Gestational Hypertension as a Risk Factor for Increased Postpartum Hemorrhage Volume in Placenta Previa: A Retrospective Study

Objective: To identify risk factors correlated with postpartum hemorrhage (PPH) volume in pregnant women diagnosed with placenta previa.

Methods: We conducted a retrospective data collection of PPH volume from consecutive pregnant women at the First People's Hospital of Zunyi between March 24, 2020, and February 28, 2024. The outcome variable, PPH volume, was divided into five categories: less than 500ml, 500-1000ml, 1001-1500ml, 1501-2000ml, and above 2000ml. This data was documented within 24 hours post-childbirth. We evaluated maternal characteristics and concurrent pregnancy conditions to identify potential risk factors for PPH volume. Both univariate and multivariate ordered logistic regression analyses were utilized to determine the association between these factors and PPH volume.

Results: A total of 246 pregnant women were included in this prospective study. The univariate analysis revealed that gestational hypertension increases the risk of an elevated volume of postpartum hemorrhage (PPH), with an odds ratio (OR) of 5.336 (95% CI 1.204-23.656). This significance persisted in the multivariate ordered logistic regression analysis(OR 6.445, 95% CI 1.414-29.371), suggesting that pregnant women diagnosed with gestational hypertension are approximately 6.445 times more likely to experience a higher volume of PPH compared to those without gestational hypertension. The mode of delivery, particularly cesarean section, was initially associated with a lower volume of PPH(OR 0.393,95% CI 0.226-0.685); however, this association was not statistically significant upon multivariate analysis.

Conclusion: Gestational hypertension significantly contributes to the increased volume of PPH in patients with placenta previa. It is imperative for clinicians to diligently monitor and manage such patients to mitigate the risk of severe PPH and related complications. More researches are warranted to validate our findings.

Keywords: Gestational Hypertension, Postpartum Hemorrhage, Placenta Previa, Risk Factors, Pregnancy Conditions

Postpartum hemorrhage (PPH), defined as excessive blood loss following childbirth, remains a significant global health concern, accounting for approximately 11% of maternal deaths worldwide [1]. Women with placenta previa, a condition where the placenta attaches abnormally close to or over the cervix, are at an increased risk of PPH due to the potential disruption of the placenta during delivery [2]. Understanding the risk factors associated with PPH in women with placenta previa is crucial for developing effective prevention and management strategies.

Several factors have been identified as potential risk factors for PPH in women with placenta previa, including maternal age, parity, mode of delivery, and co-existing pregnancy conditions [3]. Recent studies have explored the association between additional maternal characteristics and co-existing pregnancy conditions with PPH in women with placenta previa. For instance, a study found that a low maternal body mass index (BMI) was associated with an increased risk of PPH in women with placenta previa [6]. Another study investigated the association between placental abruption and PPH in women with placenta previa [7]. Even though these studies have advanced our understanding of PPH, there are still many potential risk factors for PPH, which remain unexplored and warrant further investigation.

In this study, we aimed to investigate other potential risk factors associated with PPH volume in women with placenta previa. We explored the association between various maternal characteristics, co-existing pregnancy conditions, and newborn weight with PPH volume. Our findings have the potential to inform clinical practice and guide future research on PPH prevention and management in women with placenta previa.

We conducted a retrospective study analyzing PPH volume data from consecutive pregnant women at the First People's Hospital of Zunyi between March 24, 2020, and February 28, 2024. Out of these, 342 were diagnosed with placenta previa. We excluded those with incomplete demographic or delivery details, anatomical reproductive system abnormalities, a history of malignant tumors, or previous postpartum complications. Ultimately, 246 women anticipating childbirth were included in the study. Figure 1 depicts the patient selection process for this research. The Ethics Committee of the First People's Hospital of Zunyi approved the study. Informed consent was obtained from all participants before their inclusion, and patient confidentiality was meticulously upheld throughout the study.

Maternal characteristics including age, gestational week, delivery method, pre-pregnancy BMI, smoking history, alcohol consumption history, gestational hypertension, preeclampsia, gestational diabetes, hypothyroidism, hyperthyroidism, and thrombocytopenia were collected. Information on their offspring's birth weight, as well as Apgar scores, were also included. The volume of postpartum hemorrhage within 24 hours was recorded.

Postpartum hemorrhage volume was categorized into five groups: less than 500ml, 500-1000ml, 1001-1500ml, 1501-2000ml, and more than 2000ml. Pre-pregnancy Body Mass Index (BMI) was calculated based on the individual’s weight and height using the formula BMI = Weight/ (Height^2). Delivery methods were classified into either a vaginal birth or a cesarean section. Any smoking or alcohol consumption exceeding three instances during pregnancy was recorded as 'yes'. Additionally, any accompanying diseases during pregnancy such as gestational hypertension, preeclampsia, diabetes, hyperthyroidism, and hypothyroidism were documented based on previous diagnoses. Platelet count and hemoglobin levels were examined upon admission. Thrombocytopenia was diagnosed when the platelet count was less than 100×10^9/L, and anemia was diagnosed when the hemoglobin level was less than 110 g/L. Moreover, in the case of twins, the recorded birth weight is the combined weight of both newborns.

All data analyses were conducted using SPSS statistical software(version 26.0; IBM Corp., Chicago, IL, USA). Categorical variables were expressed as frequencies and percentages, while continuous variables were expressed as mean ± standard deviation. Chi-square tests and Fisher's exact test were used to compare categorical variables, and independent samples t-tests or the nonparametric Mann-Whitney U test were used to compare continuous variables. A p-value of less than 0.05 was considered statistically significant.

Univariate logistic regression analysis was performed to assess the association between each factor (Age, Pre-pregnancy BMI, Weeks gestation, Method of delivery, Smoker, Drinker, Gestational hypertension, Preeclampsia, Twins, Diabetes, Anemia, Hyperthyroidism, Hypothyroidism, Thrombocytopenia and Weight of the newborn) and postpartum hemorrhage volume. This step helped identify factors that had a potential association with postpartum hemorrhage volume.

Multivariate ordered logistic regression analysis was performed to determine the independent factors significantly associated with postpartum hemorrhage volume while controlling for possible confounding factors. Variables significant at α = 0.20 from the univariate analysis were included in the multivariate ordered logistic regression model. Test of Parallel Lines was initially evaluated to ensure the suitability for conducting multinomial ordered logistic regression analysis. If the p-value for the parallelism assumption test exceeds 0.05, the study is deemed suitable for multinomial ordered logistic regression.

In addition, the relationship between the independent factors and postpartum hemorrhage volume was further explored with logistic regression models.

Baseline characteristics of the study population are presented in Table 1. There were no significant differences in age (p=0.271), pre-pregnancy BMI (p=0.422), or gestational age at delivery among the different postpartum blood loss groups. However, the method of delivery showed a significant association with postpartum blood loss (p<0.001), with a higher proportion of cesarean sections observed in the groups with greater blood loss. Additionally, the presence of gestational hypertension was found to be significantly associated with postpartum blood loss (p=0.049), while other medical conditions and newborn weight did not show significant associations. These findings highlight the potential impact of delivery methods and gestational hypertension on postpartum blood loss and provide insights for further investigation.

In the univariate analysis, gestational hypertension emerged as a significant risk factor for increased postpartum hemorrhage volume (OR 5.336, 95% CI 1.204-23.656, p=0.028). Notably, a strong association was found between the method of delivery and postpartum blood loss; specifically, cesarean section was associated with a reduced risk of postpartum hemorrhage (OR 0.393, 95% CI 0.226-0.685, p=0.001). No significant associations were found between postpartum hemorrhage and other factors such as age, pre-pregnancy BMI, smoking, and drinking habits, among others. The variables that were included in the multivariate ordered logistic regression, with a significance level of p<0.2, were gestational weeks, method of delivery, gestational hypertension, and hypothyroidism.

The Test of Parallelism Assumption Test yielded a p-value of 0.662, indicating that multivariate ordered logistic regression analysis is suitable for further investigation in this study. In the multivariate ordered logistic regression analysis, after adjustment for potential confounders, gestational hypertension remained significantly associated with postpartum hemorrhage volume (OR 6.445, 95% CI 1.414-29.371, p=0.016). However, the association between the method of delivery and postpartum blood loss became non-significant in the multivariate analysis (OR 0.613, 95% CI 0.304-1.236, p=0.172). Hypothyroidism was also introduced in the model but was not found to be significantly associated with postpartum hemorrhage volume (OR 1.510, 95% CI 0.604-3.776, p=0.379).

A sensitive analysis was performed to explore the association between Gestational hypertension and Postpartum blood loss. As shown in Table X, in all three models, gestational hypertension was significantly associated with postpartum blood loss. In Model 1, where no covariable was adjusted, gestational hypertension was found to significantly increase the odds of postpartum blood loss (OR 5.336, 95% CI 1.204-23.656, p=0.028). This association remained significant even after adjusting for age and pre-pregnancy BMI in Model 2 (OR 5.106, 95% CI 1.148-22.707, p=0.032) and further adjusting for weeks of gestation, method of delivery, smoking status, drinking status, preeclampsia, twins, diabetes, anemia, hyperthyroidism, hypothyroidism, thrombocytopenia, and weight of the newborn in model 3 (OR 5.917, 95% CI 1.194-29.320, p=0.029).

This retrospective cohort study investigated the risk factors associated with postpartum hemorrhage (PPH) volume in women with placenta previa. Our primary finding was that gestational hypertension emerged as a significant and independent risk factor for increased PPH volume. Conversely, cesarean section delivery was associated with a lower risk of PPH compared to vaginal birth, although this association was not statistically significant in multivariate analysis. Other investigated factors, including maternal characteristics, co-existing pregnancy conditions, and newborn weight, did not exhibit statistically significant associations with PPH volume.

Consistent with our findings, previous research has shown a lower risk of PPH with cesarean section delivery compared to vaginal birth. A systematic review and meta-analysis involving over 1 million women found a significantly reduced risk of PPH with cesarean section (OR 0.54, 95% CI 0.47-0.62) [3]. This protective effect is likely due to the controlled delivery and reduced risk of lacerations and uterine atony, common causes of PPH during vaginal birth [4].

Similarly, gestational hypertension has been established as a risk factor for PPH in prior studies. A meta-analysis of over 100,000 women reported a significantly increased risk of PPH in those with gestational hypertension (OR 2.44, 95% CI 1.85-3.20) [1]. Another large cohort study (over 2 million deliveries) confirmed gestational hypertension as an independent risk factor for PPH (OR 2.21, 95% CI 1.87-2.61) [2]. These findings suggest gestational hypertension is a consistent risk factor for PPH across various populations and study designs.

Several potential mechanisms might explain the association between gestational hypertension and PPH. Gestational hypertension may lead to vascular dysfunction, characterized by impaired endothelial function and increased vascular permeability [3]. This dysfunction can cause excessive bleeding during delivery due to fragile blood vessels and impaired platelet aggregation [4]. Additionally, gestational hypertension may be associated with a higher prevalence of maternal morbidities, such as preeclampsia and placental abruption, which further increase the risk of PPH [5].

Our study strengthens the existing evidence by providing further confirmation of the link between gestational hypertension and PPH in women with placenta previa. Additionally, our findings highlight the importance of considering gestational hypertension as a risk factor for PPH in clinical practice.

While our study provides valuable insights into PPH risk factors in women with placenta previa, further research is needed. Prospective studies with larger, multicenter cohorts are warranted to confirm our findings and investigate potential interactions between gestational hypertension and other PPH risk factors. Additionally, research into the biological mechanisms linking gestational hypertension to PPH could inform the development of targeted interventions to reduce the risk of this serious maternal complication.

The retrospective nature of our study design limits our ability to establish causal relationships. Additionally, the single-center design restricts the generalizability of our findings to other populations. Moreover, the relatively small sample size might have limited our ability to detect associations with weaker effect sizes. Future research with a prospective design, larger sample sizes, and multicenter cohorts is necessary to address these limitations and strengthen the evidence base.

Gestational hypertension is a significant risk factor for increased PPH volume in women with placenta previa. Clinicians should be vigilant in monitoring and managing women with placenta previa and gestational hypertension to minimize the risk of severe PPH and its associated complications. Further research is warranted to elucidate the underlying mechanisms and develop effective prevention and treatment strategies for PPH in this high-risk population.