1.1

Definitions and epidemiology

Several established terms help to standardize the reporting of maternal mortality ( Fig. 1 ).

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  Maternal death is defined by the World Health Organization (WHO) as the death of a woman from any cause related to or aggravated by pregnancy or its management while pregnant or within 42 days of termination of pregnancy, irrespective of the duration and site of the pregnancy [ ].

  
  
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  Late maternal deaths include deaths, from direct or indirect obstetric causes, more than 42 days but less than one year after termination of pregnancy [ ].

  
  
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  Direct maternal deaths (e.g., hypertensive disorders of pregnancy or postpartum hemorrhage) result from obstetric complications of the pregnant state, and from interventions, omissions, incorrect treatment, or from a chain of events resulting from any of the above [ ].

  
  
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  Indirect maternal deaths result from pre-existing disease or disease that developed during pregnancy and not due to direct obstetric causes but were aggravated by the physiologic effects of pregnancy [ ].

  
  
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  Pregnancy-associated deaths occur during pregnancy, at time of delivery, or within one year postpartum, regardless of the cause, location of pregnancy, or pregnancy outcome [ ].

  
  
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  Pregnancy-related deaths occur during pregnancy or up to one year after the end of pregnancy related to or aggravated by pregnancy and not from accidental or incidental causes [ ].

Common terms describing maternal mortality.

The maternal mortality ratio (MMR) is the number of maternal deaths during a given period per 100,00 live births during that same time period. The MMR allows comparison of deaths by region over a given time while accounting for differences in birth rates. While the MMR does not include late maternal deaths, late maternal death is an important contributor to maternal mortality [ ]. This terminology for maternal death allows for consistent classification of deaths that occur during pregnancy, childbirth, and the puerperium; however, the accuracy of such efforts has long been a challenge. In the US, there are currently 3 major systems of national surveillance (the National Vital Statistics System, NVSS; the Pregnancy-Related Mortality Surveillance System, PMSS; and Maternal Mortality Review Committees, MMRCs), each with inherent strengths and limitations ( Table 1 ) [ , ]. All of these government data sources rely on vital statistics data, but mortality estimates are then refined with different approaches to yield maternal mortality trends over time that are often inconsistent [ ]. For example, comparison of 2019 data extrapolated from the NVSS to PMSS, the MMR up to 42 days postpartum was 20.1 vs. 12.3 per 100,000 births (63.4% higher for NVSS), and the pregnancy-related mortality up to 1 year postpartum was 28.7 vs. 17.6 per 100,000 births (63.1% higher for NVSS) [ ]. Further accuracy in US maternal death capture and categorization is a public health priority.

1.2

Measuring trends in maternal mortality

Maternal mortality rate is thought to be underestimated, even in countries with strong reporting systems. Reporting errors can result from incomplete or misclassified data, but methodologies have been enhanced on a global scale to improve maternal mortality estimates [ ]. Globally, the maternal mortality ratio in 2020 was 223 per 100,000 live births. Between 2000 and 2020, global MMR overall fell by 34.3%, but most of the improvement occurred before 2015 propelled by the United Nations (UN) Millennium Development Goals agenda [ , ]. Progress was uneven, demonstrating substantial regional variation in MMR reduction. Eastern Europe and Southern Asia achieved the greatest overall percentage reduction of 70.1% and 67.5%, respectively, and Latin America and the Caribbean achieved the lowest reduction of 2.8%. Sub-Saharan Africa continues to bear the highest burden, with a MMR point estimate of 545 maternal deaths per 100,000 live births compared to 13 in Europe and Northern America [ ]. Notably, global reductions in MMR have stalled since 2015 in the context of myriad competing priorities and societal challenges faced by the UN Sustainable Development Goals program [ ]. Since 2016, the MMR has decreased in only 2 regions: central and South Asia, and Australia and New Zealand. MMR increased in Europe, North America, Latin America and the Caribbean, and all other regions of the world experienced stagnation in the MMR during this time [ , ].

In contrast to overall reductions in maternal mortality worldwide, the US has experienced rising rates over the past 3 decades. In 2021, there were 1205 maternal deaths, equating to an MMR of 32.9 deaths per 100,000 live births. This is an increase from 861 maternal deaths (MMR 23.8) in 2020 and 754 maternal deaths (MMR 20.1) in 2019 [ ]. Methods for identifying maternal deaths have been problematic, limited by misclassification and coding inaccuracies [ ]. The accuracy of rising mortality estimates in the US continues to be questioned, with an assertion that differences or overestimation in mortality estimates may stem from inaccurate, inconsistent use of a pregnancy checkbox on the death certificate and differential classification of pregnancy-relatedness [ , ]. While refining how maternal mortality is measured is an ongoing priority to direct public health and policy making efforts, current statistics underscore that mortality rates in the US are unacceptably high and exhibit significant racial and ethnic disparities [ ].

Mortality accounts for only a fraction of the burden of poor maternal outcomes. Both globally and in the US, the incidence of severe maternal morbidity (SMM) is orders of magnitude higher than mortality, and is increasing [ ]. For every maternal death, it is estimated that 20 or 30 more women experience morbidity, defined by the WHO as “any health condition attributed to and/or complicating pregnancy and childbirth that has a negative impact on the woman’s well-being and/or functioning.” [ ].

1.3

Etiologies

Causes and contributing factors of maternal morbidity and mortality are diverse and complex, and deaths can occur during pregnancy, delivery, or postpartum. A majority (52%) of all maternal deaths occur after delivery [ ]. In 2015, direct obstetric causes accounted for about 86% of all maternal deaths globally, led by hemorrhage and hypertensive disorders [ ]. In the US, over 82% of pregnancy related deaths in 2020 were attributed to 6 underlying causes: mental health conditions, cardiovascular conditions, infection, hemorrhage, embolism, and hypertension [ ]. The leading causes of pregnancy-related deaths overall and by race/ethnicity from 38 US states in 2020 are listed in Table 2 [ ]. Compared to a similar analysis of data from 2017 to 2019, mental health conditions continue to be the leading cause; death from cardiovascular, hypertensive, and infectious causes have increased, and stroke and hemorrhage-related deaths are lower [ , ].

Table 2

Causes of pregnancy-related deaths, overall and by race/ethnicity, from 38 US states, 2020.

 

1.4

Etiologies of maternal morbidity and mortality of relevance to the anesthesiologist

• a.
  

  Mental health conditions

Mental health conditions, including suicide or drug overdose or poisoning related to substance use disorder, are a leading cause of maternal death among high resourced countries [ , ]. One study suggests that maternal suicide-related MMR is 4.6 per 100,000 live births [ ], but experts suggest significant underestimation due to historical underreporting of deaths from self-harm and reporting methodology changes over time [ ]. Among women who died from self-harm, 35% had a documented psychiatric diagnosis of depression or anxiety, and nearly half discontinued medications [ ]. A majority of self-harm or suicide related deaths occur in the postpartum period [ , ], with peak incidence of self-harm-related mortality occurring 9–12 months postpartum [ , ]. Opioid-related deaths continue to rise in the US, and the most recent NCHS report of maternal overdose deaths from 2018 to 2021 shows the MMR tripled among pregnant and postpartum women aged 35–44 years [ ]. Most deaths occurred outside healthcare settings, underscoring the need for community outreach and postpartum psychosocial support. Risk factors for maternal suicide overlap with overdose related deaths and include major depression, substance use disorders, and intimate partner violence [ ]. Traumatic and painful birth experiences may cause significant psychosocial impairments postpartum, including depression and post-traumatic stress disorder [ ]. One systematic review identified labor pain and emergent CD as key risk factors for negative childbirth experiences [ ]. Anesthesiologists are often involved in the care of women experiencing complicated births and can play a crucial role in improving their childbirth experiences. The optimization of intrapartum and postpartum pain may have long-term sequelae for patients, particularly for those with opioid use disorder or chronic pain. General priorities for such at-risk populations are to optimize psychosocial well-being, explore non-opioid and nonpharmacologic analgesic methods, use opioids thoughtfully for breakthrough pain, monitor for respiratory depression and sedation, consider neuraxial adjuncts, and offer abdominal wall fascial plane blocks [ ].

• b.
  

  Cardiovascular disease

Cardiovascular disease (CVD) in pregnancy is an increasing contributor to maternal deaths, especially in high income countries. The increasing number of women with pregnancies during later reproductive years and women with congenital heart conditions reaching childbearing age as well as the increasing prevalence of maternal comorbid conditions such as obesity, diabetes, and hypertension have contributed to this rise [ ]. For women with CVD, the physiologic and hemodynamic stress of pregnancy and childbirth can lead to further complications, including serious or life-threatening complications. Many cardiac related deaths and serious cardiac complications are deemed preventable [ ]. Experts recommend cardiovascular screening, preconception counseling, education, risk stratification, and multidisciplinary care coordination to mitigate CVD-related complications for the cardio-obstetric patient [ ]. The American Heart Association has highlighted the importance of the obstetric anesthesiologist on a pregnancy heart team, an interdisciplinary group of specialists collaborating to develop individualized, coordinated peripartum care plans for women with CVD [ ].

• c.
  

  Infection and sepsis

Maternal sepsis remains a key contributor to morbidity and mortality worldwide. One retrospective study examining SMM occurring beyond delivery hospitalization suggests that sepsis was the top source of SMM during the postpartum period up to 1 year; focusing only on the delivery hospitalization period can miss over 80% of maternal sepsis cases [ ]. Mortality in severe sepsis and septic shock has been found to increase 7.6% for each hour delay in appropriate antibiotic treatment [ ]. Anesthesiologists must practice antibiotic stewardship, providing timely and targeted antibiotics to minimize maternal sepsis-related morbidity and mortality. Azithromycin administration may lower the risk of sepsis in women planning vaginal delivery (VD) or cesarean delivery (CD) but has not lowered mortality in US studies [ , ]. In an international meta-analysis, single-dose azithromycin intrapartum prior to VD or CD lowered maternal sepsis rate 1.1% compared to 1.7% in the placebo group; RR 0.66, 95% CI 0.56–0.77, but had no impact on mortality [ ]. Prioritizing patient-centered care is also paramount. A qualitative analysis of severe sepsis in pregnancy survivors identified themes of inadequate patient education about symptoms, atypical presentation, dismissal of concerns leading to delayed diagnosis, and challenges navigating long-term sequelae [ ].

In 2020 and 2021, COVID-19 increased risk for composite maternal morbidity and all-cause maternal mortality [ , ]. Pregnant patients with COVID-19 were more likely to be admitted to the hospital and intensive care unit (ICU) and require mechanical ventilation compared to non-pregnant COVID-19 patients, but pregnancy status was not associated with higher risk for mortality [ ]. The COVID-19 pandemic underscored that pregnant patients are vulnerable to SMM from critical illness outbreaks. Increased use in pregnancy of advanced critical care therapies including extracorporeal membrane oxygenation at specialized centers has yielded lower maternal mortality from critical illness [ ]. Timely transfer of critically ill pregnant patients to high-acuity centers for escalation of care is warranted.

• d.
  

  Postpartum hemorrhage

Postpartum hemorrhage (PPH) remains a dominant cause of maternal death and severe morbidity worldwide. In the US, the prevalence of PPH has increased over time, with uterine atony as the most common cause [ , ]. In a US database study, hemorrhage was the leading cause of maternal cardiac arrest during admission for delivery, with only 55.1% survival to hospital discharge [ ]. The need for massive blood transfusion, most commonly resulting from placenta accreta spectrum (PAS), uterine atony, placental abruption and coagulopathy, is strongly associated with severe morbidity and in-hospital death [ ]. Analyses in the United Kingdom (UK) and the US consistently demonstrate delayed recognition and management in the majority of PPH-related deaths [ , ]. Anesthesiologists can play a key role in reducing hemorrhage-related morbidity and mortality by prioritizing early detection, prompt and targeted treatment, and transfusion with correction of coagulopathy. Anesthesiologists can also lead efforts in implementing hemorrhage safety bundles, addressing compliance and barriers to implementation, and conducting quality improvement efforts [ , ]. Early consultation of patients with high-risk conditions such as suspected PAS, and multidisciplinary planning, should be coordinated by the anesthesiologist in anticipation of critical care surgery, appropriate staffing, and resources for PPH resuscitation [ ].

• e.
  

  Hypertensive disorders of p[regnancy

Hypertensive disorders of pregnancy, including preeclampsia, have risen in prevalence and remain significant contributors to maternal mortality [ ]. Hypertension (HTN)-related morbidity and mortality is potentially preventable with prompt recognition and early, aggressive treatment. In a contemporary cohort, women with severe intrapartum hypertension (SIH) received timely treatment (<60 min) in only 49% of cases, and experienced lower rates of SMM than those with delayed treatment (22.3% vs. 30.6%) [ ]. Use of a HTN management protocol, including integration of vital sign-triggered treatment prompts and algorithms in the electronic health record, can significantly reduce hypertension-related morbidity and mortality [ ]. Anesthesiologists can aid in prompt management of SIH with rapid-onset antihypertensive therapy and placement of arterial access for continuous monitoring and blood pressure control. An analysis of 8324 patients in 74 studies demonstrated that oral calcium channel blockers had greatest success, with further studies warranted for the serotonin HT2-receptor antagonist, ketanserin [ ]. Choice of antihypertensive medications should be guided by evolving literature, local medication formularies, presence of intravenous access, and patient acuity.

• f.
  

  Anesthesia-related complications

Anesthesia-related complications remain an exceedingly rare cause of SMM and mortality in high income countries. The most common risks include airway management, high neuraxial block, and unintentional dural puncture [ ]. An analysis identifying factors associated with difficult intubation yielded high body mass index, difficult airway exam features, and cervical spine limitations [ ]. In resource-limited countries, anesthesia is noted to be a major contributor to morbidity and mortality, accounting for up to 1 in 7 maternal deaths and related to a severe shortage of trained providers [ ]. Human and organizational failures leading to medication errors, such as inadvertent intrathecal tranexamic acid injection prior to CD, is a recently recognized source of anesthesia-related SMM and mortality that is entirely preventable [ ].

• g.
  

  Cesarean delivery

Cesarean delivery rates have increased worldwide, and patients undergoing CD compared to VD have higher rates of SMM due to its associated risks, including uterine rupture, abnormal placentation, and hysterectomy. Data from 154 countries covering 94.5% of world live births between 2010 and 2018 showed that 21.1% of women gave birth by CD, with high regional variability: 5% in sub-Saharan Africa up to 42.8% in Latin America, and global rates continue to increase [ ]. Contemporary CD rates in the US also increased from 32.1 to 32.4% from 2022 to 2023, despite a prior decline [ ]. Reducing CD rates is a public health priority but is not without risk; higher rates of trial of labor after cesarean (TOLAC) and higher overall VD has increased assisted VD [ ]. A 5-year report of 2192 assisted VDs yielded an SMM rate of 7.8–9.9% including 3rd and 4th degree lacerations and PPH [ ]. These conditions impact epidural utilization, anesthesiology staffing, and morbidity. Uterine rupture is the most significant complication associated with TOLAC, and can lead to severe maternal and perinatal morbidity and mortality [ ]. Anesthesiologists must remain vigilant to the frequency of epidural dosing and atypical pain in labor, as epidural dose escalation may be a clinical sign of impending uterine rupture [ ].

1.5

Disparities in maternal morbidity and mortality

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  Racial and ethnic disparities

Disparities in maternal healthcare remain unacceptably high. Rising rates of morbidity and mortality in the US and UK disproportionately affect women of racial and ethnic minority groups. Compared to non-Hispanic White (subsequently, White) women, non-Hispanic Black (subsequently, Black) women are significantly more likely to die from pregnancy-related causes. Between 2007 and 2014, Black women have had the fastest rise in maternal deaths in the US [ ]. A survey study nearly 20 years ago reported a MMR from preeclampsia, eclampsia, placental abruption, placenta previa, and PPH and found a 2.4–3.3-fold higher MMR for Black women compared to White women [ ]. Alarmingly, large racial disparities continue to persist today. Data from the US NVSS showed that the mortality rate for Black women decreased from 69.9 per 100,000 live births in 2021 to 49.5 deaths in 2022, but remained 2.6 times the rate for White women (19.9 in 2022, 26.6 in 2021) [ , ]. In the UK, a nearly 4-fold difference in mortality rates among Black compared to White women persisted between 2019 and 2021 [ ]. Preventable deaths may be higher among Black women (46–59% of deaths) compared to White women (9–33% of deaths) [ , ]. Higher MMR is also observed among Native American/Alaskan, Asian/Pacific Islander and certain subgroups of Hispanic women compared to White women [ ]. American Indian or Alaskan Native women are 2.5 times more likely to die from pregnancy-related causes compared to White women [ ]. In the UK, there is an almost 2-fold difference in mortality among non-Hispanic Asian women compared to White women [ ]. Race and ethnicity are also linked to different causes of pregnancy-related death ( Fig. 2 ).

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