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Direct-Acting Antiviral Agents (DAAs) provide safer, efficacious, tolerable, and curative therapy for women with hepatitis C. Their preferred safety and efficacy profile make them potential therapies for the elimination of perinatal transmission of hepatitis C virus (HCV). However, DAAs are not currently recommended for use during pregnancy due to limited pharmacokinetic and safety data.This review covers the different DAA drug combinations, the available data on their pharmacodynamic and pharmacokinetic properties, how the physiology in pregnancy can potentially affect DAA drug disposition, known drug-drug interactions with DAAs, and available and planned epidemiological and pharmacokinetic studies on DAA use during pregnancy. Although no large randomized clinical trials or prospective cohort studies involving DAAs have been completed in pregnancy, the currently available studies demonstrate no significant changes in pharmacokinetics, and no major safety concerns in women with hepatitis C.Initial pharmacokinetic and safety data suggest that DAAs have high efficacy and a low risk of adverse events during pregnancy. As more pharmacokinetic and epidemiologic data become available, DAAs could become a preferred option for treating HCV during pregnancy and elimination of perinatal transmission of hepatitis C virus.

ObjectivesLong-acting reversible contraceptives are effective contraceptives for women with HIV, but there are limited data on etonogestrel implant and antiretroviral therapy pharmacokinetic drug-drug interactions. We evaluated etonogestrel/antiretroviral therapy drug-drug interactions, and the effects of etonogestrel on ritonavir-boosted-atazanavir, ritonavir-boosted-lopinavir, and efavirenz pharmacokinetics.Study designWe enrolled postpartum women using etonogestrel implants and receiving ritonavir-boosted-atazanavir, ritonavir-boosted-lopinavir, or efavirenz-based regimens between 2012 and 2015. Etonogestrel implants were inserted 2 to 12 weeks postpartum. We performed pharmacokinetic sampling pre-etonogestrel insertion and 6 to 7 weeks postinsertion. We measured antiretroviral concentrations pre and postetonogestrel insertion, and compared etonogestrelconcentrations between antiretroviral regimens. We considered a minimum serum etonogestrelconcentration of90 pg/mLadequate for ovulation suppression.ResultsWe collected pharmacokinetic data for 74 postpartum women, 22 on ritonavir-boosted-atazanavir, 26 on ritonavir-boosted-lopinavir, and 26 on efavirenz. The median serum concentrations of etonogestrel when co-administered were highest with etonogestrel/ritonavir-boosted-atazanavir (604 pg/mL) and etonogestrel/ritonavir-boosted-lopinavir (428 pg/mL), and lowest with etonogestrel/efavirenz (125 pg/mL); p < 0.001. Minimum concentration (Cmin) of ritonavir-boosted-atazanavir and ritonavir-boosted-lopinavir were lower after etonogestrel implant insertion, but overall exposure, predose concentrations, clearance, and half-lives were unchanged. We found no significant change in efavirenz exposure after etonogestrel insertion.ConclusionsUnlike efavirenz, ritonavir-boosted-atazanavir and ritonavir-boosted-lopinavir were not associated with significant decreases in etonogestrel concentrations. Efavirenz was associated with a significant decrease in etonogestrel concentrations.ImplicationsThe findings demonstrate no interactions between etonogestrel and ritonavir-boosted-lopinavir or ritonavir-boosted-atazanavir, but confirm the decreased efficacy of etonogestrel with efavirenz-based antiretrovirals. This information should be used to counsel women with HIV who desire long-acting reversible contraceptives.

For many years, the medical community has relied in clinical practice on historic data about the physiological changes that occur during pregnancy. However, some newer studies have disputed a number of assumptions in these data for not being evidence-based or derived from large prospective cohort-studies. Accurate knowledge of these physiological changes is important for three reasons: Firstly, it facilitates correct diagnosis of diseases during pregnancy; secondly, it enables us to answer questions about the effects of medication during pregnancy and the ways in which pregnancy alters pharmacokinetic and drug-effects; and thirdly, it allows for proper modeling of physiologically-based pharmacokinetic models, which are increasingly used to predict gestation-specific changes and drug–drug interactions, as well as develop new knowledge on the mode-of-action of drugs, the mechanisms underlying their interactions, and any adverse effects following drug exposure. This paper reviews new evidence regarding the physiologic changes during pregnancy in relation to existing knowledge.

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.

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.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 p0.05.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 (p0.001, Adjusted Odds Ratio (AOR):5.43, 95% Confidence Interval (CI):1.20-8.05), unbooked status (p0.001, AOR:0.01, 95%CI:0.00-0.02), nulliparity (p0.001, AOR:4.15, 95%CI:2.42-7.25), short stature (p0.001, AOR:44.74, 95%CI:19.51-113.53) and birth weight (p0.001, AOR:4.52, 95%CI:2.69-7.71). The case fatality rate was 5.5% and the perinatal mortality rate was 21.9%.Majority obstructed labour have high maternal morbidity and perinatal mortality.

Pregnant people living with HIV (PLWH) are at especially high risk for progression from latent tuberculosis infection (LTBI) to active tuberculosis (TB) disease. Among pregnant PLWH, concurrent TB increases the risk of complications such as preeclampsia, intrauterine fetal-growth restriction, low birth weight, preterm-delivery, perinatal transmission of HIV, and admission to the neonatal intensive care unit. The grave impact of superimposed TB disease on maternal morbidity and mortality among PLWH necessitates clear guidelines for concomitant therapy and an understanding of the pharmacokinetics (PK) and potential drug-drug interactions (DDIs) between antitubercular (anti-TB) agents and antiretroviral therapy (ART) in pregnancy.This review discusses the currently available evidence on the use of anti-TB agents in pregnant PLWH on ART. Pharmacokinetic and safety studies of anti-TB agents during pregnancy and postpartum are limited, and available data on second-line and newer anti-TB agents used in pregnancy suggest that several research gaps exist. DDIs between ART and anti-TB agents can decrease plasma concentration of ART, with the potential for perinatal transmission of HIV. Current recommendations for the treatment of LTBI, drug-susceptible TB, and multidrug-resistant TB (MDR-TB) are derived from observational studies and case reports in pregnant PLWH. While the use of isoniazid, rifamycins, and ethambutol in pregnancy and their DDIs with various ARTs are well-characterized, there is limited data on the use of pyrazinamide and several new and second-line antitubercular drugs in pregnant PLWH. Further research into treatment outcomes, PK, and safety data for anti-TB agent use during pregnancy and postpartum is urgently needed.

OBJECTIVE: To determine if blood biomarkers measured at delivery and shortly after birth can identify growth restricted infants at risk for developing severe brain injury. STUDY DESIGN: In a cohort of very low birth weight neonates, fetal growth restricted (FGR) (birth weight < 10%) were compared to non-FGR neonates, and within the FGR group those with brain injury were compared to those without. Biomarkers were measured in cord blood at delivery, and daily for the 1st 5 days of life. RESULT: FGR was associated with significantly higher levels of interleukin (IL)-6, IL-8, IL-10 and lower levels of vascular endothelial growth factor (VEGF). FGR and brain injury were associated with significantly higher levels of IL-6, IL-8, IL-10 and glial fibrillary acidic protein (GFAP). CONCLUSION: Interleukins may be involved in a common pathway contributing to both the development of growth restriction and brain injury, and GFAP may help identify brain injury within this growth restricted group., PRECIS: Biomarkers measured in cord blood at delivery and neonatal serum after birth may identify growth restricted infants at risk for developing severe brain injury.

Introduction Postpartum hemorrhage (PPH) has remained the leading cause of maternal mortality. While anemia is a leading contributor to maternal morbidity, molecular, cellular and anemia-induced hypoxia, clinical studies of the relationship between prenatal-anemia and PPH have reported conflicting results. Therefore, our objective was to investigate the outcomes of studies on the relationships between prenatal anemia and PPH-related mortality. Materials and methods Electronic databases (MEDLINE, Scopus, ClinicalTrials.gov, PROSPERO, EMBASE, and the Cochrane Central Register of Controlled Trials) were searched for studies published before August 2019. Keywords included "anemia," "hemoglobin," "postpartum hemorrhage," and "postpartum bleeding." Only studies involving the association between anemia and PPH were included in the meta-analysis. Our primary analysis used random effects models to synthesize odds-ratios (ORs) extracted from the studies. Heterogeneity was formally assessed with the Higgins' I2 statistics, and explored using meta-regression and subgroup analysis. Results We found 13 eligible studies investigating the relationship between prenatal anemia and PPH. Our findings suggest that severe prenatal anemia increases PPH risk (OR = 3.54; 95% CI: 1.20, 10.4, p-value = 0.020). There was no statistical association with mild (OR = 0.60; 95% CI: 0.31, 1.17, p-value = 0.130), or moderate anemia (OR = 2.09; 95% CI: 0.40, 11.1, p-value = 0.390) and the risk of PPH. Conclusion Severe prenatal anemia is an important predictive factor of adverse outcomes, warranting intensive management during pregnancy. PROSPERO Registration Number: CRD42020149184; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=149184.

Medication adherence to antiretroviral medications is critical during pregnancy in women living with HIV (WLHIV) for multiple reasons. In this study, we report medication adherence to tenofovir alafenamide (TAF) compared to tenofovir disoproxil fumarate (TDF) during pregnancy in WLHIV.This is a retrospective cohort study of pregnant women living with HIV aged 18-48 years who received either tenofovir alafenamide (TAF) or tenofovir disoproxil fumarate (TDF) during pregnancy. Medication adherence was assessed during each visit in all trimesters of pregnancy, and was self-reported. Demographics and outcomes were analyzed using standard statistical tests. Logistic regression analysis models accounting for potential confounders, with adjusted odds-ratios (aORs) and associated 95% confidence intervals were reported.One hundred women met inclusion criteria, with thirty-four women on TAF and sixty-six women on TDF. While medication adherence was higher in women using TAF compared to TDF, with 76% adherent to TDF vs 83% adherent to TAF; p=0.282, in the 1Pregnant women living with HIV on TDF and TAF achieved high adherence, but medication adherence was better in the third trimester compared to the first or second trimesters of pregnancy. These findings support the need to continually assess medication adherence during pregnancy.

Contains fulltext : 235789.pdf (Publisher’s version ) (Open Access) Information on the extent of drug exposure to mothers and infants during pregnancy and lactation normally becomes available years after regulatory approval of a drug. Clinicians face knowledge gaps on drug selection and dosing in pregnancy and infant exposure during breastfeeding. Physiological changes during pregnancy often result in lower drug exposures of antiretrovirals, and in some cases a risk of reduced virologic efficacy. The International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) network and the World Health Organization (WHO)-convened Pediatric Antiretrovirals Working Group collaboratively organized a workshop of key stakeholders in June 2019 to define key standards to generate pharmacology data for antiretrovirals to be used among pregnant and lactating women; review the antiretroviral product pipeline; describe key gaps for use in low-income and middle-income countries; and identify opportunities to undertake optimal studies allowing for rapid implementation in the clinical field. We discussed ethical and regulatory principles, systemic approaches to obtaining data for pregnancy pharmacokinetic/pharmacodynamic (PK/PD) studies, control groups, optimal sampling times during pregnancy, and pharmacokinetic parameters to be considered as primary end points in pregnancy PK/PD studies. For lactation studies, the type of milk to collect, ascertainment of maternal adherence, and optimal PK methods to estimate exposure were discussed. Participants strongly recommended completion of preclinical reproductive toxicology studies prior to phase III, to allow study protocols to include pregnant women or to allow women who become pregnant after enrolment to continue in the trial. The meeting concluded by developing an algorithm for design and interpretation of results and noted that recruitment of pregnant and lactating women into clinical trials is critical.

Objective To compare perioperative outcomes by patient race/ethnicity. Methods A retrospective cohort study identified 7 331 638 childbirth hospitalizations for women aged 12-55 years in the USA between 2004-2014. Peripartum hysterectomy, in-hospital mortality, perioperative complications, length of stay, and cost of hysterectomy data were analyzed using SAS. Results Among childbirth hospitalizations (52.9% white, 13.5% black, 23.0% Hispanic, 5.2% Asian, and 5.4% other), peripartum hysterectomy occurred in 6619. The incidence of peripartum hysterectomy was 90.3 (95% confidence interval [CI] 87.7-93.0) per 100 000 hospitalizations, and higher for black (111.0, 95% CI 104.5-117.4), Hispanic (104.9, 95% CI 99.1-110.8), and Asian women (119.6, 95% CI 109.1-130.2) compared to whites (75.7, 95% CI 72.8-78.5). After adjustment, Hispanic women had an 18% higher odds of undergoing peripartum hysterectomy (odds ratio [OR] 1.18, 95% CI 1.08-1.29; P=0.004) than white women. Non-white women had a 2-3-fold higher odds of in-hospital mortality (ORblack 2.76, 95% CI 1.44-5.30; ORHispanic 1.99, 95% CI 1.04-3.82; ORAsian+other 2.44, 95% CI 1.11-5.40. Black and Asian/other women were more likely to undergo blood transfusions. Conclusion Women of color have higher rates of peripartum hysterectomy and experience higher rates of poor perioperative outcomes and mortality.

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.

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.

Our objective was to assess the safety, efficacy, and pregnancy outcomes of Tenofovir Disoproxil Fumarate (TDF) compared to Tenofovir Alafenamide (TAF) use in pregnant women with HIV (PWLHIV).This retrospective cohort study of all women who received prenatal care at a single academic center between January 1There were 66 women in the TDF group and 34 women in the TAF group. In the overall cohort, the median (interquartile range, IQR) gestational age at delivery for PWLHIV on TDF and TAF were 38.6 (IQR 37.5-39.4) and 38.1 (31.1-39.1) weeks respectively; and most women (85%) were Black/African American. Compared to PWLHIV on a TDF regimen, women on TAF, on average, gained over 3 kg more weight in the 3Although TAF use was associated with more weight gain compared to TDF, both regimens appear safe and effective during pregnancy. PWLHIV should be counseled about the potential for weight gain with TAF based regimens during pregnancy.

ImportancePregnancy 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.ObjectiveTo 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 ParticipantsThis 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.ExposuresSCD, racial disparities.Main Outcomes and MeasuresSevere 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.ResultsThe 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 P P Conclusions and RelevanceIn 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.

ImportancePregnancy 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.ObjectiveTo 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 ParticipantsThis 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.ExposuresPrenatal anemia and SCD.Main Outcomes and MeasuresSMM 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.ResultsAmong 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 RelevanceThis 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.

Objectives To compare accuracy between Premaquick (combined test for native insulin-like growth factor binding protein-1 (IGFBP-1), total IGFBP-1, and interleukin-6) and fetal fibronectin (Ffn) in predicting preterm delivery. Methods Prospective study among women at 28-36+6 gestational weeks with threatened preterm labor attending Federal Medical Center, Owerri, Nigeria, from August 2017 to February 2019. Cervico-vaginal fluids were collected and tested by Premaquick and Ffn tests. The women were followed for 14 days. Sensitivity, specificity, and negative (NPV) and positive (PPV) predictive value for delivery were compared between the tests. Results Among 213 women assessed for eligibility, 183 were enrolled and 175 completed the study. The sensitivity, specificity, PPV, NPV, and accuracy of the Premaquick versus Ffn tests were, respectively, 96.3% versus 51.9%, 97.6% versus 98.4%, 89.7% versus 87.5%, 99.2% versus 90.3% and 97.3% versus 90.0% for preterm delivery within 14 days. Ffn had higher specificity (98.5% vs 97.8%; P>0.99), but Premaquick had higher PPV (92.7% vs 90.9%; P>0.99). Conclusion Both tests seem to have high utility in predicting preterm delivery, but Premaquick showed higher accuracy in terms of sensitivity and PPV. Premaquick might be a feasible alternative to Ffn for predicting preterm delivery among symptomatic women in a low-income setting.

This retrospective study of 100 pregnant women living with HIV [66 on tenofovir disoproxil fumarate (TDF) compared to 34 women on tenofovir alafenamide (TAF)] found no significant difference in renal function in pregnant women with HIV receiving TDF versus TAF. Our results demonstrate that, in regard to renal toxicity, both TDF and TAF appear to be safe for pregnant women living with HIV, but larger prospective cohort studies in pregnant women living with HIV are encouraged.

Pharmacokinetics of drugs can be affected by physiologic changes during pregnancy. Our aim was to assess the influence of covariates on tenofovir (TFV) pharmacokinetics in pregnant and postpartum women receiving tenofovir disoproxil fumarate (TDF). Population pharmacokinetic parameter estimates and the influence of covariates were assessed using nonlinear mixed-effects modeling (NONMEM 7.4). Forty-six women had intensive pharmacokinetic evaluations during the second and third trimesters of pregnancy, with another evaluation postpartum. A two-compartment pharmacokinetic model with allometric scaling for body weight and first-order absorption best described the tenofovir plasma concentration data. Apparent oral clearance (CL/F) and volume of distribution at steady state (V(ss)/F) were increased during pregnancy. Weight, serum creatinine (SCr), pregnancy, albumin, and age were associated with TFV CL/F during univariate assessment, but in the multivariate analysis, changes in CL/F and V(ss)/F were only associated with increased body weight and enhanced renal function. Due to greater weight and lower SCr during pregnancy, CL/F was 28% higher during pregnancy than postpartum. In the final model, CL/F (liters per hour) was described as 2.07 × (SCr/0.6)(0.65) × weight(0.75), with a low between-subject variability (BSV) of 24%. The probability of target attainment (proportion exceeding area under the concentration-time curve of >1.99 μg·h/ml, the 10th percentile of average TFV exposure for nonpregnant historical controls) was 68%, 80%, 87%, and 93% above the target with 300 mg, 350 mg, 400 mg, and 450 mg of TDF, respectively, during pregnancy and 88%, 92%, 96%, and 98% above the target with same doses in postpartum women. Dose adjustment of TDF during pregnancy is not generally warranted, but any modification should be based on weight and renal function. (This study has been registered at ClinicalTrials.gov under identifier NCT00042289.)

Background Preeclampsia is a well-known cause of maternal mortality and morbidity in Ethiopia. The exact pathophysiology has not been fully understood. Calcium and magnesium deficiencies have been given emphasis to play roles in the pathophysiology. Although evidence is abundant, they are equivocal. The study aimed to see the association of dietary calcium intake, serum total calcium level and ionized calcium level with preeclampsia. It also evaluated the association between dietary calcium intake and serum calcium levels. Materials and methods An unmatched case–control study was conducted in Gandhi Memorial, Tikur Anbessa, and Zewditu Memorial Hospitals, all in Addis Ababa, between October to December, 2019. Cases were 42 women with preeclampsia and controls were 42 normotensive women. The medical and obstetric history was gathered using a structured questionnaire and the dietary calcium intake information using a 24-h dietary recall. The serum levels of total serum calcium and ionized (free) calcium were measured using an inductively coupled mass spectrophotometer. Bivariate and multivariate logistic regression and Pearson correlation test were utilized during data analysis. Results In comparison with controls, women with preeclampsia had lower mean (± 1SD) levels of ionized calcium level (1.1 mmol/l ± 0.11), total serum calcium level (1.99 mmol/l ± 0.35) and lower median (IQR) dietary calcium intake (704 mg/24 h,458–1183). The odds of having preeclampsia was almost eight times greater in those participants with low serum ionized calcium level (OR 7.5, 95% CI 2.388–23.608) and three times higher in those with low total serum calcium level (OR 3.0, 95% CI 1.024–9.370). Low dietary calcium intake also showed statistically significant association with preeclampsia (OR 3.4, 95% CI 1.092 -10.723). Serum ionized calcium level and total serum calcium level showed positive correlation of moderate strength (p = 0.004, r = 0.307), but no correlation was found between dietary calcium intake with both forms of serum calcium levels. Conclusion This study showed significant association between low dietary calcium intake and low serum calcium levels with preeclampsia, hence this can be used as a supportive local evidence for the current context-specific recommendation of calcium supplementation in societies with low-dietary calcium consumption in an attempt to prevent preeclampsia, therefore implementation study should be considered in Ethiopia to look for the feasibility of routine supplementation.

INTRODUCTION: In December 2019, SARS-CoV-2 originated from China, and spread rapidly to several countries, bringing a frightening scarcity of personal protective equipment (PPE). The CDC recommends N95 or higher-level particulate filtering respirators as part of the PPE while caring for patients with COVID-19, with facemasks as an alternative; and cloth face-coverings in public where social distancing of at least 6 ft. is not feasible. With new evidence about the efficacy of facemasks, knowledge gaps remain. AREAS COVERED: This reviews the history of respiratory viral pandemics and PPE use, exploring the influenza pandemics of the 20(th) and 21(st) century, and prior coronavirus pandemics. A literature search of PubMed and google was done between March 22(nd) to May 2(nd), and on September 28, 2020. The evidence for PPE is described, to delineate their efficacy and ‘best safe’ practices. Solutions to ameliorate pandemic preparedness to meet surge-capacity to efficiently combat future pandemics, should they arise, are discussed. EXPERT OPINION: PPE, when used appropriately in addition to other infection control measures, is effective protection during respiratory viral pandemics. The current evidence suggests that wearing facemasks in the community is protective, especially if used consistently and correctly with other infection control measures such as hand hygiene.

Background: Postpartum hemorrhage (PPH) is the leading cause of maternal mortality, with loss of uterine tonicity as the main underlying cause. While mechanistic studies suggest that anemia-induced hypoxia reduces uterine tonicity, there is no meta-analysis of relevant clinical studies. Objectives: To conduct a systematic review/meta-analysis synthesizing clinical studies of the relationship between prenatal anemia and PPH. Search Strategy: We used search terms combining hemorrhage and anemia or their derivatives, and searched PUBMED/Medline, EMBASE , Cochrane, PROSPERO and Web of Science. Selection Criteria: Original peer-reviewed articles that measured an indicator of prenatal anemia and postpartum hemorrhage or postpartum hemorrhage-related mortality in humans. Data Collection and Analysis: Our primary analysis used random effects models to synthesize odds-ratios extracted from the studies. Heterogeneity was formally assessed with the Higgins’ I2 statistics and explored using meta-regression and subgroup analysis. Main Results: Overall, anemia was not associated with PPH (OR: 1.39; 95% (CI): 0.64 – 3.01). There was no statistical association with mild (OR=0.60; 95% CI: 0.31, 1.17, p-value = 0.13), or moderate anemia (OR=2.09; 95% CI: 0.40, 11.1, p-value = 0.39) and the risk of PPH. Our findings suggest that severe prenatal anemia increases postpartum hemorrhage risk (OR=3.54; 95% CI: 1.20, 10.4, p-value = 0.02). Conclusions: Mild and moderate prenatal anemia is not associated with PPH risk. High quality prospective studies are critical to evaluating the effect of severe anemia on PPH risk and related mortality. Funding: None. Key words: Maternal anemia, Post-partum hemorrhage risk factors, Post-partum hemorrhage-related mortality, Maternal mortality, Obstetric Emergency.

BACKGROUND: Preterm birth (PTB) remains the foremost global cause of perinatal morbidity and mortality. Thus, the prevention of spontaneous PTB still remains of critical importance. In an attempt to prevent PTB in singleton pregnancies, cervical cerclage, in combination with other treatments, has been advocated. This is because, cervical cerclage is an intervention that is commonly recommended in women with a short cervix at high risk of preterm birth but, despite this, many women still deliver prematurely, as the biological mechanism is incompletely understood. Additionally, previous Cochrane Reviews have been published on the effectiveness of cervical cerclage in singleton and multiple pregnancies, however, none has evaluated the effectiveness of using cervical cerclage in combination with other treatments. OBJECTIVES: To assess whether antibiotics administration, vaginal pessary, reinforcing or second cerclage placement, tocolytic, progesterone, or other interventions at the time of cervical cerclage placement prolong singleton gestation in women at high risk of pregnancy loss based on prior history and/or ultrasound finding of ’short cervix’ and/or physical examination. History‐indicated cerclage is defined as a cerclage placed usually between 12 and 15 weeks gestation based solely on poor prior obstetrical history, e.g. multiple second trimester losses due to painless dilatation. Ultrasound‐indicated cerclage is defined as a cerclage placed usually between 16 and 23 weeks gestation for transvaginal ultrasound cervical length < 20 mm in a woman without cervical dilatation. Physical exam‐indicated cerclage is defined as a cerclage placed usually between 16 and 23 weeks gestation because of cervical dilatation of one or more centimetres detected on physical (manual) examination. SEARCH METHODS: We searched Cochrane Pregnancy and Childbirth’s Trials Register, ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform (ICTRP) (26 September 2019), and reference lists of retrieved studies. SELECTION CRITERIA: We included published, unpublished or ongoing randomised controlled trial (RCTs). Studies using a cluster‐RCT design were also eligible for inclusion in this review but none were identified. We excluded quasi‐RCTs (e.g. those randomised by date of birth or hospital number) and studies using a cross‐over design. We also excluded studies that specified addition of the combination therapy after cervical cerclage because the woman subsequently became symptomatic. We included studies comparing cervical cerclage in combination with one, two or more interventions with cervical cerclage alone in singleton pregnancies. DATA COLLECTION AND ANALYSIS: Two review authors independently screened titles and abstracts of all retrieved articles, selected studies for inclusion, extracted data, assessed risk of bias, and evaluated the certainty of the evidence for this review's main outcomes. Data were checked for accuracy. Standard Cochrane review methods were used throughout. MAIN RESULTS: We identified two studies (involving a total of 73 women) comparing cervical cerclage alone to a different comparator. We also identified three ongoing studies (one investigating vaginal progesterone after cerclage, and two investigating cerclage plus pessary). One study (20 women), conducted in the UK, comparing cervical cerclage in combination with a tocolytic (salbutamol) with cervical cerclage alone in women with singleton pregnancy did not provide any useable data for this review. The other study (involving 53 women, with data from 50 women) took place in the USA and compared cervical cerclage in combination with a tocolytic (indomethacin) and antibiotics (cefazolin or clindamycin) versus cervical cerclage alone ‐ this study did provide useable data for this review (and the study authors also provided additional data on request) but meta‐analyses were not possible. This study was generally at a low risk of bias, apart from issues relating to blinding. We downgraded the certainty of evidence for serious risk of bias and imprecision (few participants, few events and wide 95% confidence intervals). Cervical cerclage in combination with an antibiotic and tocolytic versus cervical cerclage alone (one study, 50 women/babies) We are unclear about the effect of cervical cerclage in combination with antibiotics and a tocolytic compared with cervical cerclage alone on the risk of serious neonatal morbidity (RR 0.62, 95% CI 0.31 to 1.24; very low‐certainty evidence); perinatal loss (data for miscarriage and stillbirth only ‐ data not available for neonatal death) (RR 0.46, 95% CI 0.13 to 1.64; very low‐certainty evidence) or preterm birth < 34 completed weeks of pregnancy (RR 0.78, 95% CI 0.44 to 1.40; very low‐certainty evidence). There were no stillbirths (intrauterine death at 24 or more weeks). The trial authors did not report on the numbers of babies discharged home healthy (without obvious pathology) or on the risk of neonatal death. AUTHORS' CONCLUSIONS: Currently, there is insufficient evidence to evaluate the effect of combining a tocolytic (indomethacin) and antibiotics (cefazolin/clindamycin) with cervical cerclage compared with cervical cerclage alone for preventing spontaneous PTB in women with singleton pregnancies. Future studies should recruit sufficient numbers of women to provide meaningful results and should measure neonatal death and numbers of babies discharged home healthy, as well as other important outcomes listed in this review. We did not identify any studies looking at other treatments in combination with cervical cerclage. Future research needs to focus on the role of other interventions such as vaginal support pessary, reinforcing or second cervical cerclage placement, 17‐alpha‐hydroxyprogesterone caproate or dydrogesterone or vaginal micronised progesterone, omega‐3 long chain polyunsaturated fatty acid supplementation and bed rest.

Pharmacokinetic boosting of antiretroviral (ARV) therapies with either ritonavir or cobicistat is used to achieve target drug exposure, lower pill burden, and provide simplified dosing schedules. Several ARVs require boosting, including the integrase inhibitor elvitegravir as well as protease inhibitors such as darunavir, atazanavir, and lopinavir. The use of boosted regimens in pregnant women living with HIV has been studied for a variety of ARVs; however, a recent recommendation by the US Food and Drug Administration advised against cobicistat-boosted regimens in pregnancy due to substantially lower drug exposures observed in clinical pharmacokinetic studies. The objectives of this article are to review pharmacokinetic enhancement of ARVs with ritonavir and cobicistat during pregnancy and postpartum, describe clinical implications, and provide recommendations for future research.

OBJECTIVE To determine if neonatal serum biomarkers representing different pathways of injury differ for cases of HIE of unknown cause to gain insight into timing and mechanism of injury. STUDY DESIGN In this cohort of all neonates with HIE admitted to our NICU, newborns with sentinel events were compared to those without during the 1st 3 days of life. Discard neonatal blood during the 1st 3 days of life was used for analysis. RESULTS Of 277 babies with HIE treated with whole-body hypothermia, 190 (68.6%) had blood available for biomarker analysis. 71 (37.4%) were born within our system, and 119 (62.6%) were transferred in from outside hospitals. Of these babies, 77 (40.5%) had a sentinel event and 113 (59.6%) had no sentinel event. Although the degree of metabolic acidosis was similar, repeated measures analysis showed that during the initial 3 days of life neonates born with HIE in the absence of sentinel events had 41.4% decreased VEGF (p=0.027) and 62.5% increased IL-10 serum concentrations (p=0.005). CONCLUSION These changes indicate that neonatal HIE in the absence of sentinel events is not related to an unrecognized acute intrapartum event and is possibly related to chronic hypoxia of lower severity or recovery from a remote event.

Objective To perform a systematic review and meta-analysis evaluating the efficacy of adjuvant human papillomavirus (HPV) vaccination in preventing recurrent cervical intraepithelial neoplasia (CIN) 2 or greater after surgical excision. Data sources Electronic databases (Cochrane, PubMed, EMBASE, MEDLINE, Scopus, and ClinicalTrials.gov) were searched for studies comparing surgical excision alone to surgical excision with adjuvant HPV vaccination for CIN 2 or greater. Studies published from January 1990 to January 2019 were included. Methods A total of 5,901 studies were reviewed. The primary outcomes evaluated included: recurrence of CIN 2 or greater, CIN 1 or greater, and HPV 16,18 associated CIN within 6-48 months. We used Covidence software to assist with screening, and meta-analysis was performed using Review Manager. Tabulation, integration, and results Six studies met inclusion criteria and were included in the final analysis. In total 2,984 women were included; 1,360 (45.6%) received adjuvant HPV vaccination after surgical excision, and 1,624 (54.4%) received either placebo or surgical management alone for CIN 2 or greater. Recurrence of CIN 2 or greater occurred within 6-48 months in 115 women (3.9%) overall; however, recurrence was significantly lower for vaccinated women: 26 of 1,360 women (1.9%) vs 89 of 1,624 unvaccinated women (5.9%) (relative risk [RR] 0.36 95% CI 0.23-0.55). The risk of CIN 1 or greater was also significantly lower with adjuvant HPV vaccination, occurring in 86 of 1,360 vaccinated women (6.3%) vs 157 of 1,624 unvaccinated women (9.7%) (RR 0.67 95% CI 0.52-0.85). Thirty-five women developed recurrent CIN 2 or greater lesions specific to HPV 16,18; nine received adjuvant vaccination (0.9%) vs 26 who were unvaccinated (2.0%) (RR 0.41 95% CI 0.20-0.85). Conclusion Adjuvant HPV vaccination in the setting of surgical excision for CIN 2 or greater is associated with a reduced risk of recurrent cervical dysplasia overall and a reduction in the risk of recurrent lesions caused by the most oncogenic strains (HPV 16,18). Human papillomavirus vaccination should therefore be considered for adjuvant treatment in patients undergoing surgical excision for CIN 2 or greater. Systematic review registration PROSPERO, CRD42019123786.

BackgroundThis study aims to evaluate the pharmacokinetics of an increased dose of darunavir (800 mg twice daily) with 100 mg ritonavir during pregnancy and postpartum.MethodsDarunavir (DRV) and ritonavir (RTV; r) intensive pharmacokinetic evaluations were performed at steady state during the second and third trimesters of pregnancy (DRV/r 800/100 mg bid) and 2-3 weeks postpartum (DRV/r 600/100 mg twice daily). Plasma concentrations of darunavir and ritonavir were measured using high-performance liquid chromatography. Target darunavir area under the concentration time curve (AUC) was >70% (43.6 μg × h/mL) of median AUC (62.3 μg × h/mL) in nonpregnant adults on twice daily darunavir-ritonavir 600/100 mg.ResultsTwenty-four women were included in the analysis. Darunavir AUC0-12 was lower with the increased dose during the second {[geometric mean ratio (GMR) of 0.62 (IQR 0.44-0.88); P = 0.055]} and third trimesters [GMR 0.64 (IQR 0.55-0.73); P =

OBJECTIVE: To compare AmnioQuick Duo+ versus the placental α-microglobulin-1 (PAMG-1) test for diagnosis of prolonged premature rupture of membranes (PROM). METHODS: A multicenter prospective cohort study included women with suspected PROM at six tertiary institutions in southern Nigeria between January 1 and December 31, 2015. The inclusion criteria were features of PROM lasting at least 24 hours and a pregnancy duration of more than 24 weeks. AmnioQuick Duo+ (Biosynex, Strasbourg, France) and PAMG-1 (AmniSure International, Boston, USA) tests were used to diagnose PROM, which was confirmed after delivery by any two of the following criteria: delivery within 48 hours to 7 days, chorioamnionitis, membranes perceptibly ruptured at delivery, and adverse perinatal outcomes considerably associated with prolonged PROM. RESULTS: Of 100 women assessed for eligibility, 99 were included. Sensitivity, specificity, and accuracy were, respectively, 97.3%, 100%, and 95.9% for AmnioQuick Duo+, and 93.2%, 100%, and 90.4% for PAMG-1. The differences were not significant and the diagnostic discordant rate between the two tests was 3.1%. In equivocal cases (i.e., negative pooling test result), AmnioQuick Duo+ and PAMG-1 performed equally (diagnostic accuracy, 100% vs 97.7%; P>0.99). CONCLUSION: For diagnosis of PROM, AmnioQuick Duo+ was found to be non-inferior and comparable in accuracy to the PAMG-1 test, with a diagnostic discordance rate of 3.1%.

INTRODUCTION: The purpose of this study was to evaluate whether there are additional benefits of 17-hydroxyprogesterone caproate (17-OHPC) supplementation in preventing recurrent spontaneous preterm birth in women with a prophylactic cerclage. MATERIAL AND METHODS: Electronic databases (MEDLINE, Scopus, ClinicalTrials.gov, PROSPERO, EMBASE, Scielo and the Cochrane Central Register of Controlled Trials) were searched for studies published before June 2018. Keywords included “preterm birth”, “prophylactic cerclage”, “history-indicated cerclage”, “pregnancy” and “17-hydroxyprogesterone caproate”. Studies comparing history-indicated cerclage alone with cerclage+17-OHPC were included. The primary outcome measure was preterm birth at

This study aims to evaluate the safety, acceptability, and pharmacokinetics (PK) of an increased dose of nelfinavir (NFV) during the third trimester of pregnancy. The study was registered as part of the International Maternal Pediatric Adolescent AIDS Clinical Trials network (IMPAACT-P1026s), an ongoing multicenter prospective cohort study of antiretroviral PK during pregnancy (NCT00042289). NFV intensive PK evaluations were performed at steady state during the third trimester of pregnancy and 2-3 weeks postpartum. Plasma concentrations of NFV and its active metabolite, hydroxyl-tert-butylamide (M8) were measured using high-performance liquid chromatography with ultraviolet detection. A total of 18 women are included in the analysis. NFV area under the concentration-time curve (AUC) with the increased dose during the third trimester was nearly identical to the standard dose postpartum, with a geometric mean ratio for third trimester to postpartum AUC of 0.98 (90%CI 0.71-1.35). Despite the increased dose, M8 AUC was lower during the third trimester compared to postpartum (0.53, IQR [0.38-0.75]), as was the M8/NFV AUC ratio (0.51, IQR [0.42-0.63]). NFV AUC0-12 was above target in 15 of 18 (83%) of participants during the third trimester compared to 14 of 16 (88%) postpartum. No major safety concerns were noted. Increasing the NFV dose to 1875 mg twice daily during the third trimester achieved similar concentrations postpartum compared to standard dosing (1250 mg twice daily). Increased NFV dose regimens may still have some benefit to human immunodeficiency virus (HIV)-positive pregnant women living in countries where novel protease inhibitors are currently unavailable or in individuals who are intolerant to ritonavir-boosted HIV medications.

Background Observational studies have reported varying results about the association of velamentous cord insertion (VCI) with adverse pregnancy outcomes. Objectives To evaluate the risk of preterm delivery among singleton pregnancies complicated by VCI. Search strategy Various databases were searched for English-language articles published up to February, 28, 2017, using keywords including VCI; abnormal placentation; abnormal cord insertions; adverse perinatal outcomes; and preterm birth. Outcome measures included preterm delivery; pre-eclampsia; cesarean delivery; fetal demise in utero (FDIU); and small for gestational age (SGA). Selection criteria Only studies involving VCI were included in the meta-analysis. Data collection and analysis Analyses were performed using RevMan version 5.3.5 (The Nordic Cochrane Centre, Copenhagen, Denmark). Main results There were six studies included in the analysis. The VCI and control groups comprised 16 295 and 1 366 485 women, respectively. An increased incidence of preterm delivery was found for the VCI group compared with the control group (11.8% vs 7.0%; adjusted odds ratio [aOR] 1.95, 95% confidence interval [CI] 1.85-2.04). A diagnosis of VCI was also associated with cesarean delivery (aOR 1.17, 95% CI 1.12-1.23), SGA (aOR 1.93, 95% CI 1.83-2.04), and FDIU (aOR 3.96, 95% CI 3.21-4.89). Conclusion The presence of VCI was associated with adverse pregnancy outcomes.

STUDY QUESTION: Is there an association between intake of fruits and vegetables and risk of laparoscopically confirmed endometriosis? SUMMARY ANSWER: Higher intake of fruits, particularly citrus fruits, is associated with a lower risk of endometriosis. WHAT IS KNOWN ALREADY: Two case–control studies have examined the associations between fruit and vegetable intake and endometriosis risk with contrasting results. Diets rich in fruits and vegetables include higher levels of pro-vitamin A nutrients (alpha-carotene, beta-carotene, beta-cryptoxanthin) and women with endometriosis have been reported to have lower intake of vitamin A than women without endometriosis. STUDY DESIGN SIZE, DURATION: A prospective cohort study using data collected from 70 835 premenopausal women from 1991 to 2013 as part of the Nurses’ Health Study II cohort. PARTICIPANTS/MATERIALS, SETTING, METHODS: Diet was assessed with a validated food frequency questionnaire (FFQ) every 4 years. Cases were restricted to laparoscopically confirmed endometriosis. Cox proportional hazards models were used to calculate rate ratios (RR) and 95% CI. MAIN RESULTS AND THE ROLE OF CHANCE: During 840 012 person-years of follow-up, 2609 incident cases of laparoscopically confirmed endometriosis were reported (incidence rate = 311 per 100 000 person-years). We observed a non-linear inverse association between higher fruit consumption and risk of laparoscopically confirmed endometriosis (P(significance of the curve) = 0.005). This inverse association was particularly evident for citrus fruits. Women consuming ≥1 servings of citrus fruits/day had a 22% lower endometriosis risk (95% CI = 0.69–0.89; P(trend) = 0.004) compared to those consuming

OBJECTIVE: The objective of this study is to evaluate whether omission of intrauterine cleaning increases intraoperative and postoperative complications among women who deliver via cesarean section. METHODS: We randomized 206 women undergoing primary elective cesarean deliveries to intrauterine cleaning or omission of cleaning. Postpartum endomyometritis rates across groups were the primary outcome. We also examined secondary outcomes. To detect a 20% difference in infection rate between the cleaned and the non-cleaned groups (two-tailed [alpha] = 0.05, [beta] = 0.2), 103 women were required per group. Analysis was by intention-to-treat. RESULTS: Two hundred and six were randomized as follows: 103 to intrauterine cleaning and 103 to omission of cleaning after placental delivery. There were no statistically significant differences in the rate of endomyometritis between the two groups (2.0% versus 2.9%, RR =0.60; 95% CI 0.40–1.32). There were no statistically significant differences in postpartum hemorrhage rates (5.8% versus 7.7%, RR 0.75; 95% CI 0.6–1.2), hospital readmission rates (2.9 versus 3.8%, RR 0.75; 95% CI 0.5–1.6), time to return of gastrointestinal function, need for repeat surgery, or quantitated blood loss between the two groups. CONCLUSIONS: Our randomized controlled trial provides evidence suggesting that omission of intrauterine cleaning during cesarean deliveries in women at low risk of infection does not increase intraoperative or postoperative complications.

Author(s): Eke, Ahizechukwu C; Wang, Jiajia; Amin, Khadija; Shapiro, David E; Stek, Alice; Smith, Elizabeth; Chakhtoura, Nahida; Basar, Michael; George, Kathleen; Knapp, Katherine M; Joao, Esau C; Rungruengthanakit, Kittipong; Capparelli, Edmund; Burchett, Sandra; Mirochnick, Mark; Best, Brookie M; P1026s Protocol Team | Abstract: The purpose of this study was to evaluate the pharmacokinetics of ritonavir-boosted fosamprenavir during pregnancy and postpartum. Amprenavir (the active moiety of fosamprenavir) and ritonavir intensive pharmacokinetic evaluations were performed at steady state during the second and third trimesters of pregnancy and postpartum. Plasma concentrations of amprenavir and ritonavir were measured using high-performance liquid chromatography. The target amprenavir area under the concentration-versus-time curve (AUC) was higher than the 10th percentile (27.7 μg · h/ml) of the median area under the curve for ritonavir-boosted fosamprenavir in adults receiving twice-daily fosamprenavir-ritonavir at 700 mg/100 mg. Twenty-nine women were included in the analysis. The amprenavir AUC from time zero to 12 h (AUC0-12) was lower (geometric mean ratio [GMR], 0.60 [confidence interval {CI}, 0.49 to 0.72] [P l 0.001]) while its apparent oral clearance was higher (GMR, 1.68 [CI, 1.38 to 2.03] [P l 0.001]) in the third trimester than postpartum. Similarly, the ritonavir AUC0-12 was lower in the second (GMR, 0.51 [CI, 0.28 to 0.91] [P = 0.09]) and third (GMR, 0.72 [CI, 0.55 to 0.95] [P = 0.005]) trimesters than postpartum, while its apparent oral clearance was higher in the second (GMR, 1.98 [CI, 1.10 to 3.56] [P = 0.06]) and third (GMR, 1.38 [CI, 1.05 to 1.82] [P = 0.009]) trimesters than postpartum. The amprenavir area under the curve exceeded the target for 6/8 (75%) women in the 2nd trimester, 18/28 (64%) in the 3rd trimester, and 19/22 (86.4%) postpartum, and the trough concentrations (C min) of amprenavir were 4- to 16-fold above the mean amprenavir-protein-adjusted 50% inhibitory concentration (IC50) of 0.146 μg/ml. Although amprenavir plasma concentrations in women receiving ritonavir-boosted fosamprenavir were lower during pregnancy than postpartum, the reduced amprenavir concentrations were still above the exposures needed for viral suppression.

INTRODUCTION: Tenofovir alafenamide (TAF)-containing fixed-dose drug combinations (FDCs) are increasingly being used in managing pregnant women living with HIV. However, TAF is not currently recommended during pregnancy due to limited pharmacokinetic and safety data. TAF, a newer nucleotide phosphonamidate prodrug of tenofovir (TFV), achieves high levels of tenofovir-diphosphate in lymphoid cells and hepatocytes, and 90% lower systemic concentrations of TFV compared to tenofovir disoproxil fumarate (TDF), thereby maximizing TAF’s antiviral efficacy, potency and clinical safety. AREAS COVERED: This review discusses the currently available information on the pharmacology of TAF in pregnant women living with HIV. Pharmacokinetic studies with TAF during pregnancy have yielded varying results compared to postpartum, but TAF exposures during pregnancy have been within the range of those typically observed in non-pregnant adults. The efficacy and safety of TAF in treatment-naïve pregnant women living with HIV is currently being evaluated in the VESTED study, a phase-III NIH randomized clinical trial. EXPERT OPINION: Initial pregnancy data suggest that TAF-based FDCs have high efficacy and low risk of adverse effects during pregnancy. TAF is likely to become part of first-line regimens for use in pregnant women living with HIV once additional pregnancy data from phase III trials are available.

OBJECTIVE To determine the accuracy of a semi-quantitative interleukin-6 (IL-6) vaginal secretion rapid test (Chorioquick) for detecting chorioamnionitis in women with premature rupture of membranes (PROM). METHODS A prospective cohort study in five tertiary hospitals in Nigeria involved women with confirmed PROM at term and preterm PROM with or without suspected chorioamnionitis from August 1, 2017, to October 31, 2018. Cervicovaginal fluid samples were tested for chorioamnionitis using the Chorioquick test. Samples were repeated at decision to deliver. The test was considered positive if at least the indicator 'IL-6 low' of the three Chorioquick biomarkers (low, medium, high) was positive, or negative if none of the biomarkers were positive. Chorioamnionitis was histologically confirmed post-delivery using three tissue samples. Primary outcome measures were sensitivity, specificity, and accuracy. RESULTS Of 73 women, on histological confirmation, 39 were true positive and 29 were true negative (for chorioamnionitis) to the Chorioquick test at repeat assessment. Overall, the Chorioquick test had a sensitivity of 97.5% (95% confidence interval [CI] 85.3-99.9), specificity 87.9% (70.9-96.0), and accuracy 93.2% (79.5-99.1). Sub-group analysis of women

Pharmacologic Research in Pregnant Women Facilitating inclusion of pregnant women in clinical research could help answer important questions about the effects of medication use during pregnancy and...