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.

MacDonald TM ，Hui L ，Robinson AJ ，Dane KM ，Middleton AL ，Tong S ，Walker SP ... -  《-》

Perinatal loss at term: role of uteroplacental and fetal Doppler assessment.

To examine the associations of uterine artery (UtA) Doppler indices and cerebroplacental ratio (CPR) with perinatal outcome at term. This was a retrospective cohort study conducted at a tertiary referral center that included all singleton pregnancies undergoing ultrasound assessment in the third trimester that subsequently delivered at term. Fetal biometry and Doppler assessment, including that of the umbilical artery (UA), fetal middle cerebral artery (MCA) and UtA, were recorded. Data were corrected for gestational age, and CPR was calculated as the ratio of MCA pulsatility index (PI) to UA-PI. Logistic regression analysis was conducted to examine for independent predictors of adverse perinatal outcome. The study included 7013 pregnancies, 12 of which were complicated by perinatal death. When compared with pregnancies resulting in perinatal survival, pregnancies complicated by perinatal death had a significantly higher proportion of small-for-gestational-age infants (25.0% vs 5%; P = 0.001) and a higher incidence of low (< 5th centile) CPR (16.7% vs 4.5%; P = 0.041). A subgroup analysis comparing 1527 low-risk pregnancies that resulted in fetal survival with pregnancies complicated by perinatal death demonstrated that UtA-PI multiples of the median (MoM), CPR < 5th centile and estimated fetal weight (EFW) centile were all associated significantly with the risk of perinatal death at term (all P < 0.05). After adjusting for confounding variables, only EFW centile (odds ratio (OR) 0.96 (95% CI, 0.93-0.99); P = 0.003) and UtA-PI MoM (OR 13.10 (95%CI, 1.95-87.89); P = 0.008) remained independent predictors of perinatal death in the low-risk cohort. High UtA-PI at term is associated independently with an increased risk of adverse perinatal outcome, regardless of fetal size. These results suggest that perinatal mortality at term is related not only to EFW and fetal redistribution (CPR), but also to indices of uterine perfusion. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Monaghan C ，Binder J ，Thilaganathan B ，Morales-Roselló J ，Khalil A ... -  《-》

Value of third-trimester cerebroplacental ratio and uterine artery Doppler indices as predictors of stillbirth and perinatal loss.

Placental insufficiency contributes to the risk of stillbirth. Cerebroplacental ratio (CPR) is an emerging marker of placental insufficiency. The aim of this study was to evaluate the association of third-trimester fetal CPR, uterine artery (UtA) Doppler and estimated fetal weight (EFW) with stillbirth and perinatal death. This was a retrospective cohort study including 2812 women with a singleton pregnancy who underwent an ultrasound scan in the third trimester. EFWs were converted into centiles, and Doppler indices (UtA and CPR) were converted into multiples of the median (MoM), adjusting for gestational age. Regression analysis was performed to identify, and adjust for, potential confounders, and receiver-operating characteristics (ROC) curve analysis was used to assess the predictive value. When adjusting for EFW centile and UtA mean pulsatility index (UtA-PI) MoM, CPR-MoM remained an independent predictor of stillbirth (odds ratio (OR) = 0.003 (95% CI, 0.00-0.11), P = 0.003) and perinatal mortality (OR = 0.001 (95% CI, 0.00-0.03), P < 0.001). UtA-PI ≥ 1.5 MoM was significantly associated with low CPR-MoM, even after adjusting for EFW centile (OR = 5.22 (95% CI, 3.88-7.04), P < 0.001) or small-for-gestational age (SGA; OR = 4.73 (95% CI, 3.49-6.41), P < 0.001). These associations remained significant, even when excluding pregnancies with SGA or including only cases in which Doppler indices were recorded at term (P < 0.01). For prediction of stillbirth, the area under the ROC curve, using a combination of these three parameters, was 0.88 (95% CI, 0.77-0.99) with a sensitivity of 66.7%, specificity of 92.1%, positive likelihood ratio (LR) of 8.46 and negative LR of 0.36. Third-trimester CPR is an independent predictor of stillbirth and perinatal mortality. The role of UtA Doppler, CPR and EFW in assessing risk of adverse pregnancy outcome should be evaluated prospectively.

Khalil A ，Morales-Roselló J ，Townsend R ，Morlando M ，Papageorghiou A ，Bhide A ，Thilaganathan B ... -  《-》

Prediction of adverse perinatal outcome by cerebroplacental ratio adjusted for estimated fetal weight.

To evaluate the relationship between cerebroplacental ratio (CPR) and estimated fetal weight (EFW) in low- and high-risk singleton pregnancies. Furthermore, we evaluated the role of CPR in the prediction of adverse perinatal outcome and whether CPR measurements adjusted for EFW improve its predictive value. This was a retrospective cohort study including pregnancies in which Doppler investigations of umbilical artery (UA) and fetal middle cerebral artery (MCA) were performed at ≥ 30 weeks' gestation. Pregnancies were allocated to one of three groups according to EFW centile: small-for-gestational age (SGA) with EFW < 10th centile, appropriate-for-gestational age (AGA) and large-for-gestational age (LGA) with EFW > 90th centile. CPR was calculated as the ratio between the UA pulsatility index (PI) and MCA-PI and converted to CPR multiples of the median (MoMs) according to the three EFW groups. Linear regression analysis was performed to evaluate the relationship between CPR-MoMs and EFW centiles in low-risk pregnancies. Furthermore, MoMs of CPR adjusted according to EFW centile (aCPR-MoMs) were calculated. Adverse perinatal outcome was defined as presence of pathological cardiotocography (CTG) trace, arterial cord blood pH < 7.1, 5-min Apgar score < 7 and presence of meconium-stained amniotic fluid (MSAF). A total of 3515 (3016 low risk and 499 high risk) pregnancies, delivered between January 2010 and March 2016, were included. Linear regression analysis revealed a significant positive correlation between EFW centile and CPR-MoM. Receiver-operating characteristics (ROC) curve analysis showed a significant association between CPR-MoM and pathological CTG trace (AUC, 0.539; SD, 0.014; P = 0.005) and low Apgar score (AUC, 0.609; SD, 0.041; P = 0.008), but not with low arterial pH or MSAF. There was a significant association between aCPR-MoM and pathological CTG trace (AUC, 0.540; SD, 0.014; P = 0.003), low arterial cord blood pH (AUC, 0.546; SD, 0.022; P = 0.035) and low Apgar score (AUC, 0.609; SD, 0.044; P = 0.008), but not with MSAF. However, detection rates for adverse perinatal outcomes by CPR-MoM and aCPR-MoM were low, ranging from 6.7% to 28.6% for SGA, 12.1% to 22.2% for AGA and 0% to 33.3% for LGA, for a false-positive rate of 10%. In a subgroup analysis of cases in which ultrasound examination was performed at ≥ 34 weeks of gestation and within 4 weeks of delivery (n = 1439), the ROC curves for aCPR-MoM were significantly associated with all four outcomes evaluated. CPR-MoM values are dependent on EFW centiles; therefore, we suggest that CPR-MoM should be adjusted for EFW centile. However, both CPR- and aCPR-MoM showed a low prediction rate for adverse perinatal outcome. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Sirico A ，Diemert A ，Glosemeyer P ，Hecher K ... -  《-》

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.

Binder J ，Monaghan C ，Thilaganathan B ，Morales-Roselló J ，Khalil A ... -  《-》