Normal Cerebroplacental Ratio Research Articles

Prevalence of Abnormal Cerebroplacental Ratio in Uncomplicated Full-term Pregnancy and Correlation with Adverse Perinatal Outcomes

Objective: To investigate the prevalence of abnormal cerebroplacental ratio (CPR) and predicting values for adverse perinatal outcomes in uncomplicated full-term pregnancies. Materials and Methods: This prospective cross-sectional study was conducted at Bhumibol Adulyadej Hospital, Royal Thai Air Force, Thailand between July and December 2023. The study population comprised pregnant women between the ages 18 and 45 presenting uncomplicated full-term pregnancies. Transabdominal ultrasonography in Doppler color mode was performed on all participants. Umbilical artery pulsatility index (UAPI) and middle cerebral artery pulsatility index (MCAPI) were both measured. CPR was calculated by MCAPI divided by UAPI. A CPR value was considered low if it was less than 1.03. Obstetric and perinatal outcomes were recorded including route of delivery, gestational age (GA) at delivery, obstetric complications, Apgar score, neonatal birth weight, neonatal intensive care unit (NICU) admission, and fetal non-reassuring tracing (FNR). Results: A total of 250 pregnant women were recruited. The mean maternal age and GA was 27.7 years, 39.6 weeks, respectively. Low CPR prevalence was recorded at 16.4 percent. There were 41 and 209 cases in low (<1.03) and normal (≥1.03) CPR groups, respectively. UAPI and MCAPI of the normal/low CPR group were 0.8/1.3 and 1.1/0.9 with statistical significance. CPR for predicted value of FNR (1.03) gave sensitivity, specificity, PPV, and NPV at 95.5, 91.2, 51.2 and 99.5 percent, respectively. This study presented no adverse perinatal outcomes. Conclusion: Low CPR prevalence was 16.4 percent. Normal CPR values measured within a week before birth was a good indicator of normal perinatal outcomes.

Diagnostic accuracy of cerebroplacental ratio in anticipating adverse perinatal outcome in uncomplicated appropriate for gestational age pregnancies at term

Introduction: Anticipating which babies are in danger of experiencing poor outcomes during the perinatal period in uncomplicated appropriate for gestational age (AGA) pregnancies at term is difficult in obstetric practice. Cerebroplacental ratio (CPR) is emerging as a significant indicator of negative perinatal results. The current study sought to establish how effective CPR is in predicting negative perinatal outcomes in term uncomplicated AGA pregnancies. Materials and Methods: This study was a hospital-based prospective observational cohort study conducted at a single center. Patients were chosen depending on different criteria for inclusion and exclusion. A prenatal ultrasound with a color Doppler scan was carried out to calculate CPR. Patients were grouped according to their last CPR measurement before delivery into either normal CPR or pathological CPR categories. Doppler results did not impact clinical decisions and delivery followed institutional protocols. After childbirth, data on the outcome of the perinatal period were obtained from the patients’ medical records. Negative perinatal outcomes were assessed through the delivery method, APGAR score, perinatal morbidity, and perinatal mortality. These outcomes were correlated with CPR. Results: The research included 605 women, separated into normal and pathological CPR groups. Of these, 153 (25.3%) were classified in the pathological CPR category, whereas 452 (74.7%) exhibited normal CPR. In our study, there were 138 patients who experienced adverse perinatal outcomes in the pathological CPR group, whereas 44 patients had such outcomes in the normal CPR group. The diagnostic accuracy of pathological CPR to predict any negative perinatal result was 90.25%. Conclusions: CPR shows potential in detecting fetuses at risk in full-term uncomplicated AGA pregnancies.

Placental pathology in pregnancies with late fetal growth restriction and abnormal cerebroplacental ratio

IntroductionLate fetal growth restriction (FGR) is associated with mild growth restriction and normal or mild abnormal doppler flows. The cerebroplacental ratio (CPR) has been demonstrated as more sensitive to hypoxia than its individual components in these fetuses. We hypothesized that abnormal CPR in late FGR is reflected in specific placental vascular malperfusion lesions. MethodsRetrospective cohort study of late FGR newborns between 2012 and 2022 in a tertiary hospital. Overall, 361 cases were included: 104 with pathological CPR (study group), and 257 with normal doppler flows (control group). The primary outcome was a composite of maternal vascular malperfusion lesions (MVM) and fetal vascular malperfusion lesions (FVM). Secondary outcomes were macroscopic placental characteristics and various obstetrical and neonatal outcomes. ResultsThe study group had lower birthweight compared with the normal CPR group (2063.5 ± 470.5 vs. 2351.6 ± 387.4 g. P < 0.0001), higher rates of composite adverse neonatal outcomes (34.2% vs. 22.5%, p < 0.0001), lower mean placental weight (318 ± 71.6 vs. 356.6 ± 76.5 g, p < 0.0001), as well as a higher prevalence of Vascular lesions of MVM (15.3% vs. 5.0%, p = 0.002), villous lesions of FVM (37.5% vs. 24.9%, p = 0.02), and composite FVM lesions (36.5% vs. 25.6%, p = 0.04). On multivariate regression analysis for MVM lesions and composite FVM lesions, abnormal CPR was found as an independent risk factor (aOR 2.17, 95% CI 1.63–4.19, and aOR 1.31, 95% CI 1.09–3.97, respectively). DiscussionsAbnormal CPR in late FGR is reflected in placental histopathologic vascular malperfusion lesions, and the incidence of these lesions is higher than in FGR placentas with normal CPR.

Role of Cerebro-Placental Ratio in Predicting Adverse Outcomes in Low-Risk PregnanciesA Prospective Cohort Study

Introduction: Abnormal Cerebro-Placental Ratio (CPR) is associated with a substantial risk of adverse perinatal outcomes and the test seems to be particularly useful for follow-up of foetuses with sonographically diagnosed Foetal Growth Restriction (FGR). Aim: To determine the usefulness of doppler velocimetry, especially CPR at 35 weeks of gestation or later, in predicting intrapartum foetal heart rate abnormalities and adverse neonatal outcomes in low-risk term pregnancies. Materials and Methods: The present prospective cohort study was conducted at the Department of Obstetrics and Gynaecology in Bangalore Baptist Hospital, Bangalore from September 2019 to September 2020. A total of 60 pregnant women between the ages of 18 and 35 years with low-risk pregnancies, who present for the obstetrical ultrasound at 35 weeks of gestation or later with planned delivery at the hospital were included. All lowrisk pregnant women with estimated foetal weight (EFW) &gt;10th centile and abnormal Cerebro-Placental Ratio (CPR) &lt;10th centile were compared with those with normal CPR i.e., &gt;10th centile. An adverse obstetric outcome, like foetal distress, meconium aspiration syndrome or respiratory distress syndrome, mode of delivery, admission to Neonatal Intensive Care Unit (NICU), and perinatal mortality was analysed in the study population using chi-square test or Fischer’s-exact test. Results: In this study, there was a significant association between foetal distress and CPR with Odds Ratio (OR) of 4.21 i.e., foetal distress was 4.21 times higher in the abnormal group compared to the normal group. Among 20 cases with abnormal CPR, 11 had foetal distress i.e., 55% and among 40 cases with normal CPR, nine had foetal distress i.e., 22.5%. Among those with abnormal CPR, 15% had Amniotic Fluid Index (AFI) &lt;8 and among those with normal CPR, 0% had AFI &lt;8, showing a significant association. Conclusion: In low-risk patients with EFW &gt;10th centile and abnormal CPR, there was a significant association with adverse obstetric outcomes, requiring vigilant intrapartum monitoring.

The cerebroplacental ratio and prediction of fetal growth restriction in twin pregnancies

Objectives The cerebroplacental ratio (CPR) represents the relationship between blood flow in the placenta and blood flow in the fetal brain. A low CPR in the third trimester has been associated with poor perinatal outcomes in both singleton and twin gestations. This study aimed to evaluate whether low CPR defined or high CPR discordance at 20–24 weeks in twin pregnancies is associated with an increased risk of fetal growth restriction (FGR) in the third trimester. Methods A total of 247 twin pregnancies were included in this retrospective cohort study. Monoamniotic monochorionic twins were excluded. An abnormal CPR was defined as one or both CPR <5%-ile or CPR discordance between fetuses >20%. FGR was evaluated using the last growth measurement performed between 28 and 36 weeks. Results Of the candidates for study, 177 twin pregnancies had normal CPRs and 70 twin pregnancies had abnormal CPRs. Maternal demographics were similar between groups. There was no difference in the risk of selective FGR, FGR of both twins, or growth discordance >20% in the third trimester between twin pregnancies with normal vs. abnormal CPRs at 20–24 weeks. The adjusted odds ratio for any growth disturbance was 1.00 (95% CI 0.56–1.79). Conclusions This study suggests that FGR in twins may be the consequence of numerous maternal, fetal, and placental factors, and not fully explained by redistribution of blood flow or adaptive hypoxia in the mid-trimester.

The importance of the cerebroplacental ratio for the prognosis of neonatal outcome in AGA fetuses

PurposeAs a Doppler sonographic parameter, the cerebroplacental ratio (CPR) provides information about fetal hemodynamics and the redistribution of fetal blood volume in response to a metabolic change. The present study was undertaken to determine the extent to which CPR can be used as a valid parameter in routine obstetric assessment. We investigated whether CPR can be used to assess the neonatal outcome in appropriate for gestational age (AGA) fetuses and its association with secondary cesarean section due to fetal distress.MethodsIn this retrospective analysis 1739 pregnant women were admitted to the University Women‘s Clinic Magdeburg, Germany, between January 2016 and December 2017. Of them, 710 AGA fetuses were eligible for analysis. SGA fetuses with an estimated fetal weight < 10th percentile were excluded from the study. The AGA fetuses were divided in two groups based on the CPR: 669 fetuses showed a normal CPR ≥ 1.08; 41 fetuses showed a decreased CPR < 1.08.ResultsIn our study cohort decreased CPR in AGA fetuses was associated with threefold increased rate of cesarean sections due to fetal distress (p < 0.001). Our data suggested that low CPR is a reliable predictor of an impaired neonatal outcome in AGA fetuses in terms of a lower birth weight, transfer to neonatology, longer length of hospitalization, and the presence of severe morbidity.ConclusionDecreased CPR in AGA fetuses correlated with impaired neonatal outcome and secondary cesarean section due to fetal distress. The potential role of CPR for obstetric screening should be investigated in further studies.

Cerebro placental ratio at 30–34 weeks’ gestation in the prediction of perinatal outcome in low-risk and high-risk pregnancy

Doppler ultrasound velocimetry of umbilical and fetal vessels has become an established method of antenatal monitoring, allowing the non-invasive assessment of neonatal circulation. Cerebro placental ratio (CPR) is emerging as a significant predictor of adverse pregnancy outcome. To predict perinatal outcome in low and high-risk pregnancy in early and late-onset FGR using CPR. The study group comprised 410 pregnant women at 30-34 weeks, evaluated with ultrasound Doppler study, and other routine investigations and CPR were calculated. Women were categorized into high-risk and low-risk pregnancies and followed up until delivery, and fetal outcome was noted. Period of prolongation of pregnancy was significantly lower with high-risk patients than low-risk patients (31.09 ± 13.9 vs 37.79 ± 15.1, p=0.0003). NICU admissions significantly increased with high-risk patients than low-risk patients (22.22% vs 9.4%, p=0.002). Low-risk patients underwent significantly more vaginal deliveries as compared to high-risk patients (74.22% vs 44.87%, p &amp;#60; 0.0001). Birth weight, period of prolongation of pregnancy, and gestation period were significantly lower in patients with abnormal CPR than normal CPR group (2.82 Kg vs 1.94 Kg, 37.56 weeks vs 14.64 weeks, 266.47 days vs 245.41 days, respectively). Doppler velocimetry becomes an important tool for high-risk cases and late-onset mild FGR(after 32 weeks). CPR is helpful in high-risk pregnancies and also to predict peripartum fetal distress.

Role of Cerebro-Placental Ratio in prediction of adverse perinatal outcome in hypertensive disorder of pregnancy

Hypertensive disorder of pregnancy is a multisystem disorder associated with an increased risk of perinatal mortality worldwide. Doppler velocimetry of uterine, umbilical, and fetal vessels is an established method of antenatal monitoring identifying fetus at risk. The cerebroplacental ratio (CPR) is emerging as an important predictor of the adverse perinatal outcome as it considers both umbilical and middle cerebral artery doppler. The aim of this study is to find the role of CPR in the prediction of adverse perinatal outcome in the hypertensive disorder of pregnancy. A prospective descriptive study was done on women admitted to a tertiary care hospital in Kathmandu from July 2020 to June 2021 after taking ethical clearance from Institutional Review Committee. A total of 136 hypertensive pregnant women beyond 34 weeks of gestation underwent Doppler ultrasound, and CPR ratio &lt;1.08 (done within one week of delivery) was considered abnormal. During the study, CPR was normal in 101 women (74.3%) and was abnormal in 35 women (25.7%). The study showed that the rate of cesarean section was high in women with abnormal CPR than with normal CPR (77.1% vs 45.5%). The caesarean section done for fetal distress (70.4% vs 39.1%), Apgar score &lt; 7 in 5 minutes (14.3% vs 3.0%), NICU admission rate (54.3% vs 27.7%), and duration of NICU stay (3.9 + 4.08 vs 0.79 +1.94 days) were high in women with abnormal CPR. The cerebroplacental ratio in hypertension in pregnancy can provide useful information regarding fetal well-being and help us in improving fetal outcomes.

Utility of the cerebroplacental ratio (CPR) in marijuana exposed growth restricted fetuses

Objective Fetal growth restriction (FGR) is associated with an increased risk of adverse perinatal outcomes. The cerebroplacental ratio (CPR) represents the interaction of alterations in blood flow to the fetal brain and placenta. CPR has been utilized as a superior reflection of fetal hypoxia/acidemia and therefore a better predictor of fetal morbidity. We sought to determine the role of the CPR as an adjunctive tool to identify fetuses at increased risk of adverse perinatal outcomes in a study population of marijuana (MJ) exposed FGR fetuses. Methods This was a retrospective cohort study of high-risk singleton pregnancies over a 4-year period. Self-identified daily MJ users with FGR fetuses in the 3rd trimester were isolated. Fetal biometry, amniotic fluid indices, and CPRs were calculated. A CPR <1 was considered abnormal. FGR fetuses with normal and abnormal CPRs were then compared. Results 26/192 (13.5%) of MJ exposed fetuses were diagnosed with FGR in the 3rd trimester. 12/26 (46%) had an abnormal CPR and 14 had a normal CPR (mean CPR 0.60 vs 1.57, p = .0001). The mean EFW percentile was lower in the abnormal CPR group in comparison to the group with normal CPR (3.33 vs 7.64, p = .0001). Both groups showed evidence of brain sparing with an overall mean head circumference of 17.55 in comparison to a mean abdominal circumference of 5.63. A CPR <1 was associated with more severe FGR, oligohydramnios, and abnormal UA Doppler studies. Conclusions Approximately half of the MJ exposed FGR fetuses had an abnormal CPR. In this subset of patients, >90% had severe FGR, a higher proportion had absence/reversal of end diastolic flow in the UA, and a higher proportion had oligohydramnios. This demonstrates that an abnormal CPR identifies a group of FGR fetuses at a greater risk of adverse perinatal outcomes.

870 Normalization of an abnormal second trimester cerebroplacental ratio in the third trimester equalizes perinatal risks

An abnormal cerebroplacental ratio (CPR) is associated with increased risk of adverse perinatal outcomes. It is unknown if these risks persist with normalization of the cerebroplacental ratio later in gestation. This is a sub-analysis of a retrospective cohort study that utilized data from all non-anomalous singleton pregnancies that underwent Doppler assessment of the CPR between 20-28 weeks gestation at a single tertiary referral center. The perinatal outcomes of patients who had reassessment of the CPR after 32 weeks gestation were analyzed. The final CPR obtained before delivery was used. An abnormal ratio was defined as less than 5th percentile for gestational age. Adverse perinatal outcomes included preterm delivery, a small for gestational age neonate, and neonatal intensive care unit admission. 2326 patients were included in the original study, of which 3.9% had an abnormal CPR in the second trimester. 32 (35.1%) of these patients did not have reassessment of the CPR after 32 weeks, either due to delivery before 32 weeks (37.5%) or because the ratio was not obtained (62.5%). Patients with an abnormal CPR in the second trimester that had no ultrasound reassessment in the third trimester had a significantly earlier gestational age at delivery (34.8 weeks) compared to patients with a normal CPR that had no ultrasound reassessment (38.5 weeks). Of patients with an abnormal CPR in the second trimester, 50 (54.9%) experienced normalization of the cerebroplacental ratio after 32 weeks gestation. These patients were not significantly more likely to experience preterm delivery, a small for gestational age neonate, or neonatal intensive care unit admission when compared to patients who maintained a normal ratio throughout gestation. The association of adverse perinatal outcome with an abnormal second trimester cerebroplacental ratio is driven mostly by very preterm birth (<32 weeks). In approximately half of patients, the ratio normalized in the third trimester and was then associated with an average risk for an adverse outcome.

Cerebroplacental Ratio as a Predictor of Fetal Growth Restriction and Perinatal Outcome in Women with Hypertensive Disorder in Pregnancy: A Prospective Cohort Study

Introduction: Hypertensive Disorders in Pregnancy (HDP), is a common complication of pregnancy leading to majority of adverse perinatal outcome. The timely diagnosis of fetal compromise, before irreversible damage, is possible by doing Cerebroplacental Ratio (CPR), on doppler ultrasonography. CPR is calculated as ratio of Pulsatility Index (PI) of Middle cerebral Artery and Umblical Artery (UA). It reflects both the circulatory insufficiency in UA along with adaptive changes in Middle cerebral Artery (MCA). Aim: To evaluate role of Cerebroplacental Ratio as predictor of Fetal Growth Restriction and perinatal outcome in singleton pregnancy with HDP at 28-41 weeks of gestation. Materials and Methods: A prospective observational cohort study was carried out in the Department of Obstetrics and Gynaecology, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi, India. The study included 150 women with singleton pregnancy, HDP and 28-41 weeks of gestation. Doppler ultrasound was performed and CPR calculated as ratio of MCA PI and UA PI, using ultrasound study performed within two weeks of delivery. All women were followed-up till delivery and perinatal outcome i.e., birth weight, preterm birth, cesarean for fetal distress, Meconium Stained Liquor (MSL) , APGAR at 5 minutes, still birth, Neonatal Intensive Care Unit (NICU) admission and early neonatal death, were recorded. The data entry was done in the Microsoft excel spreadsheet and the final analysis was done with the use of Statistical Package for Social Sciences (SPSS) software version 21.0. Results: Out of 150 women, 20% (30) had abnormal CPR. Abnormal CPR had significant association with Low Birth Weight (LBW) (p-value=0.0001), preterm delivery (p-value=0.0001), fetal distress (p-value=0.0001), caesarean for fetal distress (p-value=0.0001), 5-minute APGAR score &lt;7 (p-value=0.0001), NICU admission (p-value=0.0001), Meconium Stained Liquor (MSL) (p-value=0.0001) and neonatal death (p-value=0.025). CPR had 100% sensitivity and 100% Negative Predictive Value (NPV) for predicting adverse perinatal outcome with diagnostic accuracy of 47.33%. Conclusion: The CPR is an independent predictor of Fetal Growth Restriction (FGR) in women with HDP. It can also independently predict perinatal outcome in women with HDP with or without FGR. Abnormal CPR had 100% sensitivity for identifying women with high risk of adverse perinatal outcomes, whereas normal CPR, with NPV of 100%, almost excludes it.

The role of abnormal cerebroplacental ratio in predicting adverse fetal outcome in pregnancies with scheduled induction of labor.

To investigate the role of abnormal cerebroplacental ratio (CPR) in predicting adverse fetal outcome in pregnancies with induction of labor. This prospective observational study conducted at Medeniyet University Göztepe Training and Research Hospital between December 1, 2018 and October 31, 2019 enrolled women with scheduled induction of labor at or beyond 37weeks of pregnancy. Women with singleton non-anomalous fetuses with cephalic presentation and who had Bishop scores of 5 or less in pelvic examination were included in the study. Exclusion criteria were the presence of uterine scar history, non-cephalic presentation, multiple pregnancy, vacuum- or forceps-assisted delivery, and shoulder dystocia. Using fetal Doppler ultrasound, CPR was calculated (the ratio of umbilical artery to middle cerebral artery pulsatility index) and categorized into abnormal CPR (<1) and normal CPR (≥1). Data on maternal and delivery characteristics, fetal birth weight, and fetal complications were compared between the groups. A total of 145 women were included, 28 in the abnormal CPR group and 117 in the normal CPR group. Multivariate analysis revealed labor induction at a later week of pregnancy (odds ratio [OR] 10.33, P=0.001), lack of intrauterine growth restriction (IUGR) (OR 13.21, P=0.001), fetal distress (OR 8.14, P=0.003) or meconium aspiration (OR 159.91, P=0.001), and umbilical artery pH values greater than 7.31 (OR 17.51, P=0.015) to be associated with an increased likelihood of having normal (≥1) CPR values. Receiver operating characteristic analysis revealed association of normal CPR values with later labor induction (cut-off value of >38.3weeks, P=0.001), higher birth weight (cut-off value of >2460g, P=0.022) and higher umbilical artery pH (cut-off value of >7.31, P=0.007). Our findings revealed the significant role of abnormal CPR in predicting adverse fetal outcome in singleton pregnancies with scheduled induction of labor.

Cerebroplacental ratio as a predictor of intrapartum fetal compromise in term pregnancy

To predict intrapartum fetal compromise (FC) and admission to neonatal intensive care unit (NICU) by cerebroplacental ratio (CPR) in term pregnancies. A prospective observational study recruited women with singleton, term pregnancies. Ultrasound (US) was done for fetal biometry, umbilical and middle cerebral artery (UA, MCA) Doppler parameters, and CPR calculated. Intrapartum variables and neonatal data were recorded. Mean interval from US to delivery was 2.21±2.71days. Rate of operative delivery for FC was 17.47%. Multivariate logistic regression analysis showed that UA pulsatility index (PI) multiples of median (MoM) (P=0.001), MCA PI MoM (P=0.001), and CPR MoM (P=0.001) were significantly and independently associated with operative delivery for FC. Similarly, UA PI MoM (P=0.004), MCA PI MoM (P=0.009), and CPR MoM (P=0.003) were also significantly and independently associated with admission to the NICU. Rate of operative delivery for presumed FC was higher in approprate-for-gestational-age fetuses with low CPR than in small-for-gestational-age fetuses with normal CPR (43.1% and 37.5%, respectively). Lower mean CPR and CPR MoM were independently associated with the need for operative delivery for presumed FC and NICU admission at term. CPR is more likely to be associated with FC due to placental insufficiency than birth weight.

1028: Utility of the cerebroplacental ratio (CPR) in marijuana exposed growth restricted fetuses

Severe fetal growth disorders are associated with an increased risk of adverse perinatal outcome (APO). The CPR represents the interaction of alterations in blood flow to the fetal brain and placenta. It is calculated by dividing the Doppler indices of the middle cerebral artery (MCA) by those of the umbilical artery (UA). CPR has been toted as a superior reflection of fetal hypoxia/acidemia and therefore a better predictor of APO. We sought to determine the role of CPR as a predictor of severe fetal growth restriction (FGR), defined as an estimated fetal weight (EFW) less than the 5th percentile, in a study population of marijuana (MJ) exposed FGR fetuses. This was a retrospective cohort study of high-risk singleton pregnancies over a four-year period. Self-identified daily MJ users with FGR fetuses, defined as fetuses with an EFW less than the 10th percentile, in the 3rd trimester were isolated. Fetal biometry, amniotic fluid indices, and CPRs were calculated. A CPR < 1 was considered abnormal. FGR fetuses with normal and abnormal CPRs were then compared. 26 /192 (13.5%) of MJ exposed fetuses were diagnosed with FGR in 3rd trimester. 12/26 (46%) had an abnormal CPR and 14 had a normal CPR (mean CPR 0.60 vs 1.57, p = 0.0001). The mean EFW percentile was lower in the abnormal CPR group in comparison to the group with normal CPR (3.33 vs 7.64, p=0.0001). Both groups showed evidence of brain sparing with an overall mean head circumference of 17.55 in comparison to a mean abdominal circumference of 5.63. A CPR < 1 was associated with more severe FGR, oligohydramnios, and abnormal UA Doppler studies (see table 1). Approximately half of the MJ exposed FGR fetuses had an abnormal CPR. In this subset of patients, > 90% had severe FGR, a higher proportion had absence/reversal of end diastolic flow in the UA, and a higher proportion had oligohydramnios. This demonstrates that an abnormal CPR identifies a group of FGR fetuses at a greater risk for severe FGR and possibly APO.

Differential placental DNA methylation of VEGFA and LEP in small-for-gestational age fetuses with an abnormal cerebroplacental ratio.

BackgroundIn Fetal Growth Restriction ‘fetal programming’ may take place via DNA methylation, which has implications for short-term and long-term health outcomes. Small-for-gestational age fetuses are considered fetal growth restricted, characterized by brain-sparing when fetal Doppler hemodynamics are abnormal, expressed as a cerebroplacental ratio (CPR) <1. We aimed to determine whether brain-sparing is associated with altered DNA methylation of selected genes.MethodsWe compared DNA methylation of six genes in 41 small-for-gestational age placentas with a normal or abnormal CPR. We selected EPO, HIF1A, VEGFA, LEP, PHLDA2, and DHCR24 for their role in angiogenesis, immunomodulation, and placental and fetal growth. DNA methylation was analyzed by pyrosequencing.ResultsGrowth restricted fetuses with an abnormal CPR showed hypermethylation of the VEGFA gene at one CpG (VEGFA-309, p = .001) and an overall hypomethylation of the LEP gene, being significant at two CpGs (LEP-123, p = .049; LEP-51, p = .020). No differences in methylation were observed for the other genes.ConclusionsVEGFA and LEP genes are differentially methylated in placentas of small-for-gestational age fetuses with brain-sparing. Hypermethylation of VEGFA-309 in abnormal CPR-placentas could indicate successful compensatory mechanisms. Methylation of LEP-51 is known to suppress LEP expression. Hypomethylation in small-for-gestational age placentas with abnormal CPR may result in hyperleptinemia and predispose to leptin-resistance later in life.

An abnormal cerebroplacental ratio (CPR) is predictive of early childhood delayed neurodevelopment in the setting of fetal growth restriction

Fetal growth restriction accounts for a significant proportion of perinatal morbidity and death. The cerebroplacental ratio is gaining much interest as a useful tool in differentiating the "at-risk" fetus in both fetal growth restriction and appropriate-for-gestational-age pregnancies. The Prospective Observational Trial to Optimize Pediatric Health in Fetal Growth Restriction group has demonstrated previously that the presence of this "brain-sparing" effect is associated significantly with adverse perinatal outcomes in the fetal growth restriction cohort. However, data about neurodevelopment in children from pregnancies that are complicated by fetal growth restriction are sparse and conflicting. The aim of the Prospective Observational Trial to Optimize Pediatric Health in Fetal Growth Restriction NeuroDevelopmental Assessment Study was to determine whether children born after fetal growth-restricted pregnancies are at additional risk of adverse early childhood developmental outcomes compared with children born small for gestational age. The objective of this secondary analysis was to describe the role of cerebroplacental ratio in the prediction of adverse early childhood neurodevelopmental outcome. Participants were recruited prospectively from the Perinatal Ireland multicenter observational Prospective Observational Trial to Optimize Pediatric Health in Fetal Growth Restriction study cohort. Fetal growth restriction was defined as birthweight <10th percentile with abnormal antenatal umbilical artery Doppler indices. Small for gestational age was defined similarly in the absence of abnormal Doppler indices. Cerebroplacental ratio was calculated with the pulsatility indices of the middle cerebral artery and divided by umbilical artery with an abnormal value <1. Children (n=375) were assessed at 3 years with the use of the Ages and Stages Questionnaire and the Bayley Scales of Infant and Toddler Development, 3rd edition. Small-for-gestational-age pregnancies with normal Doppler indices were compared with (1) fetal growth-restricted cases with abnormal umbilical artery Doppler and normal cerebroplacental ratio or (2) fetal growth restriction cases with both abnormal umbilical artery and cerebroplacental ratio. Statistical analysis was performed with statistical software via 2-sample t-test with Bonferroni adjustment, and a probability value of .00625 was considered significant. Assessments were performed on 198 small-for-gestational-age children, 136 fetal growth-restricted children with abnormal umbilical artery Doppler images and normal cerebroplacental ratio, and 41 fetal growth-restricted children with both abnormal umbilical artery Doppler and cerebroplacental ratio. At 3 years of age, although there were no differences in head circumference, children who also had an abnormal cerebroplacental ratio had persistently shorter stature (P=.005) and lower weight (P=.18). Children from fetal growth restriction-affected pregnancies demonstrated poorer neurodevelopmental outcome than their small-for-gestational-age counterparts. Fetal growth-restricted pregnancies with an abnormal cerebroplacental ratio had significantly poorer neurologic outcome at 3 years of age across all measured variables. We have demonstrated that growth-restricted pregnancies with a cerebroplacental ratio <1 have a significantly increased risk of delayed neurodevelopment at 3 years of age when compared with pregnancies with abnormal umbilical artery Doppler evidence alone. This study further substantiates the benefit of routine assessment of cerebroplacental ratio in fetal growth-restricted pregnancies and for counseling parents regarding the long-term outcome of affected infants.

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.

Correlation of Cerebroplacental Ratio (CPR) With Adverse Perinatal Outcome in Singleton Pregnancies

For many years clinical research has been concerned with doppler sonography as a non-invasive tool for intrauterine fetal status assessment. A new focus is now placed on the measurement of cerebroplacental index (CPR) as a predictor of fetal outcome. Our aim was to investigate the relationship between the cerebroplacental ratio (CPR), the delivery mode and the fetal outcome in singleton pregnancies. A retrospective cohort study of pregnancies in which doppler sonography of middle cerebral artery (MCA) and umbilical artery (UA) was conducted up to 9 weeks before delivery took place. Patients with pathological (CPR≤1.0) and normal CPR (>1.0) were compared by umbilical cord pH, APGAR scores, birth weight, delivery week and delivery mode. A total of 2,270 singleton pregnancies were included. The APGAR score for 1, 5 and 10 minutes and the gestational age at delivery were significantly lower in the group of patients with pathological CPR (p<0.001). Overall, 50% of the cohort had a cesarean section, the difference between the groups was statistically significant (p<0.001), with a higher amount of cesareans in the group of patients with pathological CPR. The multiple regression analysis showed a significantly improved pH of delivery when cesarean section (p<0.001), female sex of fetus (p=0.013) and higher CPR (p=0.035) were present. The measurement of CPR is an important, non-invasive predictive parameter and leads to the identification of a risk collective even in the non-selected patient population and thus probably to a reduction of perinatal morbidity.

111: An abnormal Cerebro-Placental-Ratio is predictive of early childhood delayed neurodevelopment in fetal growth restricted infants

The aim of the PORTO- NeuroDevelopmental Assessment Study (PANDA) was to determine if children born after fetal growth restriction (FGR) pregnancies are at additional risk of early childhood development delays compared to children born small for gestational age (SGA). The objective of this secondary analysis was to describe the role of the cerebroplacental ratio (CPR) in the prediction of adverse early childhood neurodevelopmental outcome. Participants were prospectively recruited from the Perinatal Ireland multicenter observational PORTO study cohort. FGR was defined as birth weight <10th with abnormal antenatal Doppler indices. SGA was similarly defined in the absence of abnormal Doppler indices. CPR was calculated using the pulsatility indices of the middle cerebral and divided by umbilical artery (UA) with an abnormal value <1. Children (n=375) were assessed at three years using the Ages and Stages Questionnaire and the Bayley Scales of Infant and Toddler Development, III. SGA pregnancies with normal Doppler indices were compared with: 1) FGR cases with abnormal UA Doppler and normal CPR; or 2) FGR cases with both abnormal UA & CPR. Statistical analysis was performed using SAS version 9.2 via two-sample t-test with Bonferroni adjustment and p-value of 0.00625 significant. Assessments were performed on 198 SGA children; 136 FGR children with abnormal UA Doppler and normal CPR and 41 FGR children with both abnormal UA Doppler and CPR. At three years of age, while there were no differences in head circumference, children who also had an abnormal CPR had persistently shorter stature (p=0.005) and lower weight (p=0.18). Children from FGR affected pregnancies demonstrated poorer neurodevelopmental outcome than their SGA counterparts. FGR pregnancies with an abnormal CPR had significantly poorer neurological outcome at three years of age across all measured variables (Tables 1 & 2). We have demonstrated that growth restricted pregnancies with a CPR <1, have significantly increased risk of delayed neurodevelopment at three years of age when compared to pregnancies with abnormal UA Doppler alone. This study further substantiates the benefit of routine assessment of CPR in FGR pregnancies and for counseling parents regarding the long-term outcome of affected infants.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Emergency caesarean for intrapartum fetal compromise and admission to the neonatal intensive care unit at term is more influenced by fetal weight than the cerebroplacental ratio

Objective: Some studies have suggested that the fetal cerebroplacental ratio (CPR) is an independent predictor of intrapartum fetal compromise and admission to the neonatal intensive care unit (NICU) at term particularly in small for gestational age (SGA) compared to appropriate for gestational age (AGA) infants. The aim of this study was to evaluate the association between the CPR and emergency caesarean for intrapartum fetal compromise (CS IFC) and NICU admission at term after adjusting for estimated fetal weight (EFW) and other confounding factors.Methods: This was a retrospective study of women who birthed at the Mater Mother’s Hospital in Brisbane, Australia between for women who birthed between January 2000 and April 2017. The CPR was measured within 2 weeks of birth in women that delivered at term and assessed for correlation with CS IFC and admission to NICU. The study cohort was also stratified into four categories according to EFW and CPR thresholds. Appropriate for gestational age (EFW ≥10th centile) and normal CPR (≥10th centile), AGA and low CPR (<10th centile), SGA (EFW <10th centile) and normal CPR and SGA and low CPR.Results: Both CPR <10th centile (adjusted odds ratio (aOR) 2.60, 95% CI 1.82–3.71, p < .001) and EFW <10th centile (aOR 2.63, 95% CI 1.85–3.74, p < .001) demonstrated significant associations with CS IFC. EFW <10th centile (aOR 2.23, 95% CI 1.61–3.09, p < .001) but not CPR <10th centile (aOR 1.41, 95% CI 0.99–2.01, p = .06) was predictive of NICU admission. When stratified according to EFW and CPR thresholds, SGA had significant odds ratios for CS IFC and NICU admission regardless of CPR status. However, the AGA and low CPR cohort was only at increased risk of CS IFC (aOR 2.09, 95% CI 1.30–3.34, p = .002) but not of admission to NICU.Conclusions: At term, the CPR is an independent risk factor for CS IFC regardless of fetal weight. However, the CPR was only predictive of NICU admission in an SGA cohort. Overall, our findings suggest that fetal size is a more important variable for both CS IFC and NICU admission.