Fetal anemia causes placental and maternal cellular damage: a lesson from fetal hemoglobin Bart's disease.

INTRODUCTION: The studies about effect of fetal anemia on placental and maternal molecular changes have rarely been published. This study aimed to compare oxidative stress levels and mitochondrial function in the placenta and maternal peripheral blood mononuclear cell (PMBCs) between anemic fetuses (using fetal Hb Bart's disease as a study model) and non-anemic fetuses. METHODS: A cross-sectional study was conducted on pregnancies affected by Hb Bart's disease and non-anemic fetuses between 16 and 22 weeks of gestation. Placental tissue and maternal blood for PBMCs were collected after pregnancy termination for determination of oxidative stress and mitochondrial function. RESULTS: A total of 18 pregnancies affected by Hb Bart's disease and 12 non-anemic fetuses were enrolled. Placental thickness was significantly greater (p-value <0.001) in the affected pregnancies, whereas all Doppler indices of uteroplacental blood flow were comparable. Mitochondrial dysfunction was significantly increased (p-value <0.001) in the placenta of the affected fetuses. In the mothers of affected fetuses, there was an increase in mitochondrial oxidative stress levels with a significant increase in mitochondrial dysfunction in isolated PBMCs (p-value <0.001). DISCUSSION: In the presence of normal uteroplacental Doppler studies, fetal anemia can induce a significant increase in oxidative stress and mitochondrial dysfunction in the placentas and mothers. The findings support that the placenta can be a source of oxidative stress agents which are released into systemic circulation prior to development of maternal adverse outcomes, and may explain pathophysiology of subsequent preeclampsia in late gestation, as commonly seen in pregnancies affected by fetal Hb Bart's disease, if pregnancy is not terminated.

Fetal hemodynamic changes and mitochondrial dysfunction in myocardium and brain tissues in response to anemia: a lesson from hemoglobin Bart's disease.

OBJECTIVE: Whether or not the effects of anemia in the early phase, while the fetuses attempts to increase cardiac output to meet oxygen requirement in peripheral organs, is detrimental to the fetal developing vital organs is little-known. The objective of this is to compare prenatal cardiovascular changes and post-abortal cellular damages in the myocardium as a pumping organ and the brain as a perfused organ between anemic fetuses (using fetal Hb Bart's disease as a study model) in pre-hydropic phase and non-anemic fetuses. METHODS: Fetuses affected by Hb Bart's disease and non-anemic fetuses at 16-22 weeks were recruited to undergo comprehensive fetal echocardiography. Cord blood analysis was used to confirm the definite diagnosis of fetal Hb Bart's disease and normal fetuses. Fetal cardiac and brain tissues were collected shortly after pregnancy termination for the determination of oxidative stress and mitochondrial function, including mitochondrial ROS production and mitochondrial membrane changes. RESULTS: A total of 18 fetuses affected by Hb Bart's disease and 13 non-anemic fetuses were recruited. The clinical characteristics of both groups were comparable. The affected fetuses showed a significant increase in cardiac dimensions, cardiac function, cardiac output and brain circulation without deteriorating cardiac contractility and preload. However, in the affected fetuses, mitochondrial dysfunction was clearly demonstrated in brain tissues and in the myocardium, as indicated by a significant increase in the membrane potential change (p-value < 0.001), and a significant increase in ROS production in brain tissues, with a trend to increase in myocardium. The findings indicated cellular damage in spite of good clinical compensation. CONCLUSION: The new insight is that, in response to fetal anemia, fetal heart increases in size (dilatation) and function to increase cardiac output and blood flow velocity to provide adequate tissue perfusion, especially brain circulation. However, the myocardium and brain showed a significant increase in mitochondrial dysfunction, suggesting cellular damage secondary to anemic hypoxia. The compensatory increase in circulation could not completely prevent subtle brain and heart damage.

Maternal Visceral Fat in Prediction of Gestational Diabetes Mellitus.

Objective: To determine the diagnostic performance of maternal abdominal visceral adipose tissue thickness, measured by ultrasound, in predicting gestational diabetes mellitus (GDM). Patients and methods: A prospective diagnostic study was conducted on low-risk pregnant women attending our antenatal care clinic. All underwent abdominal visceral adipose tissue (VAT) measurement by two-dimension transabdominal ultrasound twice, at late first trimester (gestational age: GA 11-14 weeks) and second trimester (GA 18-22 weeks). All patients underwent a two-step approach for screening and diagnosis of GDM between GA 24 and 28 weeks. Results: A total of 141 women were recruited into the study; including 32 (22.7%) women with GDM, and 109 (77.3%) women of non-GDM, between GA 24 and 28 weeks. The means VAT at the 1st, 2nd trimester and the difference of VAT of GDM group were 4.0 ± 0.27 cm, 5.7 ± 1.12 cm, and 1.6 ± 0.91 cm respectively. The means VAT at 1st, 2nd trimester and the difference of VAT of non-GDM group were 3.8 ± 1.01 cm, 5.4 ± 1.07 cm, and 1.6 ± 1.12 cm respectively. There were no significant differences of VAT measurements (1st, 2nd and the difference) between both groups. The VAT thickness was slightly greater in the GDM group but the mean differences between 1st and 2nd trimester were comparable between the two groups. The diagnostic performance of VAT, maternal age and body mass index (BMI) in predicting GDM was comparable. Conclusion: Measurement of maternal visceral adipose thickness in early pregnancy is not effective in predicting GDM among Thai women, which is different from most studies conducted on western women. However, a trend of higher VAT in the GDM group was noted.

Impacts of ß-thalassemia/hemoglobin E disease on pregnancy outcomes.

OBJECTIVE: To compare obstetric outcomes between women with ß-thalassemia/hemoglobin E (ß-thal/HbE) disease and those of low-risk pregnancies, and also between the two subgroups, ß-thal0 /HbE and ß-thal+ /HbE disease. METHODS: A retrospective cohort study was undertaken on pregnant women with ß-thal/HbE disease and low-risk pregnancies, which were randomly selected with a case-to-control ratio of 1:10. RESULTS: Pregnancies with ß-thal/HbE disease were identified in 0.19% of 59 152 pregnancies, including 104 women in the study group and 1040 women in the control group. The mean gestational age and mean birth weight were significantly lower in the study group. The prevalence of fetal growth restriction, preterm birth and low birth weight were significantly increased in the study group based on both univariate and multivariate analysis. The impacts were more striking in the ß-thal0 /HbE subgroup than in the ß-thal+ /HbE subgroup. The cesarean rate was significantly higher in the study group. No maternal death or serious complication was found in this cohort. CONCLUSION: Based on this cohort, the largest ever published, ß-thal/HbE disease is significantly associated with increased incidence of fetal growth restriction, preterm birth and low birth weight. The impacts were more pronounced in the ß-thal0 /HbE subgroup. Pregnancy may be relatively safer for women with ß-thal/HbE disease.

Reference-range of arterial stiffness by cardio-ankle vascular index in normal pregnancy.

OBJECTIVE: To establish the arterial stiffness, represented by the cardio-ankle vascular index (CAVI) at various gestational ages among low-risk pregnant women. The second objective is to construct the reference range of mean arterial pressure and maternal heart rate during pregnancy. METHODS: This cross-sectional study was conducted on low risk pregnant Thai women, meeting the following inclusion criteria: 1) singleton pregnant women aged 18 years old or over; 2) gestational age between 11 and 40 weeks; 3) low-risk pregnancy without any underlying medical diseases; and 4) known final pregnancy outcomes. Pregnancy-induced hypertension, gestational diabetes and fetal growth restriction were excluded. The mean CAVI, mean arterial pressure (MAP), and heart rate were measured at each gestational age. RESULTS: A total of 329 measurements for each parameter were available for analysis. CAVI was significantly correlated with gestational age with the best fitted model: CAVI = 6.952 - 0.076(GA) + 0.001(GA)2; SD = 0.742 (R2 = 0.049; p-value < 0.001). The maternal age and pre-pregnancy BMI were correlated with CAVI. CAVI gradually increased with maternal age and decreased with increasing body mass index (BMI). The MAP and heart rate of normal pregnancy in each gestation were conducted. CONCLUSION: The reference range of CAVI in normal pregnancies as a function of gestational age and the model for predicting CAVI based on multiple regression analysis are constructed and presented. These reference ranges may be useful in predicting risk of cardiovascular disorders during pregnancy.

Comparison of fetal and neonatal cardiac morphology between the infants of mothers with well-controlled gestational diabetes mellitus and normal controls.

OBJECTIVE: To compare fetal and neonatal cardiac morphology in fetuses of mothers with gestational diabetes mellitus (GDM) with the controls. PATIENTS AND METHODS: Pregnant women at average risk of GDM underwent 100-g, 3-h-OGTT at 24-28 weeks of gestation for diagnosis of GDM. Both GDM group and the control group underwent fetal echocardiography at 32-36 weeks to assess cardiac dimensions. The neonates underwent echocardiography within 48 h after birth to assess cardiac morphology. RESULTS: A total of 154 pregnant women were recruited, including 60 in the GDM group and 94 in the control group. All of the study group were well controlled for GDM. Most baseline characteristics of both groups were comparable. All obstetric outcomes were not significantly different between the two groups. Morphological cardiac dimensions in the fetuses and newborns of both groups were also not significant different. Subgroup analysis in the study group showed no significantly different in cardiac morphology between the group with diet control and that of insulin control. CONCLUSION: Fetal and neonatal cardiac morphologic changes among mothers with well-controlled GDM are not significantly different from those in the controls. It is possible that good control of maternal blood glucose can prevent fetal and neonatal cardiac abnormalities.

Trends in the Prevalence of Diabetes Mellitus in Pregnancy during the Past Two Decades in Northern Thailand.

Background: The prevalence of gestational diabetes mellitus (GDM) and pre-gestational diabetes mellitus (PDM) has increased dramatically in the past decade in all ethnic groups. The prevalence also varies markedly among different ethnic groups. Each ethnic group must have its own data about GDM/PDM for improvement in women's health care. We conducted this study with the main objective of assessing recent trends in the prevalence of PDM/GDM among pregnant women in the northern part of Thailand during the past two decades. The secondary objective is to identify the risk factors influencing the prevalence of DM in pregnancies. Patients and Methods: The maternal-fetal medicine database was accessed to retrieve consecutive obstetric records of women who gave birth in Chiang Mai University Hospital, Thailand, from January 2003 to December 2022. This is a 20-year study period of the same protocol of GDM screening policy, using the 50 g glucose challenge test as a screening test for the average risk group and the 100 g OGTT as a diagnostic test. The women were categorized into GDM, PDM and non-DM groups. Trends or percentage changes in the prevalence of GDM/PDM during the study period were evaluated. Risk factors related to GDM/PDM were identified. Results: Among 37,027 women who gave birth during the study period, the prevalence of DM in pregnancy was 11.4% (4223 cases), including 214 cases of PDM (0.6%) and 4009 cases of GDM (10.8%). The prevalence of PDM significantly increased from 0.3% in 2003 to 1.5% in 2022; also, the prevalence of GDM significantly increased, dramatically, from 3.4% in 2003 to 22.0% in 2022. The prevalence of GDM increased in recent years in all age groups (adolescent, reproductive and elderly groups), while that of PDM did not significantly change in the adolescent group during the study period. Maternal age and pre-pregnancy BMI significantly increased in the more recent years. Independent factors significantly associated with the prevalence of PDM/GDM include maternal age, pre-pregnancy BMI, higher socio-economic status, and urban areas of residence. Recent time is still an independent risk factor after adjustment for other known factors. Conclusions: Relatively, GDM and PDM are highly prevalent in the northern part of Thailand, and their prevalence continuously increased during the past two decades. The trend of increased prevalence was evident in all age groups. Increasing maternal age and pre-pregnancy BMI mainly contributed to the increase in the prevalence of GDM and PDM in recent years. Recent time is still an independent risk factor after adjustment for other known factors, indicating that some other unexplained risk factors are associated with the increase in prevalence of DM in recent years, possibly the increase in sedentary lifestyle. Modification of lifestyle, especially reducing pre-pregnancy BMI among reproductive women, may reduce the prevalence of DM in pregnancy.

Performance of Serum Quad Test in Screening for Fetal Down Syndrome in a Large-Scale Unselected Population in a Developing Country.

Objective: To assess the effectiveness of Quad test in the detection of Down syndrome (DS) in routine practice among a large-scale population and to compare the effectiveness of Quad test based on the Western reference model (WM) and that based on Thai reference model (TM). Methods: Quad test was performed on 42,769 pregnancies at 14-21 weeks. The fetal risk of DS derived from Quad test was automatically computed based on WM and used in evaluating the effectiveness. Also, the fetal risk was calculated based on the TM. Results: Of 39,740 women with complete follow-ups including 74 fetuses with DS, with WM, the detection and false positive rates were 81.1% and 7.2%, respectively, whereas the detection and false positive rates with TM were 87.8%, and 6.8%, respectively. According to ROC curves, the performance of Quad test based on TM was slightly but significantly better than that based on WM (AUC of 0.959 vs. 0.940, p = 0.001). Conclusion: Quad test is highly effective in service settings and suitable for developing countries and the effectiveness is even higher when based on ethnicity-specific reference model.

Placenta-Derived Extracellular Vesicles in Pregnancy Complications and Prospects on a Liquid Biopsy for Hemoglobin Bart's Disease.

Extracellular vesicles (EVs) are nano-scaled vesicles released from all cell types into extracellular fluids and specifically contain signature molecules of the original cells and tissues, including the placenta. Placenta-derived EVs can be detected in maternal circulation at as early as six weeks of gestation, and their release can be triggered by the oxygen level and glucose concentration. Placental-associated complications such as preeclampsia, fetal growth restriction, and gestational diabetes have alterations in placenta-derived EVs in maternal plasma, and this can be used as a liquid biopsy for the diagnosis, prediction, and monitoring of such pregnancy complications. Alpha-thalassemia major ("homozygous alpha-thalassemia-1") or hemoglobin Bart's disease is the most severe form of thalassemia disease, and this condition is lethal for the fetus. Women with Bart's hydrops fetalis demonstrate signs of placental hypoxia and placentomegaly, thereby placenta-derived EVs provide an opportunity for a non-invasive liquid biopsy of this lethal condition. In this article, we introduced clinical features and current diagnostic markers of Bart's hydrops fetalis, extensively summarize the characteristics and biology of placenta-derived EVs, and discuss the challenges and opportunities of placenta-derived EVs as part of diagnostic tests for placental complications focusing on Bart's hydrop fetalis.

Convergent Validity of the Edinburgh Postnatal Depression Scale and the Patient Health Questionnaire (PHQ-9) in Pregnant and Postpartum Women: Their Construct Correlations with Functional Disability.

This study aimed to evaluate the convergent validity of the Edinburgh Postnatal Depression Scale (EPDS) and the Patient Health Questionnaire (PHQ-9) in Thai pregnant and postpartum women, using the 12-item WHO Disability Assessment Schedule (WHODAS) as the reference standard. Participants completed the EPDS, PHQ-9, and WHODAS during the third trimester of pregnancy (over 28 weeks in gestational age) and six weeks postpartum. The sample included 186 and 136 participants for the antenatal and postpartum data analyses, respectively. The antenatal and postpartum data showed moderate correlations between both the EPDS and the PHQ-9 scores and the WHODAS scores (Spearman's correlation coefficients = 0.53-0.66, p < 0.001). The EPDS and PHQ-9 were moderately accurate in distinguishing disability (WHODAS score ≥ 10) from non-disability (WHODAS score < 10) in pregnant and postpartum participants, but the area under the curve of the PHQ-9 receiver operating characteristic curves in postpartum participants was significantly larger than that of the EPDS, with a difference (95% CI; p-value) of 0.08 (0.16, 0.01; p = 0.044). In conclusion, the EPDS and PHQ-9 are valid for assessing PND-related disability in pregnant and postpartum women. The PHQ-9 may perform better than the EPDS in distinguishing disability from non-disability in postpartum women.

Prenatal Diagnosis of Fetal Heart Failure.

Fetal heart failure (FHF) is a condition of inability of the fetal heart to deliver adequate blood flow for tissue perfusion in various organs, especially the brain, heart, liver and kidneys. FHF is associated with inadequate cardiac output, which is commonly encountered as the final outcome of several disorders and may lead to intrauterine fetal death or severe morbidity. Fetal echocardiography plays an important role in diagnosis of FHF as well as of the underlying causes. The main findings supporting the diagnosis of FHF include various signs of cardiac dysfunction, such as cardiomegaly, poor contractility, low cardiac output, increased central venous pressures, hydropic signs, and the findings of specific underlying disorders. This review will present a summary of the pathophysiology of fetal cardiac failure and practical points in fetal echocardiography for diagnosis of FHF, focusing on essential diagnostic techniques used in daily practice for evaluation of fetal cardiac function, such as myocardial performance index, arterial and systemic venous Doppler waveforms, shortening fraction, and cardiovascular profile score (CVPs), a combination of five echocardiographic markers indicative of fetal cardiovascular health. The common causes of FHF are reviewed and updated in detail, including fetal dysrhythmia, fetal anemia (e.g., alpha-thalassemia, parvovirus B19 infection, and twin anemia-polycythemia sequence), non-anemic volume load (e.g., twin-to-twin transfusion, arteriovenous malformations, and sacrococcygeal teratoma, etc.), increased afterload (intrauterine growth restriction and outflow tract obstruction, such as critical aortic stenosis), intrinsic myocardial disease (cardiomyopathies), congenital heart defects (Ebstein anomaly, hypoplastic heart, pulmonary stenosis with intact interventricular septum, etc.) and external cardiac compression. Understanding the pathophysiology and clinical courses of various etiologies of FHF can help physicians make prenatal diagnoses and serve as a guide for counseling, surveillance and management.

Comparisons of Effectiveness in Differentiating Benign from Malignant Ovarian Masses between Conventional and Modified Risk of Malignancy Index (RMI).

OBJECTIVE: To compare the predictive performance in differentiating benign from malignant ovarian masses between the modified risk malignancy index (RMI) and the conventional RMI (RMI-1 and RMI-2). METHODS: Women scheduled for elective surgery because of adnexal masses were recruited to undergo pelvic sonography within 24 h before surgery to assess the sonographic characteristics of the masses, focusing on loculi, solid part, ascites, bilateralness, papillary projection, and color flow mapping (CFM). Preoperative CA-125 levels were also measured. Modified RMI, RMI-1, and RMI-2 systems were used to predict malignant masses. The gold standard was pathological or intraoperative diagnosis. RESULTS: A total of 342 ovarian masses, benign: 243 (71.1%); malignant: 99 (28.9%), meeting the inclusion criteria were analyzed. The sensitivity and the specificity of the modified RMI (87.9% and 81.9%) were significantly higher than those of RMI-1 (74.7% and 84.4%), and RMI-2 (79.8% and 81.1%, respectively). Based on ROC curves, the area under the curves were 0.930, 0.881 and 0.882 for modified RMI, RMI-1 and RMI-2, respectively. CONCLUSION: Modified RMI had better predictive performance than the conventional RMI in differentiating between benign and malignant ovarian masses. Modified RMI may be useful to help general gynecologists or practitioners to triage patients with an adnexal mass, especially in settings of low resources.

Serum oxytocin and corticotropin-releasing hormone levels in the third trimester of pregnancy for predicting postpartum depression in Thai women.

PURPOSE: This prospective observational study aimed to determine whether serum oxytocin (OT) or corticotrophin-releasing hormone (CRH) levels in the third trimester of pregnancy (or late pregnancy) could prospectively predict postpartum depression (PPD) at six weeks after childbirth. METHODS: We measured late pregnancy OT and CRH levels in Thai women, assessed depression using the Edinburgh Postnatal Depression Scale (EPDS) and Patient Health Questionnaire-9 (PHQ-9), and collected mothers, labor, and newborn data. At six weeks postpartum, an EPDS score ≥ 11 or PHQ-9 score ≥ 10 was defined as the presence of PPD. Multivariable binary logistic regression analysis was performed to determine the predictors of PPD. RESULTS: Of 200 participants, 136 (68.0%) were reassessed at six weeks postpartum, and 19 of them (14.0%) had PPD. Of the 19 participants with PPD, 9 met the EPDS criterion only, 3 met the PHQ-9 criterion only, and 7 met both criteria. OT levels were not significantly different between those with and without PPD (p = 0.35). CRH levels (aOR = 1.011, 95% CI = 1.001-1.023, p = 0.041), DASS-21 stress (aOR = 1.259, 95% CI = 1.132-1.400, p < 0.001), and APGAR at 1 min (aOR = 0.425, 95% CI = 0.240-0.752, p = 0.003) were significant predictors of PPD. CONCLUSIONS: Only high CRH but not OT levels in late pregnancy may predict 6-week PPD. However, combining these CRH levels, late pregnancy stress, and newborn well-being immediately after birth seems to increase the accuracy of PPD prediction.

Fetal Hemodynamic Response to Anemia in Early Gestation: Using Hemoglobin Bart's Disease as a Study Model.

OBJECTIVE: To assess fetal hemodynamic changes in response to anemia in early gestation, using fetal Hb Bart's disease as a study model. METHODS: A prospective study was conducted on pregnancies at risk for fetal Hb Bart's disease at 12-14 weeks of gestation. Fetal hemodynamics were comprehensively assessed by 2D ultrasound, Doppler velocity, and cardio-STIC just prior to the invasive procedure for diagnosis. The various hemodynamic parameters of the affected and unaffected fetuses were compared. RESULTS: Of 56 fetuses at risk, 17 had Hb Bart's disease and 39 were unaffected. The right and combined ventricular cardiac outputs (CO) were significantly higher in the affected fetuses (0.993 vs. 1.358; p < 0.001 and 1.010 vs. 1.236; p < 0.001, respectively), whereas the left CO tended to be higher but not significantly (1.027 vs. 1.113; p = 0.058). Cardiac dimensions, middle-cerebral artery peak systolic velocity, Tei index, and isovolemic contraction time were significantly increased, while the global sphericity index was significantly decreased. Interestingly, cardiac preload, ventricular wall thickness, shortening fraction, isovolemic relaxation time, and fetal heart rate were unchanged. Four fetuses had hydropic changes, but all cardiac functions were normal. CONCLUSION: Fetal anemia induces hypervolemia and increases cardiac output to meet the tissue oxygen requirement, resulting in an increase in size without hypertrophy, volume load without pressure load, and a decrease in the globular sphericity index. The heart works very well but works harder, especially systolic ventricular load. Hydrops fetalis due to anemia appears not to be caused by heart failure as previously believed but rather by volume load with high vascular permeability at least in early pregnancy.

Fetal Cardiac Inflow Characteristics in Response to Fetal Anemia: Based on Fetal Hemoglobin Bart's Disease at Mid-Pregnancy.

OBJECTIVES: To identify the inflow (filling time fraction [FTF] and E/A ratio) characteristics of fetuses with anemia, and to evaluate the performance of the inflow markers in predicting the affected fetuses. METHODS: Fetuses at risk of hemoglobin (Hb) Bart's disease at 17-22 weeks were prospectively recruited to undergo echocardiography before diagnostic cordocentesis. Cardiac Doppler images were digitally stored for off-line blinded measurements of FTF and E/A ratio. RESULTS: A total of 428 fetuses at risk of Hb Bart's disease were analyzed, including 88 affected fetuses (20.6%). The mean gestational age at the time of diagnosis was 19.43 ± 1.5 weeks. The FTFs in both sides were significantly lower in the affected fetuses, whereas the E/A ratios of both sides were significantly higher in the affected group. According to the receiver operating characteristic curves, the performance of the FTF of the right side in predicting affected fetuses was slightly better than that of the left side (area under curve: 0.707 versus 0.680, P < .001). Likewise, the performance of the E/A ratio of the tricuspid valve was slightly better than that of the mitral valve. Also, FTF was superior to E/A ratio in predicting the affected fetuses. CONCLUSIONS: New insights leading to a better understanding of the fetal cardiac response to anemia are: 1) the FTFs in both sides were significantly decreased, suggesting some degree of diastolic ventricular dysfunction; 2) the E/A ratios of both sides were significantly increased, indicating volume load; and 3) The inflow parameters may be useful as a new predictor of fetal anemia, especially among pregnancies at risk.

Hydrops Fetalis Associated with Fetal Hemoglobin H-Pakse Disease.

INTRODUCTION: Hemoglobin H-Pakse (Hb H-PS) disease is a variant of non-deletional Hb H disease associated with various degrees of anemia. The disorder is rare but commonly seen in Southeast Asia. However, the prenatal course of Hb H-PS disease has never been published. The objective of this report was to describe prenatal diagnosis and management of Hb H-PS disease, which is theoretically much more critical in fetal life than adult life. CASE PRESENTATION: The prenatal courses of two fetuses affected by Hb H-PS were comprehensively explored. Both of them showed sonographic signs of fetal anemia at 19-20 weeks of gestation (increased cardiac size and increase middle cerebral artery peak systolic velocity [MCA-PSV]). On follow-up scans, both revealed frank hydropic signs at 22-24 weeks. One fetus died at 24 weeks, shortly before the scheduled intrauterine blood transfusion (IUT). The other one underwent IUT at 22 weeks, leading to completely reversed hydropic signs, which resulted in successful outcomes that ended with the delivery of a healthy baby at term. The fetus needed only one IUT, and the course of anemic status improved in late pregnancy. IUT in this case was possibly beneficial to adult life. CONCLUSION: Fetuses with Hb H-PS may be associated with hydrops fetalis, usually occurring at mid-pregnancy. The hydrops tends to improve in late gestation. If they can pass through this most critical period in utero without anemic insults in developing organs, good long-term prognosis can be expected. This successful prenatal diagnosis and intrauterine treatment may encourage care providers to pay more attention to fetal Hb H-PS disease, to prevent anemic hypoxia in developing organs and adult diseases of fetal origin.

An Unruptured True Aneurysm of the Uterine Artery during Pregnancy.

The antenatal diagnosis of an unruptured true aneurysm of the uterine artery is extremely rare and has never been reported, whereas pseudoaneurysms associated with previous trauma or cesarean section have been reported several times. True aneurysms occur when the artery or vessel weakens and bulges, sometimes forming a blood-filled sac. Nearly all cases of pelvic true aneurysms involved ovarian arteries which ruptured during the peripartum period. The case presented here is unique in terms of being an unruptured true aneurysm of the uterine artery with a first diagnosis during pregnancy at 32 weeks of gestation and the spontaneous development of thrombosis in the aneurysm in late pregnancy, documented at 37 weeks of gestation. The diagnosis of a true aneurysm of the uterine artery was based on, (1) a demonstration of the cystic mass located in proximity to the lower segment of the uterus with ultrasound characteristics of arterial flow in the mass, and (2) the occurrence in a woman who had no history of trauma or surgery in the pelvis. The finding during cesarean section confirmed the prenatal sonographic finding. The pregnancy ended with successful outcomes.

Prenatal Course and Sonographic Features of Congenital Mesoblastic Nephroma.

Background: Congenital mesoblastic nephroma (CMN) is the most common renal tumor among fetuses and infants before the age of 6 months. It usually behaves as a benign tumor. The prenatal features and outcomes of pregnancies with fetal CMN have never been systematically reviewed and analyzed, whereas neonatal or pediatric series have been published several times. The aims of this study are to (1) describe the prenatal natural course and prenatal sonographic char-acteristics of CMN; (2) determine the outcomes of pregnancies with fetal CMN; and (3) demonstrate typical sonographic images together with video clips of prenatal CMN, as an educational example based on our index case presented here. Methods: Studies focused on fetal CMN, including those consecutively published on PubMed from 1980 to June 2022 as well as the index case presented here, were identified and validated to perform a systematic review. The data of fetal imaging and the prenatal course of pregnancies were extracted for analysis. Results: The findings derived from 41 cases of review are as follows: (1) No single case has been diagnosed in the first half of pregnancy. No cases were detected during routine anomaly screening at mid-pregnancy. All cases were de-tected in the third trimester or late second trimester. (2) Polyhydramnios is very common and is the first clinical manifestation in most cases, leading to detailed ultrasound in the second half of pregnancy. (3) Preterm birth and low birth weight are the most common adverse pregnancy out-comes, resulting in neonatal morbidity. (4) Hydrops fetalis, though relatively rare, can be associated with CMN and is a grave sign. (5) Prenatal diagnosis is essential since it is critical for the antenatal plan, comprising either referral to a tertiary care center or proper surveillance to prevent serious obstetric complications, especially preterm birth. (6) Ultrasound is the primary tool for prenatal diagnosis of CMN, whereas MRI can be used as an adjunct if some other tumors are suspicious or sonographic features are not typical for CMN. Conclusion: In contrast to CMN in neonates, fetal CMN is much more serious since it significantly impacts adverse pregnancy outcomes and perinatal morbidity and mortality. The typical prenatal course and the sonographic features of CMN are described.

The Accelerated Right Ventricular Failure in Fetal Anemia in the Presence of Restrictive Foramen Ovale.

Objective: To describe serious hemodynamic changes secondary to anemia in the case of restrictive foramen ovale (FO). Case: A 43-year-old pregnant woman, G4P0030, underwent fetal echocardiography at 35 weeks of gestation and was found to have (1) restrictive FO; (2) poor right ventricular function; (3) unbalanced hemodynamics; (4) fetal anemia (high MCA-PSV and hepatosplenomegaly). Acid-elution test indicated feto-maternal hemorrhage. Cesarean section was performed for postnatal blood transfusion. Nevertheless, the newborn developed heart failure and died after partial blood exchanges. Conclusions: Insights gained from this study are as follows: (1) Restrictive FO in structurally normal hearts can modify fetal response to anemia differently, by unequally distributing blood volume, leading to much more deteriorating right ventricular function. (2) To make decisions for intrauterine or extrauterine treatment in cases of anemia-associated heart failure, several factors must be taken into account such as gestational age, fetal cardiac function, and placental function. Because of the hyperdynamic state of newborns immediately after birth, delivery can deteriorate the compromised heart to irreversible failure. Intrauterine transfusion for a well-prepared heart just before delivery may be the best option since the baby should be well oxygenated at the time of delivery.

Fetal Atrial Flutter Associated with Atrial Septal Aneurysm.

Objective: To provide evidence that fetal atrial flutter (AF) caused by atrial septal aneurysm (ASA) can be completely cured by delivery. Methods: Cases series of three fetuses with ASA complicated by AF in late gestation, including hydrops fetalis in one case, were collected and completely followed up. Results: AF in all cases completely disappeared shortly after birth. New insights gained from this study are as follows: (1) PACs or bigeminy associated with ASA can progressively change to AF. (2) AF associated with ASA can cause hydrops fetalis and intrauterine treatment is needed; however, delivery is the definitive treatment. (3) AF associated with ASA completely resolves after birth. This is probably associated with changes in the circulation after birth, with no more blood flow crossing the foramen ovale and no turbulent flow in the ASA with reversal to hit the right atrial wall, activating ectopic pacemakers. Conclusions: This report may have clinical impact because it provides evidence that (1) in case of AF associated with ASA, the prognosis is much better than other causes and delivery should be strongly considered. (2) Fetuses diagnosed with AF should always be checked for the presence of ASA. (3) PAC/bigeminy related to ASA, different from isolated PAC, needs close follow-up for the development of SVT and AF. (4) Fetuses remote from term can benefit from intrauterine treatment to avoid hydrops fetalis, and to prolong gestation for maturity, early delivery is recommended once lung maturity is confirmed.