Pregnancy & Delivery
Recommendations from the Second International HHT Guidelines (2020)
Quality of Evidence: Very Low (Agreement 86%)
Consensus in HHT.
Strength of the Recommendation: Strong (Agreement 83%)
Clinical Considerations: Once the causative familial mutation is identified in an affected parent, then it can be screened for in future off-spring. Available options, including pre-implantation, post-conception and post-delivery testing, vary internationally. The discussion will be influenced by local legislation pertaining to pre-implantation diagnosis and termination of pregnancy.
- Pre-implantation genetic diagnosis where there is the option to transfer non-affected embryos. The course of action desired should be discussed as part of the pretest counselling.
- Post-conception options include Chorionic Villus Sampling (CVS) and Amniocentesis. These invasive diagnostic options carry a small risk of miscarriage (1% and <0.5% respectively). Given the risks, a discussion about what path the pregnant person would take once results were available is imperative. If there is no consideration of termination of pregnancy based on the HHT status of the fetus, then these tests may be reserved for other indications, such as fetal anomalies or other screen positive results.
- Post-delivery: parents can be offered genetic testing on cord blood of the infant at time of delivery. While concerns exist for the testing of asymptomatic children for adult onset conditions for which there is no potential benefit of testing in childhood, childhood AVM screening is recommended in HHT (see pediatric section), with treatment in selected cases,
Quality of Evidence: Very Low (Agreement 98%)
Expert consensus in HHT.
Strength of the Recommendation: Strong (Agreement 92%)
Clinical Considerations: MRI, without gadolinium, should be planned in second trimester, for symptomatic patients including patients with previous cerebral hemorrhage. Asymptomatic patients do not require routine screening during pregnancy.
- In asymptomatic patients, initial pulmonary AVM screening should be performed using either agitated saline transthoracic contrast echocardiography (TTCE) or low-dose non-contrast chest CT, depending on local expertise. Chest CT, when performed, should be done early in the second trimester.
- In patients with symptoms suggestive of pulmonary AVM, diagnostic testing should be performed using low-dose non-contrast chest CT. This testing can be performed at any gestational age, as clinically indicated.
- Pulmonary AVMs should be treated starting in the second trimester unless otherwise clinically indicated.
Case series demonstrated elevated risk of complications from pulmonary AVMs during pregnancy(103-105), and low risk of imaging and embolization in second trimester(106).
Clinical Considerations: Technique for embolization in pregnant patients should include measures to reduce fetal radiation exposure, including avoidance of fluoroscopy over the abdomen and pelvis, use of pulsed or low-dose fluoroscopy mode, minimizing angiography runs, and use of tight collimation. For both CT and angiography, abdominal shielding is not helpful, and may in fact increase scattered radiation to the fetus.
Quality of Evidence: Very Low (Agreement 94%)
Expert consensus in HHT.
Strength of the Recommendation: Strong (Agreement 85%)
Clinical Considerations: Pregnant women with untreated pulmonary AVMs or brain VMs, and those who have not been screened, should be considered high risk for hemorrhagic and neurologic complications, and be managed accordingly by a high-risk team with HHT expertise.
Quality of Evidence: Low (Agreement 98%)
Two case series demonstrated no evidence of hemorrhagic complications from epidural or spinal anesthesia(103, 107).
Strength of the Recommendation: Strong (Agreement 92%)
Clinical Considerations: Patients should meet with an anesthetist during early third trimester to discuss anesthesia options. The risk of complications from spinal VM during epidural anesthesia are unsubstantiated and only theoretical.
Quality of Evidence: Moderate (Agreement 94%)
Two case series demonstrated no intracranial hemorrhage during delivery from brain VMs in HHT patients(103, 107).
Strength of the Recommendation: Strong (Agreement 94%)
Clinical Considerations: If a brain VM has not previously ruptured, patients may proceed with mode of delivery based on obstetrical indications and discussion with their obstetrical care provider. Vaginal delivery is not contra-indicated. Patients with “high risk” brain VMs should be considered for Cesarean section, OR epidural, to allow passive descent of the presenting part, with consideration for an assisted second stage. Diligent management of blood pressure is imperative, in these higher risk cases, and obtaining the opinion a multi-disciplinary neuro vascular team is prudent.
A pregnant woman with HHT should be assessed for their risk of pregnancy and delivery related complications and have access to, as needed, to a multidisciplinary maternal-fetal medicine team that includes HHT experts. At the initial obstetrical visit, pregnant patients should have a thorough review of their diagnosis history and past evaluations as well as recent status, symptoms and concerns. In addition, given that offspring are at 50% risk of inheriting the pathogenic mutation, pre-pregnancy consultation with an obstetrician is recommended, for consideration of options before and during and after pregnancy for genetic diagnosis.
The term “high-risk pregnancy” is a label used to describe situations in which a pregnant woman, her fetus, or both, are at higher risk when compared to a “typical” pregnancy for complications during pregnancy, labor & delivery or post-partum. Many pregnant women with HHT are labeled as “high-risk”, as there is 1% overall risk of complication in pregnancy in patients with HHT(103). However, it is possible to stratify this risk. Risk stratification can be based upon the results of a patient’s AVM screening and/or treatment. Unscreened patients and patients with known but untreated pulmonary AVMs of significant size (>2-3 mm) are at highest risk.
The physiologic changes of pregnancy to the circulatory system include an increase in cardiac output by 30-50% and an increased blood volume by 40% by 28 weeks. Pregnancy also results in high progesterone levels, which may increase venous distensibility(178). This collective effect of these factors may result in enlargement and/or rupture of untreated pulmonary AVMs during pregnancy(104). Recent studies have estimated a risk of about 17% for non-fatal complications(107) and 2% for mortality(103). Hemothorax, hemoptysis, ischemic stroke, and pulmonary deterioration have all been reported(103, 104, 107). Pulmonary AVMs should be screened for and treated prior to pregnancy(107). If a HHT patient becomes pregnant and pulmonary AVMs have not been excluded, screening should be performed either with TTCE or with chest CT. TTCE using agitated saline is considered safe during pregnancy(179). Chest CT requires radiation, but the fetal dose is minimal(180) and can be delayed until after organogenesis as is discussed below. No IV contrast is required, and a low-dose non-contrast protocol is adequately sensitive for detecting and characterizing pulmonary AVMs.
If a pregnant patient with HHT is diagnosed with pulmonary AVMs, the decision to embolize and subject the fetus to ionizing radiation and periprocedural complications should be weighed against the risk of no treatment. The feeding artery size threshold at which to embolize asymptomatic pregnant patients has not been established but it should likely follow recommendations for the general population of 2-3 mm. Pregnant patients who are symptomatic from pulmonary AVM (e.g. hemorrhagic or neurologic complication), should undergo diagnostic CT and immediate treatment with embolization, regardless of gestational age.
In asymptomatic pregnant women, diagnostic chest CT imaging and treatment with embolization should be delayed until after organogenesis is complete (12 weeks). This timing is supported by the observation that 85-90% pulmonary AVM complications occur in the second or third trimesters(104, 105). Thus, screening and treatment of asymptomatic pulmonary AVMs should typically occur between 12-20 weeks of gestational age. The estimated fetal dose for a maternal chest CT is less than 0.5 mGy, and estimated fetal dose for pulmonary embolization is about 1-2mGy(106). Fetal radiation doses below 50mGy are considered negligible (The American College of Obstetricians and Gynecologists) and there are no known health effects associated with fetal radiation at these levels of exposure. Considering the high risk of non-fatal pulmonary AVM related complications during pregnancy (17%)(107) and mortality (2%)(103), the benefit of embolization is favored over no treatment ,in most cases.
Pregnant women with HHT who screen negative for pulmonary AVMs have similar pregnancy risk as their non-HHT counterparts. After initial evaluation at a tertiary center, they may be advised that they are suitable candidates for management outside of tertiary level care with careful attention to known complications such as worsening epistaxis and anemia. Patients should be counselled that they are not at higher risk of miscarriage than the general population(107), outcomes are generally good, but they need to be educated regarding signs and symptoms of severe complications.
Given the absence of evidence that pregnancy increases the size of brain VMs or the likelihood of hemorrhage, a diagnosis of pregnancy is not an indication for screening for brain VMs. A retrospective series from 1995(104) did not include any cases of intracranial hemorrhage among 161 pregnancies in 47 affected women. A second cohort study from the same institution in 2008(103) (both retrospective and prospective) followed up on 484 pregnancies in 197 non screened HHT women. There was one case of subarachnoid hemorrhage during the second trimester of pregnancy and another case of hemorrhage in the third trimester due to a brain AVM (0.4% rate of bleeding). A third retrospective case series published in 2014(107) analyzed 244 pregnancies in 87 women with one case of intracranial hemorrhage (0.4%) in the postpartum period in a previously unscreened patient. These published risks of brain AVM hemorrhage during pregnancy appear similar to the hemorrhage rate of brain VMs in non-pregnant patients with HHT, which is estimated at 0.4-1.0% per year(177, 181).
In cases of known, asymptomatic brain VMs, no intervention is typically required during pregnancy, due to the low risk of hemorrhage(182, 183). There is no conclusive evidence of an increased risk of first hemorrhage during pregnancy from brain VM(184). However, some higher-risk situations should be recognized, including patients with high-flow AV fistulae, patients with brain AVM and recent (< 2 years) clinical bleed, patients with brain AVM and history of bleeding during a previous pregnancy, and patients with complex brain VM with a neurosurgical opinion of higher bleeding risk. If a brain VM ruptures during pregnancy, the re-bleed rate in the 2nd/3rd trimester and postpartum and is high ~27-30%(185, 186). Mortality from a brain VM bleed in pregnancy is ~28%, which is higher than in the non-pregnant state(187). Even considering these higher-risk situations, there is no evidence justifying treating unruptured and asymptomatic brain VMs in a pregnant person, given the risks of radiosurgery, embolization and surgical resection, but a multi-disciplinary team should make decisions on a case by case basis as to whether any intervention is required.
Pregnant women with a known brain VM may labor and attempt to undergo a spontaneous vaginal delivery. There are no reports of pregnant people with HHT having a brain VM bleed during labor. This supports the recommendations for vaginal delivery as is done in pregnant people with brain VMs who do not have HHT. There may be cases in which the opinion of the multidisciplinary team is that the patient should undergo a caesarean section. This might include patients presenting with brain VM symptoms in pregnancy, or patients with prior hemorrhage from brain VMs. In all patients with brain VM, diligent management of blood pressure is imperative, to avoid swings in either direction. Modification of general anesthesia to avoid hypertension is prudent(187).
The prevalence of spinal VMs in the HHT population is very low, although higher than the general population. Routine screening for spinal VMs is not recommended due to the rarity of spinal VMs in the thoracolumbar spine in asymptomatic people with HHT. Pregnant women with HHT who have never had a spinal MRI should not have one just because pregnancy is diagnosed. Unenhanced MRI only excludes medium or large spinal VMs and gadolinium is contraindicated in pregnancy. Lomax et. al(187) mentions that pregnancy may exacerbate the symptoms of spinal VM. In a case of a known spinal VM, an anesthesiologist should be consulted to address anesthetic options on a case by case basis. The prevalence of spinal VMs in HHT is 0.5%. Spinal VMs are predominantly symptomatic in males and the pediatric population(188), are generally perimedullary (rarely in the dural space), and usually involve the thoracic spine, with a minority extending into the lumbar region (189). Since the majority of spinal VM in patients with HHT are located perimedullary, this should not affect epidural anesthesia.
There are two large studies of pregnancy in HHT and neither reported complications from epidural or spinal anesthesia(103, 107). In one study there were 92 spinal/epidurals in 185 deliveries, and in the other study, there were 484 pregnancies; no spinal hemorrhages were reported. Likewise, there are no case reports of patients with HHT, who are asymptomatic of spinal VM, developing complications from spinal VM secondary to spinal/epidural anesthesia. There is no evidence for routine screening, and no evidence to deny an unscreened pregnant person an epidural. Epidural anesthesia can safely be offered, and patients should be counseled that the risk of complication with an epidural is theoretical. It is prudent to have an epidural/spinal anesthetic performed by an experienced anesthetist.