Sieglinde Mullers

Age-related changes in platelet function are more profound in women than in men

Age is a risk factor for cardiovascular disease (CVD), however the effect of age on platelet function remains unclear. Ideally, platelet function should be assayed under flow and shear conditions that occur in vivo. Our study aimed to characterise the effect of age on platelet translocation behaviour using a novel flow-based assay that measures platelet function in less than 200 μl of blood under conditions of arterial shear. Blood from males (n = 53) and females (n = 56), ranging in age from 19–82 and 21–70 respectively were perfused through custom-made parallel plate flow chambers coated with immobilised human von Willebrand Factor (VWF) under arterial shear (1,500s−1). Platelet translocation behaviour on VWF was recorded by digital-image microscopy and analysed. The study showed that aging resulted in a significant decrease in the number of platelet tracks, translocating platelets and unstable platelet interactions with VWF. These age related changes in platelet function were more profound in women than in men indicating that age and gender significantly impacts on platelet interactions with VWF.

Outcome following selective fetoscopic laser ablation for twin to twin transfusion syndrome: an 8 year national collaborative experience

OBJECTIVE With the recognition of the role of fetoscopic laser ablation for twin to twin transfusion syndrome (TTTS), there is a requirement for auditable standards for this technically challenging and specialized treatment. The purpose of this study is to report on the perinatal and medium-term neurodevelopmental outcomes following an 8-year national single center experience in the management of TTTS using the selective fetoscopic laser ablation technique. STUDY DESIGN An audit of all cases of TTTS treated with selective laser ablation by a single national fetal medicine team was performed. Overall perinatal survival and medium-term neurodevelopmental outcomes were reported and correlated with gestational age at diagnosis, placental location, volume of amnio-reduction, Quintero staging and percentage inter-twin growth discordance. Procedure-related complications were recorded. RESULTS The overall fetal survival for the first 105 consecutive cases of TTTS was 61% (128/210 fetuses). Dual survival occurred in 47% (49/105) of cases, and with a single survival rate of 28% (30/105), perinatal survival of least one infant was achieved in 75% (79/105) of cases. No correlation was found between any clinical or sonographic marker and perinatal outcome, although dual survival was noted to be significantly decreased with increasing Quintero stage (p=0.041). Currently, 86% of survivors have been reported to have a normal medium-term neurological outcome. CONCLUSION Fetoscopic laser ablation is the established optimal treatment for severe twin to twin transfusion syndrome (TTTS). We report comparable short and medium-term outcomes following the selective fetoscopic technique comparing results from our national program with internationally published single-center outcomes, supporting the efficacy and safety of this treatment at our center.

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.

Dynamic platelet function on von Willebrand factor is different in preterm neonates and full-term neonates: changes in neonatal platelet function.

Essentials It is unclear if platelet function differs between preterm and full‐term neonates. Platelet behavior was characterized using a flow‐based assay on von Willebrand Factor (VWF). Preterms had increased platelet interaction with VWF and glycoprotein Ibα expression. Platelets from preterm neonates behave differently on VWF compared to full‐term neonates.

Platelet function in patients with a history of unexplained recurrent miscarriage who subsequently miscarry again.

OBJECTIVE This study was designed to evaluate platelet aggregation in pregnant women with a history of unexplained recurrent miscarriage (RM) and to compare platelet function in such patients who go on to have either another subsequent miscarriage or a successful pregnancy. STUDY DESIGN A prospective longitudinal study was performed to evaluate platelet function in a cohort of patients with a history of unexplained RM. Platelet reactivity testing was performed at 4-7 weeks gestation, to compare platelet aggregation between those with a subsequent miscarriage and those who had successful live birth outcomes. Platelet aggregation was calculated using a modified assay of light transmission aggregometry with multiple agonists at different concentrations. RESULTS In a cohort of 39 patients with a history of RM, 30 had a successful pregnancy outcome while nine had a subsequent miscarriage again. Women with subsequent miscarriage had reduced platelet aggregation in response to adenosine diphosphate (P value 0.0012) and thrombin receptor activating peptide (P value 0.0334) when compared to those with successful pregnancies. Women with subsequent miscarriages also had a trend towards reduced platelet aggregation in response to epinephrine (P value 0.0568). CONCLUSION Patients with a background history of unexplained RM demonstrate reduced platelet function if they have a subsequent miscarriage compared to those who go on to have a successful pregnancy.

Platelet behaviour on von Willebrand Factor changes in pregnancy: Consequences of haemodilution and intrinsic changes in platelet function

Platelet function in pregnancy is poorly understood. Previous studies of platelet function in pregnancy have used non-physiological assays of platelet function with conflicting results. This study using a physiological assay of platelet function investigated platelet interactions with von Willebrand Factor (VWF) in blood from healthy pregnant women and healthy non-pregnant controls. Blood samples (200 µl) from third-trimester pregnancies (n = 21) and non-pregnant controls (n = 21) were perfused through custom-made parallel-plate flow chambers coated with VWF under arterial shear (1,500 s−1). Multi-parameter measurements of platelet interactions with the immobilized VWF surface were recorded by digital-image microscopy and analysed using custom-designed platelet-tracking software. Platelet interactions with VWF decreased in healthy third-trimester pregnant participants relative to controls. This effect is most likely due to haemodilution which occurs physiologically during pregnancy. Interestingly, platelets in blood from pregnant participants translocated more slowly on VWF under arterial-shear conditions. These decreases in platelet translocation speed were independent of haemodilution, suggesting intrinsic changes in platelet function with pregnancy.

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.

PF.11 Abnormal Platelet Function is Seen in Women with Unexplained Recurrent Miscarriage During Pregnancy

Objective To evaluate platelet aggregation in patients with a history of recurrent miscarriage (RM) during a subsequent successful pregnancy and compare them to healthy pregnant controls. Study design A prospective longitudinal study was performed to compare platelet function in 30 patients with a history of three consecutive unexplained first trimester pregnancy losses and 30 healthy age-matched pregnant controls. Exclusion criteria included the use of anti-platelet medications such as aspirin and medical conditions that can affect platelet function. Light transmission aggregometry was used to assay platelet agonists at different times and concentrations to create dose-response curves. Results In contrast, to the increased platelet aggregation response seen in healthy controls, platelet reactivity in patients with RM peaked at 12–14 weeks gestation, highlighted by the increased aggregation response to epinephrine (p = 0.0008) and collagen (p < 0.0001) and then decreased in the third trimester in response to epinephrine (p < 0.0001), arachidonic acid (p < 0.0001) and Thrombin Receptor Activating Peptide (p < 0.0001). Conclusion Patients with a history of recurrent miscarriage have significantly different platelet function when compared to healthy controls, in particular during the first trimester. Knowledge of which patients have impaired platelet function may allow for more targeted therapy in the setting of recurrent miscarriage.

PP.36 The Impact of Unexplained Recurrent Miscarriage on Subsequent Pregnancy Outcomes

Aim We sought to determine subsequent pregnancy outcomes in a cohort of women with a history of unexplained recurrent miscarriage (RM) as compared to healthy pregnancy controls. Study design This was a prospective cohort study of women attending a dedicated RM clinic in the Rotunda Hospital in 2011. Inclusion criteria included women with a history of three consecutive first trimester losses that were unexplained in the past, no medical intervention and singleton pregnancies only. The inclusion criteria for the healthy controls included no history of stillbirth, intrauterine growth restriction, preeclampsia or preterm labour. Results Of the 42 women with RM recruited to the study nine (23%) experienced further first trimester miscarriages, one molar and one ectopic pregnancy. The remaining RM cohort with ongoing pregnancies (n = 31) were compared to healthy controls (n = 31) matched for age and BMI. The only statistical difference between the two groups was the earlier mean gestational delivery of the RM group (38 + 2 vs 39 + 4 weeks, p = 0.004) attributed to earlier induction due to their past history. Otherwise there was no significant difference with respect to pregnancy complications, delivery and neonatal outcomes. All of RM patients achieved successful term deliveries with a 74% vaginal delivery rate and a mean birthweight of 3.23 kg. Conclusion This study re-iterates the reassuring prognosis for women with a history of unexplained RM who undergo supportive care at a dedicated clinic. The majority delivered appropriately grown fetuses at term which was comparable to healthy controls.