Interventional radiology for prevention and management of postpartum haemorrhage: a single centre retrospective cohort study.

PURPOSE: Postpartum haemorrhage (PPH) remains a leading cause of maternal death despite current medical management. Surgical interventions are still needed for refractory bleeding. Interventional radiology (IR) can be a successful intermediary that avoids the need for hysterectomy. Nevertheless, IR outcome data in a peripartum setting are limited. The objective of this study is to document the efficacy and safety of IR. METHODS: Retrospective study reviewed the records of consecutive patients who underwent peripartum IR from 01/01/2010 until 31/12/2020 in a tertiary academic centre. Patients were divided in a prophylactic and a therapeutic group. Information about interventions before and after IR, and IR specific complications was retrieved. Efficacy was defined by the number of transfusions and additional surgical interventions needed after IR, and safety was assessed by the incidence of IR related complications. RESULTS: Fifty-four patients, prophylactic group (n = 24) and therapeutic group (n = 30), were identified. In both groups, IR was successful with 1.5 ± 2.9 packed cells transfused post-IR (1.0 ± 2.1 prophylactic vs 1.9 ± 3.3 therapeutic; p = 0.261). Additional surgical interventions were required in n = 5 patients (9.2%), n = 1 (4.2%) in the prophylactic vs. n = 4 (13.3%) in the therapeutic group. Complications were reported in n = 12 patients (22.2%), n = 2 (8.3%) prophylactic vs. n = 10 (33.3%) in therapeutic group. Mostly minor complications, as puncture site hematoma or bleeding, were reported in n = 4 (7.4%). Severe complications as necrosis and metabolic complications were reported in n = 2 patients (3.9%). CONCLUSION: IR for prevention and treatment of PPH was highly successful and associated with minor complications.

Uterine arteriovenous malformation: a case of challenges in diagnosis and management of a patient with a history of misdiagnosed hemorrhage.

Introduction: Uterine arteriovenous malformations (AVMs) are a rare cause of obstetrical hemorrhage. It can be congenital due to a defect during embryogenesis or acquired. Uterine AVMs can cause life threatening postpartum hemorrhage, and is most frequently misdiagnosed. This case highlights the diagnostic challenges posed by uterine arteriovenous malformation, a rare vascular anomaly that poses significant challenges in diagnosis and management. Case presentation: This case report details the clinical presentation, diagnostic challenges, and treatment approach for a 39-year-old woman. In the absence of a medical history indicative of pre-existing ailments, the individual in question has undergone two emergency cesarean sections as documented in her surgical history, in addition to two previous dilation and curettage D&C operations. The patient presented with heavy vaginal bleeding 6 months after a cesarean section. The patient's clinical presentation, imaging findings, and intraoperative observations collectively substantiate the diagnosis of uterine AVMs. Discussion: Women who have had uterine instrumentatio surgery, such as a cesarean section or dilatation and curettage (D&C) are more likely to develop acquired uterine AVMs. The absence of uterine artery embolism options compelled the use of alternative diagnostic methods, including contrast MRI, which successfully detected abnormal vascular lesions. The choice for hysterectomy was influenced by the patient's completion of childbearing and the presence of large vessels in proximity to critical regions. Conclusion: This case emphasizes the significance of adapting treatment plans based on local resource constraints and the need for ongoing efforts to enhance diagnostic capabilities in undeserved regions.

Incidence and Antepartum Risk Factors of Severe Postpartum Haemorrhage in Anaemic Pregnant Women in Lagos, Nigeria: A Secondary Cohort Analysis.

BACKGROUND: The magnitude and risk factors for postpartum haemorrhage (PPH) have been extensively investigated, although little is currently known about the incidence and predictors of severe PPH, specifically among women affected by prenatal anaemia in Nigeria. OBJECTIVES: The study determined the incidence and antepartum risk factors of severe PPH in anaemic pregnant women in five health institutions in Lagos, Southwest Nigeria. METHODS: A secondary analysis was performed using the data of pregnant women with anaemia from the "Predict-PPH" study that was conducted between January and June 2023. This study included n=570 pregnant women affected by anaemia who gave birth in five hospitals in the Lagos metropolis of Nigeria. The study outcome was severe PPH, defined as an estimated blood loss of at least 1000 mL within 24 hours of childbirth. A backward stepwise conditional approach in a multivariable logistic regression model was utilised to identify the independent risk factors for severe PPH in anaemic pregnant women. RESULTS: Of the 570 women with prenatal anaemia enrolled in the primary study, 42 (7.4%) had severe PPH. The identified independent risk factors for severe PPH were maternal obesity (adjusted OR = 3.85, 95% CI = 1.85-8.02), antepartum haemorrhage in index pregnancy (adjusted OR = 2.98, 95% CI = 1.29-6.90), uterine fibroids (adjusted OR = 6.10, 95% CI = 2.39-15.52), delivery gestational age ≥39 weeks (adjusted OR = 2.62, 95% CI = 1.23-5.56), and delivery by caesarean birth (adjusted OR = 16.75, 95% CI = 5.81-48.31). CONCLUSION: About one in 13 anaemic pregnant women enrolled in the study developed severe PPH during childbirth. Maternal obesity, antepartum bleeding in the current pregnancy, co-existing uterine fibroids in pregnancy, delivery gestational age beyond 38 weeks, and caesarean birth in the current pregnancy were factors that were significantly associated with severe PPH in anaemic pregnant women. These findings underscore the importance of increased vigilance during both the antenatal and peripartum periods to identify women with these risk factors for the initiation of timely interventions to prevent severe PPH.

Evaluation of postpartum shock index in hypertensive diseases of pregnancy: a case-control study from a tertiary reference center.

OBJECTIVES: To compare the postpartum shock index (SI) values between pregnant women with hypertensive disease of pregnancy (HDP) and normotensive controls. METHODS: The present study was conducted in Ankara City Hospital Perinatology Clinic. Postpartum SI was compared between the pregnant women with HDP (n=217) and normotensive controls (n=219). A logistic regression analysis was performed to assess the independent predictors of maximum SI ≥1. Finally, a ROC analysis was performed to calculate optimal cut-off values for postpartum SI's measured at different periods in the prediction of postpartum Hb (hemoglobin) decrease ≥2 g/dL. RESULTS: Peripartum SI (p<0.001), 15th min SI (p<0.001), 30th min SI (p<0.001), 2nd h SI (p<0.001), 6th h SI (p) of the HDP group (p<0.001) and max SI (p<0.001) values were found to be significantly lower in the study group. A weak positive and statistically significant correlation was found between the maximum SI and the decrease in Hb ≥2 g/dL (r=0.209; p=0.002). Optimal cutoff values for SI were; 0.7 at peripartum 0.7 at 15 min, 0.73 at 30 min, 0.6 at 2 h, and 0.7 at 6 h, respectively. CONCLUSIONS: Clinically significant blood loss may develop at lower SI values in hypertensive pregnant women.

The effect of assisted reproductive technology on postpartum bleeding: hormonal cycle frozen embryo transfer might increase blood loss.

BACKGROUND: Among assisted reproductive technologies, frozen thawed embryo transfer (FET) is associated with increased blood loss at delivery. Anesthesiologists need to be aware of new factors that affect postpartum blood loss. This study investigated whether FET cycles with or without hormonal support affect the amount of postpartum bleeding. METHODS: We conducted a retrospective cohort study of patients admitted for delivery at a single university hospital between January 2015 and December 2018. Patients were divided into no-assisted reproductive technology (No-ART), hormonal cycle FET (HC-FET) and natural cycle FET (NC-FET) group. The primary outcome was the amount of blood loss after delivery (median [interquartile range]), which was compared among the three groups. Multiple regression analysis was performed to investigate the factors affecting blood loss. RESULTS: Between 2015 and 2018, 3187 women delivered neonates. In vaginal delivery, postpartum blood loss in the HC-FET group (1060 [830] g) was significantly greater than in the NC-FET group (650 [485] g, P = 0.001) and in the No-ART group (590 [420] g P < 0.001). Multiple linear regression analysis showed that HC-FET (P < 0.001) was one of the independent factors for the amount of bleeding. In cesarean delivery, the HC-FET group had more blood loss than the No-ART group (910 [676] g vs. 784 [524] g, P = 0.039). However, HC-FET was not an independent factor for postpartum blood loss. CONCLUSIONS: The HC-FET group had more blood loss than the No-ART group for both vaginal and cesarean deliveries. Furthermore, HC-FET was an independent factor that increased postpartum blood loss in vaginal deliveries.

Usefulness of resuscitative endovascular balloon occlusion of the aorta (REBOA) in controlling puerperal bleeding in patients with abnormal placental implantation.

BACKGROUND AND AIMS: Abnormalities of placental implantation, which make up the spectrum of placenta accreta, are associated with high maternal morbidity and mortality due to massive bleeding during delivery. Placing aortic occlusion balloons helps control the bleeding, facilitating surgical intervention. A new device, resuscitative endovascular balloon occlusion of the aorta (REBOA), minimizes the risks and complications associated with the placement of traditional aortic balloons and is also efficacious in controlling bleeding. The aim of this study is to evaluate the usefulness, efficacy, and safety of REBOA in puerperal bleeding due to abnormalities of placental implantation. MATERIAL AND METHODS: Between November 2019 and November 2021, our interventional radiology team placed six REBOA devices in six women scheduled for cesarean section due to placenta accrete. RESULTS: Mean blood loss during cesarean section after REBOA (3507.5 mL) was similar to the amounts reported for other aortic balloons. The mean number of units of packed red blood cells required for transfusion was 3.5. Using REBOA provided the surgical team with adequate conditions to perform the surgery. There were no complications derived from REBOA, and the mean ICU stay was <2 days. CONCLUSION: The technical characteristics of the REBOA device make it a safe and useful alternative for controlling massive bleeding in patients with placenta accreta.

Postpartum Hemorrhage and Tranexamic Acid: A Literature Review.

This review aims to explore the postpartum hemorrhage (PPH) burden and the efficacy of prophylactic tranexamic acid (TXA) in PPH and recent indications of TXA. A comprehensive review of the literature was conducted using a combination of Medical Subject Headings keywords including "Postpartum haemorrhage," "Tranexamic acid," and "Cesarean section." PPH has been explored for epidemiology, risk factors, and pathophysiology in the first part of the article. Recent indications of TXA, obstetric indications, and the role of TXA as prophylaxis for PPH are discussed in the second part of this article. TXA has many indications apart from obstetric indications and shows a significant effect in controlling bleeding. Furthermore, TXA is more efficient in preventing PPH if administered during the final stage of labor and is a valuable option for managing obstetric bleeding.

Variant in ACTG2 Causing Megacystis Microcolon Hypoperistalsis Syndrome and Severe Familial Postpartum Bleeding.

INTRODUCTION: Megacystis microcolon hypoperistalsis syndrome (MMIHS) is a rare condition with high morbidity and mortality. It is characterized by megacystis, microcolon, and intestinal hypoperistalsis leading to various grades of bladder and bowel obstruction. CASE PRESENTATION: This report describes a pregnant woman with a history of bowel obstruction, urine retention, and heavy postpartum bleeding where ultrasound findings of fetal megacystis during pregnancy led to genetic testing in the family. The fetus, the pregnant woman, and four female family members were heterozygous for a pathogenic variant detected in the ACTG2 gene. The fetus was treated successfully for hydronephrosis using vesicoamniotic shunting. DISCUSSION: Early diagnosis of a fetus with MMIHS is important to secure multidisciplinary prenatal and neonatal treatment. Furthermore, gene testing must be considered when a woman presents a history of pseudo-obstruction and urine retention to prevent complications during pregnancy and labor. Finally, recurrent familial postpartum bleeding should lead to referral to genetic evaluation.

The association between preterm delivery and postpartum bleeding in otherwise uncomplicated pregnancies

Objective: The primary aim was to investigate whether preterm delivery was an independent risk factor for blood or blood products transfusion in the intrapartum or postpartum period, considered as a proxy for severe obstetric bleeding. Material and Methods: Throughout a 9-month-period, 216 uncomplicated singleton deliveries were included in a cross-sectional study after exclusion of severe maternal and fetal morbidity, such as chorioamnionitis, and use of medications including tocolytics. Maternal and neonatal data were evaluated and compared across preterm (between 24 0/7-36 6/7 weeks' gestation) and term (between 37 0/7-41 6/7 weeks' gestation) deliveries. Primary and secondary outcomes were requirement for blood or blood products transfusion until discharge and change in hemoglobin value and hematocrit from baseline to postpartum hour 6, respectively. Logistic regression models were constructed to evaluate the effect of preterm delivery on the primary outcome. Results: There were 90 (41.7%) preterm deliveries with an overall cesarean section rate of 77.8%. Preterm delivery was not an independent risk factor for the primary outcome, when route of delivery, maternal body-mass index, antenatal steroid administration, and baseline (admission) platelet and leukocyte counts were controlled for [adjusted risk ratio, 2.46; 95% confidence interval (CI), 0.69-8.77; p=0.16]. Subgroup analysis, including cesarean deliveries, revealed a similar result (adjusted risk ratio, 1.65; 95% CI, 0.42-6.48; p=0.47). Secondary outcomes, including decrease in mean or percent values of hemoglobin and hematocrit measurements, were also similar across preterm and term groups, both after vaginal and cesarean delivery (for all comparisons, p>0.05). Conclusion: Preterm delivery is not independently associated with increased requirement for blood transfusions or decreased hemoglobin and hematocrit values following otherwise uncomplicated vaginal or cesarean delivery of singletons.

Maternal bleeding complications in pregnancies affected by red blood cell alloimmunization.

OBJECTIVE: To investigate whether women with red blood cell (RBC)1 alloimmunization are more likely to experience bleeding complications during pregnancy or delivery than women without RBC alloimmunization. STUDY DESIGN: Retrospective study involving all singleton pregnancies affected by RBC alloimmunization and without pre-existing maternal bleeding disorders or placenta previa, from 1 July 1999 to 30 June 2019 ("cases"). Only bleedings not related to invasive procedures (amnio- or cordocenteses) were included. Patients who were already at increased risk of pre- or perinatal bleeding due to their medical history (pre-existing bleeding disorders, antithrombotic therapy), or known obstetrics parameters (placental abnormalities etc.) were not included a priori. Cases were compared to controls without RBC alloimmunization, matched for maternal age and body mass index, from the same tertiary referral center in Austria. RESULTS: 130 cases were compared to 130 controls. Cases had significantly more previous pregnancies and miscarriages and their newborns had lower birthweight and were more often transferred to the intensive care unit than newborns of controls. 18/130 (13.8%) cases, compared to 8/130 (6.2%) controls experienced any bleeding during pregnancy or delivery (p = 0.061). Bleeding most often happened during the third trimester (cases: 4.6% vs. controls 0.8%, p = 0.12) and during or after delivery (cases: 7.7% vs. controls: 4.6%, p = 0.168). Binary logistic regression for the prediction of any bleeding complication during pregnancy, delivery or postpartum revealed immunization against RBC antigens as the only independent contributor (p = 0.04). Age, smoking, or previous obstetric history had no influence on the likelihood of maternal bleeding complications. Neither RBC antibody specificity nor titers were predictive of maternal bleeding during pregnancy or delivery. CONCLUSION: Pregnancies affected by RBC alloimmunization might be at increased risk of maternal bleeding complications during pregnancy and delivery.

Tranexamic Acid Use in the Postpartum Period Since the WOMAN Trial: A Retrospective Chart Review.

OBJECTIVE: To analyze the use of tranexamic acid (TXA) in postpartum patients since the World Maternal Antifibrinolytic (WOMAN) trial. METHODS: A retrospective chart review was conducted from May 2017 to March 2020 at a tertiary care centre to identify all patients who received TXA for postpartum bleeding. The primary outcome was to identify the proportion of patients who received TXA as per World Health Organization guidelines created using results of the World Maternal Antifibrinolytic trial. RESULTS: A total of 231 patients were included in our analysis. Use increased over time with 18 patients in 2017, 51 in 2018, and 134 in 2019 receiving TXA. In all, 203 patients (87.9%) received TXA within recommended guidelines, and these patients were less likely to require surgery or interventional radiology (12.3% vs. 42.9%, P < 0.001) or blood transfusion (23.6% vs. 42.9%, P = 0.030), and they had a lower likelihood of overall adverse outcomes (1.62 (1.6) vs. 2.60 (2.0), P = 0.024). TXA was commonly used as the first-line agent for postpartum bleeding (48.9% of patients), more likely administered at cesarean section (77.0%) and when estimated blood loss did not meet criteria for "true" postpartum hemorrhage (41.6% of patients). Use of TXA as the first medication was associated with fewer overall adverse outcomes than misoprostol (P = 0.035). A shorter time to administration of the first medication was associated with shorter postpartum admission time (P = 0.042). CONCLUSIONS: The majority of patients received TXA within guidelines and experienced fewer adverse outcomes. Further study is needed to identify the best order of TXA administration with additional uterotonics and whether TXA should be used prophylactically in some groups for postpartum bleeding.

Intrauterine Bakri balloon tamponade plus cervical cerclage for the prevention and treatment of postpartum haemorrhage in late pregnancy complicated with acute aortic dissection: Case series.

In this study, a treatment method was assessed for the prevention and treatment of postpartum bleeding after combined surgery in patients having late pregnancy with the complication of acute Stanford type A aortic dissection. The clinical records of ten patients receiving treatment at the Second Xiangya Hospital of Central South University between March 2012 and March 2021 were retrospectively analysed. All patients were diagnosed with acute Stanford type A aortic dissection according to computed tomography angiography of the thoracic and abdominal aorta. Aortic valve function was assessed using two-dimensional echocardiography. All patients experienced uterine-incision delivery under systemic anaesthesia. During the operation, intrauterine Bakri balloon tamponade and cervical cerclage were performed. Postpartum bleeding was effectively controlled for all patients. The extracorporeal circulation time was 230-295 min, the postpartum 24 h bleeding volume was 500-870 mL, the volume of physiological saline injected into the balloon was 290-515 mL, and the intrauterine balloon compression time was 28-51 h. No postpartum bleeding occurred. A 42-days follow-up showed no late postpartum bleeding, poor uterine incision healing, or puerperal infection, and no uterine removal was performed. Intrauterine Bakri balloon tamponade plus cervical cerclage can effectively prevent intra- and postoperative postpartum bleeding in pregnant patients with aortic dissection.

The Efficiency of Temporary Uterine Artery Ligation on Prevention of the Bleeding in Cesarean Section.

OBJECTIVE: We aimed to evaluate the effect of temporary ligation of the uterine artery on postpartum bleeding during uncomplicated cesarean section. DESIGN: This was a prospective, randomized, and controlled study. We recruited a total of 200 patients, including 100 cases and 100 controls. METHODS: The bilateral uterine artery was temporarily clamped 2 cm below the uterine incision in the study group and compared with controls. Patient demographics, the amount of intraoperative bleeding, the duration of the operation, the closure time of the uterine incision, the need for additional uterotonics, the need for additional sutures, and the hemoglobin values before and after birth were assessed. RESULTS: The mean value of the amount of bleeding in the clamped and control groups was 267.3 ± 131.8 mL and 390.2 ± 116.4 mL, respectively. The amount of bleeding was significantly decreased for clamped group (p < 0.001). A significant reduction occurred in the results of pre- and postoperative values of hemoglobin and hematocrit difference, operation duration, and the closing time of the uterine incision in the experimental group which has temporary uterine artery clamping. LIMITATIONS: The cases of recurrent cesareans were not included in this study. CONCLUSION: Temporary uterine artery ligation can be used to reduce the amount of bleeding during uncomplicated cesarean delivery and prevent postpartum hemorrhage.

Manual strangulation of the uterine isthmus after placental removal to reduce blood loss during cesarean section.

INTRODUCTION: This study aimed to evaluate the effect of manual strangulation of the uterine isthmus on the amount of blood loss during cesarean section. MATERIAL AND METHODS: This is a prospective randomized controlled trial. A total of 118 participants were enrolled in the study. Manual strangulation of the uterine isthmus just after placental removal was performed during cesarean section in group I (n = 57; the strangulation group). Strangulation was not performed in group II (n = 61; the control group). Preoperative and postoperative venous blood hemoglobin, capillary hemoglobin, and absorbed blood levels during the operation were compared between the two groups. RESULTS: The median age of the patients was 28.5 (19-41). The median body mass index of the patients in the study was 27 (21-42). There were no significant differences in the demographic characteristics of the patients between the groups. The median difference between the preoperative and postoperative 4-6 h capillary hemoglobin values was significantly lower in the strangulation group (2.0 (0-9)) than in the control group (3.0 (0-8)). The amount of absorbed blood during the operation was also significantly lower in the strangulation group (164.5 ml (69-1310)) than in the control group (230 ml (35-3223)). CONCLUSIONS: Manual uterine strangulation of the uterine isthmus immediately after the removal of the placenta may induce a 30% decrease in blood loss during cesarean section.

Laparoscopic Hemostasis of Intractable Delayed Postpartum Hemorrhage.

Postpartum hemorrhage (PPH) is associated with considerable morbidity and mortality, particularly when relaparotomy is necessary. The etiology of spontaneous intractable PPH in a hemodynamically stable patient is poorly understood and remains open to speculation. Secondary, or delayed, PPH is usually defined as the excessive bleeding from the genital tract, with a loss of 500 ml or more of blood occurring after the first 24 hours after delivery until the sixth week of puerperium. In this report, we present three cases of severe, diffuse postpartum bleeding unresponsive to conventional hemostatic measures, which were successfully managed laparoscopically at our center. In all three cases, hemostasis was accomplished by using a laparoscopic procedure: with the excision of cervical stump bleeding in the first case, bilateral uterine artery ligation accompanied by laparoscopic hysterectomy in the second case, and bilateral internal iliac artery ligation in the third case.

von Willebrand disease: Diagnosis and treatment, treatment of women, and genomic approach to diagnosis.

von Willebrand disease (VWD) is the most common inherited bleeding disorder. VWD is caused by deficiencies in von Willebrand factor (VWF), a critical adhesive haemostatic protein. This review provides an overview of VWD diagnosis and treatment, special considerations in treating women with VWD, and current genomic approaches to VWD. For diagnosis and treatment in VWD, an accurate diagnosis is critical to providing effective treatments, determining appropriate laboratory monitoring and for counselling the patient and family. Diagnosis of VWD begins with the clinical assessment for the bleeding phenotype, which is usually characterized by mucocutaneous and provoked bleeding. The diagnosis of VWD is then made by laboratory investigation. Multiple assays are used to assess VWF levels and functions. The mainstays of VWD treatment are tailored by VWD type and symptoms, and can include antifibrinolytic treatment, desmopressin and VWF replacement treatment. Women with VWD are also at risk for excessive uterine bleeding, such as with menses and childbirth. In addition to standard VWD treatments, heavy menstrual bleeding can be treated with hormones. Interdisciplinary management of childbirth and prophylaxis in the postpartum period are needed to reduce the risk of postpartum haemorrhage. Genomic approaches to VWD can inform VWD diagnosis, treatment, test assay selection, reproductive planning and family counselling. Most VWD patients have an identifiable VWF gene DNA variant. Next-generation sequencing is rapidly being adopted to provide more comprehensive VWF sequence information for patients with known or suspected VWD.

Inherited platelet disorders in women.

Inherited platelet disorders (IPD) are a heterogeneous group of hemorrhagic diseases affecting both men and women, but usually associated with more evident bleeding symptoms in women due to the exposure to sexspecific hemostatic challenges, like menstruation and delivery. Indeed, up to 50% of women presenting with menorrhagia are diagnosed an IPD, moreover women with IPD can have ovulation-associated bleeding events and are at higher risk of endometriosis. Large retrospective studies have shown that women with IPD have a significantly increased risk of post-partum hemorrhage, predicted by a high bleeding score at previous history and by a platelet count below 50X109/L. In addition, in patients with IPD, female sex was associated with a higher frequency of excessive bleeding after surgery, even when excluding gynecological procedures. In conclusion, IPD may represent a serious problem for women's health, and their diagnosis and appropriate management is crucial to ensure female patients a good quality of life.

Postpartum Bleeding in Pregnant Women Receiving SSRIs/SNRIs: New Insights From a Descriptive Observational Study and an Analysis of Data from the FAERS Database.

PURPOSE: To date, the available data on the relationship between the use of selective serotonin reuptake inhibitors (SSRIs) or the serotonin and norepinephrine reuptake inhibitor (SNRI) venlafaxine and postpartum hemorrhage (PPH) are conflicting and have not been extensively investigated, especially in terms of plasma drug concentrations. We performed data mining of antidepressant-induced PPH reported to the US Food and Drug Administration's Adverse Event Reporting System database, to assess the strength of the potential association between antidepressant pharmacotherapy and PPH in pregnant women. Concurrently, we carried out a descriptive observational population (pregnant women) analysis of the correlation between the plasma concentrations of SSRIs/SNRIs used during pregnancy and the extent of bleeding at delivery. METHODS: A disproportionality analysis of individual case study reports of PPH associated with SSRIs or venlafaxine in pregnant women was performed. Reporting odds ratio was used as a measure of disproportionality analysis. Pregnant women treated with an SSRI or SNRI (venlafaxine) for depressive or anxiety disorder and who consented to plasma drug concentration monitoring at the time of delivery were recruited. Plasma drug concentration assay was performed according to validated LC-MS/MS. Based on plasma drug concentrations, patients were classified into 1 of 2 groups, in therapeutic range or below therapeutic range for the drug administered, in accordance with the Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie guideline, and correlations with blood loss were identified, with PPH defined as a blood loss of >500 mL. FINDINGS: Only 43 Individual Case Safety Reports (ICSRs) reported at least one SSRIs or venlafaxine as suspect drug in 14 years (database analyses). Forty-three women were enrolled in the study population (observational study). In 24 patients (55.8%) the plasma drug concentration was below the therapeutic threshold. Unexpectedly, the mean blood loss in the below-range group was significantly higher than that in the in-range group. PPH occurred in 30% of women: in 9.3% and in 20.7% of patients in the in-range and below-range groups, respectively. IMPLICATIONS: Although preliminary, these data indicate a rather good tolerability profile of SSRIs/SNRIs regarding postpartum bleeding. Moreover, they suggest that keeping the plasma levels of SSRIs/SNRIs low as a precautionary measure does not reduce postpartum bleeding, which was higher in the below-range group. The findings from this study suggest that the use of therapeutic drug monitoring in pregnancy, a period in which multiple variables affect drug metabolism, may allow for better treatment customization, with subsequent advantages in terms of tolerability and efficacy of treatment.