Keywords
maternal morbidity - clusters - hypertensive disorders of pregnancy - depression
Severe maternal morbidity (SMM) is a set of heterogeneous conditions that pose a high
risk for adverse effects on maternal health, including death.[1] Despite ongoing improvements in obstetric care, SMM cases have risen 75% in the
last decade in the United States, affecting more than 50,000 individuals annually.[2] The classical single-disease paradigm might not be adequate for people who experience
heterogeneous SMM events. Therefore, understanding clusters of SMM remains key to
accurately identify cases and to guide research and clinical efforts to reduce maternal
morbidity.
Using administrative data, prior clinical approaches have clustered SMM by the number
of SMM Centers for Disease Control (CDC) indicators, surgical or anesthesia complications,
and other events.[3]
[4] True SMM cases are those determined by physician adjudication and chart review;
however, this is labor-intensive and not efficient for large-scale SMM surveillance.
To address these limitations in diagnosing SMM, we take a data-driven approach to
identify clinically interpretable clusters of SMM from a larger collection of related
conditions that may be linked to underlying disease burden and thus may offer a novel
approach to surveil and understand SMM cases.
Latent class analysis (LCA) is a statistical method used to identify hidden subgroups
within a population. In clinical research, LCA can help finding distinct groups of
patients who share similar characteristics or behaviors, even when these groups are
not obvious. LCA methods have been widely used in social sciences and clinical practice,
for instance, in the identification of clusters of acute respiratory distress syndrome
and asthma that have distinct biological characteristics, outcomes, and implications
for treatment.[5]
[6]
[7] Therefore, LCA has several important features; it can support clinical interpretation
regarding the number of classes and their dominant features and through model fit
statistics inform the appropriate number of classes.
Notably, it is unknown whether clusters exist for SMM. The present study addressed
this gap by conducting an LCA of SMM indicators. We hypothesized that people with
SMM exhibit a few distinct clusters that may help identify SMM cases. These efforts
may yield clinically meaningful clusters to facilitate the development of strategies
to reduce rates and complement existing SMM surveillance tools.
Materials and Methods
Study Design, Population, and Setting
We included people who delivered (livebirth and stillbirth) at Magee-Women's Hospital
(MWH) from 2008 to 2017. MWH is a single tertiary care referral institution with nearly
11,000 deliveries per year, an obstetric and general intensive care unit (ICU) and
level III neonatal ICU (NICU). Delivery data were extracted from the electronic medical
records (EMR) after birth into the Magee Obstetric Maternal and Infant delivery (MOMI)
database. This study was approved by the University of Pittsburgh Institutional Review
Board (STUDY20050303); data were deidentified and no consent was required.
Maternal Characteristics and Comorbidities
From MOMI, we evaluated clinical comorbidities using the International Classification
of Diseases codes. Characteristics from the EMR included self-reported race (African-American
vs. Caucasian; other races were too few to analyze, [<5% of deliveries]), presence
of hypertensive disorders of pregnancy (HDP), gestational diabetes, substance abuse,
depression, Medicaid insurance coverage, and prepregnancy body mass index to classify
obesity status. To include markers of social determinants of health (SDH) not typically
found in the EMR, deliveries were linked to state birth records to categorize maternal
and partner education and the receipt of food assistance.
Severe Maternal Morbidity Indicators and Model Selection
We defined 23 SMM indicators during a delivery hospitalization as the presence of
any of the 21 CDC SMM conditions,[8] ICU admission during their delivery hospitalization,[4] or prolonged postpartum length of stay (PPLOS), defined as more than 3 standard
deviations above the mean PPLOS by mode of delivery.[9] Deliveries with SMM indicators were identified from the EMR, each delivery in our
database had one or more SMM indicators. We performed sensitivity analyses on the
stability of clustering without combinations of any blood transfusion, medical intensive
care unit (MICU), and PPLOS. To strengthen our results, we randomly selected 244 deliveries
across each of 5 years positively screened for SMM by 23 indicators for manual chart
review and physician adjudication (K.H.) following previously described methods[10] by the ACOG criteria of true SMM cases. We calculated the sensitivity of our screening
approach with administrative data. Although SMM can arise before and after delivery,
our study focused on events occurring during the delivery hospitalization consistent
with most SMM research using administrative data.
Maternal and Neonatal Outcomes
State mortality records were linked to MOMI, and outcomes were defined as maternal
death within 1 year after delivery and neonatal death within the first 28 days of
life; preterm delivery (<37 weeks of gestation) and severe preterm (<32 weeks of gestation);
small for gestational age (SGA) and severe SGA defined as birth weight <10th percentile and < 3rd percentile accounting for gestational age, respectively;[11] 5-minute Apgar scores <7; and admission to NICU at delivery hospitalization and
NICU stay of more than 48 hours.
Statistical Analysis
The 23 SMM indicators were considered as binary variables in the LCA models. Next,
we fitted a series of latent class models using deliveries that had one or more SMM
indicators. To determine the optimal number of SMM classes, we identified models with
the fewest clusters that are parsimonious, by identifying the model that generated
the minimum class membership >5% of SMM cases, low entropy, and high Bayesian information
criterion.[12]
[13]
Each SMM delivery was assigned to the latent class with the highest membership posterior
probability. Deliveries without SMM events were included in the SMM-free group. Once
we established the number of clusters (classes), maternal characteristics associated
with the derived SMM cluster were analyzed using descriptive statistics, a chi-square
test for categorical variables and analysis of variance for continuous variables as
appropriate. Using multinominal logistic regression, we then examined if a priori
variables such as HDP, gestational diabetes, depression, and SDH factors[14]
[15]
[16] were associated with the likelihood of the SMM clusters using the SMM-free group
as the reference. Next, we compared the proportions of maternal and neonatal outcomes
across the SMM cluster.
We labeled our classes based on the combination of SMM indicators with probabilities
of occurring >40% within the class. A p-value < 0.05 was considered significant. Statistical analyses were performed using
SAS software, version 9.4 and R (R Core Team, 2020), version 3.5.1.[17]
Results
Severe Maternal Morbidity Exposure and Maternal Characteristics
A total of 97,492 deliveries were evaluated. SMM events were identified in 2,666 deliveries
(2.7%). The most frequent SMM indicators were blood transfusion (46.1%), followed
by ICU admission (43.3%) and PPLOS (22.4%). The LCA model with four latent classes
achieved our selection criteria ([Supplementary Fig. S1], available in the online version). We examined the frequency of SMM indicators in
each class and the posterior probability of each indicator belonging to the SMM class
([Fig. 1] and [Supplementary Table S1], available in the online version).
Fig. 1 Probability of SMM indicators in each SMM cluster, Magee Obstetric Maternal and Infant
delivery database, 2008 to 2017. The latent classes and probabilities of each SMM
indicator were identified using latent class analysis. Labels for each cluster were
based on the combination of SMM indicators that have probabilities >40% within the
latent class. All (N = 97,492), Hemorrhage (N = 1,004), Critical Care (N = 748), Vascular (N = 654), Shock (N = 260). SMM, severe maternal morbidity.
Four SMM classes were labelled according to the SMM clinical features: Hemorrhage
(N = 1,004, 37.7%) by blood transfusions (81.5%) and sickle cell anemia (55.0%); Critical
Care (N = 748, 28.1%) by ICU admission (64.8%) and amniotic embolism (66.7%); Vascular (N = 654, 24.5%) by puerperal cerebrovascular disorders (77.8%), aneurysm (100.0%);
and Shock (N = 260, 9.8%) by shock (79.4%) and ventilatory support (81.0%), disseminated intravascular
coagulation (61.1%), and sepsis (47.8%).
All individuals with SMM were more likely to receive food assistance, have Medicaid
coverage, and to have high rates of HDP, gestational diabetes, and maternal comorbidities
than those SMM-free. There were, however, differences in some characteristics between
SMM clusters ([Table 1]). People in the Critical Care cluster had the highest frequency of HDP (63.6%) and
gestational diabetes (10.6%). The Shock cluster was noteworthy as it included people
with the highest frequencies of cardiopulmonary and neurological conditions. Additionally,
these people had the highest rates of less than high school education (46.5%) and
high rates of diagnosed depression (26.2%).
Table 1
Maternal characteristics of the derived severe maternal morbidity clusters, Magee
Obstetric Maternal and Infant delivery database, 2008 to 2017
|
Maternal characteristics[a]
|
All
|
SMM-free
|
SMM clusters
|
SMM free- SMM clusters
p-value
|
SMM clusters
P-value
|
|
|
Hemorrhage
|
Critical Care
|
Vascular
|
Shock
|
|
N = 97,492
|
N = 94,826
|
N = 1,004
|
N = 748
|
N = 654
|
N = 260
|
|
African-American
|
19,687 (20.2%)
|
18,885 (19.9%)
|
303 (30.2%)
|
211 (28.2%)
|
197 (30.1%)
|
91 (35.0%)
|
<0.001
|
0.2
|
|
Age, y
|
29 (6)
|
29 (6)
|
29 (6)
|
29 (6)
|
29 (6)
|
30 (6)
|
0.1
|
0.5
|
|
Prepregnancy BMI, kg/m2
|
26.1 (6.5)
|
26.0 (6.4)
|
27.3 (7.5)
|
29.2 (8.7)
|
28.1 (7.5)
|
28.6 (8.8)
|
<0.001
|
0.001
|
|
Parity
|
1.0 (1.3)
|
1.0 (1.2)
|
1.2 (1.6)
|
1.0 (1.4)
|
1.0 (1.5)
|
1.5 (1.9)
|
<0.001
|
<0.001
|
|
Gravida
|
2.4 (1.6)
|
2.4 (1.6)
|
2.7 (2.0)
|
2.5 (1.9)
|
2.7 (2.1)
|
3.2 (2.5)
|
<0.001
|
<0.001
|
|
Gestational age at delivery
|
39.2 (7.2)
|
39.3 (7.1)
|
38.6 (10.4)
|
36.2 (9.0)
|
37.2 (9.4)
|
36.2 (7.5)
|
<0.001
|
<0.001
|
|
HDP
|
15,516 (15.9%)
|
14,262 (15.0%)
|
347 (34.6%)
|
476 (63.6%)
|
316 (48.3%)
|
115 (44.2%)
|
<0.001
|
<0.001
|
|
Gestational diabetes
|
5,483 (5.6%)
|
5,268 (5.6%)
|
49 (7.5%)
|
79 (10.6%)
|
15 (5.8%)
|
72 (7.2%)
|
<0.001
|
0.02
|
|
Cesarean delivery
|
29,107 (29.9%)
|
27,494 (29.0%)
|
693 (69.0%)
|
438 (58.6%)
|
305 (46.6%)
|
177 (68.1%)
|
<0.001
|
<0.001
|
|
Smoking during pregnancy
|
11,198 (13.1%)
|
10,840 (13.1%)
|
124 (14.5%)
|
107 (16.5%)
|
95 (16.7%)
|
32 (14.7%)
|
<0.001
|
0.6
|
|
Maternal comorbidities
|
|
Neurological disease
|
2,052 (2.1%)
|
1,874 (2.0%)
|
43 (4.3%)
|
70 (9.4%)
|
40 (6.1%)
|
25 (9.6%)
|
<0.001
|
<0.001
|
|
Cardiovascular disease
|
966 (1.0%)
|
753 (0.8%)
|
32 (3.2%)
|
72 (9.6%)
|
66 (10.1%)
|
43 (16.5%)
|
<0.001
|
<0.001
|
|
Pulmonary disease
|
8,970 (9.2%)
|
8,475 (8.9%)
|
140 (13.9%)
|
138 (18.4%)
|
104 (15.9%)
|
113 (43.5%)
|
<0.001
|
<0.001
|
|
Substance abuse
|
3,683 (3.8%)
|
3,532 (3.7%)
|
44 (4.4%)
|
43 (5.7%)
|
45 (6.9%)
|
19 (7.3%)
|
<0.001
|
0.1
|
|
Depression
|
10,138 (10.4%)
|
9,629 (10.2%)
|
160 (15.9%)
|
172 (23.0%)
|
109 (16.7%)
|
68 (26.2%)
|
<0.001
|
<0.001
|
|
Social determinants of health characteristics
|
|
Food assistance
|
26,453 (29.5%)
|
25,608 (29.3%)
|
313 (35.6%)
|
241 (35.9%)
|
216 (36.8%)
|
75 (34.9%)
|
<0.001
|
1.0
|
|
Medicaid
|
35,030 (35.9%)
|
33,728 (35.6%)
|
465 (46.3%)
|
360 (48.1%)
|
336 (51.4%)
|
141 (54.2%)
|
<0.001
|
0.1
|
|
Mother education (<HS)
|
25,835 (28.8%)
|
24,914 (28.5%)
|
325 (37.0%)
|
279 (41.5%)
|
217 (37.0%)
|
100 (46.5%)
|
<0.001
|
0.03
|
|
Partner education (<HS)
|
24,159 (31.7%)
|
23,427 (31.5%)
|
263 (37.8%)
|
210 (43.7%)
|
190 (42.7%)
|
69 (43.7%)
|
<0.001
|
0.2
|
Abbreviations: BMI, body mass index; HDP, hypertensive disorders of pregnancy; SMM,
severe maternal morbidity; <HS, high school or less.
a Numbers provided are frequency (percent), mean (SD, standard deviation). A p-value of <0.05 is considered statistically significant.
After accounting for maternal and SDH characteristics, the occurrence of HDP was associated
with increased risk of all SMM clusters but was particularly high for the Critical
Care and Vascular groups (adjusted odds ratio [aOR]: 7.3 [95% confidence interval,
CI: 5.9–9.1]; 4.0 [95% CI: 3.2–4.9], respectively; [Table 2]). African-American race and maternal education were associated with membership in
the Hemorrhage cluster (aOR: 1.6 [95% CI: 1.3–2.0]; 1.3 [95% CI: 1.1–1.7]). Gestational
diabetes was associated with both the Critical Care and Vascular clusters. The risk
of belonging to the Shock cluster was particularly high for people with depression
(aOR: 2.7 [95% CI: 1.8–4.2) and Medicaid coverage (aOR: 1.9 [95% CI: 1.0–3.5]). Smoking
and receipt of food assistance were found to be associated with a lower likelihood
of membership in this group (aOR: 0.5, 0.6, respectively).
Table 2
Multivariable multinominal logistic regression analysis of the risk of severe maternal
morbidity clusters by maternal and socioeconomic characteristics[a], Magee Obstetric Maternal and Infant delivery database, 2008 to 2017
|
Maternal characteristics
|
Hemorrhage
|
Critical Care
|
Vascular
|
Shock
|
|
African-American vs. Caucasian
|
1.6
|
1.1
|
1.2
|
1.6
|
|
(1.3–2.0)
|
(0.9–1.5)
|
(0.9–1.6)
|
(0.9–2.6)
|
|
Hypertensive disorder of pregnancy
|
2.1
|
7.3
|
4.0
|
3.0
|
|
(1.8–2.6)
|
(5.9–9.1)
|
(3.2–4.9)
|
(2.1–4.3)
|
|
Gestational diabetes
|
1.1
|
1.4
|
1.4
|
0.6
|
|
(0.8–1.6)
|
(1.0–2.0)
|
(1.0–2.0)
|
(0.3–1.5)
|
|
Smoking during pregnancy
|
0.8
|
1.1
|
0.9
|
0.5
|
|
(0.6–1.1)
|
(0.8–1.6)
|
(0.6–1.2)
|
(0.3–1.0)
|
|
Substance abuse
|
0.8
|
1.1
|
1.3
|
1.5
|
|
(0.5–1.4)
|
(0.6–1.8)
|
(0.7–2.2)
|
(0.8–3.1)
|
|
Depression
|
1.6
|
1.6
|
1.1
|
2.7
|
|
(1.3–2.1)
|
(1.2–2.1)
|
(0.8–1.6)
|
(1.8–4.2)
|
|
Mother education (<HS)
|
1.3
|
1.1
|
0.9
|
1.7
|
|
(1.1–1.7)
|
(0.9–1.5)
|
(0.7–1.2)
|
(0.9–2.9)
|
|
Partner education (<HS)
|
0.9
|
1.2
|
1.1
|
0.8
|
|
(0.7–1.1)
|
(0.9–1.5)
|
(0.9–1.4)
|
(0.5–1.4)
|
|
Food assistance
|
1.0
|
1.0
|
1.0
|
0.6
|
|
(0.8–1.3)
|
(0.7–1.3)
|
(0.7–1.2)
|
(0.3–0.9)
|
|
Medicaid
|
1.0
|
0.9
|
1.5
|
1.9
|
|
(0.7–1.2)
|
(0.6–1.2)
|
(1.2–2.0)
|
(1.0–3.5)
|
Abbreviations: SMM, severe maternal morbidity; <HS, high school or less.
a Estimates are exponentiated coefficients from a single multinomial regression analysis
for each SMM class. The dependent variable is a discrete variable with five distinct
values: (1) no SMM during the delivery hospitalization; (2) Hemorrhage; (3) Critical
Care; (4) Vascular; (5) Shock clusters. Independent variables included in the final
model were African-American race, hypertensive disorders of pregnancy, gestational
diabetes, mother and partner education less than high school, smoking history, substance
abuse, depression, food assistance, Medicaid, and gestational age. Values represent
odds ratios (95% confidence interval).
Association of Severe Maternal Morbidity Clusters with Maternal and Neonatal Outcomes
Maternal mortality within 1 year of delivery was 5 per 10,000 deliveries overall.
Individuals with SMM had a 12-fold increase in the odds of experiencing maternal mortality
compared with those SMM-free (odds ratio: 12.0, 95% CI: 6.2–23). Maternal and infant
mortality rates were high among people with SMM, regardless of the SMM cluster. When
comparing SMM clusters, neonates born to people in the Shock cluster had the highest
rates of low Apgar scores, NICU admission, and an NICU stay longer than 48 hours and
being delivered severely preterm, whereas those in the Critical Care cluster had higher
frequencies of SGA, severe SGA, and preterm birth ([Table 3]).
Table 3
Maternal and neonatal outcomes based on severe maternal morbidity clusters, Magee
Obstetric Maternal and Infant delivery database, 2008 to 2017
|
Clinical outcomes
|
All
|
SMM-free
|
Hemorrhage
|
Critical Care
|
Vascular
|
Shock
|
SMM free- SMM clusters
p-value
|
SMM clusters
p-value
|
|
N = 97,492
|
N = 94,826
|
N = 1,004
|
N = 748
|
N = 654
|
N = 260
|
|
Maternal outcomes
|
|
Preterm[a]
|
11,492 (11.8%)
|
10,330 (10.9%)
|
317 (31.6%)
|
426 (57.0%)
|
281 (43.0%)
|
138 (53.1%)
|
<0.001
|
<0.001
|
|
Severe preterm[b]
|
3,195 (3.3%)
|
2,724 (2.9%)
|
129 (12.8%)
|
171 (22.9%)
|
105 (16.1%)
|
66 (25.4%)
|
<0.001
|
<0.001
|
|
Maternal death[c] (per 10,000)
|
5
|
4
|
30
|
40
|
61
|
77
|
<0.001
|
0.71
|
|
Neonatal outcomes
|
|
Infant death[d]
|
468 (0.5%)
|
414 (0.4%)
|
22 (2.2%)
|
12 (1.6%)
|
13 (2.0%)
|
7 (2.7%)
|
<0.001
|
0.67
|
|
5-min Apgar < 7
|
1,724 (1.8%)
|
1,526 (1.7%)
|
58 (6.1%)
|
66 (9.2%)
|
40 (6.3%)
|
34 (14.9%)
|
<0.001
|
<0.001
|
|
NICU[e]
|
12,915 (13.2%)
|
11,853 (12.5%)
|
308 (30.7%)
|
355 (47.5%)
|
274 (41.9%)
|
125 (48.1%)
|
<0.001
|
<0.001
|
|
NICU > 48 h
|
2,2520 (23.1%)
|
21,165 (22.3%)
|
393 (39.1%)
|
451 (60.3%)
|
350 (53.5%)
|
161 (61.9%)
|
<0.001
|
<0.001
|
|
SGA[f]
|
10,394 (10.7%)
|
9,966 (10.5%)
|
113 (11.3%)
|
153 (20.5%)
|
126 (19.3%)
|
36 (13.9%)
|
<0.001
|
<0.001
|
|
Severe SGA[g]
|
2,980 (3.1%)
|
2,866 (3.0%)
|
24 (2.5%)
|
37 (5.2%)
|
41 (6.4%)
|
12 (5.1%)
|
<0.001
|
0.001
|
Abbreviations: NICU, neonatal intensive care unit; SGA, small for gestational age;
SMM, severe maternal morbidity.
a Preterm is defined as delivery at <37 weeks of gestation.
b Severe preterm as delivery <32 weeks of gestation.
c Maternal death is any death within the first year of delivery.
d Infant death is any death within the first 28 days of life.
e NICU admission and NICU > 48 hours represent those who had an NICU stay longer than
48 hours.
f SGA.
g Severe SGAs are defined as birth weight <10th percentile and <3rd percentile accounting
for gestational age, respectively. A p-value < 0.05 indicates statistical significance.
Validation of Severe Maternal Morbidity Screening Indicators and Latent Clustering
SMM cases screened by 23 indicators (MICU + PPLOS + 21 CDC SMM indicators) detected
64% true SMM cases. Screening for SMM using the CDC definition alone only detected
40% of true SMM cases.[9] This underscores that our study SMM definition criteria were able to detect SMM
cases at a higher rate ([Fig. 2A]).
Fig. 2 Sensitivity of SMM screening using electronic medical records and ACOG criteria.
(A) Sensitivity of detecting SMM deliveries using different combinations of screening
indicators. (B) Sensitivity across SMM clusters using a 23-indicator screening. The solid line indicates
the average sensitivity of a 23-indicator screen. Dashed line the average sensitivity
using only the 21 CDC SMM indicators. All adjudicated cases (N = 244), Hemorrhage (N = 95), Critical Care (N = 91), Vascular (N = 47), Shock (N = 24). ACOG, American College of Obstetricians and Gynecologists; CDC, Centers for
Disease Control; SMM, severe maternal morbidity.
Excluding any blood transfusion indicator from this screening definition for SMM reduces
the sensitivity to 49 and 20%, respectively. The proportions of true SMM cases according
to SMM clusters were also individually higher than the CDC criteria: Hemorrhage, 60%;
Critical Care, 70%; Vascular, 49%; and Shock, 100% ([Fig. 2B]).
We also performed sensitivity analyses restricted to the first pregnancy and including
the 21 CDC SMM indicators only ([Supplementary Table S2], available in the online version). Additionally, we fit an LCA model excluding deliveries
that only received blood transfusions without additional SMM indicator (N = 1,892), which stably identifies the Critical Care, Vascular, and Shock clusters
and excludes most of the cases from the Hemorrhage cluster ([Supplementary Fig. S2], available in the online version).
Discussion
We identified four distinct clusters of SMM using LCA based on the presence of 23
SMM indicators. Including MICU or prolonged length of stay to the 21 CDC indicators
increases sensitivity to detect true SMM. We report four SMM clusters: Hemorrhage,
Critical Care, Vascular, and Shock and examine main differences between SMM clusters
in terms of clinical and SDH characteristics. Social, structural, and clinical factors
appear to play a key role in the likelihood of experiencing SMM conditions, and therefore,
understanding how SMM indicators cluster—and their predictors—is vital to developing
new obstetric protocols targeting those at highest risk. Future research is needed
to assess long-term consequences in this population to determine those in need of
follow-up care.
In clinical practice, there is a need to develop robust and efficient protocols to
surveil SMM. Current SMM surveillance focuses mainly on administrative data. Our new
approach reveals a novel method of surveilling by using common diagnosis clustering
within single person rather than considering individual diagnosis independently. This
approach may improve health system approaches to identifying and examining SMM clusters
as part of obstetrical quality initiatives to improve the detection of true SMM cases
and design prevention and improvement strategies.
Although preliminary, underlying mechanisms could explain the clustering between the
SMM indicators. Pregnancy is considered a stress test that can unmask poor cardiovascular
physiology[18] affecting multiorgan systems. For that reason, those who clustered in the Vascular
group could have preexisting vascular problems such as endothelial dysfunction, arterial
stiffness, or subclinical atherosclerosis and share a common mechanism that predisposes
them to SMM. In support of this paradigm, several studies have reported biomarkers
(e.g., proangiogenic vascular endothelial growth factor) associated with generalized
endothelial dysfunction, resulting in hypertension, renal and cerebral endotheliosis.[19]
[20] Thus, identifying a set of SMM indicators in the clusters may lead to a better understanding
of clinical complexity in pregnancy and form a basis for considering targeted therapies.
In addition to examining classic obstetric comorbidities as SMM risk factors, we were
interested in evaluating depression as this is likely an important driver of SMM.
Perinatal mood disorders contribute to adverse maternal outcomes[21] and our results extend these findings and demonstrate that depression is an important
risk factor for SMM, especially cases in the Shock cluster, perhaps related to a proinflammatory
state.[21] Only 50% of pregnant individuals[22] receive treatment for depression pointing to another important clinical care opportunity
to address SMM risk.
We included the Critical Care cluster in our final analysis given the evidence that
45% of individuals who die in the peripartum period were admitted to the ICU.[4] Our data along with others reveal that HDP can contribute to up to 70% of ICU admissions,[3] perhaps due to the need for critical care management among hypertensive individuals
that can range from invasive monitoring to mechanical ventilation. We also report
that gestational diabetes was associated with an increased likelihood of assignment
to this cluster, emphasizing the importance of frequent monitoring to address lifestyle
modifications to improve outcomes among affected individuals. The reasons for ICU
admission, not available in our data, merit closer examination as they could help
identify underlying factors that likely contribute to this distinct cluster.[23]
[24]
Racial disparities in SMM events have been reported, with African-American individuals
experiencing higher rates of SMM events.[25] Our data indicated this may be especially true for events in the Hemorrhage cluster.
This is also consistent with a prior study reporting that African-American individuals
have a high risk of postpartum hemorrhage even when adjusting for comorbidities.[26] Race is a social construct and a proxy to measure racism; thus, this observed disparity
requires further evaluation of other factors at the institutional level, including
hospital quality, culture of leadership, use of evidence-based practices, patient
safety, and perceived racism and discrimination that might explain these findings.[22]
Our study evaluated additional SDH markers including education, food stability, and
access to affordable care.[27] While markers of disadvantage including lower maternal educational levels and Medicaid
insurance coverage were associated with SMM clusters in our data as in other studies,[28] individuals who smoked or needed food assistance were less likely to experience
SMM events in the Shock cluster. Our findings regarding smoking and food assistance
in this cluster are surprising. Food security could be enhanced via food assistance
perhaps providing some protection from SMM events, but this is speculative and warrants
further examination.
SMM events have been associated with adverse maternal and neonatal outcomes. Maternal
mortality in the United States was reported to be 32.9 per 100,000 live births in
2021, whereas our study observed a higher rate.[29] This can be explained by the time-frame of follow-up; we included all deaths within
1 year after delivery, whereas the CDC restricts to deaths while pregnant or within
42 days after pregnancy. In addition, our tertiary institution cares for people with
high-risk pregnancies and accepts referrals from other hospitals, and thus, rates
may be expected to be higher. Of note, rates of maternal death were high across all
SMM clusters, despite varying levels of alignment with adjudicated SMM cases.
Our study has strengths and limitations worth noting. Using a single-center cohort
may limit generalizability. However, this is the first study to our knowledge that
has grouped SMM indicators using an unbiased clustering approach. Although there is
evidence that the higher the number of SMM indicators the greater the likelihood of
maternal death,[4] our study expands this and distinguishes SMM clusters derived from patterns of these
indicators. We also evaluated risk factors and maternal and neonatal outcomes associated
with each cluster.
SMM indicators rely on administrative data, which are subject to miscoding and have
limited data granularity. For example, those who required ICU admission might have
needed different levels of ICU care ranging from telemetry to cardiopulmonary support,
and thus, true severity may vary. Similarly, any blood transfusion may not be considered
a true SMM marker; for instance, the ACOG considers transfusion SMM if ≥4 blood units
are given.[9] Despite these inherent limitations of using administrative data, we demonstrated
that our administrative database was able to identify true SMM cases (range: 49–100%).
We also observed elevated rates of maternal and infant mortality detected within each
SMM cluster compared with SMM-free deliveries, further demonstrating the increased
disease burden that these clusters carry. When removing blood transfusions without
additional SMM indicators, we robustly reproduced clusters aligned with Critical Care,
Vascular, and Shock.
The use of an administrative database that is only linked to the delivery hospitalization
limits the possibility of evaluating SMM before or after the delivery; therefore,
future studies should consider merging databases that include the full scope of maternity
care. Our study data were observational thus preventing our ability to identify casual
relationships. Diagnosis definitions have changed over time. For example, severe preeclampsia
coding began only in 2012, and it is possible that certain indicators were not considered
before that time and were undercaptured.
Conclusion
Our results offer a new approach to understanding SMM and demonstrate the importance
of comorbidities such as depression and SDH markers that amplify the well-established
risk factors such as HDP. The Shock cluster was found to be driven by disadvantage
and depression risk factors and SMM cases belonging to this class had the highest
odds of adverse neonatal outcomes. Our findings can inform future research on pathways
and patterns of risk amenable to intervention to prevent SMM and its devastating maternal
and infant consequences.
