Abstract
Background:
Severe Maternal Morbidity (SMM) has increased in the United States by 45% in the last decade. While the recurrence of several adverse pregnancy outcomes from one pregnancy to the next has been established, the recurrence risk of SMM is unknown.
Objective:
To determine whether women who have SMM in a first pregnancy are at increased risk of SMM in their second pregnancy, compared to women who did not have SMM in their first pregnancy.
Methods:
This is a population-based study using linked vital statistics and hospital discharge records from the Office of Statewide Health Planning and Development in California from 1997 to 2012. The study population had their first two singleton births (live births or stillbirths) in California between 1997 and 2012 (n = 1,180,357). The primary exposure was SMM during the hospitalization at first birth and the primary outcome was SMM during the hospitalization at second birth. Prevalence and risk ratios of SMM at second birth were computed for women who did and did not have SMM at first birth, as well as for certain specific indicators of SMM.
Results:
Of the 1,180,357 women included in this analysis, 9088 (77 per 10,000 births) experienced SMM at first birth. Among these women, the prevalence of SMM at second birth was 470 per 10,000 births, compared to 68 per 10,000 births among women without SMM at first birth. This corresponded to an unadjusted risk ratio of 6.87 (95% CI 6.23, 7.57), which did not differ substantially when adjusted for factors known to be associated with SMM (6.46 [95% CI 5.86, 7.13]).
Conclusion:
Women experiencing SMM in their first pregnancy were at an approximately 6-fold increased risk of experience SMM in their second pregnancy.
Keywords: pregnancy outcome; pregnancy, high-risk; morbidity; pregnancy complications; maternal health
Background
In the United States, maternal mortality rates have increased by 25% in the last decade, from 18.8 in 2000 to 23.8 in 2014 (per 100,000 live births); this trend is in sharp contrast to falling global maternal mortality rates.1,2 Additionally, the rate of severe maternal morbidity (SMM), which includes life-threatening conditions such as hemorrhage, embolism, and stroke, has increased by 45% in the last decade, impacting 147 per 10,000 births in 2015.2,3
It is known that women who experience birth outcomes such as preterm birth, stillbirth, and small for gestational age, are at increased risk for the recurrence of these outcomes in a subsequent birth. 4–8 The recurrence of certain maternal outcomes such as preeclampsia or peripartum cardiomyopathy has also been established; although the risk of recurrence of several adverse maternal outcomes have yet to be investigated.9,10 Specifically, the risk of recurrence of SMM is unknown. Women who experience SMM are at increased risk of health problems such as hypertension, kidney failure, and heart failure after pregnancy.11 Therefore, it is possible that women who experience SMM in one birth are at increased risk of recurrent SMM.
To test this hypothesis, our objective was to determine whether women who have SMM in a first pregnancy are at increased risk of SMM in their second pregnancy, compared to women who did not have SMM in their first pregnancy.
Methods
Data
This population-based study used datasets from the California Office of Statewide Health Planning and Development (OSHPD) that include data from vital statistics and hospital discharge records from 1997 to 2012 that are linked across mothers who had multiple births during the time period.
Cohort Selection
Eligible patients had their first two singleton births (live births or stillbirths) in California between 1997 and 2012 (n = 1,180,357; Figure 1). Patients with unsuccessful linkage between vital statistics and hospital discharge records, and births from multi-fetal gestations were excluded. Births with gestational age <20 or >45 weeks were excluded due to concerns of inaccurate data enty.12
Figure 1.
Cohort Selection Process
Exposure and Outcome
The primary exposure was SMM during hospitalization at first birth, and the primary outcome was SMM during hospitalization at second birth. SMM is a composite outcome measured using a validated index developed by the CDC; the CDC index identifies births with complications qualifying as SMM using ICD-9-CM diagnosis and procedure codes corresponding to a list of 21 indicators outlined in eTable 1.13–16 Women who had a diagnosis or procedure code for at least one of these 21 indicators were considered to have experienced SMM. Transfusion codes may overestimate the prevalence of SMM when transfusion volume is unknown, and ICD-9-CM codes have no mechanism for quantifying the volume transfused.17 Therefore, we evaluated SMM with and without cases where blood transfusion was the only SMM indicator present.
Statistical Analysis
The prevalence of SMM at second birth was calculated for women who did and did not experience SMM at first birth. Additionally, we assessed the specific indicators of SMM as the exposure at first birth, with the outcome of the composite SMM index at second birth. Data are only presented for specific indicators of SMM at first birth that had least 15 births with SMM events at second birth; this cut-off is in agreement with OSHPD guidelines for maintaining confidentiality.
Risk ratios (RR) for recurrent SMM were computed using a modified Poisson regression model adjusted for the following factors known to be associated with SMM: maternal education level, payment type at birth, race/ethnicity, age at birth, and pre-pregnancy diabetes and hypertension, all reported for the first pregnancy.13 A directed acyclic graph of the causal relationships between study covariates can be found in the supplemental materials (eFigure 1). All analyses were performed in SAS 9.4 (Cary, NC).
Results
In total, 9088 women had SMM at first birth (77 per 10,000 births). Women who experienced SMM at first birth were more likely to have high school education or less; be publicly insured, non-Hispanic Black or Hispanic, and below 20 years of age at birth; and have pre-existing diabetes or hypertension, as compared to women who did not have SMM at first birth (Table 1).
Table 1.
Descriptive Characteristics of Women Who Did and Did Not Have SMM at First Birth: California, 1997-2012 (n = 1,180,357)
| Maternal Characteristicsa | Did not have SMM at First Birth (n = 1,171,269) |
Had SMM at First Birth (n = 9088) |
|---|---|---|
| n (%) | n (%) | |
| Education Level | ||
| High School or Less | 503,293 (42.9) | 4,429 (48.7) |
| Some College | 258,926 (22.1) | 1,985 (21.8) |
| Completed College | 385,316 (32.9) | 2,480 (27.3) |
| Missing | 23,734 (2.0) | 194 (2.1) |
| Payment Type | ||
| Government-Assisted | 389,476 (33.3) | 3,632 (39.9) |
| Private | 756,153 (64.6) | 5,224 (57.5) |
| Other/Missing | 25,640 (2.2) | 232 (2.6) |
| Race/Ethnicity | ||
| Non-Hispanic White | 464,954 (39.7) | 2,896 (31.9) |
| Non-Hispanic Black | 67,821 (5.8) | 738 (8.1) |
| Hispanic | 435,891 (37.2) | 3,977 (43.8) |
| Asian/Pacific Islander | 183,847 (14.6) | 1,330 (15.7) |
| Other/Missing | 18,756 (1.6) | 147 (1.6) |
| Age at Birth (years) | ||
| < 20 | 238,792 (20.4) | 2,277 (25.1) |
| 20-34 | 607,259 (51.9) | 4,430 (48.8) |
| 35-44 | 319,008 (27.3) | 2,318 (25.5) |
| ≥45 or Missing | 6,210 (0.5) | 63 (0.7) |
| Medical Comorbidity before First Pregnancy | ||
| Pre-Existing Diabetes | 19,516 (1.7) | 234 (2.6) |
| Pre-Existing Hypertension | 15,882 (1.4) | 304 (3.4) |
Descriptive characteristics are based on information from the first birth.
Abbreviations: SMM, severe maternal morbidity
Among women who had SMM at first birth, the prevalence of SMM at second birth was 470 per 10,000 births, compared to 68 per 10,000 births among women without SMM at first birth, corresponding to an unadjusted RR of 6.87 (95% CI 6.23, 7.57; Table 2). After adjusting for factors known to be associated with SMM, the RR was similar, 6.46 (95% CI 5.86, 7.13). Similar RRs were observed for SMM when we excluded blood transfusion only cases, with an unadjusted RR of 7.68 (95% CI 6.35, 9.30), and an adjusted RR of 7.18 (95% CI 5.92, 8.69).
Table 2.
Prevalence and Risk Ratios of SMM and its Specific Indicators per 10,000 Birth Hospitalizations, Among Women who Did and Did Not have that Same Outcome at their First Birth: California 1997-2012 (n = 1,180,357)
| Specific Outcome at First Birth | Women with Specified Outcome at First Birth |
Women without Specified Outcome at First Birth |
Risk Ratio (95% CI) |
|||
|---|---|---|---|---|---|---|
| Total N | Subset with any SMM at Second Birtha: N (Prevalenceb) | Total N | Subset with any SMM at Second Birtha: N (Prevalenceb) | Unadjusted | Adjustedc | |
| SMM | 9,088 | 427 (470) | 1,171,269 | 8,014 (68) | 6.87 (6.23, 7.57) | 6.46 (5.86, 7.13) |
| SMM (excluding blood transfusion) | 4,430 | 108 (244) | 1,175,927 | 3,731 (32) | 7.68 (6.35, 9.30) | 7.18 (5.92, 8.69) |
| Specific SMM Indicatorsd | ||||||
| Blood transfusion | 5,170 | 303 (586) | 1,175,187 | 8,138 (69) | 8.46 (7.55, 9.49) | 7.99 (7.12, 8.96) |
| Disseminated intravascular coagulation | 1,364 | 64 (469) | 1,178,993 | 8,377 (71) | 6.60 (5.16, 8.45) | 6.41 (5.01, 8.20) |
| Pulmonary edema/acute heart failure | 372 | 21 (565) | 1,179,985 | 8,420 (71) | 7.91 (5.16, 12.14) | 7.04 (4.59, 10.81) |
| Eclampsia | 1,398 | 31 (222) | 1,178,959 | 8,410 (71) | 3.11 (2.18, 4.42) | 2.89 (2.03, 4.11) |
| Sickle cell anemia with crisis | 32 | 19 (5938) | 1,180,325 | 8,422 (71) | 83.21 (53.05, 130.52) | 46.15 (29.28, 72.74) |
SMM including transfusion was the outcome at second birth for all comparisons, with one exception: SMM (excluding blood transfusions) at first birth was compared to SMM (excluding blood transfusions) at second birth.
Per 10,000 Birth Hospitalizations.
Adjusted for level of education, payment type, race/ethnicity, age at birth, and diabetes and hypertension before first pregnancy.
Data are only presented for specific indicators of SMM at first birth that had least 15 births with SMM events at second birth.
Abbreviations: CI, confidence interval, SMM, Severe Maternal Morbidity.
Prevalence and RRs for five indicators of SMM at first birth that had at least 15 SMM events at second birth are presented in Table 2 and include blood transfusion, disseminated intravascular coagulation, pulmonary edema/acute heart failure, eclampsia, and sickle cell anemia with crisis. The adjusted RRs for SMM at second birth among women with these specific SMM indicators at first birth ranged from 2.89 (95% CI 2.03, 4.11) for eclampsia to 46.15 (95% CI 29.28, 72.74) for sickle cell anemia with crisis.
Among the women who experienced SMM at second birth, 80.1% (n = 342) experienced the same SMM indicator as during first birth; however, sample sizes were deemed too small to calculate RRs for the recurrence of specific indicators between first and second birth.
Comment
Principal Findings
We found that women with SMM at first birth were at six- to seven-fold increased risk of SMM in their second birth. This association persisted after adjustment for factors known to be associated with SMM.
Strengths of the study
Strengths of this analysis include the large sample size, accounting for virtually all inpatient births in California from 1997 to 2012, as well as the linkages between maternal records over time.18 Given that these linked data contain information about maternal characteristics such as education, race/ethnicity, payer at birth, and pre-existing comorbidities, we were able to adjust for several variables.
Limitations of the data
A limitation of this study is the potential selection bias caused if women with SMM were less likely to have a second birth due to SMM in first birth, as these women would not have been included in our cohort. However, this is likely to bias our findings towards the null, indicating that there is still a strong risk association between SMM at first and second pregnancy. Second, life course variables such as exposures to environmental and neighborhood stressors and discrimination, and covariates such as maternal weight and smoking status were not available in our dataset and hence could not be evaluated. Third, women who left California after their first birth and had a second birth in another state were excluded from our analysis. Fourth, this study assesses SMM recurrence risk between first and second birth, and these findings may not be generalizable to higher parities. Fifth, we did not have adequate sample size to calculate RRs for the recurrence of specific indicators between births; however, we observed that of the women who experienced SMM at second birth, 80% experienced the SMM same indicator at first birth.
Interpretation
Similar findings have been reported for a handful of maternal outcomes; studies have shown an increased risk of recurrence for outcomes such as preeclampsia, a condition associated with SMM, and heart failure, an indicator of SMM.9,10 Additionally, recurrence risk for several birth outcomes has been previously established, including a three-fold increase in risk of recurrence for stillbirth, an eight-fold increase in risk of recurrence for small for gestational age, and a three-fold increase in risk of spontaneous preterm birth.4,6,19
Our findings suggest that women who experience SMM may require discussion on reproductive life planning tailored to this increased risk, as well as closer inter-conception and prenatal care if subsequent pregnancy is desired.
The incidence of SMM in our study (77 per 10,000 births) is lower than what has been reported in other studies from this time period for the whole population (101 per 10,000 births).13 Examining recurrence of SMM required women to have at least two births in the study period; women who had multiple births in California had substantially lower rates of SMM (77 per 10,000 births) than women who only had their first birth in California (124 per 10,000 births).
Conclusions
Women experiencing SMM in their first pregnancy are at a more than 6-fold increased risk of SMM in their second pregnancy. Given these findings, clinicians could consider additional robust reproductive life planning discussions and close inter-conception and prenatal care for women who experienced SMM at the time of their first birth.
Supplementary Material
Social Media Quote.
Quote: “In a population-based cohort analysis of Californian women, individuals experiencing SMM in their first pregnancy were at an approximately 6-fold increased risk of experience SMM in their second pregnancy.”
Figure to be posted: Table 2
Synopsis:
Study Question:
Our study asks whether women who have severe maternal morbidity (SMM) in a first pregnancy are at increased risk of SMM in their second pregnancy, compared to those who did not.
What’s already known:
It is known that women who experience adverse maternal and birth outcomes during pregnancy are at increased risk of these outcomes in a subsequent birth. Although the risk of recurrence of SMM is unknown, it is possible that women who experience SMM in one birth are at increased risk of recurrent SMM.
What this study adds:
Our study shows that women experiencing SMM in their first pregnancy were at an approximately 6-fold increased risk of SMM in second pregnancy.
Acknowledgments
Funding
This work was supported by funding from National Institutes of Health National Institute of Nursing Research and Office of Research on Women’s Health (NR017020). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Appendix Table 1.
SMM Indicators and Corresponding ICD-9-CM Codes During Hospitalization
| Severe Maternal Morbidity Indicator | Type | ICD-9 |
|---|---|---|
| Acute myocardial infarction | DX | 410.×× |
| Aneurysm | DX | 441.×× |
| Acute renal failure | DX | 584.5, 584.6, 584.7, 584.8, 584.9, 669.3× |
| Adult respiratory distress syndrome | DX | 518.5×, 518.81 518.82 518.84, 799.1 |
| Amniotic fluid embolism | DX | 673.1× |
| Cardiac arrest/ventricular fibrillation | DX | 427.41, 427.42, 427.5 |
| Conversion of cardiac rhythm | PR | 99.6× |
| Disseminated intravascular coagulation | DX | 286.6, 286.9, 666.3× |
| Eclampsia | DX | 642.6× |
| Heart failure/arrest during surgery or procedure | DX | 997.1 |
| Puerperal cerebrovascular disorders | DX | 430.××, 431.××, 432.××, 433.××, 434.××, 436××, 437.××, 671.5×, 674.0×, 997.02 |
| Pulmonary edema / Acute heart failure | DX | 518.4, 428.1, 428.0, 428.21, 428.23, 428.31, 428.33, 428.41, 428.43 |
| Severe anesthesia complications | DX | 668.0×, 668.1×, 668.2× |
| Sepsis | DX | 038.××, 995.91, 995.92, 670.2× |
| Shock | DX | 669.1×, 785.5×, 995.0, 995.4, 998.0× |
| Sickle cell disease with crisis | DX | 282.42, 282.62, 282.64, 282.69 |
| Air and thrombotic embolism | DX | 415.1×, 673.0×, 673.2×, 673.3×, 673.8× |
| Blood products transfusion | PR | 99.0× |
| Hysterectomy | PR | 68.3×-68.9× |
| Temporary tracheostomy | PR | 31.1 |
| Ventilation | PR | 93.90, 96.01, 96.02, 96.03, 96.05 |
Source: Center for Disease Control and Prevention16
Abbreviations: DX, diagnosis; ICD, International Classification of Diseases, Ninth Revision, Clinical Modification; PX, procedure
Appendix Figure 1.
Directed Acyclic Graph of potential confounders of SMM exposure-outcome relationship
Abbreviations: SMM, severe maternal morbidity
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