Cordocentesis-associated fetal loss and risk factors: single-center experience with 6650 cases.

OBJECTIVES: To identify procedural risk factors associated with fetal loss following cordocentesis and to determine the rate of cordocentesis-related fetal loss associated with the current cordocentesis protocol used in our institution. METHODS: This was a retrospective cohort study of pregnancies that underwent midpregnancy cordocentesis in a single center (a tertiary hospital, teaching school), between 1992 and 2018, based on data retrieved from our prospective database. All consecutive cases were validated to retrieve those meeting the eligibility criteria, which included: singleton pregnancy without underlying maternal disease, normal fetus (no structural or chromosomal abnormality or severe disorder), gestational age between 16 and 24 weeks at the time of the procedure and availability of pregnancy outcome. Cases that resulted in termination of pregnancy were excluded. We assessed the effect of prior cordocentesis model training on the fetal-loss rate and procedure-related complications, and evaluated potential risk factors of fetal loss secondary to cordocentesis, including procedure difficulty, placenta penetration, prolonged bleeding, fetal bradycardia, puncture site and early gestational age at procedure. Pregnancy outcomes were compared between the study group and a control group of women, who did not undergo cordocentesis, selected randomly at a 1:1 ratio from our obstetric database. RESULTS: A total of 10 343 procedures were performed during the study period, of which 6650 met the eligibility criteria and were included in the analysis. The fetal-loss rate in the first 60 procedures (early practice) of six operators (n = 360 procedures), who did not have prior model training, was significantly higher than that during the early practice of 18 operators (n = 1080 procedures) with prior model training (6.9% vs 1.6%; P < 0.001); whereas the fetal-loss rate in the next 60 procedures of practice was comparable between the two groups. After excluding the first 360 procedures of the groups without prior model training, the overall fetal-loss rate in pregnancies that underwent cordocentesis was significantly higher than that in the control group (1.6% vs 1.0%; P < 0.001). Considering the fetal-loss rate in the normal controls as background loss, the incremental cordocentesis-associated fetal-loss rate was 0.6%. Penetration of the placenta (odds ratio (OR), 2.65 (95% CI, 1.71-4.10)), prolonged bleeding from the puncture site (OR, 10.85 (95% CI, 5.27-22.36)) and presence of fetal bradycardia (OR, 3.32 (95% CI, 1.83-6.04)) during cordocentesis were independent risk factors associated with fetal loss. CONCLUSIONS: Cordocentesis model training markedly reduces fetal loss during the early learning curve of practice. Thus, cordocentesis practice without prior model training should not be acceptable. Significant procedural risk factors for fetal loss secondary to cordocentesis are placental penetration, prolonged bleeding and fetal bradycardia. Cordocentesis-related fetal loss may be only 0.6%, much lower than the rate reported previously. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

Associations between maternal serum free beta human chorionic gonadotropin (ß-hCG) levels and adverse pregnancy outcomes.

The objective was to determine the strength of relationship between maternal free beta human chorionic gonadotropin (ß-hCG) concentrations and rates of adverse pregnancy outcomes. Consecutive records of the database of our Down screening project were assessed for free ß-hCG levels and pregnancy outcomes. Pregnancies with foetal chromosomal or structural anomalies and those with underlying disease were excluded. Free ß-hCG levels of < 0.5, > 0.5 and < 2.0, and ≥ 2.0 MoM were categorised as low, normal and high, respectively. Of 17,082 screened women, 13,620 were available for analysis. In the first trimester (n = 8150), low ß-hCG levels significantly increased risk for intrauterine growth restriction (IUGR), preterm birth, low birth weight (LBW) and low Apgar score with relative risk of 1.66, 1.43, 1.83 and 2.89; whereas high ß-hCG group had a significant decreased risk of preterm birth and GDM with relative risk of 0.73 and 0.62. In the second trimester (n = 5470), both low and high ß-hCG groups had significant increased risks of the most common adverse outcomes, i.e. spontaneous abortion, IUGR and preterm birth. In conclusion, abnormally low (< 0.5MoM) or high (> 2.0 MoM) free ß-hCG levels are generally associated with an increased risk of adverse pregnancy outcomes. Nevertheless, high free ß-hCG levels in the first trimester may possibly decrease risk of preterm delivery and GDM.

Ventricular Diastolic Function in Normal Fetuses and Fetuses with Hb Bart's Disease Assessed by Color M-Mode Propagation Velocity using Cardio-STIC-M (Spatio-Temporal Image Correlation M-Mode).

Purpose: To determine whether ventricular diastolic dysfunction contributes to the pathogenesis of fetal cardiac failure due to fetal anemia using fetal Hb Bart's disease as a live model and cardio-STIC-M as a diagnostic tool. Materials and Methods: Color cardio-STIC volume datasets were acquired from fetuses at risk for Hb Bart's disease during 18 - 22 weeks of gestation and normal pregnancies and pregnancies with hydrops fetalis caused by Hb Bart's disease at 28 - 32 weeks. The volumes were analyzed off-line for velocity propagation (Vp) of the right and left ventricles to assess ventricular diastolic function using color cardio-STIC-M. Results: The Vp for the right and left ventricles was studied in fetuses at 18 - 22 weeks, including 64 normal fetuses (group 1) and 22 fetuses with Hb Bart's disease (group 2), and in fetuses at 28 - 32 weeks, including 22 normal fetuses (group 3) and 16 fetuses with Hb Bart's hydrops fetalis (group 4). The Vp of the fetuses in group 1 and group 2 was not significantly different. However, the Vp for the right and left ventricles in group 4 was significantly lower than in group 3 (19.02 vs. 9.78, p < 0.001; and 20.24 vs. 13.40, p < 0.001, respectively). The inter-observer variability had fair agreement with the intra-class correlation coefficient of 0.531 (95 % CI 0.393 - 0.646, p < 0.001). Conclusion: Hydrops fetalis secondary to fetal anemia is initially caused by hypervolemia rather than ventricular diastolic dysfunction while ventricular diastolic compromise is a late occurring consequence of persistent hypervolemia, different from the mechanism of hydropic changes caused by cardiac causes.

Prenatal differentiation between truncus arteriosus (Types II and III) and pulmonary atresia with ventricular septal defect.

OBJECTIVE: To describe antenatal sonographic signs that help in the differentiation of truncus arteriosus Types II and III (TA-II/III) from pulmonary atresia with ventricular septal defect (PA-VSD). METHODS: From a database of fetal echocardiographic examinations, we identified fetuses with sonographic features of a single great artery with VSD and relatively normal four-chamber view. Records were reviewed, comparing fetuses with TA-II/III and those with PA-VSD, with particular focus on: 1) characteristics of the overriding vessel, 2) appearance of the semilunar valves, 3) competence of the semilunar valves, 4) presence of major aortopulmonary collateral arteries (MAPCA), 5) main pulmonary artery being without antegrade flow, 6) site of arterial branching from the great artery and 7) other minor features, such as cardiac axis or associated anomalies. RESULTS: Seventeen fetuses were identified, eight with TA-II/III and nine with PA-VSD. Among the eight fetuses with TA-II/III, seven had abnormal valves and six had valve regurgitation, compared with none of the nine PA-VSD fetuses. Five TA-II/III fetuses had early branching to supply the lungs, whereas most fetuses with PA-VSD had more distal branching. Notably, in six of the TA-II/III fetuses, the root of the single great artery originated predominantly from the right ventricle, while all but one of the PA-VSD fetuses had typical equal overriding of the VSD. The main pulmonary artery was without antegrade flow in two cases with PA-VSD. Finally, four cases with PA-VSD had MAPCA, in two of which this was identified prenatally. CONCLUSION: Identification of abnormal arterial valves or valve regurgitation, site of origin of branching, presence of overriding of the great artery, a main pulmonary artery without antegrade flow and MAPCA are helpful in differentiating between TA-II/III and PA-VSD.

Fetal myocardial performance (Tei) index in fetal hemoglobin Bart's disease.

PURPOSE: To assess the effectiveness of Tei index in differentiating fetal Hb Bart's disease in pregnancies at risk in the first half of pregnancy. MATERIALS AND METHODS: Pregnancies meeting the inclusion criteria were consecutively recruited to the study. The inclusion criteria were as follows: 1) singleton pregnancies, 2) gestational age of 12 - 20 weeks, 3) at risk of Hb Bart's disease, 4) confirmed fetal diagnosis of Hb Bart's disease. Fetuses with frank hydrops fetalis or fetuses with chromosomal abnormalities or structural anomalies were excluded. Tei index was performed and immediately recorded before invasive prenatal diagnosis was performed. RESULTS: Of 152 fetuses, 50 were finally proven to be affected by Hb Bart disease, and the remainder was unaffected. Mean (± SD) Tei index were 0.48 ± 0.07 and 0.54 ± 0.08 in group of unaffected and affected fetuses, respectively. The mean difference was 0.05 which was statistically significant (p < 0.001). Likewise, mean (± SD) isovolumetric contraction time (ICT) in normal fetuses were also significantly different from that of affected fetuses. CONCLUSION: In the first half of pregnancy, Tei index in the fetuses with Hb Bart's disease was significantly higher than that in normal fetuses implying that Tei index may be a novel useful and non-invasive tool for early detection of fetal Hb Bart's disease among pregnancies at risk.

Fetal cardiac dimensions at 14-40 weeks' gestation obtained using cardio-STIC-M.

OBJECTIVES: To establish normative reference ranges of fetal cardiac dimensions derived from volume datasets acquired using spatiotemporal image correlation with M-mode display (cardio-STIC-M). METHODS: A cross-sectional study was undertaken on singleton pregnancies with normal fetuses and accurate gestational ages. Cardio-STIC volume datasets were acquired by experienced operators using a high-resolution ultrasound machine; these were maneuvered to obtain a four chamber-view with exactly horizontal interventricular septum (IVS). Cardiac dimensions were measured in STIC-M-mode using 4D View software. RESULTS: A total of 657 measurements, at a rate of between 15 and 37 per week, were obtained. Normal reference ranges for biventricular outer diameter, left and right ventricular inner diameter, left and right ventricular wall thickness, IVS thickness, left to right ventricular diameter ratio and left and right ventricular shortening fractions were constructed based on best-fit equations as a function of gestational age, fetal head circumference and biparietal diameter. Thirty-four volume datasets of abnormal fetal hearts were also separately assessed, many of which showed abnormal cardiac dimensions. CONCLUSIONS: This is the first report on normal ranges of fetal cardiac dimensions constructed using the new cardio-STIC-M technology. Preliminary evaluation suggests that these reference ranges may be a useful tool in the assessment of fetal cardiac abnormalities.

Fetal splenic artery peak velocity (SPA-PSV) at mid-pregnancy as a predictor of Hb Bart's disease.

PURPOSE: To determine the accuracy of splenic artery peak systolic velocity (SPA-PSV) in predicting fetal hemoglobin (Hb) Bart's disease at mid-pregnancy among fetuses at risk. MATERIALS AND METHODS: Pregnant women at risk of having a fetus with Hb Bart's disease were recruited into the study at 18 - 22 weeks of gestation and underwent SPA-PSV measurement before cordocentesis. The final diagnosis used as a gold standard was based on fetal hemoglobin typing using high performance liquid chromatography (HPLC). RESULTS: A total of 136 fetuses from 132 singleton pregnancies and 2 twin pregnancies were recruited into the study. The mean maternal age was 28.7 ± 5.4 years, the mean gestational age was 19.1 ± 1.02 weeks, and the incidence of Hb Bart's disease was 23.5 % (32 fetuses). Using SPA-PSV above 1.51 Multiple of Median (MoM) as a cut-off point, the sensitivity, specificity, positive predictive value and negative predictive value of SPA-PSV to identify affected fetuses was 84.4 % (32 from 36 cases), 98.1 %, 93.1 % and 95.3 % respectively. Nearly all normal fetuses had a normal SPA-PSV. CONCLUSION: SPA-PSV assessment at mid-pregnancy may be used as an adjunct method to identify fetuses with Hb Bart's disease with high, but not perfect, accuracy and may reduce the risk from unnecessary cordocentesis in some fetuses.

Midpregnancy cordocentesis training of maternal-fetal medicine fellows.

OBJECTIVE: To describe systematic cordocentesis training among maternal-fetal medicine (MFM) fellows. METHODS: During their 2-year training period, five MFM fellows, who had completed systematic model training, performed 1116 midpregnancy diagnostic cordocentesis procedures (mean, 223 (range, 185-259) procedures each) under expert supervision. The details of the procedures were recorded prospectively. Multiple pregnancies and those with fetal chromosomal or structural anomalies were excluded from analysis. The outcome measures included success rate, duration of the procedure, fetal loss and complications. RESULTS: Of the 1116 procedures performed, 184 were excluded because of fetal abnormalities; the remaining 932 were available for analysis. Cordocentesis was performed on free-floating umbilical cord (79.3%) and at the placental insertion site (20.7%). There was an immediate complication of transient fetal bradycardia in 10% of cases. Individual success rates ranged from 98.1 to 100% and the mean cumulative success rate had plateaued by approximately 60 procedures. The overall fetal loss rate was 1.3%. The overall mean +/- SD duration of successful procedures was 4.4 +/- 4.7 min, individual mean durations ranging from 3.7 to 5.9 min. CONCLUSIONS: MFM fellows with systematic training are able to perform cordocentesis with very high success rates, and with an acceptable procedure-related fetal loss rate. An intensive course of preclinical training with the model, and more than 60 procedures on patients under supervision is recommended.

Identification of fetuses with hemoglobin Bart's disease using middle cerebral artery peak systolic velocity.

OBJECTIVES: To determine the sensitivity and specificity of middle cerebral artery peak systolic velocity (MCA-PSV) in mid-pregnancy for the identification of homozygous alpha-thalassemia-1 (hemoglobin (Hb) Bart's disease) in fetuses at risk of the disease. METHODS: A total of 88 pregnancies (91 fetuses) at risk of Hb Bart's disease and undergoing MCA-PSV measurement before cordocentesis at 18-22 weeks of gestation were recruited into the study. Definitive diagnosis was made using the gold standard technique of Hb typing by high-performance liquid chromatography. RESULTS: The mean +/- SD age of the 88 pregnant women recruited into the study was 28.3 +/- 5.7 years, the gestational age was 18.8 +/- 1.1 weeks and the incidence of Hb Bart's disease was 22% (20 fetuses). Using MCA-PSV above 1.5 multiples of the median as a cut-off point, the sensitivity of MCA-PSV for detecting affected fetuses was 85% (17/20 cases), with a specificity of 100%, and positive and negative predictive values of 100% and 95.9% respectively. Three of 20 fetuses with Hb Bart's disease had normal MCA-PSV. CONCLUSIONS: MCA-PSV assessment in mid-pregnancy is a useful method for identifying Hb Bart's disease with high sensitivity and specificity among fetuses at risk, and may allow avoidance of unnecessary cordocentesis in some cases.

Fetal structural anomaly screening at 11-14 weeks of gestation at Maharaj Nakorn Chiang Mai Hospital.

OBJECTIVE: To determine the detection rate by ultrasound scanning of fetal anomaly by first trimester (11-14 weeks of gestation). MATERIAL AND METHOD: A prospective descriptive study of 597 pregnant women undergoing Nuchal Translucency (NT) measurement at 11-14 weeks of gestation at Maharaj Nakorn Chiang Mai Hospital. The sonographic examinations focused on NT thickness and fetal structural survey. The final diagnoses were based on neonatal outcomes assessed by the pediatricians and abortuses evaluated by the pathologists. The main outcome measure was the detection rate of fetal anomaly using ultrasonographic examination. RESULTS: Of 597 pregnant women recruited into the present study, the mean age was 29.41 +/- 5.8 years, the incidence of fetal anomaly was about 4% (24 from 597 cases). The detection rate by first ultrasound scans was 58% (14 from 24 cases) and the most common detected structural anomaly was cystic hygroma and exencephaly. The rate of undetected fetal anomalies was 42% (10 from 24 cases). Abnormal NT was found in 16 from a total of 597 cases (2.7%), most of them, however, had normal karyotype and no gross anomaly at birth. CONCLUSION: First trimester (11-14 weeks) ultrasound scan is probably a useful method for detection of fetal structural anomalies with a relatively high detection rate, and may be a good adjunct to the conventional examination.