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.

Individual and Composite Adverse Pregnancy Outcomes in a Randomized Trial on Isoniazid Preventative Therapy Among Women Living With Human Immunodeficiency Virus.

BACKGROUND: International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) P1078, a randomized noninferiority study designed to compare the safety of starting isoniazid preventive therapy (IPT) in women living with human immunodeficiency virus (HIV) either during pregnancy or after delivery, showed that IPT during pregnancy increased the risk of composite adverse pregnancy outcomes, but not individual outcomes. Many known factors are associated with adverse pregnancy outcomes: these factors' associations and effect modifications with IPT and pregnancy outcomes were examined. METHODS: Pregnant women living with HIV from 8 countries with tuberculosis incidences >60/100 000 were randomly assigned to initiate 28 weeks of IPT either during pregnancy or at 12 weeks after delivery. Using univariable and multivariable logistic regression and adjusting for factors associated with pregnancy outcomes, composite and individual adverse pregnancy outcome measures were analyzed. RESULTS: This secondary analysis included 925 mother-infant pairs. All mothers were receiving antiretrovirals. The adjusted odds of fetal demise, preterm delivery (PTD), low birth weight (LBW), or a congenital anomaly (composite outcome 1) were 1.63 times higher among women on immediate compared to deferred IPT (95% confidence interval [CI], 1.15-2.31). The odds of fetal demise, PTD, LBW, or neonatal death within 28 days (composite outcome 2) were 1.62 times higher among women on immediate IPT (95% CI, 1.14-2.30). The odds of early neonatal death within 7 days, fetal demise, PTD, or LBW (composite outcome 3) were 1.74 times higher among women on immediate IPT (95% CI, 1.22-2.49). CONCLUSIONS: We confirmed higher risks of adverse pregnancy outcomes associated with the initiation of IPT during pregnancy, after adjusting for known risk factors for adverse pregnancy outcomes.

Fetal Hemodynamic Responses to Arterial Occlusion of Acardiac Twins.

The objective of this study was to comprehensively assess fetal hemodynamic adaptions to occlusive procedures. Twin pregnancies complicated with acardiac twin and hydrops fetalis of the pump twin were recruited. The occlusive procedures - either alcoholization, radiofrequency ablation, coil embolization or occlusive glue - were performed under ultrasound guidance. Various hemodynamic parameters were assessed before, shortly after, then every 6 h for 48 h and 2-4 weeks after the procedures. Seven pregnancies were recruited. The median (range) gestational age of intervention was 21 (17-26) weeks of gestation. Before the procedures, all cases showed normal cardiac function. Just after the procedures, all cases showed an increase in Tei index and isovolumic relaxation time but returned to preocclusion levels within 6-48 h, except for two cases that were persistently high. Increased preload and poor shortening fraction were observed in two cases, leading to heart failure, with one recovery and one death in utero. Five out of the seven cases got through the critical period with a gradual return to normal hemodynamics, ending with the disappearance of hydrops and successful outcomes. It was concluded that the occlusive procedure could aggravate the overworked heart, leading to heart failure. Preocclusion preload index and Tei index may predict risk of heart failure due to the occlusion. This small series strongly suggests that the occlusion should be performed before the deterioration of cardiac function.

Fetal Heart Diameter as a Predictor of Hemoglobin Bart Disease at Midpregnancy.

OBJECTIVES: To evaluate the efficacy of the fetal heart diameter (HD) in predicting fetal hemoglobin (Hb) Bart disease at midpregnancy. METHODS: Video clips of fetal chest ultrasound examinations performed on fetuses at risk of Hb Bart disease at 18 to 22 weeks' gestation were randomly retrieved from our video clip database. The clips were replayed for fetal HD measurements, and the measured HDs were converted to z scores based on the z score model as a function of biparietal diameter. An HD z score greater than 2 or an actual HD value above the 95th percentile for gestational age was used as a cutoff in predicting Hb Bart disease. The best cutoff value of HD for identifying affected fetuses during midpregnancy was also evaluated by a receiver operating characteristic curve. RESULTS: A total of 90 video clips, including 37 affected and 53 unaffected fetuses, were measured. An HD z score greater than 2 had sensitivity of 94.6% (95% confidence interval [CI], 81.8%-99.3%) and specificity of 84.9% (95% CI, 72.4%-93.3%). An actual HD value above the 95th percentile for gestational age had sensitivity of 100% (95% CI, 90.5%-100%) and specificity of 69.8% (95% CI, 55.7%-81.7%). The best cutoff values of the HD z score and actual HD value were 2.27 (with sensitivity of 94.6% and specificity of 88.7%) and 18.15 mm (with sensitivity of 91.9% and specificity of 77.4%), respectively. CONCLUSIONS: The fetal HD is highly effective in predicting fetal Hb Bart disease among fetuses at risk at midpregnancy. Both the HD z score and the actual value can be used for noninvasive prenatal screening of fetal cardiomegaly in clinical practice.

Comparison of pregnancy outcomes after second trimester amniocentesis between procedures performed by experts and non-experts.

OBJECTIVES: To compare the rate of fetal loss in pregnancy after second trimester amniocentesis between procedures performed by experts and non-experts and to assess other pregnancy complications as secondary outcomes. METHODS: A retrospective cohort study was performed on singleton pregnancies that underwent mid-trimester amniocenteses in a single institution. The fetal loss rates of procedures performed by experts and non-experts were collected and analyzed. Other adverse pregnancy outcomes were also examined. RESULTS: In total, 14,450 amniocenteses were performed during the study period. These included 11,357 (78.6%) procedures in the group expert operators and 3,093 (21.4%) procedures in the group non-expert operators. In the non-expert group, the fetal loss rate was slightly increased but not significantly (p=0.24).In addition, the higher number of spontaneous abortions was associated with blood-stained amniotic fluid sample (p<0.001; RR=9.28). Multiple needle insertions also increased in the non-expert group significantly. However, no difference in pregnancy outcomes was found between in single and multiple needle insertions. CONCLUSIONS: The amniocentesis procedures performed by the non-experts was not increase the fetal loss rate. However, the other adverse pregnancy outcomes, including preterm birth, low birth weight and fetal growth restriction were significantly increased in the non-expert group.

Comparison of the Performances of Middle Cerebral Artery Peak Systolic Velocity and Cardiothoracic Diameter Ratio in Predicting Fetal Anemia: Using Fetal Hemoglobin Bart's Disease as a Study Model.

OBJECTIVE: The aim of the study was to compare the performances of cardiothoracic diameter ratio (CTR) and middle cerebral artery peak systolic velocity (MCA-PSV) in predicting fetal hemoglobin (Hb) Bart's disease and identify the best CTR cut-off for each gestational period. METHODS: Pregnancies at risk of fetal Hb Bart's disease (gestational ages of 12-36 weeks) were prospectively recruited to undergo ultrasound examination. The measurements of CTR and MCA-PSV were performed and recorded before invasive diagnosis. RESULTS: During the study period (2005-2019), a total of 1,717 pregnancies at risk of fetal Hb Bart's disease met the inclusion criteria and were available for analysis, including 329 (19.2%) fetuses with Hb Bart's disease. The mean gestational age at the time of diagnosis was 19.30 ± 5.6 weeks, ranging from 12 to 36 weeks. The overall performance of CTR Z-scores is superior to that of MCA-PSV multiple of median (MoM) values; area under curve of 0.866 versus 0.711, p value <0.001. The diagnostic indices of CTR and MCA-PSV are increased with gestational age. Based on receiver operating characteristic curves of CTR Z-scores, the best cut-off points of CTR at 12-14, 15-17, 18-20, 21-23, and ≥24 weeks are 0.48, 0.49, 0.50, 0.51, and 0.54, respectively. The best cut-off of MCA-PSV is 1.3 MoM, giving the best performance at 21-23 weeks with a sensitivity of 91.8% and specificity of 85.5%. CONCLUSION: The performance of CTR is much better than MCA-PSV in predicting fetal anemia caused by Hb Bart's disease. Nevertheless, whether this can be reproduced in anemia due to other causes, like isoimmunization, is yet to be explored.

Comparisons of pregnancy outcomes between twin pregnancies with and without second-trimester amniocentesis.

OBJECTIVE: To assess the amniocentesis-related pregnancy loss rate and preterm birth rate among twin pregnancies undergoing amniocentesis. METHODS: A retrospective cohort study was conducted at a tertiary center. The study group included twin pregnancies undergoing amniocentesis during 16 to 22 weeks of gestation. The control group was those not undergoing amniocentesis. All amniocenteses were performed by the MFM specialists. The main outcomes were the rate of pregnancy loss (before 24 weeks) and preterm birth. RESULTS: A total of 332 cases in the study group and 1188 controls were analyzed. The percentages of maternal age ≥35 years, high parity, and cases complicated with medical diseases were significantly higher in the study group. The pregnancy loss rate after the procedure tended to be higher, but not significant, in the study group (3.0% vs 2.2% P = .383). Likewise, the rate of preterm birth in the study group was higher, but not significant (70.5% vs 66.0% P = .130). Logistic regression analysis to adjust confounding factors showed no significance of amniocentesis on pregnancy loss and preterm birth. CONCLUSION: Though amniocentesis in twin pregnancies has theoretical risk of pregnancy loss, it is relatively safe when performed by maternal-fetal medicine specialists. This information is useful for counseling, especially when performed by experienced hands.

Z Score Reference Ranges of Fetal Cardiac Output From 12 to 40 Weeks of Pregnancy.

OBJECTIVES: To develop the Z score reference ranges of fetal cardiac output (CO) in healthy fetuses from 12 to 40 weeks of pregnancy. METHODS: A cross-sectional descriptive study was undertaken among low-risk singleton pregnancies with healthy fetuses between 12 and 40 weeks. The right ventricular cardiac output (RCO), left ventricular cardiac output (LCO), and combined cardiac output (CCO) were measured by 2-dimensional ultrasound with the Doppler velocity of the aorta and pulmonary arteries. The pregnancies were followed until delivery RESULTS: The RCO, LCO, and CCO were determined in 700 fetuses. The predictive models of the CO as a function of gestational age (GA) and biparietal diameter were identified, and the Z score reference ranges were constructed. The means and standard deviations of CO on both sides were increased with GA and biparietal diameter as power models. Nomograms for the LCO, RCO, and CCO were established (ie, RCO = 0.000148 × GA4.283034 ; SD = 0.000131 × GA4.026209 ; LCO = 0.000514 × GA3.790944 ; SD = 0.000169 × GA3.815546 ). The RCO was much more increased than the LCO with advancing GA. CONCLUSIONS: The Z score reference ranges and percentile charts of fetal CO were constructed throughout gestation with a large sample size. This may be helpful in detection of cardiac disorders, especially cardiomyopathy, cardiac anomalies, fetal anemia, and fetal growth restriction.

Fetal Cardiac Remodeling in Response to Anemia: Using Hemoglobin Bart's Disease as a Study Model.

OBJECTIVE: To assess fetal cardiac remodeling in response to anemia, by comparing the fetal cardiac dimensions and global sphericity index (GSI) of normal fetuses and fetuses with anemia using fetal Hb Bart's disease as a study model. METHODS: Fetuses at risk for Hb Bart's disease undergoing cordocentesis at 18 to 22 weeks of gestation were recruited. Fetal cardiac dimensions including GSI (cardiac length to cardiac width ratio), interventricular septum thickness (IVST), left ventricular wall thickness (LVWT) and right ventricular wall thickness (RVWT) were measured. RESULTS: 215 pregnancies at risk met the inclusion criteria, including 54 affected fetuses and 161 normal fetuses. The mean GSI was significantly lower in the affected group (1.11 ±â€Š0.06 vs. 1.26 ±â€Š0.09, p-value 0.017). The GSI of the normal group was relatively constant regardless of gestational age. The IVST and LVWT tended to increase, but not significantly, in the affected group, whereas the RVWT was minimally but significantly increased. The ROC curve for GSI had an area under curve of 0.844. The best cut-off of GSI was 1.17, giving a sensitivity of 74.1 % and a specificity of 88.2 %. CONCLUSION: Fetal cardiac remodeling in response to anemia causes a marked decrease in global GSI with minimal hypertrophy as an adaption to volume overload. Importantly, GSI is a new maker for anemia and may play a role in clinical application for early detection of fetal anemia, possibly due to any cause. Additionally, GSI measurement is simple and gestational age-independent.

Giant choledochal cyst and infantile polycystic kidneys as prenatal sonographic features of Caroli syndrome.

Caroli syndrome is a developmental disorder caused by complete or partial arrest of ductal plate remodeling, leading to dilated bile ducts along with fibrosis surrounding the portal tracts. It is most commonly associated with autosomal recessive polycystic kidney (ARPKD). We report a unique case of Caroli syndrome, diagnosed prenatally at 24 weeks of gestation in a 29-year-old Thai woman. Ultrasound findings revealed the association of a fetal giant choledochal cyst with ARPKD. Autopsy findings showed ductal plate malformation, typical of Caroli syndrome, associated with giant choledocal cyst and ARPKD.

The best cutoff value of middle cerebral artery peak systolic velocity for the diagnosis of fetal homozygous alpha thalassemia-1 disease.

OBJECTIVE: To determine the best cutoff value of middle cerebral artery peak systolic velocity (MCA-PSV) for the diagnosis of fetuses with homozygous alpha thalassemia-1 disease. METHODS: Pregnancies at risk for fetal homozygous alpha thalassemia-1 disease at 18 to 22 weeks were recruited. MCA-PSV was measured before cordocentesis for hemoglobin typing and complete blood count. The performance of the MCA-PSV for identifying affected fetuses was evaluated using a best cutoff value derived from the receiver operating characteristic (ROC) curve. RESULTS: Among 142 fetuses at risk, 46 (32.4%) fetuses were diagnosed as affected by homozygous alpha thalassemia-1 disease and were categorized as mild anemia (16.3%), moderate anemia (58.1%), and severe anemia (25.6%). With the best cutoff point of MCA-PSV > 1.30 multiples of the median (MoM) or >30.0 cm/s, the sensitivity for predicting fetal homozygous alpha thalassemia-1 was 100%. CONCLUSIONS: MCA-PSV > 1.30 MoM is the best cutoff value for the diagnosis of all degrees of fetal anemia from homozygous alpha thalassemia-1 fetuses. Because of its simplicity for interpretation and high efficacy, a cutoff value of MCA-PSV > 30 cm/s can also be used as an alternative marker for fetal anemia screening during 18 to 22 weeks of gestation.

Fetal Down syndrome screening models for developing countries; Part I: Performance of Maternal Serum Screening.

BACKGROUND: To identify the performance of fetal Down syndrome (DS) screening for developing countries. METHODS: A prospective study on MSS (maternal serum screening) with complete follow-ups (n = 41,924) was conducted in 32 network hospitals in the northern part of Thailand. Various models of MSS were tested for performance. RESULTS: MSS based on Caucasian reference range resulted in very high false positive rate (FPR; 13%) in our country, compared to the rate of 7.8% with our own (Thai) reference range, whereas the detection rate was comparable. As individual screening, C-S (contingent first trimester screening including PAPP-A, and free beta-hCG, classified as a) high risk [> 1:30], indicated for invasive diagnosis; b) intermediate risk [1:30-1500], indicated for STS; and c) low risk [< 1:1500], need no further tests.) was the most effective model (sensitivity 84.9%, FPR 7.7%) but nearly one-third needed the second trimester test (STS) because of intermediate results. Additionally, about one-third had their first visits in the second trimester and had no chance of FTS (first trimester screening). C-S plus STS had a sensitivity of 82.4% and FPR 8.1% whereas independent first and second trimester screening model (I-S) gave the sensitivity of 78.4% and FPR of 7.5% but was much more convenient and practical. CONCLUSION: C-S plus STS was the most effective models while I-S model was also effective and may be better for developing countries because of its simplicity and feasibility.

Z Score Reference Ranges of Fetal Cardiothoracic Diameter Ratio.

OBJECTIVE: This study aims to establish the z score reference ranges of cardiothoracic diameter ratio (CTR) of normal fetuses from 14 to 40 weeks' gestation. METHOD: A cross-sectional study was conducted on low-risk singleton pregnancies with healthy fetuses. The CTR was performed using simple 2-dimensional sonography on the typical fetal 4-chamber view. The reference ranges were constructed according to gestational age (GA), biparietal diameter (BPD), and head circumference (HC) as independent variables based on the best-fit models, both mean and standard deviation (SD). RESULTS: A total of 683 fetuses were measured for CTR. The best-fit equations for the mean and SD as a function of GA, BPD, and HC are as follows: (1) CTR = 0.365 + 0.004 × GA in weeks (SD = 0.031 + 0.001 × GA); (2) CTR = 0.373 + 0.014 × BPD in cm (SD = 0.034 + 0.004 × BPD); and (3) CTR = 0.373 + 0.004 × HC in cm (SD = 0.032 + 0.001 × HC). The CTR was slightly increased with advanced GA, BPD, and HC. CONCLUSION: Complete nomograms with z score reference ranges of CTR were established throughout pregnancy. These nomograms may be useful to detect cardiac abnormalities.

Second Trimester Serum Biomarker Screen for Fetal Aneuploidies as a Predictor of Preterm Delivery: A Population-Based Study.

OBJECTIVE: To determine the association between second-trimester serum Down syndrome screening (alpha-fetoprotein [AFP] free beta-human chorionic gonadotropin [b-hCG] unconjugated estriol [uE3]) and preterm birth and to create predictive models for preterm birth. METHODS: Secondary analysis on a prospective database of pregnancies undergoing second-trimester screen with complete follow-up. The multiples of medians (MoM) of the biomarkers were compared between the group of term, preterm (< 37 weeks), early preterm (< 34 weeks), and very early preterm (< 32 weeks) delivery. Predictive models were developed based on adjusted MoMs and logistic regression and diagnostic performances in predicting preterm birth were determined. RESULTS: Of 20,780 pregnancies, 1,554 (7.5), 363 (1.7), and 158 (0.8%) had preterm, early preterm, and very early preterm birth respectively. High levels of AFP and b-hCG but low levels of uE3 were significantly associated with higher rates of preterm, early preterm and very early preterm delivery. The predictive models had diagnostic performance in predicting preterm birth with the areas under the ROC curve of 0.688, 0.534, 0.599, and 0.718 for AFP, b-hCG, uE3, and combined biomarkers respectively. CONCLUSION: The second trimester Down syndrome screening could also be used as a tool of risk identification of preterm birth in the same test, without extra-effort and extra-cost.

Second-trimester maternal serum screening for fetal Down syndrome: As a screening test for hemoglobin Bart's disease: A prospective population-based study.

PURPOSE: The purpose of this study is to determine the effectiveness of second-trimester maternal serum screening for Down syndrome as a screening test for fetal hemoglobin (Hb) Bart's disease among an unselected population. METHODS: A secondary analysis of a large prospective database (20 254 pregnancies) was conducted to compare the levels of maternal serum screening, alpha-fetoprotein (AFP), free beta-human chorionic gonadotropin, and unconjugated estriol between pregnancies with Hb Bart's disease and unaffected pregnancies. RESULTS: The median AFP levels were much higher among affected fetuses (1.96 vs 1.12 multiple of the median; P < .001), yielding a sensitivity of 81.6% and specificity of 86.4%. Thus, AFP measurement is effective in predicting fetal Hb Bart's disease among an unselected population when using a cutoff value of 1.5 multiple of the median. The serum free beta-human chorionic gonadotropin levels were slightly, but significantly, higher in the affected pregnancies, while the serum unconjugated estriol levels were minimally, but significantly, lower among the affected pregnancies. CONCLUSION: Second-trimester maternal serum AFP levels were significantly elevated in cases of fetal Hb Bart's disease. Pregnancies with unexplained elevated serum AFP levels in areas of high prevalence of Hb Bart's disease should always undergo a detailed ultrasound examination to detect any early signs of fetal anemia before development of hydrops fetalis.

Prenatal sonographic monitoring of progressive cardiac damages caused by anti-Ro antibodies: A case report.

Maternal autoantibodies to Ro/SSA are often linked to congenital heart block and rarely associated with structural defects. We describe the case of a fetus with anti-Ro-mediated second-degree block at 19 weeks, which progressed to a complete block, fibroelastosis, atrioventricular valve insufficiency, and semilunar valve stenosis/insufficiency at 20, 22, 24, and 26 weeks, respectively, although the fetus received transplacental anti-arrhythmic drugs. The 2150-g fetus was vaginally delivered at 35 weeks. An external pacemaker was inserted immediately after birth and replaced with permanent pacemaker at the age of 3 months. The newborn has had a good outcome with well-controlled heart rate.

Fetal isovolumetric time intervals as a marker of abnormal cardiac function in fetal anemia from homozygous alpha thalassemia-1 disease.

OBJECTIVE: To determine whether fetal isovolumetric time intervals can be an early sonographic marker of fetal anemia in fetuses with homozygous alpha thalassemia-1. METHODS: Pregnancies at risk for fetal homozygous alpha thalassemia-1 disease at 18-22 weeks were recruited before cordocentesis for hemoglobin typing. Isovolumetric contraction time (ICT) and isovolumetric relaxation time (IRT) intervals were measured by placing pulsed wave Doppler sample volume within the left ventricle to obtain the mitral and aortic waveform. Time intervals were compared between the affected group of homozygous alpha thalassemia-1 fetuses and the unaffected group. RESULTS: Among 70 fetuses at risk, 28 cases were diagnosed as affected by homozygous alpha thalassemia-1 disease. Mean ICT and ICT + IRT intervals in the affected group were significantly longer than in the unaffected group (47.9 ± 12.5 ms vs 35.0 ± 6.7 ms, p < 0.001; and 96.2 ± 13.6 ms vs 80.9 ± 10.6 ms, p < 0.001. ICT effectively predicted affected fetuses with 71.4% sensitivity and 78.6% specificity using a cutoff value ≥40 ms. CONCLUSIONS: Isovolumetric contraction time was significantly prolonged in fetal anemia from homozygous alpha thalassemia-1 during the early stage of hydropic changes. Because of its simple measurement and high efficacy, ICT can be a useful marker for prenatal screening of abnormal cardiac function in fetal anemia. © 2017 John Wiley & Sons, Ltd.

Prenatal Diagnosis of Aortopulmonary Window: A Case Series and Literature Review.

Aortopulmonary window (APW) is a rare congenital heart defect, characterized by a connection between the ascending aorta and the pulmonary trunk before bifurcation. Prenatal diagnosis of APW is essential, as a surgical correction early after birth is required in most cases to prevent congestive heart failure secondary to high pulmonary blood flow. We report a series of three cases of APW that were detected by prenatal echocardiography. The key feature of diagnosis is demonstration of connection between the pulmonary artery and the aorta above the level of the two semilunar valves. Based on our cases and literature review, diagnostic clues for prenatal diagnosis of APW are summarized and proposed.

Appearance of Abnormal Cardiothoracic Ratio of Fetuses with Hemoglobin Bart's Disease: Life Table Analysis.

Objective To determine the timeline of the first appearance of an increased CT ratio of fetuses with hemoglobin (Hb) Bart's disease. Materials and Methods A prospective longitudinal study was conducted on pregnancies at risk for fetal Hb Bart's disease. Sonographic markers including cardiothoracic (CT) ratio and middle cerebral artery peak systolic velocity (MCA-PSV) were serially assessed and recorded from the first trimester. The definite diagnosis of fetal Hb Bart's disease based on DNA analysis (CVS), or fetal Hb typing (HPLC; cordocentesis) was performed at the first appearance of an increased CT ratio. Results Of 275 pregnancies at risk, 64 fetuses were finally proven to be affected and life table analysis was performed. Most affected fetuses showed an increased CT ratio in late first trimester and early second trimester, with median time of the first appearance at 13 weeks and all affected fetuses were detected at 23 weeks or less. The CT ratio yielded a sensitivity of 100 % at a gestational age of 23 weeks with a false-positive rate of 8 %. MCA-PSV appeared later than CT ratio. Only 9.4 % of affected cases developed abnormal MCA-PSV before an increased CT ratio. Conclusion The timeline of the first appearance of an increased CT ratio of fetuses with Hb Bart's disease was established. This may help us identify Hb Bart's disease among fetuses at risk in earlier gestation and proper schedules for serial ultrasound could be made more effectively.

Fetal septum primum excursion (SPE) and septum primum excursion index (SPEI) as sonomarkers of fetal anemia: using hemoglobin Bart's fetuses as a study model.

OBJECTIVES: The objectives the study are to evaluate the effectiveness of septum primum excursion (SPE) and SPEI (SPE index, a ratio of SPE to left atrial diameter) in predicting fetal hemoglobin (Hb) Bart's disease and to determine the correlation between Hb levels and SPE/SPEI METHODS: The database of Cardio-STIC volume datasets (VDSs) of fetuses at risk of Hb Bart's disease at 18 to 22 weeks was assessed. The VDSs were blindly analyzed offline for measurements of SPE and SPEI. RESULTS: Of 180 VDSs recruited, 44 were acquired from fetuses with Hb Bart's disease, while 136 were derived from unaffected fetuses. SPE and SPEI was inversely correlated with Hb levels (p < 0.0001). The SPE and SPEI were significantly higher in the affected group (4.1 + 1.1 mm vs 3.0 + 0.8 mm and 0.61 + 1.1 vs 0.49.1 + 0.1, respectively). SPE, at cut-off 1.3 multiple of median, gave a sensitivity and specificity of 75.0% and 72.7%, respectively, but less than a sensitivity (81.4%) and specificity (95.4%) of middle cerebral artery peak systolic velocity. CONCLUSIONS: In anemic fetuses, SPE and SPEI was inversely correlated with Hb level. Additionally, SPE, better than SPEI, may be used as an adjunctive sonographic sign to predict Hb Bart's disease but its accuracy of prediction is not good enough to be used independently or as a diagnostic test. © 2016 John Wiley & Sons, Ltd.