Fetal Thymus Size at 19-22 Weeks of Gestation: A Possible Marker for the Prediction of Low Birth Weight?

INTRODUCTION: The purpose was to compare thymus size measured during second trimester screening of fetuses who were subsequently small for gestational age at birth (weight below 10th percentile, SGA group) with fetuses with normal birth weight (control group). We hypothesized that measuring the fetal thymic-thoracic ratio (TT-ratio) might help predict low birth weight. METHODS: Using three-vessel view echocardiograms from our archives, we measured the anteroposterior thymus size and the intrathoracic mediastinal diameter to derive TT-ratios in the SGA (n = 105) and control groups (n = 533) between 19+0 and 21+6 weeks of gestation. We analyzed the association between TT-ratio and SGA adjusted to the week of gestation using logistic regression. Finally, we determined the possible TT-ratio cut-off point for discrimination between SGA and control groups by means of receiver operating characteristics (ROC) curve analysis. RESULTS: The TT-ratio was significantly higher in the SGA group than in the control group (p < 0.001). An increase of the TT-ratio by 0.1 was associated with a 3.1-fold increase in the odds of diagnosing SGA. We determined that a possible discrimination cut-off point between SGA and healthy controls was achieved using a TT-ratio of 0.390 (area under the ROC curve 0.695). CONCLUSION: An increased TT-ratio may represent an additional prenatal screening parameter that improves the prediction of birth weight below the 10th percentile. Prospective studies are now needed to evaluate the use of fetal thymus size as predictive parameter for adverse fetal outcome.

Termination of pregnancy in the second trimester - the course of different therapy regimens.

OBJECTIVES: To compare two prostaglandin analogs and two application intervals between mifepristone and the prostaglandin analog administration on the time to abortion in second trimester termination of pregnancy. Other endpoints were live birth rate and fetal lifetime after expulsion. METHODS: Retrospective data of 373 abortions performed were evaluated. Four medical induction subgroups and two feticide subgroups were considered. The definition criteria of the subgroups were the choice of administered prostaglandin analog (misoprostol vs. sulprostone) and the time interval between mifepristone and prostaglandin analog administration (48 vs. 24 h). The outcome parameters were the time to complete uterine evacuation (TCUE), the live birth rate and duration of fetal life. RESULTS: In the misoprostol subgroups, the median TCUE was 1.6 h longer in the 24-h group than in the 48-h group (p=0.950). In the sulprostone subgroups, the median TCUE was 1.9 h shorter in the 24-h group than in the 48-h group (p=0.950). The median TCUE was shorter for sulprostone than for misoprostol in all six subgroups (p<0.001). The rate of fetal live births ranged between 13.6 and 15.9% within the medical induction subgroups (p=0.969). The median fetal lifetime was slightly shorter in the sulprostone groups than in the misoprostol groups (p=0.563). CONCLUSIONS: Both application intervals and prostaglandin analogs are similarly effective. The therapy regime should be adapted to the personal preferences of the woman, the situational and clinical conditions.

Central nervous system biometry in fetuses with and without congenital heart diseases.

OBJECTIVE: To compare the fetal brain structures assessed in routine sonographic scans during the second and third trimesters in fetuses with and without congenital heart disease (CHD). METHODS: This is a retrospective cross-sectional single-center study. We measured the head circumference (HC), the transversal diameter of the cerebellum (TCD) and the sizes of the cisterna magna (CM), the cavum septi pellucidi (CSP) and the posterior ventricles (PV) between 20 and 41 weeks of gestation. We compared 160 fetuses with CHD (case group) to 160 fetuses of normal pregnancies (control group). Every patient was matched with a control, considering the gestational age at which the ultrasound was performed. We divided the CHD group into 3 subgroups: retrograde flow in the aortic arch (group 1), right heart anomaly with the antegrade flow in the aortic arch (group 2) and other CHDs with the antegrade flow in the aortic arch (group 3). RESULTS: The mean width of the PV was larger in fetuses of groups 1 and 3 in comparison to the control group (P < 0.001, P = 0.022; respectively). We found that the APGAR score at 5 min (P < 0.001, P < 0.001; respectively) and gestational age at delivery (P = 0.006, P = 0.001; respectively) were inferior in groups 1 and 3 compared to controls. CONCLUSIONS: Central nervous system biometry is altered in fetuses with CHD. PV is enlarged in CHD fetuses especially with decreased oxygen levels in the aortic arch.

Second trimester fetal thymus size in association to preterm birth.

OBJECTIVES: The aim of this study was to compare the second trimester thymus-thorax-ratio (TTR) between fetuses born preterm (study group) and those born after 37 weeks of gestation were completed (control group). METHODS: This study was conducted as a retrospective evaluation of the ultrasound images of 492 fetuses in the three vessel view. The TTR was defined as the quotient of a.p. thymus diameter and a.p. thoracic diameter. RESULTS: Fetuses that were preterm showed larger TTR (p<0.001) the second trimester than those born after 37 weeks of gestation were completed. The sensitivity of a binary classifier based on TTR for predicting preterm birth (PTB) was 0.792 and the specificity 0.552. CONCLUSIONS: In our study, fetuses affected by PTB showed enlarged thymus size. These findings led us to hypothesize, that inflammation and immunomodulatory processes are altered early in pregnancies affected by PTB. However, TTR alone is not able to predict PTB.

Importance of frame rate for the measurement of strain and synchrony in fetuses using speckle tracking echocardiography.

OBJECTIVES: To assess the influence of frame rate settings on longitudinal strain (LS) and mechanical synchrony (SYN) values in Speckle Tracking Echocardiography (STE) of healthy fetuses. METHODS: In this prospective study, we collected transversal or apical four-chamber-views of 121 healthy fetuses between 20 and 38 weeks of gestation using three different frame rate (FR) settings (≥ 110, 100 ± 10, 60 ± 10 frames per second). We assessed the segmental and the global LS of both ventricles (2C) and of the left ventricle (LV) offline with QLab 10.8 (Philips Medical Systems, Andover, MA, USA). Inter- and intraventricular SYN were calculated as time difference in peak myocardial strain between the mid-segments of left and right ventricle (interventricular, 2C_Syn) and lateral wall and septum of the left ventricle (intraventricular, LV_Syn), respectively. RESULTS: In 84.3% STE was feasible at all three FR settings. The LS increased in both views at higher FRs to a statistically noticeable extent. SYN measurements and the absolute differences at patient level between the FR settings showed no statistically noticeable alterations. CONCLUSIONS: STE is feasible at low and high FR settings. SYN emerges to be a robust parameter for fetal STE as it is less affected by the FR. High FRs enable high temporal resolutions and thus an accurate examination of fetal hearts. Future research for the technical implementation of tailored fetal STE software is necessary for reliable clinical application.

Fetal brain development in small-for-gestational age (SGA) fetuses and normal controls.

Objective To assess whether fetal brain structures routinely measured during the second and third trimester ultrasound scans, particularly the width of the cavum septi pellucidi (CSP), differ between fetuses small for gestational age (SGA), fetuses very small for gestational age (VSGA) and normal controls. Methods In this retrospective study, we examined standard ultrasound measurements of 116 VSGA, 131 SGA fetuses and 136 normal controls including the head circumference (HC), transversal diameter of the cerebellum (TCD), the sizes of the lateral ventricle (LV) and the cisterna magna (CM) from the second and third trimester ultrasound scans extracted from a clinical database. We measured the CSP in these archived ultrasound scans. The HC/CSP, HC/LV, HC/CM and HC/TCD ratios were calculated as relative values independent of the fetal size. Results The HC/CSP ratio differed notably between the controls and each of the other groups (VSGA P = 0.018 and SGA P = 0.017). No notable difference in the HC/CSP ratio between the VSGA and SGA groups could be found (P = 0.960). The HC/LV, HC/CM and HC/TCD ratios were similar in all the three groups. Conclusion Relative to HC, the CSP is larger in VSGA and SGA fetuses than in normal controls. However, there is no notable difference between VSGA and SGA fetuses, which might be an indicator for abnormal brain development in this group.

Comparison of strain and dyssynchrony measurements in fetal two-dimensional speckle tracking echocardiography using Philips and TomTec.

Background The aim of this study was to compare Philips and TomTec two-dimensional speckle tracking echocardiography (2D-STE) software measurements of strain and dyssynchrony values in healthy fetuses. Methods This was an explorative observational study in which the echocardiographic data of 93 healthy fetuses between the 20th and 38th week of gestation were determined from a four-chamber view using 2D speckle tracking. The global and segmental longitudinal strain values of both ventricles, inter-ventricular and left intra-ventricular dyssynchrony were analyzed using QLab version 10.8 (Philips Medical Systems, Andover, MA, USA) and TomTec-Arena version 2.30 (TomTec, Unterschleißheim, Germany). Results TomTec showed persistently lower values for all of the assessed strain and dyssynchrony variables. For all variables, the bias between vendors tended to increase with gestational age, though not to a significant extent. Left ventricular dyssynchrony and longitudinal strain within the mid segment of the septum correlated best between vendors; however, the limits of agreement were wide in both cases. None of the variables assessed in the two-chamber view compared well between QLAB and TomTec. Conclusion Speckle tracking software cannot be used interchangeably between vendors. Further investigations are necessary to standardize fetal 2D-STE.

Evaluation of Cervical Elastography Strain Pattern to Predict Preterm Birth.

PURPOSE: To evaluate cervical elastography strain pattern as a predictive marker for spontaneous preterm delivery (SPTD). MATERIALS AND METHODS: In this case-control study cervical length (CL) and elastographic data (strain ratio, elastography index, strain pattern score) were acquired from 335 pregnant women (20th - 34th week of gestation) by transvaginal ultrasound. Data of 50 preterm deliveries were compared with 285 normal controls. Strain ratio and elastography index were calculated by placing two regions of interest (ROIs) in parallel on the anterior cervical lip. The strain ratio was determined by dividing the higher strain value by the lower one. The elastography index was defined as the maximum of the strain ratio curve. Elastographic images were assigned a new established strain pattern (SP) score between 0 and 2 according to the distribution of strain induced by compression. RESULTS: Elastography index, SP score and CL differed between preterm and normal pregnancies (1.61 vs. 1.27, p < 0.001; SP score value of "2": n = 31 (62 %) vs. n = 36 (12.6 %), p < 0.001; CL 30.7 vs. 41.0 mm, p < 0.001; respectively). The elastography index and SP score were associated with a higher predictive potential than CL measurement alone (AUC 0.8059 (area under the curve); AUC 0.7716; AUC 0.7631; respectively). A combination of all parameters proved more predictive than any single parameter (AUC 0.8987; respectively). CONCLUSION: Higher elastography index and SP scores were correlated with an elevated risk of SPTD and are superior to CL measurement as a predictive marker. A combination of these parameters could be used as a "Cervical Index" for the prediction of SPTD.

Influence of maternal HIV infection on fetal thymus size.

Objective To reveal the effect of a maternal human immunodeficiency virus (HIV) infection on the fetal thymus size. Methods The sonographic fetal thymus size was measured retrospectively in 105 pregnancies with maternal HIV infection and in 615 uncomplicated singleton pregnancies. The anteroposterior thymic and the intrathoracic mediastinal diameter were determined in the three-vessel view and their quotient, the thymic-thoracic ratio (TT ratio), was calculated. The study group was subdivided into three groups by the maternal viral load on the date of ultrasound (<50 cop./mL, 50-1000 cop./mL, >1000 cop./mL). Furthermore, an association between prognostic factors of the HIV infection such as the lymphocyte count, CD4/CD8 ratio, HIV medication and the thymus size, was investigated using correlation analyses. Results Fetal thymus size in pregnancies of HIV-positive mothers showed to be noticeably larger than in uncomplicated pregnancies. The mean TT ratio in the HIV-positive group was 0.389 and in the control group 0.345 (P < 0.001). There was no association between any maternal HIV parameter or medication and the size of the thymus gland. Conclusion Maternal HIV infection was associated with an increased fetal thymus size. Further consequences of intrauterine HIV exposure for fetal outcome and the development of the immune system of HIV-exposed uninfected (HEU) infants must be discussed.

Fetal adrenal gland size in gestational diabetes mellitus.

Background The aim of this study was to compare the adrenal gland size of fetuses of women with gestational diabetes mellitus (GDM) with that of healthy control fetuses. Methods This prospective cross-sectional study included measurements of the adrenal gland size of 62 GDM fetuses (GDM group) and 370 normal controls (control group) between the 19th and 41st week of gestation. A standardized transversal plane was used to measure the total width and the medulla width. The cortex width and an adrenal gland ratio (total width/medulla width) were calculated from these data. Adrenal gland size measurements were adjusted to the week of gestation and compared between the two groups in a multivariable linear regression analysis. A variance decomposition metric was used to compare the relative importance of predictors of the different adrenal gland size measurements. Results For all the investigated parameters of the adrenal gland size, increased values were found in the case of GDM (P < 0.05), while adjusting for the week of gestation. GDM seems to have a greater impact on the size of the cortex than on the size of the medulla. Conclusion The fetal adrenal gland is enlarged in pregnancy complicated by GDM. The width of the cortex seems to be particularly affected.

Procedure related risk of premature delivery and fetal growth reduction following amniocentesis, transcervical and transabdominal chorionic villus sampling: a retrospective study.

Background The aim of this study was to compare transabdominal and transcervical chorionic villus sampling (CVS) as well as amniocentesis (AC) with respect to their rates of premature delivery and fetal growth restriction. Methods We retrospectively evaluated the mentioned procedures of invasive prenatal testing performed in a single center between 2001 and 2016. Seven hundred and ninety-nine cases of AC and 719 cases of CVS were included, of which 400 were performed transvaginally. Only singleton pregnancies with a normal karyotype and delivery after 24 + 0 weeks of gestation were included. Fetal growth restriction was defined as birth weight below the 10th percentile. Premature delivery was defined as delivery before 37 + 0 weeks of gestation. Data were compared to a control group without an invasive procedure. Results The frequency of premature delivery was 8.5% after transabdominal CVS, 6.3% after transcervical CVS and 10.5% after AC as compared to 10.8% in the control group. The frequency of fetal growth restriction was 8.2% after transabdominal CVS 6.8% after transcervical CVS and 8.4% after AC as compared to 9.7% in the control group. Conclusion Our study supports that the three different methods of invasive prenatal testing do not lead to a higher risk of either premature delivery or fetal growth restriction when compared to controls. We found no difference in risk profile among the three techniques.

Strain and dyssynchrony in fetuses with congenital heart disease compared to normal controls using speckle tracking echocardiography (STE).

Objective To compare myocardial strain and mechanical dyssynchrony in fetuses with congenital heart disease (CHD) to normal controls using speckle tracking echocardiography (STE). Methods In this comparative cross-sectional study 23 fetuses with CHD and 105 normal controls between 19 and 41 weeks of gestation were assessed with STE. The STE sample box was placed over the myocardium of both ventricles. The parameters of interest included the segmental strain of the left (LV-S) and right lateral ventricle wall (RV-S) and the global ventricular strain of both chambers (2C-S). In order to separately assess the LV, we placed the STE sample box over the myocardium of the LV. We calculated the strain of the LV lateral wall (LW-S), the septum (SEPT-S) and the global ventricular strain of the single LV (1C-S). Furthermore, we analyzed the differences in timing of negative peak myocardial strain between the LV and RV (two-chamber dyssynchrony, 2C-DYS) and also within the LV between the lateral wall and the septum (one-chamber dyssynchrony, 1C-DYS). Results The evaluation of strain and mechanical dyssynchrony was feasible in all cases. Compared to normal controls, fetuses with CHD showed lower segmental and global strain values and the extent of 2C-DYS and 1C-DYS was higher than in the healthy control group. Conclusion The deterioration of myocardial function in CHD can be measured with STE. The assessment of strain and dyssynchrony with STE may be useful for distinguishing fetuses with CHD from healthy fetuses.

3D Ultrasound Evaluation of the Fetal Outer Ear: Novel Biometry Ratio and Comparison of Different Surface Display Modes.

BACKGROUND: The examination of the fetal ear is a promising but still challenging approach in prenatal diagnosis. OBJECTIVES: This study investigated a novel ear length/width ratio based on anatomical landmarks. Additionally, we compared different 3D ultrasound surface rendering modes regarding their potential to depict detailed structures of the outer ear. METHOD: We measured both the ear length and width of 118 fetal ears from 20 to 40 weeks of gestation to establish a length/width ratio. Additionally, we rendered the volumes in three different surface display modes and one adapted light position. Each image was scored regarding the visibility of distinct structures of the ear relief and indicator scores were evaluated for each mode. RESULTS: The median of the length/width ratio was 1.9 with a slight decline over the gestational period. The overall visibility of the ear structures differed noticeably between the four surface display modes (p < 0.001). The post hoc comparison showed that the display mode "TrueVue" resulted in the highest indicator scores. CONCLUSION: The length/width ratio based on anatomical landmarks of the ear could prospectively be used as a marker in syndrome detection. The study showed a superiority of the surface display mode "TrueVue" for examination of the detailed ear structures.

Comparison of Longitudinal and Apical Foetal Speckle Tracking Echocardiography Using Tissue Motion Annular Displacement and Segmental Longitudinal Strain.

The aim of our prospective pilot study with exploratory analysis was to compare longitudinal and apical foetal speckle tracking echocardiography (STE) using tissue motion annular displacement (TMAD) and segmental longitudinal strain (SLS). We compared two different STE quantification tools in a longitudinal and apical four-chamber view in 57 normal foetuses between 20 and 40 wk of gestation. Myocardial mechanical dyssynchrony and strain were assessed using offline quantification software (QLab Version 10.3, Philips Medical Systems, Andover, MA, USA). We compared the dyssynchrony measurements with TMAD and SLS in longitudinal and apical four-chamber views. Furthermore, we examined the segmental strain values of both ventricles with SLS and compared the differences between longitudinal and apical measurements. Dyssynchrony measurements with TMAD and SLS and strain measurements with SLS were feasible in all cases. In the apical view, the dyssynchrony measurements with TMAD were systematically greater than those achieved with SLS (p < 0.001). For the longitudinal view, no differences were observed between tools (p = 0.153). The application of SLS provided similar results for dyssynchrony in both views (intra-class correlation coefficient [ICC] = 0.281, p = 0.623), but the strain measurements in the left and right ventricles differed significantly between views (ICC = -0.082, p = 0.011, and ICC = -0.061, p = 0.024, respectively). For TMAD, we found large differences in the dyssynchrony values between longitudinal and apical assessment (ICC = -0.060, p = 0.03). Furthermore, TMAD exhibited reduced accuracy in the system's automatic tracking algorithm, limiting the data quality. The dyssynchrony assessment is affected less by the foetal position in SLS than in TMAD. The strain readings in SLS varied depending on the view in which they were assessed. The application of TMAD cannot be recommended for foetal STE.

Quantification of fetal myocardial function in pregnant women with diabetic diseases and in normal controls using speckle tracking echocardiography (STE).

Background The purpose of our study was to quantify the fetal myocardial function in pregnant women with diabetic diseases (FDM) and in normal controls (FC) using speckle tracking echocardiography (STE). Methods In this prospective study, the myocardial strain and dyssynchrony were analyzed using STE in a transversal four-chamber view in 180 fetuses (53 FDM, 127 FC) between 19 and 39 weeks of gestation. The measurements of the global and segmental longitudinal strain of both chambers (2C) and of the single left chamber (1C) were executed offline via QLab 10.5 (Philips Medical Systems, Andover, MA, USA). We assessed dyssynchrony as the time difference between peaks in strain in the mid segments of both chambers (interventricular dyssynchrony, 2C_DYS) and of the single left chamber (intraventricular dyssynchrony, 1C_DYS). Results Measurements were feasible with a high median frame rate of 199 frames/s (1st quartile: 174, 3rd quartile: 199). The global and segmental myocardial longitudinal strain of 2C and 1C were decreased and 2C_DYS and 1C_DYS were increased in pregnancies with diabetes compared to normal controls. Conclusion Our study demonstrates that fetal hearts affected by maternal diabetes mellitus (DM) show low myocardial strain values and high interventricular dyssynchrony. Two-chamber interventricular dyssynchrony has the potential to become a diagnostic marker for DM.

Adrenal gland size in growth restricted fetuses.

Objective To compare the adrenal gland size of fetal growth restricted (FGR) and normal control fetuses. Study design In this prospective study the adrenal gland size of 63 FGR fetuses and 343 normal controls was measured between 20 and 41 weeks of gestation. The total width and the medulla width were measured in a new standardized transversal plane. The cortex width and a calculated ratio of the total and medulla width (adrenal gland ratio) were compared between both groups. Results The mean cortex width and the adrenal gland ratio in FGR fetuses were higher in comparison to the controls (P<0.001; P=0.036, respectively). The cortex width correlated positively with the gestational age (control group: P<0.001; FGR group: P=0.089) whilst the adrenal gland ratio showed no association with the gestational age (control group: P=0.153; FGR group: P=0.314). Conclusion The adrenal gland cortex width and the adrenal gland ratio were increased in FGR fetuses compared to normal fetuses.

Assessment of the Fetal Cerebral Artery: Importance of Doppler Preset Settings.

OBJECTIVES: The Doppler assessment of the middle cerebral artery (MCA) has a central role in the monitoring of high-risk pregnancies. The objective of this study was to investigate the importance of Doppler preset settings for measurement of the peak systolic velocity (PSV) and pulsatility index (PI) of the MCA. METHODS: The PI and PSV of the MCA were determined prospectively in 350 healthy fetuses between 19 and 42 weeks of pregnancy. The first measurement of the MCA (MCA.S) was performed with the conventional settings and the second (MCA.O) with an optimized setting of the maximum achievable frame rate. For the MCA.O measurement, the width of the B-mode image and the color Doppler window were adjusted as narrowly as possible. In addition, the MCA was shown in optimized high-definition zoom. Resulting values were compared with commonly used reference values. RESULTS: The PSV and PI values and frame rates of the MCA.O setting were noticeably greater than those of the MCA.S setting (P < .001 for all). For both settings, the PSV and PI values were increased compared to common reference values. CONCLUSIONS: The assessment of the MCA with the optimized Doppler default setting yielded increased PSV and PI values compared to the commonly used measurement technique. Moreover, the resulting median curves differed from the established median reference curves. Therefore, an updated standardization for measuring the MCA should be set out, and current reference values should be adjusted.

Assessment of strain and dyssynchrony in normal fetuses using speckle tracking echocardiography - comparison of three different ultrasound probes.

OBJECTIVE: To evaluate segmental left (LV-S) and right (RV-S) ventricular strain as well as longitudinal mechanical myocardial dyssynchrony as a time difference between peaks in strain of both ventricles in fetuses (two-chamber-dyssynchrony, 2C-DYS) using speckle tracking echocardiography (STE). The aim of our study was to evaluate the influence of data acquisition on the results of STE measurement using different ultrasound probes. METHODS: We prospectively recorded cardiac cycles of four-chamber views of 56 normal fetuses with three different ultrasound probes and analyzed them offline with speckle tracking imaging software. Furthermore, we looked at a possible influence of heartbeat variability (beat-to-beat variability). RESULTS: The evaluation of the parameters was feasible with all three probes in 53 cases. There was no influence of heartbeat variability and no noticeable differences in 2C-DYS, LV-S and RV-S in all cases and for all three probes determined. CONCLUSION: Assessment of strain and dyssynchrony using STE with three different probes is comparable. Further research is needed to validate dyssynchrony as a predictor for fetal outcome.

Assessment of cervical elastography strain pattern and its association with preterm birth.

OBJECTIVE: The aim of the study was to assess the cervical strain pattern by an ultrasound elastography cervix examination and to determine its association with preterm delivery. METHODS: In this study, 30 cases resulting in preterm birth and 30 gestational age-matched controls were included. A vaginal ultrasound examination with cervical length and elastography measurement was performed. We calculated four strain ratios (SR1-SR4) of the regions of interest (ROIs) arranged in pairs in four different positions on the anterior cervical lip. The strain ratios were correlated to the outcome of spontaneous preterm delivery. The inter-observer and intra-observer variability of the strain measurement was evaluated. RESULTS: We observed an association between the value of the strain ratio that was calculated from the ROIs placed side by side in the middle of the anterior lip (SR4), and preterm delivery (P<0.001). The predictive values of cervical length and SR4 were comparable (AUC 0.7394; AUC 0.8322, respectively). The combination of cervical length and SR4 was superior in predicting preterm delivery compared to both parameters alone (AUC 0.8789). The inter-observer and intra-observer variability of data acquisition and measurement was excellent. CONCLUSIONS: Our study assesses the cervical elastography strain pattern and shows a correlation to a spontaneous preterm birth.