When does obstetric coagulopathy occur and how do I manage it?

Anticipating obstetric coagulopathy is important when obstetric anaesthetists are involved in the clinical management of women with postpartum haemorrhage. Although the incidence of coagulopathy in women with postpartum haemorrhage is low, significant hypofibrinogenaemia is associated with major haemorrhage-related morbidity and thus early identification and treatment is essential to improve outcomes. Point-of-care viscoelastic haemostatic assays, including thromboelastography and rotational thromboelastometry, provide granular information about alterations in clot formation and hypofibrinogenaemia, allow near-patient interpretation of coagulopathy, and can guide goal-directed treatment. If these assays are not available, anaesthetists should closely monitor the maternal coagulation profile with standard laboratory testing during the active phase of postpartum bleeding in order to rule coagulopathy 'in or out', decide if pro-haemostatic therapies are indicated, and assess the response to haemostatic support.

Four years' experience of a ROTEM® -guided algorithm for treatment of coagulopathy in obstetric haemorrhage.

We report four years of observational data from a large UK hospital and tertiary referral unit, following the introduction of a rotational thromboelastometry-guided algorithm for treatment of coagulopathy in major obstetric haemorrhage. Fibrinogen concentrate was used to treat acquired hypofibrinogenaemia as defined by a FibTEM A5 value of < 7 mm, or 7-12 mm with ongoing or high risk of haemorrhage. Of 32,647 deliveries over 4 years, 893 (2.7%) women had an estimated blood loss ≥ 1500 ml. Two-hundred and three (23%) of these had a FibTEM A5 ≤ 12 mm and 110 received fibrinogen concentrate. We compared clinical outcomes and blood product use with 52 patients who met the same criteria, over a 12-month pre-intervention period during which shock packs were used. In the algorithm group, there was a significant reduction in the number of units (p < 0.0001) and total volume (p = 0.0007) of blood products transfused, with a reduction in transfusion-associated circulatory overload (p = 0.002). Women with placental abruption exhibited more severe coagulopathy and required higher doses of fibrinogen concentrate than women who bled due to other causes. Analysis of rotational thromboelastometry results demonstrated that coagulopathy is not observed in all women who suffer obstetric haemorrhage and cannot be predicted solely by blood loss. Therefore, formulaic treatment with blood products is not justified. When coagulopathy does occur, it appears to be multifactorial and can be severe. Point-of-care testing allows early identification and individualised treatment of coagulopathy. This is supported by the improved outcomes reported.

Up-regulation of LFA-1 allows liver-resident memory T cells to patrol and remain in the hepatic sinusoids.

Liver-resident CD8+ T cells are highly motile cells that patrol the vasculature and provide protection against liver pathogens. A key question is: how can these liver CD8+ T cells be simultaneously present in the circulation and tissue-resident? Because liver-resident T cells do not express CD103 - a key integrin for T cell residence in epithelial tissues - we investigated other candidate adhesion molecules. Using intra-vital imaging we found that CD8+ T cell patrolling in the hepatic sinusoids is dependent upon LFA-1-ICAM-1 interactions. Interestingly, liver-resident CD8+ T cells up-regulate LFA-1 compared to effector-memory cells, presumably to facilitate this behavior. Finally, we found that LFA-1 deficient CD8+ T cells failed to form substantial liver-resident memory populations following Plasmodium or LCMV immunization. Collectively, our results demonstrate that it is adhesion through LFA-1 that allows liver-resident memory CD8+ T cells to patrol and remain in the hepatic sinusoids.

Coagulopathy and placental abruption: changing management with ROTEM-guided fibrinogen concentrate therapy.

Placental abruption may cause significant haemorrhage and coagulopathy that can progress rapidly due to simultaneous consumption and depletion of clotting factors. Plasma fibrinogen levels are predictive of further haemorrhage. Rapid detection and treatment of hypofibrinogenaemia is essential in the evolving clinical and haematological situation. The use of near-patient testing of coagulation using rotational thromboelastometry (ROTEM) allows dynamic monitoring of coagulopathy. Following the introduction of fibrinogen concentrate into our unit, a ROTEM-guided algorithm was developed for use in obstetric haemorrhage. We describe four cases of placental abruption, haemorrhage and severe coagulopathy that span the introduction of the algorithm. Three cases were associated with intrauterine death and the fourth with delivery of an extremely premature neonate. Rotational thromboelastometry was used in all cases but methods of fibrinogen replacement differ, illustrating evolving management of the condition in our unit.

Accuracy and precision of the ultrasound cardiac output monitor (USCOM 1A) in pregnancy: comparison with three-dimensional transthoracic echocardiography.

BACKGROUND: Cardiac output (CO) monitoring is helpful in the assessment of critically ill pregnant women, but invasive monitors are often unsuitable for use. We aimed to measure agreement between the non-invasive ultrasound cardiac output monitor (USCOM) and three-dimensional transthoracic echocardiography (3D-TTE) in pregnant women. METHODS: Healthy pregnant women from 25 weeks gestation onwards participated. In the left lateral position at rest, CO was measured with the USCOM and 3D-TTE. A single operator performed all USCOM measurements, with a different operator performing all echocardiography. Both were blinded to results from the other device. Each USCOM trace was analysed using two modes: flowtrace (FT) and touchpoint (TP). A second, blinded USCOM reading was taken to assess reproducibility. RESULTS: USCOM readings were obtained in 92, and 3D-TTE images in 85 participants. The mean CO was 5.7, 7.7, and 6.2 litre min(-1) measured by 3D-TTE, USCOM FT, and USCOM TP, respectively. USCOM bias was +2.0 litre min(-1) (FT) and +0.4 litre min(-1) (TP). Limits of agreement were -0.2 to +4.2 litre min(-1) (FT) and -1.4 to +2.3 litre min(-1) (TP). The mean percentage difference was 32.6% (FT) and 31.4% (TP) for CO and 27.0% (FT) and 27.5% (TP) for stroke volume. Intraclass correlation between repeated USCOM readings was 0.9 (FT) and 0.86 (TP). CONCLUSIONS: USCOM has acceptable agreement with 3D-TTE for the measurement of CO in pregnancy. The positive bias of the USCOM, particularly in the FT mode, may be due to the hyperdynamic cardiovascular state in pregnancy. We suggest using the TP mode in this patient population.

Socio-economic disparities in preterm birth: causal pathways and mechanisms.

Preterm birth is the leading cause of infant mortality in industrialised societies. Its incidence is greatly increased among the socially disadvantaged, but the reasons for this excess are unclear and have been relatively unexplored. We hypothesise two distinct sets of causal pathways and mechanisms that may explain social disparities in preterm birth. The first set involves chronic and acute psychosocial stressors, psychological distress caused by those stressors, increased secretion of placental corticotropin releasing hormone (CRH), changes in sexual behaviours or enhanced susceptibility to bacterial vaginosis and chorioamnionitis, cigarette smoking or cocaine use, and decidual vasculopathy. The second hypothesised pathway is a gene-environment interaction based on a highly prevalent mutation in the gene for methylenetetrahydrofolate reductase (MTHFR), combined with low folate intake from the diet and from prenatal vitamin supplements, consequent hyperhomocysteinemia, and decidual vasculopathy. We propose to test these hypothesised pathways and mechanisms in a nested case-control study within a prospectively recruited and followed cohort of pregnant women with singleton pregnancies who deliver at one of four Montreal hospitals that serve an ethnically and socio-economically diverse population. Following recruitment during the late first or early second trimester, participating women are seen at 24-26 weeks, when a research nurse obtains a detailed medical and obstetric history; administers several scales to assess chronic and acute stressors and psychological function; obtains blood samples for CRH, red blood cell and plasma folate, homocysteine, and DNA for the MTHFR mutation; and performs a digital and speculum examination to measure cervical length and vaginal pH and to obtain swabs for bacterial vaginosis and fetal fibronectin. After delivery, each case (delivery at < 37 completed weeks following spontaneous onset of labour or prelabour rupture of membranes) and two controls are selected for placental pathological examination, hair analysis of cotinine, cocaine, and benzoylecgonine, and analysis of stored blood and vaginal specimens. Statistical analysis will be based on multiple logistic regression and structural equation modelling, with sequential construction of models of potential aetiological determinants and covariates to test the hypothesised causal pathways and mechanisms. The research we propose should improve understanding of the factors and processes that mediate social disparities in preterm birth. This improved understanding should help not only in developing strategies to reduce the disparities but also in suggesting preventive interventions applicable across the entire socio-economic spectrum.

Dystocia among women with symptomatic uterine rupture.

OBJECTIVE: The purpose of this study was to analyze cervical dilatation patterns among women with uterine rupture by means of a mathematic model and to use the results to determine optimal intervention criteria. STUDY DESIGN: This was a case-control review that compared a case patient group of 19 women with uterine rupture during labor with control groups with either no previous cesarean deliveries, vaginal birth after cesarean delivery, or failure of attempted vaginal birth after cesarean delivery. The mathematic model quantified dilatation and adjusted for conditions specific to each patient. Case patients were compared with matched control subjects by means of paired t tests, analysis of variance, odds ratios, and conditional logistic regression. RESULTS: Dystocia was present in 31.6% to 47.4% of patients with uterine rupture, versus 2.6% to 13.2% of the control group with no previous cesarean deliveries (P< or =.001). The incidence of an arrest disorder among patients with uterine rupture was similar to that seen in the control group with failure of attempted vaginal birth after cesarean delivery. However, the interval from diagnosis to rupture or cesarean delivery was 5.5 +/- 3.3 hours among case patients with uterine rupture and 1.5 +/- 1.3 hours in the control group with failure of attempted vaginal birth after cesarean delivery. CONCLUSION: When cervical dilatation was lower than the 10th percentile and was arrested for > or =2 hours, cesarean delivery would have prevented 42.1% of the cases of uterine rupture and resulted in excess 2.6% and 7.9% cesarean delivery rates among women with no previous cesarean deliveries and women with vaginal birth after cesarean delivery, respectively.

A multicenter controlled trial of fetal pulse oximetry in the intrapartum management of nonreassuring fetal heart rate patterns.

OBJECTIVE: Recent developments permit the use of pulse oximetry to evaluate fetal oxygenation in labor. We tested the hypothesis that the addition of fetal pulse oximetry in the evaluation of abnormal fetal heart rate patterns in labor improves the accuracy of fetal assessment and allows safe reduction of cesarean deliveries performed because of nonreassuring fetal status. STUDY DESIGN: A randomized, controlled trial was conducted concurrently in 9 centers. The patients had term pregnancies and were in active labor when abnormal fetal heart rate patterns developed. The patients were randomized to electronic fetal heart rate monitoring alone (control group) or to the combination of electronic fetal monitoring and continuous fetal pulse oximetry (study group). The primary outcome was a reduction in cesarean deliveries for nonreassuring fetal status as a measure of improved accuracy of assessment of fetal oxygenation. RESULTS: A total of 1010 patients were randomized, 502 to the control group and 508 to the study group. There was a reduction of >50% in the number of cesarean deliveries performed because of nonreassuring fetal status in the study group (study, 4. 5%; vs. control, 10.2%; P =.007). However, there was no net difference in overall cesarean delivery rates (study, n = 147 [29%]; vs. control, 130 [26%]; P = .49) because of an increase in cesarean deliveries performed because of dystocia in the study group. In a blinded partogram analysis 89% of the study patients and 91% of the control patients who had a cesarean delivery because of dystocia met defined criteria for actual dystocia. There was no difference between the 2 groups in adverse maternal or neonatal outcomes. In terms of the operative intervention for nonreassuring fetal status, there was an improvement in both the sensitivity and the specificity for the study group compared with the control group for the end points of metabolic acidosis and need for resuscitation. CONCLUSION: The study confirmed its primary hypothesis of a safe reduction in cesarean deliveries performed because of nonreassuring fetal status. However, the addition of fetal pulse oximetry did not result in an overall reduction in cesarean deliveries. The increase in cesarean deliveries because of dystocia in the study group did appear to result from a well-documented arrest of labor. Fetal pulse oximetry improved the obstetrician's ability to more appropriately intervene by cesarean or operative vaginal delivery for fetuses who were actually depressed and acidotic. The unexpected increase in operative delivery for dystocia in the study group is of concern and remains to be explained.

Continuous intrapartum pH, pO2, pCO2, and SpO2 monitoring.

The goal of intrapartum surveillance and its further development is better patient care for both the fetus and the gravida. A normal FHR pattern is usually associated with the delivery of a normal well-oxygenated infant; however, a nonreassuring FHR is not always associated with the delivery of a compromised infant. This situation has led to an increase in unnecessary obstetric interventions in the form of a rising cesarean section rate. Fetal scalp sampling was developed in an attempt to improve the predictive value of electronic FHR monitoring, but because this technique is not widely used, management decisions are frequently made using FHR patterns alone. Much research has been performed in the search for a continuous biochemical measurement of fetal status, including continuous pH, pO2, or pCO2 and various combinations of these methodologies. None of these measurements are used in current clinical practice, mainly owing to technical problems and difficulties associated with the continuous direct measurement of these parameters in fetal blood throughout labor. The promising new field of fetal pulse oximetry has the potential to provide reliable, meaningful, and reproducible data as shown in early cross-sectional studies and more recent longitudinal studies. By identifying developing hypoxia, this technology may reduce the uncertainty associated with electronic FHR monitoring. Fetal pulse oximetry may also provide critical information relating to the detection and management of the hypoxic fetus. Any new method of intrapartum fetal monitoring requires careful evaluation to assess its potential value before its introduction into clinical practice. The use of fetal SpO2 monitoring in the presence of a nonreassuring FHR pattern is being examined in a multicenter randomized controlled trial. This study will address the question of whether supplementary monitoring of fetal SpO2 levels can lead to a reduction in the cesarean section rate for fetal distress. The available data on fetal noninvasive pulse oximetry have been obtained from a combination of well-designed cohort studies (level II-2 evidence) or from earlier multiple time series (level II-3 evidence). The results from the US Multicenter Trial (level I evidence) should provide a significant addition to current evidence. A continuous fetal noninvasive monitor measuring fetal oxygenation directly could lead to an improvement in the sensitivity and specificity of fetal surveillance. This improvement could ultimately result in a reduction in unnecessary interventions by differentiating hypoxic fetuses from nonhypoxic fetuses and, more importantly, may lead to earlier intervention for fetuses in danger of serious compromise.

Are all growth-restricted newborns created equal(ly)?

BACKGROUND: Previous etiologic studies have defined intrauterine growth restriction (IUGR) based on a single cutoff. OBJECTIVE: To assess the relative importance of known etiologic determinants for different degrees (mild versus severe) and timing (preterm versus term) of fetal growth restriction. DESIGN: Hospital-based cohort study. SETTING: Tertiary-care university hospital. PARTICIPANTS: Sixty-five thousand two hundred eighty inborn singleton infants without major congenital anomalies delivered between January 1, 1978 and March 31, 1996. MEASUREMENTS: Comparison of adjusted odds ratios (ORs) and 95% confidence intervals for mild IUGR (defined as birth weight 75% to <85% of the mean for gestational age, the latter cutoff equivalent to the 9.9th percentile for this cohort) and severe IUGR (<75% of mean, or 2.3rd percentile), after controlling for maternal age, education, marital status, and other potential determinants by means of multiple logistic regression. RESULTS: Maternal prepregnancy overweight (body mass index [BMI] >26.0-29.0 kg/m2) and obesity (BMI >29.0 kg/m2) had stronger protective effects against mild IUGR than against severe IUGR, but most of the determinants showed the opposite pattern. This was especially true for pathologic determinants; ORs (and 95% confidence intervals) for severe versus mild IUGR were 18.5 (14.5-23.8) vs 4.6 (3.6-5.8) for severe pregnancy-induced hypertension (PIH), 3.5 (2.2-5.5) vs 2.3 (1. 5-3.4) for prepregnancy hypertension, and 3.4 (2.9-3.9) vs 2.2 (2. 0-2.4) for smoking >/=11 cigarettes/day. Primiparity, short stature, prepregnancy BMI, maternal weight gain, and cigarette smoking had significantly larger effects on term IUGR, whereas the effect of severe PIH was more than twice as large for preterm IUGR (OR = 9.7 [7.3-13.0]) as for term IUGR (OR = 4.0 [3.0-5.3]). CONCLUSION: Pathologic determinants of IUGR such as prepregnancy and PIH and cigarette smoking predispose to more severe fetal growth retardation, and PIH in particular seems to do so before 37 weeks. Growth-restricted newborns are not, therefore, all created equal(ly).

The effect of maternal epidural analgesia on fetal oxygen saturation.

OBJECTIVE: To observe fetal arteriolar oxygen saturation during maternal epidural analgesia. DESIGN: An observation study of 27 epidural top-ups. SETTING: Labour ward, St James's University Hospital and Leeds General Infirmary, Leeds University, UK. SAMPLE: Seventeen fetuses in uncomplicated labour monitored with a N400 fetal pulse oximeter. OUTCOME MEASURE: A change in fetal pulse oximetry reading following epidural analgesia. RESULTS: There is no change in fetal oxygen saturation following an uncomplicated epidural top-up (F = 0.93; df 35 and 784). CONCLUSION: An uneventful maternal epidural has no measurable effect on fetal oxygen saturation measured with a N400 pulse oximeter.

Comparing fetal pulse oximetry with scalp pH.

OBJECTIVE: To determine whether pulse oximetry has the potential to replace scalp blood pH sampling in infants with abnormal cardiotocographs. STUDY DESIGN: The average scalp oximetry reading in labor recorded with an experimental N400 system was compared with fetal scalp blood pH. RESULTS: The average oximetry readings were unrelated to the pH of aerobically sampled fetal scalp blood. There was no subgroup of acidemic infants with a low oximetry reading. CONCLUSION: Pulse oximetry readings with present technology do not reflect scalp pH. The equipment is improving, but at this time pulse oximetry is not a simple alternative for scalp capillary blood sampling.

The effect of uterine contractions on fetal oxygen saturation.

OBJECTIVE: To find out what happens to fetal arteriolar oxygen saturation during a uterine contraction. DESIGN: Prospective observational study. SETTING: Labour ward, St James's University Hospital, Leeds. SUBJECTS: Eighteen women in normal labour monitored with a fetal scalp surface pulse oximetry sensor, an intrauterine pressure catheter, and a head to cervix force transducer. METHODS: The effect of intrauterine pressure and head to cervix force on fetal arteriolar oxygen saturation was examined using time series analysis and a regression model of 159 contractions. OUTCOME MEASURE: Fetal oxygen saturation during a contraction. RESULTS: The average oxygen saturation drops after a contraction. The greatest drop in oxygen saturation is reached 92 s after the peak of a contraction and takes approximately 1 min 30 s to recover (P = 0.036). CONCLUSION: Uterine contractions during normal labour affect fetal oxygen saturation.

Fetal pulse oximetry: a new method of monitoring the fetus.

Experimental pulse oximetry devices, similar to the existing systems used in adult and neonatal monitoring, can be used on the fetus to provide safe, and rapid information about oxygenation. They have been calibrated using fetal lambs and validated in human cross-sectional studies. Experiments have shown that fetal oxygen saturation decreases during normal labour, and drops after a uterine contraction especially with oxytocin-induced tachysystole. When the mother is given oxygen the fetal oxygen saturation increases. Readings are effected by caput and movement, and trends seem to be more meaningful than absolute values. Pulse oximetry can predict fetal outcome and a normal oxygen saturation result is specific for a good outcome perhaps even if the CTG is abnormal. However the technique is still experimental and there is insufficient data to support its use as a replacement for fetal blood sampling or a discriminator for an abnormal fetal heart trace.