Objective: Spontaneous platelet aggregation has not been adequately assessed as a potential risk factor for adverse outcomes in pregnancy. Therefore the objective of this study was to assess spontaneous platelet aggregation (SPA), measured via a novel functional assay, as a risk factor for hypertensive disease and intra-uterine growth restriction (IUGR).Study design: This was a prospective longitudinal study. Spontaneous platelet aggregation was assessed as a marker of platelet reactivity using a modification of light transmission aggregometry. Platelet reactivity was assessed in four groups: non-pregnant healthy female volunteers (n = 30), longitudinally in normal uncomplicated pregnancy (n = 50), hypertensive disorder (n = 40) and IUGR (n = 30). The mean percentage SPA was plotted and compared across all groups.Results: Spontaneous platelet aggregation was significantly reduced in the first trimester compared to the non-pregnant group (p-value = 0.003). The mean aggregation for the hypertensive group was 1.9%, (95% CI -0.08 to 4.02) and for the IUGR group was 1.6%, (95% CI -0.6 to 3.72). Platelet aggregation in the hypertensive group was significantly reduced compared to the normal pregnant group (p < 0.05). Spontaneous platelet aggregation was also reduced in the IUGR group compared to normal pregnancy (p < 0.05).Conclusion: This study demonstrates that a reduction of spontaneous platelet aggregation may be a novel risk factor for adverse pregnancy outcomes such as pre-eclampsia and IUGR. The most clinically significant finding is that SPA is significantly lower in pregnancies complicated by hypertension and IUGR compared to those who had a normal pregnancy outcome. Further studies should be carried out to asses if spontaneous platelet aggregation may be a clinically useful tool for the prediction of preeclampsia and IUGR. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

OBJECTIVE:The aim of this study was to characterize platelet function in pregnant patients with a history of unexplained recurrent miscarriage (RM) in the third trimester of a subsequent viable pregnancy, a time at which platelet dysfunction may be associated with an increased obstetric risk.STUDY DESIGN:A prospective study was performed comparing 30 viable pregnancies that had reached at least 28 weeks' gestation amongst patients who had a background history of unexplained RM, with 30 healthy pregnant controls at a similar gestational age. Platelet function was determined by means of platelet aggregation in response to 5 different agonists at multiple concentrations.RESULTS:Amongst the 30 RM patients with ongoing viable pregnancies, we demonstrated significantly reduced platelet aggregation compared to the pregnant controls in the third trimester. For three out of five agonists, we demonstrated statistically significantly decreased platelet aggregation and for all five agonists we demonstrated significantly decreased platelet aggregation in the postnatal period. There were no obvious differences in obstetric outcomes.CONCLUSION:This study shows that women with a history of unexplained RM have reduced platelet function after 28 weeks' gestation in their subsequent pregnancies compared to healthy pregnant controls, but without this difference leading to any obvious increase in adverse obstetric risk.

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. (C) 2015 Elsevier Ireland Ltd. All rights reserved.

To establish 2nd and 3rd trimester ultrasound predictors of clinically significant intertwin birthweight (BW) discordance (18% as prospectively determined by this group). This prospective cohort study of 1,028 unselected twin pairs recruited over a two year period at 8 academic centers for the Evaluation of Sonographic Predictors of Restricted Growth in Twins (ESPRIT). Participants underwent 2- weekly ultrasonographic surveillance from 24 weeks gestation with surveillance of monochorionic (MC) twins 2-weekly from 16 weeks. Complete biometry was available for 960 twin pairs without TTTS. Biometric data from 20 to 40 weeks were evaluated as predictors of a BW discordance level >18%. Outcomes were adjusted for chorionicity and gestational age using stepwise logistic regression (significance level <0.05) Between 20 and 24 weeks, a BW discordance level > 18% is predicted most accurately by an intertwin discrepancy in biparietal diameter (BPD) > 5%. At 28-32 weeks an intertwin femur length (FL) discordance of 5% or greater is most useful in predicting 18% BW discordance. Late in the third trimester (32-36 weeks) abdominal circumference (AC) of 10% correlates most closely with BW discordance. The greatest sensitivity and specificity of any single predictor is an estimated fetal weight (EFW) discordance > 10% at 32 to 36 weeks. Cumulative analysis of all above sonographic predictors offers the most accurate means of predicting significant BW discordance way (sensitivity 67%, specificity 87%). Sonographic biometry in the 2nd and 3rd trimester can successfully identify twin pregnancies at risk for significant BW discordance. Although these individual parameters are helpful in predicting BW discordance, it is a sequential and cumulative pattern observed on serial evaluation that is most sensitive and specific. Importantly, for all individual biometric measurements and for composite biometry, ultrasound underestimates intertwin size discordanceTabled 1Second and third trimester predictors of significant birthweight discordance of > 18% Open table in a new tab

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.

Abnormalities of platelet function have been implicated in a number of obstetric complications and anti platelet therapy is used to prevent certain conditions. Research of platelet function in pregnancy has yielded conflicting results. We sought to critically evaluate platelet reactivity in pregnancy using an assay which allowed several agonists of varying concentrations to be assessed concurrently and aimed to clarify platelet reactivity in normal pregnancy. A prospective longitudinal study was performed throughout uncomplicated singleton pregnancies with patients recruited prior to 15 weeks’ gestation. They were controlled for a number of factors known to affect platelet reactivity. Blood samples were obtained in each trimester (n = 36). Thirty non-pregnant healthy female volunteers also had a platelet assay performed. A modification of standard light transmission aggregometry was used to assess platelet reactivity, with light absorbance measured following addition of 5 different agonists at sub-maximal concentrations. Dose-response curves were plotted and the Ec50 was calculated for each agonist. Platelet reactivity, as demonstrated by the Ec50, was significantly reduced in the 1st and 2nd trimester of pregnancy compared to the non pregnant state particularly with respect to collagen, (p = 0.002). Within the pregnancy cohort the platelet reactivity increased as the pregnancy progressed, most evident in response to arachidonic acid (AA) (p = 0.033). This study demonstrates that platelet reactivity is altered in pregnancy, highlighted by the significant reduction in reactivity seen in the 1st trimester. This information will be critically important for designing and interpreting interventions to prevent obstetric complications, such as preeclampsia.

The pregnant state must achieve a fine balance between hemorrhage and thrombosis. Platelets play a critical role in this balance yet there is a lack of clear knowledge and consensus about platelet function in pregnancy. This review will outline the mechanisms involved in platelet clot and thrombus formation, delineate the different techniques available for the assessment of platelet function and highlight the current understanding of platelet function in pregnancy. With respect to normal pregnancy, there appears to be an increase in platelet aggregation when compared with the nonpregnant state. In pregnancies complicated by pre-eclampsia and intrauterine growth restriction, platelets are further activated when compared with normal pregnancy. Platelet function testing in those with recurrent miscarriage suggests a tendency toward thrombosis. However, further studies are needed to clarify platelet function status in normal and complicated 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.

To determine abnormalities in reactivity of platelets in cases of pre-eclampsia and gestational hypertension using a novel platelet function assay. Thirty patients diagnosed with either pre-eclamspia or gestational hypertension were recruited. Inclusion criteria were singleton pregnancies between 24+0 and 39+6 with either pre-eclampsia or gestational hypertension as defined by ACOG criteria. Exclusion criteria included diabetes, clotting disorders, aspirin usage or BMI>30. All patients were in the third trimester of pregnancy and the values obtained were compared to patients (N=30) who were in the third trimester of uncomplicated normal pregnancy not affected by either pre-eclamspia or gestational hypertension. A 30ml whole blood sample was drawn according to a strict protocol to maintain platelet integrity. A platelet function assay was performed on each sample within 30 minutes of blood draw. A modification of standard light transmission aggregometry was used to assess platelet function, with light absorbance measured following addition of 5 different agonists at maximal and sub-maximal concentrations. Since platelets have multiple receptors it is necessary to study more than one receptor with the various agonists. The percentage aggregation response for each concentration of each agonist was calculated. Platelet reactivity differed significantly between the two groups of patients for each agonist. Platelet aggregation to arachidonic acid (p<0.0042), epinephrine (p<0.00001) and collagen (p<0.00001) was less reactive in pre-eclamptic and gestational hypertension than in uncomplicated third trimester patients. This pattern of platelet aggregation was not repeated for the agonists TRAP and ADP. We have demonstrated a significant reduction in platelet reactivity in patients with both pre-eclampsia and gestational hypertension compared to patients with uncomplicated pregnancies in the third trimester. These data may be of value when designing interventions for prevention or treatment of pre-eclampsia.

Platelet function has not been well characterised in pregnancy. We used a modification of light transmission aggregometry to prospectively assess SPA in normal and complicated pregnancies. The study was powered (80%) to detect a 6% change in platelet aggregation across the time-points and an 8% change for PET or IUGR. In 50 patients with normal pregnancy, platelet function was assessed in the three trimesters and post-natally. In 35 patients with pre-eclampsia (PET) and 18 patients with intra-uterine growth restriction (IUGR) platelet function was assessed in the third trimester. Comparisons between platelet function assays in the four time points of normal pregnancy were made using a mixed effects model with study participant as a random-effect, allowing for possible correlations between the repeated assessments. ANOVA was used to compare these assessments with the PET and IUGR groups. The results are presented as Bonferroni adjusted p-values. SPA increased significantly between the 1st and 2nd trimester (7% increase, p-value=0.0001); the 3rd trimester (9% increase, p-value=0.0020) and the post-natal assessment (15% increase, p-value=0.0002) in normal pregnancy. In contrast there was no increase in the platelet aggregation profile of patients with either PET or IUGR. We demonstrate for the first time a significant incremental increase in SPA with advancing gestational age in normal pregnancy. In contrast this increase in platelet aggregation does not occur in the third trimester in platelets from patients with either PET or IUGR. These results suggest that sequential analysis of SPA may be a novel marker for at risk pregnancies.

OBJECTIVE: In countries at latitudes above 42 degrees north, endogenous production of vitamin D essentially ceases from November until March.As fetal bone development is entirely dependent on the maternal pool of vitamin D there are concerns about the implications of inadequate levels.We sought to examine the prevalence of hypovitaminosis D in pregnancy and to correlate maternal vitamin D to fetal anthropometry and birthweight.STUDY DESIGN: This is a prospective cohort study.Sixty healthy pregnant women had 25-hydroxy vitamin D (25[OH]D) measured in the early pregnancy(mean 14.3ϩ/Ϫ2.6weeks), at 28 weeks and in cord blood at delivery.Two specific subgroups were analysed in order to examine results in the context of known seasonal variation in 25[OH]D.Thirty women were recruited in early pregnancy in September/October and delivered in March/April (winter cohort).A further 30 women were recruited in March/April and delivered in September/October (summer cohort).Fetal anthropometry was assessed with ultrasound at 20 and 34 weeks and at delivery birthweight, length and head circumference were recorded.RESULTS: There was a high prevalence of both hypovitaminosis D and vitamin D deficiency with a marked seasonal variation observed, Table 1.Maternal 25[OH]D correlated with fetal 25[OH]D in cord blood (pϽ0.05).In the winter cohort, a positive correlation was found between first trimester (pϭ0.04) and cord (pϭ0.02)25[OH]D, and fetal femur length at 20 weeks.Additionally a positive correlation was noted between 25[OH]D at 28 weeks (pϭ0.02)and in cord blood (pϭ0.007), and fetal femur length at 34 weeks.No significant association was noted between maternal and fetal 25[OH]D and infant birthweight, length or head circumference.CONCLUSION: The prevalence of maternal hypovitaminosis D is particularly high in women who are pregnant during winter months in northern latitudes.This may have potential detrimental effects on fetal skeletal growth.These findings add to the growing body of evidence supporting routine vitamin D supplementation in pregnancy.

ObjectiveAbnormalities of platelet function have been implicated in a range of obstetric complications. However, little information is available on changes in platelet function throughout normal pregnancy. Our objective was to assess platelet aggregation using a range of agonists across a range of concentrations at defined time points in pregnancy.Study DesignA total of 50 healthy women with uncomplicated singleton pregnancies were recruited prior to15 weeks gestation. Maternal blood samples were obtained before 15, 24 weeks and 34 weeks gestation. A modification of standard light transmission aggregometry was used to assess platelet function, with light absorbance measured following addition of 5 different agonists at sub-maximal concentrations. Since platelets have multiple receptors it is necessary to study more than one receptor with the various agonists. The percentage aggregation response for each concentration of each agonist was calculated. To characterise maximal platelet aggregation in each trimester of pregnancy dose response curves were plotted for each agonist in each trimester.ResultsPlatelet aggregation in response to three of the agonists is significantly enhanced in the second and third trimesters (p<0.0001). Fig 1 demonstrates that platelet aggregation to arachidonic acid (AA), collagen and epinephrine in the first trimester followed similar trends and differed significantly to later gestations (p<0.0001). This pattern of platelet aggregation was not repeated for the agonists TRAP and ADP.ConclusionTabled 1 ObjectiveAbnormalities of platelet function have been implicated in a range of obstetric complications. However, little information is available on changes in platelet function throughout normal pregnancy. Our objective was to assess platelet aggregation using a range of agonists across a range of concentrations at defined time points in pregnancy. Abnormalities of platelet function have been implicated in a range of obstetric complications. However, little information is available on changes in platelet function throughout normal pregnancy. Our objective was to assess platelet aggregation using a range of agonists across a range of concentrations at defined time points in pregnancy. Study DesignA total of 50 healthy women with uncomplicated singleton pregnancies were recruited prior to15 weeks gestation. Maternal blood samples were obtained before 15, 24 weeks and 34 weeks gestation. A modification of standard light transmission aggregometry was used to assess platelet function, with light absorbance measured following addition of 5 different agonists at sub-maximal concentrations. Since platelets have multiple receptors it is necessary to study more than one receptor with the various agonists. The percentage aggregation response for each concentration of each agonist was calculated. To characterise maximal platelet aggregation in each trimester of pregnancy dose response curves were plotted for each agonist in each trimester. A total of 50 healthy women with uncomplicated singleton pregnancies were recruited prior to15 weeks gestation. Maternal blood samples were obtained before 15, 24 weeks and 34 weeks gestation. A modification of standard light transmission aggregometry was used to assess platelet function, with light absorbance measured following addition of 5 different agonists at sub-maximal concentrations. Since platelets have multiple receptors it is necessary to study more than one receptor with the various agonists. The percentage aggregation response for each concentration of each agonist was calculated. To characterise maximal platelet aggregation in each trimester of pregnancy dose response curves were plotted for each agonist in each trimester. ResultsPlatelet aggregation in response to three of the agonists is significantly enhanced in the second and third trimesters (p<0.0001). Fig 1 demonstrates that platelet aggregation to arachidonic acid (AA), collagen and epinephrine in the first trimester followed similar trends and differed significantly to later gestations (p<0.0001). This pattern of platelet aggregation was not repeated for the agonists TRAP and ADP. Platelet aggregation in response to three of the agonists is significantly enhanced in the second and third trimesters (p<0.0001). Fig 1 demonstrates that platelet aggregation to arachidonic acid (AA), collagen and epinephrine in the first trimester followed similar trends and differed significantly to later gestations (p<0.0001). This pattern of platelet aggregation was not repeated for the agonists TRAP and ADP. ConclusionTabled 1

To identify changing trends in induction of labour in a large obstetric population over the last three decades. A retrospective cohort study from 1979-2008 to review the induction of labour rates in women delivering in three obstetric hospitals in a single urban area. Details were obtained from combined databases of each hospital. In the years 1979-2008 there were a total of 625,916 deliveries of viable pregnancies. 205,602 in the years 1979-1988; 191,315 in the years 1989-1998 and 228,999 in the decade 1999-2008. Looking at the three institutions as a whole, induction rates have risen from 13.7% in 1979-1988 to 18.2% in the period 1989-1998 to 22.6% in the period 1999-2008. Accordingly overall caesarean section rates have increased from 7.7 to 21% in the thirty year period. Rates of induction in primiparous women have increased from 21% to 29% in this period and the rates of caesarean sections in this group have also risen. Standard timing of induction was variable ranging from 41+3 to 42+0 across the three decades. Induction rates have increased greatly over the thirty year period of this retrospective review. Overall caesarean section rates have also increased. Review of the databases showed great variations in timing, policy and mode of induction across the three institutions. This increasing trend in induction has important implications for the future management of obstetric populations.

Background Classically monozygotic (MZ) twins are considered identical. However, there are a number of cases of MZ twins concordant for genotype but not phenotype. A review of these cases was performed in our institution. Methods Patients who had monozygotic twin pregnancies with discordant anomalies but normal karyotype were identified from the Fetal Assessment Unit Database of the Rotunda Hospital between January 2006 and July 2011. A retrospective chart review was then performed. Results Fifteen pairs of monozygotic twins who were genotypically identical but phenotypically different were identified. Average maternal age was 28.6 years. 93% were spontaneously conceived and all had ultrasound assignment of chorionicity prior to 16 weeks gestation. Discordant anomalies detected by ultrasound included two cystic hygromas, one duodenal atresia, three spinal abnormalities, three cerebral abnormalities one Congenital Diaphragmatic Hernia, two Gastroschisis, one bilateral hydronephrosis, one single vessel cord and one twin with a two vessel cord. 73% confirmed normal karyotype with invasive testing. Two patients underwent laser ablation of connecting vessels and this was associated with intrauterine demise of the affected twin. Regarding outcomes of the other pregnancies, three had intrauterine death of both twins. The twin with CDH had an early neonatal death. Conclusion This is an interesting series which highlights the non-identical nature that can occur in monozygotic twin pregnancies. Emerging data shows that there are different types of genetic/epigenetic and prenatal post-zygotic mechanisms that can cause discordance within such twin pairs. This possibility should be included in counselling patients with monozygotic pregnancies.