None of the four women with pulmonary arteriovenous malformation-related hemothorax during pregnancy had, before pregnancy, been assessed at the HHT Centre or had been screened for pulmonary arteriovenous malformations or even known to have HHT. One patient presenting with a hemothorax had presented during a previous pregnancy with a transient ischemic attack.
Hemoptysis during pregnancy occurred in two HHT cases; both were minor and did not require intervention at the time. One woman was diagnosed and treated for pulmonary arteriovenous malformation 24 years postpartum; the other woman had no significant pulmonary arteriovenous malformations when screened 6 years postpartum.
Two women with HHT had transient ischemic attacks: one during the second trimester and one in the third trimester of her pregnancy. Both women had undiagnosed pulmonary arteriovenous malformations.
Complications during delivery occurred in 10 of 185 (5%) deliveries. The most frequent delivery complication was postpartum uterine hemorrhage requiring surgical intervention (one hysterectomy, three dilatation and curettage) after 4 of 185 (2%) deliveries. Within the first 6 months postpartum, major complications occurred after 6 of 185 (3%) pregnancies.
Vaginal delivery and cesarean delivery were reported for, respectively, 129 of 185 (70%) and 56 of 185 (30%) deliveries. Of the 84 women, 63 (75%) and 21 (25%), respectively, had a vaginal delivery or cesarean delivery for their first pregnancy. Vaginal delivery was denied to six women for eight pregnancies owing to their HHT diagnosis.
Spinal or epidural anesthesia was performed in 92 of 185 (50%) deliveries in women with HHT without prior screening for a spinal arteriovenous malformation, none complicated by an epidural bleed or other serious complications. Only three women underwent magnetic resonance imaging (MRI) screening for spinal arteriovenous malformations before delivery and all were negative. None of these women had spinal or epidural anesthesia after screening.
Mean gestational age was 39.0 (SD 2.2) weeks, and mean gestational age for the first delivery was 39.0 (SD 2.3) weeks as well. Twenty-three of 185 (12%) of children were born prematurely (less than 37 weeks of gestation). Mean birth weight was 3,194 g (SD 562) for all neonates, and mean birth weight after first delivery was 3,178 g (SD 558). Low birth weight (less than 2,500 g) occurred in 18 of 185 (10%) of all neonates.
Eleven of 84 women (13%), three of whom had been treated for pulmonary arteriovenous malformations before, were screened for pulmonary arteriovenous malformations before 13 pregnancies: three with contrast echo alone, four with computed tomography (CT) of the chest only, and six with contrast echo and CT. Screening revealed no pulmonary arteriovenous malformations in five cases, microscopic pulmonary arteriovenous malformations (positive contrast echocardiography but negative CT) in five cases, and a pulmonary arteriovenous malformation was found by CT in three cases, none with a significant feeding artery. Therefore, embolization was not indicated. None of these women required embolization after pregnancy either.
Rescreening at mean of 1 year postpartum was performed after seven pregnancies in which prepregnancy screening demonstrated only nonsignificant pulmonary arteriovenous malformations and none were found to have a significant arteriovenous malformation (feeding artery of at least 3 mm).
Fifteen of 87 women (17%) were screened before or during at least one of their pregnancies for a cerebral arteriovenous malformation by MRI or CT; none had a cerebral arteriovenous malformation.
Hereditary hemorrhagic telangiectasia often is thought to increase the risk of complications during pregnancy and delivery, although limited published data are available. This is large retrospective descriptive case series of 244 pregnancies in 87 women with HHT. Major complications in the HHT population occurred in 13% of women, all of whom had not been screened or treated for the presence of pulmonary and cerebral arteriovenous malformations before pregnancy. These complications may have been preventable if screening and treatment for pulmonary arteriovenous malformations had been performed before pregnancy. In women screened and treated for the presence of pulmonary arteriovenous malformations and cerebral arteriovenous malformations (13% and 17%, respectively) before pregnancy, no complications occurred.
The incidence of hemothorax in our population is 2.1% (4/185) (95% confidence interval 0.7–5.6%) per pregnancy, which is similar to 1.4% reported by Shovlin et al.9 Transient ischemic attacks and myocardial infarction and ischemia can also be complications from pulmonary arteriovenous malformations resulting from paradoxical emboli. Most complications from pulmonary arteriovenous malformations occurred during the second or third trimester. This is most likely the result of an increased maternal blood volume to approximately 40% and increased cardiac output during pregnancy.11,12 In our series, patients presenting with hemothorax during pregnancy were at risk of poor neonatal outcomes (stillborn neonate, low birth weight) and need for cesarean delivery. Given the survivor bias of our study, we cannot comment on maternal death. The cases of hemothorax and subsequent complications may have been prevented if women had been screened and treated for pulmonary arteriovenous malformations before pregnancy given the effectiveness of embolotherapy.13
The risk of complications from cerebral arteriovenous malformations appears to be low from our data and others and yet some women were advised to have a cesarean delivery because of the diagnosis of HHT and the risk of rupture of a suspected cerebral arteriovenous malformation (even if they were not screened for the presence of a cerebral arteriovenous malformation in advance). The annual risk of hemorrhage from an HHT-related cerebral arteriovenous malformation is estimated at 0.5–1%.14 A previous study in women with sporadic cerebral arteriovenous malformations showed that pregnancy does not increase the risk of a first cerebral hemorrhage from a cerebral arteriovenous malformation,15 but the risk of rebleeding is increased, mainly during the second and third trimesters when the cardiac output and blood volume are increased. Cesarean delivery afforded no better maternal or fetal outcome than vaginal delivery in women with sporadic cerebral arteriovenous malformations.16,17 Treatment decisions for cerebral arteriovenous malformations in patients with HHT should be made on a case-by-case basis with an expert neurovascular team, preferably before pregnancy.18 When cerebral arteriovenous malformations are detected during pregnancy, treatment is generally delayed until the postpartum period.
High-output heart failure is the most common complication of liver vascular malformations in patients with HHT and it is not surprising that it occurs during pregnancy when the cardiac output increases. In the general population of individuals with HHT, the prevalence of liver vascular malformations varies between 41% and 91%19,20 and is associated with a mutation in ACVRL-1 gene in some series.21,22 We speculate that the rarity of high-output heart failure during pregnancy is likely the result of rarity of extensive liver vascular malformations during the typical age range of pregnancy and that liver vascular malformations likely become more diffuse or extensive with advanced age.23
Epistaxis frequency increased during pregnancy in women with HHT, and they were likely to report new telangiectases during pregnancy. These manifestations were not associated with significant complications.
In our clinical experience we have noticed that pregnant women with HHT are increasingly being denied spinal or epidural anesthesia because of concerns regarding puncture of possible spinal arteriovenous malformations. Spinal arteriovenous malformations are present in 0–6% of patients with HHT24,25 and have mostly been reported in children.26,27 There are no published reports of patients with HHT developing complications from epidural anesthesia based on our search of MEDLINE from 1970–2013 using the terms hereditary hemorrhagic telangiectasia, or HHT, or Osler-Weber-Rendu and epidural anesthesia or spinal anesthesia. There are several case reports of women without HHT developing paralysis after puncture of a spinal arteriovenous malformation during regional anesthesia.28,29 There are also several case reports about women without HHT developing symptoms from a spinal arteriovenous malformation during pregnancy with some cases demonstrating spontaneous regression postpartum.30 Spinal arteriovenous malformations in patients with HHT are located in the subarachnoid space of mostly the thoracic spine. Draining veins can be seen at lower levels in the subarachnoid space, exiting along the nerve root, away from the midline. During epidural anesthesia, the subarachnoid space is usually not entered, which most likely explains that to date no complications from spinal arteriovenous malformations have been reported after epidural anesthesia in patients with HHT.9 Screening for the presence of spinal arteriovenous malformations can be offered to patients with HHT, but there is no evidence to date, in the literature or in our series, to support obligatory screening.
There are several potential study limitations that warrant discussion. The study is retrospective and therefore subject to recall bias. This may have affected rates of minor complications (eg, epistaxis), but it is unlikely to have influenced the reporting of life-threatening events such as hemoptysis and heart failure. Volunteer bias is always a concern with this type of study design, which was unlikely to be an issue for our study, because 213 of 271 (79%) of women agreed to be part of the study. Overall, we believe these limitations are of minimal significance and that our results regarding pregnancy and delivery outcomes in women with HHT are meaningful. The strengths of this study are that all aspects of pregnancy are addressed: pregnancy, delivery, anesthesia, postpartum complications, and neonatal outcomes in one population.
Based on our experience and observations, we suggest the following management of women with HHT before and during pregnancy:
- Pulmonary arteriovenous malformations: prepregnancy screening for the presence of pulmonary arteriovenous malformations and preventive treatment of pulmonary arteriovenous malformations as recommended.18 If not screened before pregnancy, patients are screened and managed for pulmonary arteriovenous malformations according to the “routine screening protocols during pregnancy at Toronto HHT Centre” as mentioned in Appendix 2 (http://links.lww.com/AOG/A469).
- Spinal arteriovenous malformations: screening for the presence of spinal arteriovenous malformations is not routinely recommended given the low incidence of spinal arteriovenous malformations in patients with HHT. However, if screening is being considered, MRI is suggested, ideally prepregnancy. If screening for spinal arteriovenous malformations is considered during pregnancy, although not routinely recommended, this can be done by unenhanced MRI. We routinely recommend consultation with an anesthetist before delivery so that issues can be discussed on a case-by-case basis.
- Cerebral arteriovenous malformations: prepregnancy screening with MRI of the brain, and if a cerebral arteriovenous malformation is present, management should be decided in consultation with an expert neurovascular team.18 If women have not been screened before pregnancy, screening can be performed during the second or third trimester by MRI or delayed until the early postpartum period. Therapy for a cerebral arteriovenous malformation is generally delayed until after delivery in consultation with an expert neurovascular team. Decisions about delivery should be reached after consultation between the obstetrical and neurovascular teams. In general, asymptomatic women with a cerebral arteriovenous malformation can proceed with vaginal delivery; however, prolonged labor should be avoided and consideration be given to an assisted second stage.
In conclusion, complications during pregnancy and delivery in women with HHT appear to occur mainly in women who have not been screened and treated for arteriovenous malformations before pregnancy. Women with HHT should be screened for pulmonary and cerebral arteriovenous malformations and treated as per International HHT Guidelines, before conception. Preferably, women should be educated about possible pregnancy-related risks before pregnancy. Given that the risk of complications from epidural anesthesia are low, epidural anesthesia should not be withheld on the basis of the diagnosis of HHT, but risks and benefits should be considered on a case-by-case basis.
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18. Faughnan ME, Palda VA, Garcia-Tsao G, Geisthoff UW, McDonald J, Proctor DD, et al.; HHT Foundation International–Guidelines Working Group. International guidelines for the diagnosis and management of hereditary hemorrhagic telangiectasia. J Med Genet 2011;48:73–87.
19. Sabbà C, Pompili M. Review article: the hepatic manifestations of hereditary haemorrhagic telangiectasia. Aliment Pharmacol Ther 2008;28:523–33.
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