International Society of Thrombosis and Hemostasis 22rd Annual Meeting June 21-25, 2025 in Washington DC.

Abstract Objective Non‐White patients experience higher rates of postpartum hemorrhage (PPH) as well as associated morbidity and mortality compared to White counterparts. This study examined whether delays in intervention in patients with PPH varied by patient race and insurance status and whether delays were associated with increased morbidity. Methods We conducted a retrospective cohort study of patients with PPH (total blood loss ≥ 1000 mL) in a large health system between 2019 and 2024 using electronic medical record data. The primary exposure was patient race (White, Black, and Asian). The primary outcome was time to PPH interventions. The secondary outcome was maternal morbidity as a composite of severe PPH (defined as blood loss greater than 1500 mL), blood product transfusion, intensive care unit (ICU) transfer, or hysterectomy. Unadjusted analyses of intervention timing were performed using type 2, two‐tailed t‐tests. After adjusting for gestational age, anemia, and delivery mode, analyses of associations between maternal morbidity and time to intervention were computed using binary logistic regression. Kaplan–Meier curves were generated to compare the cumulative maternal morbidity between racial and insurance groups. Results A total of 4316 patients were included, of which 13% were Black (n = 587), 8% were Asian (n = 356), and 6% (n = 289) were publicly insured. Asian patients underwent balloon tamponade (229 vs. 87 min, p < 0.001) and uterine artery embolization (477 vs. 258 min, p = 0.005) later than White patients. Compared to White patients, Asian patients had increased odds of maternal morbidity (adjusted odds ratio [aOR], 1.66; 95% confidence interval [CI], 1.28–2.15). Kaplan–Meier curves demonstrated a lower probability of remaining morbidity‐free over time compared with those receiving intervention earlier. Additionally, significant differences were noted in time to intervention between White, Black, and Asian patients for medication (p = 0.024) and uterine balloon tamponade (p = 0.021) but not uterine artery embolization (p = 0.141) or hysterectomy (p = 0.948). Conclusion This study suggests that Asian patients experience delays to PPH care escalation as well as increased odds of maternal morbidity. This finding highlights the need for standardized PPH protocols and further research on the optimal timing of invasive interventions as well as structural factors contributing to unequal care.

Background: Global twinning rates have risen from approximately 9.1 per 1000 births in the 1980s to around 12 per 1000 in recent decades, driven by natural variations and the increasing utilization of assisted reproductive technology (ART). Nigeria is widely recognized as a global epicenter for natural twinning, exhibiting incidence rates that substantially exceed international averages. Notably, the Igbo Ora community in Oyo State, southwest Nigeria, has historically been documented as having the highest twinning prevalence globally, with multiple births recorded in nearly every household. Objectives: This systematic review and meta-analysis aimed to determine the pooled national prevalence of twin births in Nigeria, assess regional variations across the country's geopolitical zones, and compare twinning prevalence between the pre-in vitro fertilization (IVF) and IVF eras. Methods: A systematic literature search was conducted in accordance with the PRISMA guidelines. A total of 1080 records were initially identified across PubMed [60], Google Scholar [957], SCOPUS [56], CINAHL [6], and the Cochrane Library [1]. Following the removal of duplicate records, 912 unique studies underwent title and abstract screening. Of these, 784 records were excluded due to a lack of relevance to twin birth prevalence or failure to meet eligibility criteria. The full texts of the remaining 128 studies were evaluated, leading to the exclusion of 67 articles. Ultimately, 61 articles satisfied all inclusion criteria and were retained for analysis. Results: The pooled national prevalence of twin births in Nigeria was estimated at 2.82% [95% CI: 2.61–3.03]. Substantial between-study heterogeneity was observed (I2 = 100%), reflecting significant variability among the included literature; individual study prevalence estimates ranged from 1.19% to 6.47%. Geopolitical subgroup analysis revealed a pooled twin birth prevalence of 2.92% [95% CI: 2.67–3.17] in the southern region (43 articles) compared to 2.52% [95% CI: 2.08–2.96] in the northern region (18 articles). Notably, the southwest region exhibited a significantly higher prevalence when compared to all other regions combined (3.43% vs. 2.55% [95% CI: 2.32–2.78]). Regarding temporal trends, pooling of 6 articles from the pre-IVF era (1980–1985; comprising 5,475 twin deliveries out of 177,968 total births) yielded a prevalence of 3.38% [95% CI: 2.59–4.17]. Conversely, 55 articles from the IVF era (1986–2025; comprising 18,101 twin deliveries out of 653,100 total births) demonstrated a pooled prevalence of 2.74% [95% CI: 2.52–2.96]. Conclusion: These findings demonstrate that the higher prevalence of twin births in southwest Nigeria relative to other regions is primarily driven by endogenous population characteristics rather than modern fertility interventions. Future research should focus on delineating the underlying genetic, sociocultural, and environmental determinants of twinning. Concurrently, healthcare systems must integrate the sustained burden of twin pregnancies into maternal and neonatal care planning.

The significant increase in hepatitis C virus (HCV) infection prevalence among young adults, including those who may become pregnant, has led to a corresponding increase in the number of infants exposed to and infected with HCV. Despite a recommendation for universal HCV screening during pregnancy, there is not always a clear pathway to immediately initiate treatment for maternal cure, which could also prevent vertical transmission like the approach for human immunodeficiency virus (HIV) or hepatitis B virus. In 2019, the American Association for the Study of Liver Diseases/Infectious Diseases Society of America HCV Guidelines panel endorsed the use of shared decision making between providers and patients when considering HCV treatment during pregnancy. Direct-acting antivirals, including glecaprevir/pibrentasvir (GLE/PIB), have been tremendously effective in curing >95% of individuals who begin treatment along with an overall well-characterized safety profile, but data supporting their use when initiated during pregnancy are more limited. International Maternal Pediatric Adolescent AIDS Clinical Trials 2041 is a multicenter single-arm phase I/II clinical trial designed to evaluate the pharmacokinetics and safety of GLE/PIB treatment initiated in pregnant women with HCV mono-infection or HCV/HIV co-infection. In this paper, we describe the relevant background data assembled from various sources to write the protocol and design the study.

Most pregnant individuals are exposed to at least one medication, whether prescription or over the counter, during pregnancy. Despite the ubiquity of medication use in pregnancy, there remains no standardized framework to guide clinicians in selecting the most appropriate pharmacotherapy that balances maternal needs with fetal safety. This gap contributes to variability in prescribing practices and uncertainty in clinical decision making. In this article, we propose a structured schema for evaluating and selecting drug therapy during pregnancy. Our approach emphasizes careful consideration of maternal and fetal factors, integration of the unique physiologic changes of pregnancy, and systematic appraisal of the best available evidence. Recognizing the frequent absence of robust pharmacokinetic and safety data, we also provide pragmatic principles and rules of thumb to guide clinicians in estimating the likelihood of placental transfer and potential fetal exposure. This framework is designed to support clinicians in making more informed, transparent, and evidence-based decisions while also identifying areas for future research.

BackgroundBreastfeeding offers significant health benefits, and guidance for women with HIV increasingly emphasizes individualized, informed infant-feeding decisions. Breastmilk antiretroviral transfer and safety data are needed to inform shared decision-making discussions across all settings.MethodsBreastmilk transfer of ritonavir (RTV)-boosted atazanavir (ATV) was evaluated in the International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) 2026 study. Fourteen breastfeeding women with HIV receiving RTV boosted ATV 100/300 mg daily, as part of a multi-drug regimen, and their infants were enrolled in Kenya, Uganda, and South Africa between 5 and 9 days postpartum and followed through age 16–24 weeks. Paired maternal plasma, breastmilk, and infant plasma samples were collected at each visit. Concentrations were measured using validated LC-MS/MS methods. Relative infant dose (RID) was estimated assuming an infant milk intake of 150 mL/kg/day. Safety outcomes were prospectively assessed.ResultsAll 14 women reported exclusive breastfeeding. Median maternal plasma and breastmilk concentrations were 1,410 ng/mL and 432 ng/mL for ATV, and 217 ng/mL and 13.6 ng/mL for RTV, respectively. Median breastmilk-to-plasma ratios were 0.253 (ATV) and 0.081 (RTV). RID values were 1.27% (maximum 6.43%) for ATV and 0.12% (maximum 1.10%) for RTV. Infant plasma concentrations were below the lower limit of quantitation (ATV 23.4 ng/mL; RTV 9.8 ng/mL) in all 42 samples. No maternal adverse events occurred; three infants experienced unrelated grade 2 events.ConclusionsIn this cohort, ATV and RTV were detectable in maternal plasma and breastmilk but not in infant plasma, with low RID estimates and a favorable safety profile.

Bictegravir is an integrase strand transfer inhibitor available in fixed-dose combination with emtricitabine and tenofovir alafenamide for HIV treatment. The objectives of this study were to develop a population pharmacokinetic model for bictegravir during pregnancy and postpartum, identify main drivers of between-subject variability, and evaluate the role of adherence patterns in maintaining therapeutic exposure. Intensive bictegravir concentration-time data were used from IMPAACT 2026, a pharmacokinetic study of selected antiretroviral drugs during pregnancy and postpartum. Five hundred and eight bictegravir plasma concentrations from 27 participants during the second and third trimesters of pregnancy and postpartum were utilized for model development. A one-compartment structural model best described bictegravir PK. Pregnancy increased bictegravir apparent clearance (CL/F) by 61% compared to postpartum, while Black/African American race was associated with a 32% increase in apparent volume of distribution (Vd/F). Plasma albumin concentrations were associated with a 43% decrease in CL/F and body weight was associated with a 120% increase in Vd/F over the range of observed values. Monte Carlo simulations predicted median (90% prediction interval) pre-dose bictegravir concentrations of 920 ng/mL (265-2081) during the third trimester and 3399 ng/mL (1423-6391) postpartum, exceeding the protein-adjusted 95% effective concentration (162 ng/mL). Adherence simulations predicted a single missed dose at steady-state during the third trimester results in 43.7% of virtual subjects with concentrations below pharmacodynamic target, while two consecutive missed doses result in 90.4% with concentrations below target. These results show that while standard bictegravir dosing is effective during pregnancy, consistent adherence is critical to maintain effective therapeutic exposures.

BACKGROUND:There are no published data on clofazimine pharmacokinetics during pregnancy, and safety data are limited. We present data from pregnant and postpartum women receiving clofazimine for treatment of rifampicin-resistant tuberculosis (RR-TB). METHODS:IMPAACT P1026s was an observational study to assess the pharmacokinetics of tuberculosis and/or antiretroviral drugs during pregnancy. Between 2017 and 2019, pregnant women receiving ≥2 second-line antituberculosis drugs in routine care were enrolled in the second or third trimester and had intensive pharmacokinetic sampling at least once during pregnancy, and 2-8 weeks postpartum. Pharmacokinetic parameters were estimated using noncompartmental methods and compared between the antepartum and postpartum periods using geometric mean ratios (GMR) with 90% confidence intervals (CIs) and the Wilcoxon signed rank test for paired data. RESULTS:Eleven pregnant women from South Africa, 7 (64%) with HIV, were receiving clofazimine (100 mg daily) at enrollment, of which 82% received clofazimine for more than 8 weeks prior to pharmacokinetic evaluation. Nine (82%) women continued treatment postpartum. Peak plasma concentrations and area-under-the-concentration-time-curve over 12 hours were comparable to historical clofazimine pharmacokinetic data in nonpregnant women with RR-TB but were approximately 30% higher in the third trimester of pregnancy compared to the postpartum period. Eight women and 8 infants experienced at least one severe adverse event while on study but direct relatedness to clofazimine was considered unlikely. CONCLUSIONS:Overall, antepartum and postpartum clofazimine exposures were comparable to those reported in nonpregnant women with RR-TB. Exposures were lower than expected in the postpartum period, particularly compared with the third trimester of pregnancy.

This case report presents the clinical course of a 33-year-old primiparous woman whom at 30 weeks of gestation experienced preterm pre-labour rupture of membranes (PPROM) in a low-resource setting. The patient, with a history of primary infertility, was managed conservatively without antibiotics for 28 days at a resource-limited health facility, where she was treated until clinical symptoms indicating chorioamnionitis appeared, leading to her referral. She underwent an emergency caesarean section at 34 weeks gestational age due to suspected chorioamnionitis resulting in the delivery of a healthy male infant. However, the baby developed neonatal jaundice which was successfully managed with phototherapy over five days. This case provides insight into the natural course of PPROM that lasted for 28 days, a condition that would have been ethically challenging to study in a research setting. It emphasizes the difficulties of managing PPROM in low-resource environments, especially when there is no immediate access to antibiotics and advanced neonatal care.

Treatment of rifampicin-resistant tuberculosis (RR-TB) often includes fluoroquinolones, but data on long-term exposure during and after pregnancy are limited. We examined the pharmacokinetics and safety of levofloxacin in an observational cohort of pregnant and postpartum women receiving treatment for RR-TB. Participants were enrolled in their second or third trimester and underwent intensive pharmacokinetic sampling to quantify levofloxacin plasma concentrations at 20–26 weeks’ and 30–38 weeks’ gestation and at 2–8 weeks postpartum. The levofloxacin plasma concentration target was 7 µg/mL. Pharmacokinetic parameters over 12 and 24 h were described using non-compartmental analysis and within-participant comparison during pregnancy versus postpartum. Adverse events were extracted from medical records. Infants were enrolled in utero and followed on study for 4–6 months after birth. A total of 11 pregnant women, with a median age of 31 years, received RR-TB treatment including levofloxacin; 6 (55

Background:Frailty is increasingly recognized in older people living with HIV (PLWH), but optimal diagnostics are yet to be determined. Frailty indices (FI) represent an accumulation of health deficits shown to correlate better with mortality and adverse effects of aging than the frailty phenotype or chronological age. Methods:This is a retrospective cohort study of frailty assessments in PLWH aged ≥ 50 years in a multidisciplinary urban HIV clinic. Frailty was assessed using Frailty Phenotype (FP) and a new 40-variable clinical composite FI derived from routine clinical and laboratory data (CCFI). CCFI scores were categorized into robust (≤ 0.15), pre-frail (>0.15-0.4), and frail (>0.4). CCFI frailty and its association with frailty-related factors were analyzed using logistic regression. Results:The 165 participants were mostly black (94%) and male (56%), with median age 59 years (IQR 55-63), CD4 count 606 cells/μl (IQR 393-873), and 78% had HIV viral load ≤ 40 copies/ml. 70% had multimorbidity, 38% falls, 25% poor cognition, and 24% polypharmacy. By FP, 2% were frail, 65% prefrail, and 33% robust. By CCFI, 26% were frail, 67% prefrail, and 7% robust (range 0.08-0.57; mean 0.34 ±0.11). For FP categorized as robust, prefrail and frail, the mean CCFI was 0.31 ± 0.1, 0.35 ± 0.11 and 0.38 ± 0.08 respectively (P=0.06). Cognition (OR 3.64, p=0.003), falls (OR 5.09, p<0.001), polypharmacy of 6-9 medications (OR 3.07, p=0.03) and ≥ 10 medications (OR 4.25, p=0.009) and >3 comorbidities (OR 3.06, p=0.03) were associated with CCFI frailty, adjusted for age and sex. Conclusion:The majority of older PLWH were pre-frail or frail. The CCFI identified more patients as frail and had significant clinical associations compared to FP.

Background: Limited data exist on bictegravir pharmacokinetics in pregnancy among persons with HIV (PWH) and infant washout. Setting: Nonrandomized, open-label, multicenter phase-IV prospective study of bictegravir pharmacokinetics and safety in pregnant PWH and their infants. Methods: Steady-state 24-hour pharmacokinetic sampling of oral bictegravir 50 mg once daily (a component of fixed-dose combination bictegravir/emtricitabine/tenofovir alafenamide) during the second and third trimesters and postpartum was performed. Cord blood and infant washout samples were collected. Total and free bictegravir concentrations were measured by validated liquid chromatography with tandem mass spectrometry methods. Within- participant geometric mean ratios (GMR) with 90% confidence intervals (CI) were calculated to compare pharmacokinetics between second and third trimester versus postpartum. Infant HIV testing results were obtained. Results: Twenty-seven maternal-infant pairs were enrolled. Bictegravir area under the concentration-time curve from time 0 through 24 hours post-dose was 46% lower in the second trimester (n = 12; P = 0.002; GMR 0.54; 90% CI: 0.43 to 0.69) and 52% lower in the third trimester (n = 24; P < 0.0001; GMR 0.48; 90% CI: 0.43 to 0.55), compared with postpartum. C24 concentrations were above the estimated bictegravir protein-adjusted 95% effective concentration of 0.162 mg/mL. The median ratio of cord-to-maternal blood concentration was 1.38 (n = 17; quartiles: 1.17-1.63). Median T1/2 for infant bictegravir washout was 33.2 hours (quartiles: 25.7-45.9) with a Cmax of 2.06 mg/mL (quartiles: 1.37-2.72). Overall, 88%-92% of participants maintained suppression <40 copies/mL throughout pregnancy and postpartum. All available infant HIV testing results were negative. The safety profile for pregnant PWH and infants was acceptable. Conclusions: Bictegravir exposure was lower during pregnancy compared with postpartum, yet C24 concentrations were greater than the bictegravir protein-adjusted 95% effective concentration.

Standard medication-assisted treatments for opioid use disorder, like methadone or buprenorphine, pose risks in pregnancy, including maternal overdose and neonatal withdrawal syndrome. Naltrexone is a well-tolerated alternative that blocks opioid effects, aiding full recovery. However, its use in pregnant subjects is limited due to the mandatory 7-10 days of opioid abstinence before initiation and daily oral dosing adherence issues. Although a long-acting injectable (LAI) formulation of naltrexone has improved adherence and a study showed that supervised withdrawal maintains clinical benefits1, more data are needed for its full adoption in pregnancy. To address this, we aim to use a physiologically based pharmacokinetic (PBPK) modeling approach to describe LAI naltrexone pharmacokinetics in pregnancy for the first time.The physiological processes and ordinary differential equations governing drug disposition in our PBPK model have been described previously2. Naltrexone’s physicochemical properties were used to predict drug partitioning into various tissues using the Rodgers and Rowland method in the base adult intravenous (IV) model. After validating the IV model with observed data, formulation-specific parameters for intramuscular (IM) absorption were integrated to establish an adult IM model of LAI naltrexone. Following successful validation, the model was extended to pregnancy by integrating pregnancy-induced physiological changes, a fetoplacental compartment, and inclusion of myometrium and placenta as additional eliminating organ. Maternal plasma naltrexone profiles were simulated for 100 non-pregnant virtual females, both at pre-conception and during pregnancy, at the approved dose of 380 mg. Fetal naltrexone concentrations were assessed throughout pregnancy, and comparisons were made between simulated pre-conception and pregnancy, as well as maternal and fetal pharmacokinetic profiles.The base and IM PBPK models were validated with predictions within 1 – 2 absolute average folds of the observed data. Key systemic parameters affected by pregnancy, such as organ weights, blood flows, and hematocrit levels, were compared with available data due to the lack of PK data for LAI naltrexone in pregnancy. The simulated virtual females, with a mean (standard deviation) age and body weight of 23.1 (5) years and 61.1 (8.9) kg, had a mean Cmax, AUC0-7days and AUC0-28days of 29.4 ng/ml, 142 ng⋅d/ml, and 148 ng⋅d/ml, respectively. Maternal overall exposure (AUC0-28days) increased 1.4, 1.4 and 1.7 times during the first, second and third trimester of pregnancy. Although fetal Cmax was 50% lower than maternal Cmax, the overall fetal exposure (AUC0-28days) was comparable (0.97 – 1.13), suggesting it is worth investigating lower doses of naltrexone in pregnancy.This study offers crucial PK insights into LAI naltrexone during pregnancy, which could potentially facilitate informed clinical decision-making regarding naltrexone use and dosing in pregnancy.Citations: [1] Towers et al. (2020). Am J Obstet Gynecol. https://doi.org/10.1016/j.ajog.2019.07.037[2] Shenkoya et al. (2023). Pharmaceutics. https://doi.org/10.3390/pharmaceutics15102467