Association of Primary Intracerebral Hemorrhage With Pregnancy and the Postpartum Period

Abstract

Importance: Intracerebral hemorrhage (ICH) during pregnancy and the postpartum period results in catastrophic maternal outcomes. There is a paucity of population-based estimates of pregnancy-related ICH risk, including risk during the extended postpartum period.

Objective: To evaluate ICH risk during pregnancy and an extended 24-week postpartum period in a population-level cohort and to determine fetal and maternal outcomes as well as demographic and comorbidity factors associated with ICH during pregnancy and post partum.

Design, setting, and participants: This study used a cohort-crossover design in which patients serve as their own controls when no longer exposed (pregnant or post partum). Administrative data were obtained from all hospital admissions for New York, California, and Florida for a 7- to 10-year period. Participants included all women admitted for labor and delivery who were older than 12 years and did not have a prior diagnosis of ICH. Conditional Poisson regression models were used to evaluate ICH risk, and data were reported as rate ratios and 95% CIs. Data analysis was performed from August 2018 to February 2020.

Exposures: Women were tracked using hospitalization records for the duration of pregnancy (40 weeks), for 24 weeks post partum, and for an additional 64 weeks when no longer exposed.

Main outcomes and measures: Diagnosis of ICH during both 64-week observation periods was determined using validated International Classification of Diseases, Ninth Revision codes.

Results: A total of 3 314 945 pregnant women were included (mean [SD] age, 28.17 [6.47] years; 1 451 780 white [43.79%], 474 808 black [14.32%], 246 789 Asian [7.44%], and 835 917 Hispanic [25.22%]). The risk of ICH was significantly higher during the third trimester (2.9 vs 0.7 cases per 100 000 pregnancies; rate ratio, 4.16; 95% CI, 2.52-6.86) and remained elevated during the first 12 weeks post partum (4.4 vs 0.5 cases per 100 000 pregnancies; rate ratio, 9.15; 95% CI, 5.16-16.23). Advanced maternal age (adjusted odds ratio [OR], 1.08; 95% CI, 1.05-1.10), nonwhite race (adjusted ORs, 2.44 [95% CI, 1.73-3.44] for black patients, 2.12 [95% CI, 1.34-3.35] for Asian patients, and 1.59 [95% CI, 1.12-2.26] for Hispanic patients), hypertension (adjusted OR, 2.02; 95% CI, 1.19-3.42), coagulopathy (adjusted OR, 14.17; 95% CI, 9.17-21.89), preeclampsia or eclampsia (adjusted OR, 9.23; 95% CI, 6.99-12.19), and tobacco use (adjusted OR, 2.83; 95% CI, 1.53-5.23) were independently associated with ICH during pregnancy and the postpartum period. Pregnancy-related ICH was associated with a higher risk of maternal (relative risk difference, 792.6; absolute risk difference, 0.18) and fetal (relative risk difference, 5.3; absolute risk difference, 0.03) death, compared with pregnancies without ICH.

Conclusions and relevance: These findings suggest that the risk of ICH is significantly higher during the third trimester of pregnancy and the first 12 weeks post partum. There are age and race disparities in ICH risk that are associated with devastating maternal and fetal outcomes. These data illustrate the critical need for continuous monitoring and aggressive management of ICH-associated risk factors. These findings suggest that extended postpartum monitoring of high-risk women may be warranted.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Miller reported receiving grants from the National Institutes of Health, National Institute of Neurological Disorders and Stroke (grant K23NS107645) and the Louis V. Gerstner, Jr Foundation (Gerstner Scholars Program) during the conduct of the study and receiving personal fees for medicolegal consulting outside the submitted work. No other disclosures were reported.

Figures

Figure 1.. Cohort-Crossover Design With Respective Observation and Interim Periods

Patients were identified at the time of labor and delivery (denoted by the arrow) and were retrospectively observed for the 40 weeks of pregnancy and prospectively observed for a 24-week postpartum period, resulting a 64-week cohort period. At the end of the cohort period, patients were observed for a 52-week interim period for death and subsequent pregnancy. At the end of the 52-week interim period, at-risk patients (alive and not pregnant or in a postpartum period) were again observed for a 64-week crossover period.

Figure 2.. Diagram Indicating Eligible, Excluded, and Analysis Population Beginning With Total Hospital Discharges for New York (NY), California (CA), and Florida (FL) for the Duration of the Observation Period

Patients younger than age 12 years, missing linkage information, admitted outside of the pregnancy observation time window, and those with false labor, subsequent pregnancies, and nonlabor or delivery admissions were excluded. The exclusion criteria are not mutually exclusive, and patients may fall into more than 1 exclusion category. More than 3 million unique patients with labor and delivery diagnosis were included. Among these patients, those with a prior diagnosis of intracerebral hemorrhage (ICH) were also excluded, resulting in the eligible analysis population for ICH risk. The eligible population was divided into those who did and did not have an ICH diagnosis during pregnancy and the postpartum period. Those who died before the 64-week crossover period and those who were reexposed (pregnant or postpartum period) during the crossover period were excluded from the final matched cohort. Jan indicates January; and Sep, September.

Figure 3.. Rate Ratios for Intracerebral Hemorrhage During Pregnancy and Post Partum as Determined by Conditional Poisson Regression in a Matched Patient Population

The 64-week matched observation period of 2 719 443 patients is stratified into the 3 trimesters of pregnancy and 2 12-week postpartum periods. Rate ratios are indicated by squares and associated 95% confidence intervals are indicated by horizontal error bars. A dashed vertical line is present at 1 as a reference line for statistical significance.