Study shows need for identification of high-risk pregnancies and proactive management

The risk of non-traumatic intracerebral hemorrhage (ICH) was highest among pregnant women in their third trimester as well as during the first 12 weeks of the postpartum period, a large study of pregnant women has indicated.

Furthermore, women who experienced an ICH during pregnancy and in the early postpartum period had an exceedingly high mortality rate compared to women who did not. Fetal mortality in the same group of women was also high, the same study found.

“To our knowledge, this is the first population-based study to use a cohort-crossover design to evaluate ICH risk in pregnancy and an extended postpartum period and also the first to evaluate fetal outcomes associated with maternal ICH at the population level,” Jennifer Meeks, MS, Houston Methodists Research Institute in Houston, Texas and colleagues observed in JAMA Network Open.

“There is a continued need for identification of high-risk pregnancies and proactive monitoring and management of ICH-associated risk factors, particularly during the later stages of pregnancy into the extended postpartum period,” investigators concluded.

Administrative data were gathered from all hospital admissions for New York, California and Florida over a 7-10-year period.

A total of 3,314,945 women were included in the analysis.

The mean age of the cohort was 28.17 years and almost 44% of the cohort were white; 14.3% were black; 7.4% were Asian and about 25% were Hispanic.

“We used a cohort-crossover design in which patients served as their own controls,” the authors explained.

With this design, a pregnant or a postpartum woman was compared with her future nonpregnant self.

Women were then observed for an ICH event over a 64-week period, starting 40 weeks prior to the labor and delivery event and extending out to 24 weeks after the labor and delivery event.

“Each patient was followed for a total of 180 weeks,” Weeks and colleagues added.

During the 64-week cohort period, 238 women had a diagnosis of ICH for an incidence of 7.18 cases per 100,000 pregnancies.

In comparison, during the 64-week crossover period, only 68 women out of the remaining 2,719,433 at-risk women had a diagnosis of ICH, for an incidence of 2.5 cases per 100,000 pregnancies.

The rate ratio of ICH was significantly higher during the third trimester at 4.16 (95% CI, 2.52-6.86) while during the first 12 postpartum weeks, the rate ratio was 9.15 (95% CI, 5.16-16.23), the authors reported.

The authors also identified risk factors, demographic characteristics and comorbidities that increased the likelihood that a pregnant woman would experience an ICH.

They found that older age was associated with an increased ICH risk at an adjusted Odds Ratio (OR) of 1.08.

They also found:

  • Black women had almost a 2.5-fold higher risk of ICH than white women at an OR of 2.44 (95% CI, 1.73-3.44).
  • Asian women had an over 2-fold higher risk of ICH than white women at an OR of 2.12 (95% CI, 1.34-3.35).
  • Hispanic women had a 1.5-fold higher risk of ICH than white women at an OR of 1.59 (5% CI, 1.12-2.26).
  • Hypertension increased ICH risk by 2-fold at an OR of 2.02 (95% CI, 1.19-3.42) while gestational hypertension increased ICH risk by almost 3-fold at an OR of 2.73 (95% CI, 1.91-3.91).
  • Eclampsia or preeclampsia increased ICH risk by over 9-fold at an OR of 9.23 (95% CI, 6.99-12.19).
  • Coagulopathy increased ICH risk by over 14-fold at an OR of 14.17 (95% CI, 9.17-21.89).
  • Tobacco use increased ICH risk by almost 3-fold at an OR of 2.83 (95% CI, 1.53-5.23).

Of the women who experienced an ICH during either pregnancy or the first 12 weeks following delivery, 17.6% died.

“Specifically, women with ICH during pregnancy and the postpartum period were approximately 85 times more likely to die compared with women without ICH during delivery or within 52 weeks after delivery,” the authors observed, at an adjusted OR of 84.69 (95% CI, 53.59-133.84).

Fetal death also occurred in 3.3% of women who developed ICH during pregnancy compared with a fetal death rate of only 0.64% of women who did not have an ICH event during pregnancy.

“These findings support the updated guidelines for postpartum care to be considered a care continuum, rather than a single postpartum visit at 6 weeks,” Meeks and colleagues advised.

“For patients with elevated risk profiles, such as those with hypertension or preeclampsia, the need for close, continued follow-up postpartum should be emphasized,” they said.

A limitation of the study is that investigators assumed a uniform gestation period of 40 weeks for all pregnancies which could have led to trimester misclassification.

“[This] is certainly not the case in women who experience ICH in pregnancy who are at much higher risk for preterm birth,” editorialists Kazuyoshi Aoyama, MD, PhD, Hospital for Sick Children and Joel Ray, MD, University of Toronto, both in Toronto, Ontario pointed out in their commentary.

“This may introduce time selection bias because the duration of exposure to pregnancy among women in the cohort period can vary,” they added.

The study’s limitations notwithstanding, findings from the study are “informative” as Aoyama and Ray noted, given how little is known about ICH in pregnancy and during the postpartum period.

“[T]he definitive treatment of eclampsia and preeclampsia is delivery,” as they suggested.

However, even after delivery, “preeclampsia may escalate such that… the prevention of severe hypertension is crucial to avoid ICH,” Aoyama and Ray emphasized.

The American College of Obstetricians and Gynecologists recommends physicians initiate antihypertensive therapy once the systolic blood pressure exceeds 160 mm Hg and/or diastolic blood pressure exceeds 110 mm Hg.

In addition to blood pressure control, “maternal coagulation should be normalized in women with preeclampsia, including the use of intravenous tranexamic acid and fibrinogen replacements,” the editorialists observe.

The use of low-dose aspirin is also indicated between 12- and 20-weeks’ gestation in women at higher risk of developing preeclampsia although there is no evidence that aspirin reduces the risk of ICH.

Aoyama and Ray also underscore that the “timely diagnosis” of ICH is critical for subsequent management and that neuroimaging using either computed tomography or magnetic resonance imaging are both safe in pregnancy.

“If ICH arises, neurosurgical consultation is recommended, in addition to placing the affected woman in a high-acuity monitored setting,” they advised.

 

  1. The risk of intracerebral hemorrhage was highest among pregnant women in their third trimester and during the first 12 postpartum weeks after delivery.

  2. The need to identify and monitor women at high-risk for intracerebral hemorrhage argues for proactive monitoring and management of these risk factors during a continuum of care and not just at a single, 6-week postpartum visit.

Meeks had no disclosures to make.

The editorialists had no conflicts of interest to declare.

 

Cat ID: 41

Topic ID: 83,41,130,41,192

References

Meeks JR, et al “Association of primary intracerebral hemorrhage with pregnancy and the postpartum period” JAMA Network Open 2020; 3(4):e202769. DOI: 10.1001/jamanetworkopen.2020.2769.

Aoyama K, Ray JG “Pregnancy and risk of intracerebral hemorrhage” JAMA Network Open 2020; 3(4):e202844.

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