Journal of the American College of Cardiology Vol. 44, No.

1, 2004
© 2004 by the American College of Cardiology Foundation ISSN 0735-1097/04/$30.00
Published by Elsevier Inc. doi:10.1016/j.jacc.2003.11.067

Congenital Heart Disease

Outcomes of Pregnancy in
Women With Tetralogy of Fallot
Gruschen R. Veldtman, MBCHB, MRCP, Heidi M. Connolly, MD, FACC, Martha Grogan, MD, FACC,
Naser M. Ammash, MD, FACC, Carole A. Warnes, MD, MRCP, FACC
Rochester, Minnesota
OBJECTIVES We sought to determine pregnancy outcomes in patients with tetralogy of Fallot (TOF).
BACKGROUND Pregnancy outcomes in patients with TOF are incompletely defined.
METHODS Clinical, hemodynamic, and obstetric data were reviewed for women with TOF and prior
pregnancy.
RESULTS Of 72 respondents, 43 (mean age, 26 years) had 112 pregnancies (range, 1 to 5); 82
pregnancies were successful. Eight women had unrepaired TOF at the time of their 20
successful pregnancies. At first assessment (age ⱖ18 years), six patients had pulmonary
hypertension, three had moderate or severe right ventricular (RV) systolic dysfunction, and 13
had severe RV dilation due to pulmonic regurgitation. Sixteen patients had 30 miscarriages
(27%) and one term stillbirth. Mean overall birth weight was 3.2 kg (range, 2.1 to 4.2 kg).
Unrepaired TOF (p ⫽ 0.05) and morphologic pulmonary artery abnormality (p ⫽ 0.03) were
independently predictive of infant birth weight. Six patients had cardiovascular complications
during pregnancy: supraventricular tachycardia in two, heart failure in two, pulmonary
embolism in a patient with pulmonary hypertension, and progressive RV dilation in a patient
with severe pulmonic regurgitation. Five infants (6%) had congenital anomalies.
CONCLUSIONS Patients with TOF have an increased risk of fetal loss, and their offspring are more likely to
have congenital anomalies than offspring in the general population. Adverse maternal events,
although rare, may be associated with left ventricular dysfunction, severe pulmonary
hypertension, and severe pulmonic regurgitation with RV dysfunction. (J Am Coll Cardiol
2004;44:174 – 80) © 2004 by the American College of Cardiology Foundation

Tetralogy of Fallot (TOF) is the most common cyanotic
congenital heart defect and accounts for 5% to 6% of
congenital heart malformations (1). Its hallmark anterior
and superior infundibular septal displacement gives rise to
the tetrad of ventricular septal defect, aortic override,
infundibular obstruction, and right ventricular (RV) hyper-
trophy (2,3). Intracardiac repair, performed since the 1950s,
See page 181
has permitted survival into the childbearing years and
excellent quality of life (4). Long-term complications usually
relate to functional competence of the RV outflow tract and
its secondary effects on ventricular and atrial myocardial
function (5,6). Pulmonary regurgitation or stenosis may
result in RV dysfunction and failure, progressive tricuspid
valve regurgitation, atrial and ventricular arrhythmias, and
sudden cardiac death (7,8). Less common problems include
persistent left-to-right shunts and pulmonary hypertension
(PHT), ascending aortic aneurysm, and aortic valve regur-
gitation.
Although successful pregnancy has been documented in
small series (9 –13), data are incomplete for maternal and
From the Division of Cardiovascular Diseases and Internal Medicine, Mayo Clinic,
Rochester, Minnesota.
Manuscript received May 19, 2003; revised manuscript received October 24, 2003,
accepted November 24, 2003.
fetal outcomes in women with TOF. We reviewed the
Mayo Clinic records of 147 female patients with TOF to
determine the outcomes of pregnancy.
METHODS
A total of 147 women (ⱖ18 years old) with a diagnosis of
TOF were identified from the Mayo Clinic congenital heart
disease database. Medical and surgical records were re-
viewed for anatomic characteristics before repair and for
details of surgical repair and reoperation. Among patients
with pregnancies, we determined hemodynamic and clinical
status from echocardiography, cardiac catheterization, and
clinical reports. Status was determined before and after each
pregnancy when available, at first Mayo Clinic assessment as
an adult, and at latest clinical assessment. Hemodynamic
data considered for analysis were from within two years
before the last menstrual period before pregnancy and
within two years after delivery.
Patients were contacted by telephone or mail. All patients
provided an obstetric history, including details of pregnancy,
delivery, and fetal outcome. All newborns with congenital
heart disease were seen by a pediatric cardiologist, and
medical records were reviewed when appropriate. Diagnosis
of TOF was verified for all patients at the time of echocar-
diography, cardiac catheterization, or surgery. Patients with
pulmonary atresia were excluded. The protocol was re-
JACC Vol. 44, No. 1, 2004
July 7, 2004:174–80
Abbreviations and Acronyms
LV ⫽ left ventricle/ventricular
PA ⫽ pulmonary artery
PHT ⫽ pulmonary hypertension
RV ⫽ right ventricle/ventricular
TOF ⫽ tetralogy of Fallot
viewed and approved by the Mayo Foundation Institutional
Review Board.
Statistical methods. Mean, standard deviation, median,
and range were determined for continuous variables when
appropriate; frequencies were determined for nominal and
ordinal variables. Histograms were used to assess the distri-
butions of continuous variables and to determine whether
the parametric Student t test or the nonparametric Wil-
coxon rank-sum test was more appropriate for comparison
between groups. Univariate analyses were used to examine
associations between clinical and hemodynamic factors and
to determine outcome parameters affecting infant birth
weight and the number of spontaneous pregnancy losses.
Candidates found to be statistically significant or nearly
statistically significant (p ⬍ 0.13) were considered as can-
didate variables in the multivariate models: linear regression
for birth weight and binary logistic regression for pregnancy
loss. If candidate variables were found to be highly corre-
lated with each other (i.e., r ⱖ 0.8), the most significant
factor was used in the multivariate regression model.
RESULTS
A total of 147 female patients with TOF were identified. Of
these, 17 had died (no deaths occurred peripartum), 21 were
lost to follow-up, and 2 were institutionalized for develop-
mental delay. Of the 107 patients invited to participate in
the study, 72 (67%) responded and participated in this
investigation; 43 had pregnancies.
Anatomic characteristics. All patients had anatomically
confirmed TOF. The most common associated anomalies
were pulmonary artery (PA) anomalies (hypoplastic, absent,
or disconnected PA or ductal origin of PA) in 9 patients,
coronary artery anomalies in 5, and right aortic arch
anomalies in 11 (Table 1).
Table 1. Anatomical Abnormalities Before Reparative Surgery
Among 43 Women With Tetralogy of Fallot Who Had
Pregnancies
Frequency
Associated Anomaly No. % ASD/PFO closure
Right aortic arch 11 26
Pulmonary artery abnormality (hypoplastic, disconnected, 9 21
absent, or stenotic)
Coronary artery anomaly (anomalous origin or course) 5 12
Absence of pulmonary valve 3 7
Double-outlet right ventricle and/or anomalous 2 5
pulmonary venous connection
Aortopulmonary collateral vessels 1 2
Veldtman et al. 175
Pregnancy Outcomes in Tetralogy of Fallot
Table 2. Initial Reparative Surgery Characteristics of 43 Women
With Tetralogy of Fallot Who Had Pregnancies
Value
Characteristics (n ⴝ 43)*
Age at surgery, yrs 14.7 (1–60)
Ventricular septal defect closure 43 (100%)
Transannular patch 17 (40%)
Infundibular resection 17 (40%)
RV outflow tract patch (nontransannular) 7 (16%)
Pulmonary valve replacement 2 (5%)
RV/LV pressure ratio early postoperatively 0.48 (0.20–1.00)
*Continuous data are presented as mean and range; nominal data, as number of
patients and percentage of sample.
LV ⫽ left ventricular; RV ⫽ right ventricular.
Operative characteristics. In 20 patients (47%), TOF was
initially palliated with an aortopulmonary shunt; 1 patient
had a second shunt procedure. A Blalock-Taussig shunt was
used in 14 patients and a Waterston or Potts shunt in six
patients. Five of eight women with unrepaired TOF were
cyanotic during 12 pregnancies. All patients had eventual
repair, during which the ventricular septal defect was closed
and the RV outflow tract repaired. Among the 43 patients,
24 (56%) had patch reconstruction of the RV outflow, and
17 of these reconstructions (40%) were transannular; of the
remaining 19 patients, 17 had only infundibular resection
(Table 2). Sixteen patients had a second operation (Table
3), and five patients had a third operation.
Genitourinary tract abnormalities. Four women had ac-
quired anomalies of the genital tract, including endometriosis
(n ⫽ 2), fibromyoma (n ⫽ 1), and uterine carcinoma (n ⫽ 1).
Two other patients had congenital anomalies, including uterus
didelphys and vaginal agenesis.
Obstetric and neonatal outcome. Fifteen patients who
were counseled against pregnancy did not comply with
medical advice and had 36 pregnancies, of which seven
(19%) terminated spontaneously. Obstetric and neonatal
outcomes are summarized in Table 4. Among 43 respon-
dents, 112 pregnancies occurred, and 82 were successful.
Twenty uncomplicated pregnancies occurred in eight
women with unrepaired TOF. Mean hemoglobin concen-
tration at first presentation was 16.4 g/dl (range, 14.1 to
18.6 g/dl). Obstetric and neonatal outcomes are described in
Table 3. Characteristics of 20 Reoperations Among 16 Women
With Tetralogy of Fallot Who Had Pregnancies
Value
Characteristics (n ⴝ 20)*
Ventricular septal defect closure 5 (25%)
4 (20%)
Pulmonary valve replacement 10 (50%)
Conduit insertion or replacement 2 (10%)
Aortic valve repair or replacement 1 (5%)
Tricuspid valve repair or replacement 6 (30%)
RV/LV pressure ratio early postoperatively 0.4 ⫾ 0.1 (0.18–0.59)
*Continuous data are presented as mean ⫾ SD and range; nominal data, as number
of reoperations and percentage of sample.
ASD ⫽ atrial septal defect; LV ⫽ left ventricular; PFO ⫽ patent foramen ovale;
RV ⫽ right ventricular.
176 Veldtman et al.
Pregnancy Outcomes in Tetralogy of Fallot
Table 4. Obstetric and Neonatal Outcomes Among 15 Women
Counseled Against Pregnancy Because of Perceived Risk
Characteristics
Mean maternal age at first pregnancy, yrs
Median pregnancies per patient
Miscarriages†
Cesarean deliveries‡
Premature deliveries
Small for gestational age
Mean infant weight (first pregnancy), kg
*Continuous data are presented as mean or median (as indicated) and range; nominal
data, as total number and percentage of sample; †n ⫽ 36 pregnancies; ‡n ⫽ 15 women
advised against pregnancy who did not comply with medical advice; §n ⫽ 29
successful pregnancies.
Table 5. Five of the seven infants (71%) who were small for
gestational age were born to women with unrepaired TOF.
No multiparous births were reported. The mean maternal
age at first pregnancy was 26 years (range, 19 to 35 years).
All deliveries occurred at term except for one elective
cesarean delivery at 35 weeks for perceived maternal cardio-
vascular risk.
Sixteen respondents had 30 pregnancy losses, three oc-
curring in two women with unrepaired TOF. All but three
pregnancy losses occurred spontaneously during the first
trimester. The remaining pregnancy losses included a still-
birth at term in a mother with unrepaired TOF, a thera-
peutic abortion at 20 weeks for fetal hypoplastic left heart
syndrome, and one elective termination during the first
trimester. Three patients with repaired TOF had three or
more (range, 3 to 6) spontaneous first trimester pregnancy
losses. At initial assessment, the first patient had severe RV
hypertension (RV systolic pressure, 91 mm Hg) due to RV
outflow obstruction with associated moderate-to-severe RV
enlargement and dysfunction. The other two patients had
moderate elevations in their RV systolic pressure (54 and 50
mm Hg) due to supravalvar pulmonary stenosis; RV systolic
function was mildly impaired, and left ventricular (LV)
function was normal. No gynecologic data were available
about the competence of their genital tracts.
By univariate analysis, heavier birth weight correlated
with the absence of morphologic PA abnormalities (r ⫽
0.425), lower RV systolic pressure (r ⫽ 0.358), and older
Table 5. Obstetric and Neonatal Outcomes Among Eight
Women With Unrepaired Tetralogy of Fallot at the Time of
Pregnancy
Characteristics
Mean maternal age at first pregnancy, yrs
Median pregnancies per patient
Miscarriages†
Cesarean deliveries‡
Premature deliveries
Small for gestational age
Mean infant weight (first pregnancy), kg
*Continuous data are presented as mean or median (as indicated) and range; nominal
data, as total number and percentage of sample; †n ⫽ 25 pregnancies; ‡n ⫽ 8 women
with unrepaired tetralogy of Fallot at the time of pregnancy; §n ⫽ 20 successful
pregnancies.
JACC Vol. 44, No. 1, 2004
July 7, 2004:174–80
Table 6. Obstetric and Neonatal Outcomes Among 43 Women
With Tetralogy of Fallot Who Had 112 Pregnancies
Value* Characteristics Value*
26.5 (19.3–35.4) Mean maternal age at first pregnancy, yrs 26 (19–35)
2 (1–7) Median pregnancies per patient 2 (1–5)
7 (19%) Miscarriages† 30 (27%)
2 (7%)§ Cesarean deliveries‡ 10 (23%)
0 (0%) Premature deliveries§ 1 (1.2%)
4 (14%) Preeclampsia§ 2 (2.4%)
3.09 (2.07–3.8) Mean infant weight, kg 3.2 (2.1–4.2)
Congenital heart defect in offspring§ 3 (3.7%)
*Continuous data are presented as mean or median (as indicated) and range; nominal
data, as total number and percentage of sample; †n ⫽ 112 pregnancies; ‡n ⫽ 43
women with tetralogy of Fallot who had pregnancies; §n ⫽ 82 successful pregnancies.
age at delivery (r ⫽ 0.303). Women without surgical repair
had smaller infants than women with prior surgical repair
(2.573 ⫾ 0.445 kg vs. 3.258 ⫾ 0.466 kg; p ⫽ 0.001). Of the
seven infants (8.5%) who were small for their gestational
age, five were born to women with unrepaired TOF at the
time of pregnancy.
Ten women (23%) had cesarean deliveries; four were
performed for obstetric reasons and six for perceived car-
diovascular risk to the mother. Obstetric and neonatal
outcomes for the group are summarized in Table 6.
Obstetric outcome in relation to maternal hemodynamic
data is summarized in Table 7. Moderate and severe RV
dilation resulted in lower infant birth weight, but the trend
was not statistically significant. Six patients had PHT (mean
PA systolic pressure, 68 mm Hg; range, 40 to 122 mm Hg).
Among these patients, PHT was related to a previous Potts
or Waterston shunt in four, probable chronic pulmonary
thromboembolic disease in one, and an absent left PA in
one. Mothers with PHT tended to have smaller infants than
mothers with normal or only mildly increased PA systolic
pressure, but this trend was not statistically significant
(Table 7). Of the six patients with PHT, one had four first
trimester miscarriages, one had peripartum pulmonary em-
bolism, and one had supraventricular arrhythmia during
pregnancy.
The statistically significant univariate factors that corre-
sponded to birth weight (unrepaired TOF, PA abnormality,
age at primary correction, and RV systolic pressure) were
entered into a multiple variable regression analysis model.
Unrepaired TOF (p ⫽ 0.05; parameter estimate ⫽ ⫺0.36)
and morphologic PA abnormality (p ⫽ 0.03; parameter
estimate ⫽ ⫺0.20) were found to be independent predictors
Value*
of birth weight. The overall model characteristics were as
22.3 (19.3–27.0) follows: R2 ⫽ 0.37; parameter estimate ⫽ 2.66; p ⬍ 0.009.
3 (1–4)
For spontaneous pregnancy losses, we were unable to
5 (20%)
1 (5%)§ identify any risk factors on either univariate or multivariate
0 (0%) analyses.
6 (30%) Obstetric complications included blood group incompat-
2.57 (2.07–3.4) ibility (n ⫽ 1), antepartum hemorrhage (n ⫽ 2), gestational
diabetes mellitus (n ⫽ 1), and small bowel perforation (n ⫽
1) during cesarean delivery at another institution. Gesta-
tional proteinuric hypertension developed in two patients.
JACC Vol. 44, No. 1, 2004 Veldtman et al. 177
July 7, 2004:174–80 Pregnancy Outcomes in Tetralogy of Fallot

Table 7. Maternal Hemodynamic Features and Obstetric Outcomes

Mean ⴞ SD
Features Yes No p Value
Repaired tetralogy of Fallot
Birth weight, kg 3.258 ⫾ 0.466 2.573 ⫾ 0.445 0.001*
Pregnancy losses per patient 0.77 ⫾ 1.35 0.50 ⫾ 0.75 0.857
Live children per patient 1.86 ⫾ 1.0 2.13 ⫾ 0.83 0.27
Pulmonary hypertension†
Birth weight, kg 2.90 ⫾ 0.650 3.121 ⫾ 0.511 0.361
Pregnancy losses per patient 0.7 ⫾ 1.6 0.7 ⫾ 1.3 0.481
Live children per patient 1.7 ⫾ 0.8 1.8 ⫾ 0.9 0.729
Morphologic pulmonary arterial abnormality
Birth weight, kg 2.712 ⫾ 0.43 3.167 ⫾ 0.473 0.015‡
Pregnancy losses per patient 0.7 ⫾ 1.3 0.7 ⫾ 1.3 0.857
Live children per patient 1.5 ⫾ 0.8 1.9 ⫾ 1.1 0.201

None or Moderate or
Mild Severe
Pulmonic regurgitation
Birth weight, kg 3.183 ⫾ 0.544 3.005 ⫾ 0.483 0.298
Pregnancy losses per patient 0.7 ⫾ 1.0 0.5 ⫾ 1.0 0.409
Live children per patient 1.8 ⫾ 0.4 1.9 ⫾ 0.4 0.525
Tricuspid regurgitation
Birth weight, kg 3.334 ⫾ 0.603 3.043 ⫾ 0.501 0.245
Pregnancy losses per patient 1.2 ⫾ 1.3 0.7 ⫾ 1.3 0.370
Live children per patient 2.3 ⫾ 1.8 1.8 ⫾ 0.8 0.193
Right ventricular systolic dysfunction
Birth weight, kg 3.086 ⫾ 0.663 3.060 ⫾ 0.456 0.889
Pregnancy losses per patient 1.3 ⫾ 1.5 0.8 ⫾ 1.4 0.491
Live children per patient 1.3 ⫾ 1.5 1.9 ⫾ 1.0 0.491
Right ventricular dilation
Birth weight, kg 3.23 ⫾ 0.488 2.936 ⫾ 0.503 0.093
Pregnancy losses per patient 0.5 ⫾ 0.8 0.9 ⫾ 1.5 0.551
Live children per patient 1.5 ⫾ 0.8 1.9 ⫾ 0.9 0.198
*p ⫽ 0.001 by Student t test; †Pulmonary arterial pressure ⱖ40 mm Hg; ‡p ⫽ 0.015 by Student t test.

Congenital anomalies in offspring. Congenital anomalies
occurred in five infants (6%): one had a muscular ventricular
septal defect that closed spontaneously by age 12 years; one
had hypoplastic left heart syndrome, and the pregnancy was
terminated; one was born with mitral valve prolapse; one
had pyloric stenosis; and one had clubbed feet, bilateral
strabismus, and a cleft lip and palate. No unifying genetic
syndrome was identified. One mother had a documented
22q11 deletion syndrome. Her pregnancy was uneventful,
and the fetus did not have congenital anomalies.
Maternal outcome. Table 8 summarizes functional and
hemodynamic status before each pregnancy (n ⫽ 16) or at
first assessment after pregnancy (n ⫽ 66) when antepartum
hemodynamics were not available (mean interval from
pregnancy to first assessment, 16.9 years; range, 0.8 to 38.4
years). Among the 66 pregnancies for which no antepartum
hemodynamic data were available, four patients had cardiac
reoperation after the pregnancy but before the first
assessment.
Six women (7%) with repaired TOF at the time of
pregnancy reported cardiovascular complications during
pregnancy. Two women had increased frequency of palpi-
tations. In one, documented supraventricular tachycardia
was noted, and digoxin therapy controlled the heart rate.
This patient had severe PHT with an absent left PA, an RV
systolic pressure of 122 mm Hg, and severe RV dilation. No
records were available to establish underlying cardiac
rhythm in the other patient, but she had severe RV dilation
and dysfunction from severe pulmonic regurgitation.
Pulmonary edema occurred one day after delivery in a
patient with peripartum LV dysfunction of uncertain cause
and gestational proteinuric hypertension. She was treated
medically, and her LV function returned to normal. Before
pregnancy her RV systolic pressure was 62 mm Hg because
of hypoplastic obstructive PAs. In another patient, severe
LV dysfunction developed at 38 weeks of gestation; emer-
gent delivery was required. The LV dysfunction was most
likely related to peripartum cardiomyopathy because normal
systolic LV function was noted antepartum. At latest
follow-up, LV ejection fraction remained depressed (45%).
One patient with free pulmonic regurgitation had pro-
gressive RV dilation and tricuspid valve regurgitation during
pregnancy. She required pulmonary valve replacement 32
months after the delivery. She had an uncomplicated peri-
partum period. In another patient, pulmonary embolism
and circulatory collapse developed after delivery. The pa-
tient survived, and at the first assessment after her latest
178 Veldtman et al.
Pregnancy Outcomes in Tetralogy of Fallot
Table 8. Clinical and Hemodynamic Data Before Each Pregnancy
(n ⫽ 16) or at First Assessment After Pregnancy (n ⫽ 66) for 43
Women With Tetralogy of Fallot
Features Value*
Age at assessment, yrs 36.2 ⫾ 11
NYHA functional class
I 24 (56%)
II 14 (33%)
III 3 (7%)
Right ventricle
Normal or mild dilation 24 (63%)†
Moderate or severe dilation 13 (34%)†
Normal or mild dysfunction 33 (92%)‡
Moderate or severe dysfunction 3 (8%)‡
Right ventricular systolic pressure, mm Hg 57 (20–165)
Tricuspid valve regurgitation§
Normal or mild 34 (85%)
Moderate or severe 6 (15%)
Left ventricle and aorta
Left ventricular ejection fraction, % 59 (47–70)
Ascending aorta diameter, mm 35 (23–49)
*Continuous data are presented as mean ⫾ SD or as mean and range; nominal data
and ordinal data, as number of women and percentage; †Data for right ventricular size
were not available for 5 patients (n ⫽ 38); ‡Data for right ventricular function were
not available for 7 patients (n ⫽ 36); §Data for the degree of tricuspid valve
regurgitation were not available for 3 patients (n ⫽ 40).
NYHA ⫽ New York Heart Association.
pregnancy, she had severe PHT (RV systolic pressure, 89
mm Hg) suggestive of chronic pulmonary emboli.
Aortic root diameter was not significantly different be-
tween women who had pregnancies and women who did
not (35 ⫾ 6 mm vs. 35 ⫾ 10 mm; p ⫽ 0.21). No aortic
complications during pregnancy were reported. Among the
eight women without surgical repair, one had a pregnancy-
related cardiovascular complication. This patient with pul-
monary embolism and circulatory collapse was discussed
above. In 3 of the 15 women counseled against pregnancy,
cardiovascular complications developed during pregnancy.
DISCUSSION
Pregnancy places a physiologic load on the cardiovascular
system. Plasma volume increases because of conservation of
renal salt and water, cardiac output increases up to 50%
above the prepregnant level because stroke volume and heart
rate are augmented, pulmonary vascular resistance usually
falls while PA pressures are maintained despite enhanced
flow, and systemic arterial resistance usually decreases (14).
The hemodynamic burden of pregnancy combined with
the residual cardiovascular lesions after TOF repair is
potentially of concern because of the following: progression
of RV dysfunction, atrial and ventricular dysrhythmias,
thromboembolic phenomena, maternal or fetal death in the
presence of severe PHT, progressive aortic root dilation,
intrauterine growth retardation, and endocarditis. Also,
offspring of mothers with TOF are more likely to have
congenital heart disease, with a reported incidence of
approximately 3.1% (15,16).
In our series, patients who had cardiovascular complica-
tions during pregnancy also had severe RV dilation or RV
JACC Vol. 44, No. 1, 2004
July 7, 2004:174–80
dysfunction (or both), RV hypertension due to outflow
obstruction, and PHT. Unrepaired TOF and the presence
of morphologic PA abnormality (hypoplastic or discon-
nected PA or ductal origin of PA) were independently
predictive of infant birth weight.
Before successful intracardiac repair of TOF was intro-
duced in the 1950s, few patients reached childbearing age,
and successful pregnancy was uncommon. Pregnancies were
characterized by spontaneous abortions, stillbirths, and pre-
mature deliveries. Presbitero et al. (17) demonstrated that
the most important risk factor for adverse fetal outcome in
cyanotic patients was the degree of cyanosis. These authors
suggested that an arterial oxygen saturation ⬎85% and a
hemoglobin concentration ⱕ18 g/dl were more likely to
result in live birth, whereas hemoglobin concentrations ⬎20
g/dl were associated with adverse fetal outcome.
Although premature delivery was uncommon in our
series (1%), 8.5% of infants were small for their gestational
age, six of the seven (86%) being born to women with
unrepaired TOF. Our eight patients with unrepaired TOF
(mean hemoglobin concentration 16.4, 14.1 to 18.6 g/dl)
had smaller infants than the patients with repaired TOF.
Recently, in a series of women with cardiovascular disease,
Siu et al. (18) reported a 4% incidence of infants who were
small for their gestational age. The fetus was at highest risk
when the mother had a combination of obstetric risk factors
and cardiac risk factors. The incidence among healthy
controls was only 2%. Although we did not examine
obstetric risk factors, we were able to demonstrate a negative
correlation between infant birth weight and maternal unre-
paired TOF status, morphologic PA abnormality, higher
RV systolic pressure, and younger age at primary surgical
repair. Unrepaired TOF and the presence of morphologic
PA abnormality (hypoplastic or disconnected PA or ductal
origin of PA) were independently associated with infant
birth weight. Among infants with low birth weight, ⱖ50%
of their mothers have chronic disease that unfavorably
affects maternal-placental blood flow (19). One can specu-
late that PA abnormalities, particularly in the presence of
pulmonic regurgitation, may adversely affect augmentation
of maternal cardiac output at rest or during exercise. This
may result in depressed placental blood flow and, subse-
quently, intrauterine growth retardation.
Obstetric and neonatal outcome. Patients in our series
had a rate of spontaneous fetal loss of 24%, which is
substantially higher than the expected national average of
10% (20). Multiple factors may be implicated, including: 1)
the high prevalence of genital tract abnormalities in our
series; 2) residual hemodynamic lesions such as RV outflow
tract obstruction and PHT; and 3) the known increased
incidence of congenital malformations in the offspring of
women with congenital heart disease.
In our cohort, 23% of the women had cesarean deliveries,
a rate very similar to the national rate of up to 21.8%. All
but one of the cesarean deliveries were performed for
perceived cardiovascular risk to the mother or fetus.
JACC Vol. 44, No. 1, 2004
July 7, 2004:174–80
Congenital anomalies in offspring. In our series, 6% of
the infants had congenital anomalies, including congenital
heart disease, pyloric stenosis, and multiple anomalies (in
one infant). This rate is higher than the prevalence of
congenital anomalies in the general population, which is
approximately 3% (21). The recurrence rate of congenital
heart disease alone in our cohort was similar to previously
reported rates of approximately 4% (15).
Maternal outcome. Six women in our series had adverse
cardiovascular events, which included supraventricular ar-
rhythmia, heart failure, pulmonary embolism, and progres-
sive RV dilation. Previously published series have demon-
strated little or no risk to the mother with a repaired TOF.
Singh et al. (9) reported 40 successful pregnancies in 27
women, with no adverse maternal cardiovascular events.
Similarly, Nissenkorn et al. (12) demonstrated no maternal
complications in five women who had nine pregnancies, and
the authors stressed the importance of alleviating a signifi-
cant residual hemodynamic burden before pregnancy. The
earlier studies all had relatively few patients, and the authors
examined limited hemodynamic parameters. Antepartum,
five of our six patients with cardiovascular complications
had hemodynamically significant lesions, including severe
PHT with marked RV dilation, severe pulmonic regurgita-
tion with RV dysfunction, RV hypertension due to hypo-
plastic PAs, and peripartum LV dysfunction (worsened by
gestational hypertension in one patient). These data reem-
phasize that women with important hemodynamic or struc-
tural heart disease during pregnancy are at risk of adverse
cardiovascular events during pregnancy or the puerperium.
Study limitations. Although this study is the largest series
to date of women with TOF and pregnancies, there are
several limitations. The hemodynamic data were collected
retrospectively, and the obstetric data were collected directly
from the patients. Hemodynamic data before pregnancy
were often not available. Hemodynamic data at first assess-
ment were used to estimate likely hemodynamic forces
during pregnancy, when there was no intervening operation.
We obtained available medical records from referring
physicians.
The 22q11 deletion is a recognized risk of congenital
defects in offspring. This deletion was recognized in only
one mother, but routine screening for this abnormality was
not performed in our series. We also did not specifically
acquire 22q11 deletion status among infants with congenital
anomalies. Thus, the frequency of 22q11 microdeletion in
the mothers and the frequency of congenital defects in their
offspring remain unknown.
Only 67% of eligible women responded to our question-
naire. Although this low response rate potentially intro-
duced bias to our results, we expected the effect to be small.
Patients may not have responded because they had unevent-
ful pregnancies or because their pregnancies resulted in fetal
loss.
Conclusions. Adult survival in patients with repaired TOF
is now expected. Pregnancy in patients with repaired TOF
Veldtman et al. 179
Pregnancy Outcomes in Tetralogy of Fallot
is possible but carries an increased risk of fetal loss,
cardiovascular complications during pregnancy, and con-
genital heart disease in offspring. Pregnancy complications
are related to important maternal hemodynamic distur-
bances (severe PHT, severe pulmonic regurgitation with RV
dysfunction, and LV dysfunction). This reemphasizes the
critical importance of a comprehensive prepregnancy eval-
uation. From the cardiovascular standpoint, vaginal delivery
is preferred for most TOF patients. Women with any
combination of the above hemodynamic disturbances may
benefit from surgical repair, if feasible, before pregnancy.
Women with PHT or significant LV dysfunction should be
counseled about their cardiovascular risk and advised against
pregnancy.
Acknowledgments
The authors acknowledge the contributions of Douglas J.
Kocer, Jayne M. Roth, and Effie Veldtman.
Reprint requests and correspondence: Dr. Heidi M. Connolly,
Division of Cardiovascular Diseases and Internal Medicine, Mayo
Clinic, 200 First Street SW, Rochester, Minnesota 55905. E-mail:
connolly.heidi@mayo.edu.
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