This Article Abstract Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by SM, S. C. S. Articles by Colman, J. M. Search for Related Content PubMed PubMed Citation Articles by SM, S. C. S. Articles by Colman, J. M.

(Circulation. 1997;96:2789-2794.)
© 1997 American Heart Association, Inc.

Articles

Risk and Predictors for Pregnancy-Related Complications in Women With Heart Disease

Samuel C. Siu SM, MD; Mathew Sermer, MD; David A. Harrison, MD; Elizabeth Grigoriadis, MD; Grace Liu, MD; Sheryll Sorensen, RN; Jeffrey F. Smallhorn BS, MB; Dan Farine, MD; Kofi S. Amankwah, MD; John C. Spears, MD; ; Jack M. Colman, MD

From the Division of Cardiology, Department of Medicine (S.C.S., D.A.H., E.G., J.M.C.) and Department of Obstetrics and Gynecology (M.S., G.L., S.S.), The Toronto Hospital; Division of Cardiology (J.M.C.) and Department of Obstetrics and Gynecology (D.F.), Mount Sinai Hospital; Division of Cardiology (J.C.S.) and Department of Obstetrics and Gynecology (K.S.A.), Women's College Hospital; and Division of Pediatric Cardiology (J.F.S.), Hospital for Sick Children, University of Toronto, Toronto, Canada.

Correspondence to Samuel Siu, MD, GW 3-526, 200 Elizabeth St, The Toronto Hospital, Toronto, Ontario, Canada, M5G 2C4. E-mail samuel.siu{at}utoronto.ca

	Abstract

Top Abstract Introduction Methods Results Discussion References

 
Background The physiological changes of pregnancy can result in cardiovascular complications in the mother, which in turn may have fetal implications. Prior studies have focused on specific cardiac lesions or identified univariate predictors. There is a need to refine the risk stratification of women with heart disease so they can receive appropriate obstetrical counseling and care.

Methods and Results We examined the outcomes of 221 women with heart disease who underwent 276 pregnancies and received their obstetrical care at three Toronto hospitals from 1986 through 1994. Those who underwent therapeutic abortions were excluded. Among the study participants, there were 24 miscarriages and 252 completed pregnancies (pregnancies not ending in miscarriage). Maternal heart failure, arrhythmia, or stroke occurred in 45 completed pregnancies (18%). There were no maternal deaths. Poor maternal functional class or cyanosis, myocardial dysfunction, left heart obstruction, prior arrhythmia, and prior cardiac events were predictive of maternal cardiac complications. These predictors were incorporated into a point score that can be used to estimate the probability of a cardiac complication in the mother. The rate of cardiac complications for a patient with 0, 1, and >1 of the above factors was 3%, 30%, and 66%, respectively. Neonatal complications occurred in 42 completed pregnancies (17%). Neonatal events included death (2), respiratory distress syndrome (16), intraventricular hemorrhage (2), premature birth (35), and small-for-gestational-age birth weight (14). Poor maternal functional class or cyanosis was predictive of neonatal events.

Conclusions Despite low maternal and neonatal mortality, pregnancy in women with heart disease is associated with significant cardiac and neonatal morbidity. The probability of maternal cardiac or neonatal events can be predicted from baseline characteristics of the mother.

Key Words: epidemiology • heart defects, congenital • prognosis

	Introduction

Top Abstract Introduction Methods Results Discussion References

 
Pregnancy is characterized by marked increases in stroke volume and cardiac output during the antepartum period.¹ Further fluctuations in cardiac output occur at the time of labor and after delivery. In the presence of maternal heart disease, the circulatory changes of pregnancy may result in decompensation or death of the mother or fetus.² Prior cardiac surgery may not be completely protective from pregnancy-related complications because hemodynamic and electrophysiological residua are common.^{3 4}

Increasing numbers of women with heart disease are reaching adulthood as a result of advances in diagnosis and treatment of heart disease in childhood and adolescence.^{5 6} As these women contemplate pregnancy, they seek counseling regarding maternal and fetal outcome. Current recommendations are based on studies that have focused on a particular cardiac lesion, examined populations before recent diagnostic and therapeutic advances, or identified univariate predictors.^{2 7 8 9 10 11 12 13} To refine the risk stratification of women with heart disease so they can receive appropriate obstetrical counseling and care, we examined the frequency and predictors of pregnancy-related complications in women with heart disease who received their obstetrical care at three major cardiac and obstetrical centers. A prediction rule incorporating the independent predictors of cardiac complications was derived.

	Methods

Top Abstract Introduction Methods Results Discussion References

 
In this retrospective cohort study, we examined the outcomes of 276 pregnancies in 221 women (mean±SD age, 29±5 years) with heart disease who received their obstetrical care at The Toronto Hospital, Mount Sinai Hospital, and Women's College Hospitals from 1986 through 1994. Heart disease in this group was congenital, acquired, or arrhythmic in origin. To be included in this study, all patients in whom cardiac arrhythmia was the primary diagnosis must have symptomatic sustained tachyarrhythmias or bradyarrhythmias requiring treatment before pregnancy. The study group included 13 patients previously reported in two case series.^{14 15} Patients with isolated mitral valve prolapse were excluded because this condition is not associated with an increased rate of pregnancy-related complications.¹⁶ Also excluded were 23 women with heart disease (29 pregnancies) who underwent therapeutic abortions.

The three hospitals form the University of Toronto Perinatal Complex (with 12 000 deliveries annually) and provide primary obstetrical and cardiac care in Toronto as well as tertiary care for metropolitan Toronto. All pregnant women with heart disease receiving care in these hospitals undergo standardized cardiac and obstetrical evaluations during their pregnancy. Their newborns were examined by a pediatrician before hospital discharge. Outcomes of newborns who were subsequently transferred to The Hospital for Sick Children, Toronto, for ongoing care were determined from the health records of that institution.

Definitions of predictors and outcomes were determined by consensus between a cardiologist and obstetrician (S.C.S. and M.S.) before data collection. Data were obtained from independent review of health and clinic records by two coauthors. Baseline data were collected before review of outcomes and included: maternal age, gestational age at 1st antenatal visit, New York Heart Association (NYHA) functional class at first antenatal visit, parity status, presence of hypertension, prior cardiac events (heart failure, transient ischemic attack, or stroke before present pregnancy; for those who underwent prior cardiac intervention, only events after the date of intervention were considered), cardiac medications and heparin administered during pregnancy, prior cardiac surgical repair, evidence of central cyanosis, smoking and alcohol use during pregnancy, and nature of the underlying cardiac lesion.

Adverse events occurring during the antepartum, peripartum, and postpartum periods (before hospital discharge) were recorded. The primary outcomes were maternal cardiac and neonatal events. Maternal cardiac outcomes were defined as new-onset heart failure (pulmonary edema by clinical assessment or chest roentgenography and requiring therapy), symptomatic tachyarrhythmia or bradyarrhythmia (documented by ECG and requiring therapy), stroke or transient ischemic attack of cardiac origin, or cardiac death. Neonatal outcomes were defined as prematurity (birth <37 weeks' gestation), small-for-gestational-age birth weight (birth weight <10th percentile for gestational age), respiratory distress syndrome, or intraventricular hemorrhage after birth, neonatal death, or stillbirth. Secondary outcomes were pregnancy-induced hypertension and postpartum hemorrhage. Pregnancy-induced hypertension was defined as a rise in systolic (30 mm Hg) or diastolic (15 mm Hg) blood pressure (compared with baseline) or a blood pressure of >140/90 mm Hg after 20 weeks' gestation. Postpartum hemorrhage was defined as an estimated blood loss of >500 mL during vaginal delivery or >1000 mL during cesarean section. This study procedure received human subject approval from the University of Toronto.

Statistical analyses were performed for cardiac, neonatal, and each of the secondary outcomes separately using the SAS-PC program. Potential predictors of adverse outcomes in pregnancies not ending in miscarriage (completed pregnancies) were examined with ² or Fisher's exact test. Potential predictors included baseline NYHA functional class, prior corrective surgery, prior cardiac events, and nature of underlying cardiac lesion. In view of the wide spectrum of cardiac lesions that were present as well as the presence of multiple types of lesions in a single patient, the mother's cardiac lesion in each pregnancy was classified as present or absent in each of the following pathophysiological categories: shunts, left heart obstruction, right heart obstruction, left heart regurgitation, right heart regurgitation, myocardial dysfunction, complex congenital, prior arrhythmia, and pulmonary hypertension (Table 1). The presence of obstruction, regurgitation, and left ventricular systolic dysfunction was defined by validated transthoracic echocardiographic (echo) indices obtained during the antepartum period.^{17 18 19 20 21 22 23} Valve areas used to define left heart obstruction were set at a level that could be hemodynamically sig-nificant in the presence of increased cardiac output in pregnancy.^{24 25} When antepartum echo was not performed, echo data within the preceding 2 years were used unless the patient had experienced a change in clinical status or undergone intervention.

View this table: [in this window] [in a new window]   Table 1. Definitions of Pathophysiological Categories

Statistically significant (P<.10) variables on univariate analysis were entered into a multivariate logistic-regression model with the significance level set at.01. To control for other factors that may influence outcome, the model included maternal age, parity status, gestational age at the baseline visit, twin gestations, hypertension or diabetes mellitus, smoking and alcohol use, and concurrent administration of heparin or cardiac medications. Because some women underwent several pregnancies, the assumption that each pregnancy is independent was confirmed by generalized estimating equation (GEE) analysis.²⁶ When more than one predictor was identified, the coefficients from the logistic regression model were converted into a point score. The point score was cross-validated on the study population using the Bootstrap technique.^{27 28}

	Results

Top Abstract Introduction Methods Results Discussion References

 
The baseline characteristics of the study group are outlined in Table 2. The majority of patients were in NYHA class I or II at the baseline visit. The mother was in NYHA class III at the baseline visit in 9 pregnancies (unrepaired tetralogy of Fallot, 6; severe aortic or mitral stenosis, 3). Ten pregnancies occurred in cyanotic mothers previously palliated with systemic-pulmonary shunts (tetralogy of Fallot, 8; pulmonary atresia, 2). Cyanosis was defined as the presence of central cyanosis with an underlying cardiac anatomy compatible with systemic arterial desaturation.¹² The mean oxygen saturation of cyanotic mothers at the baseline visit was 86% (SD, 2%; range, 83% to 89%). In 6 pregnancies, the mothers were cyanotic and in NYHA class III as a result of unrepaired tetralogy of Fallot.

View this table: [in this window] [in a new window]   Table 2. Baseline Maternal Characteristics

There were 24 miscarriages (spontaneous fetal loss before 20 weeks' gestation). The cardiac lesions in pregnancies ending in miscarriage were tetralogy of Fallot (8), mitral stenosis (4), tricuspid atresia (3), left-to-right shunt (3), congenital aortic stenosis (2), Ebstein's anomaly (1), left atrial myxoma (1), dilated cardiomyopathy (1), and Wolff-Parkinson-White syndrome (1).

A higher proportion of pregnancies ending in miscarriage was found in mothers with poor NYHA functional class or cyanosis (Table 2).

There were 252 completed pregnancies (205 women); 27% of deliveries were by cesarean section. The live birth rate for pregnancies that continued beyond 20 weeks was 100%. Six pregnancies produced twin births. Maternal cardiac lesion, operative status, and baseline characteristics of completed pregnancies are displayed in Table 3. The etiologies of the maternal cardiac lesions were congenital, acquired, or arrhythmia in 137 (55%), 87 (34%), and 28 (11%) pregnancies, respectively. In 15 pregnancies, multiple congenital lesions was present (aortic coarctation, left-to-right shunts, or valvular lesions associated with the congenital lesions delineated on Table 3). In 2 other pregnancies, mild rheumatic mitral stenosis was present together with the principal lesions of congenital aortic stenosis and coarctation. In 103 pregnancies (41%), the mother had undergone one or more of the following types of surgical repair before conception: (1) closure of cardiac shunts (n=28), (2) tetralogy of Fallot repair (n=20), (3) repair of double-outlet right ventricle (n=3), (4) Mustard repair or Rastelli repair for D-transposition (n=2), (5) Fontan repair for tricuspid atresia (n=2), (6) systemic atrioventricular mechanical valve replacement for L-transposition (n=1), (7) mitral valve commissurotomy or repair (n=18), (8) aortic or mitral valve replacement (bioprosthetic, 8; mechanical, 7), (9) aortic coarctation repair (n=11), (10) pulmonary valvotomy (n=5), (11) aortic valvotomy (n=4), (12) resection of left atrial myxoma (n=3), (13) bioprosthetic pulmonic valve replacement (n=2), (14) resection of left atrial membrane (n=1), or (15) tricuspid valve repair (n=3). In 16 pregnancies, the mother had experienced prior heart failure or transient ischemic attack (including 2 with heart failure during prior pregnancies).

View this table: [in this window] [in a new window]   Table 3. Nature of Cardiac Lesion in Completed Pregnancies and Subsequent Outcomes

The proportion of completed pregnancies with valvular obstruction or low systemic ejection fraction is outlined in Table 3. Of the 60 pregnancies that occurred in women with left heart obstruction, 35 were in women with mitral stenosis and 29 were in those with aortic stenosis. In 4 pregnancies, the mother had combined aortic and mitral stenoses. The mean mitral valve area was 1.5±0.3 cm² (range, 0.8 to 1.9 cm²) in women with mitral stenosis. In those with aortic stenosis, the mean aortic valve area was 1.0±0.2 cm² (range, 0.5 to 1.4 cm²), and the mean peak instantaneous outflow gradient was 47±22 mm Hg (range, 23 to 116 mm Hg). Patients with aortic stenosis have valvular involvement, except for 3 patients with subaortic stenosis (2 with subaortic membrane and 1 with hypertrophic cardiomyopathy). All patients with Marfan syndrome had normal aortic root diameter. No patient who had undergone repair of coarctation had residual coarctation on echo.

Pulmonary hypertension was present in 8 completed pregnancies and was the result of atrial or ventricular septal defect (n=3), severe mitral stenosis (n=1), systemic-pulmonary shunts (n=3), or primary pulmonary hypertension (n=1). The systolic pulmonary artery pressure in this group was 71±20 mm Hg (mean±SD; range, 53 to 99 mm Hg). There were no patients with Eisenmenger syndrome.

A maternal cardiac event, neonatal event, or both occurred in 71 completed pregnancies (28%). Associations between parity status, events during previous pregnancies, twin gestations, and adverse events (cardiac or neonatal) were not identified. A cardiac event complicated 45 completed pregnancies (18%), with no maternal deaths. Most cardiac events (89%) occurred in the antepartum period and were either heart failure or cardiac arrhythmia (Table 3). One embolic stroke occurred in a woman with an atrioventricular defect. In 2 pregnancies, refractory heart failure required urgent intervention (percutaneous aortic valvuloplasty in 1 and mitral valve replacement in another). A third pregnancy was complicated by postpartum thrombosis of the mechanical mitral valve, which was successfully treated by intravenous thrombolysis.

Predictors of Cardiac Events and Prediction Rule
Multivariate analysis identified five independent predictors of maternal cardiac events: (1) prior cardiac events, (2) prior arrhythmia, 3) NYHA functional class of >II or cyanosis during the baseline antenatal visit, (4) left heart obstruction, and (5) myocardial dysfunction (Table 4). NYHA >II correlated with cyanosis and were combined in a single category. The C statistic was .81. The model resulting from GEE analysis was identical; repeated pregnancies in the same mother can be assumed to be statistically independent. Identical results were noted when the analysis was confined to the 199 pregnancies in which echo was performed in the antepartum period rather than within the previous 2 years.

View this table: [in this window] [in a new window]   Table 4. Results of Multivariate Analysis

Independent predictors of cardiac events were incorporated into a point score in which a patient was assigned 1 point for each of the predictors present (NYHA >II or cyanosis, prior arrhythmia, myocardial dysfunction, left heart obstruction, or prior cardiac events). Although the maximum possible score was 5, no pregnancy in this study had more than 3 points. An increase in the number of total points corresponds to an increasing risk of a cardiac event (Figure). The observed cardiac event rate in pregnancies with 0, 1, and >1 of the above predictors was 3%, 30%, and 66% respectively; the expected event rate in the corresponding categories was 5%, 27%, and 75%. When the threshold of the point score was set at 0 versus 1 through 3 (presence or absence of a predictor), its sensitivity and specificity were 91% and 61%, respectively; the likelihood ratio for the presence and absence of any predictor was 2.33 and 0.15, respectively. The C statistic of the prediction rule was .79, suggesting little loss in discriminative accuracy with the use of the point score. The logistic regression model was cross-validated on the original study group by the Bootstrap technique, which yielded similar parameter estimates as the original model.

View larger version (11K): [in this window] [in a new window]   Figure 1. Graph displaying the expected (in black) and observed (in white) rate of cardiac event (y axis) versus increasing number of total points (x axis) for those patients whose pregnancies did not end in miscarriage. The number of pregnancies in the 0, 1, and >1 categories was 130, 108, and 14, respectively. Pregnancies in which the number of points was either 2 or 3 were combined together because only one pregnancy had 3 points.

Predictors of Neonatal and Secondary Events
Neonatal complications occurred in 42 pregnancies (17%) and included neonatal death (2), respiratory distress syndrome (16), intraventricular hemorrhage (2), premature birth (35), and small-for-gestational-age birth weight (14). Except for one neonate who experienced meconium aspiration during a term delivery, all neonates with respiratory distress syndrome or intraventricular hemorrhage were the result of prematurity. Both neonatal deaths from respiratory distress syndrome and intraventricular hemorrhage were a result of prematurity. NYHA >II or cyanosis during the baseline visit independently predicted neonatal complications (Table 4). Premature onset of labor was associated with antepartum maternal cardiac events (23% and 9% rate of premature labor; mothers with and without antepartum cardiac events; P=.01). Of the 137 pregnancies (140 live births) in women with congenital heart disease, 4% of live births had congenital heart disease (n=6; 3 with ventricular septal defects, 1 each with atrioventricular septal defect, tricuspid atresia, pulmonary artery hypoplasia).

Postpartum hemorrhage (n=18) or pregnancy-induced hypertension (n=10) was observed in 28 completed pregnancies (11%). Women with NYHA functional class >II or cyanosis were at a higher risk for postpartum hemorrhage than those with NYHA class I or II who were not cyanotic (Table 4). Patients with aortic coarctation were at increased risk for pregnancy-induced hypertension. For neonatal and secondary outcomes, GEE analysis again confirmed the validity of treating each pregnancy as an independent entry.

	Discussion

Top Abstract Introduction Methods Results Discussion References

 
This study provides a contemporary estimate of cardiac and neonatal event rates in the setting of comprehensive antenatal care. The low maternal and neonatal mortality observed in this study may be due to greater vigilance in the care of pregnant women with heart disease or the avoidance of pregnancy by women in higher-risk groups. However, pregnant women with heart disease continue to be at risk for maternal and neonatal morbidity. Although maternal heart failure and arrhythmia did not result in maternal death in this study, we observed an association between antepartum maternal cardiac events and premature labor. Thus, a focus on maternal mortality as the only cardiac endpoint may underestimate the effect of maternal cardiac status on fetal well-being.

Poor functional status and cyanosis have been previously identified to be associated with maternal or fetal complications. Our report establishes the independent role of poor maternal functional class and cyanosis in predicting maternal and neonatal complications.^{8 9 10 12} We also quantified the association of myocardial dysfunction, preexisting arrhythmia, left heart obstruction, and history of prior cardiac events with the risk of maternal cardiac complications during pregnancy. The association between left heart obstruction and myocardial dysfunction to cardiac events is probably mediated by the changes in cardiac output, heart rate, and systemic vascular resistance during pregnancy.¹ Pregnancy may also be a proarrhythmic state.^{29 30} The mechanism of the observed association between coarctation and pregnancy-induced hypertension in this study may be related to residual baroreceptor and compliance abnormalities.³¹

In contrast to prior studies, pulmonary hypertension and prior cardiac surgery were not associated with complications in this study.^{8 9 10 32} However, there were no women with Eisenmenger syndrome in this study, probably because the results of prior studies dissuaded affected women from childbearing. The moderate elevation of pulmonary arterial pressures in our patients may confer a lower risk than that associated with Eisenmenger syndrome. Operative status was not predictive of complications in this study, possibly due to the presence of hemodynamic or electrophysiological residua.

The point score derived in this study is used to assess the risk of cardiac events from baseline clinical and echo assessments of the mother with heart disease. By combining cardiac lesions with similar hemodynamic bases into a single category, as was done previously,^{8 9} this strategy maximized the power to identify independent predictors. However, some categories, such as pulmonary hypertension, may not be predictive of complications because of small numbers. A larger patient sample may allow the identification of additional risk factors.²⁸ Thus, in the case of cardiac lesions, which are infrequently encountered in pregnant women, the risk score will supplement rather than replace lesion-specific risk factors. For example, the association between aortic root size and risk in Marfan syndrome could not be assessed because all affected patients in this study had normal aortic root size and were prophylactically treated with ß-adrenergic blockers.^{33 34} Similarly, fetal effects of amiodarone cannot be evaluated because most patients receiving cardiac medications in this study were treated with agents with known safety profiles.^{35 36 37 38}

Selection bias in this study was minimized by the current practice within our catchment area to refer pregnant women with suspected heart disease to specialized centers. Universal access to health care in the Province of Ontario, Canada, also reduced selection bias by allowing consistent follow-up of all pregnant women during pregnancy and after delivery. Measurement bias was minimized by the use of standardized antenatal records in the Province of Ontario and by the use of biologically based end points. Although cross-validated in the study population, the prediction rule will require prospective validation to establish its generalizability. After prospective validation, the prediction rule will be applicable in prepregnancy counseling as well as the obstetrical care of women with heart disease. Those at increased risk can be appropriately managed in specialized facilities, whereas those at low risk may receive their care in the community setting. The effects of pregnancy on the subsequent course of maternal cardiac lesions will require further study.

	Acknowledgments

 
This study was supported in part by grants from the Physicians' Services Incorporated Foundation and Medical Research Council of Canada. We also thank Prof F. Cook (Harvard School of Public Health, Boston, Mass) and Dr P. Lewycky (The Toronto Hospital) for their expert statistical advice and assistance.

	Footnotes

 
Presented in part at the 45th scientific session, American College of Cardiology, Orlando, Fla, 1996.

Received January 8, 1997; revision received May 28, 1997; accepted June 6, 1997.

	References

Top Abstract Introduction Methods Results Discussion References

 
1. Metcalfe J, Ueland K. Maternal cardiovascular adjustment to pregnancy. Prog Cardiovasc Dis. 1974;16:363-374.[Medline] [Order article via Infotrieve]

2. Clark SL. Cardiac disease in pregnancy. Obstet Gynaecol Clin North Am. 1991;18:237-256.

3. Stevenson WG, Klitzner T, Perloff JK. Electrophysiologic abnormalities, natural occurrence and postoperative residua and sequelae. In: Perloff JK, Child JS, eds. Congenital Heart Disease in Adults. Philadelphia, Pa: WB Saunders; 1991:259-295.

4. Stuhlmuller JE, Perloff JK, Skorton DJ. Valvular residua and sequelae after cardiac surgery or interventional cardiac catheterization. In: Perloff JK, Child JS, eds. Congenital Heart Disease in Adults. Philadelphia, Pa: WB Saunders; 1991:296-312.

5. Congenital heart disease after pediatrics: an expanding patient population: 22nd Bethesda Conference. J Am Coll Cardiol. 1991;18:311-342.[Medline] [Order article via Infotrieve]

6. Pitkin RM, Perloff JK, Koos BJ, Beall MH. Pregnancy and heart disease. Ann Intern Med. 1990;112:445-454.

7. Ueland K. Rheumatic heart disease and pregnancy. In: Elkayam U, Gleicher N, eds. Cardiac Problems in Pregnancy: Diagnosis and Management of Maternal and Fetal Disease, 2nd ed. New York, NY: Alan R Liss, Inc; 1990:99-107.

8. Shime J, Mocarski EJM, Hastings D, Webb GD, McLaughlin PR. Congenital heart disease in pregnancy: short- and long-term implications. Am J Obstet Gynecol. 1987;156:313-322.[Medline] [Order article via Infotrieve]

9. Whittemore R, Hobbins JC, Engle MA. Pregnancy and its outcome in women with and without surgical treatment of congenital heart disease. Am J Cardiol. 1982;50:641-651.[Medline] [Order article via Infotrieve]

10. McFaul PB, Dornan JC, Lamki H, Boyle D. Pregnancy complicated by maternal heart disease: a review of 519 women. Br J Obstet Gynaecol. 1988;95:861-867.[Medline] [Order article via Infotrieve]

11. Clarkson PM, Wilson NJ, Neutze JM, North RA, Calder AL, Barratt-Boyes BG. Outcome of pregnancy after the Mustard operation for transposition of the great arteries with intact ventricular septum. J Am Coll Cardiol. 1994;24:190-193.[Abstract]

12. Presbitero P, Somerville J, Stone S, Aruta E, Spiegelhalter D, Rabajoli F. Pregnancy in cyanotic congenital heart disease: outcome of mother and fetus. Circulation. 1994;89:2673-2676.[Abstract/Free Full Text]

13. Connolly HM, Warnes CA. Ebstein's anomaly: outcome of pregnancy. J Am Coll Cardiol. 1994;23:1194-1198.[Abstract]

14. Lao TT, Sermer M, MaGee L, Farine D, Colman JM. Congenital aortic stenosis and pregnancy: a reappraisal. Am J Obstet Gynecol. 1993;169:540-545.[Medline] [Order article via Infotrieve]

15. Lao TT, Sermer M, Colman JM. Pregnancy following surgical correction for transposition of the great arteries. Obstet Gynecol. 1994;83:665-668.[Medline] [Order article via Infotrieve]

16. Rayburn WF. Mitral valve prolapse and pregnancy. In: Elkayam U, Gleicher N, eds. Cardiac Problems in Pregnancy: Diagnosis and Management of Maternal and Fetal Disease, 2nd ed. New York, NY: Alan R Liss, Inc; 1990:181-188.

17. Hatle L, Angelsen B. Pulsed and continuous wave Doppler in diagnosis and assessment of various heart lesions. In: Hatle L, Angelsen B, eds. Doppler Ultrasound in Cardiology: Physical Principles and Clinical Applications, 2nd ed. Philadelphia, Pa: Lea & Febiger; 1982:97-292.

18. Skjaerpe T, Hegrenaes L, Hatle L. Noninvasive estimation of valve area in patients with aortic stenosis by Doppler ultrasound and two-dimensional echocardiography. Circulation. 1985;72:810-818.[Abstract/Free Full Text]

19. Miyatake K, Okamoto M, Kinoshita N, Ohta M, Kozuka T, Sakakibara H, Nimura Y. Evaluation of tricuspid regurgitation by pulsed Doppler and two-dimensional echocardiography. Circulation. 1982;66:777-784.[Abstract/Free Full Text]

20. Weyman AE. Right ventricular outflow tract. In: Weyman AE, ed. Principles and Practice of Echocardiography. Philadelphia, Pa: Lea & Febiger; 1994:863-900.

21. Perry GJ, Helmcke F, Nanda NC, Byard C, Soto B. Evaluation of aortic insufficiency by Doppler color flow mapping. J Am Coll Cardiol. 1987;9:952-959.[Abstract]

22. Teague SM, Heinsimer JA, Anderson JL, Sublett K, Olson EG, Voyles WF, Thadani U. Quantification of aortic regurgitation utilizing continuous-wave Doppler ultrasound. J Am Coll Cardiol. 1986;8:592-599.[Abstract]

23. Stamm RB, Carabello BA, Mayers DL, Martin RP. Two-dimensional echocardiographic measurement of left ventricular ejection fraction: prospective analysis of what constitutes an adequate determination. Am Heart J. 1982;104:135-144.

24. Rahimtoola SH. Perspective on valvular heart disease: an update. J Am Coll Cardiol. 1989;14:1-23.[Medline] [Order article via Infotrieve]

25. Carabello BA, Grossman W. Calculation of stenotic valve orifice area. In: Grossman W, ed. Cardiac Catheterization and Angiography, 3rd ed. Philadelphia, Pa: Lea & Febiger; 1986:143-154.

26. Zeger SC, Liang KY. Longitudinal data analysis for discrete and continuous outcomes. Biometrics. 1986;42:121-130.[Medline] [Order article via Infotrieve]

27. Diaconis P, Efron B. Computer-intensive methods in statistics. Sci Am. 1983;248:116-130.

28. Wasson JH, Sox HC, Neff RK, Goldman L. Clinical prediction rules: application and methodological standards. N Engl J Med. 1985;313:793-799.[Abstract]

29. Lee SH, Chen SA, Wu TJ, Chiang CE, Cheng CC, Tai CT, Chiou CW, Ueng KC, Chang MS. Effects of pregnancy on first onset and symptoms of paroxysmal supraventricular tachycardia. Am J Cardiol. 1995;76:675-678.[Medline] [Order article via Infotrieve]

30. Hong RA, Bhandari AK. Cardiac arrhythmias and pregnancy. In: Elkayam U, Gleicher N, eds. Cardiac Problems in Pregnancy: Diagnosis and Management of Maternal and Fetal Disease, 2nd ed. New York, NY: Alan R Liss, Inc; 1990:167-180.

31. Simsolo R, Grunfeld B, Gimenez M, Lopez M, Berri G, Becu L, Barontini M. Long term systemic hypertension in children after successful repair of coarctation of the aorta. Am Heart J. 1988;115:1268-1273.[Medline] [Order article via Infotrieve]

32. Gleicher N, Midwall J, Hochberger D, Jaffin H. Eisenmenger's syndrome and pregnancy. Obstet Gynecol Surv. 1979;34:721-741.[Medline] [Order article via Infotrieve]

33. Pyeritz RE. Maternal and fetal complications of pregnancy in the Marfan syndrome. Am J Med. 1981;71:784-790.[Medline] [Order article via Infotrieve]

34. Shores J, Berger KR, Murphy EA, Pyeritz RE. Progression of aortic dilatation and the benefit of long-term beta-adrenergic blockade in Marfan's syndrome. N Engl J Med. 1994;330:1335-1341.[Abstract/Free Full Text]

35. Fishman WH, Chesner M. Use of beta-adrenergic blocking agents in pregnancy. In: Elkayam U, Gleicher N, eds. Cardiac Problems in Pregnancy: Diagnosis and Management of Maternal and Fetal Disease, 2nd ed. New York, NY: Alan R Liss, Inc; 1990:351-359.

36. Rotmensch HH, Pines A, Donchin Y. Antiarrhythmic drugs in pregnancy. In: Elkayam U, Gleicher N, eds. Cardiac Problems in Pregnancy: Diagnosis and Management of Maternal and Fetal Disease, 2nd ed. New York, NY: Alan R Liss, Inc; 1990:361-379.

37. Myers SA. Antihypertensive drug use during pregnancy. In: Elkayam U, Gleicher N, eds. Cardiac Problems in Pregnancy: Diagnosis and Management of Maternal and Fetal Disease, 2nd ed. New York, NY: Alan R Liss, Inc; 1990:381-395.

38. McGehee W. Anticoagulation in pregnancy. In: Elkayam U, Gleicher N, eds. Cardiac Problems in Pregnancy: Diagnosis and Management of Maternal and Fetal Disease, 2nd ed. New York, NY: Alan R Liss, Inc; 1990:397-415.

This article has been cited by other articles:

				O. Loup, C. von Weissenfluh, B. Gahl, M. Schwerzmann, T. Carrel, and A. Kadner Quality of life of grown-up congenital heart disease patients after congenital cardiac surgery Eur. J. Cardiothorac. Surg., July 1, 2009; 36(1): 105 - 111. [Abstract] [Full Text] [PDF]

				P. Presbitero, G. G. Boccuzzi, C. J.M. Groot, and J. W. Roos-Hesselink CHAPTER 33 Pregnancy and Heart Disease ESC Textbook of Cardiovascular Medicine, January 1, 2009; 2(1): med-9780199566990-chapter - med-9780199566990-chapter. [Abstract] [Full Text] [PDF]

				C. A. Warnes, R. G. Williams, T. M. Bashore, J. S. Child, H. M. Connolly, J. A. Dearani, P. del Nido, J. W. Fasules, T. P. Graham Jr, Z. M. Hijazi, et al. ACC/AHA 2008 Guidelines for the Management of Adults With Congenital Heart Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Develop Guidelines on the Management of Adults With Congenital Heart Disease) Developed in Collaboration With the American Society of Echocardiography, Heart Rhythm Society, International Society for Adult Congenital Heart Disease, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons J. Am. Coll. Cardiol., December 2, 2008; 52(23): e143 - e263. [Full Text] [PDF]

				C. A. Warnes, R. G. Williams, T. M. Bashore, J. S. Child, H. M. Connolly, J. A. Dearani, P. del Nido, J. W. Fasules, T. P. Graham Jr, Z. M. Hijazi, et al. ACC/AHA 2008 Guidelines for the Management of Adults With Congenital Heart Disease: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Adults With Congenital Heart Disease) Developed in Collaboration With the American Society of Echocardiography, Heart Rhythm Society, International Society for Adult Congenital Heart Disease, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons J. Am. Coll. Cardiol., December 2, 2008; 52(23): 1890 - 1947. [Full Text] [PDF]

				C. A. Warnes, R. G. Williams, T. M. Bashore, J. S. Child, H. M. Connolly, J. A. Dearani, P. del Nido, J. W. Fasules, T. P. Graham Jr, Z. M. Hijazi, et al. ACC/AHA 2008 Guidelines for the Management of Adults With Congenital Heart Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Develop Guidelines on the Management of Adults With Congenital Heart Disease): Developed in Collaboration With the American Society of Echocardiography, Heart Rhythm Society, International Society for Adult Congenital Heart Disease, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons Circulation, December 2, 2008; 118(23): e714 - e833. [Full Text] [PDF]

				C. A. Warnes, R. G. Williams, T. M. Bashore, J. S. Child, H. M. Connolly, J. A. Dearani, P. del Nido, J. W. Fasules, T. P. Graham Jr, Z. M. Hijazi, et al. ACC/AHA 2008 Guidelines for the Management of Adults With Congenital Heart Disease: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Adults With Congenital Heart Disease): Developed in Collaboration With the American Society of Echocardiography, Heart Rhythm Society, International Society for Adult Congenital Heart Disease, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons Circulation, December 2, 2008; 118(23): 2395 - 2451. [Full Text] [PDF]

				V. Stangl, J. Schad, G. Gossing, A. Borges, G. Baumann, and K. Stangl Maternal heart disease and pregnancy outcome: A single-centre experience Eur J Heart Fail, September 1, 2008; 10(9): 855 - 860. [Abstract] [Full Text] [PDF]

				D L Adamson and C Nelson-Piercy Managing palpitations and arrhythmias during pregnancy Postgrad. Med. J., February 1, 2008; 84(988): 66 - 72. [Full Text] [PDF]

				D. L Adamson and C. Nelson-Piercy Managing palpitations and arrhythmias during pregnancy Heart, December 1, 2007; 93(12): 1630 - 1636. [Full Text] [PDF]

				W. Drenthen, P. G. Pieper, J. W. Roos-Hesselink, W. A. van Lottum, A. A. Voors, B. J.M. Mulder, A. P.J. van Dijk, H. W. Vliegen, S. C. Yap, P. Moons, et al. Outcome of Pregnancy in Women With Congenital Heart Disease: A Literature Review J. Am. Coll. Cardiol., June 19, 2007; 49(24): 2303 - 2311. [Abstract] [Full Text] [PDF]

				W Drenthen, P G Pieper, J W Roos-Hesselink, A C M Schmidt, B J M Mulder, A P J van Dijk, H W Vliegen, K M Sollie, A A Voors, T Ebels, et al. Non-cardiac complications during pregnancy in women with isolated congenital pulmonary valvar stenosis Heart, December 1, 2006; 92(12): 1838 - 1843. [Abstract] [Full Text] [PDF]

				W Drenthen, P G Pieper, J W Roos-Hesselink, W A van Lottum, A A Voors, B J M Mulder, A P J van Dijk, H W Vliegen, K M Sollie, P Moons, et al. Pregnancy and delivery in women after Fontan palliation Heart, September 1, 2006; 92(9): 1290 - 1294. [Abstract] [Full Text] [PDF]

				A. Uebing, P. J Steer, S. M Yentis, and M. A Gatzoulis Pregnancy and congenital heart disease BMJ, February 18, 2006; 332(7538): 401 - 406. [Full Text] [PDF]

				K Stout Pregnancy in women with congenital heart disease: the importance of evaluation and counselling Heart, June 1, 2005; 91(6): 713 - 714. [Abstract] [Full Text] [PDF]

				J. Arafeh and Y. Y. El-Sayed Cardiac Disease in Pregnancy NeoReviews, June 1, 2004; 5(6): e232 - e239. [Full Text] [PDF]

				R Thaman, A Varnava, M S Hamid, S Firoozi, B Sachdev, M Condon, J R Gimeno, R Murphy, P M Elliott, and W J McKenna Pregnancy related complications in women with hypertrophic cardiomyopathy Heart, July 1, 2003; 89(7): 752 - 756. [Abstract] [Full Text] [PDF]

				The Task Force on the Management of Grown Up Conge, Task Force members, J. Deanfield, E. Thaulow, C. Warnes, G. Webb, F. Kolbel, A. Hoffman, K. Sorenson, H. Kaemmerer, et al. Management of Grown Up Congenital Heart Disease Eur. Heart J., June 1, 2003; 24(11): 1035 - 1084. [Full Text] [PDF]

				N. Campbell, O. P. Rosaeg, and K. L. Chan Anaesthetic management of a parturient with pulmonary stenosis and aortic incompetence for Caesarean section Br. J. Anaesth., February 1, 2003; 90(2): 241 - 243. [Abstract] [Full Text] [PDF]

				S. C. Siu, M. Sermer, J. M. Colman, A. N. Alvarez, L.-A. Mercier, B. C. Morton, C. M. Kells, M. L. Bergin, M. C. Kiess, F. Marcotte, et al. Prospective Multicenter Study of Pregnancy Outcomes in Women With Heart Disease Circulation, July 31, 2001; 104(5): 515 - 521. [Abstract] [Full Text] [PDF]

				S. C Siu and J. M Colman CONGENITAL HEART DISEASE: Heart disease and pregnancy Heart, June 1, 2001; 85(6): 710 - 715. [Full Text]

				E. Foster, T. P. Graham Jr., D. J. Driscoll, G. J. Reid, J. G. Reiss, I. A. Russell, M. Sermer, S. C. Siu, K. Uzark, R. G. Williams, et al. Task Force 2: special health care needs of adults with congenital heart disease J. Am. Coll. Cardiol., April 1, 2001; 37(5): 1176 - 1183. [Full Text] [PDF]

				B.M Weiss and O.M Hess Pulmonary vascular disease and pregnancy: current controversies, management strategies, and perspectives Eur. Heart J., January 2, 2000; 21(2): 104 - 115. [PDF]

				S. SIU, D. CHITAYAT, and G. WEBB Pregnancy in women with congenital heart defects: what are the risks? Heart, March 1, 1999; 81(3): 225 - 226. [Full Text]

				M Zuber, N Gautschi, E Oechslin, V Widmer, W Kiowski, and R Jenni Outcome of pregnancy in women with congenital shunt lesions Heart, March 1, 1999; 81(3): 271 - 275. [Abstract] [Full Text]

				M A Gatzoulis, S Hechter, S C Siu, and G D Webb Outpatient clinics for adults with congenital heart disease: increasing workload and evolving patterns of referral Heart, January 1, 1999; 81(1): 57 - 61. [Abstract] [Full Text]

				PREGNANCY IN WOMEN WITH HEART DISEASE: HOW SAFE? Journal Watch (General), November 21, 1997; 1997(1121): 2 - 2. [Full Text]

				S. C. Siu, J. M. Colman, S. Sorensen, J. F. Smallhorn, D. Farine, K. S. Amankwah, J. C. Spears, and M. Sermer Adverse Neonatal and Cardiac Outcomes Are More Common in Pregnant Women With Cardiac Disease Circulation, May 7, 2002; 105(18): 2179 - 2184. [Abstract] [Full Text] [PDF]

This Article Abstract Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by SM, S. C. S. Articles by Colman, J. M. Search for Related Content PubMed PubMed Citation Articles by SM, S. C. S. Articles by Colman, J. M.