How I treat sickle cell disease in pregnancy.

ABSTRACT: Fifty years ago, people with sickle cell disease (SCD) were discouraged from becoming pregnant, but now, most should be supported if they choose to pursue a pregnancy. They and their providers, however, should be aware of the physiological changes of pregnancy that aggravate SCD and pregnancy's unique maternal and fetal challenges. Maternal problems can arise from chronic underlying organ dysfunction such as renal disease or pulmonary hypertension; from acute complications of SCD such as acute anemia, vaso-occlusive crises, and acute chest syndrome; and/or from pregnancy-related complications such as preeclampsia, sepsis, severe anemia, thromboembolism, and the need for cesarean delivery. Fetal problems include alloimmunization, opioid exposure, fetal growth restriction, preterm delivery, and stillbirth. Before and during pregnancy, in addition to the assessment and care that every pregnant patient should receive, patients with SCD should be evaluated and treated by a multidisciplinary team with respect to their unique maternal and fetal issues.

Agnostic identification of plasma biomarkers for postpartum hemorrhage risk.

BACKGROUND: Postpartum hemorrhage is difficult to predict, is associated with significant maternal morbidity, and is the leading cause of maternal mortality worldwide. The identification of maternal biomarkers that can predict increased postpartum hemorrhage risk would enhance clinical care and may uncover mechanisms that lead to postpartum hemorrhage. OBJECTIVE: This retrospective case-control study employed agnostic proteomic profiling of maternal plasma samples to identify differentially abundant proteins in controls and postpartum hemorrhage cases. STUDY DESIGN: Maternal plasma samples were procured from a cohort of >60,000 participants in a single institution's perinatal repository. Postpartum hemorrhage was defined as a decrease in hematocrit of ≥10% or receipt of transfusion within 24 hours after delivery. Postpartum hemorrhage cases (n=30) were matched by maternal age and delivery mode (vaginal or cesarean) with controls (n=56). Mass spectrometry was used to identify differentially abundant proteins using integrated peptide peak areas. Statistically significant differences between groups were defined as P<.05 after controlling for multiple comparisons. RESULTS: By study design, cases and controls did not differ in race, ethnicity, gestational age at delivery, blood type, or predelivery platelet count. Cases had slightly but significantly lower predelivery and postdelivery hematocrit and hemoglobin. Mass spectrometry detected 1140 proteins, including 77 proteins for which relative abundance differed significantly between cases and controls (fold change >1.15, P<.05). Of these differentially abundant plasma proteins, most had likely liver or placental origins. Gene ontology term analysis mapped to protein clusters involved in responses to wound healing, stress response, and host immune defense. Significantly differentially abundant proteins with the highest fold change (prostaglandin D2 synthase, periostin, and several serine protease inhibitors) did not correlate with predelivery hematocrit or hemoglobin but identified postpartum hemorrhage cases with logistic regression modeling revealing good-to-excellent area under the operator receiver characteristic curves (0.802-0.874). Incorporating predelivery hemoglobin with these candidate proteins further improved the identification of postpartum hemorrhage cases. CONCLUSION: Agnostic analysis of maternal plasma samples identified differentially abundant proteins in controls and postpartum hemorrhage cases. Several of these proteins are known to participate in biologically plausible pathways for postpartum hemorrhage risk and have potential value for predicting postpartum hemorrhage. These findings identify candidate protein biomarkers for future validation and mechanistic studies.

Novel Antithrombotic Agents in Pregnancy Anticoagulants and Antiplatelet Agents.

Increasing rates of thromboembolic complications have required increasing use of anticoagulant and antiplatelet agents during and after pregnancy. Furthermore, thromboembolism is both a cause and a complication of severe maternal morbidity requiring intensive care. As a consequence, almost all patients admitted to intensive care units receive an anticoagulant or an antiplatelet agent (or both) for either treatment or prevention of thromboembolism. In this review, we summarize commonly used anticoagulants and antiplatelet agents and outline the potential role of newly developed (novel) antithrombotic agents for pregnant and postpartum patients.

Prospective Observational Study of N-terminal Pro-Brain Natriuretic Peptide Levels in Obese and Nonobese Women during Pregnancy.

OBJECTIVE: N-terminal pro-brain natriuretic peptide (NT-proBNP), a marker of ventricular dysfunction, varies by body mass index (BMI) outside of pregnancy. This study aimed to determine whether obesity affects NT-proBNP levels in pregnancy. STUDY DESIGN: This was a prospective observational study of healthy pregnant people in the third trimester (3TM) and postpartum (PP). Patients were excluded if they had significant medical comorbidities or if their fetuses had anomalies, growth restriction or aneuploidy. NT-proBNP was measured at 28 weeks (3TM), predelivery (PD), 1 to 2 days PP (immediate postpartum [IPP]), and 4 to 6 weeks PP (delayed postpartum [DPP]). LogNT-proBNP levels were analyzed using linear mixed effects models, including BMI < or ≥30, time, and time-by-BMI interactions. RESULTS: Fifty-five people (28 [51%] with BMI ≥ 30 and 27 [49%] with BMI < 30) were enrolled. A greater proportion of obese than nonobese subjects developed hypertensive disorders of pregnancy (50 vs. 15%, p = 0.010) and obese patients had higher systolic blood pressures at all time points (p < 0.05). NT-proBNP levels (median [interquartile range] in pg/mL) were 18 (6-28) versus 26 (17-48) at 3TM, 16 (3-38) versus 43 (21-60) at PD, 58 (20-102) versus 63 (38-155) at IPP, and 33 (27-56) versus 23 (8-42) at DPP for obese compared with nonobese patients. In linear mixed effects models, logNT-proBNP was lower in obese patients at 3TM (ß = -0.89 [95% confidence interval, CI: -1.51, -0.26]) and PD (ß = -1.05 [95% CI: -1.72, -0.38]). The logNT-proBNP trends over time differed by BMI category, with higher values in obese patients at both PP time points compared with the 3TM (IPP ß = 1.24 [95% CI: 0.75, 1.73]; DPP ß = 1.08 [95% CI: 0.52, 1.63]), but only IPP for nonobese patients (ß = 0.87 [95% CI: 0.36, 1.38]). CONCLUSION: Obese patients had lower NT-proBNP levels than nonobese patients during pregnancy but not PP. The prolonged PP elevation in NT-proBNP in obese patients suggests that their PP cardiac recovery may be more prolonged. KEY POINTS: · NT-proBNP levels are lower in obese than nonobese patients during pregnancy.. · Levels remain elevated in obese, but not nonobese, patients up to 4 to 6 weeks' postpartum.. · A lower threshold for concern regarding NT-proBNP levels may be needed in obese pregnant people..

Transfusion Requirements with Hybrid Management of Placenta Accreta Spectrum Incorporating Targeted Embolization and a Selective Use of Delayed Hysterectomy.

OBJECTIVE: This study compares the number of units of red blood cells (RBCs) transfused in patients with placenta accreta spectrum (PAS) treated with or without a multidisciplinary algorithm that includes placental uterine arterial embolization (P-UAE) and selective use of either immediate or delayed hysterectomy. STUDY DESIGN: This is a retrospective study of deliveries conducted at a tertiary care hospital from 2001 to 2018 with pathology-confirmed PAS. Those with previable pregnancies or microinvasive histology were excluded. To improve the equity of comparison, analyses were made separately among scheduled and unscheduled cases, therefore patients were assigned to one of four cohorts as follows: (1) scheduled/per-algorithm, (2) scheduled/off-algorithm, (3) unscheduled/per-algorithm, or (4) unscheduled/off-algorithm. Primary outcomes included RBCs transfused and estimated blood loss (EBL). Secondary outcomes included perioperative complications and disposition. RESULTS: Overall, 95 patients were identified, with 87 patients meeting inclusion criteria: 36 treated per-algorithm (30 scheduled and 6 unscheduled) and 51 off-algorithm patients (24 scheduled and 27 unscheduled). Among scheduled deliveries, 9 (30.0%) patients treated per-algorithm received RBCs compared with 20 (83.3%) patients treated off-algorithm (p < 0.01), with a median (interquartile range [IQR]) of 3.0 (2.0, 4.0) and 6.0 (2.5, 7.5) units transfused (p = 0.13), respectively. Among unscheduled deliveries, 5 (83.3%) per-algorithm patients were transfused RBCs compared with 25 (92.6%) off-algorithm patients (p = 0.47) with a median (IQR) of 4.0 (2.0, 6.0) and 8.0 (3.0, 10.0) units transfused (p = 0.47), respectively. Perioperative complications were similar between cohorts. CONCLUSION: A multidisciplinary algorithm including P-UAE and selective use of delayed hysterectomy is associated with a lower rate of blood transfusion in scheduled but not unscheduled cases. KEY POINTS: · An algorithm with delayed hysterectomy had less transfusion in scheduled, but not unscheduled, cases.. · Over time, more cases were managed per algorithm; among scheduled cases, the transfusion rate and volume transfused decreased.. · There were similar transfusion outcomes among off-algorithm cases, regardless if delivery was scheduled..

Knowledge gaps in reproductive and sexual health in girls and women with sickle cell disease.

There is an immediate need to address long-standing questions about the reproductive health of girls and women with sickle cell disease (SCD). There are many SCD-related reproductive risks and uncertainties across girls' and women's reproductive life span, with particularly outstanding concerns about menstruation, contraception, fertility and pregnancy. Extant literature addressing women's reproductive health topics is mostly descriptive; there are few high-quality interventional studies. In 2020, the Centers for Disease Control and Prevention and the Foundation for Women and Girls with Blood Disorders convened an expert panel to assess the knowledge gaps in women's reproductive health in SCD. The panel identified significant limitations to clinical care due to the need for research. The panel also identified prominent barriers to research and care. In this report, we frame these issues, providing a roadmap for investigators, funding agencies, and policy makers to advance care for girls and women with SCD.

Women and girls with haemophilia: Lessons learned.

Severe and moderate factor VIII (FVIII) or IX (FIX) deficiencies in female carriers of haemophilia are rarely observed, but mild deficiency is quite frequent, although insufficiently recognized and registered. The confusion between the genetic diagnosis of the carriership, mainly assessed at adult age and the diagnosis of the bleeding disorder for those who have low factor levels often prevents early diagnosis of a potential bleeding risk. The factor levels in obligate or potential carriers of haemophilia can be assessed during childhood, possibly apart from genetic assays. The absence of early recognition of the bleeding disorder precludes the anticipation of menarche and the prevention of potential heavy menstrual bleeding to heavy menstrual bleeding. Standardized bleeding assessment tools (BAT) have demonstrated that women and girls with haemophilia (WGWH) have increased bleeding scores as compared to the general female population, however weakly correlating with factor levels. More recent evidence has highlighted that hemarthroses affect 4% to 19% of carriers and that some of them could experience sub-clinical joint bleeding. Desmopressin for women with FVIII deficiency and abnormal ISTH-BAT scores had a significantly lower FVIII response to DDAVP compared to those with normal bleeding scores, which could at least partially explain more postsurgical bleeding. Management of delivery of haemophilia carriers requires attention to the risks of maternal bleeding, the risks of foetal bleeding, preconception and prenatal care, strategies to reduce maternal bleeding, choice of mode of delivery to reduce foetal/neonatal bleeding, and postpartum care. Either prior to pregnancy, or during early pregnancy, a plan should be developed that addresses the needs of both the mother and her unborn baby. If the unborn baby is a male proven to be or potentially affected by moderate or severe form of haemophilia, there is a risk of severe foetal bleeding, so a planned caesarean delivery may be preferred. If the unborn baby is a carrier, or potentially affected carrier, there is still the risk of non-severe bleeding so invasive foetal procedures and operative vaginal delivery (forceps or vacuum) should be avoided. Further studies based on large cohorts will help the community to favour earlier diagnosis, increase knowledge on WGWH and promote better care.

Optimal use of intravenous tranexamic acid for hemorrhage prevention in pregnant women.

BACKGROUND: Every 2 minutes, there is a pregnancy-related death worldwide, with one-third caused by severe postpartum hemorrhage. Although international trials demonstrated the efficacy of 1000 mg tranexamic acid in treating postpartum hemorrhage, to the best of our knowledge, there are no dose-finding studies of tranexamic acid on pregnant women for postpartum hemorrhage prevention. OBJECTIVE: This study aimed to determine the optimal tranexamic acid dose needed to prevent postpartum hemorrhage. STUDY DESIGN: We enrolled 30 pregnant women undergoing scheduled cesarean delivery in an open-label, dose ranging study. Subjects were divided into 3 cohorts receiving 5, 10, or 15 mg/kg (maximum, 1000 mg) of intravenous tranexamic acid at umbilical cord clamping. The inclusion criteria were ≥34 week's gestation and normal renal function. The primary endpoints were pharmacokinetic and pharmacodynamic profiles. Tranexamic acid plasma concentration of >10 µg/mL and maximum lysis of <17% were defined as therapeutic targets independent to the current study. Rotational thromboelastometry of tissue plasminogen activator-spiked samples was used to evaluate pharmacodynamic profiles at time points up to 24 hours after tranexamic acid administration. Safety was assessed by plasma thrombin generation, D-dimer, and tranexamic acid concentrations in breast milk. RESULTS: There were no serious adverse events including venous thromboembolism. Plasma concentrations of tranexamic acid increased in a dose-proportional manner. The lowest dose cohort received an average of 448±87 mg tranexamic acid. Plasma tranexamic acid exceeded 10 µg/mL and maximum lysis was <17% at >1 hour after administration for all tranexamic acid doses tested. Median estimated blood loss for cohorts receiving 5, 10, or 15 mg/kg tranexamic acid was 750, 750, and 700 mL, respectively. Plasma thrombin generation did not increase with higher tranexamic acid concentrations. D-dimer changes from baseline were not different among the cohorts. Breast milk tranexamic acid concentrations were 1% or less than maternal plasma concentrations. CONCLUSION: Although large randomized trials are necessary to support the clinical efficacy of tranexamic acid for prophylaxis, we propose an optimal dose of 600 mg in future tranexamic acid efficacy studies to prevent postpartum hemorrhage.

Population pharmacokinetics and pharmacodynamics of Tranexamic acid in women undergoing caesarean delivery.

AIMS: The population pharmacokinetics (PK) and pharmacodynamics (PD) of tranexamic acid (TXA) have not been studied to prevent postpartum haemorrhage (PPH) in pregnant women. It is unclear which TXA dose assures sufficient PPH prevention. This study investigated population PK/PD of TXA in pregnant women who underwent caesarean delivery to determine the optimal prophylactic doses of TXA for future studies. METHODS: We analysed concentration (PK) and maximum lysis (PD) data from 30 pregnant women scheduled for caesarean delivery who received 5, 10 or 15 mg/kg of TXA intravenously using population approach. RESULTS: TXA PK was best described by a two-compartment model with first-order elimination and the following parameters: clearance (between-subject variability) of 9.4 L/h (27.7%), central volume of 10.1 L (47.4%), intercompartmental clearance of 22.4 L/h (66.7%), peripheral volume of 14.0 L (13.1%) and additive error of 1.4 mg/L. The relationship between TXA concentration and maximum lysis was characterized by a sigmoid Emax model with baseline lysis of 97%, maximum inhibition of 89%, IC50 of 6.0 mg/L (65.3%), hill factor of 8.5 (86.3%) and additive error of 7.3%. Simulations demonstrated that 500 and 650 mg of TXA maintained therapeutic targets for 30 minutes and 1 hour, respectively, in 90% of patients. CONCLUSION: This is the first population PK and PD study of TXA in pregnant women undergoing caesarean delivery. Our analysis suggests that a 650 mg dose provides adequate PPH prophylaxis up to 1 hour, which is less than the currently used 1000 mg of TXA in pregnant women.

The Society for Obstetric Anesthesia and Perinatology Interdisciplinary Consensus Statement on Neuraxial Procedures in Obstetric Patients With Thrombocytopenia.

Because up to 12% of obstetric patients meet criteria for the diagnosis of thrombocytopenia in pregnancy, it is not infrequent that the anesthesiologist must decide whether to proceed with a neuraxial procedure in an affected patient. Given the potential morbidity associated with general anesthesia for cesarean delivery, thoughtful consideration of which patients with thrombocytopenia are likely to have an increased risk of spinal epidural hematoma with neuraxial procedures, and when these risks outweigh the relative benefits is important to consider and to inform shared decision making with patients. Because there are substantial risks associated with withholding a neuraxial analgesic/anesthetic procedure in obstetric patients, every effort should be made to perform a bleeding history assessment and determine the thrombocytopenia etiology before admission for delivery. Whereas multiple other professional societies (obstetric, interventional pain, and hematologic) have published guidelines addressing platelet thresholds for safe neuraxial procedures, the US anesthesia professional societies have been silent on this topic. Despite a paucity of high-quality data, there are now meta-analyses that provide better estimations of risks. An interdisciplinary taskforce was convened to unite the relevant professional societies, synthesize the data, and provide a practical decision algorithm to help inform risk-benefit discussions and shared decision making with patients. Through a systematic review and modified Delphi process, the taskforce concluded that the best available evidence indicates the risk of spinal epidural hematoma associated with a platelet count ≥70,000 × 106/L is likely to be very low in obstetric patients with thrombocytopenia secondary to gestational thrombocytopenia, immune thrombocytopenia (ITP), and hypertensive disorders of pregnancy in the absence of other risk factors. Ultimately, the decision of whether to proceed with a neuraxial procedure in an obstetric patient with thrombocytopenia occurs within a clinical context. Potentially relevant factors include, but are not limited to, patient comorbidities, obstetric risk factors, airway examination, available airway equipment, risk of general anesthesia, and patient preference.

National trends in tranexamic acid use in the peripartum period, 2015-2019.

BACKGROUND: The purpose of this study was to measure trends in the use of tranexamic acid (TXA) during delivery in the United States and to evaluate demographic data and morbidity outcomes among these patients. METHODS: This retrospective cohort study includes data from 19 hospitals in the Universal Health Services network. We compared rates of TXA use between January 2015 and June 2019 across geographic sectors. We also evaluated associations of demographic variables and perinatal outcomes of women who received TXA. RESULTS: 209 cases of TXA use were found from analysis of 101,564 deliveries. TXA use increased over time and rates were higher in the West than in Central and East; the slope of increase over years did not differ between regions. Women who received TXA were more likely to have a history of postpartum hemorrhage (59 (28.2%) vs. 2290 (2.2%), P < 0.0001) but were not more likely to have a chronic disease, including diabetes mellitus, hypertension and heart disease. Women who received TXA were more likely to have estimated blood loss greater than or equal to 1000 mL (adjusted odds ratio (aOR) 15.3; 95% CI 11.1-21.1; P < 0.0001). Likelihood of venous thromboembolism was not significantly increased in TXA recipients (aOR 2.0; 95% CI 0.3-14.6; P = 0.49). CONCLUSION: Increasing national trends of TXA use in the peripartum period was observed, with variable increases by geographic region. Likelihood of venous thromboembolism was not significantly increased among women who received TXA. Increasing TXA use throughout the country suggests that updated hemorrhage guidelines from national obstetrical organizations can shape clinical practice.

Contraceptive Methods and the Impact of Menstruation on Daily Functioning in Women with Sickle Cell Disease.

OBJECTIVES: Women with sickle cell disease (SCD) are living longer as a result of advances in the care of their underlying disease. With the population growing of women living with SCD, reproductive health issues in this population have become an emphasized area of medical care. We sought to describe current patterns of contraception use, menstruation, and quality-of-life (QOL) measures in women with SCD. METHODS: Using a cross-sectional study design, we administered paper surveys at two academic medical centers to women aged 10 to 55 years with SCD to capture current contraceptive use, characteristics of menstrual cycles, and QOL metrics. RESULTS: Of the 103 women who participated, 12.7% (13/102) experienced a duration of menses >7 days (defined here as prolonged menstrual bleeding). Approximately half of women (51.5%, 53/103) used some form of contraception, with depot medroxyprogesterone acetate injections and condoms being the most common. During their last menstrual periods, women with both dysmenorrhea and prolonged menstrual bleeding (6.9%, 7/102) were more likely to experience more days of poor QOL, with more nights with sleep disturbance (P = 0.001) and more days with trouble taking care of themselves (P = 0.003), as well as being unable to do things they previously enjoyed (P = 0.001), compared with those with neither phenomenon (28.2%, 29/103). CONCLUSIONS: Dysmenorrhea and prolonged menstrual bleeding negatively affect the QOL of women with SCD. Menstrual histories and preventive measures for menstruation-related morbidity should be incorporated into routine evaluations of women with SCD.

Prevention and Management of Thromboembolism in Pregnancy When Heparins Are Not an Option.

Heparins, unfractionated heparin, and low molecular weight heparin, are the preferred anticoagulants in pregnancy. There are circumstances, however, in which an alternative to heparin should be considered. These circumstances include, the presence of heparin resistance, a heparin allergy manifesting as heparin-induced skin reactions or heparin-induced thrombocytopenia, and the presence of a mechanical heart valve. From time to time, the obstetrician is called on to make recommendations about anticoagulants in pregnancy, including in circumstances in which an alternative to heparin has been suggested or is necessary. In this article, these circumstances are reviewed and alternative anticoagulants are discussed.

Managing Heavy Menstrual Bleeding in Women at Risk of Thrombosis.

Management of heavy menstrual bleeding (HMB) in a woman with a history of thrombosis, or who is otherwise at high risk of thrombosis, or who takes medications for anticoagulation can present a challenge to health care providers. The goal of treating HMB is to reduce menstrual blood loss. First-line therapy is typically hormonal, and hormonal therapy can be contraindicated in women with a history of thrombosis unless they are on anticoagulation. As 70% of women on anticoagulation experience HMB, successful management of HMB may involve a modification in the anticoagulation or antiplatelet regimen, hormonal therapy tailored to the patient's situation, and/or surgical therapy.

Contraceptive Management for Women Who Are at High Risk of Thrombosis.

Managing contraception for women at high risk for thrombosis poses unique challenges. Combined estrogen and progestin contraceptives increase the risk of both venous and arterial thrombosis. They are contraindicated in women with a history of thrombosis and in other women at high risk for thrombosis. However, progestin-only contraceptives are generally considered safe in this patient population. This paper reviews the evidence linking hormonal contraception and clotting risk, outlines appropriate contraceptive methods for women at high risk for thrombosis, discusses surgical risk for sterilization in the setting of current or past thrombosis, and includes a review of the safety of hormonal methods for women who are fully anticoagulated. In general, long-acting reversible contraception is safe for women with a history of thrombosis and may offer additional noncontraceptive benefits for women who are on anticoagulant therapy, such as improved bleeding profiles.

Diagnosis and Management of VTE in Pregnancy.

Venous thromboembolism is a leading cause of maternal death. Because of the low absolute frequency of events, however, outcome-based clinical data are limited. Consequently, clinicians must additionally rely both on published guidelines and on extrapolation of data from studies focused on nonpregnant individuals. The diagnosis and treatment of deep vein thrombosis, pulmonary embolism, and cerebral vein and dural sinus thrombosis are complicated by pregnancy, and often require modifications to standard diagnostic and treatment algorithms outside of pregnancy. Treatment of VTE in pregnant women is in particular need of future research.

Management of Menopausal Symptoms for Women Who Are at High Risk of Thrombosis.

For women at elevated risk of thrombosis, clinicians are challenged to relieve menopausal symptoms without increasing the risk of thrombosis. Oral menopausal hormone therapy increases the risk of venous thromboembolism by 2-fold to 3-fold. Observational studies suggest less thrombotic risk with transdermal therapies and with progesterone over synthetic progestogens (progestins), but the data are limited. Beneficial nonpharmacologic therapies include cognitive behavioral therapy and clinical hypnosis, whereas beneficial nonhormonal pharmacologic therapies include selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors. For treatment of the genitourinary syndrome of menopause, vaginal lubricants and moisturizers, low-dose vaginal estrogen, and intravaginal dehydroepiandrosterone are options.

Blood Products in the Management of Abnormal Placentation.

A critical tool in the successful management of patients with abnormal placentation is an established massive transfusion protocol designed to rapidly deliver blood products in obstetrical and surgical hemorrhage. Spurred by trauma research and an understanding of consumptive coagulopathy, the past 2 decades have seen a shift in volume resuscitation from an empiric, crystalloid-based method to balanced, targeted transfusion therapy. The present article reviews patient blood management in abnormal placentation, beginning with optimizing the patient's status in the antenatal period to the laboratory assessment and transfusion strategy for blood products at the time of hemorrhage.

Perioperative Management of the Gynecologic Patient on Long-term Anticoagulation.

The perioperative management of patients taking antithrombotic or antiplatelet medications is based on an assessment of the individual patient's risk for thrombosis or bleeding, the specific medication involved, and the nature of the planned procedure. This article describes specific strategies for whether and how these medications should be interrupted before gynecologic procedures, when they can be restarted following the procedure, and whether bridging therapy should be considered.

The Oxytocin Product Correlates with Total Oxytocin Received during Labor: A Research Methods Study.

OBJECTIVE: Total dose of oxytocin received during labor is an important variable in studies of human labor but is difficult to calculate. We sought to identify a surrogate measure for total dose of oxytocin received. STUDY DESIGN: For each subject receiving oxytocin during labor, the oxytocin total dose received in labor was calculated as the area under the curve. Maximal oxytocin infusion rate, total duration of oxytocin infusion, and the product of both, defined as the oxytocin product, were then each correlated with the total dose of oxytocin received using the Pearson's correlation coefficient. RESULTS: Oxytocin dosing data were available from 402 women at Duke and 6,907 women from Pithagore6. The two variables alone, or combined as the oxytocin product, demonstrated a high correlation with the oxytocin total dose (r > 0.7), with the oxytocin product demonstrating the highest (r > 0.9). This was true whether labor was induced or augmented and whether delivery was vaginal or cesarean. CONCLUSION: The oxytocin product, composed of two easily obtained variables, demonstrated a very high correlation with total oxytocin dose received in labor and represents a simple and accurate surrogate for total dose of oxytocin received during labor. The oxytocin product can be used in clinical studies in which oxytocin dose is an important variable.