Background

Labor neuraxial analgesia may reduce the odds of postpartum hemorrhage, the leading indication for maternal blood transfusion during childbirth. This study tested the hypothesis that labor neuraxial analgesia is associated with reduced odds of maternal blood transfusion overall.

Methods

U.S. birth certificate data in the Natality File of the National Vital Statistics System for all 50 states from 2015 to 2018 for vaginal and intrapartum cesarean deliveries were analyzed. The exposure was labor neuraxial analgesia. The primary outcome was maternal blood transfusion, recorded on the birth certificate, which has low sensitivity for this outcome. Adjusted odds ratios and 95% CIs of blood transfusion associated with neuraxial analgesia were estimated using propensity score matching. The adjusted odds ratios were estimated overall and according to delivery mode, and treatment effect was compared between vaginal and intrapartum cesarean deliveries using an interaction term. Sensitivity analyses were performed using inverse propensity score weighting and quantitative bias analysis for outcome misclassification.

Results

Of the 12,503,042 deliveries analyzed, 9,479,291 (75.82%) were with neuraxial analgesia, and 42,485 (0.34%) involved maternal blood transfusion. After propensity score matching, the incidence of blood transfusion was 0.30% in women without neuraxial analgesia (7,907 of 2,589,493) and 0.20% in women with neuraxial analgesia (5,225 of 2,589,493), yielding an adjusted odds ratio of 0.87 (95% CI, 0.82 to 0.91) overall. For intrapartum cesarean deliveries, the adjusted odds ratio was 0.55 (95% CI, 0.48 to 0.64), and for vaginal deliveries it was 0.93 (95% CI,. 0.88 to 0.98; P value for the interaction term < 0.001). The results were consistent in the sensitivity analyses, although the quantitative bias analysis demonstrated wide variation in potential effect size point estimates.

Conclusions

Labor neuraxial analgesia may be associated with reduced odds of maternal blood transfusion in intrapartum cesarean deliveries and, to a lesser extent, vaginal deliveries. The specific effect size varies widely by delivery mode and is unclear given the poor sensitivity of the data set for the maternal transfusion primary outcome.

Editor’s Perspective
What We Already Know about This Topic
  • Labor neuraxial analgesia may reduce the risk of postpartum hemorrhage

  • It is unclear whether labor neuraxial analgesia is associated with a lower risk of maternal transfusion compared to delivery without neuraxial analgesia

What This Article Tells Us That Is New
  • Using propensity score matching, U.S. birth certificate data for 12,503,042 patients from 2015 to 2018 demonstrated an adjusted maternal transfusion incidence of 30.5 per 10,000 for patients without labor neuraxial analgesia versus 20.2 per 10,000 for patients with labor neuraxial analgesia, a 13% reduction (95% CI, 18% to 9%)

  • This estimated reduction in maternal transfusion varied by delivery mode

  • Patients undergoing vaginal deliveries with labor neuraxial analgesia demonstrated a small 7% adjusted reduction (95% CI, 12% to 2%) in maternal transfusion

  • Patients undergoing intrapartum cesarean deliveries (after a trial of labor) with labor neuraxial analgesia demonstrated a 45% adjusted reduction (95% CI, 52% to 36%) in maternal transfusion

Labor neuraxial analgesia (i.e., epidural or combined spinal epidural analgesia) is the most effective technique to alleviate pain during labor and is used in approximately 70% of U.S. births.1,2  Furthermore, labor neuraxial analgesia is suggested to be associated with reduced odds of severe maternal morbidity. Severe maternal morbidity refers to unintended adverse outcomes during childbirth, resulting in significant short- or long-term consequences to a mother’s health.3 

At least two pathways have been suggested for explaining the reduced odds of severe maternal morbidity associated with labor neuraxial analgesia. First, for women who gave birth vaginally, previous research reports that labor neuraxial analgesia is associated with reduced odds of postpartum hemorrhage.4,5  As of 2022, postpartum hemorrhage is the leading cause of preventable severe maternal morbidity and preventable maternal mortality.6–8  Furthermore, postpartum hemorrhage is one of the leading indications for blood product transfusion during childbirth and the postpartum period.9  Of concern, blood transfusion in postpartum women is reported to be associated with increased odds of transfusion reactions (e.g., transfusion-related acute lung injury) compared to nonpregnant women.10  Second, labor neuraxial analgesia may prevent the use of general anesthesia if an intrapartum cesarean delivery is required; general anesthesia is associated with increased odds of postpartum hemorrhage and maternal morbidity.11–13  The reported reduction in odds of postpartum hemorrhage associated with labor neuraxial analgesia makes it plausible to hypothesize that labor neuraxial analgesia is associated with reduced odds of blood transfusion during childbirth. Using birth certificate data for vaginal and intrapartum cesarean deliveries in the 50 states and the District of Columbia between 2015 and 2018, we conducted this study to assess the association of labor neuraxial analgesia with maternal blood transfusion.

The study protocol was deemed exempt by the Institutional Review Board of the Columbia University Irving Medical Center. A data analysis and statistical plan was written and shared with the funding agency (National Institute on Minority Health and Health Disparities, Bethesda, Maryland) before data were accessed. The study follows the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guidelines. The currently presented analysis was based on the initial analysis combined with changes made during the peer review process.

Data System

We analyzed U.S. birth certificate data contained in the restricted access Natality File of the National Vital Statistics System (National Center for Health Statistics, Hyattsville, Maryland, Centers for Diseases Control and Prevention, Atlanta, Georgia). The Natality File is based on the 2003 revised U.S. Standard Certificate of Live Birth.14  As of January 2015, the 2003 revised U.S. Standard Certificate of Live Birth was implemented in the 50 U.S. states and the District of Columbia. The Natality File is a census of all live births in the United States and contains comprehensive information on the mother, pregnancy, labor, and delivery. Residence and hospital county characteristics were abstracted from the Area Health Resource File.15 

Study Sample

The study sample included birth certificates for vaginal and intrapartum cesarean deliveries from January 2015 to December 2018. Nonintrapartum cesarean deliveries were excluded. We identified vaginal and cesarean deliveries using a specific checkbox on the birth certificate. Since the checkbox did not indicate whether a cesarean delivery was intrapartum or not, we defined a cesarean delivery as intrapartum if associated with at least one of the following characteristics indicating labor: (1) trial of labor attempted if previous cesarean delivery; (2) induction of labor; (3) augmentation of labor; (4) antibiotics received by the mother during labor; and (5) clinical chorioamnionitis diagnosed during labor or maternal temperature greater than 38°C during labor (Supplemental Digital Content Table 1, https://links.lww.com/ALN/D284). Exclusion criteria were (fig. 1): (1) missing information on labor neuraxial analgesia; (2) missing information on maternal outcome; (3) missing information on maternal race and ethnicity; (4) birth not occurring in the state of residence; (5) birth not occurring in a hospital; (6) mother not residing in the United States; and (7) missing information on residence or hospital county.

Fig. 1.

Flowchart of the study. Footnote (a), Reasons for exclusion are not mutually exclusive.

Fig. 1.

Flowchart of the study. Footnote (a), Reasons for exclusion are not mutually exclusive.

Close modal

Exposure

The exposure of interest was labor neuraxial analgesia. In the birth certificate, it is reported in a specific checkbox (“Epidural or spinal anesthesia during labor”) and defined as the “administration to the mother of a regional anesthetic for control of the pain of labor (i.e., delivery of the agent into a limited space with the distribution of the analgesic effect limited to the lower body).”16  The reported sensitivity of labor neuraxial analgesia in birth certificate data in a study conducted in two states in 2009 to 2011 and in a study conducted in New York City in 2013 was greater than 85%.17,18  The Natality File does not contain detailed information on the type of labor neuraxial analgesia precluding the analysis of the effect of neuraxial techniques (epidural or combined spinal epidural).

Outcome Measure

The outcome measure of interest was maternal blood transfusion, reported in a specific checkbox and defined as “infusion of whole blood or packed red blood cells associated with labor and delivery.”16  The reported sensitivity and positive predictive value of blood transfusion in birth certificate data in the state of Massachusetts in 2011 to 2013 were 12 and 73%, respectively.19  In a recent study analyzing birth certificate data from 2014 to 2016 in the United States, the reported incidence of blood transfusion was 0.3%.20  Birth certificates do not contain codes of the International Classification of Diseases, precluding the assessment of severe maternal morbidity as defined by the U.S. Centers for Disease Control and Prevention.21 

Maternal and Hospital Characteristics

We selected maternal and hospital characteristics for this study based on their plausible association with labor neuraxial analgesia use or with maternal blood transfusion. Maternal characteristics and comorbidities from the birth certificate data included: age (19 yr or younger, 20 to 29 yr, 30 to 39 yr, or 40 yr or older); race and ethnicity; education level (less than high school, high school with no diploma, high school graduate or general educational diploma, and college or higher); health insurance (Medicaid, private, self-pay, or other); body mass index (18.4 or lower, 18.5 to 24.9, 25.0 to 29.9, 30.0 to 34.9, or 35 kg/m2 and greater); and pre-existing or gestational diabetes or hypertension. Maternal race and ethnicity included six mutually exclusive groups: (1) non-Hispanic White (hereafter referred to as White); (2) non-Hispanic Black (Black); (3) Hispanic; (4) non-Hispanic Asian, Native Hawaiian, and Other Pacific Islander (Asian and Pacific Islander); (5) non-Hispanic American Indian and Alaskan Native (Native American); and (6) more than one race. We acknowledge that race is a social construct and that these data have inherent limitations; we include the data given evidence of inequities and racism in maternal and infant outcomes.22 

We abstracted the following residence county characteristics from the Area Health Resource File: location (urban, suburban, or rural); proportion of persons in poverty; and proportion of persons unemployed.15  Area Health Resource File data for the year 2015 were used for births in 2015 and 2016, and Area Health Resource File data for the year 2017 were used for births in 2017 and 2018.

Obstetrical characteristics from the birth certificate data included: previous cesarean section; month of gestation prenatal care began (first to third month, fourth to sixth month, seventh month or later, or no prenatal care); number of prenatal visits; delivery during a weekend; mother transferred in (i.e., transfer from another facility for maternal medical or fetal indications for delivery); nulliparous; gestational age at delivery (33 weeks or less, 34 to 38 weeks, or 39 weeks or more); multiple gestation; noncephalic presentation; induction of labor; augmentation of labor; antibiotics during labor; chorioamnionitis; attendant at birth (doctor of medicine, doctor of osteopathy, midwife, or other); and birth weight (2,499 g or less, 2,500 to 4,000 g, or greater than 4,000 g).

We abstracted the following hospital county characteristics form the Area Health Resource File file: location (urban, suburban, or rural); number of in-hospital births; number of physician anesthesiologists (per 1,000 in-hospital births); number of certified registered nurse anesthetists (per 1,000 in-hospital births); and number of obstetricians and gynecologists (per 1,000 in-hospital births). Area Health Resource File data for the year 2015 were used for births in 2015 and 2016, and Area Health Resource File data for the year 2017 were used for births in 2017 and 2018.

Statistical Analysis

We performed the statistical analysis using R software version 3.6.2 (R Foundation for Statistical Computing, Austria) and specific packages (“matching” for matching, “survival” for conditional logistic regression, and “episensr” for probabilistic sensitivity analysis).23 

Descriptive Statistics.

We calculated the labor neuraxial analgesia rate overall and according to delivery mode (vaginal or intrapartum cesarean delivery) and maternal race and ethnicity (White, Black, Hispanic, Asian and Pacific Islander, Native American, and more than one race). We compared characteristics between women with and without labor neuraxial analgesia using the absolute standardized difference, with a value greater than 10% used to define a clinically important imbalance.24 

Crude Analysis.

We calculated the incidence of blood transfusion in women with and without labor neuraxial analgesia, overall and according to delivery mode. The crude risk difference was calculated as the difference in blood transfusion incidence between women with and without labor neuraxial analgesia. Crude odds ratios of blood transfusion associated with labor neuraxial analgesia were estimated using univariate logistic regression models overall and according to delivery mode.

Adjusted Analysis.

We estimated the adjusted differences and adjusted odds ratios using the propensity score matching method, with the propensity score estimating the individual probability of receiving labor neuraxial analgesia. We calculated the propensity score using a fixed-effect logistic regression model, with labor neuraxial analgesia as the dependent variable and 33 patient- and hospital-level characteristics as the independent variables (Supplemental Digital Content Table 2, https://links.lww.com/ALN/D284). The propensity score was computed independently for each of the 4 yr of the study period. We performed a complete case analysis with 968,635 discharges excluded (7.7%). The matching procedure used the nearest neighbor approach with a caliper of 0.001, one case matched to one control, and stratification according to delivery mode and year of delivery. We assessed the balance after matching using the absolute standardized difference. In propensity score–matched data, we estimated adjusted odds ratios using conditional logistic regression models, overall and according to delivery mode. We compared the odds of blood transfusion associated with labor neuraxial analgesia between women who had a vaginal delivery and women who had an intrapartum cesarean delivery using the regression coefficient of an interaction term between labor neuraxial analgesia and delivery mode. We added to the model variables with a persistent imbalance after matching (absolute standardized difference greater than 10%). In a preplanned sensitivity analysis, we re-estimated the adjusted odds ratios of blood transfusion associated with labor neuraxial analgesia using the inverse propensity score weighting method. Weights were stabilized and truncated at 1 and 99%.

To assess potential bias due to unmeasured confounder, we calculated the E value associated with the adjusted odds ratio of blood transfusion. The E value estimates how strong an unmeasured confounder (i.e., an unknown factor associated with both labor neuraxial analgesia and blood transfusion) would need to be to explain away the observed association between labor neuraxial analgesia and blood transfusion.25  The lowest possible E value is 1 and indicates that no unmeasured confounding is needed to explain away the observed association. The higher the E value, the stronger the confounder must be to explain away the observed association.

Subgroup Analyses.

To assess the robustness of our findings, we estimated the adjusted odds ratios of blood transfusion associated with labor neuraxial analgesia in three subgroups of women: (1) women at low risk of cesarean delivery, defined as women with singleton, head-first, term (37 to 41 completed weeks) first births; (2) women at low infectious risk, defined as women who did not receive antibiotics during labor, had no clinical chorioamnionitis diagnosed during labor, and had no temperature greater than 38°C during labor; and (3) women without comorbidities, defined as women with no pre-existing or gestational diabetes, no pre-existing or gestational hypertension, no pre-eclampsia, and no eclampsia.

Sample Size and Study Power.

Since the study sample size was fixed, we estimated the minimum detectable effect using this study sample. We expected to include about 10 million birth certificates for vaginal or intrapartum cesarean deliveries, including 7 million with labor neuraxial analgesia (70%). We expected to propensity score match 2.1 million birth certificates with labor neuraxial analgesia (30%) to 2.1 million birth certificates without labor neuraxial analgesia. With an incidence of blood transfusion of 30 per 10,000 in certificates without labor neuraxial analgesia,20  a two-sided test at a significance level of 0.05, our data would have 90% power to detect a minimum odds ratio of blood transfusion associated with labor neuraxial analgesia of 0.94 (or lower).26 

Post Hoc Analyses.

We performed two post hoc analyses suggested by the reviewers to assess the degree of under-reporting of blood transfusion in birth certificate data and its impact on the adjusted odds ratio of maternal blood transfusion associated with labor neuraxial analgesia. First, we estimated the incidence of blood transfusion using the National Inpatient Sample from October 2015 to December 2018. The National Inpatient Sample is a stratified 20% sample of all discharge records from community hospitals in the United States,27  and blood product transfusion was identified using the Centers for Disease Control and Prevention algorithm based on ICD-10-CM codes.21  Second, we performed a probabilistic sensitivity analysis to correct for outcome misclassification and the odds ratios of blood transfusion associated with labor neuraxial analgesia.28  We performed this analysis in crude data and in data weighted using the inverse propensity score weighting method using the following assumptions: sensitivity of blood transfusion between 10 and 50% (uniform distribution), specificity between 75 and 100% (uniform distribution), and nondifferential misclassification of blood transfusion between women who received labor neuraxial analgesia and women who did not. Corrected median odds ratio (2.5th to 97.5th percentile) of blood transfusion associated with labor neuraxial analgesia were estimated using 100,000 iterations.

Of the 12,503,042 birth certificates meeting inclusion and exclusion criteria for analysis, 2,532,011 (20.2%) were for intrapartum cesarean deliveries (fig. 1). The number of birth certificates with labor neuraxial analgesia was 9,479,291, yielding an overall labor neuraxial analgesia rate of 75.82% (95% CI, 75.79 to 75.84%). The labor neuraxial analgesia rate was higher for intrapartum cesarean deliveries (90.77%; 95% CI, 90.73 to 90.81%) than for vaginal deliveries (72.02%; 95% CI, 71.99 to 72.05%). Among the six racial and ethnic groups, Hispanic and Native American women had the lowest labor neuraxial analgesia rate (table 1).

Table 1.

Labor Neuraxial Analgesia Rate According to Maternal Race and Ethnicity (United States, 2015 to 2018)

Labor Neuraxial Analgesia Rate According to Maternal Race and Ethnicity (United States, 2015 to 2018)
Labor Neuraxial Analgesia Rate According to Maternal Race and Ethnicity (United States, 2015 to 2018)

Compared to women delivering without labor neuraxial analgesia (table 2; Supplemental Digital Content Table 3, https://links.lww.com/ALN/D284), women delivering with labor neuraxial analgesia had a higher education level or private health insurance or lived in a county with lower unemployment rate. They had more often gestational hypertension. They received an earlier initiation of prenatal care or had a higher number of prenatal visits. They were more often nulliparous or with a previous cesarean section, had an induction or augmentation of labor, and delivered more often in an urban setting or with a doctor of medicine as an attendant at birth.

Table 2.

Comparison of Women Who Received and Women Who Did Not Receive Labor Neuraxial Analgesia, before and after Propensity Score Matching (United States, 2015 to 2018)

Comparison of Women Who Received and Women Who Did Not Receive Labor Neuraxial Analgesia, before and after Propensity Score Matching (United States, 2015 to 2018)
Comparison of Women Who Received and Women Who Did Not Receive Labor Neuraxial Analgesia, before and after Propensity Score Matching (United States, 2015 to 2018)

Crude Analysis

Before matching (table 3), the incidence of blood transfusion was 30.6 per 10,000 in women delivering without labor neuraxial analgesia and 35.1 per 10,000 in women delivering with labor neuraxial analgesia, yielding a risk difference of +4.5 per 10,000 (95% CI, 3.7 to 5.2) and a crude odds ratio of 1.15 (95% CI, 1.12 to 1.17). The risk difference was −52.7 per 10,000 (95% CI, −57.4 to −48.1) with a crude odds ratio of 0.58 (95% CI, 0.55 to 0.60) for intrapartum cesarean deliveries and +0.3 per 10,000 (95% CI, −0.3 to 1.0) with a crude odds ratio of 1.01 (95% CI, 0.99 to 1.04) for vaginal deliveries.

Table 3.

Crude Odds Ratios of Blood Transfusion Associated with Labor Neuraxial Analgesia (United States, 2015 to 2018)

Crude Odds Ratios of Blood Transfusion Associated with Labor Neuraxial Analgesia (United States, 2015 to 2018)
Crude Odds Ratios of Blood Transfusion Associated with Labor Neuraxial Analgesia (United States, 2015 to 2018)

Adjusted Analysis

After propensity score matching, 2,589,493 women delivering without labor neuraxial analgesia were matched to 2,589,493 women delivering with labor neuraxial analgesia. Among the 33 variables included in the propensity score, 3 had an absolute standardized difference greater than 10% after matching (hospital county number of in-hospital births, hospital county number of certified registered nurse anesthetists, and hospital state) and were added to the conditional logistic regression model used to estimate the adjusted odds ratios (table 2; Supplemental Digital Content Table 2, https://links.lww.com/ALN/D284).

After matching, the incidence of blood transfusion was 30.5 per 10,000 in women delivering without labor neuraxial analgesia and 20.2 per 10,000 in women delivering with labor neuraxial analgesia, yielding a risk difference of −10.4 per 10,000 (95% CI, −11.2 to −9.5; table 4). The adjusted odds ratio of blood transfusion was 0.87 for women receiving labor neuraxial analgesia (95% CI, 0.82 to 0.91) compared to women without neuraxial analgesia, with an associated E value of 1.56. In the subgroup of women with intrapartum cesarean deliveries, the risk difference was −68.2 per 10,000 (95% CI, −73.9 to −62.5), the adjusted odds ratio was 0.55 (95% CI, 0.48 to 0.64), and the associated E value was 3.04. In the subgroup of women with vaginal deliveries, the risk difference was −5.2 per 10,000 (95% CI, −6.0 to −4.4,), the adjusted odds ratio was 0.93 (95% CI, 0.88 to 0.98), and the associated E value was 1.36. The regression coefficient of the interaction term between labor neuraxial analgesia and delivery mode was −0.40 (95% CI, −0.48 to −0.31), indicating lower odds of blood transfusion associated with labor neuraxial analgesia in women who had an intrapartum cesarean delivery compared to women who had a vaginal delivery.

Table 4.

Adjusted Odds Ratios of Blood Transfusion Associated with Labor Neuraxial Analgesia Using the Propensity Score Matching Method (United States, 2015 to 2018)

Adjusted Odds Ratios of Blood Transfusion Associated with Labor Neuraxial Analgesia Using the Propensity Score Matching Method (United States, 2015 to 2018)
Adjusted Odds Ratios of Blood Transfusion Associated with Labor Neuraxial Analgesia Using the Propensity Score Matching Method (United States, 2015 to 2018)

The results were consistent when using the inverse propensity score weighting method (table 5; Supplemental Digital Content Table 4, https://links.lww.com/ALN/D284). Using the weighting method, the regression coefficient of the interaction term between labor neuraxial analgesia and delivery mode was −0.31 (95% CI, −0.36 to −0.26), indicating lower odds of blood transfusion associated with labor neuraxial analgesia in women who had an intrapartum cesarean delivery compared to women who had a vaginal delivery.

Table 5.

Sensitivity Analysis with Adjusted Odds Ratios of Blood Transfusion Associated with Labor Neuraxial Analgesia Estimated Using the Inverse Propensity Score Weighting Method

Sensitivity Analysis with Adjusted Odds Ratios of Blood Transfusion Associated with Labor Neuraxial Analgesia Estimated Using the Inverse Propensity Score Weighting Method
Sensitivity Analysis with Adjusted Odds Ratios of Blood Transfusion Associated with Labor Neuraxial Analgesia Estimated Using the Inverse Propensity Score Weighting Method

Subgroup Analyses

In the three subgroup analyses (Supplemental Digital Content Table 5, https://links.lww.com/ALN/D284), labor neuraxial analgesia was associated with a significantly decreased odds of blood transfusion in women who had an intrapartum cesarean delivery and, to a lesser extent, in women who had a vaginal delivery.

Post Hoc Analyses

The incidence of blood product transfusion during delivery hospitalizations estimated using the National Inpatient Sample was 1.1% (0.7% for vaginal deliveries and 2.1% for cesarean deliveries), which is 3.7 times the incidence of blood transfusion in birth certificate data. The results of the probabilistic sensitivity analysis for outcome misclassification (table 6) were consistent with results of the main analysis. Although the 2.5th to 97.5th percentile point estimates varied widely, the range consistently demonstrated that labor neuraxial analgesia was associated with a lower adjusted odds of maternal transfusion.

Table 6.

Probabilistic Sensitivity Analysis to Correct for Outcome Misclassification and the Odds Ratios of Maternal Blood Transfusion Associated with Labor Neuraxial Analgesia

Probabilistic Sensitivity Analysis to Correct for Outcome Misclassification and the Odds Ratios of Maternal Blood Transfusion Associated with Labor Neuraxial Analgesia
Probabilistic Sensitivity Analysis to Correct for Outcome Misclassification and the Odds Ratios of Maternal Blood Transfusion Associated with Labor Neuraxial Analgesia

In this national study of vaginal and intrapartum cesarean deliveries, labor neuraxial analgesia was associated with reduced odds of maternal blood transfusion, although the clinical significance and effect size of this observation varied by delivery mode. The results were consistent in the sensitivity analyses.

Reduction in the odds of maternal blood transfusion was more pronounced in intrapartum cesarean deliveries than in vaginal deliveries (45% vs. 7%). This difference between delivery modes was consistent in the subgroups of women at low cesarean delivery risk, low infectious risk, or without comorbidities (Supplemental Table 5, https://links.lww.com/ALN/D284). The small effect size for vaginal deliveries raises legitimate concern about its clinical relevance and reproducibility. Nevertheless, the reported effect size for maternal outcomes associated with labor neuraxial analgesia for vaginal delivery varies with the outcome examined. For example, in a study analyzing French data between 2004 and 2006, Driessen et al.4  reported 47% decreased odds of severe postpartum hemorrhage, defined as a decrease in postpartum hemoglobin concentration greater than 4 g/dl, associated with labor neuraxial analgesia. This marked decrease contrast with another study analyzing New York State data between 2010 and 2017, reporting a 14% decrease in the odds of severe maternal morbidity, as defined by the Centers for Disease Control and Prevention, and a 9% reduction in the odds of postpartum hemorrhage associated with labor neuraxial analgesia.5  In other words, the relatively small effect size for maternal blood transfusion observed in vaginal deliveries does not preclude a greater effect size for other maternal health outcomes.29  Similarly, we observed some differences in the odds of blood transfusion between the main analysis using the propensity score matching method and the sensitivity analysis using the inverse propensity score weighting method. For example, for intrapartum cesarean deliveries, the reduction was 45% (95% CI, 36 to 52%) using matching (table 4) and 37% (95% CI, 35 to 39%) using weighting (table 5). While the matching procedure tends to favor internal validity, the weighting procedure tends to favor external validity. In other words, reproducing our study using another data system may yield an estimate close to the one we obtained using the weighting method.

We cannot rule out with certainty mechanisms other than labor neuraxial analgesia per se that are responsible for the observed reduced odds of maternal blood transfusion. Indeed, in a previous study from our group limited to vaginal deliveries, we reported that labor neuraxial analgesia per se accounted for a small fraction of the reduced odds of severe maternal morbidity observed in women who received labor neuraxial analgesia.5  Other possible mechanisms may include sustained monitoring of women with labor neuraxial analgesia, enhancing early detection of blood loss immediately after childbirth, adequate intravenous access and fluid resuscitation, and continuous anesthesia provider availability and oversight of the process of labor and delivery and preparedness for acute events.30,31  In other words, use of labor neuraxial analgesia could be a proxy for provision of high-quality obstetric anesthesia care.

Limitations

Our findings should be interpreted in the context of the significant limitations related to birth certificate data. First, these data provide no information on strong risk factors for blood transfusion (e.g., anemia before pregnancy) or conditions associated with a markedly increased risk of obstetric hemorrhage (e.g., placenta accreta disorders), exposing the analysis to the risk of residual confounding. Second, the sensitivity of birth certificate data to detect blood transfusion is low, as reflected by a transfusion rate of 0.3% in our study contrasting with 1.1% in a nationally representative sample.19  Although our quantitative bias analysis suggests that this under-reporting did not affect the directionality of the associations, there is some uncertainty around the point estimate of the reduction of blood transfusion associated with labor neuraxial analgesia. Third, because birth certificate data do not provide a hospital identifier, we estimated hospital characteristics (e.g., number of anesthesia providers) at the hospital-county level. While this approach may be accurate for counties with only one hospital, it may not be accurate for counties with more than one hospital. Last, because birth certificate data do not provide a patient identifier, the analysis could not account for women who had more than one childbirth during the study period.

Conclusions

Labor neuraxial analgesia may be associated with reduced odds of maternal blood transfusion in intrapartum cesarean deliveries and, to a lesser extent, in vaginal deliveries. The specific effect size varies widely by delivery type and is unclear given the poor sensitivity of the data set for the maternal transfusion primary outcome.

Research Support

Supported by grant No. R21 MD016414 from the National Institute on Minority Health and Health Disparities, National Institutes of Health (Bethesda, Maryland), to Dr. Guglielminotti.

Competing Interests

Dr. Friedman is supported by grant No. R01 HD104943 from the National Institute of Child Health and Human Development (Rockville, Maryland) not related to this study and has served on an advisory board for Sage (Cambridge, Massachusetts) and Biogen (Cambridge, Massachusetts). Dr. Landau was a consultant for Pacira Pharmaceuticals Incorporated (Troy Hills, New Jersey) and serves on the editorial board of the journal Regional Anesthesia and Pain Medicine. Dr. Guglielminotti is supported by grant No. R01 MD018410 from the National Institute on Minority Health and Health Disparities, National Institutes of Health (Bethesda, Maryland), and grant No. R21 MH126096 from the National Institute of Mental Health, National Institutes of Health. These grants are not related to the published study. The other authors declare no competing interests.

Supplemental Tables, https://links.lww.com/ALN/D284

Table 1. Definition of intrapartum cesarean deliveries

Table 2. Variables included in the propensity score

Table 3. Hospital state of delivery

Table 4. Balance after inverse propensity score weighting

Table 5. Subgroups analyses

1.
Anim-Somuah
M
,
Smyth
RM
,
Cyna
AM
,
Cuthbert
A
:
Epidural versus non-epidural or no analgesia for pain management in labour.
Cochrane Database Syst Rev
2018
;
2018
:
CD000331
2.
Butwick
AJ
,
Bentley
J
,
Wong
CA
,
Snowden
JM
,
Sun
E
,
Guo
N
:
United States state-level variation in the use of neuraxial analgesia during labor for pregnant women.
JAMA Netw Open
2018
;
1
:
e186567
3.
Kilpatrick
SK
,
Ecker
JL
;
American College of Obstetricians and Gynecologists and the Society for Maternal–Fetal Medicine
:
Severe maternal morbidity: Screening and review.
Am J Obstet Gynecol
2016
;
215
:
B17
22
4.
Driessen
M
,
Bouvier-Colle
MH
,
Dupont
C
,
Khoshnood
B
,
Rudigoz
RC
,
Deneux-Tharaux
C
,
Pithagore
G
:
Postpartum hemorrhage resulting from uterine atony after vaginal delivery: Factors associated with severity.
Obstet Gynecol
2011
;
117
:
21
31
5.
Guglielminotti
J
,
Landau
R
,
Daw
J
,
Friedman
AM
,
Chihuri
S
,
Li
G
:
Use of labor neuraxial analgesia for vaginal delivery and severe maternal morbidity.
JAMA Netw Open
2022
;
5
:
e220137
6.
Maternal Mortality Review Committees
:
Building U.S. capacity to review and prevent maternal deaths: Report from nine maternal mortality review committee.
Available at: https://stacks.cdc.gov/view/cdc/51660. Accessed February 17, 2023
.
7.
Trost
S
,
Beauregard
J
,
Chandra
G
,
Njie
F
,
Berry
J
,
Harvey
A
,
Goodman
DA
.
Pregnancy-related deaths: Data from Maternal Mortality Review Committees in 36 US states, 2017–2019.
.
8.
Bienstock
JL
,
Eke
AC
,
Hueppchen
NA
:
Postpartum hemorrhage.
N Engl J Med
2021
;
384
:
1635
45
9.
Corbetta-Rastelli
CM
,
Friedman
AM
,
Sobhani
NC
,
Arditi
B
,
Goffman
D
,
Wen
T
:
Postpartum hemorrhage trends and outcomes in the United States, 2000–2019.
Obstet Gynecol
2023
;
141
:
152
61
10.
Thurn
L
,
Wikman
A
,
Westgren
M
,
Lindqvist
PG
:
Incidence and risk factors of transfusion reactions in postpartum blood transfusions.
Blood Adv
2019
;
3
:
2298
306
11.
Chang
CC
,
Wang
IT
,
Chen
YH
,
Lin
HC
:
Anesthetic management as a risk factor for postpartum hemorrhage after cesarean deliveries.
Am J Obstet Gynecol
2011
;
205
:
462.e1
7
12.
Butwick
AJ
,
Ramachandran
B
,
Hegde
P
,
Riley
ET
,
El-Sayed
YY
,
Nelson
LM
:
Risk factors for severe postpartum hemorrhage after cesarean delivery: Case-control studies.
Anesth Analg
2017
;
125
:
523
32
13.
Guglielminotti
J
,
Landau
R
,
Li
G
:
Adverse events and factors associated with potentially avoidable use of general anesthesia in cesarean deliveries.
Anesthesiology
2019
;
130
:
912
22
14.
Centers for Disease Control and Prevention
:
U.S. standard certificate of live birth.
Available at: https://www.cdc.gov/nchs/data/dvs/birth11-03final-ACC.pdf. Accessed February 17, 2023
.
15.
Health Resources and Services Administration
:
Area Health Resources Files (AHRF). 2018–2019.
Available at: https://data.hrsa.gov/topics/health-workforce/ahrf. Accessed February 17, 2023
.
16.
National Center for Health Statistics
:
Guide to completing the facility worksheets for the certificate of live birth and report of fetal death.
.
17.
Martin
JA
,
Wilson
EC
,
Osterman
MJ
,
Saadi
EW
,
Sutton
SR
,
Hamilton
BE
:
Assessing the quality of medical and health data from the 2003 birth certificate revision: Results from two states.
Natl Vital Stat Rep
2013
;
62
:
1
19
18.
Gregory
ECW
,
Martin
JA
,
Argov
EL
,
Osterman
MJK
:
Assessing the quality of medical and health data from the 2003 birth certificate revision: Results from New York City.
Natl Vital Stat Rep
2019
;
68
:
1
20
19.
Luke
B
,
Brown
MB
,
Liu
CL
,
Diop
H
,
Stern
JE
:
Validation of severe maternal morbidity on the US certificate of live birth.
Epidemiology
2018
;
29
:
e31
2
20.
Hartenbach
EM
,
Kuo
HD
,
Greene
MZ
,
Shrider
EA
,
Antony
KM
,
Ehrenthal
DB
:
Peripartum blood transfusion among rural women in the United States.
Obstet Gynecol
2020
;
135
:
685
95
21.
Centers for Disease Control and Prevention
:
How does CDC identify severe maternal morbidity?
.
22.
Wheeler
SM
,
Bryant
AS
,
Bonney
EA
,
Howell
EA
;
Society for Maternal–Fetal Medicine
.
Society for Maternal–Fetal Medicine special statement: Race in maternal-fetal medicine research—Dispelling myths and taking an accurate, antiracist approach.
Am J Obstet Gynecol
2022
;
226
:
B13
22
23.
R Core Team
:
R: A language and environment for statistical computing.
R Foundation for Statistical Computing
,
Vienna, Austria
.
Available at: https://www.R-project.org/. Accessed February 17, 2023
.
24.
Austin
P
:
Using the standardized difference to compare the prevalence of a binary variable between two groups in observational research.
Commun Stat Simul Comput
2009
;
38
:
1228
34
25.
VanderWeele
TJ
,
Ding
P
:
Sensitivity analysis in observational research: Introducing the E-value.
Ann Intern Med
2017
;
167
:
268
74
26.
Demidenko
E
:
Sample size determination for logistic regression revisited.
Stat Med
2007
;
26
:
3385
97
27.
Agency for Healthcare Research and Quality
:
HCUP databases. Healthcare Cost and Utilization Project (HCUP).
. Accessed January 4, 2023.
28.
Fox
MP
,
MacLehose
RF
,
Lash
TL
:
Applying Quantitative Bias Analysis to Epidemiologic Data
, 2nd edition.
Cham
,
Springer Nature Switzerland AG
,
2021
29.
Pankiv
E
,
Yang
A
,
Aoyama
K
:
Neuraxial labor analgesia for vaginal delivery and severe maternal morbidity.
JAMA Netw Open
2022
;
5
:
e220142
30.
Mhyre
JM
,
D’Oria
R
,
Hameed
AB
,
Lappen
JR
,
Holley
SL
,
Hunter
SK
,
Jones
RL
,
King
JC
,
D’Alton
ME
:
The maternal early warning criteria: A proposal from the National Partnership for Maternal Safety.
Obstet Gynecol
2014
;
124
:
782
6
31.
Association of Women’s Health Obstetric Neonatal Nurses
:
Role of the registered nurse in the care of the pregnant woman receiving analgesia and anesthesia by catheter techniques.
Nurs Womens Health
2020
;
24
:
149
51