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.

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.

Prediction of adverse perinatal outcome and the mean time until delivery in twin pregnancies with suspected pre-eclampsia using sFlt-1/PIGF ratio.

PURPOSE: An elevated soluble fms-like tyrosine kinase-1 (sFlt-1) / placental growth factor (PlGF) ratio is associated with adverse perinatal outcome (APO) and the mean time until delivery (MTUD) in singleton pregnancies complicated by pre-eclampsia (PE). Data on APO and MTUD prediction in twin pregnancies using sFlt-1/PlGF ratio are scarce. We evaluated the predictive value of the sFlt-1/PIGF ratio regarding APO and MTUD in twin pregnancies with suspected PE and/or HELLP syndrome. METHODS: This is a single center retrospective cohort study. All twin pregnancies with suspected PE/HELLP and determined sFlt-1/PIGF were included. Composite APO (CAPO) was defined as the presence of at least one of the following outcomes: respiratory distress syndrome (RDS), intubation, admission to neonatal intensive care unit (NICU) and arterial umbilical cord pH value < 7.10. Selective fetal growth restriction (s-FGR) was analyzed separately. RESULTS: For final analysis, 49 twin pregnancies were included. Median sFlt-1/PIGF ratio was not significantly different in patients with CAPO compared to those without (89.45 vs. 62.00, p = 0.669). MTUD was significantly negative correlated with sFlt-1/PIGF ratio (r = -0.409, p < 0.001). For the whole study cohort, ROC analysis revealed no predictive value for sFlt-1/PIGF and CAPO (AUC = 0.618, 95% CI: 0.387-0.849, p = 0.254). However, sFlt-1/PIGF ratio showed a predictive value for s-FGR (AUC = 0.755, 95% CI: 0.545-0.965, p = 0.032). CONCLUSION: In twin pregnancies with PE and/or HELLP, sFlt-1/PIGF ratio may be helpful for s-FGR prediction and decision-making regarding close monitoring of high-risk patients. However, further prospective studies are warranted to define the role of sFlt-1/PlGF ratio as outcome predictor in twin pregnancies.

Role of sFlt-1/PIGF ratio and uterine Doppler in pregnancies with chronic kidney disease suspected with Pre-eclampsia or HELLP syndrome.

PURPOSE: Pregnancies of women with chronic kidney disease (CKD) are at higher risk of experiencing adverse perinatal (APO) and maternal outcome (AMO). Mean uterine artery pulsatility index (mUtA-PI) as well as the ratio of soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) are helpful tools in diagnosing pre-eclampsia (PE) in women with CKD. The aim of the study was to evaluate the role of sFlt-1/PIGF ratio and mUtA-PI as predictors for APO, AMO, preterm delivery and decline of kidney function in CKD pregnancies. METHODS: A total of 28 CKD pregnancies with suspected PE/HELLP syndrome were retrospectively included, in whom both sFlt-1/PIGF and mUtA-PI were determined during the third trimester. APO was defined as fetal growth restriction, respiratory distress syndrome, intubation, admission to NICU, 5 min Apgar <7 and intracerebral hemorrhage. AMO was defined as the development of PE, HELLP syndrome or resistant hypertension. Decline of kidney function was defined as a 25% increase of creatinine level after delivery. RESULTS: Of all included women, eight (28.6%) developed a PE/HELLP syndrome. AMO (28.6%) and APO (32.1%) were frequently observed. ROC analyses revealed a predictive value for AMO and sFlt-1/PIGF or mUtA-PI. Neither sFlt-1/PIGF nor mUtA-PI could predict APO or decline of postnatal kidney function. mUtA-PI was a predictor for preterm delivery. CONCLUSION: Uterine Doppler and sFlt-1/PIGF are predictors of AMO in CKD pregnancies. Therefore, both markers might be helpful for an improved risk assessment. However, neither sFlt-1/PIGF nor mUtA-PI were able to predict a decline of postnatal kidney function or APO.

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.

[Maternal Tumor Disease as a Reason for Repeated Test Failure in Cell-Free DNA Screening]. / Mütterliches Malignom in der Schwangerschaft als Ursache eines wiederholten Testversagens im nicht-invasiven Pränataltest.

Noninvasive prenatal testing (NIPT) is a screening test for fetal chromosome disorders. Recent studies show an incidental detection of maternal malignancies in NIPT diagnostics, where the simultaneous presence of multiple aneuploidies is described as an NIPT "anomaly". In this case, the diagnosis of a maternal tumor disease was made due to a repeat NIPT failure (no call).

Application of the INTERGROWTH-21st chart compared to customized growth charts in fetuses with left heart obstruction: late trimester biometry, cerebroplacental hemodynamics and perinatal outcome.

PURPOSE: Birth weight (BW) is crucial for surgical outcome in children with left heart obstruction (LHO). Head circumference (HC) is believed to correlate with the neurocognitive outcome in LHO. Our aim was to investigate the application of international standardized growth charts from the INTERGROWTH-21st project in comparison to customized growth charts in fetal LHO. METHODS: This is a retrospective cohort study consisting of 60 singleton pregnancies complicated by fetal LHO. For the z score calculation of estimated fetal weight (EFW) and biometric parameters, the INTERGROWTH-21st calculator was used as well as algorithms of customized growth charts. Antenatal measurements were compared to newborn biometry and the association with fetal Doppler results (MCA PI: middle cerebral artery pulsatility index and CPR: cerebroplacental ratio) was examined. Furthermore, the ability of each antenatal chart to predict adverse perinatal outcome was evaluated. RESULTS: At a mean gestational age of 37 weeks, all assessment charts showed significantly smaller mean values for antenatal head circumference (HC) z scores. Highest detection rate for restricted HC growth antenatally was achieved with Hadlock charts. MCA PI and CPR were not associated with neonatal HC. A significant association was observed between EFW and 1-year survival, independent of the considered growth chart. CONCLUSIONS: Growth chart independently, antenatal HC did tend to be smaller in LHO fetuses. A significant association was observed between EFW and 1-year survival rate. Prospective investigations in CHD fetuses should be carried out with internationally standardized growth charts to better examine their prognostic value in this high-risk population.

Metalloporphyrins, used for HO-1 inhibition, themselves affect hepatic microcirculation, liver function, and hepatocellular integrity.

BACKGROUND: Metalloporphyrins (MPs) are broadly used in the studies of the role of the heme oxygenase (HO)-1 system in different stress models. However, possible side effects of the MP administration itself have to be further investigated. METHODS: Sin IV mesoporpyhrin IX (SnMP; 10 micromol/kg body weight), tin protoporpyhrin IX (SnPP; 50 micromol/kg body weight), or chromium mesoporpyhrin IX (CrMP; 40 micromol/kg body weight) were administered to Sprague-Dawley rats (each group, n=5). The hepatic microcirculation was assessed by intravital microscopy (IVM). Blood samples were taken and the activity of HO-1 inhibition was measured by the determination of bilirubin accumulation after bile duct ligation. RESULTS: CrMP administration led to a decrease in mean arterial pressure. CrMP induced a marked hemolysis, a significant decrease of sinusoidal diameter and blood flow, and a marked inflammatory response. SnMP decreased sinusoidal diameters; however, this was compensated by an increase of sinusoidal red blood cell velocity. SnPP, but not SnMP, led to an increase of the number of nonperfused sinusoids. SnPP and CrMP revealed a two-fold increase in aspartite aminotransferase values after the completion of the IVM. The administration of MPs led to a 40%-50% decrease in the levels of conjugated bilirubin therapy, indicating that they actually inhibit HO-1 activity. CONCLUSIONS: The administration of MPs affects both the systemic macrohemodynamics and the hepatic microcirculation. As SnMP displayed the smallest number of side effects, this MP can be recommended for the studies of the HO-1 action on the liver microcirculation.