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A low fetal cerebroplacental ratio (CPR) in late pregnancy is a marker of a fetus that has failed to reach its growth potential and is associated with a variety of perinatal and pregnancy complications. It is not known if it is also correlated with aberrations in angiogenic, hypoxia-responsive or inflammatory cytokine levels in the maternal circulation. We investigated if there were any differences in levels of biomarkers of angiogenesis, endothelial cell dysfunction, hypoxia and/or inflammation in term pregnancies with a low fetal CPR compared to controls. We hypothesized that as the CPR is a marker of suboptimal growth, this would be reflected in a shift towards upregulation of hypoxia-responsive factors even in non-small for gestational age fetuses.We used Multiplex ELISA to measure a panel of 28 candidate biomarkers of angiogenesis and/or hypoxia in pre-labour maternal plasma from 113 women at term, stratified for CPR10th centile vs. CPR10th centile. Plasma levels of the biomarkers were measured using 2 multiplex Luminex assays - a commercially available human angiogenesis/growth factor panel (RD Systems®), comprising 15 analytes and an in-house custom panel of a further 13 candidate biomarkers.Of the 28 candidate biomarkers investigated, we found significantly elevated levels of Carbonic Anhydrase 9 and soluble Fms-like tyrosine kinase (Vascular Endothelial Growth Factor Receptor 1), and lower levels of Placental Growth Factor in plasma from women with a low fetal CPR. The soluble Fms-like tyrosine kinase-1/Placental Growth Factor ratio was also markedly elevated in this cohort. We also demonstrated significant inverse correlations between the fetal CPR and Carbonic Anydrase 9, soluble Fms-like tyrosine kinase and Hepatocyte Growth Factor.A low fetal CPR is associated with changes in some hypoxia-responsive and angiogenesis factors in the maternal circulation in pregnancies with normally grown fetuses.

Placental growth factor (PLGF) is a biomarker of placental function. The aim of this study was to define reference ranges for maternal PLGF levels in a normotensive cohort ≥36 + 0 weeks.Prospective observational data from Mater Mothers' Hospital, Brisbane. PLGF levels were measured in women at ≥36 + 0 weeks with singleton, non-anomalous pregnancies. Women with hypertension and fetal growth restriction were excluded. PLGF (pg/mL) was assayed using DELFIA® Xpress (PerkinElmer Inc). The Generalised Additive Model for Location, Shape and Scale (GAMLSS) method was used for the calculation of gestational age-adjusted centiles. Data analysis was performed with Stata 13 (StataCorp, LLC) and R software (R Foundation for Statistical Computing, Vienna, Austria). In all women, PLGF was measured within 2 weeks of delivery.The study cohort comprised of 845 women (36 weeks n = 73, 37 weeks n = 230, 38 weeks n = 214, 39 weeks n = 172, 40 weeks n = 115, 41weeks n = 41). PLGF levels were negatively correlated with gestational age (r = -0.20, p 0.001). Median PLGF levels dropped significantly from 36 weeks to 41 weeks (169.0 pg/mL to 96.6 pg/mL, p 0.001). Gestational age specific maternal PLGF centiles were reported using fractional polynomial additive term and Box-Cox t distribution. PLGF did not perform adequately as a predictive test for adverse perinatal outcomes (AUC0.6).We have created gestational centile reference ranges for maternal PLGF from a normotensive cohort. These novel data suggest maternal PLGF levels decline ≥36 + 0 weeks. The utility of PLGF as a predictor of adverse perinatal outcomes at term, should be further investigated with clinical trials.

We sought to determine the screening performance of a low fetal cerebroplacental ratio (a marker of fetal adaptation to suboptimal growth) and maternal placental growth factor levels, respectively, both in isolation and in combination, for the detection of cesarean section for intrapartum fetal compromise and serious composite neonatal outcome. A prospective cohort study was performed on low risk women with uncomplicated singleton pregnancies from 36 weeks to delivery. Fortnightly assessment of the cerebroplacental ratio and placental growth factor was performed and intrapartum and neonatal outcomes were recorded. Values from the final assessment for each woman were corrected for gestation and assessed for screening performance, firstly as continuous variables and then as binary predictors. Of the 264 women who consented to participate in the study, 207 were included in the final analysis. Babies born by cesarean section for intrapartum fetal compromise had lower cerebroplacental ratio and placental growth factor centiles than all other deliveries. Women with babies born with the serious composite neonatal outcome had lower placental growth factor centiles. The highest Area under the Receiver Operative Characteristic Curve for cesarean section for intrapartum fetal compromise (0.92, 95% CI 0.86-0.97) and serious composite neonatal outcome (0.64, 95% CI 0.54-0.74) was achieved by a combination of the cerebroplacental ratio 20th and placental growth factor 33rd centiles respectively. This produced sensitivities, specificities and positive likelihood ratios for cesarean section for intrapartum fetal compromise and serious composite neonatal outcome of 100%, 86%, and 7.14, and 34.2%, 87.0%, and 2.63, respectively. There was no statistical difference in the Area under the Receiver Operative Characteristic Curve between the combined model and the cerebroplacental ratio alone for cesarean section for intrapartum fetal compromise nor the combined model and the cerebroplacental ratio or placental growth factor in isolation for adverse neonatal outcome. This pilot, proof of principle study describes the screening performance for detection of cesarean section for intrapartum fetal compromise in low risk women from 36 weeks gestation using the fetal cerebroplacental ratio and maternal placental growth factor levels. We found that the cerebroplacental ratio and maternal placental growth factor improved the overall predictive utility for cesarean section for intrapartum fetal compromise and adverse neonatal outcome. However, given the lack of significant difference between the combined model and its individual components it is debatable that the combined model is a superior screening test.

Prediction of intrapartum fetal compromise in uncomplicated, term pregnancies is a global obstetric challenge. Currently, no widely accepted screening test for this condition exists, although the cerebroplacental ratio (CPR) shows promise. We aimed to prospectively evaluate the screening performance of the CPR 10th centile for detection of Cesarean section for intrapartum fetal compromise (IFC) and composite adverse neonatal outcome (ANO) in low-risk women from 36 weeks and to determine the best CPR threshold from three previously described in the literature. In a blinded, prospective, observational, cohort study, 483 women with uncomplicated singleton pregnancies underwent fortnightly CPR measurement from 36 weeks to delivery and intrapartum and neonatal outcomes were recorded. The CPR 10th centile threshold screening test performance was calculated for emergency Cesarean section for IFC and composite ANO, incorporating acidosis at birth, Apgar Four hundred and fifty eight women were included in the analysis, of which 4.1% had an emergency Cesarean section for IFC and 17.9% had a composite ANO. Sensitivity and specificity for CPR The CPR 10th centile may be useful as a component of a risk assessment tool for Cesarean section for IFC in low risk pregnancies at term.

To assess prospectively fetal myocardial deformation at term in normally grown fetuses using the velocity vector imaging (VVI) two-dimensional speckle-tracking technique, and to explore myocardial deformation changes over the last 4 weeks of pregnancy.This was a prospective, observational cohort study of 276 women with an uncomplicated singleton pregnancy who underwent fortnightly ultrasound from 36 weeks' gestation until delivery at the Mater Mother's Hospital, Brisbane, Australia. Fetal myocardial deformation (assessed by global and segmental longitudinal systolic myocardial strain and strain rate of both right and left ventricles) was measured using VVI software.Mean global longitudinal left and right ventricular strain and strain rate values decreased between each time point. At 36, 38 and 40 weeks' gestation, left ventricular global strain (%) and strain rate (/s) decreased, respectively, as follows: -14.6 ± 3.8% and -1.2 ± 0.3/s at 36 weeks; -13.6 ± 3.3% and -1.1 ± 0.3/s at 38 weeks; and -12.3 ± 3.1% and -1.0 ± 0.3/s at 40 weeks. At 36, 38 and 40 weeks, mean right ventricular global strain (%) and mean strain rate (/s) decreased, respectively, as follows: -14.2 ± 3.4% and -1.2 ± 0.2/s at 36 weeks; -13.4 ± 3.0% and -1.1 ± 0.2/s at 38 weeks; and -12.8 ± 2.8% and -1.1 ± 0.2/s at 40 weeks.Global ventricular strain values diminish with advancing gestational age. Myocardial deformation imaging is feasible in late gestation and may be useful as an adjunct for the assessment of fetal cardiac function close to birth. Copyright © 2017 ISUOG. Published by John WileySons Ltd.

Objectives To prospectively investigate the relationship between fetal cardiac function and Doppler parameters with intrapartum fetal compromise (IFC) in term appropriately grown fetuses prior to labour. Secondary outcomes were to correlate prenatal cardiac function with neonatal acid base status, intrapartum fetal heart rate abnormalities adverse neonatal outcomes. Methods This was a blinded, prospective, observational, cohort study, at the Mater Mother's Hospital, Brisbane, Australia. A cohort of 270 women with uncomplicated singleton pregnancies underwent fortnightly ultrasound from 36 weeks until delivery. Fetal cardiac output and blood flow parameters were assessed and correlated with intrapartum and neonatal outcomes. Results Two hundred and seventy women were included in the analysis, of which 18.9% had an emergency operative delivery for IFC. Fetuses that had emergency delivery for IFC showed lower mean left ventricular cardiac output (LVCO) (560 + 44 ml/min vs. 617 + 72 ml/min, p10th centile that develop intrapartum fetal compromise have evidence of lower left and higher right ventricular cardiac outputs which are in turn associated with poorer condition of the newborn. The fetal CPR is also positively correlated with left ventricular cardiac output.

Objective: Redistribution of cardiac output is responsible for the “brain sparing” effect seen during periods of acute or chronic fetal stress. We investigated the relationship between prelabour ca...

Objective: To stratify apparently low-risk pregnant women into those who are at risk of adverse perinatal outcomes. Appropriate stratification would allow targeted prenatal and intrapartum management.Methods: This prospective, observational study included normotensive women with appropriately grown, non-anomalous, singleton pregnancies. Participants underwent fortnightly ultrasounds from 36 weeks’ gestation and intrapartum and neonatal outcomes were recorded. The association between uterine artery pulsatility index (UtA-PI), the cerebroplacental ratio (CPR) and estimated fetal weight (EFW) were explored along with their screening performance for CS-IFC and CNM.Results: The final cohort included 429 women. As continuous variables, UtA-PI and the CPR were not correlated (rho = −0.05, p = .33). UtA-PI >95th centile and the CPR

To investigate the association between decreased growth velocity at term, measured by estimated fetal weight z-score change, and adverse neonatal outcome and operative birth for intrapartum fetal compromise in a cohort of non-small for gestational age infants.A prospective observational study was conducted at Mater Mothers' Hospital, Brisbane, Australia. Serial ultrasound assessment was undertaken every two weeks from 36 weeks gestation until delivery to determine estimated fetal weight on 436 women with uncomplicated pregnancies. Intrapartum and neonatal outcomes were recorded. The outcome measures were adverse neonatal outcome [severe acidosis (cord pH 7.0, base deficit ≤-12 mmol/L and/or lactate6 mmol/L), low Apgar score (7 at 5 min) or neonatal intensive care unit admission] and operative delivery for intrapartum fetal compromise. Estimated fetal weight z-score change was compared between those with and without adverse neonatal outcome and operative delivery for intrapartum fetal compromise using Generalised Linear Mixed Models.The estimated fetal weight z-score per week declined for infants with the adverse neonatal outcome whilst those without demonstrated an increase [-0.04 (0.18) vs. 0.02 (0.21), p = 0.02]. There was no difference in estimated fetal weight z-score change per week in those with and without operative delivery for intrapartum fetal compromise.Reduced growth velocity in non-small for gestational age fetuses at term is associated with an increased risk of adverse neonatal outcomes.

OBJECTIVE Redistribution of cardiac output (CO) is responsible for the brain-sparing effect seen during periods of fetal stress. Our aim was to investigate prospectively the correlation between fetoplacental Doppler indices and measurements of cardiac function in uncomplicated term singleton pregnancy. METHODS This was a prospective observational study of normotensive women with appropriately grown, non-anomalous singleton pregnancy. Participants underwent fortnightly ultrasound examinations from 36 weeks' gestation until delivery, and intrapartum and neonatal outcomes were recorded. The correlation between fetoplacental Doppler indices and various measurements of cardiac function was evaluated. RESULTS The study cohort comprised 273 singleton pregnancies. The cerebroplacental ratio (CPR) was correlated positively with left ventricular CO (LVCO) (P

To investigate the relationship between the prelabour left ventricular Myocardial Performance Index (LVMPI) and intrapartum fetal compromise (IFC) in low-risk term pregnancies.A blinded, prospective observational cohort study at the Mater Mother's Hospital, Brisbane, Australia. A cohort of 284 women with uncomplicated singleton pregnancies underwent fortnightly ultrasound from 36 weeks until delivery. The LVMPI was assessed by conventional Doppler ultrasound and correlated with intrapartum outcomes. The LVMPI was also correlated with other Doppler indices of fetal wellbeing.Two hundred and seventy-three women were included in the final analysis, the median LVMPI was higher in fetuses that required any emergency operative delivery for IFC (0.56, 0.52-0.60 versus 0.54, 0.50-0.58, p = .007). The left ventricular cardiac output (LVCO) and cerebroplacental ratio (CPR) were lower in fetuses that required any emergency operative delivery for IFC compared to those that did not (164 ± 19 ml/min/kg versus 181 ± 30 ml/min/kg, p .001) (1.63 + 0.30 versus 1.90 + 0.50, p .001), respectively. The LVMPI was inversely correlated with the CPR (r = -0.20, p .01), MCA PI (r = -0.29, p .01), and LVCO (r = -0.22, p .01).Higher global LVMPI is associated with a higher risk for IFC and poorer condition of the newborn.

Introduction: Fetuses who fail to reach their genetic growth potential are thought to have sub-optimal placental function. Low placental growth factor (PlGF) levels have been shown to be predictive of placentally mediated conditions, such as pre-eclampsia or fetal growth restriction. We investigated the screening performance of PlGF for the prediction of low birth weight (Materials and Methods: Maternal PlGF levels were measured fortnightly in a blinded, prospective, observational study from 36 weeks of pregnancy. Women and clinicians were blinded to PlGF results, and pregnancies were managed according to local policies and guidelines. Intrapartum and neonatal outcomes were recorded. PlGF was analysed for association with, and predictive capacity for, low birth weight, caesarean section for intrapartum fetal compromise (CS-IFC) and adverse neonatal outcomes. Results: A total of 438 women were included in the final analysis. Lower PlGF levels were associated with low birth weight, CS-IFC and adverse neonatal outcome. For a false-positive rate of 10 and 20%, respectively, the corresponding sensitivities were 9.7-11.1% and 22.2-26.8%. Conclusion: As a sole predictor for low birth weight, CS-IFC and adverse neonatal outcome, PlGF was poor as a test.

Introduction Whilst some cases of intrapartum fetal compromise are the result of unpredictable catastrophic events, the majority arise from an unrecognised reduction in feto-placental reserve in otherwise healthy pregnancies. There is currently no reliable technique prior to labour that identifies the at-risk fetus. We aimed to investigate the relationship between maternal levels of serum placental growth factor (PlGF) and intrapartum fetal compromise in term pregnancies prior to labour. Secondary outcomes were caesarean delivery for intrapartum fetal compromise and adverse neonatal outcomes. Methods A blinded, prospective, cross sectional study set at Mater Mother's Hospital, Brisbane, Australia. Maternal PlGF concentration was assessed fortnightly from 36 weeks until delivery in 378 low-risk pregnant women. Antenatal and intrapartum care was managed according to local protocols and guidelines, and intrapartum and neonatal outcomes were recorded. Results Pregnancies that developed intrapartum fetal compromise had lower PlGF than those that did not. PlGF concentration was also lower amongst pregnancies that developed intrapartum fetal heart rate abnormalities, were delivered with abnormal cord gases or Apgar ≤7 at 5 min. Additionally, PlGF levels were lower in pregnancies with an adverse composite neonatal outcome. Discussion Lower maternal PlGF concentration is associated with intrapartum fetal compromise and poorer condition of the newborn. Maternal PlGF levels may be useful as a component of a risk stratification tool for intrapartum fetal compromise in apparently 'low risk' term pregnancies prior to labour.