<=
/span>SELECTIVE TERMINATION FOR FETAL ANOMALY / GENE=
TIC
DISORDER IN TWIN PREGNANCY AT 32+ MENSTRU=
AL
WEEKS:
Report of Four Cases
Warren M=
. Hern
&nb=
sp; =
&nb=
sp; =
&nb=
sp; =
Boulder Abortion Clinic, Boulder, Colo. and Departme=
nt
of Obstetrics and Gynecology,
University of Colorado Health Sciences Center, Denve=
r,
Colorado, USA
Key words
Selective
termination – Twin – Late pregnancy – Feticide –
Fetal
malformation – Third trimester – Genetic disorder
&nb=
sp; =
&nb=
sp; =
&nb=
sp; =
In this study,
outpatient selective termination of one abnormal fetus was performed in four
patients whose twin pregnancies had advanced to 32 or more menstrual weeks<=
/span>.
Abstract
Objectiv=
es: To conduct a pilot study of 4 case=
s of
selective termination of a single abnormal fetus in a dichorionic, diamniot=
ic
twin pregnancy advanced to 32 or more menstrual weeks of gestation. Study Design: This is a case series of 4 patient=
s in
highly unusual circumstances and treatment. Four healthy patients with desired
pregnancies complicated by the presence of an abnormal genetic or developme=
ntal
diagnosis in 1 twin were treated by selective termination of the abnormal t=
win
using intracardiac injection of potassium chloride. Results: In all 4 patients, ca=
rdiac
arrest in the abnormal twin was effected without disturbance of the healthy
twin or the mother. Postopera=
tive
maternal serum potassium levels remained at normal levels. Delivery of a healthy surviving tw=
in
occurred from 2 days to 4 weeks following the selective termination along w=
ith
delivery of a still-born abnormal twin.&nb=
sp;
Conclusion: Selective termination of an abnormal twin may be
performed on an outpatient ba=
sis in
the last weeks of pregnancy.
Introduction
Selective termin=
ation
of multiple pregnancies has commonly been performed prior to 265 menstrual
weeks for the purpose of reduction of numbers of gestations, and selective
termination for fetal anomaly prior to 25 weeks has been reported previousl=
y [1
– 3]. However, only one
report of selective termination for fetal anomaly after 30 menstrual weeks =
has
been published [4]. As the number of women who experience a desired first
pregnancy in later reproductive life increases, it is critical that these w=
omen
and their partners be able to carry a twin pregnancy to term in spite of the
presence of severe fetal anomalies or genetic disorder in one of the
twins. The alternatives have =
been
to deliver 1 healthy and 1 severely impaired child with its attendant pain,
suffering, and emotional costs, or to terminate the twin pregnancy entirely=
. Termination of the abnormal twin e=
arly
in pregnancy may result in a
significant proportion of immature delivery or spontaneous losses of the en=
tire
pregnancy including the healthy twin [1 – 3,5], although Eddleman et =
al.
[6] report an unintended pregnancy loss of 4% overall with a rate of 2.4% in
twins. Selective termination =
of the
abnormal twin in late pregnancy after 32 menstrual weeks offers the possibi=
lity
of optimum fetal development in the healthy twin should spontaneous labor o=
ccur
or in case a decision must be made for any reason to perform a cesarean
delivery of the healthy twin.
Methods
Four patients wh=
o were
referred by private or academic centers presented for selective termination=
at
32-34 menstrual weeks in a private clinic specializing in late terminations=
of
pregnancy [7]. All patients w=
ere in
their late 30s and were carrying desired twin dichorionic, diamniotic,
dyzygotic pregnancies. For 3 =
of the
patients, this was their first prengncy.&n=
bsp;
All 4 wished to continue the pregnancy to term or as long as possibl=
e to
assure survival of the healthy twin.
All patients had been evaluated extensively at experienced prenatal
centers, including university teaching hospitals, prior to treatment. All 4 had knowledge of the abnorma=
lity
affecting the unhealthy twin, its immediate recent location in the uterus, =
and
the prognosis for severe impairment in the abnormal twin. In 1 patient, polyhydramnios
accompanying the abnormal twin had an adverse effect on the mother and on t=
he
healthy twin.
Three of the patients were in exce=
llent
health. One patient was basic=
ally
healthy but was moderately obese, and she began developing early signs of
preeclapsia just before the end of the selective termination treatment. She experienced a cesarean deliver=
y of
both her stillborn and healthy twin 2 days following the selective
reduction. The other 3 contin=
ued
the pregnancies for several weeks following selective reduction and deliver=
ed 1
healthy twin as well as 1 stillborn infant.
In each patient,=
care
was taken to be certain about the location of the abnormal twin by immediat=
ely
recent clinical history including review of all medical records and
consultation with the patient's attending perinatologist. Preoperative ultrasound
evaluations were made several times on the day of the procedure and just be=
fore
the procedure began. Visualiz=
ation
of the presence and location of the amniotic membrane between the two amnio=
tic
sacs was made each time. Beca=
use of
concerns for the possibility of maternal absorption of potassium from the f=
etal
injection, a precautionary intravenous line for infusion of 1000cc normal
saline was established preoperatively in order to dilute any excess potassi=
um
levels that might be experienced and to facilitate a fluid load that could
accelerate excretion of excessive potassium ions.
With the patient=
lying
on the operating table, sometimes with a pad under a hip to prevent vena ca=
val
compression, the heart of the abnormal twin was visualized with ultrasound =
and
the maternal skin marked at that site.&nbs=
p;
A povidine/iodine prep was applied to the skin around the injection
site, and the area was covered with a sterile drape. The ultrasound probe was covered w=
ith a
sterile probe cover and controlled by the surgeon. At the injection site, 12cc of 1%
lidocaine buffered by 8.4% sodium bicarbonate was infiltrated into the skin=
and
subcutaneous tissues down to the level of the uterine wall. The skin surface was then puncture=
d with
a 16 gauge IV needle. At that=
point,
a 15cm 20 gauge echotip spinal needle was introduced percutaneously through=
the
uterine wall and into the cardiac ventricle of the abnormal fetus. Following aspiration of cardiac bl=
ood, a
solution of 15% potassium chloride (2 Meq/ml) was injected until cardiac ar=
rest
occurred. The lack of cardiac
activity was observed for several minutes before terminating the
procedure.
Following the
intracardiac fetal injection, the cardiac activity of the healthy twin was
observed and confirmed to be normal.
The patient was then returned to the recovery room and observed for
periods of up to two hours. V=
ital
signs were monitored, and postoperative serum potassium levels were
followed. All patients were
discharged from the private office setting recovery room on the same day as=
the
procedure and returned home immediately.
Cases
Case 1.<=
/b>
Patient #1 was G=
r 1 P
0 Ab 0 with a pregnancy duration of approximately 32 menstrual weeks at the
time of the first visit. Twin=
A, a
female, had been diagnosed with Goldenhar Syndrome several weeks previously=
. Although the patient had arrived at
Boulder, Colorado two weeks prior to the scheduled procedure in early Febru=
ary
2000, she began to have periodic contractions one week after arriving. She was evaluated by an obstetrical
colleague and treated with parenteral terbutaline, and her procedure was re=
scheduled
for the same day.
The needle tip w=
as
placed in the cardiac ventricle of the abnormal fetus, a small amount of
cardiac blood was aspirated, and 6 mEq of KCl was injected. Cardiac arrest occurred immediatel=
y, and
this was observed for five minutes before the needle was withdrawn. The patient was placed in the reco=
very
room and displayed no adverse effects.&nbs=
p;
All vital signs remained within normal limits. &n=
bsp; Approximately
five weeks following the selective termination, the patient delivered a hea=
lthy
male twin by cesarean delivery. The
abnormal female Twin A had an appearance consistent with Goldenhar
Syndrome. The surviving twin =
has
shown exuberant health and normal development since delivery in March, 2000=
.
Case 2.
Patient #2 was a
primagravida who presented at 32 weeks with a diagnosis of one healthy male
twin and one female twin afflicted with a 3-chambered heart and Trisomy
21. The patient was moderately
obese at 200 lb. and 5'7" but had no other apparent health problems.
Following routine
preoperative procedures, 10 mEq of KCl was injected into the cardiac ventri=
cle
of the abnormal fetus. Fetal
cardiac rhythm slowed briefly but did not completely stop. After a few minutes, an apparently
normal cardiac rhythm resumed.
The patient was =
returned
to the recovery room to rest, and she displayed no change in status includi=
ng
vital signs.
Two hours after =
the
first injection, and two and one-half hours after the first pre-medication,=
the
patient was given another parenteral dose of meperidine 75 mg and
prochlorperazine 5 mg IM. She
returned to the operating room, where 10 mEq of KCl was again injected into=
the
cardiac ventricle of the abnormal fetus.&n=
bsp;
The same sequence was observed: a slowing of the fetal heart rate for
several minutes followed by a return to normal rhythm.
A serum potassium
level drawn from the patient 1 1/2 hours following the second fetal
intracardiac injection was normal at 4.6 mEq/L.
The patient and =
her
husband were invited to return in two weeks for another attempt, and they d=
id.
At the time of t=
he
second visit, the patient now had a blood pressure reading of 142/90 and sh=
owed
3+ protein in the urine. Her
physicians at the university hospital back home were concerned about the
development of pre-eclampsia. She
was now 34 weeks pregnant.
A pre-med of 100=
mg
meperidine and 10 mg prochlorperazine was again given about 45 minutes prio=
r to
the attempted fetal intracardiac injection.
Just before the =
fetal
injection, the patient's blood pressure was 150/102 with a pulse of 80.
Following the us=
ual
preoperative preparations, 20 mEq of KCl was injected into the cardiac
ventricle of the abnormal twin.
Immediate fetal cardiac arrest occurred.
Following return=
to
the recovery room 45 minutes later, the patient's blood pressure was 148/98
with a pulse of 76. Serum pot=
assium
at that time was 4.1 mEq/L, and all other laboratory values were within nor=
mal
limits.
Diastolic blood
pressures continued to drop, with readings of 148/80 and 148/74 observed ju=
st
before discharge.
The patient was
discharged in good condition in the company of her husband three hours
following the selective termination.
She returned home by air the next day, and the following day, due to
increasing signs of pre-eclampsia, she experienced a cesarean delivery of a
healthy Twin B and stillborn Twin A.
The surviving twin has shown normal health and development during th=
e 2
1/2 years since birth.
Case 3.
Patient #3 was G=
r 3 P
2 Ab 0 with no history of cesarean delivery. She presented with a dc/da/dz twin
pregnancy in which Twin A was healthy and Twin B showed genetic and
ultrasonographic evidence of skeletal dysplasia. Both fetuses were male.
At the time of
presentation, the patient was approximately 34 menstrual weeks from LMP by
ultrasound measurement. Twin =
B had
been found to have an abnormal karyotype of 47,XY,+mar de novo[8], extra ma=
rker
chromosome. Ultrasound exam h=
ad
shown abnormally short tibia and femur with poly-hydramnios. The patient was on maintenance
terbutaline orally for contractions.
The
patient was in excellent physical health but requested prophylactic intrave=
nous
antibiotic treatment. Cefotet=
an 1
gm was prepared in 500cc normal saline for intravenous infusion during and
after the procedure.
Following routine
preparation, 20 mEq of KCl was injected into the cardiac ventricle of the
abnormal Twin B. Cardiac acti=
vity
slowed but did not stop. An
additional 10 mEq was injected, which caused a further slowing but not
cessation of cardiac rhythm. =
5 mEq
more of KCl was injected, for a total of 35 mEq, before the procedure was
terminated. Fetal cardiac arr=
est
had not occurred.
After observatio=
n for
30 minutes in the operating room, the patient was taken to the recovery roo=
m to
rest. A serum potassium=
was
drawn 90 minutes following the fetal intracardiac injection, and it was 3.6
mEq/L.
Two hours after =
the
original procedure, the patient was returned to the operating room, where T=
win
B, the abnormal twin, showed no cardiac activity. In Twin A, the cardiac activity was
normal.
The patient was discharged in good condition one hour later to the care of her perinatologist. Four weeks la= ter, labor was induced, and she delivered a healthy baby boy and a stillborn male infant. Since delivery one ye= ar prior to the preparation of this report, the surviving twin is healthy and showing normal development. <= o:p>
Case 4.
Patient No. 4 is=
a
primagravida who was approximately 32 weeks from LMP on at the beginning of
February 2003. The patient
presented with a diagnosis of a twin pregnancy with one healthy female fetus
(Twin A) in the lower uterine segment and an abnormal male Twin B with a
diagnosis of myelomeningocele and Arnold/Chiari malformation. The patient was in excellent=
physical
health with normal vital signs and a normal physical exam.
A preoperative s=
erum
potassium was 4.2 mEq/L.
Following routine
preparation, 20 mEq of KCl was injected into the cardiac ventricle of the
abnormal Twin B. It appeared =
that
part of the injected material entered the pericardial sac. Cardiac rhythm slowed but did not
stop. The procedure was termi=
nated
at that point. A serum potass=
ium
drawn ten minutes later was 4.3 mEq/L.
One hour later, =
the
injected heart of the abnormal fetus had changed in appearance with the car=
diac
walls and septum appearing thicker.
Cardiac rhythm was slow.
This time, the injection of approximately 6 mEq of KCl resulted in
immediate cessation of cardiac activity.&n=
bsp;
The remainder of the 20 mEq of KCl in the syringe was injected for a
total of 40 mEq. There was no
return of cardiac activity. &nb=
sp;
The cardiac activity of healthy Twin A remained normal.
The patient was
discharged in good condition and in the company of her husband two hours
following the repeat intracardiac fetal injection to the care of her univer=
sity
hospital physician. She retur=
ned
home by air that evening. Thr=
ee
days later, she reported that she felt well, was experiencing few contracti=
ons,
and was anticipating a routine prenatal visit the next week.
Twenty-four days=
after
the selective termination, the patient gave birth by cesarean delivery to a
healthy baby girl weighing a little over 2600 grams.
Conclusion
There are many e=
thical
issues that can be raised concerning selective termination of an abnormal f=
etus
in a twin pregnancy. The one =
group
that has reported selective terminations at the early third trimester expre=
ssed
objections to the application of this technique in late pregnancy [4]. Chervenak, et al, stated that
termination of pregnancy in the third trimester is morally justified only in
the case of a lethal or catastrophic abnormality such as anencephaly [8].
It is our view t=
hat a
decision to choose third-trimester selective termination may be made by the
woman and her partner in the case of a valid and documented fetal
abnormality. It is up to the =
physician
to determine whether he or she accepts the potential risks and ethical
questions of this procedure and fully discusses these issues with the
requesting patient and her partner.
Since the physic=
ian
does not act alone, it is necessary to have the assistance of skilled ancil=
lary
personnel who support the couple's decision and the physician's actions.
While the select=
ive
termination by intracardiac KCl injection of an abnormal fetus in late
pregnancy may present some risk to the normal fetus, to continuation of the
pregnancy, and to the mother, it offers many advantages for a couple with a
desired dichorionic, diamniotic twin pregnancy complicated by serious
abnormality in one fetus. A shared
placental circulation in a known monochorionic twin pregnancy contraindicat=
es
this specific procedure because of the risk to the healthy fetus or risk of
total pregnancy loss [11].
It appears that =
the
amount of potassium chloride necessary for the selective termination of a f=
etus
at 32+ weeks is considerably more than the amounts routinely used for selec=
tive
reductions/ terminations in previously reported series up to 24 menstrual
weeks. In the first patient, =
the
recommended dosage of 6 mEq of KCl was instantly effective, but other cases
required as much as 20 - 35 mEq in one dose.
Under the adage =
primum
no nocerum, no physician wants or accepts harm to his primary patient, =
and
the greatest fear is that the amount of material used for selective termina=
tion
might harm the healthy fetus or worse, the woman carrying the pregnancy.
With respect to =
the
lateness in pregnancy at which this technique can or should be applied, we =
note
that one of our patients was experiencing an increasingly serious
polyhydramnios in the abnormal twin which threatened her well-being as well=
as
the safety of the healthy twin.
While repeated removal of excessive amniotic fluid in such a case mi=
ght
offer one alternative, depending on the circumstances, this procedure also
carries risks that might outweigh those of selective termination in late
pregnancy. Such a
consideration could bear heavily on the ethical question of whether it is
appropriate to cause selective termination of one abnormal fetus late in the
third trimester of pregnancy.
References
1.
Berkowitz RL, Stone JL, and
Eddleman KA: One hundred
consecutive cases of selective
termination of an abnormal f=
etus
in a multifetal gestation. Ob=
stet
Gynecol 1997;90:606-610.
2. Evans MI, Goldberg JD, Horenstein =
J,
Wapner RJ, Ayoub MA, Stone J, Lipitz S, Achiron R,
Holzgreve W, Bra=
mbati
B, Johnson A, Johnson MP, Shalhoub A, and Berkowitz RL:
Selective termination for structura=
l,
chromosomal, and mendelian anomalies: International
experience. Am J Obstet Gynecol 1999;181:893-8=
97.
3.
Evans MI, Berkowitz RL, Wapne=
r RJ,
Carpenter RJ, Goldberg JD, Ayoub MA, Horenstein J,
Dommergues M, Br=
ambati
B, Nicolaides KH, Holzgreve W, and Timor-Tritsch IE:
Improvement in
outcomes of multifetal pregnancy reduction with increased experience. Am J
Obstet Gynecol
2001;184:97-103.
4. Shalev J, Meizner I, Rabnerson D,
Mashiach R, Hod M, Bar-Chava I, Peleg D, and Ben-
Rafael Z: Improving pregnancy outcome in twin
gestations with one malformed fetus by
postponing selec=
tive
feticide in the third trimester.
Fert and Steril 1999; 72(2):257-260.
5.
Lipitz S, Shale E, Meizner I,=
Yagel
S, Weinraub Z, Jaffa A, et al: Late
selective termination
of fetal abnorma=
lities
in twin pregnancies: a multicenter report.=
Br J Obstet Gynaecol
1966;103:1212-12=
16.
6. Eddleman KA, Stone JL, Lynch L,
Berkowitz RL: Selective termi=
nation
of anomalous fetuses
in multifetal
pregnancies: Two hundred cases at a single center. Am J Obstet Gynecol 2002;
187(5):1168-1172=
.
7. Hern, WM. Laminaria, induced fetal demise and
misoprostol in late abortion. Int J
Gynecol
Obstet 2001;75:279-286.
8. Chervenak FA, Farley MA, Walters L,
Hobbins JC, Mahoney MJ: When is termination of
pregnancy during=
the
third trimester morally justifiable?
N Engl J Med 1984:310:501-504.
9. Evans MI, Krivchenia EL, Gelber SE,
Wapner RJ: Selective
reduction. Clin Perinat 2003;=
30:103-111.
10.
Evans MI, Wapner RJ, Ayoub MA, Shalhoub AG, Feldman B, Yaron Y: Spontaneous
abortions =
in
couples declining multifetal pregnancy reduction. Fetal Diagnosis & Therapy
2002; 17:343-346=
.
11.
De Catte L, Camus M, Foulon W: Monochorionic high-order multiple pregnancies
and
muiltifetal preg=
nancy
reduction. Obstet Gynecol 200=
2;
100:561-566.
Selective
Termination in Late Pregnancy =
Fetal Diagnosis and Therapy 2004; 19:292-295
Received:
April 7, 2003 =
&nb=
sp; =
&nb=
sp; =
Fetal Diagn Ther 2004;19:292-295
Accepted:
September 2, 2003 =
&nb=
sp; =
&nb=
sp;
DOI: 10.1159/000076714
Address correspondence to:
Warren
M. Hern, M.D., M.P.H., Ph.D.
Boulder
Abortion Clinic
1130
Alpine
Boulder,
Colorado 80304
Tel:
(303) 447-1361
FAX:
(303) 447-0020
email:
bachern@drhern.com
<=
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