Cerebroplacental Ratio Multiples Of The Median Research Articles

MicroRNA-132 is overexpressed in fetuses with late-onset fetal growth restriction.

Background and AimsTo evaluate the expression of microRNA 132 (miR‐132) in fetuses with normal growth and in fetuses with late‐onset growth restriction (FGR).MethodsIn a prospective cohort study, 48 fetuses (24 with late‐onset FGR and 24 with normal growth) were scanned with Doppler ultrasound after 34 weeks to measure the umbilical artery and middle cerebral artery pulsatility indices and followed until birth. Subsequently, blood samples from the umbilical cord were collected to evaluate the expression of miR‐132 by means of Real‐time quantitative polymerase chain reaction, determining the existence of normality cut‐offs and associations with birth weight (BW) centile, cerebroplacental ratio multiples of the median (CPR MoM), and intrapartum fetal compromise (IFC).ResultsIn comparison with normal fetuses, late‐onset FGR fetuses showed upregulation of miR‐132 (33.94 ± 45.04 vs. 2.88 ± 9.32 2−ddC t, p < 0.001). Using 5 as a cut‐off we obtained a sensitivity of 50% and a specificity of 96% for the diagnosis of FGR, while for IFC these values were respectively 27% and 73%. Expression of miR‐132 was associated with BW centile but not with CPR MoM. Finally, the best detection of IFC was achieved combining miR‐132 expression and CPR MoM (AUC = 0.69, p < 0.05).ConclusionFetuses with late‐onset FGR show upregulation of miR‐132. Further studies are needed to investigate the role of miR‐132 in the management of late‐onset FGR.

Predictors of adverse perinatal outcome up to 34 weeks, a multivariable analysis study

The objective was to evaluate the best predictors of adverse perinatal outcome (APO) in foetuses examined up to 34 weeks and delivered by spontaneous or induced labour. This was a retrospective study of 129 pregnancies that underwent an ultrasound Doppler examination at 23–34 weeks and entered into labour within 30 days. Cerebroplacental ratio (CPR) and mean uterine artery pulsatility index (mUtA PI) were converted into multiples of the median (MoM) and estimated foetal weight (EFW) into centiles to adjust for gestational age (GA). Sonographic and clinical parameters were evaluated using logistic regression analysis. The multivariable model for the prediction of APO presented a notable accuracy: Detection rate (DR) was 39.5% for a false positive rate (FPR) of 5% and 56.8% for a FPR of 10%, AUC 0.82, p < .0001. Significant predictors were GA, EFW centile, and CPR MoM, but not mUtA PI MoM. Moreover, the type of labour onset did not exert any influence on APO. In conclusion, up to 34 weeks, prediction of APO after spontaneous or induced labour may be done measuring CPR and EFW. IMPACT STATEMENT What is already known on this subject? Earlier in pregnancy, foetal growth restriction is caused by placental disease causing progressive hemodynamic changes. These changes have been exhaustively described. Conversely, information about the best predictors of adverse outcome is scarce. What do the results of this study add? The findings of this study show that prior to 34 weeks and up to 1 month before labour, labour outcome might be predicted by gestational age, foetal cerebroplacental ratio (CPR) and estimated foetal weight (EFW). What are the implications of these findings for clinical practice and/or further research? If CPR behaves as a good marker of outcome not only at the end of pregnancy but also earlier in gestation, it might be interrogated along with EFW in foetuses attempting vaginal delivery to determine the risk of adverse outcome.

The Diagnostic Ability of the Cerebroplacental Ratio for the Prediction of Adverse Perinatal Outcome and Intrapartum Fetal Compromise within One Day of Delivery

Objectives: The objectives of this study were to evaluate the diagnostic abilities of the cerebroplacental ratio (CPR) for the prediction of adverse perinatal outcome (APO) and cesarean section for intrapartum fetal compromise (CS-IFC) within 1 day of delivery. Design: Retrospective observational case-control study. Methods: This was a study of 254 high-risk fetuses attending the day hospital unit of a tertiary referral hospital that underwent an ultrasound examination at 32–41 weeks and gave birth within 1 day of examination. APO was defined as a composite of abnormal intrapartum fetal heart rate or intrapartum fetal scalp pH <7.20 requiring urgent cesarean section, neonatal umbilical cord pH <7.10, 5-min Apgar score <7, and postpartum admission to neonatal or pediatric intensive care units. CS-IFC was defined in case of abnormal intrapartum fetal heart rate or intrapartum fetal scalp pH <7.20 requiring urgent cesarean section. The diagnostic ability of CPR for the prediction of APO and CS-IFC was calculated alone and in combination with estimated fetal weight and gestational clinical parameters, including the type of labor onset, using ROC curves and logistic regression analysis. Results: CPR in multiples of the median (MoM) was a moderate predictor of APO (area under the curve [AUC] = 0.77, p < 0.0001) and CS-IFC (AUC = 0.82, p < 0.0001). The predictive abilities of the multivariable model for APO (AUC = 0.81, p < 0.0001) and CS-IFC (AUC = 0.82, p < 0.0001) did not differ from those of CPR alone . Limitations: The small number of cases and the scarcity of information concerning labor induction. Conclusion: In high-risk pregnancies, CPR MoM is a moderate predictor of APO and CS-IFC when performed within 24 h of delivery.

Association between fetoplacental Doppler results, placental pathology, and angiogenic factors among pregnant women with anxiety

ObjectiveThis study aimed to evaluate whether state and trait anxiety among pregnant women were associated with fetoplacental Doppler findings, abnormal placental pathology, and placental angiogenic factors. Materials and methodsA total of 102 pregnant women at 32–35 gestational weeks were recruited and examined prospectively. State and trait anxiety were measured using the State-Trait Anxiety Inventory. Using Doppler ultrasound, pulsatility index (PI) of the umbilical artery (UA), middle cerebral artery (MCA), and uterine artery (UtA) and cerebroplacental ratio (CPR) were determined. Doppler parameters were converted into multiples of the median (MoM). Abnormal placental pathology was classified into 2 groups: vascular underperfusion (VU) and histological chorioamnionitis (HCA). Immunohistochemical analysis was performed to examine placental cells staining positive for placental growth factor (PLGF) and hypoxia-inducible factor-1-α (HIF-1α), which are markers for angiogenesis and hypoxic status, respectively. ResultsWomen with high state anxiety scores had low MCA-PI MoM and CPR MoM, while those with high trait anxiety scores had low MCA-PI MoM. VU was associated with a higher incidence of high trait anxiety scores, and HCA was associated with a higher incidence of high state and trait anxiety scores. Regression analysis showed a relationship between maternal state anxiety on MCA-PI MoM and HCA after controlling for covariates. Maternal trait anxiety exhibited relationships with VU and HCA after adjustment. ConclusionOur results demonstrated that maternal anxiety is associated with altered fetal cerebral blood flow and abnormal placental pathology but is not associated with uteroplacental insufficiency and placental angiogenic factors.

Prediction of adverse perinatal outcome by serum placental growth factor and soluble fms-like tyrosine kinase-1 in women undergoing induction of labor.

To investigate the additive value of serum placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1), measured within 24 h prior to induction of labor, to the performance of screening for adverse perinatal outcome provided by maternal risk factors and the cerebroplacental ratio (CPR). This was a prospective observational study of 795 singleton pregnancies undergoing induction of labor at ≥ 37 weeks' gestation. Before induction of labor, Doppler ultrasound was used to measure the pulsatility index (PI) in the umbilical artery (UA) and fetal middle cerebral artery (MCA) and maternal blood was obtained for measurement of serum PlGF and sFlt-1. The measured UA-PI, MCA-PI and their ratio (CPR) were converted to multiples of the median (MoM) after adjustment for gestational age, and the measured PlGF and sFlt-1 were converted to MoM after adjustment for gestational age, maternal characteristics and the machine used for the assays. Univariable and multivariable logistic regression analysis was used to determine factors that provided a significant contribution in the prediction of adverse perinatal outcome, defined as the presence of any one of Cesarean section for non-reassuring fetal status in labor, umbilical arterial or venous cord blood pH ≤ 7 and ≤ 7.1, respectively, 5-min Apgar score < 7 or admission to the neonatal intensive care unit for ≥ 24 h. The detection rate (DR) and false-positive rate (FPR) in screening for adverse perinatal outcome were determined. In pregnancies with adverse perinatal outcome, compared to those without, median serum PlGF MoM was lower (0.44; interquartile range (IQR), 0.30-0.82 vs 0.60; IQR, 0.36-1.07; P = 0.003), but median sFlt-1 MoM was not significantly different (P = 0.080). Multivariable regression analysis demonstrated that, in the prediction of adverse perinatal outcome, there was significant contribution from maternal risk factors and CPR MoM but not PlGF MoM or sFlt-1 MoM. The performance of screening for adverse perinatal outcome achieved by maternal risk factors alone (DR of 28.9% at FPR of 10%) was not improved by the addition of CPR (DR of 33.8% at FPR of 10%) (area under the curve, 0.702; 95%CI, 0.654-0.750 vs 0.712; 95%CI, 0.664-0.760; P = 0.233). Serum PlGF and sFlt-1, measured within 24 h prior to induction of labor, do not provide a significant additional contribution to maternal risk factors in the prediction of adverse perinatal outcome. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Cerebral-placental-uterine ratio as novel predictor of late fetal growth restriction: prospective cohort study.

Fetal growth restriction (FGR) is a major risk factor for stillbirth and most commonly arises from uteroplacental insufficiency. Despite clinical examination and third-trimester fetal biometry, cases of FGR often remain undetected antenatally. Placental insufficiency is known to be associated with altered blood flow resistance in maternal, placental and fetal vessels. The aim of this study was to evaluate the performance of individual and combined Doppler blood flow resistance measurements in the prediction of term small-for-gestational age and FGR. This was a prospective study of 347 nulliparous women with a singleton pregnancy at 36 weeks' gestation in which fetal growth and Doppler measurements were obtained. Pulsatility indices (PI) of the uterine arteries (UtA), umbilical artery (UA) and fetal vessels were analyzed, individually and in combination, for prediction of birth weight < 10th , < 5th and < 3rd centiles. Doppler values were converted into centiles or multiples of the median (MoM) for gestational age. The sensitivities, positive and negative predictive values and odds ratios (OR) of the Doppler parameters for these birth weights at ∼ 90% specificity were assessed. Additionally, the correlations between Doppler measurements and other measures of placental insufficiency, namely fetal growth velocity and neonatal body fat measures, were analyzed. The Doppler combination most strongly associated with placental insufficiency was a newly generated parameter, which we have named the cerebral-placental-uterine ratio (CPUR). CPUR is the cerebroplacental ratio (CPR) (middle cerebral artery PI/UA-PI) divided by mean UtA-PI. CPUR MoM detected FGR better than did mean UtA-PI MoM or CPR MoM alone. At ∼ 90% specificity, low CPUR MoM had sensitivities of 50% for birth weight < 10th centile, 68% for < 5th centile and 89% for < 3rd centile. The respective sensitivities of low CPR MoM were 26%, 37% and 44% and those of high UtA-PI MoM were 34%, 47% and 67%. Low CPUR MoM was associated with birth weight < 10th centile with an OR of 9.1, < 5th centile with an OR of 17.3 and < 3rd centile with an OR of 57.0 (P < 0.0001 for all). CPUR MoM was also correlated most strongly with fetal growth velocity and neonatal body fat measures, as compared with CPR MoM or UtA-PI MoM alone. In this cohort, a novel Doppler variable combination, the CPUR (CPR/UtA-PI), had the strongest association with indicators of placental insufficiency. CPUR detected more cases of FGR than did any other Doppler parameter measured. If these results are replicated independently, this new parameter may lead to better identification of fetuses at increased risk of stillbirth that may benefit from obstetric intervention. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Does Uterine Doppler Add Information to the Cerebroplacental Ratio for the Prediction of Adverse Perinatal Outcome at the End of Pregnancy?

Objective: To evaluate whether the addition of the mean uterine arteries pulsatility index (mUtA PI) to the cerebroplacental ratio (CPR) improves its ability to predict adverse perinatal outcome (APO) at the end of pregnancy. Methods: This was a prospective study of 891 fetuses that underwent an ultrasound examination at 34–41 weeks. The CPR and the mUtA PI were converted into multiples of the median (MoM) and the estimated fetal weight (EFW) into centiles according to local references. APO was defined as a composite of abnormal cardiotocogram, intrapartum pH requiring cesarean section, 5′ Apgar score <7, neonatal pH <7.10 and admission to pediatric care units. The accuracies of the different parameters were evaluated alone and in combination with gestational characteristics using univariate and multivariate analyses by means of the Akaike Information Criteria (AIC) and the area under the curve (AUC). Finally, a comparison was similarly performed between the CPR and the cerebro-placental-uterine ratio (CPUR; CPR/mUtA PI) for the prediction of APO. Results: The univariate analysis showed that CPR MoM was the best parameter predicting APO (AIC 615.71, AUC 0.675). The multivariate analysis including clinical data showed that the best prediction was also achieved with the CPR MoM (AIC 599.39, AUC 0.718). Moreover, when EFW centiles were considered, the addition of UtA PI MoM did not improve the prediction already obtained with CPR MoM (AIC 591.36, AUC 0.729 vs. AIC 589.86, AUC 0.731). Finally, the prediction by means of CPUR did not improve that of CPR alone (AIC 623.38, AUC 0.674 vs. AIC 623.27, AUC 0.66). Conclusion: The best prediction of APO at the end of pregnancy is obtained with CPR whatever is the combination of parameters. The addition of uterine Doppler to the information yielded by CPR does not result in any prediction improvement.

Cerebroplacental ratio assessment in early labor in uncomplicated term pregnancy and prediction of adverse perinatal outcome: prospective multicenter study.

It has been suggested that the use of Doppler ultrasound in term pregnancies with normal-sized fetuses is able to identify those at high risk of subclinical placental function impairment. The objective of this study was to evaluate the relationship between cerebroplacental ratio (CPR) measured in early labor and perinatal and delivery outcomes in a cohort of uncomplicated singleton term pregnancies. This was a prospective multicenter observational study conducted at three tertiary centers between January 2016 and July 2017. Low-risk term pregnancies, defined by the absence of maternal morbidity or pregnancy complication, accompanied by normal ultrasound and clinical screening of fetal growth in the third trimester, with spontaneous onset of labor were included. Umbilical artery (UA) and fetal middle cerebral artery (MCA) Doppler was assessed on admission for early labor. All measurements were performed in between uterine contractions and according to international standards. CPR was computed by dividing MCA pulsatility index by UA pulsatility index and converted into multiples of the median (MoM) in order to adjust for gestational age. Doctors and midwives involved in the clinical management of the women were blinded to the results of the Doppler evaluation. Mode of delivery and perinatal outcome were compared between pregnancies with reduced CPR MoM, defined as CPR MoM within the lowest decile of the study population, and those with normal CPR MoM. Receiver-operating characteristics curve analysis was used to assess the predictive performance of CPR for obstetric intervention due to fetal distress and composite adverse perinatal outcome. Overall, 562 women were included. The rate of obstetric intervention for suspected fetal distress in labor was more than three times higher among cases with reduced CPR MoM compared to those with normal CPR MoM (9/54 (16.7%) vs 28/508 (5.5%); P= 0.004). Furthermore, a significantly higher rate of composite adverse perinatal outcome was found in fetuses with CPR MoM < 10th percentile compared to those with CPR MoM ≥ 10th percentile (6/54 (11.1%) vs 19/508 (3.7%); P= 0.012). CPR had low sensitivity and low positive predictive value for prediction of obstetric intervention due to fetal distress (24.3% and 18.0%, respectively) and composite adverse perinatal outcome (24.0% and 11.1%, respectively). Data on a wide cohort of low-risk term pregnancies in early labor showed that, while reduced CPR is associated with a higher risk of obstetric intervention due to fetal distress and composite adverse perinatal outcome, it is a poor predictor of adverse perinatal outcome. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Reduced fetal movements and cerebroplacental ratio: evidence for worsening fetal hypoxemia.

To investigate the fetal cerebroplacental ratio (CPR) in women presenting with reduced fetal movements (RFM). This was a retrospective cohort study of data collected over an 8-year period at a fetal medicine unit at a tertiary referral center. The cohort comprised 4500 singleton pregnancies presenting with RFM at or after 36 weeks' gestation and 1527 control pregnancies at a similar gestational age without RFM. Fetal biometry and Doppler parameters were recorded and converted into centiles and multiples of the median (MoM). CPR was defined as the ratio between the fetal middle cerebral artery (MCA) pulsatility index (PI) and the umbilical artery (UA) PI. Subgroup analysis for fetal size and for single vs multiple episodes of RFM was performed. Compared with controls, pregnancies with RFM had lower MCA-PI MoM (median, 0.95 vs 0.97; P< 0.001) and CPR MoM (median, 0.97 vs 0.99; P= 0.018). Compared with women presenting with single episodes of RFM, pregnancies with multiple episodes (≥ 2 episodes) had lower CPR MoM (median, 0.94 vs 0.98; P= 0.003). On subgroup analysis for fetal size, compared with controls, appropriate-for-gestational-age fetuses in the RFM group had lower MCA-PI MoM (median, 0.96 vs 0.97; P= 0.003) and higher rate of CPR below the 5th centile (5.3% vs 3.6%; P= 0.015). Logistic regression analysis demonstrated an association of risk of recurrent RFM with maternal age (OR, 0.96; 95% CI, 0.93-0.99), non-Caucasian ethnicity (OR, 0.72; 95% CI, 0.53-0.97), estimated fetal weight centile (OR, 1.01; 95% CI, 1.00-1.02) and CPR MoM (OR, 0.24; 95% CI, 0.12-0.47). Pregnancies complicated by multiple episodes of RFM show significantly lower CPR MoM and MCA-PI MoM compared with those with single episodes and controls. This is likely to be due to worsening fetal hypoxemia in women presenting with recurrent RFM. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Is cerebroplacental ratio a marker of impaired fetal growth velocity and adverse pregnancy outcome?

The cerebroplacental ratio has been proposed as amarker of failure to reach growth potential near term. Low cerebroplacental ratio, regardless of the fetal size, is independently associated with the need for operative delivery for presumed fetal compromise and with neonatal unit admission at term. The main aim of this study was to evaluate whether the cerebroplacental ratio at term is a marker of reduced fetal growth rate. The secondary aim was to investigate the relationship between a low cerebroplacental ratio at term, reduced fetal growth velocity, and adverse pregnancy outcome. This was a retrospective cohort study of singleton pregnancies in a tertiary referral center. The abdominal circumference was measured at 20-24 weeks' gestation and both abdominal circumference and fetal Dopplers recorded at or beyond 35 weeks, within 2 weeks of delivery. Abdominal circumference and birthweight values were converted into Z scores and centiles, respectively, and fetal Doppler parameters into multiples of median, adjusting for gestational age. Abdominal circumference growth velocity was quantified using the difference in the abdominal circumference Z score, comparing the scan at or beyond 35 weeks with the scan at 20-24 weeks. Both univariable and multivariable logistic regression analyses were performed to investigate the association between low cerebroplacental ratio and the low abdominal circumference growth velocity (in the lowest decile) and to identify and adjust for potential confounders. As a sensitivity analysis, we refitted the model excluding the data on pregnancies with small-for-gestational-age neonates. The study included 7944 pregnancies. Low cerebroplacental ratio multiples of median was significantly associated with both low abdominal circumference growth velocity (adjusted odds ratio, 2.10; 95% confidence interval, 1.71-2.57, P <0.001) and small for gestational age(adjusted odds ratio, 3.60; 95% confidence interval, 3.04-4.25, P<.001). After the exclusion of pregnancies resulting in small-for-gestational-age neonates, a low cerebroplacental ratio multiples of the median remained significantly associated with both low abdominal circumference growth velocity (adjusted odds ratio, 1.76; 95% confidence interval, 1.34-2.30, P < .001) and birthweight centile (adjusted odds ratio, 0.99; 95% confidence interval, 0.998-0.995, P < .001). The need for operative delivery for fetal compromise was significantly associated with a low cerebroplacental ratio (adjusted odds ratio, 1.40; 95% confidence interval, 1.10-1.78, P= .006), even after adjusting for both the umbilical artery pulsatility index multiples of the median and middle cerebral artery pulsatility index multiples of median. The results were similar, even after the exclusion of pregnancies resulting in small-for-gestational-age neonates (adjusted odds ratio, 1.39; 95% confidence interval, 1.06-1.84, P= .018). Low cerebroplacental ratio multiples of the median remained significantly associated with the risk of operative delivery for presumed fetal compromise (P < .001), even after adjusting for the known antenatal and intrapartum risk factors. These associations persisted, even after the exclusion of small-for-gestational-age births. In appropriate-for-gestational-age-sized fetuses, abdominal circumference growth velocity was significantly lower in those with a low cerebroplacental ratio multiples of the median than in those with normal cerebroplacental ratio multiples of the median (P < .001). The cerebroplacental ratio is a marker of impaired fetal growth velocity and adverse pregnancy outcome, even in fetuses whose size is considered appropriate using conventional biometry.

The vertebroplacental ratio as an alternative to the cerebroplacental ratio in the evaluation of the fetus at the end of pregnancy

Objective: Low cerebroplacental ratio (CPR) near term has emerged as a marker of fetal adverse outcome. The aim of this study was to evaluate the predictive accuracy of an alternative ratio using the vertebral artery (VA) (vertebroplacental ratio or VPR) for acid–base status at birth.Methods: This was a prospective cohort study of 1470 pregnancies undergoing an ultrasound assessment of the umbilical artery, middle cerebral artery and VA Doppler beyond 34 weeks’ gestation within 14 days of delivery. The CPR multiples of the median (MoM) and VPR MoM were calculated to adjust for gestational age. The relationship between the fetal Dopplers and the umbilical cord pH (arterial and venous) was evaluated statistically, and depicted graphically using three-dimensional (3D) trend surfaces, 2D contour graphs and ROC curves.Results: All the studied parameters were poorly associated with neonatal acid–base status, although this association was slightly better for venous pH. The importance of BW centile was smaller than that of CPR and VPR MoM, however, both hemodynamic parameters were similarly associated with neonatal pH.Conclusions: Concerning fetal surveillance near term, the importance of cerebroplacental hemodynamics surpasses that of BW. Furthermore, in the evaluation of fetal wellbeing VPR behaves as a valid alternative to CPR.

Protein S100β in Late-Pregnancy Fetuses with Low Birth Weight and Abnormal Cerebroplacental Ratio

Objective: To evaluate the umbilical cord venous S100β levels in late-pregnancy fetuses with abnormal growth and cerebral redistribution. Methods: The pulsatility index of the umbilical and middle cerebral arteries and the cerebroplacental ratio (CPR) were measured in 132 fetuses at ≥34 weeks, and the CPR was converted into multiples of the median (MoM). A blood sample from the umbilical vein was collected at birth, and the umbilical venous S100β levels were evaluated in small and non-small for gestational age (SGA) fetuses, with and without abnormal Doppler indices. The levels of S100β were correlated with birth weight (BW) centile, CPR MoM and cord venous pH. Results: While CPR MoM correlated with BW centile, S100β showed no correlation with any of the studied fetal parameters. In addition, no differences were observed in S100β level according to BW centile or Doppler parameters, neither was there any difference between SGA with low CPR MoM and non-SGA with normal CPR MoM. Conclusion: Late-pregnancy fetuses with abnormal growth or cerebral redistribution have normal cord blood levels of S100β at birth. In these fetuses, the potential consequences of chronic hypoxemia on the fetal brain might not be detectable using tissue necrosis markers.

Fetal tricuspid annulus plane systolic excursion (fTAPSE) at term – association with cerebroplacental ratio, birthweight and neonatal pH

Objective: To study at term the association of the fetal tricuspid annulus plane systolic excursion (fTAPSE) with gestational age (GA), birthweight (BW), cerebroplacental ratio (CPR) and neonatal pH.Methods: fTAPSE was evaluated in 309 fetuses in relation with GA and BW. Standardized values for fetal size using the head circumference were also studied in relation with CPR multiples of the median (MoM) and BW centile, evaluating the existence of differences in small-for-gestational-age (SGA) fetuses and in fetuses with low CPR. In addition, in a subgroup of 286 fetuses, standardized fTAPSE was evaluated according to neonatal venous and arterial pH.Results: fTAPSE correlated with BW but not with GA. In addition, although standardized values correlated with BW centile and CPR MoM, they did not differ either in SGA fetuses or in fetuses with abnormal CPR. Finally, no correlation was found between fTAPSE and neonatal pH.Conclusions: In the term fetus, fTAPSE changes with absolute fetal weight, reflecting the physiological variations occurring with fetal size. However, it is very scarcely influenced by fetal Doppler or BW centile and does not associate with neonatal pH. These data support the idea that the fetal heart is not a valuable target in the study of late-onset growth restriction.

Neonatal Acid-Base Status in Fetuses with Abnormal Vertebro- and Cerebro-Placental Ratios

Objective: A low cerebro-placental ratio (CPR) at term suggests the existence of failure to reach growth potential (FRGP) with a higher risk of poor neonatal acid-base status. This study aimed to evaluate whether similar findings were also seen in the vertebral artery (vertebro-placental ratio, VPR), supplying 30% of the cerebral flow. Methods: We studied term fetuses classified into groups according to birth weight (BW), CPR and VPR. BW was expressed in centiles and ratios in multiples of the median (MoM). Subsequently, associations with neonatal pH values were evaluated by means of regression curves and Mann-Whitney tests. Results: VPR MoM correlated with BW centiles (p < 0.0001, R² = 0.042) and its distribution resembled that of CPR MoM (p < 0.001). When both arteries were compared, adequate-for-gestational-age (AGA) fetuses with either low CPR or low VPR had lower neonatal venous pH values (p < 0.05, p < 0.01, respectively). However, in case of small-for-gestational-age (SGA) fetuses, only those with low VPR had significantly lower neonatal arterial and venous pH values (p < 0.05). Conclusions: Blood flow in the vertebral artery mimics that in the middle cerebral artery supporting the FRGP model. Both CPR and VPR identify AGA fetuses with lower neonatal pH values, but only VPR identifies SGA with lower pH values. Hypoxemia might be reflected as a generalized cerebral vasodilation demonstrated as low CPR and VPR.

Discordance in fetal biometry and Doppler are independent predictors of the risk of perinatal loss in twin pregnancies

Impaired fetal growth might be better evaluated in twin pregnancies by assessing the intertwin discordance rather than the individual fetal size. The aim of this study was to investigate the prediction of perinatal loss in twin pregnancy using discordance in fetal biometry and Doppler. This was a retrospective cohort study in a tertiary referral center. The estimated fetal weight (EFW), umbilical artery (UA) pulsatility index (PI), middle cerebral artery (MCA) PI, cerebroplacental ratio (CPR), and their discordance recorded at the last ultrasound assessment before delivery or demise of one or both fetuses were converted into centiles or multiples of the median (MoM). The discordance was calculated as the larger value-smaller value/larger value. A logistic regression analysis was performed to identify, and adjust for, potential confounders. The predictive accuracy was assessed using receiver-operating characteristic curve analysis. The analysis included 620 (464 dichorionic diamniotic and 156 monochorionic diamniotic) twin pregnancies (1240 fetuses). Perinatal loss of one or both fetuses complicated 16 pregnancies (2.6%). The combination of EFW discordance and CPR discordance had the best predictive performance (area under the curve, 0.96; 95% confidence interval, 0.92-1.00) for perinatal mortality. The detection rate, false-positive rate, positive likelihood ratio, and negative likelihood ratio were 87.5%, 6.7%, 13.08, and 0.13, respectively. The EFW centile, EFW below the 10th centile (small for gestational age), UA PI discordance, MCA PI discordance, and MCA PI MoM were significantly associated with the risk of perinatal loss on univariate analysis, but these associations became nonsignificant after adjusting for other confounders (P = .097, P = .090, P = .687, P = .360, and P = .074, respectively). The UA PI MoM, CPR MoM, EFW discordance, and CPR discordance were all independent predictors of the risk of perinatal loss, even after adjusting for potential confounders (P = .022, P = .002, P < .001, and P = .010, respectively). EFW discordance and CPR discordance are independent predictors of the risk of perinatal loss in twin pregnancies. Their combination could identify the majority of twin pregnancies at risk of perinatal loss. These findings highlight the importance of discordance in Doppler indices of fetal hypoxia, as well as fetal size, in assessing the risk of perinatal mortality.

Changes in fetal Doppler indices as a marker of failure to reach growth potential at term

To evaluate whether changes in the middle cerebral artery (MCA), umbilical artery (UA) and cerebroplacental ratio (CPR) Doppler indices at term might be used to identify those appropriate-for-gestational-age (AGA) fetuses that are failing to reach their growth potential (FRGP). This was a retrospective cohort study of data obtained in a single tertiary referral center over a 10-year period from 2002 to 2012. The UA pulsatility index (PI), MCA-PI and CPR were recorded between 37+0 and 41+6 weeks within 14 days before delivery. The Doppler parameters were converted into multiples of the median (MoM), adjusting for gestational age, and their correlation with birth-weight (BW) centiles was evaluated by means of regression analysis. Doppler indices were also grouped according to BW quartiles and compared using Kruskal-Wallis and Dunn's post-hoc tests. The study included 11576 term fetuses, with 8645 (74.7%) classified as AGA. Within the AGA group, fetuses with lower BW had significantly higher UA-PI, lower MCA-PI and lower CPR MoM values. Large-for-gestational-age (LGA) fetuses were considered as the group least likely to be growth-restricted. The CPR MoM < 5(th) centile (0.6765 MoM) in these fetuses was used as a threshold for diagnosing FRGP. Using this definition, in the AGA pregnancies the percentage of fetuses with FRGP was 1% in the 75-90(th) BW centile group, 1.7% in the 50-75(th) centile group, 2.9% in the 25-50(th) centile group and 6.7% in the 10-25(th) centile group. AGA pregnancies may present with fetal cerebral and placental blood flow redistribution indicative of fetal hypoxemia. Fetal Doppler assessment may be of value in detecting AGA pregnancies that are subject to placental insufficiency, fetal hypoxemia and FRGP. Future studies are needed to evaluate the appropriate threshold for the diagnosis of FRGP and the diagnostic performance of this new approach for the management of growth disorders.

Reproducibility of the ventilatory response of the newborn to carbon dioxide during sleep : G. Cohen, C. Xu and D.J. Henderson-Smart, (Introduced by A. Wilkinson), Perinatal Medicine, King George V Hospital, Sydney, Australia

The cerebroplacental ratio has been proposed as a marker of failure to reach growth potential near term. Low cerebroplacental ratio, regardless of the fetal size, is independently associated with the need for operative delivery for presumed fetal compromise and with neonatal unit admission at term.The main aim of this study was to evaluate whether the cerebroplacental ratio at term is a marker of reduced fetal growth rate. The secondary aim was to investigate the relationship between a low cerebroplacental ratio at term, reduced fetal growth velocity, and adverse pregnancy outcome.This was a retrospective cohort study of singleton pregnancies in a tertiary referral center. The abdominal circumference was measured at 20–24 weeks’ gestation and both abdominal circumference and fetal Dopplers recorded at or beyond 35 weeks, within 2 weeks of delivery. Abdominal circumference and birthweight values were converted into Z scores and centiles, respectively, and fetal Doppler parameters into multiples of median, adjusting for gestational age. Abdominal circumference growth velocity was quantified using the difference in the abdominal circumference Z score, comparing the scan at or beyond 35 weeks with the scan at 20–24 weeks. Both univariable and multivariable logistic regression analyses were performed to investigate the association between low cerebroplacental ratio and the low abdominal circumference growth velocity (in the lowest decile) and to identify and adjust for potential confounders. As a sensitivity analysis, we refitted the model excluding the data on pregnancies with small-for-gestational-age neonates.The study included 7944 pregnancies. Low cerebroplacental ratio multiples of median was significantly associated with both low abdominal circumference growth velocity (adjusted odds ratio, 2.10; 95% confidence interval, 1.71–2.57, P <0.001) and small for gestational age (adjusted odds ratio, 3.60; 95% confidence interval, 3.04–4.25, P < .001). After the exclusion of pregnancies resulting in small-for-gestational-age neonates, a low cerebroplacental ratio multiples of the median remained significantly associated with both low abdominal circumference growth velocity (adjusted odds ratio, 1.76; 95% confidence interval, 1.34–2.30, P < .001) and birthweight centile (adjusted odds ratio, 0.99; 95% confidence interval, 0.998–0.995, P < .001). The need for operative delivery for fetal compromise was significantly associated with a low cerebroplacental ratio (adjusted odds ratio, 1.40; 95% confidence interval, 1.10–1.78, P = .006), even after adjusting for both the umbilical artery pulsatility index multiples of the median and middle cerebral artery pulsatility index multiples of median. The results were similar, even after the exclusion of pregnancies resulting in small-for-gestational-age neonates (adjusted odds ratio, 1.39; 95% confidence interval, 1.06–1.84, P = .018). Low cerebroplacental ratio multiples of the median remained significantly associated with the risk of operative delivery for presumed fetal compromise (P < .001), even after adjusting for the known antenatal and intrapartum risk factors. These associations persisted, even after the exclusion of small-for-gestational-age births. In appropriate-for-gestational-age–sized fetuses, abdominal circumference growth velocity was significantly lower in those with a low cerebroplacental ratio multiples of the median than in those with normal cerebroplacental ratio multiples of the median (P < .001).The cerebroplacental ratio is a marker of impaired fetal growth velocity and adverse pregnancy outcome, even in fetuses whose size is considered appropriate using conventional biometry.