The suboptimal clinical applicability of prognostic prediction models for severe postpartum hemorrhage: a meta-epidemiological study.

OBJECTIVE: To systematically investigate clinical applicability of the current prognostic prediction models for severe postpartum hemorrhage (SPPH). STUDY DESIGN AND SETTING: A meta-epidemiological study of prognostic prediction models was conducted for SPPH. A pre-designed structured questionnaire was adopted to extract the study characteristics, predictors and the outcome, modelling methods, predictive performance, classification ability for high-risk individuals, and clinical use scenarios. The risk of bias among studies were assessed by the Prediction model Risk Of Bias ASsessment Tool. RESULTS: Twenty-two studies containing 27 prediction models were included. The number of predictors in the final models varied from 3 to 53. However, one-third of the models (11) did not clearly specify the timing of predictor measurement. Calibration was found to be lacking in 10 (37.0%) models. Among 20 models had an incidence rate of predicted outcome below 15.0%, none of the models estimated the area under the precision-recall curve, and all reported positive predictive values were below 40.0%. Only two (7.4%) models specified the target clinical setting, while seven (25.9%) models clarified the intended timing of model use. Lastly, all 22 studies were deemed to be at high risk of bias. CONCLUSION: Current SPPH prediction models have limited clinical applicability due to methodological flaws, including unclear predictor measurement, inadequate calibration assessment, and insufficient evaluation of classification ability. Additionally, there is a lack of clarity regarding the timing for model use, target users, and clinical settings. These limitations raise concerns about the reliability and usefulness of these models in real-world clinical practice.

Hepatitis B virus infection during pregnancy and the risk of postpartum hemorrhage: a protocol for systematic review and meta-analysis.

Background: Hepatitis B virus (HBV) infection is a significant public health issue worldwide, with a hepatitis B surface antigen (HBsAg) seroprevalence of 3.5%. Maternal HBV infection during pregnancy, a common comorbidity, is associated with an increase in the risk of adverse obstetric and perinatal outcomes. However, the relationship between maternal HBV infection and postpartum hemorrhage (PPH), a leading contributor to maternal morbidity and mortality, is currently uncertain. The aim of this study is to comprehensively clarify the potential impact of maternal HBV on PPH risk. Methods and Analysis: The authors initially searched five English databases and three Chinese databases from their inception to 26th June 2023. Two reviewers will independently conduct study selection, data extraction, and quality assessment. Cohort and case-control studies investigating the effect of maternal HBV infection on PPH will be included, with study quality assessed using the Newcastle-Ottawa Scale (NOS). Meta-analyses will be performed using a fixed-effects model for I 2≤50% or a random-effects model otherwise. Several categories of subgroup analyses (e.g. sample size more than 1000 vs. less than 1000) and sensitivity analyses (e.g. omit NOS scores less than 7) will be conducted, and publication bias will be assessed through funnel plots, Begg's and Egger's tests using STATA 18.0. Ethics and Dissemination: This systematic review and meta-analysis do not require ethics approval and the results will be published in peer-reviewed journals. The findings of this systematic review will provide evidence on the impact of maternal HBV infection on PPH, which will contribute to better prevention and management of PPH in clinical practice and a better understanding of the disease burden of HBV infection. PROSPERO registration number: CRD42023442626.

A population-based cohort of drug exposures and adverse pregnancy outcomes in China (DEEP): rationale, design, and baseline characteristics.

The DEEP cohort is the first population-based cohort of pregnant population in China that longitudinally documented drug uses throughout the pregnancy life course and adverse pregnancy outcomes. The main goal of the study aims to monitor and evaluate the safety of drug use through the pregnancy life course in the Chinese setting. The DEEP cohort is developed primarily based on the population-based data platforms in Xiamen, a municipal city of 5 million population in southeast China. Based on these data platforms, we developed a pregnancy database that documented health care services and outcomes in the maternal and other departments. For identifying drug uses, we developed a drug prescription database using electronic healthcare records documented in the platforms across the primary, secondary and tertiary hospitals. By linking these two databases, we developed the DEEP cohort. All the pregnant women and their offspring in Xiamen are provided with health care and followed up according to standard protocols, and the primary adverse outcomes - congenital malformations - are collected using a standardized Case Report Form. From January 2013 to December 2021, the DEEP cohort included 564,740 pregnancies among 470,137 mothers, and documented 526,276 live births, 14,090 miscarriages and 6,058 fetal deaths/stillbirths and 25,723 continuing pregnancies. In total, 13,284,982 prescriptions were documented, in which 2,096 chemicals drugs, 163 biological products, 847 Chinese patent medicines and 655 herbal medicines were prescribed. The overall incidence rate of congenital malformations was 2.0% (10,444/526,276), while there were 25,526 (4.9%) preterm births and 25,605 (4.9%) live births with low birth weight.

The use of Chinese herbal medicines throughout the pregnancy life course and their safety profiles: a population-based cohort study.

BACKGROUND: Chinese herbal medicines have been long used among pregnant populations in China. However, despite the high susceptibility of this population to drug exposure, it continued to remain unclear about how often they were used, to what extent they were used at different pregnancy stages, and whether their use was based on sound safety profiles, particularly when used in combination with pharmaceutical drugs. OBJECTIVE: This descriptive cohort study aimed to systematically investigate the use of Chinese herbal medicines throughout pregnancy and their safety profiles. STUDY DESIGN: A large medication use cohort was developed by linking a population-based pregnancy registry and a population-based pharmacy database, which documented all prescriptions at both outpatients and inpatients from conception to 7 days after delivery, including pharmaceutical drugs and processed Chinese herbal medicine formulas that were approved by the regulatory authority and prepared under the guidance of national quality standards. The prevalence of the use of Chinese herbal medicine formulas, prescription pattern, and combination use of pharmaceutical drugs throughout pregnancy were investigated. Multivariable log-binomial regression was performed to assess temporal trends and further explore the potential characteristics associated with the use of Chinese herbal medicines. Of note, 2 authors independently conducted a qualitative systematic review of patient package inserts of the top 100 Chinese herbal medicine formulas used to identify their safety profiles. RESULTS: This study included 199,710 pregnancies; of those pregnancies, 131,235 (65.71%) used Chinese herbal medicine formulas, including 26.13% during pregnancy (corresponding to 14.00%, 8.91%, and 8.26% in the first, second, and third trimesters of pregnancy) and 55.63% after delivery. The peak uses of Chinese herbal medicines occurred between 5 and 10 weeks of gestation. The use of Chinese herbal medicines significantly increased over the years (from 63.28% in 2014 to 69.59% in 2018; adjusted relative risk, 1.11; 95% confidence interval, 1.10-1.13), which was particularly great during pregnancy (from 18.47% in 2014 to 32.46% in 2018; adjusted relative risk, 1.84; 95% confidence interval, 1.77-1.90). Our study observed 291,836 prescriptions involving 469 Chinese herbal medicine formulas, and the top 100 most used Chinese herbal medicines accounted for 98.28% of the total prescriptions. Of those, a third (33.39%) were dispensed at outpatient visits; 6.79% were external use, and 0.29% were administered intravenously. However, Chinese herbal medicines were very often prescribed in combination with pharmaceutical drugs (94.96% overall), involving 1175 pharmaceutical drugs with 1,667,459 prescriptions. The median of pharmaceutical drugs prescribed in combination with Chinese herbal medicines per pregnancy was 10 (interquartile range, 5-18). The systematic review of drug patient package inserts found that the 100 most frequently prescribed Chinese herbal medicines contained a total of 240 herb constituents (median, 4.5); 7.00% were explicitly indicated for pregnancy or postpartum conditions; 43.00% were reported with efficacy or safety data from randomized controlled trials. Information was lacking about whether the medications had any reproductive toxicity, were excreted in human milk, or crossed the placenta. CONCLUSION: The use of Chinese herbal medicines was prevalent throughout pregnancy and increased over the years. The use of Chinese herbal medicines peaked in the first trimester of pregnancy and was very often used in combination with pharmaceutical drugs. However, their safety profiles were mostly unclear or incomplete, suggesting a strong need for postapproval surveillance for the use of Chinese herbal medicines during pregnancy.