Utilization
of Prenatal
Diagnosis
For
Cystic
Fibrosis
Over
the
Past
Seven
Years
ilse Jedlicka-Kohler, PhD; Manfred G#{246}tZ,MD; and Irmgard Eichler, MD
ABSTRACT. Objective. First trimester prenatal
diag-nosis (PD) by DNA analysis for cystic fibrosis (CF) has
been available for parents of affected children since May
1986.
Methods. In a prospective study 37 couples with a single child affected by CF were investigated. Fathers and mothers were interviewed simultaneously, and their
attitudes towards further childbearing and potential
uti-lization of PD ascertained. Parental answers were treated as one. A 7-year follow-up allowed comparison between intended and actual behavior.
Results. At the time of the interview, 16 parents (43%) were determined to have further children. Nineteen parents
(51%) said they would certainly or probably utilize PD in case of pregnancy. Their predominant reason for favoring PD was
the strong desire to have a healthy child (47%). Among the 18 rejechis(49%)thefearofanunsolvableconffictincaseofan
affected fetus prevailed (39%). Twenty-four pregnancies
actu-ally occurred in 18 families. Utilization of PD was arranged in
five 21%) and finally performed in four (17%) cases.
Conclusion. Availability of PD does not substantially change the repmductive behavior of parents of children with
civ.
for this were multifactorial, with anticipateddif-ficulty in deciding to continue or terminate pregnancy being
predominant Pediatrics 199494i13-16; behavioi cystic
fthm-sL
-
dia, psydwlogy.ABBREVIATIONS. CF. cystic fibrosis; PD, prenatal diagnosis.
A large proportion of families with a child with
cystic fibrosis (CF) tend to stop having further chil-then to avoid the one-in-four risk of another affected
child.” In one study 20% of the investigated 50
mothers even indicated they would commit suicide rather than have another child with CF.3
In cystic fibrosis, the most frequent monogenic hereditary defect in Caucasians, the defective gene causes altered membrane function in a variety of
organs, ranging from the lungs to the sweat glands.
Although median survival age doubled from 14 to 28 years between 1969 and 1990k with a predicted
me-dian life expectancy for babies born today of up to 40
years5 the disease still remains incurable. Demanding
lifelong therapy, physical limitations, and ensuing
psychosocial restrictions contribute to progressively decreasing quality of life.
From the University Children’s Hospital, Vienna, Austria.
The results of this study were presented, in part, at the Sixth Annual North American Cystic Fibrosis Conference, Washington, DC, October 15-18,
1992.
Received for publication Jun 16, 1993; accepted Dec 15, 1993.
PEDIATRICh (IS5N 0031 4005). Copyright C 1994 by the American
Acad-amy of Pediatrics.
Given the severity of the disease, availability of first trimester prenatal diagnosis (PD) by DNA anal-ysis was considered to increase substantially the
re-productive options for couples with an affected
child. This assumption was supported by findings of studies before PD was generally available, exploring what parents might do in a hypothetical situation.’ Then, pronounced interest in this option was
re-vealed. Eighty-one to 94% of parents of children with
CF favored the development of fetal diagnosis”, and
85% had the intention to use PD should pregnancy
occur.6 The purpose of this prospective study, there-fore, was to explore the reproductive behavior of parents of children with CF who faced the actual availability of a preventive strategy. Our specific
aims were 1) to examine the effect of availabifity of
PD on family planning, 2) to identify attitudes to-wards PD, 3) to find out to what extent parents intended to have PD prior to a subsequent
preg-nancy,
and 4) to assess actual performance of PD in case of pregnancy.Subjects
MATERIALS AND METHODS
Since mid-1986 the CF Center at the UniVersity Children’s Hospital in Vienna has been able to provide first trimester prenatal diagnosis by
DNA analysis. This center serves a third ofthe Austrian FpOpUIa6OTh StartinginMay l98#{243}weselected families who met the following cnteia:
1) The child with
c
born after January 1980 and had to be thefirstborn and still the only child atthe beginning of the study. This was
toavoid thepreviouslyreported finding thatthehigherthebirth rank of
thechild withO, thelessprobableasubsequentpregnancy.6 From May
1986 onwards all parents of newly diagnosed children enrolled in our
center were enlisted in our study. 2) No children from previous
mar-riage. 3) Biological parents were married or cohabiting. A stable
rela-tionship was considered a basic requirement for amassing future family planning. 4) Maternal age at the birth of the child with F had to be
below 30 years in order to avoid the bias of older gravidas. Subject
recruitment ended in April 1991 and follow-up was finished in Apiil
1993. This irttervalallowed even theparentsof theyoungestchild at least 2 years to consider a subsequent pregnancy.
Methods
Information about PD was performed twice by the
pediatri-dana (MG, IE). Parents whose child was born between May 1986
and April 1991 received this information in the context of
corn-munication of diagnosis and again within a month. To parents whose child was born between January 1980 and April 1986 PD was explained between May and September 1986 at a regular clinic visit and repeated at the consecutive appointment 1 to 3 months later.
The psychologist (I J-K) conducted a structured interview with
both parents present 4 to 8 weeks following the second
commu-nication of information on PD. Parents were interviewed during a
regular dinic visit at the hospital. Each session lasted 60 to 90
minutes. In part 1 of the interview, parents’ baseline knowledge of
14 PRENATAL DIAGNOSIS FOR CYSTIC FIBROSIS to ensure that the information given by the pediatricians had been
retained. In case of false answers, correct information was pro-vided. In part 2 of the interview a number of standardized
ques-tions were asked. Items focused on: assessment of initially
planned family size before and reproductive plans after the birth of the CF child; attitudes towards prenatal diagnosis; assessment of the potential utilization of PD. Parents’ responses represent
their shared views. Part 3 of the interview gave parents the
op-portunity to verbalize concerns and to pose questions.
Data collection included review of medical records for
infor-mation on age at diagnosis, age at counseling, and health status of the child. Severity of disease was calculated by the pediatricians
according to the Shwachman score? from case history, pulmonary
physical findings, and cough, growth, and nutrition. As chest
radiographs are taken routinely only once a year, not all children had recent documentation of this item. Therefore, chest
radio-graphs were not considered, thus rendering the maximum
Shwachman score available at 75.
Statistics
Questionnaire data were entered into a Statistical Package for the Social Sciences.8
Differences between firstborn children with CF whose mothers
had a subsequent pregnancy and children remaining without sibs,
in relation to age and health status, were examined using t tests and Mann-Whitney U tests depending on the distribution of the
variable under consideration. Differences between intended and
performed utilization of PD were assessed by means of the McNemar’s test for paired groups.
P values of <.05 or less were accepted as significant.
RESULTS
The psychologist interviewed 37 sets of parents; 35 were married and two cohabiting. At diagnosis, cM!-dren’s median age was 1 month (range, 0 to 40 months), and, at the time their parents were first counseled about PD, it was 3 months (range, 0 to 63
months). A mean Shwachman score of 63 (range, 46
to 72) at the time of counseling about PD reflects good health in most of the children (maximum score without chest radiograph, 75). Eleven children were
born before May 1986 and 26 thereafter. Mean fol-low-up was 5.1 years (range, 24 months to 7 years).
At the time of the interview 16 (43%) couples were determined to have two or more children whereas 21 (57%) decided against further offspring. Compared to their intentions before the child with CF was born a number of parents changed their plans.
Attitudes Towards Prenatal Diagnosis
Parents were asked if they intended to use PD
should pregnancy occur. Fifty-one percent thought that they would certainly or probably use it, while 49% answered that they would certainly or probably not use it. Parents were requested to state their rea-sons for favoring or rejecting PD in their own words. Reasons were manyfo!d as shown in Tables 1 and 2 with many parents
giving
two answers.TABLE 1. Reasons for Favoring Prenatal Diagnosis (n = 19)
n %
9
Desire to have a healthy child 47
Unbearable psychological distress caused by two 6 32 children with CF
Inabifity to master the demanding and time consuming 6 32
management of two affected children
Wish for a surviving child 2 11
Early emotional adjustment/relief 1 5
To perform selective termination I 5
TABLE 2. Reasons for Rejecting Prenatal Diagn osis (n = 18)
n %
Fear of an unsolvable conflict in case of an 7 39
affected fetus
implicit downgrading of the child with CF 6 33
Moral constraints 4 22
Religious beliefs 3 17
Good health in the child with CF 3 17
Frightening anticipation of repeated I 6 pregnancies and terminations
Fetus treated as a “guinea-pig” I 6
Increased risk of fetal mortality I 6
Normal intellectual development rules out PD I 6
Hope that, due to the I in 4 risk, the I 6
subsequent child will be healthy
The predominant reason for favoring PD (Table 1)
was the strong desire for a healthy child (47%). The
desire to have a surviving child, as expressed by two couples, differs in its meaning from the wish for a healthy child as it implicitly predicts the death of the child with CF. The anticipation of an unbearable emotional burden caused by two children with CF (32%) was as pronounced as the fear of insufficient capacity to care for the children. It is noteworthy, that only one couple definitely stated the intention to use PD as a means to terminate the pregnancy in case of an affected fetus.
Interestingly, ethical considerations (22%) and re-ligious beliefs (17%) were not predominant among rejectors of PD (Table 2). Parents’ major concerns were the anticipated difficulty in deciding to con-tinue or terminate the pregnancy when facing an affected fetus (39%). They preferred to avoid the anxiety of having to think about the implications of an affected fetus by avoiding the possibffity of PD entirely. Thirty-three percent of parents valued their relationship to the living child with CF and felt that the use of PD would lead to a disdain and disrespect for the firstborn.
Reproductive Behavior
Over the 7-year observation period, 24
pregnan-cies occurred in 18 families (49%). Nine out of these
18 couples had not changed their reproductive plans
after the CF diagnosis and decided for subsequent
children despite the disease in their firstborn child,
four couples reduced the number of planned
cM!-dren from three to two. Four families who had
de-cided against further offspring due to CF changed their mind. One family who initially had wanted only one child faced an unexpected pregnancy.
Age at diagnosis, age at first communication of PD and Shwachman score at the time of counseling did not differ statistically significantly between the
first-born children with CF whose mothers had a
subse-quent pregnancy and those who had not. This result suggests that age and health status of the child were not predictive of the occurrence of pregnancy.
Utilization of Prenatal Diagnosis
Among the 18 couples who had subsequent preg-nancies (Table 3), 11 (61 %) intended utilization of PD at the time of the interview. When pregnancy was
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TABLE
sequent
3.
Decision-Pregnancy
making Process in 18 Parents With
Sub-Family PD Intended
When Interviewed
PD Arranged
When Pregnant
Outcome of Pregnancy
I (3) No No (3) Spontaneous abortion (2)
Went to term (1)
2 (3) Yes No (3) Went to term (1)
Spontaneous abortion (2) 3 (2) No No (2) Went to term (2)
4 (2) Yes No (2) Elective termination (2)
5 (1) No No Went to term
6 (1) No No Went to term
7 (1) No No Went to term
8 (1) Yes No Went to term
9 (1) Yes No Went to term
10 (1) Yes Yes Went to term
11 (1) Yes No Went to term
12 (1) No No Went to term
13 (1) No No Elective termination
14 (1) Yes Yes Went to term
15 (1) Yes Yes* Spontaneous abortion
16 (1) Yes Yes Went to term
17 (1) Yes No Went to term
18(1) Yes Yes In progress
Number of pregnancies given in parentheses. *Spontaneous abortion preceded PD.
detected, statistically significantly less couples (n = 5) chose this option (:
P
< .05).In four families two and three pregnancies,
respec-tively, occurred. For analysis of utilization of PD
each pregnancy was considered a separate event, taking into account that every pregnancy offers and
requires an individual decision-making process. PD
was arranged in five (21%) and eventually
per-formed in four (17%) cases, because one mother
ex-perienced a spontaneous abortion on the very day choriomc villus biopsy was to be performed.
All seven parents who initially had rejected PD remained unchanged. They decided in altogether 10 pregnancies against PD. Those 11 couples who had planned to use PD were less uniform, as only five stuck to their intention, whereas six eventually
re-fused testing in nine cases. This result demonstrates
that as testing became a reality the majority of par-ents in favor of PD changed their minds and made a new decision It is noteworthy that in six cases (29%) pregnancy was reported too late for PD by DNA analysis, ie, beyond 16-week gestation. This finding
suggests that some parents thus avoided a difficult
choice and an emotional dilemma.
Outcome of Pregnancies
Overall outcome of 24 pregnancies revealed six healthy children. In one case, although the family had met the selection criteria, it turned out that the father of the second child was different from the father of the firstborn. Nine children born are af-fected by CF. Five spontaneous abortions occurred,
three after a definite decision against PD had been
made. There were two spontaneous abortions in one family both at 6-week gestation, where the potential utilization of PD remained unclear but rejection of
this option had been apparent in the preceding preg-nancy that went to term. Three pregnancies resulted in elective termination after rejection of PD, two due
to the fear of an affected child and one because of
heart malformation diagnosed by ultrasound.
DISCUSSION
The objectives of this study were to ascertain parents’
views on prenatal diagnosis and to examine the actual utilization by following the families for up to 7 years. To
our knowledge this is the first study that has avoided the
previously described effect of birth rank order on further
childbearing by
solely
induding families with a singlechild with F. Furthermore, because counseling was
un-dertaken outside the context of reproduction, intentions
unbiased by the need for urgent decision-making could
be investigated.
The major finding that only a minority of those
parents who undertook pregnancy agreed to PD
(21 %) questions the predictive value of
investiga-tions
dealing with hypothetical reproductive deci-sions (ie, in the absence of availabffity of test), at least for CF. Meanwhile, three studies from the United States, though not really comparable with regard tostudy design and sample selection, reported uptake
rates of 13% and 29%, respectively, thus also reflect-ing low rates of utilization of antenatal diagnosis by mothers of children with CF.9” These low uptake rates suggest that the intention to use PD was more pronounced when 1) PD was not available or 2) the study subjects were not facing an at-risk pregnancy that personally concerned them. In other chronic diseases such as sickle cell disease,’2 thalassaemia major,’3 Down’s syndrome or neural tube defect,’4 and spina bifida’5 utilization of PD was generally
much higher. The demand for PD can be influenced
by factors such as the type of the diagnostic
proce-dure, the type of fetal abnormality, the physical and psychological characteristics of the disease, the amount and intensity of treatment required, and the predicted prognosis. We assume that in CF these factors influenced parents’ subjective appraisal of disease severity thus partly explaining differences in demand for PD compared to other diagnoses.
In our study, attitudes towards PD were many-fold. About half of parents did not regard PD as a beneficial option. Instead, the anticipation of an in-evitable conifict between the fear of an affected child and the fear of possibly not being prepared to termi-nate the pregnancy predominated; feelings of guilt towards the child with CF and a number of personal
reasons and concerns mirror the tremendous distress
caused by what was considered to be an urgently awaited reproductive option. We assume that the element of choice partly explains parents’ reluctance to face a decision about continuing or terminating the pregnancy. In contrast to their first pregnancy, by undergoing PD, the responsibility for the birth of an affected child is no more a result of fate or coinci-dence. It is the parents who must decide whether the child is to live or not to live. Obviously, parents are placed in an unusually difficult position. They only have the choice between two undesirable goals where either decision brings with it emotional costs.
Psychologists call this situation an
16 PRENATAL DIAGNOSIS FOR CYSTIC FIBROSIS alternatives. The latter was preferred among parents declining PD.
Actual utilization of PD in our sample was lower
than intended. Although we only observed a shift
from intending to use PD towards rejecting it, an
inverse shift also might occur. We suggest that
ge-netic counseling and information about PD should
be provided to all parents no matter what their initial
reaction. When parents underwent the psychological
interview, most were not yet familiar with the dis-ease but preoccupied with the threatening facts such as incurabifity and diminished life expectancy. Due
to the dramatic progress in the therapy of CF, many
children pass through their early years without
sig-nificant health problems, not distinguishable from their peers in terms of cognitive and psychosocial development. It is in these early years that parents make a decision about further offspring. We
assume
that parents’ growing experiences with the near normal
and pleasing development of their child, coupled with the potential for even better prognosis due to the
ex-pected advances in pharmacologic and gene therapy
partly
accounts for the lower thanintended
use
of PD.We speculate that this also might be a reason why a
number of parents who initially did not want any more
children eventually decided in favor of further
off-spring. In addition, we observed that quite a number of
parents reported different opinions on subsequent
cM!-dren, sometimes varying a few times within a month.
These shifts usually were related to changing health conditions of their child, learning other pafients
histo-lies, hospital admission, and the ongoing experience
with CF. We condude from these observations and the
above mentioned results that parents’ decisions to
re-frain from further children alter over time. Therefore,
irreversible procedures such as sterilization should not
be recommended.
In contrast to other researchers we have not
ad-dressed the issue of abortion. For reasons of the
extreme hypothetical nature of the question and the
anticipated emotional inability to predict such a
de-cision years ahead parents were not asked about
their personal willingness to abort a fetus with CF.
Since the four fetal diagnoses performed predicted
healthy children no termination of pregnancy had to be considered. Still, the topic deserves attention. As in hypothezised and actual utilization of PD,
predic-tion of termination similarly shows discrepant
re-suits. In a study by Botkin et al., 29% of pregnant
women with no family history of CF would abort for
CF.’6 Among parents of a child with CF 20% and
52%, respectively, would terminate an affected
preg-nancy.’7”8 contrast, the range of actually
per-formed terminations after positive PD for CF was 64
to 100%.19_21
Due to the young age of the children and their
parents, among families where no subsequent
preg-nancy had occurred till the end of the study, future pregnancies may be expected, thus possibly shifting
our results. We therefore reassessed those parents’
attitudes towards further children and PD in March
1993. Seven couples stated they definitely would not have another child. Eight of the remaining 12 couples
rejected and four favored PD. With respect to the
observed shift from parents initially in favor of PD to rejecting it when pregnancy occurred, we therefore speculate that the reported utilization rate of PD will not drastically change in the near future.
ACKNOWLEDGMENTS
We thank Wolfgang Dorda, MD, MSc, for his statistical advice and Andrea Kofinger, MTA, for her help in data processing.
REFERENCES
1. Kaback M, Zippin D, Boyd P, Cantor R. Attitudes toward prenatal diagnosis of cystic fibrosis among parents of affected children. In: Lawson D, ad. CysticFibrosis: Horizons. Proceedings ofthe 9thInternational
Cystic Fibrosis Congress, June 9-15,1984. Chichester, NY: Wiley; 1984:
15-28
2. JE, Te Meerman GJ,Knol K, Ten Kate U’. Effect of
screening for cystic fibrosis on the influence ofgenetic counseling. Clin Cenet. 198732271-275
3. Allan JL,Townley RRW, Phelan PD. Family responses to cystic fibrosis. Aust Paediat J.1974;10:136-146
4. Fitz5immonsSC. The changing epidemiology ofcystic fibrosis. JPediatr.
1993;1221-9
5. Elborn JS,Shale DJ, Britton JR. Cystic fibrosis: current survival and
population estimates to the year 2000. Thorax. 1991;46:881-885
6. Evers-Kiebooms G, Denayer L, Cassiman JJ, Van den Berghe H. Family
planning dedsions after the birth of a cystic fibrosis child. Scand I Gastroenterol. 198823(suppl 143):38-46
7. Shwachman H, Kulczycki LL Long-term study of 105 patients with cystic fibrosis. Am IDis Child. 195896:6-15
8. Nie NH, Hull H,JenkinSJG, Steinbrenner K,Bent DH. SPSS: Statistical
Packagefor the Social Sciences. Second edition. New York McGraw-Hill,
1975
9. Helton J, Accurso F, Robinson N, Harmon R. Reproductive decision
making in newborn screen families. Pediatr Pulmonol. 1990;(suppl 5)282
10. Wertz DC, Janes SR. Rosenfield JM, Erbe RW. Attitudes toward the
prenatal diagnosis of cystic fibrosis: Factors in decision making among affected families. Am IHum Genet. 199Z5th1077-1085
11. Uoyd.StiIIJ, Powers C, Wessel H, Lewis K Impact ofGenetic Discoveries
on Pregnancy Outcome. Presented at the 17th European Cystic Fibrosis
Conference; June 17-21, 1991; Copenhagen, Denmark
12. Patron M, Brugiatelli M, Ward RHT, MOdeU B. Factors affecting the
uptake of prenatal diagnosis for sickle cell disease. IMed Genet. 1992; 29’820-823
13. MOdeII B, Ward RHT, Fairweather DVI. Effect of introducing antenatal
diagnosis on reproductive behaviour offamilies at risk for thalassaemia major. Br Med 1. 1980280:1347-1350
14. Evers-Kiebooms C,Swerts A, Van Den Berghe H.Psychological aspects of amniocentesis: An,dety feelings in three different risk groups. Clin Genet. 198833:1%-206
15. Kyle D, Cummins C,Evans S. Factors affecting the uptake ofscreening for neural tube defect. Br JObstet Gynaecol. 198895:560-564
16. Botkin JR, Aleniagno S. Carrier screening for cystic fibrosis: A pilot
study of the attitudes of pregnant women. Am IPublic Health. 199Z82: 723-725
17. Wertz DC, Rosenfield JM, Janes SR, Erbe RW. Attitudes toward
abor-tion among parents of children with cystic fibrosis. Am IPublic Health. 199181992-9%
18. Al-Jader LN, Goodchild MC, Ryley HC, Harper PS. Attitudes of parents of cystic fibrosis children towards neonatal screening and antenatal diagnosis. Clin Genet. 199038:460-465
19. Feldman GL, Lewiston N, FernbaCh SD, at aL Prenatal diagnosis of
cystic fibrosisbyusing linked DNA markers in138 pregnanciesat 1-in-4
risk. Am IMed Genet. 198933238-241
20. Bone A, Muller F,NezelofC, etaL Prenatal diagnosis in 200 pregnancies with a 1-in-4 risk of cystic fibrosis. Hum Genet. 1986;74:288-297
21. Super M, Ivinson A, Schwarz M, at aL Clinic experience of prenatal diagnosis of cystic fibrosis by use of linked DNA probes. Lancet. 1987; 2:782-784
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1994;94;13
Pediatrics
Ilse Jedlicka-Köhler, Manfred Götz and Irmgard Eichler
Utilization of Prenatal Diagnosis For Cystic Fibrosis Over the Past Seven Years
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Ilse Jedlicka-Köhler, Manfred Götz and Irmgard Eichler
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