Can growth in dichorionic twins be monitored with individualized growth assessment?

OBJECTIVE: To characterize fetal growth in dichorionic twins using individualized growth assessment (IGA), a method based on individual growth potential estimates. METHODS: This secondary analysis included 286 fetuses/neonates from 143 dichorionic twin pregnancies that were part of the ESPRiT (Evaluation of Sonographic Predictors of Restricted Growth in Twins) study. The sample was subcategorized according to birth weight into appropriate-for-gestational-age (AGA) (n = 243) and small-for-gestational-age (SGA) (n = 43) cohorts. Serial biometric scans evaluating biparietal diameter, head circumference (HC), abdominal circumference, femur diaphysis length and estimated weight at 2-week intervals were used to evaluate fetal growth, while measurements of birth weight, crown-heel length and HC determined neonatal growth outcome. Six abnormalities (hypoxic ischemic encephalopathy, periventricular leukomalacia, necrotizing enterocolitis, respiratory distress, sepsis and death) constituted the evaluated adverse neonatal outcomes (ANO). IGA was used to: evaluate differences in second-trimester growth velocities between singletons (from a published dataset) and dichorionic twins (138 AGA twins with normal third-trimester growth); describe the degree to which actual third-trimester growth in twins followed expected growth (111 AGA twins, normal fetal growth and neonatal growth outcomes); determine if the fetal growth pathology score 1 (-FGPS1) could detect, quantify and classify twin growth pathology (224 AGA, 42 SGA); and assess the relationship between -FGPS1 and ANO (24 SGA twins with progressive growth restriction confirmed by abnormal neonatal growth outcome). RESULTS: The differences in second-trimester growth velocity between singletons and twins (means and variances) were small and not statistically significant. Percent deviations from the expected third-trimester size trajectories were within the 95% reference ranges derived from singletons at 95.7% (1677/1752) of timepoints studied. Abnormal growth was detected in 37.9% of AGA twins and 85.7% of SGA twins. Growth restriction was more heterogeneous in AGA twins, while in SGA twins progressive growth restriction was the principal type (66.7%). -FGPS1 patterns previously defined in singletons classified 97.5% of pathological twin cases. In our most severe form of growth restriction (progressive), there were only three (12.5%) ANOs related to growth abnormalities, all in cases with -FGPS1 values more negative than -2.0%. Using these criteria, the frequency of ANO was 33%. CONCLUSIONS: With respect to growth, dichorionic twins can be considered as two singletons in the same uterus. Normally growing dichorionic twins have the same growth potential as singletons with normal growth outcome. These twins also follow expected third-trimester growth trajectories with the same precision as do singletons. Third-trimester growth pathology can be detected, quantified and classified using -FGPS1 as in singletons. Limited evidence of a relationship between fetal growth abnormalities and adverse neonatal outcome was found. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

A retrospective cohort study of the characteristics of unsuccessful operative vaginal deliveries.

INTRODUCTION: Unsuccessful operative vaginal delivery (OVD) is associated with high rates of materno-fetal morbidity. We aimed to examine institutional rates of unsuccessful OVDs (uOVD) and compare them with successful OVD (sOVD) in order to identify factors to aid patient selection and education. METHODS: A 6-month retrospective cohort study was performed on all unsuccessful and successful OVDs in a tertiary level maternity hospital in the Republic of Ireland. Maternal demographics and obstetric factors were assessed to evaluate potential underlying risk factors for unsuccessful operative vaginal delivery versus successful vaginal delivery. RESULTS: There were 4,191 births during the study period with an OVD rate of 14.2% (n = 595) with 28 (4.7% of OVDs) being unsuccessful. Unsuccessful OVD were predominately nulliparous (25; 89.2%) with a mean maternal age of 30.1 years (range 20-42), with more than half (n = 15, 53.5%) being induced. The most common indication for induction was prolonged rupture of membranes (PROM) (n = 7, 25%) which was significantly different from the successful OVD group. A senior obstetrician was significantly more likely to be the primary operator in uOVD when compared to sOVD. (82.1 % V 54.1% p < 0.01). The majority of unsuccessful OVD were vacuum deliveries (n = 17; 60.7%), with a significantly higher mean birthweight when compared to successful OVD (3.695 kg V 3.483 kg; p < 0.01). Following an unsuccessful OVD, women were more likely to have a postpartum haemorrhage (64.2 % V 31.5% p < 0.01) and their infant was more likely to require admission to the neonatal intensive care unit (NICU) (32.1 % V 5.8% p < 0.01) when compared with successful OVD. CONCLUSION: Risk factors for unsuccessful OVD were higher birth weight and induction of labour. There was a higher incidence of postpartum haemorrhage and NICU admission when compared with successful OVD.

Fetoscopic Laser Ablation for Twin-to-Twin Transfusion Syndrome: A 15-year Review of Perinatal Survival.

Objective Twin to twin transfusion syndrome (TTTS) complicates 5-15% of monochorionic twin pregnancies and untreated is associated with a 90% mortality rate. The aim was to present the perinatal survival of patients with TTTS treated with laser ablation, by a national fetal medicine team. Methods This was a review of all cases of TTTS treated with fetoscopic laser ablation performed from March 2006 through to December 2020. All patients treated with fetoscopic laser were identified from the hospital database. The perinatal outcomes for the overall cohort and the individual Quintero stages were determined. Results A total of 155 cases of TTTS underwent fetoscopic laser ablation during the study period. The median gestational age at diagnosis was 19+1 weeks, with a mean growth discordance of 23.6%. The Quintero stage at diagnosis was: Stage 1 6.5% (10/155), Stage 2 49% (76/155), Stage 3 38.7% (60/155), Stage 4 5.8% (9/155). There was at least one survivor in 83.2% (129/155) of pregnancies, with dual survival in 52.9% (82/155). An increase in the rate of any survivor was observed from 75% (2006-2014) to 94% (2014-2020) (p<0.05). Dual survival decreased with increasing Quintero Stage (p<0.05). 80.6% (125/155) of pregnancies delivered prior to 34+6 weeks gestation. Conclusion Fetoscopic laser ablation is the recommended first line treatment for severe TTTS. We observed a survival rate of at least one twin in 83.2% pregnancies which is comparable to internationally published data on single-centre outcomes.

Third-trimester growth diversity in small fetuses classified as appropriate-for-gestational age or small-for-gestational age at birth.

OBJECTIVE: We have shown previously that third-trimester growth in small fetuses (estimated fetal weight (EFW) < 10th percentile) with birth weight (BW) < 10th percentile is heterogeneous using individualized growth assessment (IGA). We aimed to test our hypothesis that individual growth patterns in small fetuses with BW > 10th percentile are also variable but in different ways. METHODS: This was a study of 191 cases with EFW < 10th percentile and BW > 10th percentile (appropriate-for-gestational-age (AGA) cohort), derived from the PORTO study. Composite size parameters were used to quantify growth pathology at individual third-trimester timepoints (individual composite prenatal growth assessment score (-icPGAS)). The fetal growth pathology score 1 (-FGPS1), calculated cumulatively from serial -icPGAS values, was used to characterize third-trimester growth patterns. Vascular-system evaluation included umbilical artery (UA) and middle cerebral artery (MCA) Doppler velocimetry. Outcome variables were birth age (preterm/term delivery) and BW (expressed as growth potential realization index for weight (GPRIWT ) and percentile). The findings from the AGA cohort were compared with those from small fetuses (EFW < 10th percentile) with BW < 10th percentile (small-for-gestational-age (SGA) cohort). RESULTS: The AGA cohort was found to have 134 fetuses (70%) with normal growth pattern and 57 (30%) with growth restriction based on IGA criteria. Seven growth-restriction -FGPS1 patterns were observed, including the previously defined progressive, late, adaptive and recovering types. The recovering type was the most common growth pattern in the AGA cohort (50.9%). About one-third of fetuses without any evidence of growth restriction had significant unexplained abnormalities in the UA (34%) and MCA (31%) and elevated mean GPRIWT values (113 ± 12.5%). Comparison of the AGA and SGA cohorts indicated a significant difference in the distribution of -FGPS1 growth patterns (P = 0.0001). Compared with the SGA cohort, the AGA cohort had more fetuses with a normal growth pattern (70% vs 38%) and fewer cases with growth restriction (30% vs 62%). While the recovering type was the most common growth-restriction pattern in the AGA cohort (51%), the progressive type was the primary growth-restriction pattern in the SGA cohort (44%). No difference in the incidence of MCA or UA abnormality was found between the SGA and AGA cohorts when comparing subgroups of more than 10 fetuses. CONCLUSIONS: Both normal-growth and growth-restriction patterns were observed in the AGA cohort using IGA, as seen previously in the SGA cohort. The seven types of growth restriction defined in the SGA cohort were also identified in AGA cases, but their distribution was significantly different. In one-third of cases without evidence of growth pathology in the AGA cohort, Doppler abnormalities in the UA and MCA were seen. This heterogeneity underscores the difficulty of accurate classification of fetal and neonatal growth status using conventional population-based methods. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Embolus Analog Trajectory Paths Under Physiological Flowrates Through Patient-Specific Aortic Arch Models.

Atrial fibrillation (AF) is the most common irregular heartbeat among the world's population and is a major contributor to cardiogenic embolisms and acute ischemic stroke (AIS). However, the role AF flow plays in the trajectory paths of cardiogenic emboli has not been experimentally investigated. A physiological simulation system was designed to analyze the trajectory patterns of bovine embolus analogs (EAs) (n = 720) through four patient-specific models, under three flow conditions: steady flow, normal pulsatile flow, and AF pulsatile flow. It was seen that EA trajectory paths were proportional to the percentage flowrate split of 25-31% along the branching vessels. Overall, AF flow conditions increased trajectories through the left- (LCCA) and right (RCCA)-common carotid artery by 25% with respect to normal pulsatile flow. There was no statistical difference in the distribution of clot trajectories when the clot was released from the right, left, or anterior positions. Significantly, more EAs traveled through the brachiocephalic trunk (BCT) than through the LCCA or the left subclavian. Yet of the EAs that traveled through the common carotid arteries, there was a greater affiliation toward the LCCA compared to the RCCA (p < 0.05).

Sonographic markers of fetal adiposity and risk of Cesarean delivery.

OBJECTIVE: Increased fetal size is associated with shoulder dystocia during labor and subsequent need for assisted delivery. We sought to investigate if increased fetal adiposity diagnosed sonographically in late pregnancy is associated with increased risk of operative delivery. METHODS: This secondary analysis of the Genesis Study recruited 2392 nulliparous women with singleton pregnancy in cephalic presentation, in a prospective, multicenter study, to examine prenatal and intrapartum predictors of Cesarean delivery. Participants underwent ultrasound and clinical evaluation between 39 + 0 and 40 + 6 weeks' gestation. Data on fetal biometry were not revealed to patients or to their managing clinicians. A fetal adiposity composite of fetal thigh adiposity and fetal abdominal wall thickness was compiled for each infant in order to determine whether fetal adiposity > 90th centile was associated with an increased risk of Cesarean or operative vaginal delivery. RESULTS: After exclusions, data were available for 2330 patients. Patients with a fetal adiposity composite > 90th centile had a higher maternal body mass index (BMI) (25 ± 5 kg/m2 vs 24 ± 4 kg/m2 ; P = 0.005), birth weight (3872 ± 417 g vs 3585 ± 401 g; P < 0.0001) and rate of induction of labor (47% (108/232) vs 40% (834/2098); P = 0.048) than did those with an adiposity composite ≤ 90th centile. Fetuses with adiposity composite > 90th centile were more likely to require Cesarean delivery than were those with adiposity composite ≤ 90th centile (P < 0.0001). After adjusting for birth weight, maternal BMI and need for induction of labor, fetal adiposity > 90th centile remained a risk factor for Cesarean delivery (P < 0.0001). A fetal adiposity composite > 90th centile was more predictive of the need for unplanned Cesarean delivery than was an estimated fetal weight > 90th centile (odds ratio, 2.20 (95% CI, 1.65-2.94; P < 0.001) vs 1.74 (95% CI, 1.29-2.35; P < 0.001). Having an adiposity composite > 90th centile was not associated with an increased likelihood of operative vaginal delivery when compared with having an adiposity composite ≤ 90th centile (P = 0.37). CONCLUSIONS: Fetuses with increased adipose deposition are more likely to require Cesarean delivery than are those without increased adiposity. Consideration should, therefore, be given to adding fetal thigh adiposity and abdominal wall thickness to fetal sonographic assessment in late pregnancy. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

The Mechanical Characterisation of Bovine Embolus Analogues Under Various Loading Conditions.

Embolus Analogues (EAs) can provide understanding of the mechanical characteristics of blood clots of cardiac origin. Bovine EAs (n = 29) were fabricated with varying concentrations of thrombin (0-20 NIHU/ml blood). Histological staining confirmed that EA composition compared sufficiently with human samples reported in literature. EAs were mechanically described under seven testing conditions: tensile, compression, shear wave ultrasound elastography (SWE), parallel plate rheometry, indentation, creep and relaxation. The Young modulus of bovine EAs in tension varied from 7 kPa (5% strain) to 84 kPa (50% strain). The compressive Young modulus increased with increasing thrombin concentration, which was in agreement with the SWE results. There was no significant difference in Young modulus throughout the clot (p < 0.05). The EAs displayed a non-linear response under parallel plate rheometry, creep and stress relaxation. The 3rd order Mooney-Rivlin constitutive equation and Standard Linear Solid model were used to fit the non-linear stress-strain response and time-dependent properties, respectively. This is the first study in which bovine EAs, with and without addition of thrombin, are histologically and mechanically described with corresponding proposed constitutive equations. The equations and experimental data determined can be applied for future numerical and experimental testing of mammalian EAs and cardiac source clots.

Comparison of bioreactance and echocardiographic non-invasive cardiac output monitoring and myocardial function assessment in primagravida women.

BACKGROUND.: Non-invasive cardiac output monitoring (NICOM) using bioreactance (BRT) in pregnancy is gaining interest but lacks validation. We compared simultaneous cardiac output (CO) measurements obtained using the NICOM ® (BRT-CO) and echocardiography (echo-CO), and assessed the relationship between maternal characteristics and myocardial performance. METHODS.: Paired stroke volume (SV) and CO readings were obtained using NICOM ® and echocardiography, in a group of healthy nulliparous women throughout a 15 min period. Agreement between NICOM ® and echocardiography was assessed using Bland-Altman analysis and the intraclass correlation coefficient (ICC). Left ventricular (LV) function was assessed using systolic strain and tissue Doppler velocities (S', E', and A' waves). RESULTS.: Thirty-five women with a median [interquartile range] age, weight, and gestation of 29 [26-34] yr, 71 [64-79] kg, and 28 [21-29] weeks, respectively, were enrolled. There was good agreement between NICOM ® -measured and echocardiographically measured SV [mean bias 6 ml (limits of agreement -18 to 29); ICC 0.8 (95% confidence interval 0.6-0.9), P <0.001] and CO [mean bias 0.2 litres (limits of agreement -1.3-1.7); ICC 0.8 (95% confidence interval 0.7-0.9), P <0.001; mean percentage error ±26%; coefficient of error (precision)=3.4%]. The mean ( sd ) LV S' was 9.7 (2.3) cm s -1 . The mean ( sd ) LV strain was -18.6 (2.6)%. There was a negative relationship between BMI and LV diastolic function measured using the E':A' ratio ( r = -0.51, P <0.01). CONCLUSIONS.: Stroke volume and CO measurements obtained using NICOM ® were comparable to those obtained using echocardiography, with acceptable limits of agreement. Increased maternal BMI negatively impacts LV diastolic function measured using tissue Doppler imaging.

Liver fluke control on sheep farms in Northern Ireland: A survey of changing management practices in relation to disease prevalence and perceived triclabendazole resistance.

Reports of resistance to triclabendazole (TCBZ) among fluke populations have increased in recent years. Allied to this, there has been a rise in the prevalence of the disease, which has been linked to climate change. Results from questionnaire surveys conducted in Northern Ireland (NI) in 2005 (covering the years 1999-2004) and 2011 (covering the years 2008-2011) have provided an opportunity to examine the extent to which fluke control practices have changed over a prolonged time-frame, in light of these changes. A number of differences were highlighted. There was a significant shift away from the use of TCBZ over time, with it being replaced largely by closantel. The timing of treatments had moved earlier in the year, perhaps in response to climate change (and an altered pattern of disease). In relation to the frequency of drug treatments, there were no major changes in the overall pattern of drug treatments between the two survey points, although on both occasions approximately one-third of flock owners gave more than 3 treatments per year to ewes. In lowland areas in 2011, flock owners were rotating drug classes more often (each year and at each treatment) than in 2005, whereas in upland areas, flock owners were rotating less often and more were not rotating at all. Between 2005 and 2011, the percentage of flock owners giving quarantine treatments to bought-in stock had halved, to a very low level (approximately 10%). Using data from a complementary TCBZ resistance survey (Hanna et al., 2015), it has been shown that the way in which data are selected and which efficacy formula is applied can influence the calculation of drug efficiency and impact on diagnosis of resistance.

Postnatal MRI Brain in Infants Treated for Twin-Twin Transfusion Syndrome.

Untreated twin-twin transfusion syndrome (TTTS) is associated with significant mortality and neurological impairment. Fetoscopic laser surgery (FLS) is the treatment of choice. We sought to assess intracranial abnormalities in TTTS twins following treatment. In this prospective, blinded study MRI scans were performed on 3 groups; (1) monochorionic diamniotic (MCDA) twins with TTTS who had undergone FLS (n = 10), (2) MCDA twins without TTTS (n = 8) and (3) dichorionic twins (n = 8). Scans were scored as either normal or abnormal. The primary outcome was a composite of abnormal MRI brain or intrauterine fetal demise. The primary outcome occurred in 6/10 (60%) of the TTTS group versus 3/8 (37.5%) in the MCDA group. The primary outcome was significantly different across all study groups [p = 0.029; X2 = 7.112]. We found that twins treated for TTTS are more likely to have abnormalities on MRI brain at term than other twin groups. This group merits term-corrected MRI as part of their postnatal assessment.

Fasciola hepatica: Specificity of a coproantigen ELISA test for diagnosis of fasciolosis in faecal samples from cattle and sheep concurrently infected with gastrointestinal nematodes, coccidians and/or rumen flukes (paramphistomes), under field conditions.

Chronic fasciolosis is often diagnosed by faecal egg counting (FEC), following concentration of the eggs in the sample by a zinc sulphate floatation method. However, concentration by a sedimentation technique gives improved sensitivity. Interpretation of FEC results for fasciolosis is complicated by factors such as the long pre-patent period and irregular egg shedding. Thus, FEC reduction tests (FECRT), when used alone, are not completely reliable for diagnosis of anthelmintic susceptibility or resistance in local fluke populations, especially when parasite burdens are small. A Fasciola hepatica coproantigen ELISA test has been introduced which more accurately reflects the presence of flukes in the host bile ducts in late pre-patent infections, and absence of flukes following successful chemotherapeutic intervention. The aim of the present study was to elucidate the specificity of the F. hepatica coproantigen ELISA technique, particularly regarding potential cross-reactivity with rumen fluke (paramphistome), gastrointestinal nematode and coccidian infections. The method involved parallel testing of a large battery of faecal samples from field-infected cattle and sheep using floatation and sedimentation FECs and coproantigen analysis. No evidence was found for significant false positivity in the F. hepatica coproantigen ELISA due to paramphistome, coccidian and/or gastrointestinal nematode co-infections. With sedimentation FECs less than 10 F. hepatica eggs per gram (epg), the likelihood of a positive coproantigen result for the sample progressively decreased. Diagnosis of fasciolosis should be based on consideration of both FEC and coproantigen ELISA findings, to ensure optimum sensitivity for pre-patent and low-level infections.

Fasciola hepatica: a comparative survey of adult fluke resistance to triclabendazole, nitroxynil and closantel on selected upland and lowland sheep farms in Northern Ireland using faecal egg counting, coproantigen ELISA testing and fluke histology.

In order to investigate the incidence and distribution of adult fluke resistance to the fasciolicide tricalbendazole (TCBZ) amongst populations of Fasciola hepatica in sheep flocks in Northern Ireland (NI), individual rectal faeces samples were collected from 3 groups of 20 sheep, before (pre-dose), and 21 days after (post-dose) treatment of the animals with TCBZ, nitroxynil or closantel, on each of 13 well-managed sheep farms distributed across the province. The efficacy of each flukicide was determined for each farm, using faecal egg count reduction (FECRT) and F. hepatica coproantigen ELISA testing. In certain flocks, 2 sheep with high pre-dose faecal egg counts (FEC) were killed 3 days and 21 days respectively after TCBZ treatment, and the histology of the fluke reproductive organs was compared with that of flukes from untreated sheep, and from sheep treated with nitroxynil or closantel 2 days prior to death, using haematoxylin and eosin (H&E) staining and an in situ hybridisation method (TdT-mediated dUDP nick end labelling [TUNEL]) to demonstrate apoptosis. Results from FECRT revealed that in all flocks with a high fluke burden, TCBZ was ineffective in treating chronic fasciolosis, and this finding was generally supported by the results of the coproantigen reduction test (CRT). The histology of reproductive organs of flukes from TCBZ-treated sheep in these flocks was normal, when compared with untreated flukes, and this, together with the FECRT and CRT findings, indicated a likely diagnosis of TCBZ resistance in all the flocks with a high fluke burden. In contrast, nitroxynil and closantel were found to be fully effective against TCBZ-resistant flukes in each of the flocks bearing a high chronic fluke burden. All of the flocks with a high fluke burden and TCBZ resistance were managed on lowland in the South and East of NI. Upland flocks, in the North and West, had low fluke burdens, or were clear of infection; and FECs were too low to allow valid resistance testing. The study highlights the high level of penetration of TCBZ resistance throughout F. hepatica populations in areas of intensively managed sheep production with a high level of fluke challenge. Further, it emphasises the importance of pre-emptive chemotherapeutic action against chronic fasciolosis, using flukicides effective against the egg-producing adult flukes to minimise pasture contamination for the next season's lamb crop. This study also exemplifies the use of several complementary methods (FECRT; CRT; fluke histology; comparative anthelmintic efficacy testing) for confirmation of a diagnosis of fluke drug resistance.

Changing trends in diabetes mellitus in pregnancy.

The purpose of this study was to identify any changing trends in the incidence and caesarean section (CS) rate of pre-gestational diabetes mellitus (DM) and gestational diabetes mellitus (GDM) over a 10- year period, between 1999 and 2008. Although the incidence of pre-gestational DM has not significantly changed over the course of the last 10 years, there is an obvious rising trend in the incidence of GDM. Despite an increase in the overall CS rate during this time period, a parallel increase in the CS rate has not been observed among women whose pregnancies are complicated either by gestational or by pre-gestational diabetes (PGD).

Umbilical and fetal middle cerebral artery Doppler reference ranges in a twin population followed longitudinally from 24 to 38 weeks' gestation.

OBJECTIVE: To construct monochorionic diamniotic (MCDA) and dichorionic diamniotic (DCDA) twin reference ranges for umbilical artery (UA) pulsatility index (PI), UA resistance index (RI), fetal middle cerebral artery (MCA) PI and peak systolic velocity (PSV) and cerebroplacental ratio (CPR) from 24 weeks' to 38 weeks' gestation and compare these with published normal values for singleton pregnancies. METHODS: This prospective multicenter cohort study included 1028 unselected twin pairs recruited over a 2-year period. Participants with dichorionic twins underwent fortnightly ultrasound surveillance from 24 weeks' gestation, with monochorionic twins being followed every 2 weeks from 16 weeks until delivery. A total of 7536 fetal Doppler examinations in 618 twin pregnancies were included in the analysis, with reference ranges for MCDA and DCDA pregnancies constructed for each of the Doppler indices using multilevel modeling. RESULTS: UA-PI and UA-RI appear to be higher in twins than in singletons, and MCA-PI and MCA-PSV appear to be lower. The CPR also appears to be lower in twins than in singletons. Similar MCA indices were observed in MCDA and DCDA twins. CONCLUSION: We have established longitudinal reference ranges for UA-PI and UA-RI, MCA-PI and MCA-PSV and CPR in twin pregnancies, which appear to differ from those in singleton pregnancies. The derived twin-specific reference ranges may be more appropriate in the surveillance of these high-risk pregnancies. Applying the singleton CPR cut-off of ≤ 1.0 may lead to a large number of false-positive diagnoses of cerebral redistribution in twin fetuses.

Platelet reactivity changes significantly throughout all trimesters of pregnancy compared with the nonpregnant state: a prospective study.

OBJECTIVE: Platelets play an important role in the pathophysiology of uteroplacental disease and platelet reactivity may be an important marker of uteroplacental disease activity. However, platelet reactivity has not been evaluated comprehensively in normal pregnancy. We sought to evaluate platelet reactivity using a number of agonists at defined time points in pregnancy using a novel platelet assay and compare these with a nonpregnant cohort. DESIGN: Prospective longitudinal study. SETTING: Outpatient department of a large tertiary referral centre. SAMPLE: Eighty participants with 30 nonpregnant women and 50 pregnant women assessed longitudinally. METHODS: This was a prospective cohort study performed longitudinally throughout uncomplicated singleton pregnancies with participants recruited before 15 weeks of gestation. They were controlled for a number of factors known to affect platelet reactivity. Blood samples were obtained in each trimester. Thirty nonpregnant healthy female volunteers also had a platelet assay performed. A modification of standard light transmission aggregometry was used to assess platelet function, with light absorbance measured following the addition of five different agonists at submaximal concentrations. Dose-response curves were plotted for each agonist for the nonpregnant cohort and in each trimester for the pregnant cohort. MAIN OUTCOME MEASURES: Dose-response curves and median effective concentration. RESULTS: When compared with the nonpregnant controls a significant reduction was demonstrated in platelet reactivity to collagen during the first trimester of pregnancy (P < 0.0001). Platelet aggregation increased significantly from the first to third trimesters in response to collagen and arachidonic acid. CONCLUSION: Platelet reactivity varies according to pregnancy state, gestational age and agonist. The finding that platelet reactivity is reduced in the first trimester of pregnancy may be useful for the interpretation of further studies examining the role of platelet reactivity in the first trimester of pregnancies that develop uteroplacental disease.

Anthelmintic resistance in Northern Ireland (I): prevalence of resistance in ovine gastrointestinal nematodes, as determined through faecal egg count reduction testing.

The prevalence of anthelmintic resistance in Northern Ireland sheep flocks was evaluated between July and October 2011. Sampling kits were sent to 172 flock owners and returns were received from 91. Within this survey population, 27 flock owners used benzimidazole products, 10 used levamisole products, 15 used avermectin products, 26 used milbemycin products and 4 flock owners used the amino acetonitrile derivative, Monepantel. The remaining 9 flock owners used combination drenches (broad spectrum wormer plus fasciolicide). However, 15 sets of samples were ineligible for faecal egg count reduction testing due to either too low an egg count or insufficient faecal volume. Treatment efficacy below 95%, indicating significant resistance, was detected in 81% (n=24) of flocks tested for benzimidazole resistance; in 14% (n=1) of flocks tested for levamisole resistance; and in 50% (n=7) and 62% (n=13) of flocks tested for avermectin and milbemycin resistance, respectively. Monepantel resistance was absent in all (n=3) flocks tested. Combination products (broad spectrum nematocide plus flukicide) containing levamisole were entirely effective, while treatment efficacy below 95% was detected in 60% (n=3) of flocks where the nematocide in the combination product was a benzimidazole. Where parasite identification based on coproculture was completed, Trichostrongylus was the dominant genus detected in all cases post-treatment, indicating the occurrence of anthelmintic-resistant Trichostrongylus spp. populations. Benzimidazole efficacy was highest in treating Trichostrongylus spp. (51%) and lowest when treating Teladorsagia spp. Levamisole was 100% effective in treating Cooperia, but ineffective (0%) in treating Trichostrongylus spp. Avermectin efficacy was highest when treating Haemonchus contortus (100%) and Teladorsagia spp. (73%), with a marginally lower efficacy against Trichostrongylus spp. (71%). Moxidectin efficacy was 33% against Trichostrongylus spp., 68% against Teladorsagia spp., 97% against Cooperia spp. and 100% against Haemonchus contortus infections.

Anthelmintic resistance in Northern Ireland (III): uptake of 'SCOPS' (Sustainable Control of Parasites in Sheep) recommendations by sheep farmers.

Reports of anthelmintic resistance to multiple drugs in individual parasite species, and in multiple parasite species across virtually all livestock hosts, are increasingly common. A working group of UK researchers and practitioners devised a set of guidelines in 2003 (Sustainable Control of Parasites in Sheep, 'SCOPS') aimed at maintaining anthelmintic efficacy on farms. Over the years that followed, these guidelines were promoted through meetings, promotional literature and the agricultural press. Results from questionnaires conducted in Northern Ireland (NI) in 2005 (covering 1999-2004) and 2011 (covering 2008-2011) have provided an opportunity to examine the extent to which these campaigns have influenced parasite control on sheep farms. The percentage of flocks at risk of under-dosing through inaccurate weight estimation in NI has increased by 15.9% since 2005. The number of flocks at risk of under-dosing through non-calibrated equipment has increased by 14.3% since 2005. The size of the in refugia population may have potentially doubled, as indicated by an increased compliance with the recommendation (wherever possible) to leave a portion of the flock untreated. However, whether this is indeed the case cannot be explicitly determined without a measure of the impact of various factors, including host immunity, environment/climate, previous anthelmintic treatment and the species of parasite present.

Anthelmintic resistance in Northern Ireland. II: Variations in nematode control practices between lowland and upland sheep flocks.

A questionnaire to obtain information on nematode control practices and sheep management was sent to over 1000 farmers in Northern Ireland. Replies were received from 305 flock owners, and data from 252 of them were analysed. Farms were divided into lowland and upland areas. Sizes of pasture and stocking rates on lowland and upland farms were 59.5 hectares, 6.99 sheep/hectare and 62.9 hectares and 10.01 sheep/hectare, respectively. Mean drenching rates for lambs and adults were 2.33 and 2.44, respectively, in lowland flocks and 2.73 and 2.71, respectively, in upland flocks. Between 2008 and 2011, the most frequently identified compounds in use were benzimidazoles and moxidectin in lowland flocks, and benzimidazoles and avermectins in upland flocks. Over the same period the most frequently identified commercial formulations were Tramazole(®), Panacur(®) and Allverm(®) (white drench), Levacide(®) (yellow drench), Oramec(®) (clear drench; avermectin), Cydectin(®) (clear drench; moxidectin) and Monepantel(®) (orange drench). Most respondents (56.35%) treated their lambs at weaning and the most common time to treat ewes was identified to be pre-mating (67.86% of respondents). The results of the questionnaire survey revealed that lowland annual drench frequency was 2.33 and 2.44 in lambs and ewes, respectively, although drench frequencies were higher in upland flocks: 2.73 and 2.71 for lambs and ewes, respectively. Annual drench rotation was practiced by 43.96% of flock owners, but whether this was true rotation or pseudo-rotation (i.e., substitution of one anthelmintic product by another product belonging to the same chemical group of anthelmintics) could not be explicitly determined.