Fetal cardiovascular function in a late-onset SGA and FGR cohort: CURIOSA study.

Purpose The measurement of fetal cardiovascular function parameters is not yet established in prenatal diagnostics. Now that the research field of fetal programming is becoming increasingly important, this might change. Fetal cardiovascular changes have been described above all in early/severe fetal growth restriction (FGR). The aim of this study was to investigate functional echocardiographic parameters in fetuses with late-onset small for gestational age (SGA)/FGR. Materials and methods A prospective cohort of SGA fetuses (including FGR) and a control group with similar distribution of gestational age were studied. Parameters of systolic, diastolic and global cardiac function, morphometry and measurements of the fetal abdominal aorta were collected. Results A total of 149 SGA fetuses and 143 control fetuses were included from 32 weeks until term. The total SGA group was further divided into SGA 3rd-10th (fetuses between the 3rd and 10th weight percentile) and FGR subgroups. In the total SGA group, relative right and left ventricular wall thickness, left E/A ratio, isovolumetric contraction time and left myocardial performance index were significantly increased compared to controls after adjustment for gestational age. MAPSE, TAPSE, ejection time, left cardiac output and abdominal aortic distensibility were significantly lower. The changes were more pronounced in the FGR subgroup. Conclusion Even in a group of late-onset SGA/FGR situation, echocardiographic parameters are already altered in utero. Zusammenfassung Ziel Die Messung fetaler kardiovaskulärer Funktionsparameter ist in der Pränataldiagnostik noch nicht etabliert. Nachdem das Forschungsgebiet der fetalen Programmierung einen immer höheren Stellenwert hat, könnte sich das bald ändern. Vor allem bei früher fetaler Wachstumsrestriktion (FGR) sind kardiovaskuläre Veränderungen beschrieben. Ziel dieser Studie war es dies bei Feten mit spät einsetzender FGR zu untersuchen. Material und Methode Eine prospektive Kohorte von Feten, die zu klein für das Gestationsalter (SGA) sind (einschließlich FGR) sowie eine Kontrollgruppe ähnlichen Gestionsalters wurden untersucht. Es wurden Parameter der systolischen, diastolischen sowie globalen Herzfunktion, der Morphometrie sowie Messungen der fetalen Aorta abdominalis erhoben. Ergebnisse Insgesamt wurden 149 SGA Feten sowie 143 Kontrollfeten ab 32 Schwangerschaftswochen eingeschlossen. Die Gesamt-SGA Gruppe wurde für eine Subgruppenanalyse weiterhin in eine SGA (SGA 3-10: Feten zwischen der 3. und 10. Gewichtsperzentile) sowie eine FGR Subgruppe unterteilt. In der Gesamt-SGA Gruppe zeigten sich im Vergleich zu den Kontrollen nach Adjustierung an das Gestationsalter die relative rechte sowie linke Ventrikelwanddicke, das linke E/A-Verhältnis, die isovolumetrische Kontraktionszeit und der linke myokardiale Performanceindex signifikant erhöht. MAPSE, TAPSE, die Ejektionszeit, das linke Herzzeitvolumen und die Beweglichkeit der Aorta abdominalis waren signifikant geringer. Die Ergebnisse waren im Subgruppenvergleich in der FGR Subgruppe ausgeprägter. Schlussfolgerung Auch in einer Gruppe spät einsetzender SGA/FGR Situation sind echokardiographische Parameter bereits intrauterin verändert.

Role of Ductus Venosus Doppler Sonography for the Prediction of Perinatal Outcome in Term Pregnancies Complicated by Gestational Diabetes Mellitus.

PURPOSE: Ductus venosus (DV) Doppler velocimetry reflects fetal cardiac function. Gestational diabetes mellitus (GDM) is assumed to impair cardiac function due to fetal hyperglycemia. The purpose of this study was to assess the ability of DV Doppler to predict an adverse perinatal outcome (APO) in term pregnancies with GDM. METHODS: This is a retrospective cohort study including GDM pregnancies of singleton, non-anomalous fetuses without any signs of placental dysfunction. All GDM women who primarily had a vaginal delivery attempt and in which DV Doppler was examined from 37+0 weeks on were included. Receiver operating characteristic curve (ROC) analyses were performed to assess the predictive value of DV pulsatility index (DV-PI) regarding a composite APO (CAPO). Furthermore, a subgroup analysis was performed regarding the presence of a large-for-gestational-age (LGA) newborn. RESULTS: A total of n=89 cases were included. Overall, CAPO occurred in 26 out of 89 cases (29.2%). All DV Doppler examinations showed a positive A wave. DV-PI was>95th percentile in 8 out of 89 cases (9%). Overall, ROC analysis showed no significant association of DV-PI with CAPO (AUC=0.523, p=0.735). However, regarding individual APO parameters, ROC analysis showed a significant association of DV-PI with 5th-min AGPAR (AUC=0.960, p=0.027), which was not confirmed after exclusion of LGA cases. CONCLUSION: In GDM pregnancies at term, DV Doppler sonography seems to have no benefit for APO prediction.

Role of the cerebro-placental-uterine ratio in predicting adverse perinatal outcome in low-risk pregnancies at term.

PURPOSE: The cerebroplacental ratio (CPR) is associated with adverse perinatal outcome (APO) in low-risk pregnancies near term. A Doppler parameter, which also includes information from the uterine vessels could potentially improve detection of subclinical placental dysfunction. The aim of this study is to investigate the performance of cerebro-placental-uterine ratio (CPUR) related to APO prediction in low-risk term pregnancies in > 40 + 0 weeks. METHODS: This is a retrospective cohort study. All low-risk pregnancies in which feto-maternal Doppler was examined from 40 + 0 weeks and an appropriate for gestational age fetus was present were included. ROC (receiver operating characteristic curves) analyses were performed to assess the predictive value of CPUR. The presence of at least one of the following outcome parameters was defined as composite APO (CAPO): operative delivery (OD) due to intrapartum fetal compromise (IFC), admission to the neonatal intensive care unit, umbilical cord arterial pH ≤ 7.15, 5 min APGAR ≤ 7. RESULTS: A total of n = 114 cases were included. Mean gestational age at examination and delivery were 40 + 3 weeks and 40 + 6 weeks, respectively. Overall, CAPO occurred in 38 of 114 cases (33.3%). ROC analyses showed a significant association of CPUR (AUC = 0.67, p = 0.004) and CPR (AUC = 0.68, p = 0.002) with CAPO. Additionally, CPUR (AUC = 0.64, p = 0.040) showed a predictive value for OD due to IFC. CONCLUSION: The CPUR in > 40 + 0 weeks showed a predictive value for CAPO and OD due to IFC in low-risk pregnancies. However, the extent to which CPUR can be used to optimize delivery management warrants further investigations in prospective interventional studies.

Evaluation of right ventricular myocardial deformation properties in fetal hypoplastic left heart by two-dimensional speckle tracking echocardiography.

PURPOSE: Right ventricular (RV) function influences the outcome of hypoplastic left heart (HLH) patients. This study aimed to confirm the assumption of prenatal RV remodeling and possible influencing factors of myocardial restructuring using two-dimensional speckle tracking echocardiography (2D STE). METHODS: This is a retrospective cross-sectional cohort study including HLH fetuses and gestational age-matched controls. Based on a four-chamber view, cine loops were stored with 60 frames per second. Global longitudinal peak systolic strain (GLPSS) of the RV was retrospectively determined and compared to healthy controls. Furthermore, HLH subgroups were built according to the presence of left ventricular endocardial fibroelastosis (LV-EFE) and restrictive foramen ovale (FO) to investigate the effect of these compromising factors on myocardial deformation. RESULTS: A total of 41 HLH fetuses and 101 controls were included. Gestational age at fetal assessment was similarly distributed in both groups (controls: 26.0 ± 5.6 weeks vs. HLH: 29.1 ± 5.6 weeks). Relating to RV-GLPSS values, fetuses with HLH demonstrated lower mean values than healthy control fetuses (- 15.65% vs. - 16.80%, p = 0.065). Cases with LV-EFE (n = 11) showed significantly lower mean values compared to such without LV-EFE (n = 30) (RV-GLPSS: - 12.12% vs. - 16.52%, p = 0.003). No significant differences were observed for cases with FO restriction (n = 10). CONCLUSIONS: In HLH the RV undergoes prenatal remodeling, leading to an adaptation of myocardial function to LV conditions. Further explorations by STE should expand knowledge about RV contraction properties in HLH and its impact on surgical outcome.

Prognostic Value of Cerebroplacental Ratio in Appropriate-for-Gestational-Age Fetuses Before Induction of Labor in Late-Term Pregnancies.

PURPOSE: To evaluate the relationship between cerebroplacental ratio (CPR) and the need for operative delivery due to intrapartum fetal compromise (IFC) and adverse perinatal outcome (APO) in appropriate-for-gestational-age (AGA) late-term pregnancies undergoing induction of labor. The predictive performance of CPR was also assessed. MATERIALS AND METHODS: Retrospective study including singleton AGA pregnancies that underwent elective induction of labor between 41 + 0 and 41 + 6 weeks and were delivered before 42 + 0 weeks. IFC was defined as persistent pathological CTG or pathological CTG and fetal scalp pH < 7.20. Operative delivery included instrumental vaginal delivery (IVD) and cesarean section (CS). APO was defined as a composite of umbilical artery pH < 7.20, Apgar score < 7 at 5 minutes, and admission to the neonatal intensive care unit for > 24 hours. RESULTS: The study included 314 women with 32 (10 %) IVDs and 49 (16 %) CSs due to IFC and 85 (27 %) APO cases. Fetuses with CPR < 10th percentile showed a significantly higher rate of operative delivery for IFC (40 % (21/52) vs. 23 % (60/262); p = 0.008) yet not a significantly higher rate of APO (31 % (16/52) vs. 26 % (69/262); p = 0.511). The predictive values of CPR for operative delivery due to IFC and APO showed sensitivities of 26 % and 19 %, specificities of 87 % and 84 %, positive LRs of 2.0 and 1.2, and negative LRs of 0.85 and 0.96, respectively. CONCLUSION: Low CPR in AGA late-term pregnancies undergoing elective induction of labor was associated with a higher risk of operative delivery for IFC without increasing the APO rate. However, the predictive value of CPR was poor.

Perinatal Outcome and its Prediction Using Longitudinal Feto-Maternal Doppler Follow-Up in Late Onset Small for Gestational Age Fetuses - A Prospective Cohort Study.

PURPOSE: To describe the perinatal outcome of a prospective cohort of late-onset small-for-gestational-age (SGA) fetuses and to test adverse perinatal outcome (APO) prediction using Doppler measurements. METHODS: Singleton pregnancies from 32 weeks with suspicion of SGA (followed-up each 2 weeks) and randomly selected healthy controls at a university hospital were included. The whole SGA group was divided into the FGR subgroup or SGA percentile 3-10 subgroup. The following Doppler measurements were evaluated prospectively: umbilical artery (UA) pulsatility index (PI), middle cerebral artery (MCA) PI, cerebro-placental ratio (CPR), and mean uterine artery (mUtA) PI. APO was defined as arterial cord blood pH ≤ 7.15 and/or 5-minute Apgar ≤ 7 and/or emergency operative delivery and/or admission to the neonatal unit. Induction of labor was indicated according to a stage-based protocol. RESULTS: A total of 149 SGA and 143 control fetuses were included. The number of operative deliveries was similar between both groups (control: 29 %, SGA: 28 %), especially the cesarean delivery rate after the onset of labor (11 % vs. 10 %). Most SGA cases ended up in induction of labor (61 % vs. 31 %, p < 0.001). The areas under the curve (AUC) for APO prediction were similar using the last UA PI, MCA PI, CPR, and mUtA PI and barely reached 0.60. The AUC was best for the FGR subgroup, using the minimal CPR or maximum mUtA PI z-score of all longitudinal measurements (AUC = 0.63). CONCLUSION: SGA fetuses do not have a higher rate of operative delivery if managed according to a risk stratification protocol. Prediction of APO is best for SGA and FGR using the "worst" CPR or mUtA PI but it remains moderate.

Myocardial deformation analysis in late-onset small-for-gestational-age and growth-restricted fetuses using two-dimensional speckle tracking echocardiography: a prospective cohort study.

OBJECTIVES: An association between fetal growth restriction (FGR) and increased predisposition to cardiovascular disease (CVD) is suggested. The aim of this study was to evaluate subclinical signs of fetal cardiac remodeling in late-onset small-for-gestational-age (SGA) and growth-restricted fetuses using two-dimensional speckle tracking echocardiography (2D-STE). METHODS: This is a prospective cohort study, including 117 late-onset (≥32 weeks) SGA (birthweight≤10th centile) fetuses and 102 gestational age matched controls. A subgroup analysis was performed: FGR was defined based on either BW (0.05). Regarding global and segmental LPSS and LSR values of LV/RV, subgroup analysis revealed no significant difference between the FGR (n=81), SGA centile 3-10 (n=36) and control group. CONCLUSIONS: A mild degree of placental dysfunction seems not to influence myocardial deformation properties measured by 2D-STE.

Cardiovascular outcome of former late-onset small-for-gestational-age children at 1 year of age: CURIOSA study.

OBJECTIVE: Late-onset small-for-gestational-age (SGA) fetuses usually show normal uterine artery Doppler and were long considered to have a good peri- and postnatal outcome. Recently, these fetuses were identified to have a risk factor for cardiovascular disease. The aim of our study was to evaluate former SGA children concerning their cardiovascular risk and nutrition behavior at the age of 1 year. METHODS: We performed a prospective longitudinal cohort study at the University Hospital "Klinikum rechts der Isar" of the Technical University of Munich. Singleton pregnancies from 32 weeks with suspicion of SGA and healthy control pregnancies were included. RESULTS: A total of 100 former SGA children and 113 controls with normal weight (AGA) were examined at 1 year of age. Drop-out for 1-year follow-up was 27%. SGA children had significantly higher systolic (92.8 ± 9.8 mmHg vs. 87.5 ± 10.7 mmHg, p = 0.001), diastolic (63.1 ± 8.5 mmHg vs. 60.0 ± 10.3 mmHg, p = 0.028) and mean (73.0 ± 7.8 vs. 69.2 ± 9.7 mmHg, p = 0.004) blood pressure than AGA children. Comparing two breastfeeding periods (0-4 months vs. > 7 months), a downward trend in blood pressure values for longer breastfeeding periods was shown. CONCLUSION: Our study showed that even late-onset small-for-gestational-age fetuses seem to have cardiovascular problems, although they were previously thought to be "healthy". Up to now, blood pressure measurement is not part of indicated health checks in former SGA or even fetal growth-restricted children which should be changed. Further studies are needed to investigate cardiovascular prevention programs in children.

Does gestational age at term play a role in the association between cerebroplacental ratio and operative delivery for intrapartum fetal compromise?

INTRODUCTION: To assess the impact of gestational age at term on the association between cerebroplacental ratio (CPR) and operative delivery for intrapartum fetal compromise (IFC) and prognostic performance of CPR to predict operative delivery for IFC. MATERIAL AND METHODS: This was a retrospective cohort study including 2052 singleton pregnancies delivered between 37+0 and 41+6  weeks of gestation in a single tertiary referral center over an 8-year period. CPR was measured within 1 week of delivery. IFC was defined as the presence of persistent pathological cardiotocography pattern or the combination of pathological cardiotocography pattern and fetal scalp pH < 7.20. Operative delivery included instrumental vaginal delivery and cesarean section. Pregnancies were grouped according to birthweight (small for gestational age [SGA, birthweight <10th centile] and appropriate for gestational age [AGA, birthweight 10th-90th centile]) and gestational age by week at delivery. Rates of operative delivery were compared between the subgroups. Prognostic value of CPR was assessed using receiver operating characteristic curve. RESULTS: Of the study cohort, 308 (15%) had a CPR <10th centile, 374 (18%) operative delivery for IFC, and 298 (15%) were SGA at birth. Overall, the rates of operative delivery for IFC were higher in the low CPR group both in SGA (35% vs. 22%; p = 0.023) and in AGA (23% vs. 16%; p = 0.007). According to gestational age by week at delivery, fetuses with low CPR showed higher rates of operative delivery for IFC with advancing gestational age, mainly in pregnancies delivered at 40 weeks (54% vs. 23%; p = 0.004) and at 41 weeks (60% vs. 19%; p = 0.010) for SGA and at 41 weeks (39% vs. 20%; p = 0.001) for AGA. The predictive value of CPR remained stable throughout term and was poor both in SGA and in AGA. CONCLUSIONS: Both SGA and AGA fetuses with low CPR showed higher rates of operative delivery for IFC at term with advancing gestational age. Prognostic value of CPR throughout term was poor.

Natural history of pulmonary atresia with intact ventricular septum (PAIVS) and critical pulmonary stenosis (CPS) and prediction of outcome.

OBJECTIVES: To analyse prenatal parameters predicting biventricular (BV) outcome in pulmonary atresia with intact ventricular septum/critical pulmonary stenosis (PAIVS/CPS). METHODS: We evaluated 82 foetuses from 01/08 to 10/18 in 3 centres in intervals 1 (< 24 weeks), 2 (24-30 weeks) and 3 (> 30 weeks). RESULTS: 61/82 (74.4%) were livebirths, 5 (8.2%) lost for follow-up, 3 (4.9%) had compassionate care leaving 53 (64.6% of the whole cohort and 86.9% of livebirths) with intention to treat. 9 died, 44/53 (83.0%) survived. 24/38 (63.2%) with information on postnatal outcome had BV outcome, 14 (36.8%) non-BV outcome (2 × 1.5 circulation). One with BV outcome had prenatal valvuloplasty. Best single parameter for BV outcome was tricuspid/mitral valve (TV/MV) ratio (AUC 0.93) in intervals 2 and 3 (AUC 0.92). Ventriculo-coronary-arterial communications (VCAC) were present in 11 (78.6%) in non-BV outcome group vs. 2 (8.3%) in BV outcome group (p < 0.001). Tricuspid insufficiency (TI)-Vmax > 2.5 m/s was present in BV outcome group in75.0% (18/24) vs. 14.3% (2/14) in non-BV outcome group. Including the most predictive markers (VCAC presence, TI- Vmax < 2.5 m/s, TV/MV ratio < cutoff) to a score, non-BV outcome was correctly predicted when > 1 criterion was fulfilled in all cases. After recently published criteria for foetal intervention, only 4/9 (44.4%) and 5/14 (35.7%) in our interval 2 + 3 with predicted non-BV outcome would have been candidates for intervention. Two (1 × intrauterine intervention) in interval 2, two in interval 3 reached BV outcome and one 1.5 circulation without intervention. CONCLUSION: TV/MV ratio as simple parameter has high predictive value. After our score, non-BV outcome was correctly predicted in all cases. Criteria for foetal intervention must further be evaluated.

Cerebroplacental and Uterine Doppler Indices in Pregnancies Complicated by Congenital Heart Disease of the Fetus.

PURPOSE: Children with congenital heart disease (CHD) are known to have impaired neurodevelopment possibly influenced by altered cerebroplacental hemodynamics antenatally. We compared fetomaternal Doppler patterns in different CHD groups with published normative values during gestation. MATERIALS AND METHODS: Retrospective cohort study consisting of 248 CHD fetuses. Subgroups were generated according to the expected ascending aorta oxygen saturation: low portion of high oxygenated umbilical venous (UV) blood (group 1: n = 108), intermediate portion of UV blood due to intracardiac mixing with oxygen poor systemic blood (group 2: n = 103), high (group 3: n = 13) and low portion of UV blood without mixing of blood (group 4: n = 24). Doppler examination included umbilical artery and middle cerebral artery pulsatility index (UA-PI, MCA-PI), cerebroplacental ratio (CPR) and mean uterine artery (mUtA) PI. For mean comparisons at different gestational ages (GA), estimated marginal means from regression models are reported for GA 22 weeks (wks), GA 30 wks and GA 38 wks. RESULTS: Z-score transformed values of MCA-PI (zMCA-PI) were significantly lower in group 1 compared to all other subgroups at GA 30 wks (p < 0.05). At 38 wks, group 1 had significantly lower values of zMCA-PI and zCPR compared to groups 2 and 4. Group 1 fetuses showed a significant association between zMCA-PI and zCPR (negative) and GA as well as zmUtA-PI (positive) and GA compared to reference values. CONCLUSION: Our data confirm that CHD fetuses have a higher rate of cerebral redistribution in the third trimester. Changes in Doppler patterns were mainly observed in CHD with a low portion of UV blood in the ascending aorta.

Assessment of the maxilla-mandible-nasion angle in normal and aneuploid foetuses in the first trimester of pregnancy.

PURPOSE: This retrospective study aims to determine whether the maxilla-mandible-nasion (MMN) angle can be reliably measured in the first trimester, to describe normal ranges, and to determine if significant changes occur in foetuses with aneuploidies. METHODS: The MMN angle was measured in stored 2D-ultrasound images of 200 normal fetal profiles between 11+0 and 13+6 weeks of gestation. Each image was analyzed by two observers at two independent time points. Bland-Altmann analysis was performed to evaluate the reliability of the measurements. Additionally, the MMN angle was measured on sonograms from 140 aneuploid foetuses. RESULTS: The mean MMN angle in normal foetuses from 11 to 14 weeks of gestation was 15.4°. Reliability of the measurement was high when repeatedly measured by the same observer (ICC = 0.92 and 0.82) and between two observers (ICC = 0.77 and 0.63). Average MMN values in foetuses with trisomy 21, 13, and Turner syndrome were significantly higher than those measured in normal foetuses. The highest differences were observed in foetuses with trisomy 13. Among those, 62% had an MMN angle above the 95th percentile and 92% above the normal mean. CONCLUSION: The MMN angle can be reliably measured in early pregnancy and is abnormal in about 60% of foetuses with trisomy 13.

Intrapartum PRSA: a new method to predict fetal acidosis?-a case-control study.

PURPOSE: Phase-rectified signal averaging method (PRSA) represents an analysis method which applied on fetal cardiotocography (CTG) allows the quantification of the speed of fetal heart rate changes. By calculating the average deceleration capacity (ADC) an assessment of the fetal autonomic nervous system (ANS) is possible. The objective of this study was to test its ability to predict perinatal acidosis. METHODS: A case-control study was performed at a University Hospital in Munich. All intrapartum CTG heart rate tracings saved during a 7-year period were considered for analysis. All neonates born with an umbilical arterial blood pH ≤ 7.10 were considered as cases. Controls were defined as healthy fetuses born with a pH ≥ 7.25. The main matching criteria were gestational age at delivery, parity, birth mode, and birth weight percentile. Exclusion criteria were a planned caesarean section, fetal malformations, and multiple pregnancies. ADC and STV were then calculated during the last 60, the last 45, and the last 30 min intervals prior to delivery. RESULTS: Of all stored birth CTG recordings, 227 cases met the inclusion criteria and were studied. ADC was significantly higher in fetuses born with acidemia (4.85 bpm ± 3.0) compared to controls (3.36 bpm ± 2.2). The area under ROC curve was 0.659 (95% CI 0.608-0.710) for ADC and 0.566 (0.512-0.620) for STV (p = 0.013). CONCLUSIONS: This study confirms that the assessment of ADC using PRSA represents a good additional tool for the prediction of acute fetal acidosis during delivery.

Role of sFlt-1/PlGF ratio and feto-maternal Doppler for the prediction of adverse perinatal outcome in late-onset pre-eclampsia.

PURPOSE: The sFlt-1 (soluble fms-like tyrosine kinase-1)/PlGF (placental growth factor) ratio and uterine artery Doppler have shown to be helpful in the diagnosis of pre-eclampsia (PE). The predictive value of the cerebroplacental ratio (CPR) regarding adverse perinatal outcome (APO) in low-risk pregnancies is intensively discussed. We evaluated the extent to which sFlt-1/PlGF ratio and feto-maternal Doppler may be useful in predicting APO in singleton pregnancies complicated by late-onset PE and/or HELLP syndrome. METHODS: This is a retrospective study from 2010 to 2018 consisting of singleton pregnancies with confirmed diagnosis of late-onset (lo ≥ 34 weeks) PE/HELLP syndrome in which sFlt-1/PlGF ratio and feto-maternal Doppler (mUtA-PI: mean uterine artery pulsatility index and CPR) were determined. The ability of sFlt-1/PlGF ratio, mUtA-PI, CPR and their combination to predict APO or SGA was evaluated using receiver operating characteristic (ROC) curves. RESULTS: 67 patients were included in the final analysis. Of these, sFlt-1/PlGF was > 110 (defining angiogenic lo PE) in 40.3% (27/67), mUtA-PI was above the 95th centile in 34.3% (23/67) patients and CPR was lower than the 5th centile in 10.4% (7/67). Abnormal sFlt-1/PlGF and mUtA-PI as well as CPR were associated with a lower birth weight (BW). Late-preterm birth (< 37 weeks) as well as postnatal diagnosis of small for gestational age (SGA: BW < 3rd centile) was significantly more often in angiogenic lo PE cases. Neither sFlt-1/PIGF nor CPR or mUtA-PI were APO predictors. Only for sFlt-1/PlGF, ROC analysis revealed a significant predictive value for postnatal SGA (AUC = 0.856, p = 0.001, 95% CI 0.75-0.97). There was no statistical added value of combined SGA predictors as compared to sFlt-1/PlGF alone. CONCLUSIONS: In patients with lo PE, adding sFlt-1/PlGF ratio to routine antepartum fetal surveillance may be useful to identify cases of postnatal SGA. However, further prospective studies are warranted to define the role of feto-maternal Doppler and sFlt-1/PlGF ratio as outcome predictors.

Head Biometry in Fetuses with Isolated Congenital Heart Disease.

PURPOSE: Altered cerebral hemodynamics are involved in changes in head biometry in fetuses with congenital heart disease (CHD). We compared head growth in different CHD groups with published normative values and investigated whether CHD groups differ from each other in terms of head circumference (HC) development over gestational age (GA). MATERIALS AND METHODS: Retrospective cohort study consisting of 248 CHD fetuses. Subgroups were generated according to the expected ascending aorta oxygen saturation: Low placental blood content (BC) and therefore low oxygen delivery to the brain (group 1: n = 108), intermediate placental and systemic BC due to intracardiac mixing of blood (group 2: n = 103), high placental BC (group 3: n = 13) and low placental BC and low oxygen delivery to the brain without mixing of blood (group 4: n = 24). Furthermore, group 1 was divided into antegrade (n = 34) and retrograde (n = 74) flow through the aortic arch. Comparisons were made at a GA of 22, 30 and 38 weeks. RESULTS: Estimated values of zHC (z-score transformed) were not significantly different between the four CHD groups at the three time points in gestation (all p > 0.05). Within group 1 fetuses with retrograde aortic arch flow showed a significant negative association between HC and GA compared to reference values (b = -0.054, p < 0.001) and had significantly lower zHC values at 38 weeks (-0.836) compared to fetuses with antegrade flow (0.366, p = 0.009). CONCLUSION: Our data do not confirm that CHD fetuses in general have a significantly smaller HC. HC becomes smaller throughout gestation depending on the direction of aortic arch flow.

Atrial and Ventricular Deformation Analysis in Normal Fetal Hearts Using Two-Dimensional Speckle Tracking Echocardiography.

OBJECTIVE: Two-dimensional speckle tracking echocardiography (2D-STE)-based strain values of the left and the right ventricle have been established; however, less is known about atrial deformation. The aim of our study was to assess both atrial strain and ventricular strain using 2D-STE in a cardiac 4-chamber view and to investigate the effect of possible influencing factors such as gestational age. METHODS: Fetal echocardiography was performed on a Toshiba Aplio 500 ultrasound system. Based on an apical or basal 4-chamber view of the fetal heart, left and right ventricular longitudinal peak systolic strain (LVLPSS and RVLPSS) as well as left and right atrial longitudinal peak systolic strain (LALPSS and RALPSS) were assessed by 2D-STE. RESULTS: A total of 101 healthy fetuses were included. The mean gestational age (GA) was 26.0 ± 5.6 weeks. GA was significantly positively correlated (p < 0.05) with LVLPSS and RVLPSS and significantly negatively correlated (p < 0.05) with LALPSS and RALPSS. The mean values for LVLPSS and RVLPSS were -17.44 ± 2.29% and -16.89 ± 1.72%. The mean values for LALPSS and RALPSS were 34.09 ± 4.17% and 35.36 ± 2.90%. CONCLUSION: Ventricular and atrial deformation analysis in 2D-STE was technically feasible and showed comparable values to current data. For future research on myocardial function (MF) of the fetus, considering GA as an influencing factor for deformation analysis seems to be adequate. Especially, atrial deformation analysis allows the assessment of diastolic myocardial function. Further research needs to clarify the clinical meaning of these myocardial deformation indices in fetuses at risk.

Myocardial function in fetuses with lower urinary tract obstruction: Is there a cardiac remodeling effect due to renal damage?

OBJECTIVES: Cardiac remodeling due to renal dysfunction may have an impact on myocardial function (MF) of fetuses with lower urinary tract obstruction (LUTO). The aim was to identify possible differences in MF in LUTO fetuses compared with healthy controls and to look for interactions between urine biochemistry and MF indices. METHODS: This is a cohort study consisting of 31 LUTO fetuses and 45 healthy controls. Subgroups were generated according to intrauterine therapy (group 1: LUTO after therapy, group 2: LUTO without therapy at the time of examination, and group 3: controls). MF indices were measured using pulsed wave tissue Doppler imaging and M-mode. Furthermore, results of fetal urine biochemistry were gathered retrospectively. RESULTS: Among other findings, right ventricular (RV) e'/a' ratio was lower in group 1 compared with group 3 (p = .050). According to gestational age (GA) level-dependent analysis, RV isovolumetric relaxation time was significantly longer in group 2 compared with group 1 and group 3 at GA level 1 (19 wk of gestation). A significant positive correlation between RV e'/a' ratio and ß-2-microglobulin as well as α-1-microglobulin and potassium could be observed. CONCLUSION: We observed differences in MF and an association between ventricular filling pattern and renal protein secretion in LUTO fetuses. This can be interpreted as a sign of intrauterine cardiac remodeling.

Wall motion tracking in fetal echocardiography-Application of low and high frame rates for strain analysis.

OBJECTIVE: Compared to adults, fetal heart rates (HR) are elevated necessitating higher frame rates (FR) for strain analysis by speckle tracking echocardiography. The aim of this study was to investigate the influence of high FR compared to low FR on strain analysis in 2D speckle tracking. METHODS: Fetal echocardiography was prospectively performed and acquired from the apical or basal four-chamber views of the heart. Images were optimized for clear delineation of myocardial walls and stored in either raw Digital Imaging and Communications in Medicine (DICOM) cine-loop format for offline analysis with a low FR of 60 frames per second (fps) or in the original FR (acoustic FR = AFR). For each loop, right (RV) and left (LV) ventricular fetal longitudinal peak systolic strain (LPSS) values were assessed by 2D Wall Motion tracking. RESULTS: One hundred and three healthy fetuses were included with a mean gestational age of 26.3 ± 5.5 weeks. Mean AFR was 127 ± 26 fps. A mean FR/HR ratio was assessed of 0.42 and 0.90 between the low FR and AFR group, respectively. Relating to LPSS values, there was a significant difference between low FR and AFR for both ventricles (LV: -16.5% ± 3.9% (low FR) vs -13.6% ± 3.5% (AFR); and RV: -15.1% ± 3.6% (low FR) vs -12.6% ± 3.7% (AFR), both P < 0.001). CONCLUSIONS: Fetal LV and RV LPSS values derived with high AFR were significantly lower than corresponding LPSS values analyzed with low FR of 60 fps. Future studies are needed to clarify the clinical importance of this relationship.

Measurement of inferior facial angle and prefrontal space ratio in first trimester fetuses with aneuploidies: a retrospective study.

Objective To determine whether the measurement of inferior facial angle (IFA) and prefrontal space ratio (PFSR) in two-dimensional (2D) ultrasound images in the first trimester of pregnancy is reliable and to describe these markers in normal and aneuploid fetuses. Methods IFA and PFSR were measured in stored 2D midsagittal images of 200 normal and 140 aneuploid fetal profiles between 11 + 0 and 13 + 6 weeks of gestation. Limits of agreement (LOAs) and intraclass correlation coefficients (ICCs) for inter- and intraobserver differences were calculated. Results The mean IFA in normal fetuses was 76.5° ± 6.3. Between the two measurement rounds of the same observer, the LOAs were -5.4 to 7.1 (obs. 1) and 7.4 to 8.4 (obs. 2). For IFA measurements by the same observer the ICC was 0.88 (obs. 1) and for measurements by two different observers the ICC was 0.74. The mean PFSR was 0.76 ± 0.40 and the intraobserver LOAs were -0.372 to 0.395 (obs. 1) and -0.555 to 0.667 (obs. 2). For PFSR measurements by the same observer the ICC was 0.89 (obs. 1) and for measurements by two different observers the ICC was 0.65. Among aneuploid fetuses, IFA was below the normal range in one third of the cases with trisomy 18. PFSR was below the 95% prediction limit in 16.2% of fetuses with trisomy 21% and 17.9% of fetuses with trisomy 18. Conclusion IFA can be reliably measured in 2D ultrasound images in the first trimester of pregnancy with a high interobserver agreement and may provide information about retrognathia associated with various syndromes and aneuploidies at early stages of pregnancy.

Performance of computerized cardiotocography-based short-term variation in late-onset small-for-gestational-age fetuses and reference ranges for the late third trimester.

PURPOSE: Fetal Doppler changes are well characterized in early-onset small-for-gestational-age (SGA) and fetal growth restriction (FGR) but less well characterized where the condition is late-onset. The aim of the study was to evaluate the role of computerized CTG (cCTG)-based short-term variation (STV) in late-onset SGA and FGR as an additional monitoring modality and to establish STV reference ranges in late third trimester healthy pregnancies. METHODS: Of 86 late-onset SGA fetuses diagnosed after 32 weeks, 66 were diagnosed with FGR. 138 healthy pregnancies acted as controls. All underwent umbilical artery pulsatility index (PI), middle cerebral artery PI, cerebroplacental ratio and mean uterine artery PI. cCTG recordings were analyzed by Sonicaid FetalCare software for STV calculation as described by Dawes/Redman. RESULTS: Median interval between inclusion and delivery was 13 (interquantile range = 4-30) days in the FGR group, 22 (12-37) days in the SGA group and 25 (10-40) days in the control group. STV was not different between controls (11.2 ms, 9.7-13.1), late-onset SGA (11.2 ms, 8.1-12.6) and FGR (10.5 ms, 8.5-12.4) fetuses. A greater proportion of late-onset SGA fetuses had STV < 5th percentile (7/86) compared to controls (4/138) (8.1% vs. 2.9%, p = 0.077). In the control group a significant positive correlation was seen between STV, and 1-min (ρ = 0.195, p = 0.026), 5-min (ρ = 0.247, p = 0.004) and 10-min (ρ = 0.211, p = 0.014) Apgar values. CONCLUSIONS: We report no significant difference in STV median values between controls, SGA and FGR pregnancies. However, more SGA fetuses had a low STV compared to controls. Prospective longitudinal studies are needed to investigate if low STV is a useful surveillance method for late-onset FGR.