Abstract

Aims Nowadays, most women born with aortic coarctation reach childbearing age. However, data on outcome of pregnancy in women after repair of aortic coarctation are scarce. The aim of this study was to report on maternal and neonatal outcome of pregnancy in women after aortic coarctation repair.

Methods and results The CONCOR national registry on congenital heart disease in The Netherlands was reviewed for women of childbearing age (≥18 years old) with a history of aortic coarctation repair. Medical history and maternal, obstetrical, and neonatal outcome were determined. Fifty-four of the 100 women included had a history of pregnancy. The 54 women had 126 pregnancies resulting in 98 successful pregnancies, 22 miscarriages, and six abortions. The success rate was estimated as 0.778 (SE 0.002) including abortions and 0.817 (SE 0.002) excluding abortions. There were 85 vaginal deliveries, seven vaginal deliveries with epidural analgesia, and six caesarean sections. There were two neonatal deaths. A total of 26 pregnancies were complicated by a hypertensive disorder of pregnancy. There were 21 pregnancies in 14 women complicated by hypertension and five pregnancies in four women complicated by pre-eclampsia. The hypertension- and pre-eclampsia-probabilities were estimated as 0.183 (SE 0.285) and 0.061 (SE 0.211), respectively. During pregnancy, five patients had an increase ≥15 mmHg across the site of repair at echocardiography, but only one patient required reintervention for recoarctation after delivery. Four of the 98 children (4%) had a congenital heart defect.

Conclusion Pregnancy is well tolerated in women after repair of aortic coarctation. However, an excess of miscarriages and hypertensive disorders of pregnancy were found.

Introduction

Survival of patients with congenital heart disease has dramatically improved due to the advances in cardiovascular surgery and paediatric cardiology. Experience of pregnancy in these patients is scant and there is a continuous need to update our knowledge.1 Coarctation of the aorta accounts for 6–8% of the patients with congenital heart disease.2 Most females born with aortic coarctation are expected to reach childbearing age with a previous history of surgical repair. We present the largest study to date, on outcome of pregnancy in patients after repair of aortic coarctation. Aim of this study was to report on maternal and neonatal outcome of pregnancy and fertility in women after repair of aortic coarctation.

Methods

In 2004, the CONCOR registry (CONgenital CORvitia; www.concor.net) was reviewed for all women with a main diagnosis of aortic coarctation and who were ≥18 years at the time of the study. The CONCOR database is the national registry of patients with congenital heart disease in The Netherlands and was founded in 2000 with financial support of The Netherlands Heart Foundation and the Interuniversity Cardiology Institute of The Netherlands. All patients were followed in one of the eight participating tertiary academic medical centres in The Netherlands.

The institutional review board or Ethics Committee approved the protocol. Patients were contacted by mail and asked to participate. The patients with no response were contacted by phone and asked once more to participate in this study. After written informed consent, the medical records of participating patients with a history of pregnancy were reviewed. Cardiological data included information based on echocardiography, magnetic resonance imaging (MRI), and cardiac catheterization (depending on available data). Data were collected on associated congenital cardiovascular anomalies and status of the aortic valve. Type of repair and age at repair were noted, including aortic aneurysms, need for reoperation, and medication. Hypertension was defined as present if reported in the cardiological records of the patients.

A detailed questionnaire was obtained from each patient by phone. The results of the questionnaire were compared with obstetrical data from medical records when available. Data included information on fertility (infertility: documented by gynaecologist, >2 years of attempts to get pregnant), miscarriages (spontaneous foetal loss before 20 weeks of gestation), and/or elective abortions. Detailed information concerning each completed (>20 weeks of gestation) pregnancy was recorded (when applicable pre-, peri- and post-partum data): mode of delivery; parity status; use of cigarettes, alcohol, and/or drugs; and use of medication. Documented complications were grouped into cardiac, general, obstetric, and neonatal events. Cardiovascular complications: symptomatic documented arrhythmia or heart failure (according to treating cardiologist) requiring treatment, myocardial infarction, stroke, endocarditis, thrombo-embolic complication and/or cardiac death, gestational hypertension (new onset hypertension after 20 weeks of gestation, >140 mmHg systolic or 90 mmHg diastolic without proteinuria), the continued presence of sustained hypertension, pre-eclampsia (gestational hypertension with >0.3 g of proteinuria/24 h urine sample), eclampsia (pre-eclampsia with grand mal seizures), superimposition of pre-eclampsia on chronic hypertension,3 and haemolysis elevated liver enzymes low platelets (HELLP) syndrome. General complications: all-cause hospitalization (except delivery), infections requiring antibiotic treatment, gestational diabetes, and/or death. Obstetric complications: assisted (forceps/vacuum/caesarean) delivery, prolongation of second stage of delivery (nullipara >2 h, multipara >1 h), premature labour (spontaneous onset of labour <37 weeks gestation), and post-partum haemorrhage [vaginal delivery >500 mL, caesarean section (CS) >1000 mL, documented by gynaecologist and requiring transfusion]. Neonatal complications: premature birth (delivery <37 weeks of gestation), small-for-gestational-age birth weight (<10th percentile),4 foetal demise (intra-uterine death ≥20 weeks of gestation), perinatal death (within the first month after birth), and/or recurrence of congenital heart disease.

Clintrial data-entry program was used to record information and was converted to SPSS (version 10.1) for statistical analysis. After checking for normality, mean values and standard deviations were calculated for normally distributed continuous variables. For variables that were not normally distributed, median and range were calculated. Comparisons of continuous variables between groups were made by unpaired Student's t-tests. In case of a skewed distribution, the Mann–Whitney U test was used. When comparing frequencies, we applied the χ2 test. The statistical tests used were two-sided and the significance level was set at 0.05. Clinical outcome data were compared with known incidences of normal pregnancies in The Netherlands and the available world literature,5 and the available literature on outcome of pregnancy in patients after repair of aortic coarctation.6,7 We analysed pregnancy outcome (success, hypertension, or pre-eclampsia) with a random-effects model, assuming that the outcome-probabilities differed between women according to a beta-distribution. In this way, we take account for the possible correlation between the outcomes of repeated pregnancies in the same woman. The average outcome-probability of the beta-distribution and its standard deviation was estimated with the available data.

Results

A total of 178 female patients with aortic coarctation were identified. Eleven patients with Turner syndrome were excluded. The remaining 167 patients were contacted by mail and asked to participate. One hundred subjects (60%) responded and were included in this study. Of the entire group of 100 included patients, 46 women (46%) had not been pregnant. Fifty-four women had a history of pregnancy.

Cardiovascular history

Baseline characteristics of the enroled patients are summarized in Table 1. All patients with a history of pregnancy had initial repair of aortic coarctation and associated cardiovascular anomalies before becoming pregnant. Thirty-three of the entire group of 100 patients (33%) had undergone a total of 52 reinterventions.

Contraception and fertility

No problems of sub-infertility were reported. Forty-six women (46%) had no history of pregnancy of which 36 patients (78%) would like to bear children in the future. None of these patients had a current child wish. Reasons reported for being childless are shown in Table 2.

Fifty-four women (54%) had a history of pregnancy. All patients became pregnant spontaneously. Five women (9%) had been advised against pregnancy because of perceived maternal and foetal risk. Three of these patients were negatively advised between 1970 and 1980. One patient had been advised against a second pregnancy because of complications of respiratory insufficiency due to heart failure and pulmonary arterial hypertension during the first pregnancy and delivery. One patient with one child suffered a cerebrovascular accident and was negatively advised based on perceived maternal risk and social grounds. Only five patients (9%) had discussed the topic of contraception with their cardiologist.

Obstetrical data

Data are available of 126 pregnancies in 54 women (Table 3). There were 98 successful pregnancies, 22 miscarriages, and six abortions. The success rate was estimated as 0.778 (SE 0.002) including abortions and 0.817 (SE 0.002) excluding abortions. At the time of the study, one woman was pregnant for the second time. This second pregnancy was not included in this study. There were no twin pregnancies. Five patients had elective abortions (three because of socio-economic reasons, one because of perceived maternal risk, and one because of an affected child with hypoplastic left ventricle). One woman had an ectopic pregnancy that was unsuccessful. Only four women were sustained hypertensive at the time of their miscarriage.

In 68 of the 98 live birth pregnancies (68%), one or more foetal echocardiograms were performed.

All-cause hospitalization with the exception of admission for delivery was seen in 13 women, mostly occurring during the first trimester (Table 3).

Sixteen women had one child, 30 had two children, three had three children, two had four children, and one had five children. Of the 98 births, six (6%) were caesarean deliveries, two of which were performed for breech presentations, two for foetal distress, one for abruptio placentae, and one for perceived maternal cardiovascular risk.

Six women had premature deliveries: in three women (in one woman two times), labour was induced because of pre-eclampsia, in two because of breech presentations, and one of unknown cause (Table 4). In 17 other women, labour was induced because of: post-maturity in seven women (one woman three times), perceived maternal risk in two women (one woman two times), pre-eclampsia in one woman, other maternal reasons in five women. During 70 deliveries (71%), endocarditis prophylaxis was administered. A clear indication for endocarditis prophylaxis was lacking in 33 (33%) of these deliveries. In nine patients with instrumental delivery, endocarditis prophylaxis was not administered.

Neonatal data

There were 98 live births after a median pregnancy duration of 40 weeks (Table 4). Seven children (7%) were born prematurely and four of them were small for gestational age. Of the 98 births, four children (4%) were born with congenital heart disease. Two children had aortic coarctation, one child a bicuspid aortic valve, and one a ventricular septal defect. Two other children died shortly after birth: one because of respiratory insufficiency due to prematurity, the other because of hypoxic encephalopathy due to abruptio placentae.

Maternal outcome

No serious cardiovascular complications occurred. There were no cases of aortic dissection, intracranial haemorrhage, documented arrhythmia, or endocarditis. One patient with a hypoplastic right lung and moderate pulmonary arterial hypertension became respiratory insufficient at 36 weeks of pregnancy. She underwent primary CS under epidural analgesia. After delivery, she was monitored in the ICU for 5 days for pulmonary hypertension, respiratory insufficiency, and systemic hypertension. She recovered but was advised against a second pregnancy.

A total of 26 pregnancies (22%) were complicated by a hypertensive disorder of pregnancy. There were 21 pregnancies in 14 women with hypertension and five pregnancies in four women with pre-eclampsia. The hypertension- and pre-eclampsia-probabilities were estimated as 0.183 (SE 0.285) and 0.061 (SE 0.211), respectively. Seven patients had sustained hypertension before their first pregnancy. Seven women, not formerly known with systemic hypertension, developed gestational hypertension. In three patients (four pregnancies), pre-eclampsia was superimposed on sustained hypertension.

The relationship between pregnancy-induced hypertension and arm/leg blood pressure difference and echocardiographic gradients could not be established because no serial data could be retrieved from the medical records. In none of the 54 patients were serial arm and leg blood pressure differences during pregnancy performed. In eight patients, serial echocardiographic gradient measurements were available for analysis. In five of these patients (three with pre-pregnancy sustained hypertension and two with pre-pregnancy normotension), an increase in echo Doppler gradient ≥15 mmHg in the thoracic descending aorta was observed. Only one patient had significant recoarctation and underwent reintervention several months after delivery.

Discussion

This study reports on 126 pregnancies in 54 women after repair of aortic coarctation, which renders it the largest, reported series thus far. The present study shows that pregnancy is well tolerated in post-coarctectomy patients. However, an excess of miscarriages and frequent occurrence of hypertensive disorders of pregnancy were observed.

Cardiovascular physiology undergoes profound changes during pregnancy. Cardiac output increases 30–50% during the second trimester due to increases in both stroke volume and heart rate.1,8,9 Furthermore, blood vessel remodelling takes place due to hormonal factors, which leads to weakening of the arterial wall.10 During labour, cardiac output further increases due to pain and uterine contractions.1,11 By 2–6 weeks post-partum, both cardiac output and heart rate have returned to pre-pregnant levels.12

In our study, no aortic rupture or dissection was observed. Pregnancy in aortic coarctation patients has been a source of concern because of sporadically reported cases of aortic dissection during pregnancy.7,13 Histological changes in the wall of the ascending aorta similar to those in Marfan syndrome have been found in patients with bicuspid aortic valve and aortic coarctation.1416 This intrinsic aortopathy associated with aortic coarctation combined with the physiological and hormonal changes during pregnancy may increase the risk of aortic dilation, rupture, or dissection in patients with aortic coarctation.7 Serial echocardiograms before, during, and after pregnancy were not performed in the majority of the patients. It is unknown whether pregnancy induces irreversible aortic dilatation in aortic coarctation patients because studies are lacking. In the study of Meijboom et al.,17 on outcome of 33 pregnancies in patients with Marfan syndrome and an aortic root <45 mm, no increase of the aortic dilatation rate was observed during pregnancy. These data suggest that the risk of acute aorta complications during pregnancy is low in aortic coarctation patients with no or only slight dilatation of their aorta. Repeat echocardiography and/or MRI is indicated in those women with known ascending and/or descending aorta dilatation.18

In the normal population, up to 8% of all gestations are affected by hypertensive disorders of pregnancy.3 In our study, a far higher incidence was found; the hypertension and pre-eclampsia probabilities were estimated as 0.183 (SE 0.285) and 0.061 (SE 0.211), respectively. This incidence of pre-eclampsia in our study is similar to that reported by Beauchesne et al.,7 but lower than reported by Saidi et al.6 In three patients (four pregnancies), pre-eclampsia was superimposed on sustained hypertension. It is known from studies on pregnancies, in the normal population, that women with sustained hypertension are at increased risk to develop superimposed pre-eclampsia (25%) with pre-term delivery, foetal growth restriction or demise, abruptio placentae, congestive heart failure, and acute renal failure.3 This suggests that doctors caring for aortic coarctation patients should especially be vigilant for hypertensive complications during pregnancy in post-coarctectomy women with pre-pregnancy sustained hypertension.

Beauchesne et al.7 found that in eight women after repair of aortic coarctation with gestational hypertension, four patients (50%) had haemodynamically significant residual aortic gradients. The authors concluded that systemic hypertension during pregnancy in post-coarctectomy patients is related to significant aortic gradients. In our study, serial echocardiographic assessment of residual aortic gradients was only performed in eight patients. Five of these patients had an increase of the echo Doppler pressure gradient ≥15 mmHg, but only one patient required reintervention for recoarctation after delivery. In this patient, a blood pressure difference of 70 mmHg was measured during pregnancy, which dropped to 30 mmHg after delivery.19 So, the limited data available suggest that pregnancy may ‘unmask’ residual aortic gradients due to the circulatory changes associated with pregnancy.

In our study, the miscarriage rate was 18%. This miscarriage rate in our coarctation patients is as high as it is in women with complex congenital heart disease.20 This percentage is far higher than the miscarriage rate of 9% reported by Beauchesne et al.7 and to the expected national rate of 10%.5 The reason for this significant difference is not clear. Left-sided cardiac defects, such as coarctation of the aorta or hypoplastic heart syndrome, have among the highest reported risk of recurrence in offspring.21 This might explain the excess of miscarriages in women with aortic coarctation. However, selection bias may have occurred in both studies. No relationship was found between the presence of sustained hypertension and the occurrence of a miscarriage. In only four of the 22 miscarriages (18%), the patient was known with sustained hypertension.

In this study, 87% of the 98 deliveries were vaginal deliveries without epidural analgesia and 6% were CSs, of which three were emergency CSs. In the studies of Beauchesne et al.7 and Saidi et al.,6 the rates of CS reported were far higher: 30–40%. Our results are more in agreement with current guidelines, which state that vaginal delivery in patients with congenital heart disease is recommended with very few exceptions.22 Many authors advocate vaginal delivery with epidural analgesia with a low threshold for instrumentation or even CS.18,23,24 Our study demonstrates that excellent maternal and neonatal outcome of pregnancy can be obtained in women after repair of aortic coarctation using a conservative approach. Instrumentation, without maternal pushing in the second stage, or CS may be desirable in the occasional patient with uncontrollable systemic hypertension, marked aortic root dilatation, or severe recoarctation.23 Endocarditis prophylaxis was administered in 33% without a clear indication (instrumental delivery and/or premature rupture of membranes). This is probably representative for daily clinical practice. The incidence of bacteraemia in uncomplicated vaginal delivery is 1–5%.2527 This incidence increases up to 10% with premature rupture of membranes and with instrumental delivery.28 Many obstetricians and gynaecologists administer endocarditis prophylaxis without adhering to current guidelines to minimize even the slightest chance of this uncommon but serious complication or because time for antibiotics administration is often lacking when instrumentation is indicated.

Four of the 98 children (4%) were born with congenital heart disease. This is in agreement with the previous studies.6,7 Two children had aortic coarctation. For patients with congenital heart disease, the recurrence risk in offspring is highest for left-sided heart lesions and familial clustering with autosomal dominant, autosomal recessive, and complex patterns of inheritance have been described (heritability rates ranging from 0.58 for aortic coarctation up to 0.89 for bicuspid aortic valve).29,30 This recurrence risk may be even higher when miscarriages are included. Unfortunately, the risk of recurrence for any single family is difficult to predict because little is known about the specific causes.21 However, doctors caring for women with aortic coarctation should be aware of the increased recurrence risk in their offspring and should target counselling and resources appropriately.

Limitations

Several potential limitations must be noted. The retrospective design necessitated a review of patient's medical records and consequently, missing values are inevitable. Selection bias may have occurred, because 40% of the patients asked to participate did not respond, which may have influenced the results. Furthermore, this study was performed in women who had survived pregnancy and were alive at the time of this study.

Conclusions

Overall, maternal and neonatal outcome of pregnancy in women after repair of aortic coarctation is excellent. In this largest study to date, no major cardiovascular complications were encountered, but an excess of miscarriages and hypertensive disorders of pregnancy are common. Women with a history of coarctation repair, who contemplate pregnancy, should have haemodynamic assessment and genetic counselling, preferably before conception. Patients with pre-pregnancy sustained hypertension, aortic root dilatation, or recoarctation should probably be followed closely for early detection and prevention of obstetrical and/or cardiovascular complications. Vaginal delivery is the preferred mode of delivery with, in most cases, no need for epidural analgesia and instrumentation. A large, national prospective study will be undertaken to confirm the results of this and other studies on outcome of pregnancy in patients after repair of aortic coarctation.

Acknowledgement

This study was supported by The Netherlands Heart Foundation Grant 2002 B 125 to P.G.P. and the Interuniversity Cardiology Institute, The Netherlands (ICIN).

Table 1

Clinical characteristics

 Patients n=100 
Median age, years (range) 31.5 (19.5–68.1) 
Median age at repair, years (range) 6.2 (0.04–23.3) 
Associated cardiovascular defects  
 Patent arterial duct 13 (13) 
 Ventricular septal defect 10 (10) 
 Bicuspid aortic valve 51 (51) 
 Congenital aortic valvar stenosis 12 (12) 
 Atrial septal defect 3 (3) 
 Subvalvar aortic stenosis 5 (5) 
Type of repair  
 Resection and end-to-end 87 (87) 
 Subclavian flap aortoplasty 8 (8) 
 Patch aortoplasty 4 (4) 
 Interposition graft 1 (1) 
Reasons for reintervention  
 Recoarctation 13 (13) 
 Congenital aortic valvar stenosis 12 (12) 
 Ascending aortic aneurysm 2 (2) 
 Distal aortic arch aneurysm 4 (4) 
 Other 2 (2) 
Hypertension at the time of study 30 (30) 
 Patients n=100 
Median age, years (range) 31.5 (19.5–68.1) 
Median age at repair, years (range) 6.2 (0.04–23.3) 
Associated cardiovascular defects  
 Patent arterial duct 13 (13) 
 Ventricular septal defect 10 (10) 
 Bicuspid aortic valve 51 (51) 
 Congenital aortic valvar stenosis 12 (12) 
 Atrial septal defect 3 (3) 
 Subvalvar aortic stenosis 5 (5) 
Type of repair  
 Resection and end-to-end 87 (87) 
 Subclavian flap aortoplasty 8 (8) 
 Patch aortoplasty 4 (4) 
 Interposition graft 1 (1) 
Reasons for reintervention  
 Recoarctation 13 (13) 
 Congenital aortic valvar stenosis 12 (12) 
 Ascending aortic aneurysm 2 (2) 
 Distal aortic arch aneurysm 4 (4) 
 Other 2 (2) 
Hypertension at the time of study 30 (30) 

Data are presented as n (%).

Table 2

Primary reasons for being childless

 n=46 
Assumed risk of pregnancy related to cardiovascular history 
Age (too young) 29 
No child wish 
No partner 
Currently trying to become pregnant 
Social–economical situation (career, education) 
 n=46 
Assumed risk of pregnancy related to cardiovascular history 
Age (too young) 29 
No child wish 
No partner 
Currently trying to become pregnant 
Social–economical situation (career, education) 
Table 3

Obstetrical data on 126 pregnancies and 98 deliveries in 54 women

Variable Value 
Maternal age at first pregnancy (years), median (range) 28 (20–34) 
Pregnancies, number, median (range) 1 (1–5) 
Number of miscarriages 22 (18) 
Number of abortions 6 (6) 
All-cause hospitalization  
 Foetal growth retardation 2 (2) 
 Gestational hypertension 4 (4) 
 Pre‐eclampsia 5 (4) 
 Vaginal blood loss 1 (1) 
 Hyperemesis gravidarum 1 (1) 
 Respiratory insufficiency 1 (1) 
Place of delivery  
 Tertiary referral centre 37 (38%) 
 Secondary care centre 56 (57%) 
 Home (midwife) 5 (5%) 
Mode of delivery  
 Vaginal without epidural analgesia 85 (39) 
 Vaginal with epidural analgesia 7 (7) 
 Forcipal extraction 2 (2) 
 Vacuum extraction 19 (13) 
 Primary cesarean delivery 3 (3) 
 Secondary cesarean delivery 3 (3) 
Variable Value 
Maternal age at first pregnancy (years), median (range) 28 (20–34) 
Pregnancies, number, median (range) 1 (1–5) 
Number of miscarriages 22 (18) 
Number of abortions 6 (6) 
All-cause hospitalization  
 Foetal growth retardation 2 (2) 
 Gestational hypertension 4 (4) 
 Pre‐eclampsia 5 (4) 
 Vaginal blood loss 1 (1) 
 Hyperemesis gravidarum 1 (1) 
 Respiratory insufficiency 1 (1) 
Place of delivery  
 Tertiary referral centre 37 (38%) 
 Secondary care centre 56 (57%) 
 Home (midwife) 5 (5%) 
Mode of delivery  
 Vaginal without epidural analgesia 85 (39) 
 Vaginal with epidural analgesia 7 (7) 
 Forcipal extraction 2 (2) 
 Vacuum extraction 19 (13) 
 Primary cesarean delivery 3 (3) 
 Secondary cesarean delivery 3 (3) 

Data are expressed as number of events (number of women with at least one event) unless indicated otherwise.

Table 4

Data on 98 live births

Variable Value 
Pregnancy duration, weeks, median (range) 40 (28–43) 
Premature delivery 7 (6) 
Small for gestational age 4 (4) 
Infant weight (g), median (range) 3440 (1470–4970) 
Congenital heart defect in infant 4 (4) 
Variable Value 
Pregnancy duration, weeks, median (range) 40 (28–43) 
Premature delivery 7 (6) 
Small for gestational age 4 (4) 
Infant weight (g), median (range) 3440 (1470–4970) 
Congenital heart defect in infant 4 (4) 

Data are expressed as number of events (number of women with at least one event) unless indicated otherwise.

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