Original Article
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Pregnancy Outcomes in Marfan Syndrome: A Retrospective Cohort Study Noura Hassan, MD1
Valerie Patenaude, MSc2
Lisa Oddy, MSc2
1 Department of Obstetrics and Gynecology, Jewish General Hospital,
McGill University, Montreal, Quebec, Canada 2 Centre for Clinical Epidemiology and Community Studies, Jewish General Hospital, Montreal, Quebec, Canada
Haim A. Abenhaim, MD, MPH1,2
Address for correspondence Haim A. Abenhaim, MD, MPH, FRCSC, Department of Obstetrics and Gynecology, Jewish General Hospital, 5790 Cote-Des-Neiges Road, Pav H, Room 325, Montreal, Quebec, H3S 1Y9, Canada (e-mail: [email protected]).
Abstract
Keywords
► ► ► ►
Marfan syndrome pregnancy outcomes maternal morbidity maternal mortality
Objective Marfan syndrome (MFS) is a rare connective tissue disease with significant risk for adverse cardiovascular outcomes. Our objective was to evaluate pregnancy and cardiovascular outcomes in pregnant women with MFS. Study Design We conducted a population-based retrospective cohort study using the Healthcare Cost and Utilization Project Nationwide Inpatient Sample (HCUP NIS) database from 2003 to 2010. We used unconditional regression analyses to compare maternal and fetal outcomes among pregnancies in women with and without MFS. Results Out of the 7,094,400 births in our cohort, 339 deliveries were to women with MFS. There was one maternal death and six aortic dissections among women with MFS. Births to women with MFS were more likely to be premature, odds ratio (OR) 2.15 (1.60– 2.89), have intrauterine growth restricted and small for gestational age infants, OR 2.06 (1.24–3.43). Women with MFS were more likely to deliver by cesarean section, OR 1.91 (1.53–2.38) and were at higher risk of major morbidities including cardiac arrhythmias, OR 10.64 (5.49–20.61) and pneumothorax, OR 51.95 (6.18, 437.10). Conclusion Pregnant women with MFS are at a particularly high risk of adverse pregnancy and cardiovascular events. Preconception counseling should take these risks into consideration and appropriate pregnancy care in tertiary centers should be considered.
Marfan syndrome (MFS) is a rare genetic disorder affecting elastin, a connective tissue responsible for vascular and organ elasticity. Although, MFS is a rare disorder with an estimated prevalence of 1 in 3,000 to 1 in 5,0001 it has significant potential for morbidity. Multiple organ systems are affected by this disorder, but aortic dissection and heart failure are the leading causes of premature mortality in this population.2 Among the various physiological adaptations known to occur in pregnancy, cardiovascular adaptations in response to increased blood volumes and oxygen demands are most likely to affect women with MFS.3 Specifically, the decreased tissue elasticity in MFS may compromise the vascular system’s
ability to sustain the key physiological changes of pregnancy.4,5 Although, research evaluating different maternal outcomes in pregnancies exists, most published articles addressing this population are underpowered for the detection of rare but potentially serious outcomes. The largest study to date consists of 199 pregnancies and 170 births among women with MFS.6 Furthermore, no studies have compared pregnancy outcomes of patients with MFS to the general population. For this reason, we performed a populationbased study to better characterize pregnancy outcomes of patients with MFS.
received October 1, 2013 accepted after revision March 31, 2014 published online June 4, 2014
Copyright © 2015 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel: +1(212) 584-4662.
DOI http://dx.doi.org/ 10.1055/s-0034-1376179. ISSN 0735-1631.
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Am J Perinatol 2015;32:123–130.
Pregnancy Outcomes in Marfan Syndrome
Hassan et al.
Methods We performed a population-based retrospective cohort study using the Healthcare Cost and Utilization Project Nationwide Inpatient Sample (HCUP NIS) database for an 8-year period, from 2003 to 2010. This is the largest all-payer database containing information on patient demographics, hospital resource utilization, diagnoses, and procedures (classified using International Classification of Disease, Ninth Revision [ICD-9 codes]) undertaken during inpatient hospital stays for patients across the United States of America (US). Up to 15 codes may be linked to each admission. Data from approximately 1,000 hospitals (including rural, urban, and teaching hospitals) are included to create a representative 20% sample of US community hospitals. The first step of our study was to create a cohort of births within the HCUP NIS database. This was done by identifying subject records containing birth-related diagnostic codes (ICD-9 codes v27.x or 65x.x or 66x.x). These codes are exclusive to births occurring during the given hospital admission. The second step was to identify those births occurring in our exposure of interest, MFS, and this was done by identifying those admissions that contained the ICD-9 diagnostic code 759.82. Those without this code were categorized as non-MFS. Our analysis was performed in two steps. First, we described the baseline clinical and socioeconomic characteristics among the two groups. Second, we performed multivariate logistic regression analysis to determine which outcomes were independently associated with MFS. We adjusted for age and ethnicity to obtain our corrected odds ratios. t-test and chi-squared test were used to determine statistical significance of our findings for continuous and categorical variables, respectively. We used SAS 9.1 (SAS Institute, Cary, NC) software to perform these analyses. Approval for the use of the database was obtained from the Jewish General Hospital’s Research Ethics Committee for the completion of this project.
Results Our cohort consisted of 7,094,400 women who were admitted to a US hospital for a birth. Of these women, 339 were reported to have MFS. Women with MFS were younger than the nonaffected population; most were less than 25 years old. A greater proportion of MFS women were white and covered by a public insurance plan. Income was similar for both groups. Multiple pregnancy rates, smoking status, and essential hypertension rates were similar in both groups. Greater proportions of subjects with MFS were hospitalized in an urban teaching hospital (►Table 1). The effect of MFS on antepartum and intrapartum maternal outcomes is shown in ►Table 2. We found a decreased risk of gestation diabetes mellitus (GDM) in MFS patients compared with controls. Although, a higher proportion of MFS women had essential hypertension (2 vs. 0.8%), they were not at increased risk for preeclampsia. Only one MFS patient had eclampsia, representing 0.3% of the group compared with American Journal of Perinatology
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0.08%. No statistical difference was noted between the groups for preterm premature rupture of membranes and chorioamnionitis. There were no reported uterine ruptures in the MFS group (data not shown). The most common mode of delivery for patients with MFS was by cesarean section (►Table 2). Patients with MFS were less likely to undergo spontaneous vaginal delivery. Total 6.8% of MFS deliveries were done using forceps compared with 1% in the control group. Vacuum delivery accounted to 8.6% of the MFS group. Overall, 15% of our MFS cohort underwent an operative vaginal delivery. All these findings were statistically significant. Fetal and neonatal outcomes are listed in ►Table 3. Preterm birth rates and intrauterine growth restriction/small for gestational age (IUGR/SGA) were significantly higher in the MFS group. There was no difference in rates of intrauterine fetal demise between the groups. Major morbidity and mortality is listed in ►Table 4. There was one maternal death in the MFS group. Six women with MFS had aortic dissection; both these findings were statistically significant. Cardiovascular outcomes were worse in the MFS group compared with controls with a significantly higher rate of arrhythmia. There were no reported acute myocardial infarcts or endocarditis cases (data not shown). Disseminated intravascular coagulation (DIC), venous thromboembolism (VTE), pneumothorax, transfusions, and hospital stay 6 days were also more likely in the MFS group than in the control group. We found a slightly increased risk of postpartum hysterectomies; 0.3% of the MFS group had this outcome compared with 0.08% of the control group however this rare outcome was not found to be statistically significant. There were no reported intracranial hemorrhages or pelvic joint injuries (data not shown).
Discussion This is the first population-based study investigating pregnancy outcomes of patients with MFS. We identified 339 deliveries to women with MFS, representing the largest described number of cases in the literature to our knowledge. We found a significantly increased risk of maternal death and aortic dissection in MFS patients compared with controls. We also found a significantly elevated risk of cesarean section and operative vaginal delivery in the MFS group compared with the general population. New associations between MFS and peripartum morbidities were established herein; these include DIC, VTE, and pneumothorax. Our data on obstetrical and neonatal/fetal outcomes were mostly consistent with what is currently known. The prevalence of MFS in our cohort was 1 in 20,927 patients. This is significantly lower than the prevalence in the general population quoted at 1 in 5,000 to 1 in 3,000. This may be because MFS is underreported in the HCUP NIS database. Another possibility is that patients with MFS voluntarily choose to avoid pregnancy for medical reasons. A European study described a cohort of women affected with MFS in which approximately 10% were voluntarily childless for medical reasons related to their disease.7
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Table 1 Baseline characteristics Characteristics
Marfan syndrome N ¼ 339 N (%)
No Marfan syndrome N ¼ 7,094,061 N (%)
< 25
159 (46.90)
2,450,310 (34.54)
25–34
155 (45.72)
3,810,121 (53.71)
35
25 (7.37)
827,292 (11.66)
173 (51.03)
2,836,342 (39.98)
Black
45 (13.27)
742,708 (10.47)
Hispanic
41 (12.09)
1,337,963 (18.86)
Asian or Pacific Islander
4 (1.18)
270,651 (3.82)
Other/unknown
76 (22.41)
1,906,397 (26.88)
Medicare
16 (4.72)
39,074 (0.55)
Medicaid
166 (48.97)
2,961,612 (41.75)
Private including HMO
134 (39.53)
3,636,842 (51.27)
Others (self-pay, no charge, other, unknown)
23 (6.78)
456,533 (6.44)
17 (5.01)
784,969 (11.07)
Age (y)
White
Insurance type
Hospital location Rural Urban nonteaching
99 (29.20)
3,065,195 (43.21)
Urban teaching
222 (65.49)
3,208,424 (45.23)
$1–38,999
102 (30.09)
1,883,463 (26.55)
$39,000–47,999
89 (26.25)
1,753,344 (24.72)
$48,000–62,999
82 (24.19)
1,684,463 (23.74)
$63,000 or more/unknown
66 (19.47)
1,772,791 (24.99)
Multiple pregnancy
6 (1.77)
114,607 (1.62)
Smokers
26 (7.67)
358,911 (5.06)
Essential hypertension
7 (2.06)
59,429 (0.84)
Aortic aneurysm
17 (5.01)
60 (0.00)
Aortic valve disease
4 (1.18)
1,136 (0.02)
Other valvular disease
59 (17.40)
35,636 (0.50)
Income
Other
Abbreviation: HMO, health maintenance organization.
As expected, aortic dissection was significantly higher among women with MFS compared with controls. Multiple case reports on aortic dissection in pregnancy have been published8–14 but none of these describe the probability of this event. Previous studies have shown higher rates of aortic rupture; 4.5,15 4.4,16,17 and 3.1%,18 respectively. The combined rate of dissection for these four studies is approximately 3%.19 Yet, in a more recent, relatively large American study, there were no reported aortic dissections.6 Our findings suggesting a rate of 1.77% are overall consistent with what has been described in the literature. There was one maternal death recorded in our study whereas none were reported in the previously quoted studies. Although it is well established
that aortic rupture is associated with a high mortality rate, this is the first study demonstrating an increased risk of death in pregnant patients with MFS. Maternal obstetrical outcomes between our groups were generally similar. The only outcome that was significantly less common in the MFS group compared with controls was GDM. Statistical adjustments suggest that this is partially related to younger age and ethnicity. Yet, the significant adjusted odds ratio suggests that there are factors implicated that we cannot identify; this may be worth investigating in the future. Although an increased risk of placenta previa among women with MFS has been suggested,20 we did not observe this in our cohort. It has also been suggested that connective tissue American Journal of Perinatology
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Ethnicity
Pregnancy Outcomes in Marfan Syndrome
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Table 2 Maternal pregnancy and delivery outcomes adjusted for baseline characteristics Outcomes
Marfan syndrome N ¼ 339 N (%)
No Marfan syndrome N ¼ 7,094,061 N (%)
Crude OR (95% CI)
Adjusted OR (95% CI)
Adjusted p-value
Preeclampsia
11 (3.24)
273,052 (3.85)
0.85 (0.47, 1.54)
0.60 (0.32, 1.12)
0.106
Eclampsia
1 (0.29)
5,877 (0.08)
3.59 (0.51, 25.41)
2.75 (0.38, 19.67)
0.313
Gestational diabetes
8 (2.36)
369,118 (5.20)
0.45 (0.23, 0.90)
0.51 (0.25, 1.02)
0.058
Antepartum hemorrhage
1 (0.29)
113,526 (1.60)
0.19 (0.03, 1.30)
0.17 (0.03, 1.18)
0.073
Placenta previa
3 (0.88)
42,268 (0.60)
1.50 (0.48, 4.65)
1.54 (0.49, 4.82)
0.461
PPROM
5 (1.47)
80,543 (1.14)
1.30 (0.54, 3.15)
1.15 (0.47, 2.80)
0.761
Chorioamnionitis
5 (1.47)
122,764 (1.73)
0.86 (0.36, 2.07)
0.79 (0.32, 1.92)
0.603
Postpartum hemorrhage
11 (3.24)
192,940 (2.72)
1.22 (0.67, 2.21)
1.13 (0.62, 2.08)
0.693
Antepartum
Intrapartum
Delivery Spontaneous vaginal
131 (38.64)
4,516,219 (63.66)
0.36 (0.29, 0.45)
0.36 (0.29, 0.45)
< 0.001
Forceps
23 (6.78)
72,157 (1.02)
7.08 (4.64, 10.82)
6.35 (4.10, 9.83)
< 0.001
Vacuum
29 (8.55)
330,342 (4.66)
1.95 (1.34, 2.85)
2.01 (1.36, 2.96)
< 0.001
Cesarean section
156 (46.02)
2,175,343 (30.66)
1.93 (1.56, 2.39)
1.91 (1.53, 2.38)
< 0.001
Abbreviations: CI, confidence interval; OR, odds ratio; PPROM, preterm premature rupture of membranes.
disease may increase the risk of uterine rupture21 yet this outcome did not occur in our MFS group. We did not observe any association between MFS and hypertensive diseases of pregnancy; this is consistent with what has been previously described in the literature. Preeclampsia rates ranging from 3 to 5% were reported6,7; this is similar to our control population. We found important differences between modes of delivery among women with MFS as compared with women without MFS. The cesarean section rate in our MFS cohort was considerably higher than reported in the literature. Previously published American studies have reported rates of 12 and 22%,6,18 respectively, and several European studies have reported even lower cesarean section rates of 6,15 8,16 and 15%,7 respectively. This discordance is uncertain since the nature of our study does not allow us to make causal links between the subjects’ medical condition and choice of inter-
vention. However, our sample provides a broad representation of an unselected sample, thus shedding light on general outcomes in the MFS population. Furthermore, out baseline cesarean section rate is 31% which is reflective of more recent cesarean section rates. Use of forceps and vacuum for delivery of MFS patients was also significantly higher than the control group. Operative vaginal delivery rates were reported to be even higher in previous American studies. One group reported that all MFS patients receiving routine antepartum cardiac care who delivered vaginally (i.e., 82% of the cohort) had forceps or vacuum-assisted deliveries.6 Another group reported a 30% forceps-assisted delivery rate.18 European groups had much lower rates of 19,7 8,16 and 4%,15 respectively. Overall, our findings on mode of delivery for patients with MFS differ from what has been previously reported, but
Table 3 Fetal outcomes adjusted for baseline characteristics Outcomes
Marfan syndrome N ¼ 339 N (%)
No Marfan syndrome N ¼ 7,094,061 N (%)
Crude OR (95% CI)
Adjusted OR (95% CI)
Adjusted p-value
IUFD
3 (0.88)
47,990 (0.68)
1.31 (0.42, 4.09)
1.26 (0.40, 3.95)
0.687
IUGR/SGA
16 (4.72)
138,060 (1.95)
2.51 (1.52, 4.14)
2.06 (1.24, 3.43)
0.006
Weight < 500 g
14 (4.13)
130,485 (1.84)
2.30 (1.35, 3.93)
1.95 (1.13, 3.35)
0.016
Weight 500–999 g
2 (0.59)
7,599 (0.11)
5.53 (1.38, 22.21)
3.19 (0.72, 14.12)
0.127
Preterm birth (< 37 wk)
57 (16.81)
521,016 (7.34)
2.55 (1.92, 3.39)
2.15 (1.60, 2.89)
< 0.001
Abbreviations: CI, confidence interval; IUFD, intrauterine fetal demise; IUGR, intrauterine growth restriction; OR, odds ratio; SGA, small for gestational age. American Journal of Perinatology
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Table 4 Major maternal morbidity and mortality adjusted for baseline characteristics Outcomes
Marfan syndrome N ¼ 339 N (%)
No Marfan syndrome N ¼ 7,094,061 N (%)
Crude OR (95% CI)
Adjusted OR (95% CI)
Adjusted p-value
Maternal death
1 (0.29)
585 (0.01)
35.94 (5.05, 255.85)
22.38 (2.92, 171.81)
0.003
Aortic dissection
6 (1.77)
19 (0.00)
6,727.42 (2,670.04, 16,950.40)
–
< 0.001
Aortic repair
1 (0.29)
93 (0.00)
226.15 (31.50, 1,623.81)
42.54 (3.62, 500.33)
0.003
Cardiac arrest
1 (0.29)
13,989 (0.20)
1.50 (0.21, 10.66)
0.97 (0.13, 7.07)
0.979
Arrhythmias
9 (2.65)
18,198 (0.26)
10.64 (5.49, 20.61)
Heart failure
2 (0.59)
3,049 (0.04)
13.95 (3.50, 55.63)
1.77 (0.37, 8.32)
0.472
Post-partum cardiomyopathy
1 (0.29)
1,611 (0.02)
13.03 (1.83, 92.79)
1.87 (0.25, 14.05)
0.545
DIC
2 (0.59)
5,753 (0.08)
7.33 (1.83, 29.38)
–
0.005
VTE
4 (1.18)
16,157 (0.23)
5.24 (1.96, 14.04)
–
0.001
Pneumothorax
1 (0.29)
194 (0.00)
108.42 (15.18, 774.17)
51.95 (6.18, 437.10)
< 0.001
Postpartum hysterectomy
1 (0.29)
6,433 (0.09)
3.27 (0.46, 23.21)
–
0.236
Transfusions
8 (2.36)
63,214 (0.89)
2.72 (1.36, 5.47)
1.86 (0.90, 3.84)
0.095
Hospital stay 6 d
36 (10.62)
185,322 (2.61)
4.47 (3.17, 6.31)
2.79 (1.93, 4.04)
< 0.001
Cardiovascular
Noncardiovascular
Abbreviations: CI, confidence interval; DIC, disseminated intravascular coagulation; OR, odds ratio; VTE, venous thromboembolism.
appear to be reflective of current practices in the US. Women with severe cardiovascular disease, particularly those with aortic diameters greater than 4 cm, are considered to be at high risk of rupture and adverse outcomes.22 One group delivered all these patients by elective cesarean section.6 Although, there are no definitive cutoffs or stringent recommendations to this effect, the 2010 American guidelines suggest cesarean section as a preferred mode of delivery in patients with severe illness.22 Operative vaginal deliveries are also known to decrease physiological stress in the second stage of labor. Consequently, this mode of delivery was more frequently encountered in the MFS group compared with controls. It is likely that our cesarean section rate is high because patients with mild-to-moderate disease severity who could have had operative vaginal deliveries underwent cesarean sections due to obstetrician’s preference. However, as previously described, we cannot ascertain these speculations since our study design does not allow us to assess disease severity markers including aortic diameter. Overall, patients with MFS had worse neonatal and fetal outcomes than controls. Preterm delivery was very common in our MFS cohort, affecting 17% of this group. This is consistent with what has been proposed based on the pathophysiology of MFS. It has been speculated that the abnormal connective tissue in these patients is responsible for cervical incompetence, causing preterm delivery.21 However, results of previous studies were conflicting in this regard. Some groups found an increased risk of preterm birth in MFS7,23,24 while others found no difference.6,15,16,18 Our
MFS cohort is the largest of all previously published studies allowing us to achieve more reliable conclusions with relatively narrow confidence intervals. We were unable to determine the gestational age at which the preterm deliveries occurred making it difficult to recommend specific prophylactic measures such as cerclage to prevent MFS patients from experiencing preterm labor. IUGR and SGA were found to be significantly more common in our MFS group compared with controls. Most of the literature to this effect shows increased rates of IUGR/ SGA6,7,15; smaller studies showed no difference.18,23 It is known that pharmacotherapy such as antihypertensives and β-blockers commonly used for reduction of aortic root diameter progression are associated with fetal growth restriction.25 Though we cannot assess therapeutic interventions in our cohort, we suspect that this therapy contributed to this outcome. MFS patients receiving standard of care have higher rates of IUGR/SGA infants than the general population. Intrauterine fetal demise rates were similar in both groups. These findings are consistent with previous studies. Unfortunately, the dataset does not allow for the assessment of neonatal course including need to stay in the neonatal intensive care unit or neonatal death; further research is needed to clarify the risk of perinatal morbidity and mortality in infants of mothers with MFS. Overall, our results suggest that MFS is associated with significant maternal morbidity in the peripartum period. Our MFS sample had significantly increased risks of cardiovascular complications including arrhythmias and showed a trend American Journal of Perinatology
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toward more cardiac arrests, cardiomyopathy, and heart failure. Given that patients with MFS are known to have valvulopathy, we had expected to see increased rates of cardiac insufficiency. They did not, however, have any events of endocarditis; we speculate that this is due to adequate prophylactic antibiotic therapy. Of note is that this is the first study reporting an increased rate of arrhythmias in pregnant patients with MFS. Although, it had been speculated that this group was at higher risk for this complication,19 no previous studies had demonstrated this association. This reinforces the importance of having concurrent care with a cardiologist for assessment of need for defibrillator implantation as recommended by Goland and Elkayam.19 We found that women with MFS were at a fivefold increased risk of venous thromboembolic disease than the control group. This is a novel finding that has never been described previously; our group is the first to identify this significant outcome. These findings are important given the potential for morbidity and mortality. High cesarean section rates in our MFS population may partially account for this morbidity, but this alone cannot explain such a flagrant difference. It is unclear why this might be, though we speculate that the MFS group’s cardiovascular/valvular disease may put them at higher risk for VTE. The American guidelines recommend that patients with previous VTE be given prophylactic therapy because they have a threefold risk of having this outcome in subsequent pregnancies.26 Given that the risk is fivefold in MFS; our group deems it reasonable to prescribe prophylactic anticoagulation therapy to these women throughout pregnancy and postpartum. We also found a significantly increased risk of DIC. This is most likely a repercussion of significant blood loss occurring in the context of aortic dissection. Though we had expected to detect this association, no previous studies had demonstrated this relationship. Likewise, we found a significantly increased risk of transfusion in patients with MFS compared with the control group. Since we did not detect an increased risk of postpartum hemorrhage in MFS, we speculate that most transfusions provided to this population are in the context of aortic dissection or compromised cardiac function requiring increased oxygen carrying capacity. MFS is known to be associated with a high risk of spontaneous pneumothorax. However, no previous studies had shown an increased risk of pneumothorax in the peripartum period. Perhaps clinicians should consider routine incentive spirometry for all MFS patients during hospitalization in addition to more rigorous chest physiotherapy for those who underwent surgical interventions. The retrospective nature of our study limits the amount of data we could collect and interpret. Relevant antepartum events including threatened preterm labor and antepartum bleeding were not captured in our study if they did not occur during the index admission. Furthermore, significant neonatal outcomes including congenital anomalies could not be collected because these codes are linked to the infant’s chart. Finally, there is a small risk of information bias introduced by the limited number of ICD-9 codes (maximum 15) that can be entered under each admission. This, however, is unlikely to American Journal of Perinatology
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influence our results given that patients of reproductive age are generally relatively healthy with little comorbidity. In conclusion, we demonstrate that MFS in pregnancy is associated with a significantly increased risk of overall maternal morbidity and mortality as well as an increased risk of adverse fetal and neonatal outcomes. In light of these findings, women with MFS should receive preconception counseling regarding these risks and be referred for tertiary level care to ensure required resources are readily available for these high-risk pregnancies.
Note The funding was obtained from the authors’ institution.
Conflict of Interest The authors report no conflict of interest.
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retrospective study in a Dutch population. Eur J Obstet Gynecol Reprod Biol 2001;98(1):28–35 Lipscomb KJ, Smith JC, Clarke B, Donnai P, Harris R. Outcome of pregnancy in women with Marfan’s syndrome. Br J Obstet Gynaecol 1997;104(2):201–206 Pacini L, Digne F, Boumendil A, et al. Maternal complication of pregnancy in Marfan syndrome. Int J Cardiol 2009;136(2):156–161 Rossiter JP, Repke JT, Morales AJ, Murphy EA, Pyeritz RE. A prospective longitudinal evaluation of pregnancy in the Marfan syndrome. Am J Obstet Gynecol 1995;173(5):1599–1606 Goland S, Elkayam U. Cardiovascular problems in pregnant women with Marfan syndrome. Circulation 2009;119(4):619–623 Lalchandani S, Wingfield M. Pregnancy in women with Marfan’s Syndrome. Eur J Obstet Gynecol Reprod Biol 2003;110(2):125–130 Anum EA, Hill LD, Pandya A, Strauss JF III. Connective tissue and related disorders and preterm birth: clues to genes contributing to prematurity. Placenta 2009;30(3):207–215 Hiratzka LF, Bakris GL, Beckman JA, et al; American College of Cardiology Foundation; American Heart Association Task Force on Practice Guidelines; American Association for Thoracic Surgery; American College of Radiology; American Stroke Association; Society of Cardiovascular Anesthesiologists; Society for Cardiovascular Angiography and Interventions; Society of Interventional
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Radiology; Society of Thoracic Surgeons; Society for Vascular Medicine. 2010 ACCF/AHA/AATS/ACR/ASA/SCA/SCAI/SIR/STS/ SVM guidelines for the diagnosis and management of patients with thoracic aortic disease: executive summary. A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, American Association for Thoracic Surgery, American College of Radiology, American Stroke Association, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, Society of Interventional Radiology, Society of Thoracic Surgeons, and Society for Vascular Medicine. Catheter Cardiovasc Interv 2010; 76(2):E43–E86 Michaelson-Cohen R, Elstein D, Ioscovich A, et al. Severe heart disease complicating pregnancy does not preclude a favourable pregnancy outcome: 15 years’ experience in a single centre. J Obstet Gynaecol 2011;31(7):597–602 Rahman J, Rahman FZ, Rahman W, al-Suleiman SA, Rahman MS. Obstetric and gynecologic complications in women with Marfan syndrome. J Reprod Med 2003;48(9):723–728 Volach V, Elami A, Gilon D, Pollak A, Ginosar Y, Ezra Y. Pregnancy in Marfan syndrome after aortic root replacement: a case report and review of the literature. Congenit Heart Dis 2006;1(4):184–188 American College of Obstetricians and Gynecologists. Thromboembolism in pregnancy. Obstet Gynecol 2011;118:718–729
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Pregnancy Outcomes in Marfan Syndrome
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123
Pregnancy Outcomes in Marfan Syndrome: A Retrospective Cohort Study Noura Hassan, MD1
Valerie Patenaude, MSc2
Lisa Oddy, MSc2
1 Department of Obstetrics and Gynecology, Jewish General Hospital,
McGill University, Montreal, Quebec, Canada 2 Centre for Clinical Epidemiology and Community Studies, Jewish General Hospital, Montreal, Quebec, Canada
Haim A. Abenhaim, MD, MPH1,2
Address for correspondence Haim A. Abenhaim, MD, MPH, FRCSC, Department of Obstetrics and Gynecology, Jewish General Hospital, 5790 Cote-Des-Neiges Road, Pav H, Room 325, Montreal, Quebec, H3S 1Y9, Canada (e-mail: [email protected]).
Abstract
Keywords
► ► ► ►
Marfan syndrome pregnancy outcomes maternal morbidity maternal mortality
Objective Marfan syndrome (MFS) is a rare connective tissue disease with significant risk for adverse cardiovascular outcomes. Our objective was to evaluate pregnancy and cardiovascular outcomes in pregnant women with MFS. Study Design We conducted a population-based retrospective cohort study using the Healthcare Cost and Utilization Project Nationwide Inpatient Sample (HCUP NIS) database from 2003 to 2010. We used unconditional regression analyses to compare maternal and fetal outcomes among pregnancies in women with and without MFS. Results Out of the 7,094,400 births in our cohort, 339 deliveries were to women with MFS. There was one maternal death and six aortic dissections among women with MFS. Births to women with MFS were more likely to be premature, odds ratio (OR) 2.15 (1.60– 2.89), have intrauterine growth restricted and small for gestational age infants, OR 2.06 (1.24–3.43). Women with MFS were more likely to deliver by cesarean section, OR 1.91 (1.53–2.38) and were at higher risk of major morbidities including cardiac arrhythmias, OR 10.64 (5.49–20.61) and pneumothorax, OR 51.95 (6.18, 437.10). Conclusion Pregnant women with MFS are at a particularly high risk of adverse pregnancy and cardiovascular events. Preconception counseling should take these risks into consideration and appropriate pregnancy care in tertiary centers should be considered.
Marfan syndrome (MFS) is a rare genetic disorder affecting elastin, a connective tissue responsible for vascular and organ elasticity. Although, MFS is a rare disorder with an estimated prevalence of 1 in 3,000 to 1 in 5,0001 it has significant potential for morbidity. Multiple organ systems are affected by this disorder, but aortic dissection and heart failure are the leading causes of premature mortality in this population.2 Among the various physiological adaptations known to occur in pregnancy, cardiovascular adaptations in response to increased blood volumes and oxygen demands are most likely to affect women with MFS.3 Specifically, the decreased tissue elasticity in MFS may compromise the vascular system’s
ability to sustain the key physiological changes of pregnancy.4,5 Although, research evaluating different maternal outcomes in pregnancies exists, most published articles addressing this population are underpowered for the detection of rare but potentially serious outcomes. The largest study to date consists of 199 pregnancies and 170 births among women with MFS.6 Furthermore, no studies have compared pregnancy outcomes of patients with MFS to the general population. For this reason, we performed a populationbased study to better characterize pregnancy outcomes of patients with MFS.
received October 1, 2013 accepted after revision March 31, 2014 published online June 4, 2014
Copyright © 2015 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel: +1(212) 584-4662.
DOI http://dx.doi.org/ 10.1055/s-0034-1376179. ISSN 0735-1631.
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Am J Perinatol 2015;32:123–130.
Pregnancy Outcomes in Marfan Syndrome
Hassan et al.
Methods We performed a population-based retrospective cohort study using the Healthcare Cost and Utilization Project Nationwide Inpatient Sample (HCUP NIS) database for an 8-year period, from 2003 to 2010. This is the largest all-payer database containing information on patient demographics, hospital resource utilization, diagnoses, and procedures (classified using International Classification of Disease, Ninth Revision [ICD-9 codes]) undertaken during inpatient hospital stays for patients across the United States of America (US). Up to 15 codes may be linked to each admission. Data from approximately 1,000 hospitals (including rural, urban, and teaching hospitals) are included to create a representative 20% sample of US community hospitals. The first step of our study was to create a cohort of births within the HCUP NIS database. This was done by identifying subject records containing birth-related diagnostic codes (ICD-9 codes v27.x or 65x.x or 66x.x). These codes are exclusive to births occurring during the given hospital admission. The second step was to identify those births occurring in our exposure of interest, MFS, and this was done by identifying those admissions that contained the ICD-9 diagnostic code 759.82. Those without this code were categorized as non-MFS. Our analysis was performed in two steps. First, we described the baseline clinical and socioeconomic characteristics among the two groups. Second, we performed multivariate logistic regression analysis to determine which outcomes were independently associated with MFS. We adjusted for age and ethnicity to obtain our corrected odds ratios. t-test and chi-squared test were used to determine statistical significance of our findings for continuous and categorical variables, respectively. We used SAS 9.1 (SAS Institute, Cary, NC) software to perform these analyses. Approval for the use of the database was obtained from the Jewish General Hospital’s Research Ethics Committee for the completion of this project.
Results Our cohort consisted of 7,094,400 women who were admitted to a US hospital for a birth. Of these women, 339 were reported to have MFS. Women with MFS were younger than the nonaffected population; most were less than 25 years old. A greater proportion of MFS women were white and covered by a public insurance plan. Income was similar for both groups. Multiple pregnancy rates, smoking status, and essential hypertension rates were similar in both groups. Greater proportions of subjects with MFS were hospitalized in an urban teaching hospital (►Table 1). The effect of MFS on antepartum and intrapartum maternal outcomes is shown in ►Table 2. We found a decreased risk of gestation diabetes mellitus (GDM) in MFS patients compared with controls. Although, a higher proportion of MFS women had essential hypertension (2 vs. 0.8%), they were not at increased risk for preeclampsia. Only one MFS patient had eclampsia, representing 0.3% of the group compared with American Journal of Perinatology
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0.08%. No statistical difference was noted between the groups for preterm premature rupture of membranes and chorioamnionitis. There were no reported uterine ruptures in the MFS group (data not shown). The most common mode of delivery for patients with MFS was by cesarean section (►Table 2). Patients with MFS were less likely to undergo spontaneous vaginal delivery. Total 6.8% of MFS deliveries were done using forceps compared with 1% in the control group. Vacuum delivery accounted to 8.6% of the MFS group. Overall, 15% of our MFS cohort underwent an operative vaginal delivery. All these findings were statistically significant. Fetal and neonatal outcomes are listed in ►Table 3. Preterm birth rates and intrauterine growth restriction/small for gestational age (IUGR/SGA) were significantly higher in the MFS group. There was no difference in rates of intrauterine fetal demise between the groups. Major morbidity and mortality is listed in ►Table 4. There was one maternal death in the MFS group. Six women with MFS had aortic dissection; both these findings were statistically significant. Cardiovascular outcomes were worse in the MFS group compared with controls with a significantly higher rate of arrhythmia. There were no reported acute myocardial infarcts or endocarditis cases (data not shown). Disseminated intravascular coagulation (DIC), venous thromboembolism (VTE), pneumothorax, transfusions, and hospital stay 6 days were also more likely in the MFS group than in the control group. We found a slightly increased risk of postpartum hysterectomies; 0.3% of the MFS group had this outcome compared with 0.08% of the control group however this rare outcome was not found to be statistically significant. There were no reported intracranial hemorrhages or pelvic joint injuries (data not shown).
Discussion This is the first population-based study investigating pregnancy outcomes of patients with MFS. We identified 339 deliveries to women with MFS, representing the largest described number of cases in the literature to our knowledge. We found a significantly increased risk of maternal death and aortic dissection in MFS patients compared with controls. We also found a significantly elevated risk of cesarean section and operative vaginal delivery in the MFS group compared with the general population. New associations between MFS and peripartum morbidities were established herein; these include DIC, VTE, and pneumothorax. Our data on obstetrical and neonatal/fetal outcomes were mostly consistent with what is currently known. The prevalence of MFS in our cohort was 1 in 20,927 patients. This is significantly lower than the prevalence in the general population quoted at 1 in 5,000 to 1 in 3,000. This may be because MFS is underreported in the HCUP NIS database. Another possibility is that patients with MFS voluntarily choose to avoid pregnancy for medical reasons. A European study described a cohort of women affected with MFS in which approximately 10% were voluntarily childless for medical reasons related to their disease.7
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Table 1 Baseline characteristics Characteristics
Marfan syndrome N ¼ 339 N (%)
No Marfan syndrome N ¼ 7,094,061 N (%)
< 25
159 (46.90)
2,450,310 (34.54)
25–34
155 (45.72)
3,810,121 (53.71)
35
25 (7.37)
827,292 (11.66)
173 (51.03)
2,836,342 (39.98)
Black
45 (13.27)
742,708 (10.47)
Hispanic
41 (12.09)
1,337,963 (18.86)
Asian or Pacific Islander
4 (1.18)
270,651 (3.82)
Other/unknown
76 (22.41)
1,906,397 (26.88)
Medicare
16 (4.72)
39,074 (0.55)
Medicaid
166 (48.97)
2,961,612 (41.75)
Private including HMO
134 (39.53)
3,636,842 (51.27)
Others (self-pay, no charge, other, unknown)
23 (6.78)
456,533 (6.44)
17 (5.01)
784,969 (11.07)
Age (y)
White
Insurance type
Hospital location Rural Urban nonteaching
99 (29.20)
3,065,195 (43.21)
Urban teaching
222 (65.49)
3,208,424 (45.23)
$1–38,999
102 (30.09)
1,883,463 (26.55)
$39,000–47,999
89 (26.25)
1,753,344 (24.72)
$48,000–62,999
82 (24.19)
1,684,463 (23.74)
$63,000 or more/unknown
66 (19.47)
1,772,791 (24.99)
Multiple pregnancy
6 (1.77)
114,607 (1.62)
Smokers
26 (7.67)
358,911 (5.06)
Essential hypertension
7 (2.06)
59,429 (0.84)
Aortic aneurysm
17 (5.01)
60 (0.00)
Aortic valve disease
4 (1.18)
1,136 (0.02)
Other valvular disease
59 (17.40)
35,636 (0.50)
Income
Other
Abbreviation: HMO, health maintenance organization.
As expected, aortic dissection was significantly higher among women with MFS compared with controls. Multiple case reports on aortic dissection in pregnancy have been published8–14 but none of these describe the probability of this event. Previous studies have shown higher rates of aortic rupture; 4.5,15 4.4,16,17 and 3.1%,18 respectively. The combined rate of dissection for these four studies is approximately 3%.19 Yet, in a more recent, relatively large American study, there were no reported aortic dissections.6 Our findings suggesting a rate of 1.77% are overall consistent with what has been described in the literature. There was one maternal death recorded in our study whereas none were reported in the previously quoted studies. Although it is well established
that aortic rupture is associated with a high mortality rate, this is the first study demonstrating an increased risk of death in pregnant patients with MFS. Maternal obstetrical outcomes between our groups were generally similar. The only outcome that was significantly less common in the MFS group compared with controls was GDM. Statistical adjustments suggest that this is partially related to younger age and ethnicity. Yet, the significant adjusted odds ratio suggests that there are factors implicated that we cannot identify; this may be worth investigating in the future. Although an increased risk of placenta previa among women with MFS has been suggested,20 we did not observe this in our cohort. It has also been suggested that connective tissue American Journal of Perinatology
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Ethnicity
Pregnancy Outcomes in Marfan Syndrome
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Table 2 Maternal pregnancy and delivery outcomes adjusted for baseline characteristics Outcomes
Marfan syndrome N ¼ 339 N (%)
No Marfan syndrome N ¼ 7,094,061 N (%)
Crude OR (95% CI)
Adjusted OR (95% CI)
Adjusted p-value
Preeclampsia
11 (3.24)
273,052 (3.85)
0.85 (0.47, 1.54)
0.60 (0.32, 1.12)
0.106
Eclampsia
1 (0.29)
5,877 (0.08)
3.59 (0.51, 25.41)
2.75 (0.38, 19.67)
0.313
Gestational diabetes
8 (2.36)
369,118 (5.20)
0.45 (0.23, 0.90)
0.51 (0.25, 1.02)
0.058
Antepartum hemorrhage
1 (0.29)
113,526 (1.60)
0.19 (0.03, 1.30)
0.17 (0.03, 1.18)
0.073
Placenta previa
3 (0.88)
42,268 (0.60)
1.50 (0.48, 4.65)
1.54 (0.49, 4.82)
0.461
PPROM
5 (1.47)
80,543 (1.14)
1.30 (0.54, 3.15)
1.15 (0.47, 2.80)
0.761
Chorioamnionitis
5 (1.47)
122,764 (1.73)
0.86 (0.36, 2.07)
0.79 (0.32, 1.92)
0.603
Postpartum hemorrhage
11 (3.24)
192,940 (2.72)
1.22 (0.67, 2.21)
1.13 (0.62, 2.08)
0.693
Antepartum
Intrapartum
Delivery Spontaneous vaginal
131 (38.64)
4,516,219 (63.66)
0.36 (0.29, 0.45)
0.36 (0.29, 0.45)
< 0.001
Forceps
23 (6.78)
72,157 (1.02)
7.08 (4.64, 10.82)
6.35 (4.10, 9.83)
< 0.001
Vacuum
29 (8.55)
330,342 (4.66)
1.95 (1.34, 2.85)
2.01 (1.36, 2.96)
< 0.001
Cesarean section
156 (46.02)
2,175,343 (30.66)
1.93 (1.56, 2.39)
1.91 (1.53, 2.38)
< 0.001
Abbreviations: CI, confidence interval; OR, odds ratio; PPROM, preterm premature rupture of membranes.
disease may increase the risk of uterine rupture21 yet this outcome did not occur in our MFS group. We did not observe any association between MFS and hypertensive diseases of pregnancy; this is consistent with what has been previously described in the literature. Preeclampsia rates ranging from 3 to 5% were reported6,7; this is similar to our control population. We found important differences between modes of delivery among women with MFS as compared with women without MFS. The cesarean section rate in our MFS cohort was considerably higher than reported in the literature. Previously published American studies have reported rates of 12 and 22%,6,18 respectively, and several European studies have reported even lower cesarean section rates of 6,15 8,16 and 15%,7 respectively. This discordance is uncertain since the nature of our study does not allow us to make causal links between the subjects’ medical condition and choice of inter-
vention. However, our sample provides a broad representation of an unselected sample, thus shedding light on general outcomes in the MFS population. Furthermore, out baseline cesarean section rate is 31% which is reflective of more recent cesarean section rates. Use of forceps and vacuum for delivery of MFS patients was also significantly higher than the control group. Operative vaginal delivery rates were reported to be even higher in previous American studies. One group reported that all MFS patients receiving routine antepartum cardiac care who delivered vaginally (i.e., 82% of the cohort) had forceps or vacuum-assisted deliveries.6 Another group reported a 30% forceps-assisted delivery rate.18 European groups had much lower rates of 19,7 8,16 and 4%,15 respectively. Overall, our findings on mode of delivery for patients with MFS differ from what has been previously reported, but
Table 3 Fetal outcomes adjusted for baseline characteristics Outcomes
Marfan syndrome N ¼ 339 N (%)
No Marfan syndrome N ¼ 7,094,061 N (%)
Crude OR (95% CI)
Adjusted OR (95% CI)
Adjusted p-value
IUFD
3 (0.88)
47,990 (0.68)
1.31 (0.42, 4.09)
1.26 (0.40, 3.95)
0.687
IUGR/SGA
16 (4.72)
138,060 (1.95)
2.51 (1.52, 4.14)
2.06 (1.24, 3.43)
0.006
Weight < 500 g
14 (4.13)
130,485 (1.84)
2.30 (1.35, 3.93)
1.95 (1.13, 3.35)
0.016
Weight 500–999 g
2 (0.59)
7,599 (0.11)
5.53 (1.38, 22.21)
3.19 (0.72, 14.12)
0.127
Preterm birth (< 37 wk)
57 (16.81)
521,016 (7.34)
2.55 (1.92, 3.39)
2.15 (1.60, 2.89)
< 0.001
Abbreviations: CI, confidence interval; IUFD, intrauterine fetal demise; IUGR, intrauterine growth restriction; OR, odds ratio; SGA, small for gestational age. American Journal of Perinatology
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Table 4 Major maternal morbidity and mortality adjusted for baseline characteristics Outcomes
Marfan syndrome N ¼ 339 N (%)
No Marfan syndrome N ¼ 7,094,061 N (%)
Crude OR (95% CI)
Adjusted OR (95% CI)
Adjusted p-value
Maternal death
1 (0.29)
585 (0.01)
35.94 (5.05, 255.85)
22.38 (2.92, 171.81)
0.003
Aortic dissection
6 (1.77)
19 (0.00)
6,727.42 (2,670.04, 16,950.40)
–
< 0.001
Aortic repair
1 (0.29)
93 (0.00)
226.15 (31.50, 1,623.81)
42.54 (3.62, 500.33)
0.003
Cardiac arrest
1 (0.29)
13,989 (0.20)
1.50 (0.21, 10.66)
0.97 (0.13, 7.07)
0.979
Arrhythmias
9 (2.65)
18,198 (0.26)
10.64 (5.49, 20.61)
Heart failure
2 (0.59)
3,049 (0.04)
13.95 (3.50, 55.63)
1.77 (0.37, 8.32)
0.472
Post-partum cardiomyopathy
1 (0.29)
1,611 (0.02)
13.03 (1.83, 92.79)
1.87 (0.25, 14.05)
0.545
DIC
2 (0.59)
5,753 (0.08)
7.33 (1.83, 29.38)
–
0.005
VTE
4 (1.18)
16,157 (0.23)
5.24 (1.96, 14.04)
–
0.001
Pneumothorax
1 (0.29)
194 (0.00)
108.42 (15.18, 774.17)
51.95 (6.18, 437.10)
< 0.001
Postpartum hysterectomy
1 (0.29)
6,433 (0.09)
3.27 (0.46, 23.21)
–
0.236
Transfusions
8 (2.36)
63,214 (0.89)
2.72 (1.36, 5.47)
1.86 (0.90, 3.84)
0.095
Hospital stay 6 d
36 (10.62)
185,322 (2.61)
4.47 (3.17, 6.31)
2.79 (1.93, 4.04)
< 0.001
Cardiovascular
Noncardiovascular
Abbreviations: CI, confidence interval; DIC, disseminated intravascular coagulation; OR, odds ratio; VTE, venous thromboembolism.
appear to be reflective of current practices in the US. Women with severe cardiovascular disease, particularly those with aortic diameters greater than 4 cm, are considered to be at high risk of rupture and adverse outcomes.22 One group delivered all these patients by elective cesarean section.6 Although, there are no definitive cutoffs or stringent recommendations to this effect, the 2010 American guidelines suggest cesarean section as a preferred mode of delivery in patients with severe illness.22 Operative vaginal deliveries are also known to decrease physiological stress in the second stage of labor. Consequently, this mode of delivery was more frequently encountered in the MFS group compared with controls. It is likely that our cesarean section rate is high because patients with mild-to-moderate disease severity who could have had operative vaginal deliveries underwent cesarean sections due to obstetrician’s preference. However, as previously described, we cannot ascertain these speculations since our study design does not allow us to assess disease severity markers including aortic diameter. Overall, patients with MFS had worse neonatal and fetal outcomes than controls. Preterm delivery was very common in our MFS cohort, affecting 17% of this group. This is consistent with what has been proposed based on the pathophysiology of MFS. It has been speculated that the abnormal connective tissue in these patients is responsible for cervical incompetence, causing preterm delivery.21 However, results of previous studies were conflicting in this regard. Some groups found an increased risk of preterm birth in MFS7,23,24 while others found no difference.6,15,16,18 Our
MFS cohort is the largest of all previously published studies allowing us to achieve more reliable conclusions with relatively narrow confidence intervals. We were unable to determine the gestational age at which the preterm deliveries occurred making it difficult to recommend specific prophylactic measures such as cerclage to prevent MFS patients from experiencing preterm labor. IUGR and SGA were found to be significantly more common in our MFS group compared with controls. Most of the literature to this effect shows increased rates of IUGR/ SGA6,7,15; smaller studies showed no difference.18,23 It is known that pharmacotherapy such as antihypertensives and β-blockers commonly used for reduction of aortic root diameter progression are associated with fetal growth restriction.25 Though we cannot assess therapeutic interventions in our cohort, we suspect that this therapy contributed to this outcome. MFS patients receiving standard of care have higher rates of IUGR/SGA infants than the general population. Intrauterine fetal demise rates were similar in both groups. These findings are consistent with previous studies. Unfortunately, the dataset does not allow for the assessment of neonatal course including need to stay in the neonatal intensive care unit or neonatal death; further research is needed to clarify the risk of perinatal morbidity and mortality in infants of mothers with MFS. Overall, our results suggest that MFS is associated with significant maternal morbidity in the peripartum period. Our MFS sample had significantly increased risks of cardiovascular complications including arrhythmias and showed a trend American Journal of Perinatology
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< 0.001
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toward more cardiac arrests, cardiomyopathy, and heart failure. Given that patients with MFS are known to have valvulopathy, we had expected to see increased rates of cardiac insufficiency. They did not, however, have any events of endocarditis; we speculate that this is due to adequate prophylactic antibiotic therapy. Of note is that this is the first study reporting an increased rate of arrhythmias in pregnant patients with MFS. Although, it had been speculated that this group was at higher risk for this complication,19 no previous studies had demonstrated this association. This reinforces the importance of having concurrent care with a cardiologist for assessment of need for defibrillator implantation as recommended by Goland and Elkayam.19 We found that women with MFS were at a fivefold increased risk of venous thromboembolic disease than the control group. This is a novel finding that has never been described previously; our group is the first to identify this significant outcome. These findings are important given the potential for morbidity and mortality. High cesarean section rates in our MFS population may partially account for this morbidity, but this alone cannot explain such a flagrant difference. It is unclear why this might be, though we speculate that the MFS group’s cardiovascular/valvular disease may put them at higher risk for VTE. The American guidelines recommend that patients with previous VTE be given prophylactic therapy because they have a threefold risk of having this outcome in subsequent pregnancies.26 Given that the risk is fivefold in MFS; our group deems it reasonable to prescribe prophylactic anticoagulation therapy to these women throughout pregnancy and postpartum. We also found a significantly increased risk of DIC. This is most likely a repercussion of significant blood loss occurring in the context of aortic dissection. Though we had expected to detect this association, no previous studies had demonstrated this relationship. Likewise, we found a significantly increased risk of transfusion in patients with MFS compared with the control group. Since we did not detect an increased risk of postpartum hemorrhage in MFS, we speculate that most transfusions provided to this population are in the context of aortic dissection or compromised cardiac function requiring increased oxygen carrying capacity. MFS is known to be associated with a high risk of spontaneous pneumothorax. However, no previous studies had shown an increased risk of pneumothorax in the peripartum period. Perhaps clinicians should consider routine incentive spirometry for all MFS patients during hospitalization in addition to more rigorous chest physiotherapy for those who underwent surgical interventions. The retrospective nature of our study limits the amount of data we could collect and interpret. Relevant antepartum events including threatened preterm labor and antepartum bleeding were not captured in our study if they did not occur during the index admission. Furthermore, significant neonatal outcomes including congenital anomalies could not be collected because these codes are linked to the infant’s chart. Finally, there is a small risk of information bias introduced by the limited number of ICD-9 codes (maximum 15) that can be entered under each admission. This, however, is unlikely to American Journal of Perinatology
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influence our results given that patients of reproductive age are generally relatively healthy with little comorbidity. In conclusion, we demonstrate that MFS in pregnancy is associated with a significantly increased risk of overall maternal morbidity and mortality as well as an increased risk of adverse fetal and neonatal outcomes. In light of these findings, women with MFS should receive preconception counseling regarding these risks and be referred for tertiary level care to ensure required resources are readily available for these high-risk pregnancies.
Note The funding was obtained from the authors’ institution.
Conflict of Interest The authors report no conflict of interest.
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American Journal of Perinatology
Vol. 32
No. 2/2015
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Pregnancy Outcomes in Marfan Syndrome
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Copyright of American Journal of Perinatology is the property of Thieme Medical Publishing Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
