Pharmacokinetics and Safety of Remdesivir in Pregnant and Non-Pregnant Women with COVID-19: Results from IMPAACT 2032.

BACKGROUND: Pregnant people with COVID-19 experience higher risk for severe disease and adverse pregnancy outcomes, but no pharmacokinetic (PK) data exist to support dosing of COVID-19 therapeutics during pregnancy. We report PK and safety data for intravenous remdesivir in pregnancy. METHODS: IMPAACT 2032 was a phase IV prospective, open-label, non-randomized opportunistic study of hospitalized pregnant and non-pregnant women receiving intravenous remdesivir as part of clinical care. Intensive PK sampling was performed on infusion days 3, 4, or 5 with collection of plasma and peripheral blood mononuclear cells (PBMCs). Safety data were recorded from first infusion through 4 weeks post-last infusion and at delivery. Geometric mean ratios (GMR) (90% confidence intervals [CI]) of PK parameters between pregnant and non-pregnant women were calculated. RESULTS: Fifty-three participants initiated remdesivir (25 pregnant; median (IQR) gestational age 27.6 (24.9, 31.0) weeks). Plasma exposures of remdesivir, its two major metabolites (GS-704277 and GS-441524), and the free remdesivir fraction were similar between pregnant and non-pregnant participants. Concentrations of the active triphosphate (GS-443902) in PBMCs increased 2.04-fold (90% CI 1.35, 3.03) with each additional infusion in non-pregnant versus pregnant participants. Three adverse events in non-pregnant participants were related to treatment (one Grade 3; two Grade 2 resulting in treatment discontinuation). There were no treatment-related adverse pregnancy outcomes or congenital anomalies detected. CONCLUSIONS: Plasma remdesivir PK parameters were comparable between pregnant and non-pregnant women, and no safety concerns were identified based on our limited data. These findings suggest no dose adjustments are indicated for intravenous remdesivir during pregnancy.

Prophylactic tranexamic acid for reducing intraoperative blood loss during cesarean section in women at high risk of postpartum hemorrhage: A double-blind placebo randomized controlled trial.

BACKGROUND: Postpartum hemorrhage remains a leading cause of maternal mortality especially in developing countries. The majority of previous trials on the effectiveness of tranexamic acid in reducing blood loss were performed in low-risk women for postpartum hemorrhage. A recent Cochrane Systematic Review recommended that further research was needed to determine the effects of prophylactic tranexamic acid for preventing intraoperative blood loss in women at high risk of postpartum hemorrhage. OBJECTIVE: This study aimed to evaluate the effectiveness and safety of tranexamic acid in reducing intraoperative blood loss when given prior to cesarean delivery in women at high risk of postpartum hemorrhage. STUDY DESIGN: The study is a double-blind randomized controlled trial. METHODS: The study consisted of 200 term pregnant women and high-risk preterm pregnancies scheduled for lower-segment cesarean delivery at Enugu State University of Science and Technology, Teaching Hospital, Parklane, Enugu, Nigeria. The participants were randomized into two arms (intravenous 1 g of tranexamic acid or placebo) in a ratio of 1:1. The participants received either 1 g of tranexamic acid or placebo (20 mL of normal saline) intravenously at least 10 min prior to commencement of the surgery. The primary outcome measures were the mean intraoperative blood loss and hematocrit change 48 h postoperatively. RESULTS: The baseline sociodemographic characteristics were similar in both groups. The tranexamic acid group when compared to the placebo group showed significantly lower mean blood loss (442.94 ± 200.97 versus 801.28 ± 258.68 mL; p = 0.001), higher mean postoperative hemoglobin (10.39 + 0.96 versus 9.67 ± 0.86 g/dL; p = 0.001), lower incidence of postpartum hemorrhage (1.0% versus 19.0%; p = 0.001), and lower need for use of additional uterotonic agents after routine management of the third stage of labor (39.0% versus 68.0%; p = 0.001), respectively. However, there was no significant difference in the mean preoperative hemoglobin (11.24 ± 0.88 versus 11.15 ± 0.90 g/dL; p = 0.457), need for other surgical intervention for postpartum hemorrhage (p > 0.05), and reported side effect, respectively, between the two groups. CONCLUSION: Prophylactic administration of tranexamic acid significantly decreases postpartum blood loss, improves postpartum hemoglobin, decreases the need for additional uterotonics, and prevents postpartum hemorrhage following cesarean section in pregnant women at high risk of postpartum hemorrhage. Its routine use during cesarean section in high-risk women may be encouraged.The trial was registered in the Pan-African Clinical Trial Registry with approval number PACTR202107872851363.

Blood pressure thresholds for the diagnosis of hypertensive disorders of pregnancy in sickle cell disease.

In this retrospective cohort study of singleton pregnancies in people with sickle cell disease (SCD) delivered at two academic centres between 1990 and 2021, we collected demographic and SCD-related data, pregnancy outcomes, and the highest systolic and diastolic blood pressure (SBP and DBP) at seven time periods. We compared the characteristics of subjects with new or worsening proteinuria (NWP) during pregnancy to those without. We then constructed receiver operating characteristic (ROC) curves to determine the blood pressure (BP) that best identifies those with NWP. The SBP or DBP thresholds which maximized sensitivity and specificity were 120 mmHg SBP (sensitivity: 55.2%, specificity: 73.5%) and 70 mmHg DBP (sensitivity: 27.6%, specificity: 67.7%). The existing BP threshold of 140/90 mmHg lacked sensitivity in both genotype groups (HbSS/HbSß0 : SBP = 21% sensitive, DBP = 5.3% sensitive; HbSS/HbSß+ : SBP = 10% sensitive, DBP = 0% sensitive). Finally, percent change in SBP, DBP and MAP were all poor tests for identifying NWP. Existing BP thresholds used to diagnose hypertensive disorders of pregnancy (HDP) are not sensitive for pregnant people with SCD. For this population, lowering the BP threshold that defines HDP may improve identification of those who need increased observation, consideration of early delivery and eclampsia prophylaxis.

Natural history of blood pressure in sickle cell disease pregnancy.

In this retrospective cohort study of singleton pregnancies in people with sickle cell disease (SCD) delivered at two academic centres between 1990 and 2021, we collected demographic and SCD-related data, pregnancy outcomes, and the highest systolic and diastolic blood pressure (SBP and DBP) at seven time periods. We compared blood pressure values and trajectories in the composite cohort and in each genotype group to control values in a non-SCD pregnancy dataset. There were 290 pregnancies among 197 patients with SCD. Sixteen per cent (n = 47) of pregnancies had a hypertensive disorder of pregnancy (HDP); the rates did not differ by genotype. The mean SBP and DBP were lower in the HbSS/HbSß0 group than in the non-SCD control group at all timepoints. Mean SBP and DBP trajectories were similar between the HbSS/HbSß0 group and non-SCD controls, whereas the mean SBP and DBP in the HbSC/HbSß+ group decreased between the first and second trimesters and plateaued between the second and third trimesters. There were no differences in blood pressure trajectory by haemoglobin >/< 10 gm/dL or by chronic transfusion status. Overall, pregnant people with SCD have lower blood pressure than unaffected pregnant people, raising the possibility that HDP are underdiagnosed, particularly in people with HbSS/HbSß0 .

Pharmacokinetics and safety of first-line tuberculosis drugs rifampin, isoniazid, ethambutol, and pyrazinamide during pregnancy and postpartum: results from IMPAACT P1026s.

Physiological changes during pregnancy may alter the pharmacokinetics (PK) of antituberculosis drugs. The International Maternal Pediatric Adolescent AIDS Clinical Trials Network P1026s was a multicenter, phase IV, observational, prospective PK and safety study of antiretroviral and antituberculosis drugs administered as part of clinical care in pregnant persons living with and without HIV. We assessed the effects of pregnancy on rifampin, isoniazid, ethambutol, and pyrazinamide PK in pregnant and postpartum (PP) persons without HIV treated for drug-susceptible tuberculosis disease. Daily antituberculosis treatment was prescribed following World Health Organization-recommended weight-band dosing guidelines. Steady-state 12-hour PK profiles of rifampin, isoniazid, ethambutol, and pyrazinamide were performed during second trimester (2T), third trimester (3T), and 2-8 of weeks PP. PK parameters were characterized using noncompartmental analysis, and comparisons were made using geometric mean ratios (GMRs) with 90% confidence intervals (CI). Twenty-seven participants were included: 11 African, 9 Asian, 3 Hispanic, and 4 mixed descent. PK data were available for 17, 21, and 14 participants in 2T, 3T, and PP, respectively. Rifampin and pyrazinamide AUC0-24 and C max in pregnancy were comparable to PP with the GMR between 0.80 and 1.25. Compared to PP, isoniazid AUC0-24 was 25% lower and C max was 23% lower in 3T. Ethambutol AUC0-24 was 39% lower in 3T but limited by a low PP sample size. In summary, isoniazid and ethambutol concentrations were lower during pregnancy compared to PP concentrations, while rifampin and pyrazinamide concentrations were similar. However, the median AUC0-24 for rifampin, isoniazid, and pyrazinamide met the therapeutic targets. The clinical impact of lower isoniazid and ethambutol exposure during pregnancy needs to be determined.

Reduction in preterm birth among COVID-19-vaccinated pregnant individuals in the United States.

BACKGROUND: Most studies investigating preterm birth and COVID-19 vaccination have suggested no difference in preterm birth rates between vaccinated and unvaccinated pregnant individuals; however, 1 recent study suggested a protective effect of COVID-19 vaccination on preterm birth rates in Australia. OBJECTIVE: This study aimed to determine whether a similar association and protective effect of COVID-19 vaccination on preterm birth would be found in our multistate, US cohort. STUDY DESIGN: A cohort study was conducted using the Vizient Clinical Database, which included data from 192 hospitals in 38 states. Pregnant individuals who delivered between January 2021 and April 2022 were included. Propensity score matching was used to match a "treated" group of pregnant individuals with any COVID-19 vaccination (incomplete or complete vaccination) to a group that had not received any COVID-19 vaccination (the "untreated" group). A complete vaccination series of ≥2 doses of the Moderna or Pfizer vaccines or at least 1 dose of the Johnson & Johnson vaccine was considered. An incomplete series was receipt of 1 dose of the Pfizer or Moderna vaccine. We examined the association between COVID-19 vaccination status and preterm birth at <28, <34, and <37 weeks of gestation. Multivariable logistic regression models were used to adjust for potential confounders, with adjusted odds ratios as the measure of treatment effect. RESULTS: Matching with replacement was performed for 5749 treated participants. After propensity score matching, there was no difference in maternal demographics of age, race, insurance status, parity, or comorbid conditions. Vaccinated individuals were 26% less likely to deliver at <37 weeks of gestation (adjusted odds ratio, 0.74; 95% confidence interval, 0.73-0.75; P<.001), 37% less likely to deliver at <34 weeks of gestation (adjusted odds ratio, 0.63; 95% confidence interval, 0.61-0.64; P<.001), and 43% less likely to deliver at <28 weeks of gestation (adjusted odds ratio, 0.57; 95% confidence interval, 0.55-0.60; P<0.001) than unvaccinated individuals. CONCLUSION: Vaccination against COVID-19 may be protective against preterm birth.

Physiologic Changes During Pregnancy and Impact on Small-Molecule Drugs, Biologic (Monoclonal Antibody) Disposition, and Response.

Pregnancy is a unique physiological state that results in many changes in bodily function, including cellular, metabolic, and hormonal changes. These changes can have a significant impact on the way small-molecule drugs and monoclonal antibodies (biologics) function and are metabolized, including efficacy, safety, potency, and adverse effects. In this article, we review the various physiologic changes that occur during pregnancy and their effects on drug and biologic metabolism, including changes in the coagulation, gastrointestinal, renal, endocrine, hepatic, respiratory, and cardiovascular systems. Additionally, we discuss how these changes can affect the processes of drug and biologic absorption, distribution, metabolism, and elimination (pharmacokinetics), and how drugs and biologics interact with biological systems, including mechanisms of drug action and effect (pharmacodynamics) during pregnancy, as well as the potential for drug-induced toxicity and adverse effects in the mother and developing fetus. The article also examines the implications of these changes for the use of drugs and biologics during pregnancy, including consequences of suboptimal plasma drug concentrations, effect of pregnancy on the pharmacokinetics and pharmacodynamics of biologics, and the need for careful monitoring and individualized drug dosing. Overall, this article aims to provide a comprehensive understanding of the physiologic changes during pregnancy and their effects on drug and biologic metabolism to improve the safe and effective use of drugs.

The relationship between COVID-19 vaccination status in pregnancy and birthweight.

BACKGROUND: Despite findings that maternal COVID-19 infection in pregnancy is associated with low birthweight (weight of ≤2500 g), previous studies demonstrate no difference in low birthweight risk between COVID-19 vaccinated and unvaccinated pregnant persons. Few studies, however, have examined the association between unvaccinated, incomplete vaccination, and complete vaccination on low birthweight, and they have been limited by small sample sizes and lack of adjustment for covariates. OBJECTIVE: We sought to address key limitations of prior work and evaluate this association between unvaccinated, incomplete, and complete COVID-19 vaccination status in pregnancy and low birthweight. We predicted a protective association of vaccination on low birthweight that varies by number of doses received. STUDY DESIGN: We performed a population-based retrospective study using the Vizient clinical database, which included data from 192 hospitals in the United States. Our sample included pregnant persons who delivered between January 2021 and April 2022 at hospitals that reported maternal vaccination data and birthweight at delivery. Pregnant persons were categorized into 3 groups as follows: unvaccinated; incompletely vaccinated (1 dose of Pfizer or Moderna); or completely vaccinated (1 dose of Johnson & Johnson or ≥2 doses of Moderna or Pfizer). Demographics and outcomes were analyzed using standard statistical tests. We performed multivariable logistic regression to account for potential confounders between vaccination status and low birthweight in the original cohort. Propensity score matching was used to reduce bias related to the likelihood of vaccination, and the multivariable logistic regression model was then applied to the propensity score-matched cohort. Stratification analysis was performed for gestational age and race and ethnicity. RESULTS: Of the 377,995 participants, 31,155 (8.2%) had low birthweight, and these participants were more likely to be unvaccinated than those without low birthweight (98.8% vs 98.5%, P<.001). Incompletely vaccinated pregnant persons were 13% less likely to have low birthweight neonates compared to unvaccinated persons (odds ratio, 0.87; 95% confidence interval, 0.73-1.04), and completely vaccinated persons were 21% less likely to have low birthweight neonates (odds ratio, 0.79; 95% confidence interval, 0.79-0.89). After controlling for maternal age, race or ethnicity, hypertension, pregestational diabetes, lupus, tobacco use, multifetal gestation, obesity, use of assisted reproductive technology, and maternal or neonatal COVID-19 infections in the original cohort, these associations remained significant for only complete vaccination (adjusted odds ratio, 0.80; 95% confidence interval, 0.70-0.91) and not incomplete vaccination (adjusted odds ratio, 0.87; 95% confidence interval, 0.71-1.04). In the propensity score-matched cohort, pregnant persons who were completely vaccinated against COVID-19 were 22% less likely to have low birthweight neonates compared to unvaccinated and incompletely vaccinated individuals (adjusted odds ratio, 0.78; 95% confidence interval, 0.76-0.79). CONCLUSION: Pregnant persons who were completely vaccinated against COVID-19 were less likely to have low birthweight neonates compared to unvaccinated and incompletely vaccinated individuals. This novel association was observed among a large population after adjusting for confounders of low birthweight and factors influencing the likelihood of receiving the COVID-19 vaccine.

Antiretroviral Treatment of HIV/AIDS During Pregnancy.

This Insights in the Women's Health series describes the availability, timing, and risks of antiretroviral therapy (ART) in pregnant individuals who have HIV infection.

A Five-Year Review of Feto-Maternal Outcome of Antepartum Haemorrhage in a Tertiary Center.

Background: Pregnancies complicated with antepartum-haemorrhage is high risk pregnancies associated with adverse maternal, fetal-and-perinatal-outcomes. It contributes significantly to fetal and maternal mortality especially in the developing countries. Proper antenatal care and prompt intervention is necessary to forestall adverse and improve outcome. Objective: To determine the prevalence, sociodemographic characteristics, risk factors, fetomaternal outcome of pregnancies with antepartum haemorrhage. Methods: The case files of the patients were retrieved from the medical records department. The total number of deliveries within the study period was obtained from the labour ward records. The feto-maternal-outcome-measures were; prevalence of caesarean-section, postpartum-haemorrhage, hysterectomy, need for blood-transfusion, maternal-death, prematurity, need for admission in intensive-care-unit and still births. The data was analysed using SPSS version 21. Chi-square was used to test for significance. Results: Within the 5-year period under review, out of a total of 6974 deliveries, 234 had antepartum-haemorrhage (3.4% prevalence rate). Abruptio-placentae was the commonest cause and accounted for 69.5% of the cases (prevalence of 2.1%) while placenta praevia accounted for 28.2% of the cases (prevalence rate of 0.9%). The mean age of the women was 31.8±5.3 years. The mean parity was 3.4±1.7 and majority (63.8%) of the women were unbooked. The commonest identifiable risk factors were multiparity and advanced maternal age. One-hundred-and sixty-six (77.9%) women were delivered through the abdominal route. Postpartum-haemorrhage occurred in 22.1% (47) of the cases while prematurity was the commonest fetal complications. Maternal mortality was 0.47% (1) while still birth was 44.1% (94). Conclusion: There is high prevalence of antepartum-haemorrhage in our environment. Abruptio-placentae was the commonest cause and associated with significant adverse fetomaternal-outcome when compared with placenta-praevia. Thus, good and quality antenatal care as well as high index of suspicion, prompt diagnosis and treatment remain the key to forestall these complications and improve fetomaternal-outcome.

Severe Maternal Morbidity and Mortality in Sickle Cell Disease in the National Inpatient Sample, 2012-2018.

Importance: Pregnancy outcomes are historically poor among people with sickle cell disease (SCD) in the US, most of whom have Black race. Whether outcomes have improved is unknown. Objective: To tabulate adverse pregnancy outcomes among patients with SCD, comparing outcomes of deliveries among Black people with SCD with those of Black people without SCD and a control non-Black population, and to measure the association of racial disparities with adverse outcomes in SCD pregnancies. Design, Setting, and Participants: This cross-sectional study was a secondary analysis involving data from National Inpatient Sample, a nationally representative sample of 20% of acute hospital admissions in the US, between 2012 and 2018. The data set included all admissions with codes for delivery of a pregnancy among people aged 11 to 55 years. Data were analyzed from September 2021 to August 2022. Exposures: SCD, racial disparities. Main Outcomes and Measures: Severe maternal morbidity (SMM) as measured by the US Centers for Disease Control and Prevention's index alongside other outcomes; multiple logistic regression was used to compare the odds for adverse pregnancy outcomes. Results: The sample included 5 401 899 deliveries, including 3901 deliveries among people with SCD and 742 164 deliveries among people with Black race. Compared with the non-Black control group, patients with SCD and Black patients were younger (mean [SD] age: SCD, 27.2 [5.9] years; Black, 27.1 [6.1] years vs 28.7 [5.9] years) and more likely to have public insurance (SCD, 2609 deliveries [67.3%]; Black, 496 828 deliveries [65.4%] vs 1 880 198 deliveries [40.8%]). The maternal mortality rate in deliveries among people with SCD was 26 times greater than in the non-Black control group and more than 10 times greater than among Black pregnant people without SCD (Per 10 000 deliveries: SCD 13.3; 95% CI, 5.7-31.2; Black race, 1.2; 95% CI, 1.0-1.5; non-Black control 0.5; 95% CI, 0.5-0.6). Compared with the control group, SCD deliveries had higher odds of SMM (adjusted odds ratio [aOR], 7.22; 95% CI, 6.25-8.34; P < .001), especially cerebrovascular events (aOR, 22.00; 95% CI, 15.25-31.72; P < .001) and thromboembolism (aOR, 17.34; 95% CI, 11.55-26.03; P < .001). Racial disparities explained a median (IQR) 28.9% (21.2%-33.1%) of the increased risk in deliveries to people with SCD and between 40% and 50% of the increased risk for acute kidney failure (excess risk [ER], 56.9%; 95% CI, 54.3%-59.3%), intrauterine fetal demise (ER, 47.8%; 95% CI, 46.6%-49.1%), and eclampsia (ER, 42.1%; 95% CI, 37.9%-46.1%). Conclusions and Relevance: In this large cross-sectional study of pregnancy outcomes in people with SCD, the risk for SMM was higher compared with deliveries among people without SCD, especially for thrombotic events, organ failure, and death. Racial disparities were associated with adverse outcomes. Our findings compel scientific, clinical, and political effort to improve outcomes for pregnant people with SCD.

Comparisons of Severe Maternal Morbidity and Other Adverse Pregnancy Outcomes in Pregnant People With Sickle Cell Disease vs Anemia.

Importance: Pregnancy in sickle cell disease (SCD) is high risk, but whether prenatal anemia, which is treatable with red blood cell transfusions, is a mediator associated with adverse pregnancy outcomes (APOs) is not known. Objective: To compare rates and odds of severe maternal morbidity (SMM) and other APOs in pregnancies among individuals with SCD vs those without SCD but with prenatal anemia. Design, Setting, and Participants: This cross-sectional study was conducted using data from 2012 to 2018 from the National Inpatient Sample, a nationally representative sample of 20% of acute hospital admissions in the United States. All admissions with codes for delivery of a pregnancy among people aged 11 to 55 years were included. Only admissions coded with Black race were included. Data were analyzed from September 2021 through August 2022. Exposures: Prenatal anemia and SCD. Main Outcomes and Measures: SMM was tabulated per the Center for Disease Control and Prevention SMM Index alongside other APOs. Multiple logistic regression was used to compare the odds for APOs and risk ratios (RRs) to compare rates of APOs. Results: Among 764 455 total delivery admissions among patients identified as Black (mean [SD] age at delivery, 27.00 [6.08] years), 3200 deliveries were coded with maternal SCD, 34 808 deliveries were coded with maternal anemia, and 726 447 deliveries were control. Most patients were publicly insured (499 060 [65.4%]). For most outcomes, including SMM and mortality per 10 000 deliveries, the SCD group had higher rates (SMM: 5.9%; 95% CI, 5.1%-6.8%; maternal mortality: 13.0 deaths; 95% CI, 4.9 to 35.0 deaths) than anemia (SMM: 2.1%; 95% CI, 2.0%-2.3%; maternal mortality: 0.9 deaths; 95% CI, 0.3 to 2.8 deaths) or control groups (SMM: 1.1%; 95% CI, 1.0%-1.1%; maternal mortality: 1.2 deaths; 95% CI, 1.0 to 1.5 deaths). SCD (adjusted odds ratio [aOR], 5.51; 95% CI, 4.71-6.45) and anemia groups (aOR, 2.00; 95% CI, 1.84-2.17) had higher adjusted odds of SMM compared with the control group. However, for many complications associated with ischemia or abnormal placentation, CIs of aORs for SCD and anemia groups overlapped (eg, eclampsia: aOR, 2.74; 95% CI, 1.51-4.96 vs aOR, 1.40; 95% CI, 1.08-1.81). For these complications, RRs for SCD vs anemia were between 1.0 and 2.1 (eg, eclampsia: 1.76; 95% CI, 0.93-3.32). For complications associated with thrombosis or SCD-specific pathologies, rates and aORs were greater for the SCD vs anemia group. For these complications, RRs were between 3.70 and 10.90. For example, rates of acute respiratory distress syndrome, including acute chest syndrome, were 56 of 3144 deliveries (1.8%) vs 122 of 34 686 deliveries (0.4%), and the RR was 4.99 (95% CI, 3.65-6.84). Conclusions and Relevance: This study found that risks associated with prenatal anemia and SCD were similar for many APOs, especially those associated with ischemia and abnormal placentation, suggesting that prenatal anemia may be a mediator associated with pregnancy risk in individuals with SCD.

Postpartum hemorrhage protocols and benchmarks: improving care through standardization.

Postpartum hemorrhage remains a leading cause of maternal morbidity and mortality in the United States. Several state maternal morbidity and mortality committees have reviewed areas of opportunity concerning postpartum hemorrhage management and found that common patterns include delays in recognition and response to hemorrhage. Hospital systems and state perinatal quality collaboratives have found that comprehensive, interdisciplinary response to postpartum hemorrhage care improves patient outcomes and, in some instances, reduces racial disparities. A key component of this focus involves the implementation of stage-based hemorrhage protocols for postpartum hemorrhage management. Stage-based hemorrhage protocols are designed to reduce delays in the diagnosis and management and avoid the pitfalls of cognitive biases. These protocols are complex, and their effectiveness is tied to the quality of their implementation. Systematic benchmarking and development of quality metrics for adherence to postpartum hemorrhage bundles would be expected to improve clinical outcomes, but evidence regarding the effectiveness of this practice in the literature is limited. Here, key features of stage-based interventions and evidence regarding the use of quality metrics for postpartum hemorrhage protocol adherence have been outlined.

Understanding clinical outcome measures reported in HIV pregnancy studies involving antiretroviral-naive and antiretroviral-experienced women.

HIV infection is a clinically significant public health disease and contributes to increased risk of maternal and fetal morbidity and mortality. HIV pregnancy studies use outcome measures as metrics to show how people with HIV feel, function, or survive. These endpoints are crucial for tracking the evolution of HIV illness over time, assessing the effectiveness of antiretroviral therapy (ART), and comparing outcomes across studies. Although the need for ideal outcome measures is widely acknowledged, selecting acceptable outcome measures for these HIV pregnancy studies can be challenging. We discuss the many outcome measures that have been implemented over time to assess HIV in pregnancy studies, their benefits, and drawbacks. Finally, we offer suggestions for improving the reporting of outcome measures in HIV in pregnancy studies. Medical professionals can best care for pregnant women living with HIV receiving ART by having a thorough understanding of these outcome metrics.

Preventing postpartum hemorrhage with combined therapy rather than oxytocin alone.

Postpartum hemorrhage is the leading cause of maternal morbidity and mortality worldwide, with uterine atony estimated to account for 70% to 80% of cases, thereby remaining the single most common cause. Pharmacotherapy remains the first-line preventative therapy for postpartum hemorrhage. These therapies may be single (oxytocin, carbetocin, methylergonovine, ergometrine, misoprostol, prostaglandin analogs, or tranexamic acid) or combination therapies, acting in an additive, infra-additive, or synergistic fashion to prevent postpartum hemorrhage. Evidence is strong for the use of oxytocin, the first-line uterotonic agent in the United States for prevention of postpartum hemorrhage. Although carbetocin, a long-acting analog of oxytocin, is not yet available for use in the United States, it is likely the most effective single pharmacologic therapy for prevention of postpartum hemorrhage and need for additional uterotonics. Use of second-line uterotonics such as methylergonovine, misoprostol, and carboprost in combination with oxytocin has an additive or synergistic effect and a greater risk reduction for postpartum hemorrhage prevention compared with oxytocin alone. Therefore, combined therapy rather than oxytocin alone should be advised for preventing postpartum hemorrhage. Tranexamic acid has been found to be both effective and safe for decreasing maternal mortality in women with postpartum hemorrhage, and prophylactic use of tranexamic acid may decrease the need for packed red blood cell transfusions and/or uterotonics. The WOMAN-2 Trial, designed to assess if tranexamic acid prevents postpartum hemorrhage in women with moderate to severe anemia undergoing vaginal delivery, is currently recruiting participants. The additive, infra-additive, or synergistic action of oxytocin in combination with other second-line therapies deserves further study.

Emerging Predictors of Obstructed Labour in a Single Nigerian Centre Population of a Low Resource Setting.

Background and Objective: Despite the stigma attached to obstructed labour in Nigeria, it has remained largely uninvestigated. Study determined the prevalence, emerging predictors, management modalities and complications of obstructed labour, compare them with cases without obstructed labour who delivered within the same period. Materials and Methods: A retrospective study and case-controlled analysis of obstructed labour managed at Nnamdi Azikiwe University Teaching Hospital, Nnewi, South-East, Nigeria were undertaken. One control per case was randomly selected from the remaining births by selecting the non-obstructed labour cases. Bivariate analysis was performed by the Chi-squared test and conditional logistic regression analysis was used to determine variables associated with obstructed labour. Statistical significance was accepted when the p<0.05. Results: Of all the 5,301 deliveries during the study period, 80 cases of obstructed labour were recorded, giving a prevalence of 1.5%. Only 73 case files were available with complete information for the study's further analysis. A conditional logistic regression analysis, the risk factors were teenage pregnancy (p<0.001, Adjusted Odds Ratio (AOR):5.43, 95% Confidence Interval (CI):1.20-8.05), unbooked status (p<0.001, AOR:0.01, 95%CI:0.00-0.02), nulliparity (p<0.001, AOR:4.15, 95%CI:2.42-7.25), short stature (p<0.001, AOR:44.74, 95%CI:19.51-113.53) and birth weight (p<0.001, AOR:4.52, 95%CI:2.69-7.71). The case fatality rate was 5.5% and the perinatal mortality rate was 21.9%. Conclusion: Majority obstructed labour have high maternal morbidity and perinatal mortality.