This study aimed to review the characteristics, management, and outcomes of 153 cases of fetal tachyarrhythmia diagnosed at two Swedish centers from 1990 to 2012. The majority of cases were atrial flutter (28%) or atrioventricular reentrant tachycardia (63%). Transplacental treatment was commenced in 99 cases and resulted in rhythm normalization in two-thirds of treated cases. Non-hydropic fetuses all had favorable outcomes, while hydropic fetuses had a mortality rate of 16%. Sotalol treatment had a higher cardioversion rate than digoxin for AVRT but not for atrial flutter. This study found that transplacental treatment was often insufficient for cardioversion and

1. REGULAR ARTICLE
Foetal tachyarrhythmia treatment remains challenging even if the vast
majority of cases have a favourable outcome
Britt-Marie Ekman-Joelsson (britt-mari.ekman-joelsson@vgregion.se)1
, Mats Mellander1
, Linda Lagnefeldt2
, Sven-Erik Sonesson2
1.Paediatric Cardiology, Department of Women’s and Children’s Health, The Queen Silvia Children’s Hospital, Gothenburg, Sweden
2.Department of Women’s and Children’s Health, Karolinska Institutet, Stockholm, Sweden
Keywords
Digoxin, Foetus, Gender, Sotalol, Tachyarrhythmia
Correspondence
B-M Ekman-Joelsson, Paediatric Cardiology,
Department of Women’s and Children’s Health,
The Queen Silvia Children’s Hospital, Gothenburg,
Sweden.
Tel: +46313438377 |
Fax: +4631845029 |
Email: britt-mari.ekman-joelsson@vgregion.se
Received
14 October 2014; revised 7 January 2015;
accepted 1 July 2015.
DOI:10.1111/apa.13111
ABSTRACT
Aim: The optimal treatment for foetal tachyarrhythmia remains controversial, and this study
aimed to fill this gap in the knowledge.
Methods: We retrospectively reviewed all cases of foetal tachyarrhythmia diagnosed at two
tertiary foetal cardiology centres in Sweden from 1990 to 2012.
Results: Of the 153 cases, 28% had atrial flutter (AF), 63% had atrioventricular reentrant
tachycardia (AVRT) and 9% had other mechanisms. Hydrops was present in 45, less
frequently in AF than in AVRT. Transplacental treatment was commenced in 99 and the
rhythm normalised in two-thirds, without any significant difference in cardioversion rates
between AF and AVRT cases or nonhydropic and hydropic foetuses. Sotalol treatment had
a higher cardioversion rate than digoxin in AVRT (63% versus 33%, p < 0.05) but not in
AF (57% versus 56%). Two or more drugs were used in 38%. Neonatal survival was
100% in nonhydropic and 84% in hydropic cases. After a median of eight years, 11/134
patients still had arrhythmias, one had died due to arrhythmia and another had undergone
cardiac transplantation.
Conclusion: Transplacental treatment was frequently insufficient to obtain cardioversion in
nonhydropic and hydropic foetuses, but all nonhydropic cases had favourable outcomes.
Larger prospective studies are needed to optimise the treatment of cases with hydrops.
INTRODUCTION
Foetal tachyarrhythmia has a significant mortality rate that
has not changed much from the 8% identified by a review
by Bergmans in 1985 (1) to the 4% to 11% observed in later
studies (2–7). There have been no randomised studies of
foetal tachyarrhythmia treatment published, most studies
have been based on a limited number of cases, and the
optimal choice of drugs for transplacental treatment still
remains controversial. Our objective was to fill this gap in
the knowledge by conducting a study on a large cohort of
foetuses, diagnosed at two tertiary paediatric cardiology
centres in Sweden. The primary aim of the study was to
review the distribution and characteristics of different types
of tachyarrhythmia, their management and long-term out-
come. The units included in the study had been using sotalol
treatment since 1991 and therefore had many years’ expe-
rience of using this drug in transplacental antiarrhythmic
treatment (8). Our secondary aim was to compare the
efficacy and safety of treatment with digoxin and sotalol.
PATIENTS AND METHODS
We retrieved 153 consecutive pregnancies with a diagnosis
of foetal tachyarrhythmia from our databases between
January 1990 and December 2012. Of these, 63 were from
the tertiary paediatric cardiology unit at Queen Silvia
Children’s Hospital, Gothenburg, and 90 were from the
tertiary paediatric cardiology unit at Astrid Lindgren Chil-
dren’s Hospital, Stockholm. Maternal, postnatal and
Abbreviations
A, Atrial; AET, Atrial ectopic tachycardia; AF, Atrial flutter; AV,
Atrioventricular; AVRT, Atrioventricular reentrant tachycardia;
CAT, Chaotic atrial tachycardia; JET, Junctional ectopic tachy-
cardia; PJRT, Permanent junctional reciprocating tachycardia;
SD, Standard deviation; V, Ventricular; VA, Ventriculoatrial; VT,
Ventricular tachycardia.
Key Notes
The optimal treatment for foetal tachyarrhythmia
remains controversial, and this study aimed to fill this
gap in the knowledge.
We retrospectively reviewed all 153 cases of foetal
tachyarrhythmia diagnosed at two tertiary foetal cardi-
ology centres in Sweden from 1990 to 2012.
Transplacental treatment was insufficient to obtain
cardioversion in one-third of the treated cases and
hydropic foetuses had a mortality rate of 16%, but all
nonhydropic cases had a favourable outcome.
1090 ©2015 Foundation Acta Pædiatrica. Published by John Wiley Sons Ltd 2015 104, pp. 1090–1097
Acta Pædiatrica ISSN 0803-5253

2. paediatric medical records were reviewed and, if necessary,
echocardiographic recordings were re-evaluated. We col-
lected information on the mother and her pregnancy, the
foetal tachycardia and its haemodynamic consequences and
management and the outcome up until the latest postnatal
follow-up. The study was approved by the human research
committees at the Karolinska Institutet, Stockholm, and
Gothenburg University, Gothenburg.
Classification of arrhythmias
Foetal tachyarrhythmia was defined as a ventricular rate of
at least 180 beats per minute (bpm). The tachycardia was
considered incessant if it was present more than 50% of
the time during 24-hour cardiotocography monitoring or
auscultation once per hour. Other cases that did not
show these features were considered intermittent. Hospital
surveillance before treatment tended to be shorter in the
Stockholm unit, and sometimes the classification relied on
the observations made during the 45 minutes or so needed
for the echocardiographic examination. Foetal hydrops was
defined as the presence of two or more of the following
findings: ascites, skin oedema, pericardial effusion and
pleural effusion.
Foetal echocardiography was used to classify the elec-
trophysiological mechanism causing the tachycardia, by
recognising the chronological relationships between atrial
(A) and ventricular (V) depolarisations, which were, in
turn, identified by their mechanical (M-mode) or haemo-
dynamic (Doppler) consequences (9). Atrial flutter (AF)
was diagnosed when the atrial rate exceeded 350 bpm and
was associated with a 2:1 atrioventricular (AV) relation-
ship in all cases. Cases with a regular rhythm and 1:1 AV
conduction were classified as atrioventricular reentrant
tachycardia (AVRT) when the ventriculoatrial (VA) time
interval was short (VAAV time interval) and as atrial
ectopic tachycardia (AET) or permanent junctional recip-
rocating tachycardia (PJRT) when the interval was long
(VAAV time interval). Tachycardias with simultaneous
onset of atrial and ventricular contractions or AV dissoci-
ation with a ventricular rate exceeding that in the atria were
diagnosed as junctional ectopic (JET) or ventricular (VT)
tachycardia. All foetuses with irregular long VA tachycardia
also had very short periods of AF, but were classified by the
dominating mechanism as chaotic atrial tachycardia (CAT).
Intrauterine antiarrhythmic treatment
Both centres used similar treatment regimens. Transplacen-
tal digoxin treatment usually started with an oral loading
dose of 1.5–2.0 mg given on a 24- to 36-hour basis, followed
by a daily maintenance dose of approximately 0.5 mg to
obtain a maternal drug level in the upper therapeutic range.
Cases with severe hydrops frequently received an intra-
venous loading dose of 1.0 mg over a 24-hour period,
followed by injections of 0.25–0.5 mg on days two and
three. Sotalol treatment routinely started with an oral dose
of 80 mg twice daily and increased to 160 mg twice daily
within three days, depending on the degree of foetal
hydrops. In rare cases, it was increased to a maximum
dosage of 160 mg three times a day. Flecainide treatment
started with a dose of 100 mg two to three times a day and
increased to a maximum dosage of 400 mg per day.
If a second drug was started before the third day of
treatment, it was defined as combination therapy. Car-
dioversion was considered to have occurred when the
arrhythmia had not been observed for one week and free
from arrhythmia recurrence when it was not observed
until birth.
Statistical methods
Original birthweight measurements were converted to a
standard deviation (SD) score using national Swedish
growth charts (10). Statistical analysis was performed using
Statistica 12.0 (StatSoft, Tulsa, Oklahoma, USA). Contin-
uous variables were accepted as normally distributed if the
skewness and kurtosis were within Æ1.0. The t-test or the
Mann–Whitney U-test was used to compare groups as
appropriate. For categorical data, we used Fisher’s exact or
the chi-square test. We also used logistic regression analysis
to validate the effects of gestational age, heart rate and
incessant or intermittent tachycardia as predictors of foetal
hydrops at diagnosis and to validate the effects of gesta-
tional age, heart rate, incessant or intermittent tachycardia
and hydrops at diagnosis as predictors of intrauterine
treatment. p 0.05 was considered statistically significant.
Data are presented as the mean Æ 1 SD or the median
and range.
RESULTS
There was a slight difference in the methods that the two
centres used to define the persistence of the tachycardia.
Despite this, we could not demonstrate any systematic
differences regarding the different types of arrhythmias, the
proportion of cases with incessant or intermittent tachy-
cardia, with or without hydrops, or those offered antiar-
rhythmic treatment. As a result, the cases from both centres
are reported together. In seven cases, the type of arrhythmia
was not reported in the medical records from the time of
treatment or reclassified after birth.
Demographic data at the time of diagnosis and the action
taken are reported in Table 1. The majority of the 153
pregnancies (91%) included had a diagnosis of AF (n = 42)
or AVRT (n = 97). Foetuses with AF had a longer gesta-
tional age, a lower heart rate and a smaller proportion with
hydrops than those with AVRT. However, the proportion of
cases with incessant tachycardia and the proportion offered
treatment were around two-thirds in both the AF and AVRT
groups. When we compared patients with and without
foetal hydrops, we found that those with foetal hydrops
had a shorter gestational age (29.8 Æ 3.4 versus
31.4 Æ 4.8 weeks, p 0.05), a higher heart rate (247 Æ 27
versus 226 Æ 24 bpm, p 0.001) and higher levels of
incessant tachycardia (91 versus 49%, p 0.001). Logistic
regression analysis demonstrated that a short gestational
age (p 0.05) was a risk factor for foetal hydrops in cases
with AF and that incessant tachycardia (p 0.001) and
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Ekman-Joelsson et al. Long-term outcome in foetal tachyarrhythmia

3. high heart rate (p 0.05) were risk factors for foetal
hydrops in cases with AVRT. Intrauterine treatment was
commenced in 65% of cases, observation without treatment
was used in 25% and 10% of the cases were delivered so
that they could be treated after birth. Cases managed by
intrauterine treatment had a shorter gestation (30.1 Æ 3.9
versus 32.5 Æ 5.2 weeks, p 0.005), a higher heart rate
(238 Æ 25 versus 222 Æ 26 bpm, p 0.001), a higher inci-
dence of incessant tachycardia (86 versus 18%, p 0.001)
and a higher incidence of hydrops (43 versus 4%, p 0.001)
than those observed without treatment or delivered. Inces-
sant tachycardia (p 0.001), heart rate (p 0.01) and
gestational age (p 0.01) were the best predictors of
whether cases with AF or AVRT were managed by
intrauterine treatment or not.
Two foetuses had a severe cardiac malformation in
addition to arrhythmia. One had a hypoplastic right heart
and AVRT and did well without any treatment. The second
had AF and a severe Ebstein’s malformation with severe
hydrops, which progressed in spite of a normalised ventric-
ular rate and finally resulted in foetal death. A third foetus
had an inherited form of dilated cardiomyopathy, in
association with incessant AVRT, that became intermittent
during transplacental treatment, but still resulted in
intrauterine death eight days after the treatment started.
As we considered that primary cardiac disease would have
had a major impact on the outcome in these two last cases,
they were excluded from the following analysis.
Treatment and foetal outcome in nonhydropic cases
Transplacental antiarrhythmic treatment was started in
56 (52%) of the nonhydropic foetuses, with an overall
intrauterine cardioversion rate of 70% (Table 2). The car-
dioversion rates were not different for foetuses with AF or
AVRT or for those with incessant or intermittent tachycar-
dia. We also found that foetuses that normalised their
cardiac rhythm had a shorter gestation (29.9 Æ 3.8 versus
33.3 Æ 2.9 weeks, p 0.005) and a higher heart rate
(237 Æ 22 versus 218 Æ 16 bpm, p 0.005) at diagnosis
than those without cardioversion.
We started 55 of the 56 cases on digoxin (n = 31), sotalol
(n = 20) or both (n = 4), and 23% were treated with two or
more antiarrhythmic drugs (Table 2). Providing digoxin or
sotalol as a single therapy resulted in the same conversion
rates in cases with AF, and the combination did not seem
to have any additional effect. In cases with AVRT, the
cardioversion rate of digoxin (44%) was not significantly
different from sotalol (77%) or the combination of both
(86%). Approximately two-thirds of the cardioversions
occurred in the first seven days of treatment, but in some
cases it took two weeks of treatment to stop the arrhythmia.
The median time to conversion was slightly shorter in cases
with AF than AVRT (Table 2), but we found no difference
between cases responding to digoxin (median 5.0 days) or
sotalol (median 5.5 days) as the first-line therapy.
Cases where arrhythmia stopped were delivered at a later
gestational age and were less likely to be delivered by
Caesarean section. Only one of the 17 cases without
cardioversion was delivered before 35 gestational weeks,
and the survival of the nonhydropic foetuses was 100%.
Treatment and foetal outcome in hydropic cases
Transplacental treatment was not given to two hydropic
foetuses with intermittent AVRT. One case diagnosed at
29 weeks resolved spontaneously and the other was initially
diagnosed at 35 weeks with a normal heart rate, but poor
variability and barely visible, sporadic atrial contractions.
Periods of tachycardia occurred two days later, a Caesarean
section was performed and the baby was diagnosed with
AVRT. The results for the other 41 hydropic foetuses are
presented in Table 3. The overall cardioversion rate was
61%, without any difference between AF and AVRT cases,
Table 1 Demographic data and management of 153 cases with foetal tachyarrhythmia at the time of diagnosis
AF AVRT p PJRT, AET CAT JET, VT
Cases 42 97 8 3 3
GA at diagnosis
(weeks)
32.3 Æ 3.6
(25-39)
30.4 Æ 4.5
(19-40)
0.05 29.6 Æ 5.8
(19-36)
36 Æ 4.4
(31-39)
29 Æ 6.0
(23-35)
Heart rate (beats/min) 221 Æ 23
(180-290)
241 Æ 25
(190-295)
0.001 203 Æ 24
(180-250)
218 Æ 11
(210-225)
207 Æ 21
(190-230)
Incessant tachycardia 30 (71%) 60 (62%) ns 5 (63%) 2 1
Major CHD, CMP 1 (2%) 2 (2%) 0 0 0
Foetal hydrops 7 (17%) 35 (36%) 0.05 3 (38%) 0 0
Prenatal management
Pharmacological
treatment
28 (67%) 64 (66%) ns 5 (63%) 1 1
Delivery; vaginal, CS 1, 6 (17%) 1, 5 (6%) ns 0 1, 1 0
Observation without
intervention
7 (17%) 27 (28%) ns 3 (38%) 0 2
Values are presented as means Æ SD (range) or number of cases (percentage). P-values denote AF versus AVRT. Abbreviations used: AF = Atrial flutter;
AVRT = Atrioventricular reentrant tachycardia; PJRT = Permanent junctional reciprocating tachycardia; AET = Atrial ectopic tachycardia; CAT = Chaotic atrial
tachycardia; JET = Junctional ectopic tachycardia; VT = Ventricular tachycardia; GA = Gestational age; CHD = Congenital heart disease; CMP = Cardiomyopathy;
CS = Caesarean section; ns = Not significant.
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4. and without any association with gestational age or heart
rate at presentation.
The cardioversion rates in the cases with AF and AVRT
were not significantly different when digoxin or sotalol was
used as the first-line therapy (Table 3). In the few cases with
cardioversion, we found no significant difference between
the two drugs when it came to the time from when
treatment started to when conversion occurred, with a
median of 7.5 days for digoxin and 3.5 days for sotalol.
More than one antiarrhythmic drug was needed in 24
(59%) of cases, and direct foetal therapy was used in six. In
two cases, conversion was achieved by injecting digoxin, at
75-100 micrograms per kg for estimated foetal weight, into
the umbilical vein followed by adenosine. In the other four
Table 2 Foetal outcome of transplacental treatment in 56 nonhydropic foetuses
AF AVRT p PJRT, AET CAT JET, VT
Treated cases 21 31 2 1 1
Incessant tachycardia 20 (95%) 23 (74%) ns 1 0 0
Cardioversion in utero 13 (62%) 24 (77%) ns 1 1 0
Cardioversion during
First-line therapy
Digoxin 8/13 (62%) 7/16 (44%) ns 1/1 0/1
Sotalol 3/5 (60%) 10/13 (77%) ns 1/2
Digoxin + sotalol 1/3 1/1
Flecainide 1/1
Second-line therapy
Digoxin + sotalol 1/3 5/6 (83%)
Third-line therapy
Flecainide 0/1
Time to cardioversion (days) 4 (1–11) 7 (2–14) 0.05 14 5
Freedom of recurrence 12 (57%) 21 (67%) ns 1 1
Perinatal mortality 0 0 0 0 0
Values are presented as number of cases (percentage) or medians (range). P-values denote AF versus AVRT. Abbreviations used are as in Table 1.
Table 3 Foetal outcome of transplacental treatment in 41 hydropic foetuses
AF AVRT p PJRT, AET
Treated cases 6* 32†
3
Incessant tachycardia 5 (83%) 31 (97%) ns 3
Cardioversion in utero 3 (50%) 21 (66%) ns 1
Cardioversion during
First-line therapy
Digoxin 1/3 3/14 (21%) ns 1/3
Sotalol 1/2 5/12 (42%) ns
Digoxin + sotalol 0/1 1/4
Flecainide 1/1
Amiodarone 1/1
Second-line therapy
Digoxin direct foetal 1/2
Digoxin + sotalol 1/3 4/11 (36%) 0/1
Sotalol 1/1
Flecainide 0/1 1/2
Third-line therapy
Flecainide 2/4
Fourth-line therapy
Sotalol 1/1
Time to cardioversion (days) 19 (8–32) 7 (1–27) ns 21
Freedom of recurrence 3 (50%) 19 (59%) ns 1
Heart rate control/haemodynamic
improvement
6 24 (75%) ns 3
Perinatal mortality 0* 7 (22%)†
ns 0
Values are presented as number of cases (percentage) or medians (range). P-values denote AF versus AVRT. Abbreviations used are as in Table 1.
*One case with severe Ebstein’s anomaly and †
one with a familial cardiomyopathy are excluded.
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Ekman-Joelsson et al. Long-term outcome in foetal tachyarrhythmia

5. cases, digoxin and/or adenosine were given at much lower
dosages, with none or only very short-lasting effects.
Transplacental flecainide treatment was effective in four
of eight cases, and amiodarone was successful in the single
case where it was used. In around 50% of cases, the
arrhythmia ceased within seven days, but some cases were
not definitely converted before three to four weeks of
treatment. Arrhythmia did not cease in 16 foetuses: in eight
cases, we observed heart rate control and decreased
hydropic changes and one neonate was delivered less than
one week after starting treatment. These 16 foetuses also
included seven cases of intrauterine demise, who all had
AVRT and were grossly hydropic at diagnosis. Three died
within 48 hour of diagnosis and another three died within
eight days, including two that had been converted to a
normal rhythm one to two days before, but with a severely
compromised ventricular function. One was treated with
digoxin, and the other five received a combination of
digoxin and sotalol. In the seventh case, diagnosed at
20 weeks and still in tachycardia two months later, the
mother refused further medication and the baby died two
days later. This means that our arrhythmia-related mortality
rate in hydropic foetuses was 7/43 (16%).
Maternal side effects
Side effects were reported by 21 of the 99 women who
received antiarrhythmic drugs: ten who were prescribed
digoxin, three who used sotalol and eight who used a
combination of both. In two cases, preeclampsia with
decreased renal function and severe digoxin intoxication
developed within 24 hours of treatment and they were
delivered by Caesarean section at 32 and 33 weeks of
gestation. One woman needed intensive care treatment, but
both the women and their babies survived without sequelae.
Other less dramatic side effects were nausea, vomiting,
tiredness, visual impairment, dizziness and loss of sensation.
Neonatal outcome
Six cases were lost to follow-up, and the neonatal outcomes
of the 138/144 babies that were born alive are presented
in Table 4. Termination of arrhythmia was associated with
not having a Caesarean section, a longer time delay from
diagnosis to delivery and a later gestational age at delivery.
Preterm delivery was observed in 28% of the cases and
three-quarters of the 12% delivered before 35 weeks of
gestation had a hydropic foetus at presentation. Two-thirds
of our foetuses were boys, and the girls had a higher rate
of intrauterine conversion (86 versus 63%, p 0.05) and
a lower degree of postnatal arrhythmia (24 versus 55%,
p 0.01).
Neonatal neurological morbidity was observed in three
cases. In one case, this was due to a postnatal cerebral
haemorrhage, and in the other two cases, this was due to
prenatal cerebral infarction, probably secondary to throm-
boembolism (11).
Postnatal arrhythmia was seen in cases that did not
respond to intrauterine treatment and was also seen in 25%
of those with cardioversion (Table 4). Electroconversion
was used in two cases with AF and one with AVRT. There
was a small difference in the time from diagnosis to delivery
between patients with AF and AVRT (5.1 Æ 4.4 versus
7.5 Æ 5.4 weeks, p 0.05), but they were delivered at the
same gestational age and all other neonatal outcome
measures were similar. Postnatal arrhythmias were
observed within two weeks of delivery in 19/38 (50%)
cases with AF, 31/85 (36%) with AVRT, 1/3 with AET, 2/4
with PJRT, 1/2 with JET and none of the four cases with
CAT or VT. In addition to the two severe cardiac malfor-
mations diagnosed prenatally, two small ventricular septal
defects and one atrial septal defect were found in another
three cases with AF.
Postnatal treatment and long-term outcome
Outcome data on 134 of the 144 live born babies are
presented in Table 5. Postnatal antiarrhythmic treatment
was started in 94 (70%) patients and treatment was more
frequently provided in cases with foetal hydrops than those
who were nonhydropic (87 versus 68%, p 0.05), but there
was no difference in frequency between AF and AVRT
cases. The duration of treatment was typically six (1–12)
months, 11 (8%) still had recurrence of arrhythmia after
one year of age and six were treated with radiofrequency
ablation. One case with PJRT and poor ventricular function
at diagnosis had cardioversion and functional normalisa-
tion after birth, but arrhythmia recurred, accompanied by
ventricular deterioration, and a cardiac transplant was
carried out at eight years of age.
Neurological sequelae were present in five cases. Two of
the three with neurological symptoms at birth had hemi-
paresis, but no sequela was documented in the third.
Another two children had a mild neurodevelopmental
delay and a fifth had an unclear neurological disease, with
paraparesis, and died at five months of age. Tumours were
diagnosed in two infants and one had a lethal metabolic
disease. There were five postnatal deaths, including one at
two months of age, which was thought to be due to a
cardiac issue due to an arrhythmia, as the child had AVRT
and was on amiodarone prophylaxis.
DISCUSSION
The 153 foetuses in our cohort presented with different
types of tachyarrhythmia: 63% had AVRT, 28% had AF
and other mechanisms accounted for 9% of cases. Foetal
hydrops was more prevalent in patients with AVRT than
AF. It was associated with incessant tachycardia and a
higher heart rate in AVRT, but had a stronger relationship
to shorter gestational age in AF. These latter observations
were not unexpected, as AVRT has a higher ventricular rate
than AF, with 2:1 AV conduction, allowing less time for
ventricular filling and atrial contractions against a closed
AV-valve causing marked retrograde systemic venous pul-
sations not seen in cases with fluttering atria. Intrauterine
treatment was started in approximately two-thirds of our
cases. This distribution of arrhythmias and the proportion
of cases with incessant tachycardia, hydrops and receiving
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Long-term outcome in foetal tachyarrhythmia Ekman-Joelsson et al.

6. prenatal treatment were similar to observations made by
other investigators (3,6,7,12–14).
Treatment and foetal outcome
The optimal goal of foetal tachycardia treatment is the full-
term delivery of a nonhydropic foetus in sinus rhythm.
However, transplacental and direct foetal antiarrhythmic
treatment does carry risks for both the mother and foetus,
making heart rate control, avoiding significant prematurity
and survival of a healthy child and mother an acceptable
alternative. Decisions based on these concerns probably
explain our observation that nonhydropic foetuses without
intrauterine cardioversion were diagnosed later in gestation
and with a lower heart rate than those that normalised their
cardiac rhythm. In accordance with this concept, we also
observed that only one of the 17 nonhydropic foetuses that
did not revert to sinus rhythm was delivered before
35 weeks of gestation.
Our rates of conversion were lower than the 83% for
tachycardia control reported for nonhydropic foetuses, but
they were comparable to observations in hydropic cases (5).
Our data also harmonise well with conversion rates noted by
Jaeggi et al. after two to three weeks of treatment, but were
somewhat lower when we looked at the final conversion
Table 4 Neonatal outcome of 138 surviving foetuses with tachyarrhythmia
No drug therapy
Therapy nonhydropic Therapy hydropic
Foetal cardioversion
No foetal
cardioversion p Foetal cardioversion
No foetal
cardioversion p
Cases: reported, lost 52, 2 36, 3 16, 1 25, 0 9, 0
Caesarean section 20/43 (47%) 9/28 (32%) 12/15 (80%) 0.005 12/24 (50%) 9/9 (100%) 0.01
Time from diagnosis to
delivery (weeks)
6.1 Æ 5.8 9.0 Æ 4.4 3.6 Æ 2.8 0.001 7.1 Æ 4.9 2.7 Æ 1.9 0.05
GA at delivery (weeks) 38.5 Æ 1.9 (33-42) 38.8 Æ 2.1 (34-42) 36.8 Æ 1.5 (34-40) 0.005 36.5 Æ 3.3 (30-41) 33.4 Æ 1.2 (31-35) 0.05
GA 37 weeks 8 (15%) 5 (13%) 6 (38%) ns 11/24 (46%) 9 (100%) 0.005
Sex (boy/girl) 34/18 23/13 13/3 ns 12/12 8/1 0.05
Birthweight (SD score) 0.72 Æ 1.20 0.25 Æ 1.13 0.56 Æ 1.30 ns 0.49 Æ 0.94 1.83 Æ 1.36 0.01
Birthweight (2/Æ2/2SD) 1/33/4 0/23/2 0/11/3 ns 0/15/1 0/4/4 0.05
Asphyxia
(Apgar 7 at five minutes) 1 1 3
CPAP, ventilator 1, 1 1, 3
Pleural, abdominal drainage 1, 1
Postnatal arrhythmia 16/52 (31%) 6/36 (17%) 15/16 (94%) 9/25 (36%) 8/9 (89%)
Electroconversion 3
Values are presented as number of cases (percentage) or means Æ SD (range). P-values denote cases with versus without cardioversion. Abbreviations used:
CPAP = Continuous positive airway pressure. Other abbreviations as in Table 1.
Table 5 Postnatal treatment and long-term outcomes in 134 cases with foetal tachyarrhythmia.
AF AVRT PJRT, AET
CAT, VT JET
Nonhydropic Hydropic Nonhydropic Hydropic p Nonhydropic Hydropic Nonhydropic Nonhydropic
Cases: reported, lost 32, 3 6, 0 58, 4 25, 2 4, 1 3, 0 4, 0 2, 0
Follow-up time (years) 7 (0.5–18) 9 (1–11) 7 (0.2–21) 12 (0.2–22) 6 (1–13) 10 (4–7) 8 (4–10) 7
Antiarrhythmic treatment 26 (81%) 6 (100%) 35 (60%) 21 (84%) ns 2 3 0 2
Arrhythmia after one year 0 0 7 (12%) 2 (8%) ns 0 2 0 0
RF ablation 3 (5%) 2 (8%) ns 1
Cardiac transplant 1
Neurological sequela NDI PP* HP+NDI (IVH)
NDI HP (CAI)
Other malformation/
disease
Medulloblastoma Neuroblastoma*
Metabolic disease*
Cardiac/noncardiac
postnatal death
0 0/1 0/1 1/2 0 0
Values are presented as median (range) or number of cases (percentage). P-values denote AF versus AVRT. Abbreviations used: RF = Radiofrequency;
NDI = Neurodevelopmental impairment; PP = Paraparesis; HP = Hemiparesis; IVH = Intraventricular haemorrhage; CAI = Cerebral artery infarction. Other
abbreviations as in Table 1.
*Postnatal death.
©2015 Foundation Acta Pædiatrica. Published by John Wiley Sons Ltd 2015 104, pp. 1090–1097 1095
Ekman-Joelsson et al. Long-term outcome in foetal tachyarrhythmia

7. rates of cases with AVRT (7). These observations support
our theory that the lower rate of conversion in nonhydropic
foetuses in our study might be due to differences in weighing
the risks of continuing intrauterine treatment against deliv-
ery and treatment of the newborn baby.
Digoxin was the most common first line of treatment,
with an overall conversion rate of 52% in nonhydropic
cases and 25% in hydropic cases. When sotalol was
provided as a single therapy, it had a conversion rate of
70% in nonhydropic foetuses and 50% in hydropic foetuses.
Combining the nonhydropic and hydropic cases demon-
strated that sotalol was significantly more efficient than
digoxin in converting AVRT (63 versus 33%, p 0.05), but
not AF (57 versus 56%). We could not, however, demon-
strate any significant difference in the final conversion rate
between AVRT and AF (71 versus 59%) or between
nonhydropic and hydropic foetuses (70 versus 61%).
After excluding one foetus with severe Ebstein’s anomaly
and another with hereditary cardiomyopathy, we experi-
enced seven prenatal deaths related to arrhythmia. All
occurred shortly after diagnosis in severely hydropic cases
with AVRT. It is unlikely that significant foetal antiarrhyth-
mic drug levels had been reached in at least three cases. In
another three cases, including two who converted to sinus
rhythm with very poor ventricular function, we cannot
exclude the possibility that the negative inotropic effect of
sotalol might have contributed to the deaths. Foetal deaths
shortly after initiating transplacental treatment in hydropic
foetuses with AVRT have previously been reported for
sotalol, flecainide and digoxin. This indicates a need for
urgent cardioversion without further compromise of ven-
tricular function in cases such as this (3,5,12,15,16). Smaller
case studies have shown promising results with transpla-
cental amiodarone treatment, with or without coadminis-
tration of foetal intramuscular digoxin (17–19). In addition,
this treatment has disadvantages and the optimal treatment
in hydropic AVRT cases still needs to be established.
In this study, 99 cases received transplacental treatment,
61 with sotalol as a single or combination therapy, without
any serious complications in the foetus. Serious maternal
complications were only seen in two mothers who devel-
oped preeclampsia and digoxin intoxication. There were
no deaths in foetuses with AF or AVRT without hydrops
and 16% mortality in cases with hydrops, consistent with
previous studies (5,7). Based on these data, and the
publication of excellent results using sotalol as a first-line
treatment, we believe that this drug definitely has a place in
the treatment of AF and nonhydropic foetuses with AVRT
(12,14). As expected, we found PJRT, AET and JET more
resistant to treatment, with only two of the six cases that
received transplacental treatment converting to sinus
rhythm. Only one of the four CAT or VT cases was
considered to need transplacental treatment and was
successfully converted.
Neonatal and long-term outcome
Even if cardioversion prolonged pregnancy and resulted in
fewer Caesarean sections, almost none of the newborn
babies had problems related to prematurity, irrespective of
intrauterine conversion or not. Four of the five cases with
asphyxia and/or in need of mechanical respiratory support
occurred among noncardioverted foetuses with hydrops
at diagnosis. Yet, the majority did well and there was
no neonatal mortality, confirming the haemodynamic
improvement we also observed in the foetuses without
cardioversion who survived to birth. In all, five had
neurological symptoms at long-term follow-up, three of
the 34 in the hydropic cohort and two of the 103 in the
nonhydropic cohort. Due to the design of this study, this is
probably an underestimation. Cerebral injury as a compli-
cation of foetal tachycardia has been reported to affect
between 4% and 40% of hydropic foetuses (5,20,21). One
study that investigated this issue more specifically reported
a good neurological outcome in eight of the 11 hydropic
cases investigated at follow-up (22).
We do not have any explanation for the gender effect
observed in this study. However, our observation that girls
were more likely to convert during intrauterine treatment
and had a lower risk of postnatal arrhythmia contradicts the
results obtained by others (13).
Our analysis of the incidence of postnatal arrhythmias is
hampered by the fact that many of the cases were started
on prophylactic treatment shortly after birth. This might
explain why our incidence of 25% in foetally converted
cases is somewhat lower than the 30–45% reported by other
studies (13,14). In our study, recurrence of arrhythmia was
documented in 8% of cases after one year of age and this
occurred exclusively in cases with AVRT or PJRT. Cases
with CAT or VT did not receive any postnatal treatment,
and all cases with AF were resolved before one year of age.
Retrospective data spanning a 22-year period are some-
times difficult to retrieve and reanalyse. Treatment strate-
gies of a rare disease such as foetal tachycardia might also
change during a study period of this length. On the other
hand, two of the authors were responsible for the foetal
cardiology services at the two centres, using the same
treatment protocol and exchanging experiences throughout
the study period. As both centres are the only tertiary
paediatric cardiology services in their respective regions for
both foetal and paediatric arrhythmia cases, almost all
foetal tachycardia cases are likely to have been included in
the study. However, our long-term observations have to be
interpreted with caution, as the most of the children we
studied have not yet become teenagers, a period when
tachycardia has a tendency to recur.
CONCLUSION
This study demonstrates the need for an accurate diagnosis
of the type of arrhythmia and a thorough evaluation of
the haemodynamic condition when treating a foetus with
tachycardia. Several antiarrhythmic drugs were frequently
needed and, in many cases, more than one to two weeks
elapsed from start of treatment to cardioversion, indicating
the need for knowledge of the impact of antiarrhythmic
treatment on both the mother and her foetus. Our results
1096 ©2015 Foundation Acta Pædiatrica. Published by John Wiley Sons Ltd 2015 104, pp. 1090–1097
Long-term outcome in foetal tachyarrhythmia Ekman-Joelsson et al.

8. suggest that sotalol can be used without any maternal or
foetal complications in most cases of foetal tachycardia.
Sotalol was as efficient as digoxin in cases with AF, and it
produced a higher conversion rate than digoxin in AVRT.
Severely hydropic cases with AVRT experienced significant
mortality shortly after starting treatment, suggesting that
other alternatives with more prompt cardioversion and
less negative inotropic effect on an already compromised
myocardium should be used. Transplacental treatment
failed to convert one-third of the treated cases, but the
treatment usually resulted in a prolonged pregnancy,
together with improvements in the foetal haemodynamic
situation also in these nonresponders. This, in turn, resulted
in an overall 93% survival rate, with only few cases with
long-term cardiac or neurological morbidity.
FUNDING
Financial support was provided through the regional
agreement on medical training and clinical research
(ALF) between Stockholm County Council and the
Karolinska Institutet and by the Swedish Heart Lung
Foundation and the Freemasons in Stockholm Foundation
for Children’s Welfare.
CONFLICT OF INTEREST
The authors have no conflict of interests to declare.
References
1. Bergmans MG, Jonker GJ, Kock HC. Fetal supraventricular
tachycardia. Review of the literature. Obstet Gynecol Surv
1985; 40: 61–8.
2. Hansmann M, Gembruch U, Bald R, Manz M, Redel DA. Fetal
tachyarrhythmias: transplacental and direct treatment of the
fetus-a report of 60 cases. Ultrasound Obstet Gynecol 1991; 1:
162–8.
3. van Engelen AD, Weijtens O, Brenner JI, Kleinman CS, Copel
JA, Stoutenbeek P, et al. Management outcome and follow-up
of fetal tachycardia. J Am Coll Cardiol 1994; 24: 1371–5.
4. Frohn-Mulder IM, Stewart PA, Witsenburg M, Den Hollander
NS, Wladimiroff JW, Hess J. The efficacy of flecainide versus
digoxin in the management of fetal supraventricular
tachycardia. Prenat Diagn 1995; 15: 1297–302.
5. Simpson JM, Sharland GK. Fetal tachycardias: management
and outcome of 127 consecutive cases. Heart 1998; 79: 576–81.
6. Krapp M, Kohl T, Simpson JM, Sharland GK, Katalinic A,
Gembruch U. Review of diagnosis, treatment, and outcome of
fetal atrial flutter compared with supraventricular tachycardia.
Heart 2003; 89: 913–7.
7. Jaeggi ET, Carvalho JS, De Groot E, Api O, Clur SA, Rammeloo
L, et al. Comparison of transplacental treatment of fetal
supraventricular tachyarrhythmias with digoxin, flecainide, and
sotalol: results of a nonrandomized multicenter study.
Circulation 2011; 124: 1747–54.
8. Sonesson SE, Fouron JC, Wesslen-Eriksson E, Jaeggi E,
Winberg P. Foetal supraventricular tachycardia treated with
sotalol. Acta Paediatr 1998; 87: 584–7.
9. Fouron JC. Fetal arrhythmias: the Saint-Justine hospital
experience. Prenat Diagn 2004; 24: 1068–80.
10. Niklasson A, Albertsson-Wikland K. Continuous growth
reference from 24th week of gestation to 24 months by gender.
BMC Pediatr 2008; 8: 8.
11. Sonesson SE, Winberg P, Lidegran M, Westgren M. Foetal
supraventricular tachycardia and cerebral complications. Acta
Paediatr 1996; 85: 1249–52.
12. Shah A, Moon-Grady A, Bhogal N, Collins KK, Tacy T, Brook
M, et al. Effectiveness of sotalol as first-line therapy for fetal
supraventricular tachyarrhythmias. Am J Cardiol 2012; 109:
1614–8.
13. Moodley S, Sanatani S, Potts JE, Sandor GG. Postnatal
outcome in patients with fetal tachycardia. Pediatr Cardiol
2013; 34: 81–7.
14. van der Heijden LB, Oudijk MA, Manten GT, ter Heide H,
Pistorius L, Freund MW. Sotalol as first-line treatment for fetal
tachycardia and neonatal follow-up. Ultrasound Obstet
Gynecol 2013; 42: 285–93.
15. Allan LD, Chita SK, Sharland GK, Maxwell D, Priestley K.
Flecainide in the treatment of fetal tachycardias. Br Heart J
1991; 65: 46–8.
16. Oudijk MA, Michon MM, Kleinman CS, Kapusta L,
Stoutenbeek P, Visser GH, et al. Sotalol in the treatment of
fetal dysrhythmias. Circulation 2000; 101: 2721–6.
17. Pezard PG, Boussion F, Sentilhes L, Lepinard C, Couvreur
MH, Victor J, et al. Fetal tachycardia: a role for amiodarone as
first- or second-line therapy? Arch Cardiovasc Dis 2008; 101:
619–27.
18. Cuneo BF, Strasburger JF. Management strategy for fetal
tachycardia. Obstet Gynecol 2000; 96: 575–81.
19. Strasburger JF, Cuneo BF, Michon MM, Gotteiner NL, Deal BJ,
McGregor SN, et al. Amiodarone therapy for drug-refractory
fetal tachycardia. Circulation 2004; 109: 375–9.
20. Lisowski LA, Verheijen PM, Benatar AA, Soyeur DJ,
Stoutenbeek P, Brenner JI, et al. Atrial flutter in the perinatal
age group: diagnosis, management and outcome. J Am Coll
Cardiol 2000; 35: 771–7.
21. Boldt T, Eronen M, Andersson S. Long-term outcome in fetuses
with cardiac arrhythmias. Obstet Gynecol 2003; 102: 1372–9.
22. Oudijk MA, Gooskens RH, Stoutenbeek P, De Vries LS, Visser
GH, Meijboom EJ. Neurological outcome of children who were
treated for fetal tachycardia complicated by hydrops.
Ultrasound Obstet Gynecol 2004; 24: 154–8.
©2015 Foundation Acta Pædiatrica. Published by John Wiley Sons Ltd 2015 104, pp. 1090–1097 1097
Ekman-Joelsson et al. Long-term outcome in foetal tachyarrhythmia