Carbetocin vs. oxytocin at elective caesarean delivery: a double-blind, randomised, controlled, non-inferiority trial of low- and high-dose regimens.

Carbetocin or oxytocin are given routinely as first-line uterotonic drugs following delivery of the neonate during caesarean delivery to prevent postpartum haemorrhage. Low doses may be as effective as high doses with a potential reduction in adverse effects. In this double-blind, randomised, controlled, non-inferiority trial, we assigned low-risk patients undergoing elective caesarean delivery under spinal anaesthesia to one of four groups: carbetocin 20 µg; carbetocin 100 µg; oxytocin 0.5 IU bolus + infusion; and oxytocin 5 IU bolus + infusion. The study drug was given intravenously after delivery of the neonate. Uterine tone was assessed by the obstetrician 2, 5 and 10 minutes after study drug administration according to an 11-point verbal numerical rating scale (0 = atonic, 10 = excellent tone). The primary outcome measure was uterine tone 2 min after study drug administration. The pre-specified non-inferiority margin was 1.2 points on the 11-point scale. Secondary outcomes included uterine tone after 5 and 10 minutes, use of additional uterotonics, blood loss and adverse effects. Data were available for 277 patients. Carbetocin 20 µg resulting in uterine tone of (median (IQR [range])) 8 (7-8 [1-10]) was non-inferior to carbetocin 100 µg with tone 8 (7-9 [3-10]), median (95%CI) difference 0 (-0.44-0.44). Similarly, oxytocin 0.5 IU with tone 7 (6-8 [3-10]) was non-inferior to oxytocin 5 IU with tone 8 (6-8 [2-10]), median (95%CI) difference 1 (0.11-1.89). Carbetocin 20 µg was also non-inferior to oxytocin 5 IU, and oxytocin 0.5 IU was non-inferior to carbetocin 100 µg. Uterine tone after 5 and 10 minutes, use of additional uterotonics, blood loss and adverse effects were similar in all groups.

Complex foraging behaviours in wild birds emerge from social learning and recombination of components.

Recent well-documented cases of cultural evolution towards increasing efficiency in non-human animals have led some authors to propose that other animals are also capable of cumulative cultural evolution, where traits become more refined and/or complex over time. Yet few comparative examples exist of traits increasing in complexity, and experimental tests remain scarce. In a previous study, we introduced a foraging innovation into replicate subpopulations of great tits, the 'sliding-door puzzle'. Here, we track diffusion of a second 'dial puzzle', before introducing a two-step puzzle that combines both actions. We mapped social networks across two generations to ask if individuals could: (1) recombine socially-learned traits and (2) socially transmit a two-step trait. Our results show birds could recombine skills into more complex foraging behaviours, and naïve birds across both generations could learn the two-step trait. However, closer interrogation revealed that acquisition was not achieved entirely through social learning-rather, birds socially learned components before reconstructing full solutions asocially. As a consequence, singular cultural traditions failed to emerge, although subpopulations of birds shared preferences for a subset of behavioural variants. Our results show that while tits can socially learn complex foraging behaviours, these may need to be scaffolded by rewarding each component. This article is part of a discussion meeting issue 'The emergence of collective knowledge and cumulative culture in animals, humans and machines'.

Sociability increases survival of adult female giraffes.

Studies increasingly show that social connectedness plays a key role in determining survival, in addition to natural and anthropogenic environmental factors. Few studies, however, integrated social, non-social and demographic data to elucidate what components of an animal's socio-ecological environment are most important to their survival. Female giraffes (Giraffa camelopardalis) form structured societies with highly dynamic group membership but stable long-term associations. We examined the relative contributions of sociability (relationship strength, gregariousness and betweenness), together with those of the natural (food sources and vegetation types) and anthropogenic environment (distance from human settlements), to adult female giraffe survival. We tested predictions about the influence of sociability and natural and human factors at two social levels: the individual and the social community. Survival was primarily driven by individual- rather than community-level social factors. Gregariousness (the number of other females each individual was observed with on average) was most important in explaining variation in female adult survival, more than other social traits and any natural or anthropogenic environmental factors. For adult female giraffes, grouping with more other females, even as group membership frequently changes, is correlated with better survival, and this sociability appears to be more important than several attributes of their non-social environment.

Hierarchically embedded interaction networks represent a missing link in the study of behavioral and community ecology.

Because genes and phenotypes are embedded within individuals, and individuals within populations, interactions within one level of biological organization are inherently linked to interactors at others. Here, we expand the network paradigm to consider that nodes can be embedded within other nodes, and connections (edges) between nodes at one level of organization form "bridges" for connections between nodes embedded within them. Such hierarchically embedded networks highlight two central properties of biological systems: 1) processes occurring across multiple levels of organization shape connections among biological units at any given level of organization and 2) ecological effects occurring at a given level of organization can propagate up or down to additional levels. Explicitly considering the embedded structure of evolutionary and ecological networks can capture otherwise hidden feedbacks and generate new insights into key biological phenomena, ultimately promoting a broader understanding of interactions in evolutionary theory.

Carbetocin at elective caesarean section: a sequential allocation trial to determine the minimum effective dose in obese women.

Postpartum haemorrhage is a leading cause of maternal death during childbirth. There is an increasing incidence of atonic postpartum haemorrhage in developed countries, and maternal obesity has been proposed as a contributing factor. The dose-response relationship of carbetocin in obese women has not yet been determined. We conducted a double-blind, dose-finding study of carbetocin using a biased coin up-and-down design in women with a body mass index ≥ 40 kg.m-2 undergoing elective caesarean section. The determinant for a successful response was satisfactory uterine tone, with no intra-operative need for additional uterotonic drugs. Secondary outcomes included the use of additional uterotonic drugs postoperatively, estimated blood loss and adverse effects of carbetocin administration. Thirty women were recruited to the study. The median (IQR [range]) body mass index was 44.93 (41.5-55.2 [40-66.5]) kg.m-2 . The ED90 of carbetocin was estimated as 62.9 (95%CI 57.0-68.7) µg using the truncated Dixon and Mood method, and 68 (95%CI 52-77) µg using the isotonic regression method. The estimated blood loss was 880 (621-1178 [75-2442]) ml. The overall rates of hypotension and hypertension after delivery were 40% and 6.7%, respectively, while nausea occurred in 26.7% of women. The ED90 for carbetocin in obese women at elective caesarean section is lower than the dose of 100 µg currently recommended by the Society of Obstetricians and Gynaecologists of Canada, but is approximately four times higher than the previously demonstrated ED90 of 14.8 µg in women with body mass index < 40 kg.m-2 .

Diurnal variation in the production of vocal information about food supports a model of social adjustment in wild songbirds.

Wintering songbirds have been widely shown to make economic foraging decisions to manage the changing balance of risks from predation and starvation over the course of the day. In this study, we ask whether the communication and use of information about food availability differ throughout the day. First, we assessed temporal variation in food-related vocal information produced in foraging flocks of tits ( Paridae) using audio recordings at radio-frequency identification-equipped feeding stations. Vocal activity was highest in the morning and decreased into the afternoon. This pattern was not explained by there being fewer birds present, as we found that group sizes increased over the course of the day. Next, we experimentally tested the underlying causes for this diurnal calling pattern. We set up bird feeders with or without playback of calls from tits, either in the morning or in the afternoon, and compared latency to feeder discovery, accumulation of flock members, and total number of birds visiting the feeder. Irrespective of time of day, playbacks had a strong effect on all three response measures when compared to silent control trials, demonstrating that tits will readily use vocal information to improve food detection throughout the day. Thus, the diurnal pattern of foraging behaviour did not appear to affect use and production of food-related vocalizations. Instead, we suggest that, as the day progresses and foraging group sizes increase, the costs of producing calls at the food source (e.g. competition and attraction of predators) outweigh the benefits of recruiting group members (i.e. adding individuals to large groups only marginally increases safety in numbers), causing the observed decrease in vocal activity into the afternoon. Our findings imply that individuals make economic social adjustments based on conditions of their social environment when deciding to vocally recruit group members.

Uterotonics in elective caesarean delivery: a randomised non-inferiority study comparing carbetocin 20 µg and 100 µg.

Postpartum haemorrhage is the leading cause of maternal mortality worldwide and prophylactic uterotonic drug administration after the delivery of the infant is advised. Carbetocin is recommended as an uterotonic, but the minimum effective dose has not been verified. We compared the efficacy of two doses of intravenous carbetocin (20 µg and 100 µg) in women undergoing elective caesarean delivery. This was a randomised, double-blind, non-inferiority study in women at low risk of postpartum haemorrhage. Carbetocin was administered on delivery of the anterior shoulder of the neonate. Uterine tone was assessed by the obstetrician 2 min and 5 min after carbetocin administration according to an 11-point numerical rating scale (0 = atonic uterus and 10 = firm uterus). The primary outcome was uterine tone 2 min after carbetocin administration. The pre-specified non-inferiority margin was 1 point on the 11-point scale. Secondary outcomes included: uterine tone at 5 min; use of additional uterotonics within 24 h; blood loss; and adverse effects. Data were available for 53 women in the carbetocin-20 group and for 55 women in the carbetocin-100 group. The mean (SD) uterine tone at 2 min was 7.5 (1.9) in the carbetocin-20 group and 8.0 (1.5) in the carbetocin-100 group. The lower limit of the one-sided 95%CI for the mean difference was outside the non-inferiority margin (at -1.1; p = 0.11) meaning non-inferiority of carbetocin 20 µg compared with carbetocin 100 µg could not be confirmed. However, the secondary outcome measures of uterine tone at 5 min, blood loss and use of additional uterotonics were similar in both groups.

Experimental disturbances reveal group-level costs of social instability.

In group-living species, social stability is an important trait associated with the evolution of complex behaviours such as cooperation. While the drivers of stability in small groups are relatively well studied, little is known about the potential impacts of unstable states on animal societies. Temporary changes in group composition, such as a social group splitting and recombining (i.e. a disturbance event), can result in individuals having to re-establish their social relationships, thus taking time away from other tasks such as foraging or vigilance. Here, we experimentally split socially stable groups of captive zebra finches (Taeniopygia guttata), and quantified the effects of repeated disturbance events on (1) group foraging efficiency, and (2) co-feeding associations when subgroups were recombined. We found that the efficiency of groups to deplete a rich, but ephemeral, resource patch decreased after just a single short disturbance event. Automated tracking of individuals showed that repeated disturbances reduced efficiency by causing social relationships to become more differentiated and weaker, resulting in fewer individuals simultaneously accessing the patch. Our experiment highlights how short-term disturbances can severely disrupt social structure and group functionality, revealing potential costs associated with group instability that can have consequences for the evolution of animal societies.

Individual variation in local interaction rules can explain emergent patterns of spatial organization in wild baboons.

Researchers have long noted that individuals occupy consistent spatial positions within animal groups. However, an individual's position depends not only on its own behaviour, but also on the behaviour of others. Theoretical models of collective motion suggest that global patterns of spatial assortment can arise from individual variation in local interaction rules. However, this prediction remains untested. Using high-resolution GPS tracking of members of a wild baboon troop, we identify consistent inter-individual differences in within-group spatial positioning. We then apply an algorithm that identifies what number of conspecific group members best predicts the future location of each individual (we call this the individual's neighbourhood size) while the troop is moving. We find clear variation in the most predictive neighbourhood size, and this variation relates to individuals' propensity to be found near the centre of their group. Using simulations, we show that having different neighbourhood sizes is a simple candidate mechanism capable of linking variation in local individual interaction rules-in this case how many conspecifics an individual interacts with-to global patterns of spatial organization, consistent with the patterns we observe in wild primates and a range of other organisms.

Consistent individual differences in the social phenotypes of wild great tits, Parus major.

Despite growing interest in animal social networks, surprisingly little is known about whether individuals are consistent in their social network characteristics. Networks are rarely repeatedly sampled; yet an assumption of individual consistency in social behaviour is often made when drawing conclusions about the consequences of social processes and structure. A characterization of such social phenotypes is therefore vital to understanding the significance of social network structure for individual fitness outcomes, and for understanding the evolution and ecology of individual variation in social behaviour more broadly. Here, we measured foraging associations over three winters in a large PIT-tagged population of great tits, and used a range of social network metrics to quantify individual variation in social behaviour. We then examined repeatability in social behaviour over both short (week to week) and long (year to year) timescales, and investigated variation in repeatability across age and sex classes. Social behaviours were significantly repeatable across all timescales, with the highest repeatability observed in group size choice and unweighted degree, a measure of gregariousness. By conducting randomizations to control for the spatial and temporal distribution of individuals, we further show that differences in social phenotypes were not solely explained by within-population variation in local densities, but also reflected fine-scale variation in social decision making. Our results provide rare evidence of stable social phenotypes in a wild population of animals. Such stable social phenotypes can be targets of selection and may have important fitness consequences, both for individuals and for their social-foraging associates.

Selection for territory acquisition is modulated by social network structure in a wild songbird.

The social environment may be a key mediator of selection that operates on animals. In many cases, individuals may experience selection not only as a function of their phenotype, but also as a function of the interaction between their phenotype and the phenotypes of the conspecifics they associate with. For example, when animals settle after dispersal, individuals may benefit from arriving early, but, in many cases, these benefits will be affected by the arrival times of other individuals in their local environment. We integrated a recently described method for calculating assortativity on weighted networks, which is the correlation between an individual's phenotype and that of its associates, into an existing framework for measuring the magnitude of social selection operating on phenotypes. We applied this approach to large-scale data on social network structure and the timing of arrival into the breeding area over three years. We found that late-arriving individuals had a reduced probability of breeding. However, the probability of breeding was also influenced by individuals' social networks. Associating with late-arriving conspecifics increased the probability of successfully acquiring a breeding territory. Hence, social selection could offset the effects of nonsocial selection. Given parallel theoretical developments of the importance of local network structure on population processes, and increasing data being collected on social networks in free-living populations, the integration of these concepts could yield significant insights into social evolution.

Individual personalities predict social behaviour in wild networks of great tits (Parus major).

Social environments have an important effect on a range of ecological processes, and form a crucial component of selection. However, little is known of the link between personality, social behaviour and population structure. We combine a well-understood personality trait with large-scale social networks in wild songbirds, and show that personality underpins multiple aspects of social organisation. First, we demonstrate a relationship between network centrality and personality with 'proactive' (fast-exploring) individuals associating weakly with greater numbers of conspecifics and moving between flocks. Second, temporal stability of associations relates to personality: 'reactive' (slow-exploring) birds form synergistically stable relationships. Finally, we show that personality influences social structure, with males non-randomly distributed across groups. These results provide strong evidence that songbirds follow alternative social strategies related to personality. This has implications not only for the causes of social network structure but also for the strength and direction of selection on personality in natural populations.

Social networks predict patch discovery in a wild population of songbirds.

Animals use social information in a wide variety of contexts. Its extensive use by individuals to locate food patches has been documented in a number of species, and various mechanisms of discovery have been identified. However, less is known about whether individuals differ in their access to, and use of, social information to find food. We measured the social network of a wild population of three sympatric tit species (family Paridae) and then recorded individual discovery of novel food patches. By using recently developed methods for network-based diffusion analysis, we show that order of arrival at new food patches was predicted by social associations. Models based only on group searching did not explain this relationship. Furthermore, network position was correlated with likelihood of patch discovery, with central individuals more likely to locate and use novel foraging patches than those with limited social connections. These results demonstrate the utility of social network analysis as a method to investigate social information use, and suggest that the greater probability of receiving social information about new foraging patches confers a benefit on more socially connected individuals.

Is mode of delivery associated with postpartum depression at 6 weeks: a prospective cohort study.

OBJECTIVE: To examine the relationship between delivery mode and postpartum depression at 6 weeks following hospital discharge. DESIGN: A prospective cohort study. SETTING: Eleven hospitals in Ontario, Canada. SAMPLE: A total of 2560 women ≥16 years of age who delivered singleton, live infants at term. METHODS: Women completed a questionnaire in hospital and 74% (n = 1897) participated in a structured telephone interview 6 weeks after discharge. Additional data were extracted from labour and delivery records. Generalised estimating equations (GEEs) were used to investigate factors associated with postpartum depression. MAIN OUTCOME MEASURE: Women were screened for depression at 6 weeks following hospital discharge using the Edinburgh Postnatal Depression Scale (EPDS). A score of ≥12 on the EPDS was used as a measure of the primary outcome, depression. RESULTS: Mode of delivery was not independently associated with postpartum depression, and did not factor into the main-effects model. The multivariable analysis identified 11 predictor variables for depression: young maternal age (OR 5.27; 95% CI 2.73-10.15); maternal hospital readmission (OR 3.02; 95% CI 1.46-6.24); non-initiation of breastfeeding (OR 2.02; 95% CI 0.99-4.11); good, fair, or poor self-reported postpartum health (OR 1.82; 95% CI 1.19-2.80); urinary incontinence (OR 1.79; 95% CI 1.06-3.03); multiparity (OR 1.59; 95% CI 1.22-2.08); low mental health functioning (OR 1.20; 95% CI 1.15-1.25); low subjective social status (OR 1.16; 95% CI 1.02-1.33); high number of unmet learning needs in hospital (OR 1.12; 95% CI 1.03-1.22); low social support (OR 1.06; 95% CI 1.03-1.09); and low physical health functioning (OR 1.03; 95% CI 1.003-1.055). An exploratory interaction model revealed that caesarean section was associated with higher odds of becoming depressed in Canadian-born women, but that in women born outside of Canada it was associated with a lower risk of becoming depressed. CONCLUSIONS: Delivery mode had no significant impact on the development of postpartum depression in the main-effects model. However, it may interact with place of birth and other unmeasured factors to create a risk for depression.

Mediastinal tumour in a pregnant patient presenting as acute cardiorespiratory compromise.

A parturient at 35 weeks' gestation presented with severe shortness of breath, orthopnea and signs of fetal compromise. She was diagnosed with a large mediastinal tumour occupying 65% of transthoracic diameter, and a pericardial effusion. The trachea, both mainstem bronchi, pulmonary artery and superior vena cava were compressed. Her dyspnea continued despite relief of the cardiac tamponade by percutaneous drainage. Tissue obtained via anterior mediastinotomy, performed under local anesthesia infiltration, revealed a definitive diagnosis of non-Hodgkin's lymphoma. The patient improved symptomatically following initiation of steroids and chemotherapy. She was delivered by elective cesarean section under epidural anesthesia on the fifth day after starting chemotherapy. The postoperative course was complicated by the development of a large pleural effusion that required drainage. Mother and baby were well at three and six-month follow up oncology visits.

Prospective multicenter study of pregnancy outcomes in women with heart disease.

BACKGROUND: The maternal and neonatal risks associated with pregnancy in women with heart disease receiving comprehensive prenatal care have not been well defined. METHODS AND RESULTS: We prospectively enrolled 562 consecutive pregnant women with heart disease and determined the outcomes of 599 pregnancies not ending in miscarriage. Pulmonary edema, arrhythmia, stroke, or cardiac death complicated 13% of pregnancies. Prior cardiac events or arrhythmia, poor functional class or cyanosis, left heart obstruction, and left ventricular systolic dysfunction independently predicted maternal cardiac complications; the cardiac event rate can be predicted using a risk index incorporating these predictors. Neonatal complications (20% of pregnancies) were associated with poor functional class or cyanosis, left heart obstruction, anticoagulation, smoking, and multiple gestations. CONCLUSIONS: Pregnancy in women with heart disease is associated with significant cardiac and neonatal complications, despite state-of-the-art obstetric and cardiac care. Maternal cardiac risk can be predicted with the use of a risk index.

Maternal neutrophil apoptosis in normal pregnancy, preeclampsia, and normotensive intrauterine growth restriction.

OBJECTIVE: In normal pregnancy there is both a neutrophilia and a mild neutrophil activation. In preeclampsia both direct and indirect evidence supports further marked neutrophil activation. In the pathogenesis of preeclampsia peripheral blood neutrophils may play a vital role in communicating between the preeclamptic placenta and the maternal vascular endothelium and contribute to the endothelial cell dysfunction that characterizes the maternal syndrome of preeclampsia. Preeclampsia shares many elements with the systemic inflammatory response syndrome. Neutrophils, key effectors of the systemic inflammatory response syndrome, are associated with hepatic necrosis and adult respiratory distress syndrome, both of which most commonly kill women with preeclampsia. We hypothesized that delayed neutrophil apoptosis could explain (1) the neutrophilia of normal pregnancy and (2) the differential maternal responses to the shared placental abnormality of preeclampsia and normotensive intrauterine growth restriction. STUDY DESIGN: Neutrophils were isolated (dextran 500, Ficoll [Amersham Pharmacia Biotech AB, Uppsala, Sweden], and erythrocyte lysis) from (1) case patients with preeclampsia at

The effect of indomethacin tocolysis in preterm labour on perinatal outcome: a randomised placebo-controlled trial.

OBJECTIVE: To determine whether indomethacin tocolysis in preterm labour is associated with a better perinatal outcome than placebo. DESIGN: A randomised placebo-controlled trial. SETTING: Two university teaching hospitals with level three neonatal intensive care units. POPULATION: Women in preterm labour with intact membranes between 23 and 30 weeks of gestation. METHODS: Random allocation to tocolysis with indomethacin (50 mg followed by 25 mg 6 hourly for 48 hours) or placebo in a double-blind fashion. MAIN OUTCOME MEASURES: The primary outcome, perinatal mortality or severe neonatal morbidity, was defined as perinatal death, necrotising enterocolitis, bronchopulmonary dysplasia, intraventricular haemorrhage or peri-ventricular leucomalacia. Data were analysed using odds ratios (OR) and 95% confidence intervals (95% CI). RESULTS: Between March 1995 and February 1996, 34 women (39 babies) were recruited. The baseline characteristics of the two groups were similar. No patient was lost to follow up. In the indomethacin group, gestation was prolonged by > 48 hours in 13/16 (81%) of women vs 10/18 (56%) in the placebo group. The incidence of perinatal mortality or severe neonatal morbidity was not significantly different between the groups, but occurred in twice as many babies in the indomethacin group as in the placebo group--6/19 (32%) vs 3/20 (15%) OR (95% CI) 2.62 (0.44-18.8). There was one perinatal death, of a baby delivered at 24 weeks of gestation. This occurred in the indomethacin group. CONCLUSION: There is no evidence that indomethacin tocolysis is beneficial, and further trials are needed to assess the impact of indomethacin tocolysis in preterm labour.