In the United States, pregnant and birthing persons die at a higher rate (more than 20/100,000 live births) than in other high-income countries,1 and this rate has increased by an estimated 27% from 2000 to 2014.2 Reducing these deaths has thus become a public health and clinical priority, and substantial research, public health, and quality improvement efforts now focus on reducing the primary causes of pregnancy-related mortality, including hemorrhage, hypertension, and venous thromboembolism (Box 1).3–5 However, recent evidence from several states suggests that drug use (illicit or prescription), suicide, and homicide, which are not typically included in estimates of maternal or pregnancy-related mortality6—but which fall under the broader definition of pregnancy-associated (Box 1) mortality—are prevalent and increasing causes of death during pregnancy and the first year postpartum.7–12
To date, few national estimates of the burden of pregnancy-associated deaths due to drugs, suicide, or homicide exist. Wallace et al9 have provided some of the only national estimates of mortality during pregnancy and postpartum due to homicide, suicide, and injury using death certificates from 2005 to 2010, including a range of estimates adjusted for underreporting. Our objective was to estimate pregnancy-associated mortality ratios (ie, deaths/100,000 live births) in the United States overall and those attributable to drug use, suicide, and homicide from 2010 to 2019 and compare this with mortality among nonpregnant or postpartum females of reproductive age.
We used U.S. death certificate records from 2010 to 2019, with state identifiers obtained from the National Center for Health Statistics. We obtained the count of live births in each state for each year overall and by race and ethnicity from the Centers for Disease Control and Prevention WONDER database. Race was included in our study because prior research indicates substantial disparities in pregnancy-associated death by race and ethnicity.9,10 We emphasize that race is not a biological variable, but a social construct. To create a comparison group of females of reproductive age, we restricted our study population to deaths of people identified as female and between the ages of 15 and 44 years, acknowledging that we have excluded birthing persons identified as male on the death certificate. We included data from only those states (and the District of Columbia) that had adopted the 2003 Revised Death Certificate by January 1, 2010 (Arkansas, Arizona, Connecticut, Delaware, District of Columbia, Florida, Georgia, Idaho, Illinois, Indiana, Kansas, Michigan, Missouri, Montana, North Dakota, Nebraska, New Hampshire, New Jersey, New Mexico, Nevada, New York, Ohio, Oklahoma, Oregon, Rhode Island, South Carolina, South Dakota, Texas, Utah, Vermont, Washington, Wyoming) because the revised death certificate includes the standard pregnancy checkbox (see the next paragraph). To include as much of the U.S. birthing population as possible, we also included data from Maryland, where the unrevised death certificate was used throughout the study period and includes a pregnancy checkbox that identifies timing of death relative to pregnancy in the same way as the standard pregnancy checkbox, and California, where the unrevised death certificate asks only if the decedent was pregnant in the past year. Thus, we included data from 33 states plus the District of Columbia for a total of 28,856,437 live births.
We defined pregnancy-associated deaths as deaths during or within 1 year of pregnancy using two sources of information to capture as many pregnancy-associated deaths as possible. The 2003 Revised Death Certificate contains a standardized pregnancy checkbox that asks whether the decedent fell into one of the following categories: 1) not pregnant within past year, 2) not pregnant but pregnant within 42 days of death, 3) not pregnant but pregnant 43 days to 1 year before death, 4) pregnant at time of death, 5) unknown if pregnant within past year. We considered any death as “pregnancy-associated” if categories 2, 3, or 4 were checked. We also coded deaths with International Classification of Diseases, Tenth Revision (ICD-10) codes associated with death from obstetric causes (A34 [obstetric tetanus] and 000–099 [pregnancy, childbirth, and the puerperium]), including late maternal deaths, as pregnancy-associated death. We further classified pregnancy-associated death into causes of death based on ICD-10 codes indicating obstetric causes, drug-related causes (unintentional or of undetermined intent), suicide, homicide, and other causes (see Appendix 1, available online at https://links.lww.com/AOG/C548, for ICD-10 codes.). All remaining deaths of females aged 15–44 years were considered not pregnant or postpartum.
We categorized the race or ethnicity of the decedent as indicated on the death certificate into five groups, following the Office of Management and Budget classifications: non-Hispanic American Indian or Alaska Native, non-Hispanic Asian or Pacific Islander, non-Hispanic Black, Hispanic, non-Hispanic White. If the certificate indicated Hispanic ethnicity, the death was categorized as Hispanic, regardless of race or ethnicity.13 We also categorized age (younger than 20, 20–24, 25–29, 30–34, 35 years or older), educational attainment (less than high school, high school diploma, some college, Bachelor's degree or more, or unknown), and marital status (married or not married) of the decedent. Timing of pregnancy-associated death is reported using the pregnancy checkbox and was classified as: pregnant at the time of death, pregnant 1–42 days before death, or pregnant 43–365 days before death; the specific timing of pregnancy-associated death is not available for deaths in California. For obstetric deaths identified by ICD-10 code alone (ie, no pregnancy checkbox), we followed Wallace et al9 in classifying timing of these deaths using ICD-10 code when possible (Appendix 2, available online at https://links.lww.com/AOG/C548).
To compare pregnancy-associated death with death among females of reproductive age, we examined the number and proportion of all deaths stratified by whether the decedent was not pregnant or postpartum at the time of death, pregnant at the time of death, not pregnant at the time of death but pregnant within 42 days of death, pregnant within 43–365 days before death, or pregnant within 1 year of death but with unknown timing, overall and by age, race or ethnicity, educational attainment, marital status, and cause of death. These calculations excluded deaths in California, for which we did not have data on specific timing of death relative to pregnancy information.
We calculated the pregnancy-associated death ratio by year for each cause and generated 95% CIs for pregnancy-associated death ratios assuming a χ2 distribution:
To compare pregnancy-associated death ratios at the start of the study period (2010) to the end (2019), we used the incidence rate (ir) command in Stata to calculate rate ratios (RRs) and 95% CIs.
We also calculated the proportion of deaths due to drug-related causes, suicide, homicides, and obstetric causes occurring during pregnancy, in the first 42 days postpartum, and within 43–365 days postpartum. We then calculated the number of pregnancy-associated deaths and pregnancy-associated death ratios by age category and race or ethnicity, as prior research indicates substantial disparities in pregnancy-associated death by these factors.9,10 We calculated RRs and 95% CIs using the incidence rate command in Stata. We chose the referent group as the group with the largest number of births (ages 25–29 and non-Hispanic White).
To account for underreporting of pregnancy-associated death on the death certificate, we relied on one of the few published studies that quantifies the magnitude of underreporting by cause of death. Specifically, Horon and Cheng14 used Maryland death certificate data from 2001 to 2008 to combined with a comprehensive review of medical records and a linkage to birth and fetal death certificate to identify pregnancy-associated deaths due to a variety of causes. The authors then calculated the proportion of these pregnancy-associated deaths (overall and by cause) that were identified on the death certificate. The authors found that 35.1%, 42.9%, and 42.5% of pregnancy-associated deaths due to substance use, suicide, and homicide, respectively, were reported as such on the death certificate. We used these proportions (p) and built on the procedure developed by Wallace and colleagues9 to calculate the expected pregnancy-associated death ratio for drug-related deaths, suicide, and homicide, assuming that these proportions were applied to our data. We used the following equation, where p is the proportion of deaths due to cause identified from the death certificate alone and yields the expected number of “true” deaths due to cause if only of those deaths are marked as such on the death certificate.
We conducted robustness checks excluding the two states that did not adopt the 2003 Revised Death Certificate by January 1, 2010 (California and Maryland). We also conducted an analysis excluding women older than age 40 years, because prior research finds plausible overreporting of maternal deaths among this age group.15 Finally, we considered a definition of suicide in which we assigned ICD-10 codes Y10–Y19 (poisoning deaths of undetermined intent) as suicide instead of drug-related.
This research was approved by the Institutional Review Board at Michigan State University. Analyses were conducted using Stata MP.
We identified 11,782 pregnancy-associated deaths from 2010 to 2019 using U.S. death certificate data for all 33 states plus the District of Columbia. Of these deaths, 11,354 (96.4%) were identified using the pregnancy checkbox, and an additional 428 (3.6%) were identified using ICD-10 codes. The majority of deaths (6,561 or 55.7%) had both the pregnancy checkbox and an obstetric ICD-10 code.
Of people who died during pregnancy, 54.6% died due to maternal or obstetric causes, 10.5% due to drug-related causes, 4.9% due to suicide, and 8.0% due to homicide (Table 1 and Appendix 3, available online at https://links.lww.com/AOG/C548). In comparison, more than three quarters of deaths within 42 days postpartum were due to maternal or obstetric causes. During the late postpartum period (43–365 days postpartum), drug-related deaths and suicide made up 17.0% and 8.3%, respectively, of all deaths, compared with 16.5% and 8.1% of all deaths of females of reproductive age. Moreover, homicide accounted for 8.0% of all deaths during pregnancy and 5.9% of deaths in the late postpartum period, compared with 3.4% of deaths of females of reproductive age. The number and proportion of all deaths of females aged 15–44 years stratified by timing relative to pregnancy and by age, race or ethnicity, educational attainment, and marital status is presented in Appendix 2, https://links.lww.com/AOG/C548.
Of the 11,782 pregnancy-associated deaths from 2010 to 2019, 11.4% were due to drugs, 5.4% were due to suicide, and 5.4% were due to homicide, whereas 59.3% were due to obstetric causes and 18.5% were due to other causes (Table 2). For the entire period of 2010–2019, the pregnancy-associated death ratio due to drug-related causes was 4.7 per 100,000 live births (95% CI 4.4–4.9). For both suicide and homicide, the pregnancy-associated death ratio was 2.2 per 100,000 live births (Table 1) (95% CI 2.2–2.4 for both).
The pregnancy-associated death ratio due to drug-related causes rose 190%, from 2.7 per 100,000 in 2010 to 7.8 per 100,000 in 2019 (Fig. 1) (RR 2.9, 95% CI 2.2–3.8). The pregnancy-associated death ratio due to suicide increased approximately 30% from 2010 to 2019, from 1.9 per 100,000 to 2.5 per 100,000, but this increase was not statistically significant (RR 1.3, 95% CI 0.9–1.9). The homicide pregnancy-associated death ratio increased 63% (RR 1.6, 95% CI 1.1–2.3), from 1.8 per 100,000 to 3.0 per 100,000 in 2019.
For deaths due to drug-related causes, 34.3% occurred during pregnancy, 19.2% occurred in the first 42 days postpartum, and 46.4% occurred between 43 and 365 days postpartum. For deaths due to suicide, these percentages were 36.2, 12.9, and 50.9, respectively, and for homicides, the percentages were 56.8, 8.3, and 34.9. For obstetric causes of deaths, the percentages were 35.9, 35.0, and 26.1, with 3.4% having unknown timing (Fig. 2).
The pregnancy-associated death ratio for drug-related causes was highest among decedents identified as Non-Hispanic American Indian or Alaska Native (10.1/100,000), followed by Non-Hispanic White (7.2/100,000), and Non-Hispanic Black (3.4/100,000) (Table 3). The pregnancy-associated death ratio for suicide was also highest among decedents identified as non-Hispanic American Indian or Alaska Native (7.7/100,000), followed by Non-Hispanic White (2.8/100,000), and Non-Hispanic Asian and Pacific Islander (2.0/100,000). Homicide was most prevalent among Non-Hispanic Black decedents (7.0/100,000), followed by Non-Hispanic American Indian or Alaska Native (2.1/100,000).
Drug-related deaths were most common among people aged 35 years or older (6.1/100,000), followed by those aged 25–29 years (5.2/100,000) and those aged 20–24 and 30–34 years (4.3/100,000 (Table 3). Suicide was most common among people in the youngest age category (15–19 years, pregnancy-associated death ratio 3.5/100,000), followed by those aged 35 years or older (2.9/100,000) and those aged 20–24 years (2.4/100,000). The pregnancy-associated death ratio for homicide was highest among people aged 15–19 years (4.9/100,000), followed by those aged 20–24 years (3.7/100,000).
When applying the Horon and Cheng14 estimated proportion of “true” pregnancy-associated deaths identified by the death certificate to our data, we found that the pregnancy-associated death ratio per 100,000 for drug-related causes would be 13.0 (vs 4.7 in the observed data); for suicide, the pregnancy-associated death ratio would be 5.1 (vs 2.2); and for homicide, the pregnancy-associated death ratio would be 5.2 (vs 2.2) (Appendix 4, available online at https://links.lww.com/AOG/C548). If we add the misclassified deaths due to these causes to the total 11,782 deaths found based on the death certificate, there would be a total of 15,895 pregnancy-associated deaths. Of these, drug-related deaths would account for 23.6%, suicide for 9.3%, and homicide for 9.4%, compared with the percentages calculated from the observed data of 11.4, 5.4, and 5.4 (Table 2).
Compared with our main analyses, when we excluded California and Maryland, we found slightly higher pregnancy-associated death ratios due to drugs, suicide, and homicide, and when excluding women aged older than 40 years, we found slightly smaller pregnancy-associated death ratios for drug-related deaths, suicides, and homicides (Appendices 5 and 6, available online at https://links.lww.com/AOG/C548). When we assigned ICD-10 codes Y10–Y19 (poisoning deaths of undetermined intent) as suicide instead of drug-related, the pregnancy-associated mortality ratio due to suicide changed from 2.2 to 2.5 per 100,000 live births and the ratio due to drug-related causes changed from 4.7 to 4.4 per 100,000 live births (Appendix 7, available online at https://links.lww.com/AOG/C548).
Using U.S. death certificate records from 2010 to 2019 from 33 states and the District of Columbia, we found that drug-related deaths, suicide, and homicide accounted for 22.2% of all deaths during pregnancy and the first year after pregnancy (ie, pregnancy-associated death). All three causes of death increased over the study period, with drug-related pregnancy-associated death increasing 190%.
Approximately half of all drug-related and suicide deaths occurred between 6 weeks and 1 year postpartum and another 20% of drug-related deaths occurred during the first 6 weeks postpartum, consistent with reports from Utah8 and Massachusetts.12 Indeed, drug-related and suicide deaths account for a larger proportion of deaths between 43 and 365 days postpartum than among all deaths of females of reproductive age. The high risk of drug-related and suicide death in the late postpartum period may be due to lack of continuous postpartum care, lack of specialized mental health and substance use services, increasing stress of caring for a newborn, lack of structural supports (eg, stable housing), stigma or fear of punitive consequences, hormonal changes, and decreased tolerance after abstinence during pregnancy.16,17 Pregnancy-associated homicides, on the other hand, occurred disproportionately during pregnancy (56.8%), and homicide made up a substantially larger share of deaths during pregnancy (8.0%) than among all females of reproductive age (3.4%).
These data also demonstrate unacceptable racial and ethnic inequities in pregnancy-associated deaths. Pregnant and birthing people identified as American Indian or Alaska Native had much higher rates of drug-related death and suicide compared with all other racial or ethnic groups. Non-Hispanic White people had the second highest rates of pregnancy-associated drug and suicide death. Non-Hispanic Asian and Pacific Islander people, who had the lowest pregnancy-associated death ratio for both drug-related deaths and homicide, had the third highest ratio for suicide. Non-Hispanic Black people had disproportionately high pregnancy-associated death ratios due to homicide, consistent with data from 2005 to 2010.9 Pregnancy-associated drug-related deaths were most common among those aged 35 years or older, whereas suicide and homicide were most common among the youngest birthing people.
Our findings are consistent with those of Wallace et al,9 who used death certificate data from 2005 to 2010 and reported a pregnancy-associated suicide mortality ratio of 1.6 per 100,000 live births and a homicide ratio of 2.2 per 100,000 live births. Our study indicates that these pregnancy-associated death ratios have increased over time and in 2019 were 2.5 and 3.0, respectively. Our findings also comport with those of Gemmill et al,18 who identified increases in opioid-related deaths during pregnancy and postpartum using national death certificate data from 2010 to 2016, with particularly steep increases from 2014 to 2016. Our study builds on this previous research by using the most recent 10 years of national data available, by estimating mortality due to all drug types, and by examining disparities among multiple racial or ethnic and age groups and trends over time from 2010 to 2019, a key time period during which the United States experienced the Great Recession, declines in fertility rates,19 and an escalating opioid epidemic.20 Our findings are also congruent with those from in-depth maternal mortality reviews of pregnancy-related deaths conducted in 14 states,21 which found that pregnancy-related deaths due to mental health conditions were particularly common among non-Hispanic White people and during the late postpartum period. This study also found that 100% of these mental-health related deaths were considered preventable.21
We also demonstrate that the contribution of drug-related deaths, suicide, and homicide to overall pregnancy and postpartum mortality is likely much higher than our unadjusted estimates due to underuse of the pregnancy checkbox for these causes of death. After adjustment for underreporting, these deaths may account for more than 40% of all pregnancy-associated deaths (vs 22.2%). We note that the data used in this study were not collected explicitly for this purpose. Because only one study—using Maryland data from 2001 to 2008—has validated the death certificate against an in-depth review of pregnancy-associated deaths, estimates of underreporting are uncertain and underreporting remains a major barrier to producing valid estimates of the burden of these deaths nationwide. Another potential limitation is that some suicides may be misclassified as unintentional drug-related deaths. Indeed, the California Pregnancy Associated Mortality Review report found that about half of accidental deaths during pregnancy or postpartum were identified as suicides on review.22 Prior research also suggests potential underestimation and misclassification of overdose mortality, especially for deaths involving opioids.23,24 Thus, our analyses may underestimate the relative contribution of suicides and drug use to pregnancy-associated death. Overall, our findings are limited by inconsistent uptake of the 2003 Revised Death Certificate by states in the United States, resulting in our inclusion of only 33 states and D.C.
Our findings indicate that deaths due to drug-use, suicide, and homicide are a substantial and increasing contributor to pregnancy-associated mortality. Preventing these deaths could have saved the lives of more than 2,600 pregnant and birthing people from 2010 to 2019. Loss of these lives is particularly devastating to infants and families and has long-term repercussions on infants who lose their parent.25,26 Our findings point to the need to generate scientific evidence on risk factors and prevention approaches for pregnancy-associated death due to drugs, suicide, and homicide. Potential avenues include: 1) screening for substance use, suicidality, psychological distress, and intimate partner violence, which has been linked to both pregnancy-associated homicide and suicide,27 combined with the ability for health care professionals to connect people with resources28,29; 2) coordination of obstetric care with other areas such as addiction medicine, behavioral health, and social services30; and, perhaps most importantly, 3) attention to structural barriers to accessing care and support, including housing, transportation, child care, domestic abuse, stigma, and fear of legal ramifications or social service interventions.31
Definitions of Key Terms
Maternal death1: Female death from any cause related to or aggravated by pregnancy or its management (excluding accidental or incidental causes) during pregnancy and childbirth or within 42 days of termination of pregnancy, irrespective of the duration and site of the pregnancy.
Pregnancy-related death6: Death of a woman while pregnant or within 1 year of the end of a pregnancy from any cause related to or aggravated by the pregnancy or its management. Pregnancy-associated death6: Death of a woman while pregnant or within 1 year of the end of a pregnancy from any cause.
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