Risk factors for blood component therapy in parturients—Case–control study

Postpartum hemorrhage is a major cause of maternal morbidity and mortality, so early identification of patients at risk is crucial. In this study, we aim to assess the risk factors for major transfusion in parturients.

time, preparing for transfusion requires the drawing of a blood sample from the patient to obtain typing and screening for common antibodies, a process that takes approximately 1 h, especially in cases of major transfusion (≥3 PRBC). 6 To identify at-risk women early and prevent delay in treatment, population-based studies demonstrated a number of risk factors for PPH 5,7 as well as risk evaluation models for blood transfusion in obstetrical patients. 8 Due to the variability and inconsistency in risk assessment models, particularly among multiparous women and cases involving major packed cell transfusion, we have undertaken an investigation to re-evaluate the relevant risk factors in our specific population.

| Study population
We conducted a case-control study of all the women who delivered in a single university-affiliated tertiary hospital between 2011 and 2019.
Cases included women who were treated with major transfusion (≥3 PRBC) compared with two control groups: women who were treated with 1-2 PRBC and those who were not treated with blood therapy. To control for major confounding variables that were found to be important risk factors for PRBC treatment, we matched our cases to control groups based on two variables: multiple pregnancy 4,8 and previous history of three or more cesarean sections. 9,10 The matching ratio was 1:4:4 for cases and control groups, respectively.
Women who had missing data regarding pairing variables or blood therapy treatment were excluded, as well as women who underwent abortion or delivered before 20 weeks of pregnancy. All of the other deliveries were included.
We compared the demographic and clinical characteristics along with the risk factors for major transfusion between case and control groups.

| Statistical analysis
Univariate analysis techniques were used to identify differences between case and control groups. One-way ANOVA of variance or Kruskal-Wallis tests (in the case of non-normally distributed variables) were used to assess the significance of continuous variables.
In the same way, we used the χ 2 test (or Fisher exact test, as needed) for categorical variables. The univariate analysis was also verified by conditional logistic regression using a single variable in a Cox

regression.
A multivariable logistic regression model, controlling for variables that were found to be statistically different between groups, was used to determine the role of the independent variables.
Multivariate analysis was also verified by conditional logistic regression using a Cox regression.
We used Python software to perform computerized randomization matching. The data were analyzed using SPSS software version 21.0 (IBM, Armonk, NY, USA). A P value less than 0.05 was considered significant. The power of 80% was calculated using the WinPePi program.

| Data collection
The medical charts were retrieved from the computerized delivery room logbooks. The database encompassed pregestational and obstetrical characteristics such as maternal age, pregestational body mass index (BMI; calculated as weight in kilograms divided by the square of height in meters), parity, gravidity, previous cesarean deliveries, and multiple pregnancy in the index delivery. Moreover, gestational clinical and obstetrical characteristics were obtained such as post-gestational BMI, gestational age, hemoglobin level and platelet count at admission, macrosomia, spontaneous delivery, anesthesia, the length of second and third phases of delivery, mode of delivery, pre-eclampsia, intrauterine or intrapartum fetal death, and suspected uterine rupture.
Abnormal placentation included cases of low-lying placenta, placenta previa, and vasa previa. Placenta accreta spectrum cases were excluded.
Preterm delivery was determined as less than 37 weeks of pregnancy. Grand-multiparity was defined as a history of five and above births (live or stillborn). Macrosomia was defined as newborn weight more than 4000 g. 11 Spontaneous labor was defined as delivery without any induction. Prolonged second and third phases of labor were determined by whether they lasted over 180 and 30 minutes, respectively. 12 Antenatal anemia and thrombocytopenia were respectively characterized as hemoglobin levels less than 10 g/dL and platelet counts of less than 100 000/μL.
The study protocol was approved by the Institutional Review Board (Helsinki Committee) of Sourasky Tel Aviv Medical Center.
Data analysis was performed with an unidentified database so informed consent was not needed.

| RE SULTS
Overall, 87 242 deliveries occurred during the study period. Of them, 83 777 deliveries had data regarding pairing variables that we included in the present study. Among the study population, 1602 women (1.8%) were treated with PRBC, 246 of whom (0.3%) required major transfusion.
Of all the cases, 214 women were included in the present study and were paired with 1712 controls; women who were treated with 1-2 PRBC and women who were not. Women with missing data on the pairing variables were excluded from the study (Figure 1).
The pregestational clinical and obstetrical characteristics are detailed in Table 1. Women in the major transfusion group were older compared with women in the control groups: 34 years (interquartile range [IQR] 30-37.25 years) versus 32 years (IQR 29-36 years) (P < 0.001). Having one to four previous deliveries was less common among women who were treated with 1-2 PRBC, compared with the other groups (38.3% vs. 58.9% and 56.7%, P < 0.001).
Gestational characteristics are described in Table 2. Antenatal anemia was found in 8% of all deliveries and was more prevalent in women who were treated with PRBC compared with the control group (19.8% and 19.1% vs. 5.7%, P < 0.001). Similarly, retained placenta was more common among women who were treated with blood transfusion (27.4% and 23.5% compared with 6.6%, P < 0.001).
In a multivariate conditional logistic regression model controlling for antenatal thrombocytopenia, preterm delivery, spontaneous labor, intrauterine or intrapartum fetal death, and previous repeated pregnancy loss, several risk factors were found to be associated with major transfusion compared with women who were not treated with PRBC ( Abbreviations: BMI, body mass index (calculated as weight in kilograms divided by the square of height in meters); PRBC, packed red blood cells. a Data are presented as median (interquartile range) or as number (percentage).
b P value is also significant in comparison between major transfusion and no treatment groups.
c P value is also significant in comparison between major transfusion and 1-2 packed cell groups.
Multivariate analyses also compared women who were treated with 1-2 PRBC with women who were not treated with PRBC (Table 4), and women who were treated with major transfusion with women who were treated with 1-2 PRBC (Table 5).

| DISCUSS ION
The present study investigated risk factors for major transfusion in parturients. We matched our cases to control groups based on two variables: multiple pregnancy and previous history of three or more cesarean sections.
Our major findings were that: (1) the estimated postpartum blood transfusion rate was 1.8% and (2) retained placenta and antenatal anemia were the strongest independent risk factors for major transfusion.
The rate of blood transfusion therapy varies from 0.3% to 7.85% 13 and can exceed 25% in low-income countries. 14 Similar to other studies, 8,15 the blood transfusion rates were 1.8% and 0.3% for major transfusion in the present study.
Antenatal anemia was found to be the most significant risk factor for PRBC transfusion as well as for major transfusion. As the result of physiologic changes during pregnancy, third-trimester anemia is defined as hemoglobin level below 11 g/dL. 16 The present study demonstrates that a decrease in 1 g/dL of the lower value of normal hemoglobin leads to an increase in the risk for blood transfusion by up to 12 times. Our findings are consistent with the risk evaluation for transfusion demonstrated by Xing et al., 8 and also with patient blood management in PPH based on hemoglobin level, which was described in a recent study. 17 Besides anemia, retained placenta was found to be an independent risk factor for PRBC transfusion. This can be explained by impaired uterine contraction following delivery. Hence, active management of the third phase of labor is recommended. 18 Other studies also reported retained placenta as a risk factor for PPH 19 and for PRBC transfusion. 8 As maternal age increases, obstetrical complications become more frequent, 15 including PPH 20,21 and treatment with blood component transfusion. 8 In the present study, women who were treated with major transfusion were older compared with the control Preterm delivery accounts for up to 12% of deliveries worldwide 23 and is associated with maternal and neonatal morbidity. 24 One of the preterm delivery mechanisms is placental abruption, which in some cases can lead to prolonged bleeding and anemia. 25 In the center in which the present study was conducted, cell blood count is taken from all of the women with preterm delivery at admission. When controlling for anemia, preterm delivery is a protective factor for treatment with blood transfusion. Hence, it is likely that this protective effect is biased as a result of hemoglobin levels in preterm parturients.
Recent studies reported multiparity as a risk factor for PPH. 4,7 However, we did not find it to be a risk factor for blood transfusion.
Nevertheless, a history of one to four deliveries was associated with a protective effect on treatment with 1-2 PRBC. In line with the studies cited above, multiparous women are managed with extreme caution and active management of the third stage of labor in our tertiary hospital. Consequently, we believe that selection bias im- a potential relation between anemia in pregnancy and high parity. 26 The association between multiparity, hemorrhage, and blood transfusion might be confounded by antenatal anemia.
We aimed to investigate risk factors for major transfusion in order to predict women at risk. In contrast, the present study has several strengths, including the great number of women eligible in our study and the casecontrol method matching, which allows a stratified analysis for major confounding variables. Moreover, the single-center design allowed uniform PPH and blood products transfusion protocols.
In conclusion, prediction of treatment with major transfusion in or after labor can prevent morbidity and mortality. We found that

CO N FLI C T O F I NTE R E S T S TATE M E NT
The authors have no conflicts of interest.

DATA AVA I L A B I L I T Y S TAT E M E N T
Research data are not shared.