Cathy Monteith

Evaluation of normalization of cerebro-placental ratio as a potential predictor for adverse outcome in SGA fetuses

Background: Intrauterine growth restriction accounts for a significant proportion of perinatal morbidity and mortality currently encountered in obstetric practice. The primary goal of antenatal care is the early recognition of such conditions to allow treatment and optimization of both maternal and fetal outcomes. Management of pregnancies complicated by intrauterine growth restriction remains one of the greatest challenges in obstetrics. Frequently, however, clinical evidence of underlying uteroplacental dysfunction may only emerge at a late stage in the disease process. With advanced disease the only therapeutic intervention is delivery of the fetus and placenta. The cerebroplacental ratio is gaining much interest as a useful tool in differentiating the at‐risk fetus in both intrauterine growth restriction and the appropriate‐for‐gestational‐age setting. The cerebroplacental ratio quantifies the redistribution of the cardiac output resulting in a brain‐sparing effect. The Prospective Observational Trial to Optimize Pediatric Health in Intrauterine Growth Restriction group previously demonstrated that the presence of a brain‐sparing effect is significantly associated with an adverse perinatal outcome in the intrauterine growth restriction cohort. Objective: The aim of the Prospective Observational Trial to Optimize Pediatric Health in Intrauterine Growth Restriction study was to evaluate the optimal management of fetuses with an estimated fetal weight <10th centile. The objective of this secondary analysis was to evaluate if normalizing cerebroplacental ratio predicts adverse perinatal outcome. Study Design: In all, 1116 consecutive singleton pregnancies with intrauterine growth restriction completed the study protocol over 2 years at 7 centers, undergoing serial sonographic evaluation and multivessel Doppler measurement. Cerebroplacental ratio was calculated using the pulsatility and resistance indices of the middle cerebral and umbilical artery. Abnormal cerebroplacental ratio was defined as <1.0. Adverse perinatal outcome was defined as a composite of intraventricular hemorrhage, periventricular leukomalacia, hypoxic ischemic encephalopathy, necrotizing enterocolitis, bronchopulmonary dysplasia, sepsis, and death. Results: Data for cerebroplacental ratio calculation were available in 881 cases, with a mean gestational age of 33 (interquartile range, 28.7–35.9) weeks. Of the 87 cases of abnormal serial cerebroplacental ratio with an initial value <1.0, 52% (n = 45) of cases remained abnormal and 22% of these (n = 10) had an adverse perinatal outcome. The remaining 48% (n = 42) demonstrated normalizing cerebroplacental ratio on serial sonography, and 5% of these (n = 2) had an adverse perinatal outcome. Mean gestation at delivery was 33.4 weeks (n = 45) in the continuing abnormal cerebroplacental ratio group and 36.5 weeks (n = 42) in the normalizing cerebroplacental ratio group (P value <.001). Conclusion: The Prospective Observational Trial to Optimize Pediatric Health in Intrauterine Growth Restriction group previously demonstrated that the presence of a brain‐sparing effect was significantly associated with an adverse perinatal outcome in our intrauterine growth restriction cohort. It was hypothesized that a normalizing cerebroplacental ratio would be a further predictor of an adverse outcome due to the loss of this compensatory mechanism. However, in this subanalysis we did not demonstrate an additional poor prognostic effect when the cerebroplacental ratio value returned to a value >1.0. Overall, this secondary analysis demonstrated the importance of a serial abnormal cerebroplacental ratio value of <1 within the <34 weeks’ gestation population. Contrary to our proposed hypothesis, we recognize that reversion of an abnormal cerebroplacental ratio to a normal ratio is not associated with a heightened degree of adverse perinatal outcome.

Left ventricular rotational mechanics in infants with hypoxic ischemic encephalopathy and preterm infants at 36 weeks postmenstrual age: A comparison with healthy term controls.

There is a paucity of data on left ventricle (LV) rotational physiology in neonates. We aimed to assess rotational mechanics in infants with hypoxic ischemic encephalopathy (HIE) and premature infants (<32 weeks) at 36 weeks postmenstrual age (PMA) (preterm group) and compare them with healthy term controls (term controls). We also compared the parameters in preterm infants with and without chronic lung disease (CLD).

Prenatal detection of major congenital heart disease – optimising resources to improve outcomes

INTRODUCTION Congenital heart disease (CHD) is the most common major structural fetal abnormality and the benefits of prenatal detection are well described. The objective of this study was to evaluate the precision of prenatal diagnosis at a single tertiary referral unit over two three year periods (2006, 2007, 2008 and 2010, 2011, 2012), before and after a prenatal screening protocol for CHD was developed to include extended cardiac views, mandatory recall for suboptimal views, and a multidisciplinary Fetal Cardiac clinic was established. There exists a single national centre for paediatric cardiothoracic surgery in Ireland, a situation which facilitates near complete case ascertainment. MATERIALS AND METHODS Surgery records of the National Childrens Cardiac Centre were interrogated for all cases of major congenital heart defects requiring surgical intervention in the first six months of life. Minor procedures such as ligation of a patent ductus arteriosus and isolated atrial septal defect repairs were excluded. Analyses of the Fetal Medicine database at the Rotunda Hospital (a stand-alone tertiary level perinatology centre with 8500 deliveries per year) and the mortality data at the Perinatal Pathology department were conducted. The Cochrane-Armitage trend test was used to determine statistical significance in prenatal detection rates over time. RESULTS 51,822 women delivered during the study period, and the incidence of major congenital heart disease either that underwent surgical intervention or that resulted in perinatal mortality, was 238/51,822 (0.5%). Prenatal detection of major CHD increased from 31% to 91% (p<0.001). Detection of critical duct-dependant lesions rose from 19% to 100%. CONCLUSION We attribute the dramatic improvement in prenatal detection rates to the multifaceted changes introduced during the study period. Improved prenatal detection for births that are geographically remote from the National Paediatric Cardiac Centre will require local replication of this prenatal programme.

Early onset preeclampsia is associated with an elevated mean platelet volume (MPV) and a greater rise in MPV from time of booking compared with pregnant controls: results of the CAPE study

Abstract Objective: To characterise Mean platelet volume (MPV) in patients with early onset preeclampsia (EOPE) and unaffected controls from time of first antenatal visit until the postpartum. Materials and methods: Retrospective secondary analysis of an observational study in an Irish tertiary referral centre with 9000 deliveries annually. The MPV of 27 women with EOPE was compared to 19 unaffected controls. The inclusion criteria for the disease state was the development of EOPE defined by the National Institute for Health and Care Excellence (NICE) guideline, as new onset hypertension presenting after 20 weeks and prior to 34 weeks with significant proteinuria. Between October 2013 and July 2015 we recruited 27 women with EOPE and 19 pregnant controls. Statistical analysis was performed using paired T-test of Mann-Whitney test where appropriate and a P-value <0.05 was deemed significant. Results: At time of diagnosis and late in the third trimester MPV was significantly increased to 9.0 (±0.3) fL in cases of EOPE in comparison to 8.5 (±0.6) fL in normotensive controls (P<0.05). There was no significant difference during the first trimester or postpartum when comparing the MPV in EOPE to controls. Conclusion: Despite an increased MPV at time of diagnosis of EOPE this study did not demonstrate a potential use for increased MPV as a first trimester screening tool.

Hepatitis C virus-associated thrombocytopenia in pregnancy: impact upon multidisciplinary care provision.

Abstract Objective: Recent studies have implicated hepatitis C virus (HCV) in the pathogenesis of immune thrombocytopenia. In pregnancy-associated immune thrombocytopenia, multidisciplinary management is required due to a potential for bleeding complications. We performed a retrospective review of HCV-infected pregnant women and age-matched controls who were not infected with HCV. Methods: One hundred and six women with a HCV viral load were identified from 2009 to 2011. Results: Thrombocytopenia was identified in 10.3% of HCV-infected pregnant women and 1.6% of age-matched controls (P<0.001). Mean platelet count during pregnancy was 120±23×109/L in HCV-infected women and at delivery was significantly lower in HCV-infected women than in controls (P=0.01). Despite the significant difference in platelet counts, there was no significant difference in estimated blood loss (EBL) at delivery. Regional anaesthesia was performed in 73% of thrombocytopenic HCV-infected women and no complications were recorded. There were no fetal bleeding complications. Conclusion: In the first study to date to investigate the impact of HCV on maternal platelet count we demonstrated a significantly higher frequency of thrombocytopenia and a significantly lower platelet count in HCV-infected pregnant women compared with controls. Interestingly, thrombocytopenia had no detectable impact on EBL at delivery.

The Impact of Maternal Gestational Hypertension and the Use of Anti-Hypertensives on Neonatal Myocardial Performance

Background: Assessment of myocardial performance in neonates using advanced techniques such as deformation imaging and rotational mechanics has gained considerable interest. The applicability of these techniques for elucidating abnormal myocardial performance in various clinical scenarios is becoming established. We hypothesise that term infants born to mothers with gestational hypertension (GH) may experience impaired performance of the left and right ventricles during the early neonatal period. Objectives: We aimed to assess left and right ventricular (LV and RV) function using echocardiography in infants born to mothers with GH and compare them to a control group. Methods: Term infants (>36+6 weeks) born to mothers with GH underwent assessment to measure biventricular function using ejection fraction (EF), deformation imaging, left-ventricle rotational mechanics (apical rotation, basal rotation, twist, twist rate, and untwist rate), and right ventricle-specific functional parameters (tricuspid annular plane systolic excursion and fractional area change) in the first 48 h after birth. A control group comprising infants born to healthy mothers was used for comparison. Results: Fifteen infants with maternal GH and 30 age-matched controls were enrolled. The GH infants exhibited no differences in birthweight or LV or RV length, but they had lower EF (54 vs. 61%; p < 0.01), LV global longitudinal strain (-20 vs. -25%; p < 0.01), and LV twist (11 vs. 16°; p = 0.04). There were no differences in any of the RV functional parameters. Conclusion: Infants born to mothers with GH exhibited lower LV function than healthy controls, while RV function appeared to be preserved. This relationship warrants further exploration in a larger cohort.

Elevated plasma TFPI activity causes attenuated TF-dependent thrombin generation in early onset preeclampsia

Early onset preeclampsia (EOP) is a pregnancy-specific proinflammatory disorder that is characterised by competing thrombotic and bleeding risks. It was the aim of this study to characterise thrombin generation, a major determinant of thrombotic and bleeding risk, in order to better understand the haemostatic balance in patients with EOP. Patients with EOP were recruited at the Rotunda Hospital, Dublin. Twenty-six cases of EOP were recruited over a 21-month period, out of 15,299 deliveries at the Rotunda. Blood samples were collected into sodium citrate plus corn trypsin inhibitor anticoagulated vacutainers, platelet-poor plasma was prepared, and calibrated automated thrombography was used to assess thrombin generation. Results were compared to age and sex-matched non-pregnant controls (n=13) and age- and gestation-matched pregnant controls (n=20). The rate and extent of thrombin generation triggered by low-dose tissue factor (TF) was significantly reduced in patients with EOP compared to pregnant controls, most significantly in cases of severe EOP. EOP patients displayed a trend towards an increased response to endogenous activated protein C and thrombomodulin relative to pregnant controls. Plasma tissue factor pathway inhibitor (TFPI) activity was increased in EOP patients. Inhibition of TFPI abolished the attenuation of thrombin generation stimulated by low-dose TF. In conclusion, patients with EOP are characterised by an attenuated coagulation response characterised by reduced thrombin generation stimulated by low-dose TF and elevated plasma TFPI activity. These changes in coagulation may modulate thrombotic risk and bleeding risk in patients with EOP.

Reply to letter to the editor entitled “Non-Invasive cardiac output monitoring (NICOM ® ) can predict the evolution of uteroplacental disease—results of the prospective HANDLE study”

We thank Dr. Perry et al. [1] for their recent interest in the HANDLE study and would like to respond to some of their comments relating to our recent publication on the role of bioreactance obtained haemodynamic variables in the prediction of the uteroplacental diseases preeclampsia (PE) and fetal growth restriction (FGR) [2]. Our cohort did not exclude those with advanced maternal age (range 16–44 years) or obesity (body mass index range 16.26– 39.89; n = 54 (14.8%) with a BMI >30). This technology has previously been applied by my co-authors to a high risk population with a history of PE [3]. Therefore, our objective for this cohort was to better identify the at risk nulliparous parturient. As such multiparous women and those with a history of PE were excluded. In our methodology we detailed the power calculation from an anticipated 5% nulliparous PE rate in our local population and recruited 422 expecting to capture 20 PE cases. The anticipated 5% and subsequent 20 cases of nulliparous PE rate was previously achieved in another study carried out in our unit using transthoracic echocardiography in low risk nulliparous women [4]. Our group have also recently demonstrated very acceptable agreement between bioreactance and echocardiography for the measurement of stoke volume (mean bias 6 mL, LOA 18–29 mL, ICC 0.8) and measurement of cardiac output (mean bias 0.2L, LOA 1.3–1.7L, ICC 0.8) this cohort with a mean percentage error of 26% and a precision of 3.4% [5]. We entirely agree that FGR is not diagnosed by an EFW of <10th centile. It is well established that the detection rate fetal growth restriction (FGR) via clinical examination is suboptimal [6]. The authors completely agree that those fetus at greatest risk are those for whom the estimated fetal weight is less than the third centile. However, even when a definition of a birthweight <10th centile is applied there is a significant differencce in the haemodynamic status of the mother which therefore poses a potential for earlier recognition and better management of those pregnancies. As detailed in the manuscript only one third of infants with a birthweight <10th centile were suspected antenatally in this cohort. Although the data was not presented in the referred manuscript there were no differences in the haemodynamics of pregnancies where the birthweight was <3rd centile and those <10th centile. Whilst Perry et al. suggest a smaller mother would have a lower cardiac output we did not observe this difference. There was no difference in maternal cardiac index (adjusted for body surface area) of FGR and unaffected pregnancies. We thank Dr Perry et al. for their acknowledgement surrounding the strength of the postnatal element of this study. This has not been addressed in this manuscript and the postnatal persistence of a high resistance vasculature is the subject of a further manuscript which is currently under submission.

Erratum to: P47 A review of Massive Obstetric Haemorrhage (MOH) in the East of Ireland and its association with Maternal Obesity

Introduction: Massive obstetric haemorrhage (MOH), blood loss of >2000 ml, is a life-threatening emergency in the postpartum. The aim of this review is to address the incidence of maternal obesity, a modifiable risk factor contributing to MOH. Methods: This 6-year retrospective review involved the interrogation of the annual clinical reports of the tertiary maternal centres in the East of Ireland between the years 2009-2014. We assessed patient risk factors for developing MOH in the antenatal period with a focus on maternal obesity (Body Mass Index (BMI) ≥30 Kg/m2). Associations between categorical variables were tested using Pearson’s chisquare test. Results: The incidence of MOH was 2.21/1,000 livebirths during the 6-year period. Of those women 20.5% of cases had BMIs recorded and 34.72% of those with recorded BMI were obese. Within the obese cohort, patients suffered an average blood loss of 2820 ml in the first 24 hours postpartum, with 88% requiring a blood transfusion. There was a significant association between maternal obesity and developing MOH: (X2 (1) = 32.63, p-value < 0.001). Discussion: Maternal obesity is a preventable risk factor that contributes to MOH. As detailed in the most recent report by the World Health Organization (WHO) presented at the 2015 European