Termination of pregnancy following prenatally diagnosed central nervous system malformations.

PURPOSE: To analyze fetal cerebral malformations with late termination of pregnancy (TOP) and to evaluate the rate of cases that could have been detected earlier using international recommended requirements of sonographic examination of the fetal central nervous system (CNS). MATERIALS AND METHODS: Cases of singleton pregnancies above 18 + 0 weeks of gestation ending in late TOP due to fetal CNS malformations between 2002 and 2011 were retrospectively reviewed. The cases were divided into isolated and non-isolated cerebral malformations. Prevalence and timing of TOP were assessed relative to the identified malformations. RESULTS: During this 10-year period, 212 (20.8%) out of 1017 late TOPs were performed in pregnancies with fetal cerebral malformations. 59 cases were excluded because of chromosomal anomalies. 86 (56.2%) of the remaining 153 cases were isolated cerebral malformations while 67 (43.8%) were non-isolated. TOP after viability (≥ 24 + 0 weeks of gestation) was performed in 61.4% (94/153). Substantial morbidity (n = 80; 52.3%) and mental retardation (n = 33, 38.4%) made up the leading prognostic groups. In about 80% of detectable anomalies, diagnosis of CNS malformation could have been made earlier by following international guidelines of fetal CNS examination at second trimester scan. CONCLUSION: General implementation of ultrasound screening in maternity care can significantly reduce the number of late TOPs in Germany.

Color Tissue Doppler to Analyze Fetal Cardiac Time Intervals: Normal Values and Influence of Sample Gate Size.

PURPOSE: To assess the time intervals of the cardiac cycle in healthy fetuses in the second and third trimester using color tissue Doppler imaging (cTDI) and to evaluate the influence of different sizes of sample gates on time interval values. MATERIALS AND METHODS: Time intervals were measured from the cTDI-derived Doppler waveform using a small and large region of interest (ROI) in healthy fetuses. RESULTS: 40 fetuses were included. The median gestational age at examination was 26 + 1 (range: 20 + 5 - 34 + 5) weeks. The median frame rate was 116/s (100 - 161/s) and the median heart rate 143 (range: 125 - 158) beats per minute (bpm). Using small and large ROIs, the second trimester right ventricular (RV) mean isovolumetric contraction times (ICTs) were 39.8 and 41.4 ms (p = 0.17), the mean ejection times (ETs) were 170.2 and 164.6 ms (p < 0.001), the mean isovolumetric relaxation times (IRTs) were 52.8 and 55.3 ms (p = 0.08), respectively. The left ventricular (LV) mean ICTs were 36.2 and 39.4 ms (p = 0.05), the mean ETs were 167.4 and 164.5 ms (p = 0.013), the mean IRTs were 53.9 and 57.1 ms (p = 0.05), respectively. The third trimester RV mean ICTs were 50.7 and 50.4 ms (p = 0.75), the mean ETs were 172.3 and 181.4 ms (p = 0.49), the mean IRTs were 50.2 and 54.6 ms (p = 0.03); the LV mean ICTs were 45.1 and 46.2 ms (p = 0.35), the mean ETs were 175.2 vs. 172.9 ms (p = 0.29), the mean IRTs were 47.1 and 50.0 ms (p = 0.01), respectively. CONCLUSION: Isovolumetric time intervals can be analyzed precisely and relatively independent of ROI size. In the near future, automatic time interval measurement using ultrasound systems will be feasible and the analysis of fetal myocardial function can become part of the clinical routine.

Hematological changes in severe early onset growth-restricted fetuses with absent and reversed end-diastolic flow in the umbilical artery.

BACKGROUND: Erythropoietin seems to play an important role in the regulation of fetal hypoxemia. The present prospective study was designed to determine if changes in erythropoietin levels can be found in fetuses with severe early-onset growth restriction and hemodynamic compromise. METHODS AND RESULTS: Erythropoietin, hemoglobin, hematocrit, platelet counts, normoblasts, lacate, arterial and venous blood gasses in the umbilical cord were determined in 42 fetuses with fetal growth restriction (IUGR) with absent (zero-flow) and 26 IUGR fetuses with retrograde end-diastolic flow (reverse-flow) in the umbilical artery. Color Doppler measurements were performed on the middle cerebral artery (PI) and ductus venosus [(S-a)/D and (S-a)/Vmean]. Erythropoietin concentrations were significantly lower in the zero-flow group (median: 128.0 mU/mL; range: 60.3-213 mU/mL) compared with the reverse-flow group (median: 202.5 mU/mL; range: 166-1182 mU/mL). Significant differences in median lactate concentrations were observed between the zero-flow group: 3.28 mmol/L (range; 2.3-4.7 mmol/L), and reverse-flow group: 5.6 mmol/L (range: 3.8-7.5 mmol/L). Fetuses with reverse-flow had significantly lower median platelet counts than fetuses with zero-flow (74 vs. 155/µL) and significantly lower normoblast counts (63 vs. 342/100 WBC). CONCLUSIONS: Fetuses with severe IUGR due to chronic placental insufficiency and absent or reversed flow in the umbilical artery show increased erythropoietin levels.

Short-Time Impact of Laser Ablation of Placental Anastomoses on Myocardial Function in Monochorionic Twins with Twin-to-Twin Transfusion Syndrome.

Purpose To evaluate pre- and post-procedure myocardial function in monochorionic twins with TTTS who underwent laser ablation of placental anastomoses using pulsed wave tissue Doppler imaging (pw TDI). Materials and Methods 20 monochorionic twin gestations with TTTS were included and underwent laser ablation at our center between 2011 and 2014. Prior to and after the intervention, cardiac function was assessed by measuring the mitral annular plane systolic excursion (MAPSE), the tricuspid annular plane systolic excursion (TAPSE), Tei index, isovolumetric contraction time (ICT), ejection time (ET), isovolumetric relaxation time (IRT) for the left ventricle in pulsed wave Doppler (pw D) ultrasound as well as ICT, ET, IRT and Tei index in pw TDI for the left and right ventricle. E-, A-, E´- and A´-wave peak velocity and the systolic downward motion (S´) were measured for both ventricles and the E/A, E/E´ and E´/A´ ratios were calculated. In a mean of 1.3 (SD 0.6) days after laser ablation, this measurement protocol was repeated. Results Pre-intervention recipients had longer ICT, ET and IRT in pw D and pw TDI compared to donors not reaching statistical significance for most parameters. Statistically significant were prolonged ICT in pw D (p 0.01) and ET (p 0.01) in pw TDI in recipients. In donor fetuses preoperative myocardial function did not differ significantly from postoperative myocardial function except in increased left ventricular ejection time of the left ventricle in pw TDI (p 0.04) and an increased E´/A´ratio (p 0.01). After laser coagulation, myocardial function was slightly altered in recipients as ICT and IRT shortened and Tei indices decreased but only reaching statistical significance in shortened IRTs in pw TDI for both ventricles. Conclusion Laser ablation of placental anastomoses in TTTS might influence myocardial function in the postoperative period. Shortened IRT intervals may reflect an improvement of diastolic function in recipients.

Ebstein's Anomaly of the Tricuspid Valve in the Fetus - A Multicenter Experience.

Purpose To assess the spectrum of associated anomalies, the intrauterine course, the outcome and possible prognostic markers in prenatally diagnosed Ebstein's anomaly (EA). Materials and Methods All cases of EA diagnosed over a period of 13 years with a minimum follow-up of 1 year were retrospectively collected in 4 tertiary referral centers in Germany. Results In the study period 76 cases of EA were prenatally diagnosed. The mean gestational age at diagnosis was 25.0 weeks (range: 13 - 35). 41 (53.9 %) cases were isolated and 35 (46.1 %) had other cardiac and/or extracardiac anomalies. 19 (25.0 %) pregnant women opted for termination of pregnancy, intrauterine fetal death occurred in 7 cases (9.2 %), neonatal death in 14 cases (18.4 %), death in infancy or childhood in 9 cases (11.8 %) and 27 children (35.5 %) were alive at the last follow-up. After exclusion of terminations, the only parameter inversely correlated with intrauterine survival was hydrops fetalis. Prognostic parameters significantly associated with postnatal non-survival were an abnormal Celermajer index (right atrium/heart ratio > 0.7), cardiomegaly (cardiothoracic circumference ratio > 0.5), absence of antegrade flow over the pulmonary valve and earlier diagnosis in pregnancy. Conclusion Prenatally diagnosed EA has a high morbidity and mortality with the highest loss rate in the intrauterine and neonatal period. In our study, hydrops fetalis was the only parameter significantly associated with intrauterine demise, while other prenatal markers were only significantly associated with postnatal mortality.

Fetal pulmonary venous blood flow velocities in a normal population and new calculated reference values.

OBJECTIVE: The aim of this study is to establish new Doppler reference values in a population with normal pulmonary veins during different phases of the fetal cardiac cycle for maximum blood flow velocities during ventricular systole (S), early ventricular diastole (D), atrial contraction (a), intensity-weighted mean velocity (Vmean) and the indices derived from these parameters [(S - a)/D] and [(S - a)/Vmean]. METHODS: The pulsed-wave color advanced dynamic flow Doppler technique was used in a prospective cross-sectional study of 365 low-risk pregnancies between 18 and 41 completed gestational weeks. Reference ranges were calculated for the individual measuring parameters based on a growth function from a four-parameter class of monotonic continuous functions according to the smallest square principle. RESULTS: During the observation period of 18 to 41 gestational weeks, a continuous increase was evident in maximum flow velocities for ventricular systole (S), early ventricular diastole (D), atrial contraction (a) and intensity-weighted mean velocity (Vmean) of 14.7 to 431.1, 12.5 to 426.2, 5.4 to 411.9 and 8.7 to 421.6 cm/s, respectively. Venous indices, however, showed a decrease with increasing gestational age: (S - a)/D from 0.9 to 0.7 and (S - a)/Vmean from 1 to 0.9. CONCLUSION: The newly established normal values for the fetal pulmonary vein can be used in standardized Doppler sonography measurement to assess the left atrial pressure in the fetal heart. © 2016 John Wiley & Sons, Ltd.

Termination of pregnancy after prenatal diagnosis of spina bifida: a German perspective.

PURPOSE: To analyze fetal cases with spina bifida undergoing termination of pregnancy according to chromosomal analysis and further diagnosed sonographic findings. METHODS: Retrospective analysis of cases with spina bifida leading to termination of pregnancy in a tertiary referral center from 2002 to 2011. RESULTS: In the study period, 246 cases of spina bifida were diagnosed in our center and 157 parents chose termination of pregnancy. The time of diagnosis was on average 2 days before the first presentation at our department (22 + 3, range: 12 + 3 - 33 + 3 weeks of gestation). Among 157 pregnancies with spina bifida and termination of pregnancy, further malformations could be detected in 46 (29.3 %) cases. An abnormal karyotype could be found in 13 (18.1 %). Severe ventriculomegaly or mild/moderate ventriculomegaly was present in 109 (69.4 %) and 29 (18.5 %) of the cases, respectively, while banana sign was detectable in 153 cases (97.5 %). In the majority, the upper lesion level was lumbar (71.3 %). In 67 cases (42.7 %), termination of pregnancy took place in or after the 24th week of gestation. CONCLUSION: Direct and indirect signs of spina bifida were detectable in nearly all cases independent of the gestational age. Therefore, the diagnosis could have been made in all cases with late termination. Implementation of a uniform prenatal care including first-trimester scan with potential signs for open spina bifida and second-trimester anomaly scan with indirect intracranial findings and direct detection of spinal lesion could lead to an earlier diagnosis and help to reduce late termination of pregnancy in neural tube defects.

Fetal colour tissue Doppler imaging (cTDI): biventricular reference ranges for the time segments of the cardiac cycle in second and third trimesters of gestation.

PURPOSE: To construct biventricular reference ranges for isovolumic time intervals (isovolumic contraction time, ICT; isovolumic relaxation time, IRT) and ejection time (ET) for colour tissue Doppler imaging (cTDI) between 15 and 37 weeks' in healthy fetuses. METHODS: This was a prospective multicentre cross-sectional study involving 160 singleton pregnancies between 15 and 37 weeks of gestation, using cTDI. ICT, ET, IRT and myocardial performance index (MPI) were analysed offline using a small region of interest (ROI) within the basal part of the right and left ventricular wall immediately distal to the annulus. Regression analysis was used to determine gestational age-adjusted reference ranges and to construct nomograms for cTDI parameters. RESULTS: Right and left ventricular ICT (p = 0.004 and p < 0.001) and ET (p = 0.011 and p = 0.050) increased, whereas IRT (p = 0.862 and p = 0.067) and MPI (p = 0.476 and p = 0.777) remained constant with gestational age. CONCLUSIONS: This is the first study to evaluate fetal isovolumic time intervals in the second and third trimesters of gestation using cTDI. Normal data for fetal isovolumic time intervals and biventricular MPI by colour tissue Doppler imaging are provided. The reference ranges may be useful in research or clinical studies and can be used in fetuses with compromised cardiac function.

Reference ranges for ductus venosus velocity ratios in pregnancies with normal outcomes.

OBJECTIVES: The purpose of this study was to establish reference ranges for ductus venosus velocity ratios. METHODS: Singleton pregnancies from 11 to 38 weeks with exactly established gestational ages (GAs) were recruited for the study. Pregnancies with fetal anomalies, growth abnormalities, maternal medical complications, stillbirth, birth weight below the 10th or above the 90th percentile, and neonatal anomalies were excluded. The ductus venosus pulsatility index for veins (PIV) and velocity ratios (S/v, S/D, v/D, S/a, v/a, and D/a, where S indicates ventricular systole [s-wave], v, ventricular end-systolic relaxation [v-descent], D, passive diastolic ventricular filling [D-wave], and a, active ventricular filling during atrial systole [a-wave]) were calculated. Separate regression models were fitted to estimate the mean and standard deviation at each GA for each ratio. RESULTS: A total of 902 velocity wave ratios and ductus venosus PIVs were used for reference ranges. The S/v, S/D, and v/D ratios were not changed with GA (P > .05 for all). The PIV and S/a, v/a, and D/a ratios were reduced with GA (P < .0001 for all). Significant reductions in the means and standard deviations of the PIV and S/a, v/a, and D/a ratios were observed between 17 and 18 weeks' gestation. Therefore, nomograms were separately created between 11 and 17 weeks and 18 and 38 weeks. CONCLUSIONS: We created reference ranges for ductus venosus velocity ratios between 11 and 38 weeks' gestation in normal pregnancies. These reference ranges may prove beneficial for evaluation of fetal conditions that are associated with cardiovascular abnormalities.

Comparison of global and regional right and left ventricular longitudinal peak systolic strain, strain rate and velocity in healthy fetuses using a novel feature tracking technique.

AIMS: To compare the feature tracking derived measurements of the right (RV) and left ventricular (LV) myocardium in healthy fetuses and evaluate the correlation with advancing pregnancy. METHODS: Global and segmental longitudinal peak systolic strain, strain rate and velocity of the RV and LV myocardium were assessed with feature tracking technique in 150 healthy fetuses (13-39, median 22 weeks). RESULTS: RV global and free wall strain and strain rate values were significantly higher than those in the LV segments (P<0.001 and P<0.001). In all segments on both ventricles longitudinal peak systolic velocity measurements exhibited a significant base to apex gradient (P<0.001) and increased with advancing pregnancy (P<0.001). LV global strain and strain rate values remained constant throughout gestation, whereas RV measurements decreased (P<0.05). With advancing pregnancy the difference between RV and LV global longitudinal velocity increased significantly, whereas the difference of strain and strain rate decreased significantly. CONCLUSION: RV deformation parameters and velocity values are significantly higher compared to LV values. LV deformation parameters are stable throughout gestation, whereas RV measurements decrease significantly. The difference between global RV and LV myocardial values were significant throughout gestation, velocity values increased, whereas deformation parameters decreased.

Prenatal detection of a giant isolated coronary fistula.

Prenatal detection of an isolated congenital coronary artery fistula (ICCAF) requires an examination of the affected fetal hemodynamic situation by the fistula. Early pediatric cardiological presentation is needed, since prenatal changes may have relevant postpartal consequences.

Evaluation of two commercially available ELISA kits for the determination of melatonin concentrations in amniotic fluid throughout pregnancy.

Background The aim of the present study is to evaluate the utility of extraction versus non-extraction-based commercial melatonin ELISA kits for determining the melatonin concentration in amniotic fluid obtained in early and late pregnancy. Methods Pregnancy duration less than 28 weeks was defined as early and from 28 weeks until delivery as late gestation. Nine samples were obtained in early and 18 in late pregnancy. Two commercially available melatonin ELISA kits (melatonin ELISA RE54021, including methanol-based extraction and direct saliva melatonin ELISA RE 54041, not including an extraction step, both from IBL-International, Germany) were used to determine melatonin concentrations in amniotic fluid. Results The mean melatonin concentration in ELISAs assayed by the non-extraction was significantly lower than those assayed after extraction. Subgroup analysis showed that there was no significant difference between melatonin concentration measured by non-extraction versus extraction ELISA in early pregnancy (11.2 ± 7.4 vs. 12.2 ± 7.7, respectively, P = 0.463) but that the mean melatonin concentration in late pregnancy was significantly lower when assayed by non-extraction ELISA than when assayed by extraction ELISA (14.8 ± 9.3 vs. 145.1 ± 179.3, respectively; P < 0.001). Agreement between both measurements in late pregnancy was rather poor (r2 = 0.271, P = 0.022), as opposed to the good correlation found in early pregnancy (r2 = 0.929, P < 0.001). Conclusions The present study revealed that a melatonin assay without an extraction step, such as direct saliva ELISA, does not seem to be a valid method to determine the melatonin concentration of amniotic fluid, especially in late gestation.

Cardiorenal syndrome is present in human fetuses with severe, isolated urinary tract malformations.

OBJECTIVE: We analyzed the association between renal and cardiovascular parameters in fetuses with isolated severe urinary tract malformations. METHODS: 39 fetuses at a mean gestational age of 23.6 weeks with nephropathies or urinary tract malformations and markedly impaired or absent renal function were prospectively examined. Fetal echocardiography was performed, and thicknesses of the interventricular septum, and left and right ventricular wall were measured. Blood flow velocity waveforms of the umbilical artery, middle cerebral artery, and ductus venosus were obtained by color Doppler ultrasound. Concentrations of circulating n-terminal pro-B-type natriuretic peptide (nt-proBNP), cystatin C, ß2-microglobulin, and hemoglobin were determined from fetal blood samples. RESULTS: Malformations included 21 cases of obstructive uropathy, 10 fetuses with bilateral nephropathy, and 8 cases of bilateral renal agenesis. Marked biventricular myocardial hypertrophy was present in all cases. The ratio between measured and gestational age-adjusted normal values was 2.01 (interventricular septum), 1.85, and 1.78 (right and left ventricular wall, respectively). Compared to controls, levels of circulating nt-proBNP were significantly increased (median (IQR) 5035 ng/L (5936 ng/L) vs. 1874 ng/L (1092 ng/L); p<0.001). Cystatin C and ß2-microglobulin concentrations were elevated as follows (mean ± SD) 1.85±0.391 mg/L and 8.44±2.423 mg/L, respectively (normal range 1.66±0.202 mg/L and 4.25±0.734 mg/L, respectively). No correlation was detected between cardiovascular parameters and urinary tract morphology and function. Despite increased levels of nt-proBNP cardiovascular function was preserved, with normal fetal Doppler indices in 90.2% of cases. CONCLUSION: Urinary tract malformations resulting in severe renal impairment are associated with biventricular myocardial hypertrophy and elevated concentrations of circulating nt-proBNP during fetal life. Cardiovascular findings do not correlate with kidney function or morphology.

Second- and third-trimester termination of pregnancy in women with uterine scar - a retrospective analysis of 111 gemeprost-induced terminations of pregnancy after previous cesarean delivery.

BACKGROUND: This study was conducted to evaluate and analyze the efficacy and safety of using gemeprost for second- and third-trimester termination of pregnancy (TOP) in women with uterine scar due to previous cesarean section. STUDY DESIGN: Retrospective analysis of 111 medical TOPs for fetal anomaly or death at 14 to 34 weeks of gestation in women with a history of cesarean section was performed at a German tertiary care center from 2005 to 2009. Abortion was induced via intravaginal application of the prostaglandin analogue gemeprost (1 mg) every 6 h. RESULTS: One hundred eleven women with one (89.2%) or two (10.8%) previous cesarean sections underwent medical TOP with gemeprost. The median induction-to-expulsion interval was 18 h 24 min (range, 2 h 20 min-168 h 28 min), and in 34 (30.6%) cases, the induction interval was longer than 24 h. The overall incidence of severe complications was 9/111 (8.1%), including one case of silent uterine rupture (with the need for blood transfusion), four cases of atonic and three secondary hemorrhages and one case of peritonitis due to uterine perforation during curettage. Failure of induction (induction-to-expulsion >48 h) occurred in 11 cases (9.9%). CONCLUSION: Gemeprost-induced TOP in the second and third trimester in women with uterine scar due to previous cesarean section is effective and has a low complication rate.