Management of fetuses with apparent normal growth and abnormal cerebroplacental ratio: A risk-based approach near term.

INTRODUCTION: Cerebroplacental ratio (CPR) has been shown to be an independent predictor of adverse perinatal outcome at term and a marker of failure to reach the growth potential (FRGP) regardless of fetal size, being abnormal in compromised fetuses with birthweight above the 10th centile. The main aim of this study was to propose a risk-based approach for the management of pregnancies with normal estimated fetal weight (EFW) and abnormal CPR near term. MATERIAL AND METHODS: This was a retrospective study of 943 pregnancies, that underwent an ultrasound evaluation of EFW and CPR at or beyond 34 weeks. CPR values were converted into multiples of the median (MoM) and EFW into centiles according to local references. Pregnancies were then divided into four groups: normal fetuses (defined as EFW ≥10th centile and CPR ≥0.6765 MoM), small for gestational age (EFW <10th centile and CPR ≥0.6765 MoM), fetal growth restriction (EFW <10th centile and CPR <0.6765 MoM), and fetuses with apparent normal growth (EFW ≥10th centile) and abnormal CPR (<0.6765 MoM), that present FRGP. Intrapartum fetal compromise (IFC) was defined as an abnormal intrapartum cardiotocogram or pH requiring cesarean delivery. Risk comparisons were performed among the four groups, based on the different frequencies of IFC. The risks of IFC were subsequently extrapolated into a gestational age scale, defining the optimal gestation to plan the birth for each of the four groups. RESULTS: Fetal growth restriction was the group with the highest frequency of IFC followed by FRGP, small for gestational age, and normal groups. The "a priori" risks of the fetal growth restriction and normal groups were used to determine the limits of two scales. One defining the IFC risk and the other defining the appropriate gestational age for delivery. Extrapolation of the risk between both scales placed the optimal gestational age for delivery at 39 weeks of gestation in the case of FRGP and at 40 weeks in the case of small for gestational age. CONCLUSIONS: Fetuses near term may be evaluated according to the CPR and EFW defining four groups that present a progressive risk of IFC. Fetuses in pregnancies complicated by FRGP are likely to benefit from being delivered at 39 weeks of gestation.

Deprived areas and adverse perinatal outcome: a systematic review.

PURPOSE: This systematic review aimed to assess if women living in deprived areas have worse perinatal outcomes than those residing in high-income areas. METHODS: Datasets of PubMed, ScienceDirect, CENTRAL, Embase, and Google Scholar were searched for studies comparing perinatal outcomes (preterm birth, small-for-gestational age, and stillbirth) in deprived and non-deprive areas. RESULTS: A total of 46 studies were included. The systematic review of the literature revealed a higher risk for adverse perinatal outcomes such as preterm birth, small for gestational age, and stillbirth in deprived areas. CONCLUSION: Deprived areas are associated with adverse perinatal outcomes. More multifactorial studies are needed to assess the weight of each factor that composes the socioeconomic gradient of health in adverse perinatal outcomes.

Comparison of ductus venosus Doppler and cerebroplacental ratio for the prediction of adverse perinatal outcome in high-risk pregnancies before and after 34 weeks.

INTRODUCTION: The objective of the study was to compare the accuracy of the ductus venosus pulsatility index (DV PI) with that of the cerebroplacental ratio (CPR) for the prediction of adverse perinatal outcome at two gestational ages: <34 and ≥34 weeks' gestation. MATERIAL AND METHODS: This was a retrospective study of 169 high-risk pregnancies (72 < 34 and 97 ≥ 34 weeks) that underwent an ultrasound examination of CPR, DV Doppler and estimated fetal weight at 22-40 weeks. The CPR and DV PI were converted into multiples of the median, and the estimated fetal weight into centiles according to local references. Adverse perinatal outcome was defined as a composite of abnormal cardiotocogram, intrapartum pH requiring cesarean delivery, 5' Apgar score <7, neonatal pH <7.10 and admission to neonatal intensive care unit. Values were plotted according to the interval to labor to evaluate progression of abnormal Doppler values, and their accuracy was evaluated at both gestational periods, alone and combined with clinical data, by means of univariable and multivariable models, using the Akaike information criteria (AIC) and the area under the curve (AUC). RESULTS: Prior to 34 weeks' gestation, DV PI was the latest parameter to become abnormal. However, it was a poor predictor of adverse perinatal outcome (AUC 0.56, 95% CI: 0.40-0.71, AIC 76.2, p > 0.05), and did not improve the predictive accuracy of CPR for adverse perinatal outcome (AUC 0.88, 95% CI: 0.79-0.97, AIC 52.9, p < 0.0001). After 34 weeks' gestation, the chronology of the DV PI and CPR anomalies overlapped, but again DV PI was a poor predictor for adverse perinatal outcome (AUC 0.62, 95% CI: 0.49-0.74, AIC 120.6, p > 0.05), that did not improve the CPR ability to predict adverse perinatal outcome (AUC 0.80, 95% CI: 0.67-0.92, AIC 106.8, p < 0.0001). The predictive accuracy of CPR prior to 34 weeks persisted when the gestational age at delivery was included in the model (AUC 0.91, 95% CI: 0.81-1.00, AIC 46.3, p < 0.0001, vs AUC 0.86, 95% CI: 0.72-1, AIC 56.1, p < 0.0001), and therefore was not determined by prematurity. CONCLUSIONS: CPR predicts adverse perinatal outcome better than DV PI, regardless of gestational age. Larger prospective studies are needed to delineate the role of ultrasound tools of fetal wellbeing assessment in predicting and preventing adverse perinatal outcome.

Cerebroplacental Ratio Prediction of Intrapartum Fetal Compromise according to the Interval to Delivery.

INTRODUCTION: A controversy exists about the accuracy of the cerebroplacental ratio (CPR) for the prediction of cesarean section for intrapartum fetal compromise (CS-IFC). Our aim was to evaluate whether the interval to delivery modifies the accuracy of CPR either as a single marker or combined with estimated fetal weight centile (EFWc), type of labor onset (TLO), and other clinical variables. METHODS: This was a multicenter retrospective study of 5,193 women with singleton pregnancies who underwent an ultrasound scan at 35+0-41+0 weeks and gave birth within 1 month of examination, at any of the participating hospitals in Spain, UK, and Italy. CS-IFC was diagnosed in case of an abnormal intrapartum fetal heart rate or intrapartum fetal scalp pH <7.20, requiring urgent cesarean section. The diagnostic ability of CPR in multiples of the median (CPR MoM) was evaluated at different intervals to delivery, alone and combined with EFWc, TLO, and other pregnancy data such as maternal age, maternal body mass index, parity, and fetal sex, for the prediction of CS-IFC by means of ROC curves and logistic regression analysis. RESULTS: The predictive ability of CPR MoM for CS-IFC worsened with the interval to delivery. In general, the best prediction was obtained prior to labor and by adding information related to EFWc and TLO (AUC 0.71 [95% CI: 0.64-0.79], 0.73 [95% CI: 0.66-0.80], and 0.75 [95% CI: 0.69-0.81]; p < 0.0001). Addition of more clinical data did not improve prediction. In addition, results did not vary when only cases with spontaneous onset of labor were studied. CONCLUSION: CPR MoM prediction of CS-IFC at the end of pregnancy worsens with the interval to delivery. Accordingly, it should be done in the short term and considering EFWc and TLO.

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 STATEMENTWhat 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.

Maternal and neonatal outcomes of pregnancies complicated by late fetal growth restriction undergoing induction of labor with dinoprostone compared with cervical balloon: A retrospective, international study.

INTRODUCTION: The aim of this study was to compare vaginal dinoprostone and mechanical methods for induction of labor (IOL) in pregnancies complicated by late fetal growth restriction. MATERIAL AND METHODS: Multicenter, retrospective, cohort study involving six referral centers in Italy and Spain. Inclusion criteria were pregnancies complicated by late fetal growth restriction as defined by Delphi consensus criteria. The primary outcome was the occurrence of uterine tachysystole; secondary outcomes were either cesarean delivery or operative vaginal delivery for non-reassuring fetal status, a composite score of adverse neonatal outcome and admission to neonatal intensive care unit (NICU). Univariate and multivariate logistic regression analysis was used to analyze the data. RESULTS: A total of 571 pregnancies complicated by late fetal growth restriction undergoing IOL (391 with dinoprostone and 180 with mechanical methods) were included in the analysis. The incidence of uterine tachysystole (19.2% vs. 5.6%; p = 0.001) was higher in women undergoing IOL with dinoprostone than in those undergoing IOL with mechanical methods. Similarly, the incidence of cesarean delivery or operative delivery for non-reassuring fetal status (25.6% vs. 17.2%; p = 0.027), composite adverse neonatal outcome (26.1% vs. 16.7%; p = 0.013) and NICU admission (16.9% vs. 5.6%; p < 0.001) was higher in women undergoing IOL with dinoprostone than in those undergoing IOL with mechanical methods. At logistic regression analysis, IOL with mechanical methods was associated with a significantly lower risk of uterine tachysystole (odds ratio 0.26, 95% confidence interval 0.13-0.54; p < 0.001). CONCLUSIONS: In pregnancies complicated by late fetal growth restriction, IOL with mechanical methods is associated with a lower risk of uterine tachysystole, cesarean delivery or operative delivery for non-reassuring fetal status, and adverse neonatal outcome compared with pharmacological methods.

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.

Comparison between Cerebroplacental Ratio and Umbilicocerebral Ratio in Predicting Adverse Perinatal Outcome in Pregnancies Complicated by Late Fetal Growth Restriction: A Multicenter, Retrospective Study.

INTRODUCTION: The role of cerebroplacental ratio (CPR) or umbilicocerebral ratio (UCR) to predict adverse intrapartum and perinatal outcomes in pregnancies complicated by late fetal growth restriction (FGR) remains controversial. METHODS: This was a multicenter, retrospective cohort study involving 5 referral centers in Italy and Spain, including singleton pregnancies complicated by late FGR, as defined by Delphi consensus criteria, with a scan 1 week prior to delivery. The primary objective was to compare the diagnostic accuracy of the CPR and UCR for the prediction of a composite adverse outcome, defined as the presence of either an adverse intrapartum outcome (need for operative delivery/cesarean section for suspected fetal distress) or an adverse perinatal outcome (intrauterine death, Apgar score <7 at 5 min, arterial pH <7.1, base excess of >-11 mEq/mL, or neonatal intensive care unit admission). RESULTS: Median CPR absolute values (1.11 vs. 1.22, p = 0.018) and centiles (3 vs. 4, p = 0.028) were lower in pregnancies with a composite adverse outcome than in those without it. Median UCR absolute values (0.89 vs. 0.82, p = 0.018) and centiles (97 vs. 96, p = 0.028) were higher. However, the area under the curve, 95% confidence interval for predicting the composite adverse outcome showed a poor predictive value: 0.580 (0.512-0.646) for the raw absolute values of CPR and UCR, and 0.575 (0.507-0.642) for CPR and UCR centiles adjusted for gestational age. The use of dichotomized values (CPR <1, UCR >1 or CPR <5th centile, UCR >95th centile) did not improve the diagnostic accuracy. CONCLUSION: The CPR and UCR measured in the week prior delivery are of low predictive value to assess adverse intrapartum and perinatal outcomes in pregnancies with late FGR.

Overexpression of microRNAs miR-25-3p, miR-185-5p and miR-132-3p in Late Onset Fetal Growth Restriction, Validation of Results and Study of the Biochemical Pathways Involved.

In a prospective study, 48 fetuses were evaluated with Doppler ultrasound after 34 weeks and classified, according to the cerebroplacental ratio (CPR) and estimated fetal weight (EFW), into fetuses with normal growth and fetuses with late-onset fetal growth restriction (LO-FGR). Overexpression of miRNAs from neonatal cord blood belonging to LO-FGR fetuses, was validated by real-time PCR. In addition, functional characterization of overexpressed miRNAs was performed by analyzing overrepresented pathways, gene ontologies, and prioritization of synergistically working miRNAs. Three miRNAs: miR-25-3p, miR-185-5p and miR-132-3p, were significantly overexpressed in cord blood of LO-FGR fetuses. Pathway and gene ontology analysis revealed over-representation of certain molecular pathways associated with cardiac development and neuron death. In addition, prioritization of synergistically working miRNAs highlighted the importance of miR-185-5p and miR-25-3p in cholesterol efflux and starvation responses associated with LO-FGR phenotypes. Evaluation of miR-25-3p; miR-132-3p and miR-185-5p might serve as molecular biomarkers for the diagnosis and management of LO-FGR; improving the understanding of its influence on adult disease.

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.

MicroRNA-148b-3p and MicroRNA-25-3p Are Overexpressed in Fetuses with Late-Onset Fetal Growth Restriction.

OBJECTIVE: It was the aim of this study to describe a micro-RNA (miRNA) profile characteristic of late-onset fetal growth restriction (FGR) and to investigate the pathways involved in their biochemical action. METHODS: In this prospective study, 25 fetuses (16 normal and 9 with FGR [estimated fetal weight <10th centile plus cerebroplacental ratio <0.6765 multiples of the median]) were evaluated with Doppler ultrasound after 36 weeks. Afterwards, for every fetus, plasma from umbilical vein blood was collected at birth, miRNA was extracted, and full miRNA sequencing was performed. Subsequently, comparisons were done in order to obtain those miRNAs that were differentially expressed. RESULTS: The FGR fetuses expressed upregulation of two miRNAs: miR-25-3p and, especially, miR-148b-3p, a miRNA directly involved in Schwann cell migration, neuronal plasticity, and energy metabolism (p = 0.0072, p = 0.0013). CONCLUSIONS: FGR fetuses express a different miRNA profile, which includes overexpression of miR-25-3p and miR-148b-3p. This information might improve our understanding of the pathophysiological processes involved in late-onset FGR. Future validation and feasibility studies will be required to propose miRNAs as a valid tool in the diagnosis and management of FGR.

Comparison of Cerebroplacental Ratio, Intergrowth-21st Standards, Customized Growth, and Local Population References for the Prediction of Fetal Compromise: Which Is the Best Approach?

OBJECTIVE: The aim of this work was to compare the accuracy of the cerebroplacental ratio (CPR), Intergrowth 21st standards (IG21), customized growth (CG), and local population references (LPR) in the prediction of intrapartum fetal compromise (IFC). METHODS: This was a prospective study of 714 fetuses that underwent an ultrasound examination at 34-41 weeks and were delivered within a 2-week interval. The CPR was converted into multiples of the median and the estimated fetal weight (EFW) transformed into CG, IG21, and LPR centiles. IFC was defined as a composite of abnormal cardiotocogram, intrapartum pH requiring cesarean section, 5-min Apgar score, and admission to pediatric care units. The accuracies of the CPR and the EFW centiles for the prediction of IFC were evaluated alone and in combination with other gestational characteristics using univariate and multivariate analysis. RESULTS: Individually, the CPR was the parameter that best predicted the existence of IFC (AUC = 0.66). The multivariate analysis showed that the best prediction was again achieved with the CPR, alone or in combination with any of the EFW centiles (AUC = 0.74). No significant differences were seen between the different centile methods. CONCLUSION: The best prediction of IFC is obtained with CPR. Evaluation of CPR should be encouraged in term and late-preterm fetuses.

Risk of operative delivery for intrapartum fetal compromise in small-for-gestational-age fetuses at term: an internally validated prediction model.

BACKGROUND: Small-for-gestational-age fetuses are at an increased risk of intrapartum fetal compromise requiring operative delivery. Factors associated with the risk of intrapartum fetal compromise are yet to be established, and a comprehensive model accounting for both the antenatal and intrapartum variables is lacking. OBJECTIVE: We aimed to develop and validate a predictive model for the risk of operative delivery for presumed intrapartum fetal compromise in fetuses suspected to be small for gestational age at term. STUDY DESIGN: This was a single-center cohort study of small-for-gestational-age fetuses, defined as estimated fetal weight below the 10th centile in singleton pregnancies at term. The variables included known risk factors for operative delivery because of fetal compromise: maternal characteristics, estimated fetal weight, abdominal circumference, Doppler parameters, gestational age at delivery, induction of labor, and intrapartum risk factors (presence of meconium, augmentation of labor using oxytocin, the use of epidural analgesia, intrapartum pyrexia, and hemorrhage). The receiver-operating characteristics curve analysis was used to investigate the predictive accuracy. Internal validation of the models was performed with bootstrapped data sets. RESULTS: A total of 927 term pregnancies with 18.7% operative deliveries were included. The antenatal model (area under the curve, 0.69; 95% confidence interval, 0.65-0.73) using only the antenatal risk factors included parity, abdominal circumference centile, gestational age at delivery beyond 39 weeks' gestation, and the cerebroplacental ratio multiples of median. The combined model (area under the curve, 0.76; 95% confidence interval, 0.72-0.80), using both the antenatal and intrapartum risk factors, included the gestational age at delivery beyond 39 weeks' gestation (odds ratio, 1.62; 95% confidence interval, 1.14-2.56), the cerebroplacental ratio multiples of median (odds ratio, 0.38; 95% confidence interval, 0.18-0.79), parity (odds ratio 0.35; 95% confidence interval, 0.22-0.54), induction of labor (odds ratio 1.63; 95% confidence interval, 1.11-2.40), augmentation using oxytocin (odds ratio, 1.84; 95% confidence interval, 1.23-2.73) and the use of epidural analgesia (odds ratio, 2.80; 95% confidence interval, 1.94-4.04). The results indicate that the model has good discrimination and, according to the Hosmer-Lemeshow test, has good fit (P = .591). CONCLUSION: The prediction model demonstrates 6 important risk factors that are associated with the risk of operative delivery for fetal compromise in small-for-gestational-age fetuses at term. The model shows good discrimination and fit and has the potential to be used for clinical decision making and to counsel women about their individual intrapartum risk.

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

BACKGROUND: 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. OBJECTIVE: 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. STUDY DESIGN: 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. RESULTS: 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). CONCLUSION: 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.

Protein S100ß in Late-Pregnancy Fetuses with Low Birth Weight and Abnormal Cerebroplacental Ratio.

OBJECTIVE: To evaluate the umbilical cord venous S100ß 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 S100ß levels were evaluated in small and non-small for gestational age (SGA) fetuses, with and without abnormal Doppler indices. The levels of S100ß were correlated with birth weight (BW) centile, CPR MoM and cord venous pH. RESULTS: While CPR MoM correlated with BW centile, S100ß showed no correlation with any of the studied fetal parameters. In addition, no differences were observed in S100ß 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 S100ß at birth. In these fetuses, the potential consequences of chronic hypoxemia on the fetal brain might not be detectable using tissue necrosis markers.

Abnormal Middle Cerebral Artery Doppler Associates with Spontaneous Preterm Birth in Normally Grown Fetuses.

OBJECTIVE: Our aim was to evaluate whether Doppler changes in the fetal middle cerebral (MCA) and umbilical arteries (UA) suggesting fetal hypoxemia precede the onset of spontaneous preterm birth (PTB). METHODS: We studied 2,340 appropriate-for-gestational-age singleton pregnancies that had MCA and UA pulsatility indices (PI) recorded at 28-32 weeks. Values including the cerebroplacental ratio (CPR) were converted into multiples of the median and evaluated according to both gestational age at the onset of labor and the interval between ultrasound and labor. ROC analysis was used to calculate the ability in the prediction of spontaneous PTB before 32, 34 and 37 weeks' gestation. RESULTS: While no correlations were observed for the UA PI and CPR, lower MCA PI values were associated with an earlier onset of labor (p < 0.001) and a shorter ultrasound-labor interval (p = 0.028). The ROC analysis at different gestational ages and intervals to labor indicated that MCA PI values were poorly predictive of spontaneous PTB (all areas under the curve <0.7). CONCLUSIONS: Low MCA PI values at 28-32 weeks are associated with subsequent spontaneous PTB, indicating that fetal hypoxemia unrelated with placental disease might be implicated in the onset of labor. This association, however, is unlikely to be useful in the prediction of PTB.

Is fetal cerebroplacental ratio an independent predictor of intrapartum fetal compromise and neonatal unit admission?

OBJECTIVE: We sought to evaluate the association between fetal cerebroplacental ratio (CPR) and intrapartum fetal compromise and admission to the neonatal unit (NNU) in term pregnancies. STUDY DESIGN: This was a retrospective cohort study in a single tertiary referral center over a 14-year period from 2000 through 2013. The umbilical artery pulsatility index, middle cerebral artery pulsatility index, and CPR were recorded within 2 weeks of delivery. The birthweight (BW) values were converted into centiles and Doppler parameters converted into multiples of median (MoM), adjusting for gestational age using reference ranges. Logistic regression analysis was performed to identify, and adjust for, potential confounders. RESULTS: The study cohort included 9772 singleton pregnancies. The rates of operative delivery for presumed fetal compromise and neonatal admission were 17.2% and 3.9%, respectively. Doppler CPR MoM was significantly lower in pregnancies requiring operative delivery or admission to NNU for presumed fetal compromise (P < .01). On multivariate logistic regression, both CPR MoM and BW centile were independently associated with the risk of operative delivery for presumed fetal compromise (adjusted odds ratio [OR], 0.67; 95% confidence interval [CI], 0.52-0.87; P = .003 and adjusted OR, 0.994; 95% CI, 0.992-0.997; P < .001, respectively). The latter associations persisted even after exclusion of small-for-gestational-age cases from the cohort. Multivariate logistic regression also demonstrated that CPR MoM was an independent predictor for NNU admission at term (adjusted OR, 0.55; 95% CI, 0.33-0.92; P = .021), while BW centile was not (adjusted OR, 1.00; 95% CI, 0.99-1.00; P = .794). The rates of operative delivery for presumed fetal compromise were significantly higher for appropriate-for-gestational-age fetuses with low CPR MoM (22.3%) compared to small-for-gestational-age fetuses with normal CPR MoM (17.3%). CONCLUSION: Lower fetal CPR, regardless of the fetal size, was independently associated with the need for operative delivery for presumed fetal compromise and with NNU admission at term. The extent to which fetal hemodynamic status could be used to predict perinatal morbidity and optimize the mode of delivery merits further investigation.

The association between fetal Doppler and admission to neonatal unit at term.

OBJECTIVE: Fetal cerebroplacental ratio is emerging as a better proxy than birthweight for placental insufficiency and as a marker of fetal compromise at term. The extent to which these fetal Doppler changes are related to neonatal outcomes has not been systematically assessed. The main aim of this study was to evaluate the association between estimated fetal weight percentile, cerebroplacental ratio recorded at 34(+0)-35(+6) weeks' gestation, and neonatal unit admission at term. STUDY DESIGN: This was a retrospective cohort study in a tertiary referral center over an 11 year period from 2002 to 2012. The umbilical artery pulsatility index (PI), middle cerebral artery PI, and cerebroplacental ratio were recorded at 34(+0)-35(+6) weeks. Weight values were converted into percentiles and Doppler parameters into multiples of the median (MoM), adjusting for gestational age. Logistic regression analysis was performed to identify, and adjust for, potential confounders. RESULTS: We identified 2518 pregnancies in which a scan was performed at 34(+0)-35(+6) weeks and delivery occurred at or beyond 37 weeks. In the 2485 pregnancies included in the analysis, the umbilical artery PI MoM was significantly higher, and the middle cerebral artery PI and cerebroplacental ratio MoM significantly lower in the babies requiring neonatal unit admission (P < .05). However, the estimated fetal weight percentile was not significantly different between those who required neonatal unit admission and those who did not (P = .087). According to multivariate logistic regression, cerebroplacental ratio MoM (odds ratio, 0.39; 95% confidence interval, 0.19-0.79; P = .008) and gestational age at delivery (odds ratio, 0.70; 95% confidence interval, 0.61-0.80; P < .001) were significantly associated with the risk of neonatal unit admission, whereas maternal age and birthweight percentile were not (P = .183 and P = .460, respectively). Irrespective of birthweight or estimated fetal weight percentile, the fetal cerebroplacental ratio appears to be a better predictor of the need for neonatal unit admission (P < .001). CONCLUSION: Lower cerebroplacental ratio and gestational age at delivery, but not fetal size, were independently associated with the need for admission to the neonatal unit at term in a high-risk patient group. The extent to which fetal hemodynamic assessment could be used to predict perinatal morbidity and optimize the timing of delivery merits further investigation.

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.