Changes in Pregnancy-Related Mortality Associated With the Coronavirus Disease 2019 (COVID-19) Pandemic in the United States

Abstract

OBJECTIVE: 

To examine pregnancy-related mortality ratios before (January 2019–March 2020) and during (April 2020–December 2020 and 2021) the coronavirus disease 2019 (COVID-19) pandemic overall, by race and ethnicity, and by rural–urban classifications using vital records data.

METHODS: 

Mortality and natality data (2019–2021) were obtained from the Centers for Disease Control and Prevention’s WONDER database to estimate pregnancy-related mortality ratios, which correspond to any death during pregnancy or up to 1 year after the end of a pregnancy from causes related to the pregnancy per 100,000 live births. Pregnancy-related mortality ratios were determined from International Classification of Diseases, Tenth Revision codes A34, O00–O96, and O98–O99. Overall pregnancy-related mortality ratios were partitioned by whether COVID-19 was listed as a contributory cause, and quarterly estimates were compared between 2019 and 2021. Pregnancy-related mortality ratios were compared by race and ethnicity and rural–urban residence before (2019–March 2020) and during (April 2020–December 2020 and 2021) the COVID-19 pandemic.

RESULTS: 

Pregnancy-related mortality was significantly higher in 2021 (45.5/100,000 live births) compared with during the pandemic in 2020 (36.7/100,000 live births) and before the pandemic (29.0/100,000 live births). Pregnancy-related mortality ratios increased across all race and ethnicity and rural–urban residence categories in 2021. The largest increase occurred among American Indian/Alaska Native people during 2021 compared with April–December of 2020 (pregnancy-related mortality ratio 160.8 vs 79.0/100,000 live births, 104% relative change, P=.017). Medium–small metropolitan (52.4 vs 37.7/100,000 live births, 39.0% relative change, P<.001) and rural (56.2 vs 46.5/100,000 live births, 21.0% relative change, P=.05) areas had a larger increase in 2021 compared with April–December 2020 compared with large urban areas (39.1 vs 33.7/100,000 live births, 15.9% relative change, P=.009).

CONCLUSION: 

Pregnancy-related mortality ratios increased more rapidly in 2021 than in 2020, consistent with rising rates of COVID-19–associated mortality among women of reproductive age. This further exacerbated racial and ethnic disparities, especially among American Indian/Alaska Native birthing people.

In Brief

Pregnancy-related mortality ratios rose substantially in 2021, with increases corresponding with a concurrent listing of coronavirus disease 2019 (COVID-19) on the death certificate.

In 2020, the United States reported a pandemic-specific rate of 25.1 maternal deaths and 11.6 late maternal deaths per 100,000 live births, a 33% and 41% relative increase over prepandemic years, respectively.¹ Studies indicate that unvaccinated pregnant people are more likely to develop severe coronavirus disease 2019 (COVID-19) illness.^2–4 During the early period of the COVID-19 pandemic, the health of birthing and postpartum people may also have been indirectly affected, because this period of transition resulted in changes in prenatal care delivery and utilization,^5,6 access to a birthing partner at delivery,^7,8 and general isolation from traditional sources of postpartum health care and social support.^9,10

However, questions remained regarding the continued effect of the pandemic on pregnant and postpartum people in 2021, when vaccines became widely available.^11,12 The latter part of 2021 also saw the emergence of more transmissible severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants.¹¹ Using 2019–2021 mortality data, we compared pregnancy-related mortality ratios between 2019 and 2021. We further compared detailed race and ethnicity and rural–urban residence categories before (January 2019–March 2020) and during (April 2020–December 2020 and 2021) the COVID-19 pandemic.

METHODS

Publicly available mortality and natality data were obtained from the Centers for Disease Control and Prevention’s WONDER database for data years 2019–2021,¹³ which determined numerators (deaths) and denominators (births). This study was exempt from review under the United States Department of Health and Human Services regulation for secondary data analysis. We applied the Centers for Disease Control and Prevention’s definition of pregnancy-related death: “…the death of a woman while pregnant or within 1 year of the end of pregnancy from any cause related to or aggravated by the pregnancy.”¹⁴ This definition was operationalized using International Classification of Diseases, Tenth Revision (ICD-10) codes that correspond to both the cause and timing (pregnancy, childbirth, and the puerperium) in which the death occurred. Therefore, we combined maternal deaths (deaths during pregnancy or within 42 days of the end of pregnancy; ICD-10 codes A34, O00–O95, O98–O99) and late maternal deaths (deaths 43 days to 1 year after the end of pregnancy; ICD-10 code O96) to determine the numerator.

Although the National Center for Health Statistics (NCHS) typically reports only maternal mortality ratios, we examined the broader pregnancy-related mortality ratio measure, because it is increasingly recognized that the risk of pregnancy-related causes of death remains elevated in the first year postpartum and our prior research showed that both maternal and late maternal deaths increased during the start of the COVID-19 pandemic in 2020.^1,15 Consistent with NCHS¹⁶ and World Health Organization guidelines,¹⁷ a COVID-19 cause code (U07.1) would not be listed as an underlying cause of a pregnancy-related death. Therefore, COVID-19 was ascertained as a contributory cause from the multiple causes of death data file.

Pregnancy-related mortality ratios and 95% CIs were calculated as the number of pregnancy-related deaths per 100,000 live births. We examined pregnancy-related mortality ratio by quarter (quarter 1: January–March; quarter 2: April–June; quarter 3: July–September; quarter 4: October–December) and partitioned by whether the death included a COVID-19 contributory cause or not. Next, pregnancy-related mortality ratios were assessed by race and ethnicity and rural–urban residence before (2019–quarter 1 of 2020) and during (quarter 2–quarter 4 of 2020 and 2021) the pandemic. Race and ethnicity was classified as Hispanic (all races) and non-Hispanic Black, American Indian/Alaska Native, Asian, or White. Six rural–urban residence categories were collapsed to three to ensure reliable estimates: large urban (large central, large fringe metropolitan), medium–small urban (medium, small metropolitan), or rural (micropolitan, noncore areas).

To assess patterns in pregnancy-related mortality ratios relative to overall COVID-19 cases, supplementary analyses examined 3-month moving averages of monthly pregnancy-related mortality ratios plotted along with monthly COVID-19 deaths among women of reproductive age (15–44 years).¹³ Additionally, we partitioned the pregnancy-related mortality ratio into maternal and late maternal mortality ratios with and without a COVID-19 contributory cause and compared these ratios by prepandemic and pandemic time periods. Given smaller numbers among American Indian/Alaska Native birthing people, we wanted to assess the robustness of trends after including an additional prepandemic year (2018) and combined pandemic years (quarter 2–quarter 4 of 2020 and 2021) into one group and compared annual change between data years. All pregnancy-related mortality ratios and maternal and late maternal mortality ratios reported in this study met standards of reliability (numerator at least 16 deaths) consistent with prior analyses.^1,18 Differences were assessed by z-tests of proportions (P<.05 was considered statistically significant) and computed using Stata 16.1.

RESULTS

The pregnancy-related mortality ratio increased 26% between quarter 1 and quarter 2 of 2020 (30.3/100,000 live births vs 38.3/100,000 live births, P=.004) (Fig. 1). Pregnancy-related mortality ratios remained around this level from quarter 3 of 2020 through quarter 2 of 2021 (range 35.6–38.6/100,000 live births). Pregnancy-related mortality ratios rose to 56.9 per 100,000 live births in quarter 3 of 2021 and remained high in quarter 4 of 2021 (49.1/100,000 live births), which was a significant increase from the same respective quarters in 2020 (quarter 3: 36.2/100,000 live births, P<.001; quarter 4: 35.6/100,000 live births, P<.001). The pregnancy-related mortality ratio without a COVID-19 contributory cause remained fairly consistent with prepandemic levels for each quarter, ranging from a peak of 33.1 per 100,000 live births in quarter 2 of 2020 to a nadir of 29.6 per 100,000 live births in quarter 3 of 2021. Monthly pregnancy-related mortality ratios mirrored patterns for overall COVID-19 mortality among women of reproductive age, particularly in the surge in deaths in the latter part (quarter 3–quarter 4) of 2021 (Appendix 1, available online at https://links.lww.com/AOG/D112).

Fig. 1.: Quarterly pregnancy-related mortality ratios by coronavirus disease 2019 (COVID-19) contributory cause, 2019–2021, United States. Q, quarter.

When stratified by race and ethnicity, the pregnancy-related mortality ratio was higher overall during each year of the COVID-19 pandemic than before the pandemic for all race and ethnicity groups (Fig. 2) (Appendix 2, available online at https://links.lww.com/AOG/D112). Although American Indian/Alaska Native birthing people experienced a nonsignificant increase in pregnancy-related mortality ratio from prepandemic to 2020, they had the highest increase in pregnancy-related mortality ratio in 2021 (160.8/100,000 live births) compared with the earlier period of the pandemic (quarter 2–quarter 4 of 2020: 79.0/100,000 live births, P=.017), corresponding to a doubling of the pregnancy-related mortality ratio (absolute change: 81.8/100,000 live births, 104% relative change). This trend remained after the inclusion of 2018 to the prepandemic group and combining all pandemic time periods (60.9/100,000 live births before the pandemic vs 125.0/100,000 live births during the pandemic, P<.001) to assess the sensitivity of estimates due to small numbers among American Indian/Alaska Native individuals (data not shown).

Fig. 2.: Pregnancy-related mortality ratios by race and ethnicity during vs before the coronavirus disease 2019 (COVID-19) pandemic, 2019–2021, United States. Race and ethnicity categories are single-race categories. All race categories are non-Hispanic origin. Hispanic origin includes all races.

Among remaining racial and ethnic groups, comparing prepandemic pregnancy-related mortality with that in 2020 (quarter 2–quarter 4), non-Hispanic Black birthing people had the largest absolute increase (81.2 vs 97.7/100,000 live births, P=.009, 20.3% relative change) and Hispanic birthing people had the largest relative increase (19.3 vs 29.8/100,000 live births, 54% relative change, P<.001) (Fig. 2) (Appendix 2, https://links.lww.com/AOG/D112). Comparing 2020 (quarter 2–quarter 4) with 2021 rates, non-Hispanic Black had the largest absolute increase (16.5/100,000 live births; P=.009) and Hispanic birthing people had the largest relative increase (34% P=.001). Non-Hispanic White birthing people experienced a statistically significant increase across both periods, but much smaller absolute and relative changes; non-Hispanic Asian birthing people experienced non–statistically significant increases across both time periods (Appendix 2, https://links.lww.com/AOG/D112).

Pregnancy-related mortality ratios increased during the pandemic for all rural–urban residence categories (Fig. 3). Large urban areas had the highest absolute and relative increase comparing prepandemic and early pandemic (quarter 2–quarter 4 of 2020) periods (25.3 vs 33.7/100,000 live births, respectively, P<.001, 33.3% relative change) (Fig. 3) (Appendix 2, https://links.lww.com/AOG/D112). In contrast, medium–small metropolitan (37.7 vs 52.4/100,000 live births, P<.001, 39% relative change) and rural areas (46.5 vs 56.2/100,000 live births, P=.05; 21% relative change) had larger increases in pregnancy-related mortality ratios between quarter 2–quarter 4 of 2020 and 2021 (Fig. 3) (Appendix 2, https://links.lww.com/AOG/D112).

Fig. 3.: Pregnancy-related mortality ratios by rural–urban residence during vs before the coronavirus disease 2019 (COVID-19) pandemic, 2019–2021, United States. Six rural–urban residence categories were collapsed to three to ensure reliable estimates: large urban (large central, large fringe metropolitan), medium and small urban (medium, small metropolitan), and rural (micropolitan, noncore areas).

To examine timing of deaths, pregnancy-related mortality ratios were partitioned into maternal and late maternal mortality ratios (Appendix 3, available online at https://links.lww.com/AOG/D112). Maternal deaths (during pregnancy or within 42 days from the end of pregnancy) made up a larger proportion of overall pregnancy-related deaths compared with late maternal deaths (43 days–1 year from the end of pregnancy). Maternal mortality ratios increased significantly across each time period from prepandemic (20.1/100,000 live births), pandemic 2020 (25.1/100,000 live births, P<.001), and pandemic 2021 (32.9/100,000 live births, P<.001). Late maternal mortality ratios also showed increasing ratios with each time period, but this was significant only when comparing early pandemic (2020) (11.6/100,000 live births) and prepandemic rates (8.9/100,000 live births, P<.001). No significant change was observed when comparing late maternal mortality ratios in 2021 with those in quarter 2–quarter 4 of 2020 (12.6 vs 11.6/100,000 live births, P=.25). Patterns of COVID-19 contributory causes for maternal and late maternal deaths were similar over time.

DISCUSSION

Pregnancy-related mortality increased during the pandemic, particularly after June 2021, which coincided with the introduction of the SARS-CoV-2 Delta variant in the United States.¹¹ Although we cannot isolate the role of COVID-19, the quarterly peaks in pregnancy-related mortality ratio coincided with a greater proportion of deaths listed with COVID-19 as a contributory cause. The pregnancy-related mortality ratio followed similar patterns to overall COVID-19 deaths among women of reproductive age in late summer of 2021. Prior research has shown that racial and ethnic disparities in maternal mortality and pregnancy-associated deaths were exacerbated early in the pandemic (2020).^1,19 Our findings show that these patterns intensified in 2021, with a particularly high pregnancy-related mortality ratio among American Indian/Alaska Native individuals, a group that experienced higher rates of overall COVID-19 mortality in 2021.²⁰ Medium–small metropolitan and rural areas also experienced a larger increase in pregnancy-related mortality ratio than was observed for large urban areas in 2021, reflecting a similar shift to nonurban areas seen for COVID-19 mortality in 2021.²¹

This research is subject to several limitations. Death certificate data are the primary source for reporting overall and cause-specific mortality statistics in the United States.²² Although death certificates have limitations, they remain a timely and critical source for understanding emerging trends and patterns and to inform public health programs. For pregnancy-related mortality, death certificates rely on a pregnancy checkbox for reporting pregnancy-related deaths.²³ Inclusion of a pregnancy checkbox on death certificates is recommended by the World Health Organization to address under-reporting of pregnancy on death certificates.²⁴ However, prior studies have documented over-reporting of deaths from pregnancy-related causes, particularly among deaths in women aged 45 years or older.^25,26 To account for this misclassification, the NCHS revised their coding of these deaths to rely only on the written text on the death certificate for female decedents aged 45 years or older and the pregnancy checkbox for deaths among females younger than age 45 years.²⁷ Our analyses rely on data collected after the implementation of this correction.

Other data sources in the United States also report pregnancy-related mortality; however, these data sources are not publicly available and currently have not provided data after 2018.^14,28 Additionally, a listing of COVID-19 as a contributory cause on the death certificate may be under-reported, particularly earlier in the pandemic due to the unavailability or inaccuracy of testing. National Center for Health Statistics guidance indicates that, if the death certificate indicated “probable” or “likely” COVID-19, a U07.1 ICD-10 code would still be used.²⁹ Small numbers further limit exploration of COVID-19 as a contributory cause in some subgroups.

Finally, reporting of race and ethnicity on death certificates may be misclassified, particularly for American Indian/Alaska Native decedents.³⁰ Because of small numbers, we were unable to correct for potential misclassification.³¹ Given that misclassification is considered to be relatively constant over time,³⁰ this would be an unlikely explanation for the changes in 2021. Although all rates presented met reliability standards, pregnancy-related mortality ratios among American Indian/Alaska Native birthing people may also be subject to random variability due to small numbers. Our sensitivity analysis combining data years to ensure more reliable estimates showed that this pattern remained substantial and statistically significant. Continued surveillance in 2022 and focused intervention to mitigate concerning trends in pregnancy-related mortality are needed.

In summary, pregnancy-related mortality ratios increased more rapidly in 2021 than in 2020, consistent with rising rates of COVID-19–associated mortality among women of reproductive age. This further exacerbated racial and ethnic disparities, especially among American Indian/Alaska Native birthing people.