROUND: FNAIT occurs in 1 : 1-2000 live births, whereas maternal immunisation against human leukocyte antigen (HLA) class I is common. Whether HLA class I antibodies alone can cause FNAIT is debatable. MATERIAL AND METHODS: A total of 260 patient samples were referred between 2007 and 2012. Referrals with maternal HLA class I antibodies and no other cause for the neonatal thrombocytopenia were included for analysis (cases, n = 23). HPA-1a negative mothers were excluded. Control groups were screened positive mothers of healthy neonates (controls, n = 33) and female blood donors (blood donors, n = 19). LABScreen single antigen HLA class I beads was used for antibody analysis. Clinical records were reviewed for cases. RESULTS: All groups had broad antibody reactivity. Cases had more antibodies with high SFI levels compared with the controls (SFI>9999; medians 26, 6 and 0; P < 0·05) and higher overall median HLA-ABC and HLA-B SFI (P < 0·05). Many of the antibodies were reactive with rare alleles. When reviewing the clinical records, several of the cases had other contributing factors to the thrombocytopenia. There was no correlation between foetal platelet count and antibody levels. CONCLUSION: Mothers of thrombocytopenic neonates had higher levels of HLA class I antibodies compared with control groups of women with healthy children and female blood donors. However, clinical outcome and antibody response correlated poorly in the heterogeneous case group, indicating a multifactorial cause to the thrombocytopenia in the majority of cases.

Prenatal ultrasound and childhood autism: long-term follow-up after a randomized controlled trial of first- vs second-trimester ultrasound.

OBJECTIVE: To analyze whether the frequency of autism spectrum disorder (ASD) in a cohort of Swedish children differs between those exposed to ultrasound in the 12(th) week and those exposed to ultrasound in the 18(th) week of gestation. METHODS: The study cohort consisted of approximately 30 000 children born between 1999 and 2003 to mothers who had been randomized to a prenatal ultrasound examination at either 12 or 18 weeks' gestation as part of the framework for a study on nuchal translucency screening. The outcome measure in the present study was the rate of ASD diagnoses among the children. Information on ASD diagnoses was based on data from the Swedish social insurance agency concerning childcare allowance granted for ASD. RESULTS: Between 1999 and 2003, a total of 14 726 children were born to women who underwent a 12-week ultrasound examination and 14 596 to women who underwent an 18-week ultrasound examination. Of these, 181 (1.2%) and 176 (1.2%) children, respectively, had been diagnosed with ASD. There was no difference in ASD frequency between the early and late ultrasound groups. CONCLUSIONS: Women subjected to at least one prenatal ultrasound examination at either 12 or 18 weeks' gestation had children with similar rates of ASD. However, this result reflects routine care 10-15 years ago in Sweden. Today, higher intensity ultrasound scans are performed more frequently, at earlier stages during pregnancy and for non-medical purposes, implying longer exposure time for the fetus. This change in the use of ultrasound necessitates further follow-up study of the possible effects that high exposure to ultrasound during the gestational period has on the developing brain. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Cost-effectiveness of first trimester non-invasive fetal RHD screening for targeted antenatal anti-D prophylaxis in RhD-negative pregnant women: a model-based analysis.

OBJECTIVE: To estimate the cost-effectiveness of first trimester non-invasive fetal RHD screening for targeted antenatal versus no routine antenatal anti-D prophylaxis (RAADP) or versus non-targeted RAADP. DESIGN: Model based on a population-based cohort study. SETTING: The Swedish health service. POPULATION: Intervention subjects in the underlying cohort study were RhD-negative pregnant women receiving first trimester fetal RHD screening followed by targeted anti-D in 2010-2011 (n = 6723). Historical comparators were RhD-negative women who delivered in 2008-2009 when standard care did not include RAADP (n = 7099). METHODS: Healthcare costs for the three strategies were included for the first and subsequent pregnancies. For the comparison with non-targeted RAADP, the immunisation rate was based on the observed rate for targeted therapy and adjusted downwards by removing the influence of false negatives. MAIN OUTCOME MEASURE: Additional cost per RhD immunisation averted. RESULTS: Compared with RAADP, targeted prophylaxis was associated with fewer immunisations (0.19 versus 0.46% per pregnancy) and lower costs (cost-savings of €32 per RhD-negative woman). The savings were from lower costs during pregnancy and delivery, and lower costs of future pregnancies through fewer immunisations. Non-targeted anti-D was estimated to result in 0.06% fewer immunisations and an additional €16 in cost-savings per mother, compared with targeted anti-D. CONCLUSION: Based on effect data from a population-based cohort study, targeted prophylaxis was associated with lower immunisation risk and costs versus no RAADP. Based on effect data from theoretical calculations, non-targeted RAADP was predicted to result in lower costs and immunisation risk compared with targeted prophylaxis. TWEETABLE ABSTRACT: Fetal RHD screening and targeted prophylaxis resulted in lower immunisation risk and costs compared with no RAADP.

Traction force during vacuum extraction: a prospective observational study.

OBJECTIVE: To investigate the traction force employed during vacuum extractions. DESIGN: Observational cross-sectional study. SETTING: Obstetric Department, Karolinska University Hospital, Sweden, and the Swedish National Congress of Obstetrics and Gynaecology, 2013. POPULATION: Two hundred women with vacuum extraction at term and 130 obstetricians participating in a simulated setting. METHODS: In a normal clinical setting, we used a specially adapted device to measure and record the force used to undertake vacuum extraction. In a subsequent part of the study, the force employed for vacuum extraction by a group of obstetricians in a fictive setting was estimated and objectively measured. MAIN OUTCOME MEASURES: Applied force during vacuum extraction in relation to the estimated level of difficulty in the delivery; perinatal diagnoses of asphyxia or head trauma; estimated force compared with objectively measured force employed in the fictive setting. RESULTS: The median (minimum-maximum) peak forces for minimum, average and excessive vacuum extraction in the clinical setting were 176 N (5-360 N), 225 N (115-436 N), and 241 N (164-452 N), respectively. In 34% of cases a force in excess of 216 N was employed. There was no correlation between the umbilical arterial pH at delivery and the traction force employed during extraction. Four cases of mild hypoxic ischaemic encephalopathy were observed, three of which were associated with a delivery whereby excessive traction force was employed during the vacuum extraction. In the fictive setting, the actual exerted force was twice the quantitative estimation. The measured forces in the clinical setting were four times higher than that estimated in the fictive setting. CONCLUSIONS: Higher than expected levels of traction force were used for vacuum extraction delivery. As obstetricians tend to underestimate the force applied during vacuum extraction, objective measurement with instantaneous feedback may be valuable in raising awareness.

European non-invasive trisomy evaluation (EU-NITE) study: a multicenter prospective cohort study for non-invasive fetal trisomy 21 testing.

OBJECTIVE: To evaluate the performance of a directed non-invasive prenatal testing method of cell-free DNA analysis for fetal trisomy 21 (T21) by shipping the whole blood samples from Europe to a laboratory in the USA. METHODS: A European multicenter prospective, consecutive cohort study was performed enrolling pregnant women from Sweden and the Netherlands. Blood samples were drawn just prior to a planned of invasive diagnostic procedure in a population at increased risk for fetal T21 and then shipped to the USA without any blood processing. Chromosome-selective sequencing was carried out on chromosome 21 with reporting high risk or low risk of T21. Karyotyping or rapid aneuploidy detection was used as the clinical reference standard. RESULTS: Of the 520 eligible study subjects, a T21 test result was obtained in 504/520 (96.9%). Risk assessment was accurate in 503/504 subjects (99.8%). There was one false negative result for T21 (sensitivity 17/18, 94.4%, and specificity 100%). CONCLUSION: This is the first prospective European multicenter study showing that non-invasive prenatal testing using directed sequencing of cell-free DNA applied to blood samples shipped across the Atlantic Ocean, is highly accurate for assessing risk of fetal T21.

Stromal cells from term fetal membrane are highly suppressive in allogeneic settings in vitro.

Bone marrow-derived mesenchymal stromal cells (BM-MSCs) have immunosuppressive properties and have been used to treat steroid-refractory acute graft-versus-host disease (GVHD) in stem cell transplant patients. Cells with similar capacities can also be found in term placental tissue. We have isolated stromal cells from term fetal membrane (FMSCs), umbilical cords (UCSCs) and placental villi (PVSCs) as well as from bone marrow and compared their immunoregulatory capacity in allogeneic settings. We found that FMSCs and UCSCs suppressed proliferation significantly in mixed lymphocyte reactions (MLRs), whereas PVSCs showed inconsistent suppressive effects. When added to MLR cultures, FMSCs suppressed the production of interferon (IFN)-γ and interleukin (IL)-17, whereas UCSCs and PVSCs promoted the production of IL-17 instead. Secretion of IL-10 was increased after addition of FMSCs and UCSCs. In this setting, BM-MSCs had no significant effect on secretion of IFN-γ, IL-17 or IL-10 in MLR cultures. When analysing the expression of adhesion markers, we noted that FMSCs expressed the highest levels of CD29 (ß1), CD49d (α4) and CD54 (ICAM-1) compared to the other types of stromal cells. Thus, our data indicate that stromal cells isolated from term fetal membrane have great immunosuppressive capacity in terms of proliferation and production of proinflammatory cytokines from alloreactive T cells, and also promote anti-inflammatory IL-10. They express high levels of integrins that may be of importance in homing to inflamed tissues. Fetal membrane may provide a valuable source of cells with immunosuppressive properties and could possibly be used for treatment of acute GVHD and other inflammatory disorders.

Temporal frequency requirements for tissue velocity imaging of the fetal heart.

OBJECTIVES: The high velocity and short duration of myocardial motion requires a high sampling rate to obtain adequate temporal resolution; this issue becomes even more important when taking into consideration the high fetal heart rate. In this study we have established optimal sampling requirements for assessing the duration of various cardiac cycle events and myocardial velocities of the fetal heart using color-coded tissue velocity imaging (TVI). METHODS: Recordings from 30 fetuses were acquired at an initial frame rate of 180-273 frames/s. All TVI recordings were performed from an apical four-chamber view and stored as cineloops of five to 10 consecutive cardiac cycles for subsequent offline analysis using software enabling a reduction in frame rate. Different components of the myocardial velocity curve, obtained from the basal part of the ventricular septum, were measured at the initial frame rate and compared with their equivalents at gradually decreased frame rates. RESULTS: As acquisition frame rate was reduced, there was a marked increase in deviation from the initial values, resulting in an underestimation of all systolic and diastolic velocities. For the measured durations, there was a clear tendency to underestimate isovolumetric contraction and relaxation, and a clear tendency to overestimate ventricular ejection and diastolic E-wave and A-wave. An acceptable ⩽ 5% deviation from the value obtained at the highest frame rate corresponded to measurements obtained at above 150-200 frames/s. CONCLUSIONS: A high sampling rate of at least 200 frames/s is necessary for adequate reconstruction of TVI data for the fetal heart. Frame rates that are too low result in considerable loss of temporal and velocity information.

Endometrial endothelial cells are derived from donor stem cells in a bone marrow transplant recipient.

BACKGROUND: The endometrium is a dynamic, cyclically regenerating tissue: a unique model of physiological angiogenesis in adults. However, the source of new endothelial cells (ECs) for vessel regrowth is obscure. We studied if male EC could be detected in the endometrial blood vessels of female human or mouse recipients of haematological stem cells from male donors. METHODS: Endometrial biopsies, obtained from one patient after non-myeloablative allogeneic bone marrow transplantation and two controls, were analysed by immunohistochemistry of CD34 and VEGFR2 antibodies for the immunophenotyping of EC, and FISH probes for the detection of donor cells. Chimerism was analysed using real-time PCR. The same experiment was also applied on the animal model. RESULTS: At the time of a Caesarean section in a female bone marrow transplanted patient, an average 14% of her endometrial EC were donor-derived. One year later, that figure was 10%. In contrast, none of two non-transplanted females demonstrated a mismatch in endometria at Caesarean section. In samples from female mice, harvested 40 days after a haematological stem cell transplant, a 6% average of donor-derived EC was detected. CONCLUSIONS: Bone marrow-derived endothelial progenitors contribute to the formation of new blood vessels in the endometrium.

Human chorionic gonadatropin (hCG) during third trimester pregnancy.

OBJECTIVE: Separate reference values were recently established for routine blood samples during last trimester pregnancy. Previously, these were based on blood samples from healthy men or non-pregnant women. Normal changes in variation in the levels of steroid hormones in the last weeks of pregnancy before delivery are also incompletely investigated. This study of the preterm hormone levels was carried out in the search for events leading to increased contractility that might occur in the predelivery weeks and potentially influence the initiation of delivery. MATERIAL AND METHODS: Blood samples during pregnancy weeks 33, 36 and 39 as well as 1-3 h postpartum were collected from pregnant women (19-39 years, mean age 30) with at least one previous pregnancy without hypertension or pre-eclampsia. All women (n = 135) had had a vaginal delivery and spontaneous start of labour. The blood samples were analysed for serum hCG, oestradiol and progesterone. Postpartum, the values were retrospectively rearranged to correspond with the actual week before the day of delivery. RESULTS: During the last trimester of normal pregnancy, a gradual increase was found in oestradiol (median 45980 to 82410 pmol/L), progesterone (median 341 to 675 nmol/L) and a gradual decrease in hCG (median 31833 to 19494 IU/L). Furthermore, a significant (p<0.03) decrease in hCG was found from the third to the second week before delivery, while oestradiol and progesterone continued to increase. CONCLUSIONS: Hormone levels during third-trimester pregnancy have not previously been systematically investigated. Recent data suggest that hCG may have a role as an endogenous tocolytic in normal pregnancy by directly promoting relaxation of uterine contractions. In the present study a significant decrease in serum hCG level was found 2-3 weeks before the spontaneous start of labour. This might contribute to increasing the contractility in the uterine muscle and gradually initiate the onset of labour.

Identification of expandable human hepatic progenitors which differentiate into mature hepatic cells in vivo.

BACKGROUND: Liver diseases include a wide spectrum of both acute and chronic conditions which are associated with significant morbidity and mortality worldwide. Hepatocyte transplantation has therapeutic potential in the treatment of liver diseases, but its clinical use is hampered by the lack of donor tissue. Generation of hepatocytes in vitro from adult or fetal liver cell progenitors or, alternatively, identification of a progenitor population which in vivo can generate mature liver cells could solve this problem. METHODS: CD117+/CD34+/Lin- human fetal liver cells were isolated by magnetic cell sorting and expanded in culture. Both freshly isolated and in vitro expanded cells in various passages were studied for their ability to be functional in hepatic parenchyma following d-galactosamine (GalN) induced injury in nude C57 black mice. RESULTS: Freshly isolated and in vitro expanded CD117+/CD34+/Lin- cells, when transplanted intrasplenically into GalN treated mice, morphologically and functionally differentiated into hepatocytes and cholangiocytes. Human specific albumin, alpha fetoprotein, cytokeratin 19, and antitrypsin mRNA were expressed in mouse liver. In addition, the human progenitor cells expressed glucose-6-phosphatase, glycogen, albumin, gamma glutamyl transpeptidase, and dipeptidyl peptidase IV after transplantation. Expanded cells in various passages maintained their capacity to differentiate into functional liver cells. CONCLUSIONS: Fetal liver CD117+/CD34+/Lin- progenitors and their progeny proliferated in vitro and also functionally differentiated into mature hepatic cells in an acute liver injury model. Successful in vitro expansion of liver progenitor cells provides a basis for developing cell therapy strategies, metabolic and toxicity testing systems, and may serve as a vehicle for gene therapy.

Immunomodulatory effects of human foetal liver-derived mesenchymal stem cells.

Adult mesenchymal stem cells (MSCs) have been suggested to decrease lymphocyte proliferation in vitro. We hypothesised that foetal MSCs (fMSCs) would have an immunosuppressive effect on allograft responses in vitro. Human MSCs were isolated and cultured from first-trimester foetal livers and characterised by flow cytometry. fMSC stained positive for CD29, CD44, CD166, CD105, SH-3 and SH-4, and negative for CD14, CD34 and CD45. When plated on adipogenic, chondrogenic and osteogenic media, fMSC differentiated into the respective cell lineage. Compared to adult MSC (aMSC), the proliferative capacity of fMSC was higher. Mitogen stimulation of PBL was inhibited by fMSC. The greatest inhibition (78%) was seen when 30,000 fMSCs were added to 150,000 lymphocytes stimulated by phytohaemagglutinin. Adult and fMSCs were added to mixed lymphocyte cultures (MLC) containing peripheral blood lymphocytes or foetal liver cells. Unlike aMSC, fMSCs did not inhibit MLC. fMSC could be culture-expanded several million folds with no loss of phenotype characteristics, which makes them ideal for ex vivo expansion. fMSC inhibit lymphocyte proliferation induced by mitogens, but not alloreactivity as measured by MLC.