Cardiac adaptation and malformation in twin-twin transfusion syndrome and selective fetal growth restriction: A systematic review.

OBJECTIVES: This systematic review explores cardiac adaptation in monochorionic (MC) twins with twin-twin transfusion syndrome (TTTS) or selective fetal growth restriction (sFGR) and assesses the risk of congenital heart defects (CHDs). METHODS: Adhering to PRISMA guidelines, 63 studies were reviewed (49 on cardiac adaptation, 13 on CHD, one on both). A narrative synthesis of cardiac adaptation patterns was performed. Additionally, a meta-analysis compared the livebirth prevalence of CHD in TTTS and sFGR against uncomplicated MC twins. RESULTS: In TTTS recipients, cardiac function may be impaired for diastolic, systolic, as well as global functions, while in donors, cardiac function is generally preserved. In sFGR, large twins may show hypertrophic cardiomyopathy, and small twins may show impaired systolic function. Co-occurrence of TTTS and sFGR magnifies cardiac impact but is often underreported. Meta-analysis for CHD prevalence revealed a relative risk ratio of 3.5 (95% CI: 2.5-4.9) for TTTS and 2.2 (95%CI: 1.3-3.5) for sFGR compared with uncomplicated MC twins. CONCLUSIONS: This study highlights the well-documented cardiac adaptation in TTTS, contrasting with limited understanding in sFGR. Elevated CHD risks were observed in both conditions. Enhanced cardiovascular surveillance is warranted in complicated MC twin pregnancies. Future research should explore cardiac adaptation in sFGR and its long-term consequences.

Automated quantitative evaluation of fetal atrioventricular annular plane systolic excursion before and after intrauterine blood transfusion in pregnancies affected by red blood cell alloimmunization.

INTRODUCTION: Maternal red blood cell alloimmunization during pregnancy can lead to hemolysis and various degrees of fetal anemia, which can be treated with intrauterine blood transfusion (IUT) to prevent adverse outcomes. Knowledge about fetal myocardial function and adaptation is limited. The aim of the present study was to measure fetal atrioventricular plane displacement before and after IUT and compare these measurements with previously established reference ranges. MATERIAL AND METHODS: An observational study was conducted on pregnant women affected by red blood cell alloimmunization. Fetal echocardiography was performed before and after IUT. The atrioventricular plane displacement of the left and right ventricular walls and interventricular septum, described as mitral, septal, and tricuspid annular plane systolic excursion (MAPSE, SAPSE, and TAPSE, respectively), was assessed using color tissue Doppler imaging with automated analysis software. A Mann-Whitney U test was used to compare the z scores to the normal mean before and after IUT. RESULTS: Twenty-seven fetuses were included. The mean z score for pre-IUT MAPSE was significantly increased compared with the reference ranges, +0.46 (95% confidence interval [CI] +0.17 to +0.75; p = 0.039), while the mean z scores for post-IUT SAPSE and TAPSE were significantly decreased, -0.65 (95% CI -1.11 to -0.19; p < 0.001) and -0.60 (95% CI -1.04 to -0.17; p = 0.003), respectively. The difference in atrioventricular plane displacement z scores before and after IUT was statistically significant in all three locations. The median difference between the pre-IUT and post-IUT z scores was -0.66 (95% CI -1.03 to -0.33, p < 0.001) for MAPSE, -1.05 (95% CI -1.43 to -0.61, p < 0.001) for SAPSE, and -0.60 (95% CI -1.19 to -0.01, p = 0.046) for TAPSE. CONCLUSIONS: This study suggests that atrioventricular plane displacement, when determined using automated analysis software, may represent a quantitative parameter, describing fetal myocardial function and adaptation before and after IUT.

Importance of antenatal identification of small for gestational age fetuses on perinatal and childhood outcomes: A register-based cohort study.

INTRODUCTION: Fetal growth restriction (FGR) is associated with increased risk for stillbirth, perinatal morbidity, cerebral palsy, neurodevelopmental disorders and cardiovascular disease later in life. Identifying small-for-gestational-age (SGA) fetuses is crucial for the diagnosis of FGR. The aim of this study was to investigate the association between antenatal identification of SGA fetuses and severe adverse perinatal and childhood outcome. MATERIAL AND METHODS: A register-based cohort study of all newborns delivered in Stockholm in 2014 and 2017. INCLUSION CRITERIA: singleton pregnancies without chromosomal aberrations or structural abnormalities, with a gestational age at delivery between 22+0 and 43+0 (n = 48 843). Data from childbirth records were linked to data from nationwide Swedish registers. Pregnancy including offspring data were reviewed. Adverse outcomes for non-identified and identified SGA newborns were compared using logistic regression models. Primary outcome was a composite outcome called severe adverse outcome, defined as at least one of the following: stillbirth, severe newborn distress (Apgar score <4 at 5 min, pH <7 or resuscitation activities >10 min), severe neonatal outcome (hypoxic ischemic encephalopathy 2-3, necrotizing enterocolitis, neonatal seizures, intraventricular hemorrhage grade 3-4, bronchopulmonary disease or death at <1 year), severe childhood outcome (cognitive impairment or motor impairment or cerebral palsy or hearing impairment or visual impairment or death at 1-3 years old). Secondary outcomes were stillbirth, severe newborn distress, severe neonatal outcome, severe childhood outcome. RESULTS: No association was found between antenatal identification of SGA fetuses and severe adverse outcome using the complete composite outcome (adjusted odds ratio [aOR] 1.19, 95% confidence interval [CI] 0.93-1.53). In subgroup analyses, non-identified SGA fetuses had an almost fivefold increased risk for stillbirth (aOR 4.79, 95% CI 2.63-8.72) and an increased risk for severe newborn distress (aOR 1.36, 95% CI 1.02-1.82), but a decreased risk for severe childhood outcome (aOR 0.63, 95% CI 0.40-0.99). No association was found between antenatal identification of SGA and severe neonatal outcome. CONCLUSIONS: Non-identified SGA fetuses have an increased risk for stillbirth and severe newborn distress. Conversely, identified SGA fetuses have an increased risk for severe childhood outcome.

The outcomes of team-based learning vs small group interactive learning in the obstetrics and gynecology course for undergraduate students.

INTRODUCTION: Team-based learning (TBL) is a well-established active teaching method which has been shown to have pedagogical advantages in some areas such as business education and preclinical disciplines in undergraduate medical education. Increasingly, it has been adapted to clinical disciplines. However, its superiority over conventional learning methods used in clinical years of medical school remains unclear. The aim of this study was to compare TBL with traditional seminars delivered in small group interactive learning (SIL) format in terms of knowledge acquisition and retention, satisfaction and engagement of undergraduate medical students during the 6-week obstetrics and gynecology clerkship. MATERIAL AND METHODS: The study was conducted at Karolinska Institutet, a medical university in Sweden, and had a prospective, crossover design. All fifth-year medical students attending the obstetrics and gynecology clerkship, at four different teaching hospitals in Stockholm (approximately 40 students per site), in the Autumn semester of 2022 were invited to participate. Two seminars (one in obstetrics and one in gynecology) were designed and delivered in two different formats, ie TBL and SIL. The student:teacher ratio was approximately 10:1 in the traditional SIL seminars and 20:1 in the TBL. All TBL seminars were facilitated by a single teacher who had been trained and certified in TBL. Student knowledge acquisition and retention were assessed by final examination scores, and the engagement and satisfaction were assessed by questionnaires. For the TBL seminars, individual and team readiness assurance tests were also performed and evaluated. RESULTS: Of 148 students participating in the classrooms, 132 answered the questionnaires. No statistically significant differences were observed between TBL and SIL methods with regard to student knowledge acquisition and retention, engagement and satisfaction. CONCLUSIONS: We found no differences in student learning outcomes or satisfaction using TBL or SIL methods. However, as TBL had a double the student to teacher ratio as compared with SIL, in settings where teachers are scarce and suitable rooms are available for TBL sessions, the method may be beneficial in reducing faculty workload without compromising students' learning outcomes.

Validity evidence supporting clinical skills assessment by artificial intelligence compared with trained clinician raters.

BACKGROUND: Artificial intelligence (AI) is becoming increasingly used in medical education, but our understanding of the validity of AI-based assessments (AIBA) as compared with traditional clinical expert-based assessments (EBA) is limited. In this study, the authors aimed to compare and contrast the validity evidence for the assessment of a complex clinical skill based on scores generated from an AI and trained clinical experts, respectively. METHODS: The study was conducted between September 2020 to October 2022. The authors used Kane's validity framework to prioritise and organise their evidence according to the four inferences: scoring, generalisation, extrapolation and implications. The context of the study was chorionic villus sampling performed within the simulated setting. AIBA and EBA were used to evaluate performances of experts, intermediates and novice based on video recordings. The clinical experts used a scoring instrument developed in a previous international consensus study. The AI used convolutional neural networks for capturing features on video recordings, motion tracking and eye movements to arrive at a final composite score. RESULTS: A total of 45 individuals participated in the study (22 novices, 12 intermediates and 11 experts). The authors demonstrated validity evidence for scoring, generalisation, extrapolation and implications for both EBA and AIBA. The plausibility of assumptions related to scoring, evidence of reproducibility and relation to different training levels was examined. Issues relating to construct underrepresentation, lack of explainability, and threats to robustness were identified as potential weak links in the AIBA validity argument compared with the EBA validity argument. CONCLUSION: There were weak links in the use of AIBA compared with EBA, mainly in their representation of the underlying construct but also regarding their explainability and ability to transfer to other datasets. However, combining AI and clinical expert-based assessments may offer complementary benefits, which is a promising subject for future research.

Team-based learning (TBL) in clinical disciplines for undergraduate medical students-a scoping review.

BACKGROUND: Team-based learning (TBL) is an evidence-based pedagogical method that has been used in undergraduate medical education since 2001. However, its use in clinical disciplines is rarely reported, and the impact of its implementation is not known. The aim of this study was to explore and map the published literature on the impact of implementing TBL in clinical disciplines in undergraduate medical education. METHODS: A comprehensive search of Medline, Education Resources Information Center (ERIC), and Web of Science databases was performed on November 24, 2021 and updated April 6, 2023, using relevant Medical Subject Headings (MeSH) and free-text terms. Original research studies reporting on the implementation of TBL in clinical disciplines in undergraduate medical education published in peer-reviewed English language journals were included irrespective of their methodological design. RESULTS: The initial search identified 2,383 records. Of these, 49 met the inclusion criteria. Most of the studies (n = 44, 90%) described the implementation of a modified version of TBL in which one or more TBL steps were missing, and one study had undefined protocol for the implementation. The most reported outcomes were knowledge acquisition (n = 38, 78%) and students' satisfaction or attitudes toward TBL (n = 34, 69%). Despite some differences in their results, the studies found that implementing TBL is associated with increased knowledge acquisition (n = 19, 39%), student engagement (n = 6, 12%), and student satisfaction (n = 31, 63%). CONCLUSIONS: Most of the studies reported positive results in students' satisfaction and students' engagement, whilst the results on knowledge acquisition and retention were more contradictory. In most of the studies, TBL was implemented in a modified form and diverse comparators were used. The methodological quality also varied. Thus, no unequivocal conclusions could be drawn regarding the value of implementing TBL in clinical disciplines. More studies with rigorous methodologies are needed in this field.

Perinatal outcome in monoamniotic twin pregnancies during a 10-year period: a single center, descriptive study.

PURPOSE: To retrospectively investigate perinatal outcome of monoamniotic twin pregnancies in a tertiary center during a 10 year period. METHODS: A retrospective analysis of all monoamniotic pregnancies managed at Karolinska University Hospital, Stockholm, Sweden 2010-2019 was performed. The primary outcomes were live birth rate, neonatal death and perinatal survival. The secondary outcomes were late miscarriage, gestational age at delivery and frequency of fetal complications. RESULTS: Twenty-two monoamniotic pregnancies, with 44 fetuses, were identified. Thirty-five of 44 fetuses (80%) were liveborn. Of 36 fetuses reaching 24 weeks gestation, 35 (97%) were liveborn. There were no neonatal deaths, thus the perinatal survival was 97%. The mean gestational age at birth was 32.5 weeks (SD ± 1.5). CONCLUSIONS: The live birth rate and perinatal survival of monoamniotic pregnancies managed at Karolinska University Hospital was high and comparable to previously published data.

The prognosis of common arterial trunk from a fetal perspective: A prenatal cohort study and systematic literature review.

OBJECTIVE: The limited number of large fetal cohort studies on common arterial trunk (CAT) impedes prenatal counseling at midgestation. This study evaluates the prognosis of CAT from a fetal perspective. METHOD: Fetuses with a prenatally diagnosed CAT were extracted from the PRECOR registry (2002-2016). We evaluated fetal and postnatal survival and the presence of additional morbidity at last follow-up. Literature databases were searches systematically for additional cases. RESULTS: Thirty-eight cases with a prenatal diagnosis of CAT were identified in our registry, of which 18/38 (47%) opted for pregnancy termination (TOP). Two cases resulted in spontaneous intrauterine demise (10%, 2/20), six cases demised postnatally (33%, 6/18), leaving 60% (12/20) alive, after exclusion of TOP, at a mean age of six (range: 2-10 years). Additional morbidity was found in 42% (5/12) of survivors, including 22q11.2 deletion syndrome, Adams-Oliver syndrome and intestinal atresia, whereas 8% (1/12) had developmental delay. The remaining 30% (6/12) of survivors appeared isolated with normal development. All of whom six required replacement of the initial right ventricle to pulmonary artery conduit. Additionally, we reviewed 197 literature cases on short-term outcome. CONCLUSION: The risk of fetal and neonatal demise, as well as significant morbidity amongst survivors, should be included in prenatal counseling for CAT.

Reference ranges of fetal superior vena cava blood flow velocities and pulsatility index in the second half of pregnancy: a longitudinal study.

BACKGROUND: Fetal superior vena cava (SVC) is essentially the single vessel returning blood from the upper body to the heart. With approximately 80-85% of SVC blood flow representing cerebral venous return, its interrogation may provide clinically relevant information about fetal brain circulation. However, normal reference values for fetal SVC Doppler velocities and pulsatility index are lacking. Our aim was to establish longitudinal reference intervals for blood flow velocities and pulsatility index of the SVC during the second half of pregnancy. METHODS: This was a prospective study of low-risk singleton pregnancies. Serial Doppler examinations were performed approximately every 4 weeks to obtain fetal SVC blood velocity waveforms during 20-41 weeks. Peak systolic (S) velocity, diastolic (D) velocity, time-averaged maximum velocity (TAMxV), time-averaged intensity-weighted mean velocity (TAMeanV), and end-diastolic velocity during atrial contraction (A-velocity) were measured. Pulsatility index for vein (PIV) was calculated. RESULTS: SVC blood flow velocities were successfully recorded in the 134 fetuses yielding 510 sets of observations. The velocities increased significantly with advancing gestation: mean S-velocity increased from 24.0 to 39.8 cm/s, D-velocity from 13.0 to 19.0 cm/s, and A-velocity from 4.8 to 7.1 cm/s. Mean TAMxV increased from 12.7 to 23.1 cm/s, and TAMeanV from 6.9 to 11.2 cm/s. The PIV remained stable at 1.5 throughout the second half of pregnancy. CONCLUSIONS: Longitudinal reference intervals of SVC blood flow velocities and PIV were established for the second half of pregnancy. The SVC velocities increased with advancing gestation, while the PIV remained stable from 20 weeks to term.

Volume blood flow-based indices of fetal brain sparing in the second half of pregnancy: A longitudinal study.

INTRODUCTION: Cerebroplacental ratio (CPR) and umbilicocerebral ratio (UCR) are clinically used as a measure of fetal brain sparing. These are calculated as the ratios between the pulsatility indices (PIs) of middle cerebral (MCA) and umbilical (UA) arteries, and are an indirect representation of the balance between cerebral and placental perfusion. Volume blood flow (Q)-based ratios, ie Q-CPR or Q-UCR, would directly reflect the distribution of fetal cardiac output to the placenta and brain. Thus, we aimed to determine the development pattern of Q-CPR and Q-UCR during the second half of pregnancy, construct reference intervals, and evaluate their association with CPR and UCR. MATERIAL AND METHODS: In a longitudinal cohort study of low-risk pregnancies, the inner diameter of the fetal superior vena cava (SVC) and umbilical vein (UV) was measured and velocity waveforms were obtained from the MCA, UA, UV and SVC using ultrasound at approximately 4-weekly intervals from 20 to 41 weeks. The CPR was calculated as PIMCA /PIUA and the inverse ratio was the UCR. Cerebral and placental blood flows were estimated as the product of mean velocity and cross-sectional area of the SVC and UV, respectively. Q-CPR was calculated as QSVC /QUV and the inverse as the Q-UCR. Gestational age-specific reference intervals were calculated and associations between variables were tested using multilevel regression modeling. RESULTS: Longitudinal reference intervals of Q-CPR and Q-UCR were established based on 471 paired measurements of QSVC and QUV obtained serially from 134 singleton pregnancies. The mean Q-CPR increased from 0.4 to 0.8 during the second half of pregnancy and Q-UCR declined from 2.5 to 1.3, while the CPR and UCR had U-shaped curves but in opposite directions. No significant correlation was found between CPR and Q-CPR (R = 0.10; P = .051), or UCR and Q-UCR (R = 0.09; P = .11), and the agreement between PI-based and Q-based indices of fetal brain sparing was poor. CONCLUSIONS: Indices of fetal brain sparing based on placental and cerebral volume blood flow differ from those calculated from UA and MCA PIs. They correlated poorly with conventional CPR and UCR, indicating that they may provide additional/different physiological information. Reference values of Q-CPR and Q-UCR established here can be useful to investigate their clinical value further.

Fetal cardiac function at intrauterine transfusion assessed by automated analysis of color tissue Doppler recordings.

BACKGROUND: Fetal anemia is associated with a hyperdynamic circulation and cardiac remodeling. Rapid intrauterine transfusion (IUT) of blood with high hematocrit and viscosity into the umbilical vein used to treat this condition can temporarily further affect fetal heart function. The aim of this study was to evaluate the short-term changes in fetal myocardial function caused by IUT using automated analysis of cine-loops of the fetal heart obtained by color tissue Doppler imaging (cTDI). METHODS: Fetal echocardiography was performed before and after IUT. cTDI recordings were obtained in a four-chamber view and regions of interest were placed at the atrioventricular plane in the left ventricular (LV), right ventricular (RV) and septal walls. Myocardial velocities were analyzed by an automated analysis software to obtain peak myocardial velocities during atrial contraction (Am), ventricular ejection (Sm), rapid ventricular filling (Em) and Em/Am ratio was calculated. Myocardial velocities were converted to z-scores using published reference ranges. Delta z-scores (after minus before IUT) were calculated. Correlations were assessed between variables and hemoglobin before IUT. RESULTS: Thirty-two fetuses underwent 70 IUTs. Fourteen were first time transfusions. In the LV and septal walls, all myocardial velocities were significantly increased compared to normal values, whereas in the RV only Sm was increased before IUT (z-scores 0.26-0.52). In first time IUTs, there was a negative correlation between LV Em (rho = - 0.61, p = 0.036) and LV Em/Am (rho = - 0.82, p = 0.001) z-scores and hemoglobin before IUT. The peak myocardial velocities that were increased before IUT decreased, whereas LV Em/Am increased significantly after IUT. CONCLUSIONS: This study showed that peak myocardial velocities assessed by cTDI are increased in fetuses before IUT reflecting the physiology of hyperdynamic circulation. In these fetuses, the fetal heart is able to adapt and efficiently handle the volume load caused by IUT by altering its myocardial function.

Automated analysis of color tissue Doppler velocity recordings of the fetal myocardium using a new algorithm.

BACKGROUND: Tissue Doppler imaging (TDI) can be used to assess fetal cardiac function and it has been shown to detect changes associated with hypoxia in animal models. However, the analysis is cumbersome and time consuming. The main objective of this study was to evaluate the feasibility of a new algorithm developed for the automated analysis of color TDI velocity recordings of the fetal myocardium. Furthermore, we wanted to assess the effect of different sizes of region of interests (ROI) on the measurement of cardiac cycle time intervals and myocardial velocities at different gestations. METHODS: This study included analysis of 261 TDI velocity traces obtained from 17 fetal echocardiographic examinations performed longitudinally on five pregnant women. Cine-loops of fetal cardiac four chamber view were recorded with color overlay in TDI mode and stored for off-line analysis. ROIs of different sizes were placed at the level of the atrioventricular plane in the septum and in the right and left ventricular walls of the fetal heart. An automated algorithm was then used for the analysis of velocity traces. RESULTS: Out of the total 261 velocity traces, it was possible to analyze 203 (78 %) traces with the automated algorithm. It was possible to analyze 93 % (81/87) of traces recorded from the right ventricular wall, 82 % (71/87) from the left ventricular wall and 59 % (51/87) from the septum. There was a trend towards decreasing myocardial velocities with increasing ROI length. However, the cardiac cycle time intervals were similar irrespective of which ROI size was used. CONCLUSIONS: An automated analysis of color TDI fetal myocardial velocity traces seems feasible, especially for measuring cardiac cycle time intervals, and has the potential for clinical application.

Reference values for fetal tissue velocity imaging and a new approach to evaluate fetal myocardial function.

OBJECTIVES: Myocardial function can be evaluated using color-coded tissue velocity imaging (TVI) to analyze the longitudinal myocardial velocity profile, and by expressing the motion of the atrioventricular plane during a cardiac cycle as coordinated events in the cardiac state diagram (CSD). The objective of this study was to establish gestational age specific reference values for fetal TVI measurements and to introduce the CSD as a potential aid in fetal myocardial evaluation. METHODS: TVI recordings from 125 healthy fetuses, at 18 to 42 weeks of gestation, were performed with the transducer perpendicular to the apex to provide a four-chamber view. The myocardial velocity data was extracted from the basal segment of septum as well as the left and right ventricular free wall for subsequent offline analysis. RESULTS: During a cardiac cycle the longitudinal peak velocities of septum increased with gestational age, as did the peak velocities of the left and right ventricular free wall, except for the peak velocity of post ejection. The duration of rapid filling and atrial contraction increased during pregnancy while the duration of post ejection decreased. The duration of pre ejection and ventricular ejection did not change significantly with gestational age. CONCLUSION: Evaluating fetal systolic and diastolic performance using TVI together with CSD could contribute to increase the knowledge and understanding of fetal myocardial function and dysfunction. The pre and post ejection phases are the variables most likely to indicate fetuses with abnormal myocardial function.

Fetal Superior Vena Cava Blood Flow and Its Fraction of Cardiac Output: A Longitudinal Ultrasound Study in the Second Half of Pregnancy.

Introduction: In the fetus, a large proportion of the superior vena cava blood flow (QSVC) comes from the brain. To provide the possibility of using this blood flow as a representation of fetal brain circulation, we aimed to determine the fetal QSVC and its fraction of cardiac output during the second half of physiological pregnancies. Materials and Methods: This was a prospective longitudinal study specifically designed for studying fetal hemodynamic development. Healthy women with singleton low-risk pregnancies were included. Ultrasonography was performed at 4-weekly intervals from 20+0 gestational weeks to term. Doppler velocity recordings of the superior vena cava (SVC) and cardiac ventricular outflow tracts were used to obtain the time-averaged maximum velocities (TAMxV). Vessel diameters were measured to calculate their cross-sectional areas (CSA): π(diameter/2)2. Blood flow (Q) was computed as: h *TAMxV*CSA, h being the spatial blood velocity profile, to obtain QSVC and cardiac outputs. The sum of left and right ventricular cardiac outputs constituted the combined cardiac output (CCO). Ultrasound biometry based estimated fetal weight and brain weight were used to normalize the flow. QSVC was also expressed as the fraction (%) of CCO. Gestational age specific percentiles were established for each blood flow parameter using multilevel modeling. Results: Totally, 134 of the 142 included women were eligible for the study with 575 sets of observations. The SVC mean diameter (19-52 mm), mean TAMxV (8.83-16.14 cm/s), and QSVC (15.4-192.0 ml/min) increased significantly during the second half of pregnancy (p < 0.001) while the mean QSVC normalized by estimated fetal weight (49 ml/min/kg) and by estimated brain weight (50 ml/min/100 g) were relatively stable. Similarly, the mean CCO increased (156-1,776 ml/min; p < 0.001) while the normalized CCO (509 ± 13 ml/min/kg) and QSVC as a fraction of CCO (10 ± 0.92%) did not change significantly with gestational age. Conclusion: We provide reference values for fetal QSVC which increases significantly with gestation, and constitutes roughly 10% of the fetal CCO at any time during the second half of pregnancy.