B-flow/spatiotemporal image correlation M-mode ultrasound provides novel method to quantify spiral artery remodeling during normal human pregnancy.

OBJECTIVES: During human pregnancy placental extravillous trophoblasts replace the vascular smooth muscle and elastic tissue within the walls of the uterine spiral arteries, thereby remodeling these arteries into distensible low resistance vessels to promote placental perfusion. The present study, determined whether B-flow/ spatio-temporal image correlation (STIC) M-mode ultrasonography provides an in vivo imaging method to digitally quantify spiral artery luminal distensibility, as a physiological index of spiral artery remodeling, during advancing stages of normal human pregnancy. METHODS: A prospective longitudinal observational study was conducted to quantify spiral artery distensibility, i.e. vessel luminal diameter at systole minus diameter at diastole, by B-flow/STIC M-mode ultrasonography during the first, second and third trimesters in 290 women exhibiting normal pregnancy. Maternal serum levels of placental growth factor (PlGF) and soluble fms-like tyrosine kinase (sFlt-1), growth factors that modulate events important in spiral artery remodeling, were quantified in a subset of the subjects at the first, second and third semesters. RESULTS: Median [first quartile, third quartile] spiral artery distensibility progressively increased (P < 0.0001) between the first trimester (0.17 [0.14, 0.21]), second (0.23 [0.18, 0.28]) and third (0.26 [0.21, 0.35]) trimesters of pregnancy. Spiral artery volume flow (ml/cardiac cycle) progressively increased (P < 0.001) between the first 2.49 [1.38, 4.99], second 3.86 [2.06, 6.91] and third 7.79 [3.83, 14.98] trimesters. Coinciding with the elevation in spiral artery distensibility, the median ratio of serum PlGF/sFlt-1 levels increased (P < 0.001) between the first (7.2 [4.5, 10], second (22.7 [18.6, 42.2]) and third (56.2 [41.9, 92.5] trimesters. CONCLUSIONS: The present study shows that B-flow/STIC M-mode ultrasonography provides an in vivo imaging technology to digitally quantify structural/physiological expansion of the walls of the spiral arteries during the cardiac cycle as a consequence of their transformation into compliant vessels during advancing stages of normal human pregnancy. This article is protected by copyright. All rights reserved.

Consensus protocol for management of early and late twin-twin transfusion syndrome: Delphi study.

OBJECTIVE: Fetoscopic laser photocoagulation (FLP) is a well-established treatment for twin-twin transfusion syndrome (TTTS) between 16 and 26 weeks' gestation. High-quality evidence and guidelines regarding the optimal clinical management of very early (prior to 16 weeks), early (between 16 and 18 weeks) and late (after 26 weeks) TTTS are lacking. The aim of this study was to construct a structured expert-based clinical consensus for the management of early and late TTTS. METHODS: A Delphi procedure was conducted among an international panel of experts. Participants were chosen based on their clinical expertise, affiliation and relevant publications. A four-round Delphi survey was conducted using an online platform and responses were collected anonymously. In the first round, a core group of experts was asked to answer open-ended questions regarding the indications, timing and modes of treatment for early and late TTTS. In the second and third rounds, participants were asked to grade each statement on a Likert scale (1, completely disagree; 5, completely agree) and to add any suggestions or modifications. At the end of each round, the median score for each statement was calculated. Statements with a median grade of 5 without suggestions for change were accepted as the consensus. Statements with a median grade of 3 or less were excluded from the Delphi process. Statements with a median grade of 4 were modified according to suggestions and reconsidered in the next round. In the last round, participants were asked to agree or disagree with the statements, and those with more than 70% agreement without suggestions for change were considered the consensus. RESULTS: A total of 122 experts met the inclusion criteria and were invited to participate, of whom 53 (43.4%) agreed to take part in the study. Of those, 75.5% completed all four rounds. A consensus on the optimal management of early and late TTTS was obtained. FLP can be offered as early as 15 weeks' gestation for selected cases, and can be considered up to 28 weeks. Between 16 and 18 weeks, management should be tailored according to Doppler findings. CONCLUSIONS: A consensus-based treatment protocol for early and late TTTS was agreed upon by a panel of experts. This protocol should be modified at the discretion of the operator, according to their experience and the specific demands of each case. This should advance the quality of future studies, guide clinical practice and improve patient care. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Placenta accreta spectrum conservative management and coagulopathy: case series and systematic review.

OBJECTIVE: Management of placenta accreta spectrum (PAS) with the placenta kept in situ aims to preserve fertility and minimize blood loss. However, this method is itself associated with a risk of coagulopathy and subsequent bleeding. Our aim is to evaluate coagulopathy in cases of PAS managed conservatively and its pathophysiology. METHODS: We reviewed our database for cases of PAS where the placenta was kept in situ. In addition, we performed a systematic review of articles on PAS where the placenta was left in situ and was complicated by coagulopathy. PubMed was searched for publications between 1980 and 2023. Our eligibility criteria included studies where no additional interventions were performed other than keeping the placenta entirely in situ, and where coagulopathy was reported. RESULTS: After screening and full-text article selection, 10 studies were included in the review. A review of our databases yielded a case series of PAS managed conservatively with placenta in situ. When adding our case series to the results of our systematic review, a total of 87 cases were found to be managed conservatively, with 28 cases of coagulopathy. Of these, 11 cases had known time at which coagulopathy developed. The median time of coagulopathy was 58 (IQR=17) days post-delivery. CONCLUSIONS: Our findings highlight that conservative management with PAS in situ poses a risk of coagulopathy. Keeping the placenta in situ after delivery prolongs the risk factors that are integral to PAS. The pathophysiology behind coagulopathy is comparable to that of concealed placental abruption (CPA), due to the disrupted maternofetal interface and the collection of blood in the placenta. The presence of large placental lakes could thus be an indicator of developing coagulopathy. This article is protected by copyright. All rights reserved.

Perinatal outcomes of fetoscopic laser surgery for twin-twin transfusion syndrome in triplet pregnancy: cohort study, systematic review and meta-analysis.

OBJECTIVES: The aims of this study were to investigate the perinatal outcome of dichorionic triamniotic (DCTA) and monochorionic triamniotic (MCTA) triplet pregnancies complicated by twin-twin transfusion syndrome (TTTS) treated with fetoscopic laser photocoagulation (FLP) in two academic fetal centers, and to conduct a systematic review of previously published data to investigate perinatal survival in this targeted population. METHODS: The first part of the study was a retrospective cohort study of prospectively collected data of consecutive triplet pregnancies with TTTS that underwent FLP at two fetal treatment centers between 2012 and 2020. Demographic, preoperative and operative variables and postoperative outcome were collected. Perinatal outcomes were investigated. The second part of the study was a systematic review and meta-analysis of studies evaluating the outcome of DCTA and/or MCTA triplet pregnancies, including our cohort study. PubMed, Web of Science and Scopus were searched from inception to September 2020. Primary outcomes were fetal survival (survival to birth), neonatal survival (survival to 28 days of age) and gestational age (GA) at birth. RESULTS: A total of 31 sets of triplets with TTTS managed with FLP were included in the cohort study. Of these, 24 were DCTA and seven were MCTA. There were no significant differences in preoperative and operative variables between the two groups. There were also no significant differences between groups in GA at delivery or perinatal survival rate, including fetal and neonatal survival of at least one triplet, at least two triplets and all three triplets. Nine studies, including our cohort study, were included in the systematic review (156 DCTA and 37 MCTA triplet pregnancies treated with FLP). The overall fetal and neonatal survival was 79% (95% CI, 75-83%) and 75% (95% CI, 71-79%), respectively, in DCTA cases and 74% (95% CI, 52-92%) and 71% (95% CI, 49-89%), respectively, in MCTA cases. The rate of preterm birth before 28 weeks and before 32 weeks' gestation was 14% (95% CI, 4-29%) and 61% (95% CI, 50-72%), respectively, in DCTA triplets and 21% (95% CI, 3-45%) and 82% (95% CI, 62-96%), respectively, in MCTA triplets. CONCLUSIONS: Triplet pregnancies with TTTS are at high risk of adverse perinatal outcome and preterm birth, regardless of chorionicity. The rate of survival after FLP in MCTA triplets was higher in our study than that reported in previous studies and is currently comparable with survival in DCTA triplets, which could be due to improved surgical skills. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

B-flow/spatiotemporal image correlation M-mode: novel ultrasound method that detects decrease in spiral artery luminal diameter in first trimester in primate model of impaired spiral artery remodeling.

OBJECTIVE: To determine if B-flow/spatiotemporal image correlation (STIC) M-mode ultrasonography detects a decrease in spiral artery luminal diameter and volume flow during the first trimester in a non-human primate model of impaired spiral artery remodeling (SAR). METHODS: Pregnant baboons were treated daily with estradiol benzoate on days 25-59 of the first trimester (term, 184 days), or remained untreated. On day 60 of gestation, spiral artery luminal diameter (in seven untreated and 12 estradiol-treated baboons) and volume flow (in four untreated and eight estradiol-treated baboons) were quantified by B-flow/STIC M-mode ultrasonography. In addition, in 15 untreated and 18 estradiol-treated baboons, the percent of spiral arteries remodeled by extravillous trophoblasts was quantified ex vivo by immunohistochemical image analysis on placental basal plate tissue collected via Cesarean section on day 60. Findings were compared between treated and untreated animals. The correlation between spiral artery luminal diameter and percent of SAR was assessed in three untreated and six estradiol-treated baboons which underwent both B-flow/STIC M-mode ultrasound and quantification of SAR. RESULTS: The proportion of spiral arteries greater than 50 µm in diameter remodeled by extravillous trophoblasts was 70% lower in estradiol-treated baboons than in untreated animals (P = 0.000001). Spiral artery luminal diameter in systole and diastole, as quantified by B-flow/STIC M-mode in the first trimester of pregnancy, was 31% (P = 0.014) and 50% (P = 0.005) lower, respectively, and volume flow was 85% lower (P = 0.014), in SAR-suppressed baboons compared with untreated animals. There was a significant correlation between spiral artery luminal diameter as quantified by B-flow/STIC M-mode ultrasonography and the percent of SAR (P < 0.05). CONCLUSION: B-flow/STIC M-mode ultrasonography provides a novel real-time non-invasive method to detect a decrease in uterine spiral artery luminal diameter and volume flow during the cardiac cycle, reflecting decreased distensibility of the vessel wall, in the first trimester in a non-human primate model of defective SAR. © 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Efficacy of long-term indomethacin therapy in prolonging pregnancy after fetoscopic laser surgery for twin-to-twin transfusion syndrome: a collaborative cohort study.

OBJECTIVE: To evaluate the efficacy of long-term indomethacin therapy (LIT) in prolonging pregnancy and reducing spontaneous preterm birth (PTB) in patients undergoing fetoscopic laser surgery (FLS) for the management of twin-to-twin transfusion syndrome (TTTS). DESIGN: Retrospective cohort study of prospectively collected data. SETTING: Collaborative multicentre study. POPULATION: Five hundred and fifty-seven consecutive TTTS cases that underwent FLS. METHODS: Long-term indomethacin therapy was defined as indomethacin use for at least 48 hours. Log-binomial regression was used to estimate the relative risk of PTB in the LIT group compared with a non-LIT group. Cox regression was used to evaluate the association between LIT use and FLS-to-delivery survival. MAIN OUTCOME MEASURES: Gestational age (GA) at delivery. RESULTS: Among the 411 pregnancies included, a total of 180 patients (43.8%) received LIT after FLS and 231 patients (56.2%) did not. Median GA at fetal intervention did not differ between groups (20.4 weeks). Median GA at delivery was significantly higher in the LIT group (33.6 weeks) compared with the non-LIT group (31.1 weeks; P < 0.001). FLS-to-delivery interval was significantly longer in the LIT group (P < 0.001). The risks of PTB before 34, 32, 28 and 26 weeks of gestation were all significantly lower in the LIT group compared with the non-LIT group (relative risks 0.69, 0.51, 0.37 and 0.18, respectively). The number needed to treat with LIT to prevent one PTB before 32 weeks of gestation was four, and to prevent one PTB before 34 weeks was five. CONCLUSION: Long-term indomethacin after FLS for TTTS was found to be associated with prolongation of pregnancy and reduced risk for PTB. TWEETABLE ABSTRACT: Long-term indomethacin used after fetoscopic laser surgery for twin-to-twin transfusion syndrome is effective in prolonging pregnancy and reducing the risk for preterm birth; especially extreme preterm birth.

First-trimester fetal cardiac examination using spatiotemporal image correlation, tomographic ultrasound and color Doppler imaging for the diagnosis of complex congenital heart disease in high-risk patients.

OBJECTIVE: A four-dimensional (4D) fetal echocardiographic technique utilizing spatiotemporal image correlation, tomographic ultrasound imaging display (STIC-TUI echo) and color Doppler has previously been shown to be effective in displaying the examination planes constituting the extended cardiac examination. The aim of this study was to evaluate the performance of this first-trimester STIC-TUI echo technique in identifying complex congenital heart disease (CHD) in high-risk pregnancies. METHODS: This was a prospective study of patients presenting at first-trimester screening who were at high risk for CHD owing to pregestational diabetes, in-vitro fertilization (IVF), increased nuchal translucency (NT) thickness, first-trimester tricuspid regurgitation or reversed ductus venosus (DV) a-wave, a previous child with CHD or who were on anticonvulsant medication. First-trimester STIC-TUI echo was performed, and the findings were correlated with second-trimester echocardiography and post-delivery echo findings in survivors. RESULTS: One hundred and sixty-four fetuses from 152 patients were enrolled (77 diabetics, 38 IVF, 14 with increased NT, 23 cases of tricuspid regurgitation or reversed a-wave in the DV, 22 with prior CHD and two on anticonvulsants). STIC-TUI echo was abnormal in 20 (12%), showing atrioventricular canal defect (n = 9), hypoplastic left heart (n = 2), pulmonary stenosis (n = 2), right aortic arch (n = 1), interrupted aortic arch (n = 1), tricuspid atresia (n = 1), heterotaxy (n = 1), persistent truncus arteriosus (n = 1), double outlet right ventricle and ventricular septal defect (n = 1) and double inlet ventricle with transposition of the great arteries (n = 1). 85% of these anomalies were evident in the four-chamber view plane of the TUI display, and the remainder were diagnosed in the outflow tract planes with color Doppler imaging. In 13, CHD was isolated while seven had extracardiac anomalies. Thirteen fetuses had aneuploidy and all 13 underwent first-trimester termination of pregnancy. In the remaining seven, second-trimester echocardiography and neonatal echo/postmortem examination confirmed anomalies (two stillborn neonates, one neonatal death, four live births). Two cases of CHD missed by first-trimester STIC-TUI echo were diagnosed on second-trimester echo. Accordingly, first-trimester STIC-TUI echo had 91% sensitivity and 100% specificity for the detection of CHD. CONCLUSIONS: First-trimester 4D echocardiography using a standardized application of STIC, TUI and color Doppler imaging is effective in displaying the imaging planes that are necessary for achieving the diagnosis of complex cardiac anomalies in high-risk patients. Optimal imaging of the four-chamber view with two-dimensional ultrasound is the major determinant of successful volume acquisition.

Semiquantitative classification of ductus venosus blood flow patterns.

OBJECTIVES: To identify the range of waveform abnormalities in the ductus venosus (DV) characterized by their timing in the cardiac cycle and to evaluate if they can be categorized into distinct patterns. METHODS: DV velocity ratios were calculated from peak velocities during ventricular systole (S), end-systolic ventricular relaxation (v), early diastole (D) and atrial systole (a) (S/v, S/D, v/D, S/a, v/a and D/a ratios). The ratios were converted to their Z-scores and elevation > 2 SD was assigned as abnormal. Combinations of ratio abnormalities were grouped to define distinct waveform patterns and their distribution was related to the clinical presentation. RESULTS: Five-hundred and forty-two abnormal DV waveforms fell into three principal patterns. In Pattern 1 only the a-wave-related ratios were abnormal (180, 33.2%), in Pattern 2 the v/D ratio was abnormal (143, 26.3%) and in Pattern 3 combinations of a-wave abnormalities in the presence of a normal v/D ratio were normal (94, 17.3%). CONCLUSIONS: Interpretation of venous waveform patterns is complex because the multiphasic waveforms reflect events in the cardiac cycle that may be differentially affected by clinical pathology. We sought to present a classification for the DV flow profile that characterizes abnormal flow confined to atrial systole and occurs during ventricular relaxation or during holodiastole. Further research is warranted to determine the significance of these patterns in specific fetal conditions.

Correlation analysis of ductus venosus velocity indices and fetal cardiac function.

OBJECTIVE: To examine the relationships between the ductus venosus (DV) pulsatility index for veins (PIV), individual DV velocity ratios and diastolic and global myocardial cardiac function. METHODS: Doppler measurements of the DV, atrioventricular (AV) valves and ventricular in- and outflow were analyzed. The DV-PIV and velocity ratios for individual phases (systole (S), end-systolic relaxation (v), early diastole (D), atrial systole (a), and S/v, S/D, S/a, v/D, v/a and D/a ratios) were calculated. The ratio of early and late diastolic peak velocities across AV valves was calculated (E/A ratio). Left modified myocardial performance index (MPI) was calculated from time intervals between valve clicks defining isovolumetric contraction/relaxation and ejection times. All values were transformed to Z-scores. The distributions of DV velocity ratios and DV-PIV were correlated with cardiac Doppler parameters. RESULTS: A total of 1163 examinations from 213 fetuses, most of which were at risk for cardiac dysfunction, were included in the study. In 742 the PIV was normal and in 421 PIV was elevated > 2 SD above the normal mean. The DV-PIV correlated with velocity ratios (P < 0.0001) but not with E/A ratios and the MPI. S/v and v/D ratios were related to tricuspid and mitral E/A ratios and left ventricular MPI. The S/D ratio was only related to both E/A ratios. There was no relationship between a-wave-related velocity ratios and cardiac function. CONCLUSIONS: Velocity ratios of the DV show relationships with cardiac function that are not reflected by the PIV alone. In cases of suspected fetal cardiac dysfunction based on elevated DV-PIV, analysis of velocity ratios or direct cardiac evaluation is suggested to determine the underlying pathophysiology.

Childhood cognitive development after fetal growth restriction.

OBJECTIVE: To examine the relationship between prenatal umbilical artery (UA) and internal carotid artery (ICA) Doppler findings and cognitive development at 3 and 6 years in low-birth-weight children. METHODS: This was a study of 209 low-birth-weight (< 10(th) centile) children born after 28 gestational weeks with UA resistance index (RI) measured within 2 weeks before delivery. Children with normal UA- and ICA-RI were defined as small-for-gestational age (SGA) and those with abnormal UA or ICA Doppler findings as having fetal growth restriction (FGR). Cognitive ability at 3 and 6 years' corrected age was assessed using the fourth edition of the Stanford-Binet Intelligence Scale (SBIS) and compared between SGA and FGR groups. An SBIS score < 85 was considered to indicate delayed development. RESULTS: The median gestational age at diagnosis of abnormal fetal growth was 36.6 (range, 28-41) weeks. There were 87 (41.6%) children classified as having FGR and 122 (58.4%) as SGA. The mean global SBIS score at 3 years was 109.4 (SD, 22.8) and at 6 years it was 110.5 (SD, 13.9). Overall, 22 (10.5%) children had delayed development at 3 years. Total SBIS scores and individual domain scores did not differ between FGR and SGA groups at 3 or 6 years and similar proportions in each group had delayed development. CONCLUSION: Abnormal prenatal UA and ICA Doppler findings are not associated with lower developmental scores in low-birth-weight children delivered in the third trimester of pregnancy.

Hematologic profile of neonates with growth restriction is associated with rate and degree of prenatal Doppler deterioration.

OBJECTIVE: To examine the relationship between hematologic parameters at birth and prenatal progression of Doppler abnormalities in fetal growth restriction (FGR). METHODS: The study was a secondary analysis of FGR patients (abdominal circumference < 5th percentile and umbilical artery pulsatility index (UA-PI) elevation) with at least three examinations prior to delivery. Prenatal progression was classified as rapid, moderate or slow based on the interval between diagnosis and delivery and the extent of UA, middle cerebral artery and ductus venosus Doppler abnormalities. Associations between diagnosis-to-delivery interval, Doppler Z-scores, progression and hematologic parameters at birth were examined. RESULTS: Of 130 patients, 54 (41.5%) had rapid, 51 (39.2%) moderate and 25 (19.2%) slow deterioration, delivering within 4, 6 and 9 weeks of diagnosis, respectively. The strongest association of moderate and rapid deterioration was with a low platelet count (r2 = 0.37 and 0.70, respectively; P < 0.0001). In patients with moderate deterioration, platelet count correlated inversely with UA-PI (ρ = -0.44, P = 0.001) and was lowest when end-diastolic velocity was absent. With rapid progression, platelet count correlated inversely with nucleated red blood cell count (ρ = -0.51, P < 0.001) but no longer with UA-PI. CONCLUSION: Our observations suggest a relationship between prenatal clinical progression of FGR and hematologic abnormalities at birth. Accelerating cardiovascular deterioration is associated with decreased platelet count, which can be explained by placental consumption or dysfunctional erythropoiesis and thrombopoiesis.

Decreased fetal cardiac performance in the first trimester correlates with hyperglycemia in pregestational maternal diabetes.

OBJECTIVE: In-vitro animal studies suggest that high glucose levels impair fetal cardiac function early in gestation. We aimed to study whether evidence of first-trimester myocardial dysfunction can be detected in fetuses of women with pregestational diabetes mellitus. METHODS: Women with diabetes mellitus underwent fetal echocardiography at 11-14 weeks' gestational age. In fetuses with normal anatomy, the cardiac preload, diastolic function, global myocardial performance and placental afterload were studied by Doppler of the ductus venosus (DV), mitral and tricuspid early/atrial (E/A) ratios, left and right ventricular myocardial performance index (MPI) and umbilical artery (UA) Doppler, respectively. Cases were matched for gestational age and UA and DV Doppler with controls that had no diabetes mellitus. RESULTS: Sixty-three singleton diabetic pregnancies were matched with 63 controls. Mean gestational age at enrollment was 12.6 (range, 11.1-13.6) weeks. Diabetic mothers had moderate to poor glycemic control (median (range) glycosylated hemoglobin A1 (HbA1c), 7.5 (5.1-12.7)%, and the HbA1c level was ≥ 7% in 37 (59%)). Fetuses of diabetic mothers exhibited worse measures of diastolic dysfunction: the isovolumetric relaxation time (IRT) was significantly prolonged (left ventricle: 36.9 ± 7.4 ms vs. 45.8 ± 6.8 ms; right ventricle: 35.6 ± 8 ms vs. 46.4 ± 7.3 ms, P < 0.0001 for both). The mitral E/A ratio was lower in diabetics (0.55 ± 0.06 vs. 0.51 ± 0.08, P = 0.03), and the global myocardial performance was lower in both ventricles (left ventricle MPI: 0.5 ± 0.08; right ventricle MPI: 0.52 ± 0.08, P = 0.03 and P < 0.0001, respectively). This lower global myocardial performance was caused by a prolonged myocardial relaxation time, which was most marked in diabetics with an HbA1c of ≥ 7% (P < 0.001 vs. controls for both ventricles). There were no significant correlations between cardiac Doppler parameters and DV, UA indices and fetal heart rate (P > 0.05 for all). CONCLUSIONS: Fetuses of poorly controlled diabetic mothers demonstrate significant differences in first-trimester diastolic myocardial function compared with non-diabetic controls. The decrease in myocardial performance is more marked with increasing HbA1c and appears to be independent of preload and afterload. The ability to document these cardiac functional changes this early in pregnancy opens potential new avenues to understand the consequences of maternal glycemic status.

Duration of persistent abnormal ductus venosus flow and its impact on perinatal outcome in fetal growth restriction.

OBJECTIVE: To study if the duration of individual Doppler abnormalities is an independent predictor of adverse outcome in fetal growth restriction (FGR) caused by placental dysfunction. METHODS: This was a secondary analysis of patients with FGR (abdominal circumference < 5(th) percentile and umbilical artery (UA) pulsatility index (PI) elevation) who had at least three examinations before delivery. Days of duration of absent/reversed UA end-diastolic velocity (UA-AREDV), low middle cerebral artery PI (brain sparing), ductus venosus (DV) and umbilical vein Doppler abnormalities were related to stillbirth, major neonatal morbidity and intact survival. RESULTS: One hundred and seventy-seven study participants underwent a total of 1069 examinations. The duration of an absent/reversed a-wave in the DV (DV-RAV) was significantly higher in stillbirths (median, 6 days) compared with intact survivors and those with major morbidity (median, 0 days for both; P = 0.006 and P = 0.001, respectively). Duration of brain sparing was also longer in stillbirth cases compared with intact survivors (median, 19 days vs. 9 days, P = 0.02). Stepwise multinomial logistic regression showed that gestational age at delivery was a significant codeterminant of outcome for all arterial Doppler abnormalities when the DV a-wave was antegrade. However, when present, the duration of DV-RAV was the only contributor to stillbirth (probability of stillbirth = 1/(1 + exp - (interval to delivery × 1.03 - 2.28)), r2 = 0.73). Receiver-operating characteristics curve statistics showed that a DV-RAV for > 7 days predicted stillbirth (100% sensitivity, 80% specificity, likelihood ratio = 5.0, P < 0.0001). In contrast, neither neonatal death nor neonatal morbidity was predicted by the days of persistent DV-RAV. CONCLUSIONS: The duration of absent or reversed flow during atrial systole in the DV is a strong predictor of stillbirth that is independent of gestational age. While prematurity remains the strongest predictor of neonatal risks it is unlikely that pregnancy can be prolonged by more than 1 week in this setting.

Standardization of the first-trimester fetal cardiac examination using spatiotemporal image correlation with tomographic ultrasound and color Doppler imaging.

OBJECTIVE: The challenges of the first-trimester examination of the fetal heart may in part be overcome by technical advances in three-dimensional (3D) ultrasound techniques. Our aim was to standardize the first-trimester 3D imaging approach to the cardiac examination to provide the most consistent and accurate display of anatomy. METHODS: Low-risk women with normal findings on first-trimester screening at 11 to 13 + 6 weeks had cardiac ultrasound using the following sequence: (1) identification of the four-chamber view; (2) four-dimensional (4D) volume acquisition with spatiotemporal image correlation (STIC) and color Doppler imaging (angle = 20 degrees, sweep 10 s); (3) offline, tomographic ultrasound imaging (TUI) analysis with standardized starting plane (four-chamber view), slice number and thickness; (4) assessment of fetal cardiac anatomy (four-chamber view, cardiac axis, size and symmetry, atrioventricular valves, great arteries and descending aorta) with and without color Doppler. RESULTS: 107 consecutive women (age, 16-42 years, body mass index 17.2-50.2 kg/m(2)) were studied. A minimum of three 3D volumes were obtained for each patient, transabdominally in 91.6%. Fetal motion artifact required acquisition of more than three volumes in 20%. The median time for TUI offline analysis was 100 (range, 60-240) s. Individual anatomic landmarks were identified in 89.7-99.1%. Visualization of all structures in one panel was observed in 91 patients (85%). CONCLUSION: Starting from a simple two-dimensional cardiac landmark-the four-chamber view-the standardized STIC-TUI technique enables detailed segmental cardiac evaluation of the normal fetal heart in the first trimester.

Progression of Doppler abnormalities in intrauterine growth restriction.

OBJECTIVE: To identify the sequence of progression of arterial and venous Doppler abnormalities from the onset of placental insufficiency in intrauterine growth restriction (IUGR). METHODS: Prospective observational study of singletons with IUGR (abdominal circumference < 5(th) percentile) who underwent serial standardized umbilical artery (UA), middle cerebral artery (MCA), ductus venosus (DV) and umbilical vein (UV) Doppler surveillance. Time intervals between progressive Doppler abnormalities and patterns of deterioration were related to UA Doppler status and gestational age. RESULTS: Six hundred and sixty-eight longitudinal examinations were performed in 104 fetuses, identifying three patterns of progression: (1) Mild placental dysfunction (n = 34) that remained confined to the UA/MCA. The UA became abnormal at a median of 32 weeks' gestation but the pulsatility index never exceeded 3 SD above normal. Progression took a median of 33 days, requiring delivery at a median of 35 weeks. (2) Progressive placental dysfunction (n = 49). Initially normal UA Doppler PI at 29 weeks' gestation increased beyond 3 SD, progressing to abnormal MCA, absent/reversed UA diastolic flow, abnormal DV, UV pulsations in 9-day intervals requiring delivery by 33 weeks. (3) Severe early-onset placental dysfunction (n = 21). Markedly elevated UA PI established by 27 weeks' gestation was associated with rapid (7-day intervals) progression to abnormal venous Doppler with median delivery at 30.6 weeks. Gestational age at onset, time to delivery and progression intervals were different between patterns (all P < 0.05). CONCLUSION: The characteristics of cardiovascular manifestations in IUGR are determined by the gestational age at onset and the severity of placental disease. Recognition of these factors is critical for planning fetal surveillance in IUGR.

Effect of parity on maternal cardiac function during the first trimester of pregnancy.

OBJECTIVE: To investigate maternal cardiac adaptation in the first trimester of pregnancy with increasing maternal parity. METHODS: This was a cross-sectional study carried out at the antenatal clinic of a teaching hospital. We examined 4689 pregnant women at 11 + 0 to 13 + 6 weeks of gestation, performing two-dimensional echocardiography of the maternal left ventricle. There were 2352 parous and 2337 nulliparous women. The relationships between parity, maternal cardiac function and neonatal birth weight were analyzed. RESULTS: Parous compared to nulliparous women had a significantly higher median cardiac output (5.6 vs. 5.2 L/min) and median cardiac index (2.3 vs. 2.1 L/min/m(2)). This was owing to a significantly higher median stroke volume (73.5 vs. 70.5 mL), heart rate (76 vs. 75 bpm), left ventricular outflow diameter (20.4 vs. 20.0 mm) and lower total vascular resistance (1190.8 vs. 1253.7 dyne s/cm(5)) and median uterine artery pulsatility index (1.6 vs. 1.7). Mean arterial blood pressure was not significantly different between the groups. There was a progressive increase in all maternal cardiac variables, apart from total peripheral resistance, which decreased with increasing parity. Birth weight was higher in parous compared to nulliparous women (3.39 vs. 3.23 kg) and it was independently related to maternal hemodynamic variables and demographic and social characteristics (age, height, weight, ethnicity, smoking). CONCLUSION: Pregnancy in parous compared to nulliparous women is characterized by higher maternal cardiac output and birth weight.

Maternal cardiac function and uterine artery Doppler at 11-14 weeks in the prediction of pre-eclampsia in nulliparous women.

OBJECTIVE: To assess maternal cardiac function in nulliparous women in the first trimester of pregnancy and evaluate its potential role for predicting pre-eclampsia and small for gestational age (SGA). DESIGN: Prospective, observational, cross-sectional study. SETTING: Maternity unit of a teaching hospital. POPULATION: Nulliparous women with singleton pregnancies presenting consecutively for routine antenatal care (n= 534). METHODS: Two-dimensional and M-mode echocardiography and uterine artery Dopplers were carried out at 11-14 weeks. MAIN OUTCOME MEASURES: Cardiac output (CO), stroke volume (SV), mean arterial pressure (MAP), total vascular resistance and uterine artery pulsatility index (UAPI) were compared in four outcome groups according to the development of pre-eclampsia and/or SGA. RESULTS: Compared with the normal outcome group (n= 457), in those with pre-eclampsia but not SGA (n = 8), CO and MAP were increased; in the group with pre-eclampsia and SGA (n= 19) MAP, TRP and UAPI were increased and in the group with SGA but no pre-eclampsia (n= 50) total peripheral resistance and UAPI were increased. Independent predictors of pre-eclampsia were MAP, SV and UAPI and of SGA SV and UAPI. CONCLUSIONS: Alterations in maternal cardiac function and UAPI are observed in the first trimester of pregnancy in nulliparous women that subsequently develop pre-eclampsia and/or SGA.

Computerized fetal heart rate analysis, Doppler ultrasound and biophysical profile score in the prediction of acid-base status of growth-restricted fetuses.

OBJECTIVE: To investigate the performance of non-stress test (NST), computerized fetal heart rate analysis (cCTG), biophysical profile scoring (BPS) and arterial and venous Doppler ultrasound investigation in the prediction of acid-base status in fetal growth restriction. METHODS: Growth-restricted fetuses, defined by abdominal circumference < 5(th) percentile and umbilical artery (UA) pulsatility index > 95(th) percentile, were tested by NST, cCTG, BPS, and UA, middle cerebral artery (MCA), ductus venosus (DV) and umbilical vein (UV) Doppler investigation. The short-term variation (STV) of the fetal heart rate was calculated using the Oxford Sonicaid 8002 cCTG system. Relationships between antenatal test results and cord artery pH < 7.20 were investigated, using correlation, parametric and non-parametric tests. RESULTS: Fifty-six of 58 patients (96.6%) received complete assessment of all variables. All were delivered by pre-labor Cesarean section at a median gestational age of 30 + 6 weeks. The UA pulsatility index (PI) was negatively correlated with the cCTG STV (Pearson correlation - 0.29, P < 0.05). The DV PI was negatively correlated with the pH (Pearson correlation - 0.30, P < 0.02). The cCTG mean minute variation and pH were not significantly correlated (Pearson correlation 0.13, P = 0.34). UV pulsations identified the highest proportion of neonates with a low birth pH (9/17, 53%), the highest number of false positives among patients with an abnormal BPS, abnormal DV Doppler and a STV < 3.5 ms, and also stratified false negatives among patients with an equivocal or normal BPS. Abnormal DV Doppler correctly identified false positives among patients with an abnormal BPS. cCTG reduced the rate of an equivocal BPS from 16% to 7.1% when substituted for the traditional NST. Elevated DV Doppler index and umbilical venous pulsations predicted a low pH with 73% sensitivity and 90% specificity (P = 0.008). CONCLUSION: In fetal growth restriction with placental insufficiency, venous Doppler investigation provides the best prediction of acid-base status. The cCTG performs best when combined with venous Doppler or as a substitute for the traditional NST in the BPS.