Intracerebral Hemorrhage: A Life‐Threatening Complication of Hypertension During Pregnancy

Abstract

Intracerebral hemorrhage (ICH) is an infrequent but severe complication in pregnant women with hypertension. The authors describe a patient with chronic hypertension who developed superimposed preeclampsia and spontaneous ICH during the thirty‐fifth week of pregnancy. ICH was diagnosed by computed tomographic scan. She underwent successful emergent cesarean section and neurosurgical decompression of the ICH. Both intraoperative surveillance and postoperative magnetic resonance angiographic examination of the cerebral vessels failed to identify an aneurysm or arteriovenous malformation. The authors discuss the diagnosis and management in this case and review the literature regarding this challenging complication of pregnancy and preeclampsia. Controversies regarding treatment of hypertension during pregnancy are discussed in light of the impact on the management of this patient.

Large population‐based studies on stroke report that intracerebral hemorrhage (ICH) is rare in young women. A small increased risk of this potentially fatal condition is noted during pregnancy; however, the risk increases in the presence of hypertension. Successful management of peripartum ICH requires coordination with an obstetrician and neurosurgeon. Effective prevention of this complication warrants careful blood pressure (BP) management during pregnancy.

CASE REPORT

A 42‐year‐old African American woman presented at 7.5 weeks' gestation (with twins) for evaluation of mildly elevated BP. She had been initially diagnosed with hypertension 8 years earlier, just before her first pregnancy. After initiating antihypertensive treatment with extended‐release nifedipine, her BP was predominantly 130 to 140/80 to 85 mm Hg. These readings persisted through the first and second trimester of her first pregnancy. Toward the end of the third trimester, systolic readings ranged between 140 and 145 mm Hg. She delivered a healthy girl at term by cesarean section.

By the time of her second pregnancy, her BP was consistently <140/90 mm Hg. The patient wished to remain off medication. During assessment at 7.5 weeks' gestation, her BP was reported as high as 160/80 mm Hg. She was referred to us for additional recommendations on management. During assessment in our office, her BP was as high as 166/88 mm Hg. Echocardiography revealed mild concentric left ventricular hypertrophy. Resumption of extended‐release nifedipine was initially recommended, but the patient was familiar with antihypertensive medications and wished to initiate therapy with methyldopa. Methyldopa 250 mg twice daily was prescribed. Overall BP improved but remained elevated with systolic readings of 148 to 166 mm Hg and diastolic readings of 78 to 88 mm Hg. The dose of methyldopa was gradually increased to 750 mg twice daily. During the 34th week of pregnancy, she was admitted to the high‐risk pregnancy unit with headache, elevated BP (165/100 mm Hg), and definite proteinuria (>300 mg). These findings met criteria for preeclampsia superimposed on chronic hypertension. Fetal examination showed loss of one fetus, but no adverse effect on the other. Evaluation of the surviving fetus showed appropriate gestational development. Nifedipine was resumed and she received intravenous magnesium sulfate. The subsequent course was unremarkable. Systolic BP during this time ranged between 128 and 146 mm Hg, and diastolic BP ranged from 80 to 86 mm Hg.

Two weeks later, she developed sudden‐onset severe headache, seizure, and left‐sided upper and lower extremity weakness. Her BP increased substantially with readings as high as 210/140 mm Hg. Fetal heart rate increased to over 140 beats per minute. After endotracheal intubation and general anesthesia, emergent cesarean section was performed and she delivered a healthy girl. Computed tomography of the mother's head showed a large right intraparenchymal hematoma (Figure). Neurosurgical consultation recommended emergent decompression and evacuation of the cerebral hemorrhage. Medical therapy was initiated, including 25 g of intravenous mannitol to reduce intracranial pressure and 1 g of phenytoin sodium to prevent seizures. Two grams of cefazolin were prophylactically given en route to the operating room. During surgery, a large blood clot was evacuated. Surrounding blood vessels were carefully evaluated for aneurysms or arteriovenous malformations as the potential cause of intracranial bleeding, but none was detected. The patient did well postoperatively. No recurrent hemorrhage occurred. A persistent partial hemiplegia and slurred speech remained. To further evaluate for cerebral vessel abnormality, magnetic resonance angiography (MRA) of the brain was performed 8 days postoperatively, which confirmed that no aneurysm or vessel malformation was present.

Figure.

Image of computed tomographic scan of head. Arrows indicate the area of hemorrhage.

DISCUSSION

This case illustrates a classic presentation and hospital course of a patient with chronic hypertension who develops preecclampsia followed by spontaneous ICH. A rare but grave complication of pregnancy, ICH accounts for 5% to 12% of all maternal deaths. Bateman and associates ¹ retrospectively analyzed approximately 20% of all discharges from nonfederal hospitals for the years 1993 through 2002. They identified 423 women aged 15 to 44 years with a pregnancy‐related ICH. By using US Census data, the researchers estimated that 6.1 pregnancy related ICHs occurred per 100,000 deliveries and 7.1 pregnancy‐related ICHs per 100,000 at‐risk person‐years (compared with 5.0 per 100,000 person years for nonpregnant women in the age range considered). Consistent with previous reports, ² the increased risk of ICH associated with pregnancy was found largely attributed to ICH occurring in the postpartum period, while risk during the antepartum period was comparable to a nonpregnant age‐related population. ³ , ⁴ Bateman and colleagues ¹ reported that the in‐hospital mortality rate for pregnancy‐related ICH was 20.3%, accounting for 7.1% of all pregnancy‐related mortality.

Significant independent risk factors for pregnancy related ICH include advanced maternal age (in particular, age older than 35 years); African American race; preexisting hypertension (chronic hypertension), gestational hypertension, preecclampsia (or ecclampsia), preexisting hypertension with superimposed preeclampsia/eclampsia, or coagulopathy; and tobacco abuse/dependence. Most published data support the view that preeclampsia and eclampsia are important risk factors for pregnancy‐related ICH; however, controversy does exist. In our patient, preeclampsia was diagnosed before the ICH. Cerebrovascular malformations (brain arteriovenous malformations, cavernous malformations, unruptured cerebral aneurysms, dural arteriovenous malformations, and venous malformations) are evident in 20% to 67% of patients with pregnancy‐related ICH. ⁵ , ⁶ Bateman and colleagues ¹ reported the presence of a cerebrovascular malformation in 7.1% of patients with pregnancy‐related ICH, compared with 0.002% in the general population; however, the overall rate of ICH related to cerebrovascular malformations per 100,000 person‐years was similar in pregnant and nonpregnant women. This finding does not support the notion that pregnancy increases the risk of rupture of existing cerebrovascular malformations. ⁶ In our case, no underlying vascular malformation or aneurysm was found by either intraoperative surveillance or postoperative MRA. This controversy may be resolved from the ongoing prospective population‐based studies. ⁷ , ⁸

Just before the occurrence of ICH, BP in our patient ranged from 150 to 170 mm Hg systolic and 100 to 120 mm Hg diastolic. She was found to have proteinuria during the hospitalization, meeting the criteria for preeclampsia superimposed on chronic hypertension.

The threshold of BP in pregnancy for which initiation of antihypertensive treatment is indicated is under debate. The decision to prescribe medication for pregnant women with chronic hypertension is based on the idea that treatment will lower maternal risk for cardiovascular complications without posing risk to neonatal development. Some studies suggest that chronic maternal hypertension may have implications on fetal health. Chronic maternal hypertension as well as preeclampsia is associated with low birth weight. ⁹ Most women with stage 1 or stage 2 hypertension are at low overall risk, particularly over the short time period of pregnancy. Furthermore, lowering BP may impair utero‐placental perfusion and consequently inhibit proper fetal development. Thus, not all women with hypertension (eg, systolic 140–179 mm Hg or diastolic 90–109 mm Hg) need to be treated. Not all experts agree with this; they consider treatment of elevated BP levels (even at levels >140/90 mm Hg) in pregnant women to be of importance, especially in a woman with chronic hypertension and evidence of target organ involvement. It should be remembered that a “normal” BP level during the first and second trimesters may be between 90 and 110/70 and 80 mm Hg. Martin and associates ¹⁰ reported 28 pregnant patients who sustained a stroke (25 of 27 patients with arterial hemorrhage and the remaining 2 patients had arterial thrombosis). All patients with hemorrhagic stroke were found to have systolic BP >155 mm Hg (95.8% >160 mm Hg), while 12.5% of patients exhibited pre‐stroke diastolic pressures ≥110 mm Hg. The authors concluded that consideration must be given for treatment of women whose systolic hypertension exceeds 155 to 160 mm Hg. However, a meta‐analysis found that regardless of the type of hypertension or agents used in antihypertensive treatment, fetal growth was significantly impaired by the reduction in mean arterial pressure induced by antihypertensive therapy (a 10‐mm Hg decrease in mean arterial pressure was associated with a 176‐g decrease in birth weight). ¹¹ , ¹²

Our patient with chronic hypertension stopped her medication when she became pregnant because she was concerned about fetal risks. Antihypertensive medication was resumed at 7.5 weeks' gestation because of elevated office readings in the setting of hypertensive heart disease (concentric left ventricular hypertrophy). Resumption of extended‐release nifedipine was initially suggested because her BP had been well controlled on this medication during most of her first pregnancy and throughout the period between pregnancies. Continuation of well‐tolerated medication is recommended by the guidelines in the Working Group Report on High BP in Pregnancy. ¹³ In these guidelines, initiation or resumption of antihypertensive treatment is generally recommended for diastolic BP >100 to 110 mm Hg or systolic pressures >150 to 160 mm Hg. The Seventh Report of the Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High BP (JNC 7) ¹⁴ guidelines recommend methyldopa, β‐blockers, and vasodilators as the first‐choice medications in pregnancy. Our patient was well controlled on nifedipine XL, which she discontinued at the onset of her second pregnancy. When antihypertensive therapy was reinstituted, methyldopa was eventually chosen because of the patient's desire to minimize fetal risk by using an antihypertensive medication with the most recognized safety experience in pregnancy. This medication as monotherapy is, however, rarely effective in reducing BP to optimal levels.

CONCLUSIONS

Our case demonstrates the importance of treating hypertension during pregnancy to prevent serious complications such as ICH. It is possible that these complications might be prevented. To date, there is no consensus regarding the levels of BP that warrant treatment during pregnancy. The main controversy for physicians managing mild hypertension during pregnancy is to know when to tolerate mild elevations in BP and when to initiate treatment so as to avoid complications such as those that occurred with this patient. Further studies are required to determine thresholds for treatment and the best strategies for the management of BP during pregnancy.