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What If the Prenatal Diagnosis of a Lethal Anomaly Turns Out to Be Wrong?



Advances in prenatal diagnosis create a unique set of clinical ethics dilemmas. Doctors routinely obtain genetic screening, radiologic images, and biophysical profiling. These allow more accurate diagnosis and prognosis than has ever before been possible. However, they also reveal a wider range of disease manifestations than were apparent when prenatal diagnosis was less sophisticated. Sometimes, the best estimates of prognosis turn out to be wrong. The infant's symptoms may be less severe or more severe than anticipated based on prenatal assessment. We present a case in which a prenatal diagnosis was made of severe osteogenesis imperfecta, leading to a decision to induce delivery at 31 weeks. On postnatal evaluation, the infant's disease did not appear to be as bad as had been anticipated. We discuss the ethical implications of such diagnostic and prognostic errors.
What If the Prenatal Diagnosis of a
Lethal Anomaly Turns Out to Be Wrong?
André Kidszun, MD,
Jennifer Linebarger, MD,
Jennifer K. Walter, MD, PhD, MS,
W. Paul, MA,
Anja Fruth, MD,
Eva Mildenberger, MD,
John D. Lantos, MD
Departments of
Neonatology, and
Obstetrics and
Gynecology, and
Institute for the History, Philosophy,
and Ethics of Medicine, University Medical Center, Mainz,
Children’s Mercy Hospital, Kansas City, Missouri;
Children’s Hospital of Philadelphia, Philadelphia,
Drs Kidszun, Linebarger, Lantos, Walter, Paul, Fruth,
and Mildenberger contributed to the design of
this paper, the drafting of the manuscript, and the
review of the manuscript; and all approved the fi nal
DOI: 10.1542/peds.2015-4514
Accepted for publication Dec 15, 2015
Address correspondence to John D. Lantos, MD,
Children’s Mercy Hospital, 2401 Gillham Rd, Kansas
City, MO 64108. E-mail:
PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online,
Copyright © 2016 by the American Academy of
indicated they have no fi nancial relationships
relevant to this article to disclose.
FUNDING: Parts of this work were funded by the
Deutsche Forschungsgemeinschaft, grant 2015/1,
GRK “Life sciences–Life writing.”
have indicated they have no potential confl icts of
interest to disclose.
As a result of advances in prenatal
diagnosis, doctors can now conduct a
much more sophisticated and precise
diagnostic and prognostic evaluation
of the fetus than has ever been
possible before. Genetic screening,
radiologic imaging, and biophysical
profiling generate information
that can inform discussions with
parents about both prenatal and
postnatal medical management. But
sometimes, prenatal evaluation leads
to expectations that are not confirmed
on postnatal evaluation. Usually,
this is not the result of a completely
mistaken diagnosis. Instead, it is
because many diseases manifest
across a range of specific findings and
may be less severe, or more severe,
than anticipated. We present a case in
which a prenatal diagnosis was made
of severe osteogenesis imperfecta
(OI), leading to a decision to induce
delivery at 31 weeks. On postnatal
evaluation, the infant’s disease did
not appear to be as bad as had been
anticipated. We present comments
from the treatment team and 2 experts
in pediatric palliative care.
During routine midtrimester
ultrasound screening, the fetus of
a 21-year-old primigravida was
diagnosed with a severe skeletal
malformation. In the following days,
amniocentesis and serial ultrasound
examinations were performed to
establish the exact diagnosis. At 30
weeks of gestation, severe OI was
diagnosed. The identified point
mutation “c.3008G>a, p.Gly1003Asp”
in the Col1A2 gene had been
previously associated with OI type II:
the so-called “perinatal-lethal” type.
Evidence of thoracic hypoplasia,
decreased bone density of the
cranium, and multiple intrauterine
bone fractures supported this
diagnosis of a very severe and most
likely “lethal” type of OI.
Parents had been involved in all
stages of the diagnostic process and
Advances in prenatal diagnosis create a unique set of clinical ethics
dilemmas. Doctors routinely obtain genetic screening, radiologic images,
and biophysical profiling. These allow more accurate diagnosis and
prognosis than has ever before been possible. However, they also reveal a
wider range of disease manifestations than were apparent when prenatal
diagnosis was less sophisticated. Sometimes, the best estimates of
prognosis turn out to be wrong. The infants symptoms may be less severe
or more severe than anticipated based on prenatal assessment. We present
a case in which a prenatal diagnosis was made of severe osteogenesis
imperfecta, leading to a decision to induce delivery at 31 weeks. On
postnatal evaluation, the infants disease did not appear to be as bad as had
been anticipated. We discuss the ethical implications of such diagnostic and
prognostic errors.
PEDIATRICS Volume 137 , number 5 , May 2016 :e 20154514
To cite: Kidszun A, Linebarger J, Walter JK, et al.
What If the Prenatal Diagnosis of a Lethal Anomaly
Turns Out to Be Wrong?. Pediatrics. 2016;137(5):
by guest on May 24, 2016Downloaded from
appeared to be highly committed
to care for their infant irrespective
of any anticipated health disorders.
However, being faced with a disease
that was considered “lethal, ” the
mother felt incapable of continuing
her pregnancy. She was horrified
by the idea that her infant suffered
from fractures in utero and then
subsequently died around or shortly
after birth. On the other hand,
feticide was out of question for both
parents. An ethics consultation with
participation of obstetricians and
neonatologists was held. Mothers’
and child’s best interests were
balanced and a medical induction
of labor and primary palliative care
of the infant was considered an
acceptable therapeutic approach.
At 31+0 weeks of gestation, a
male preterm infant was delivered
vaginally from a breech position.
His birth weight was 1170 g. Under
close observation of the neonatal
team, the boy was given to mother’s
breast immediately after birth. His
respiratory adaption was uneventful
without any medical intervention. No
signs of discomfort were observed.
After a while, he was placed in an
incubator and after another while
he was transferred to the neonatal
unit where intravenous fluids were
administered. He was eupneic and
breathing in room air. His parents
asked that his do not resuscitate
order be cancelled and that he be
given life-prolonging treatment.
The next day, an ethics consultation
was summoned as the medical team
was uncertain whether it should
continue palliative care.
The Treatment Team Comments
OI is a genetic disorder with
a prevalence of 1:20 000. It
is characterized by a distinct
predisposition to multiple bone
fractures and can be diagnosed
in utero at the end of the first
2, 3
findings of multiple fractures, bone
demineralization, and shortening
and deformity of the long bones have
been used to distinguish the “lethal”
OI type II from other forms of OI
and other skeletal disorders.
4, 5
this way of differentiating “lethal”
from milder forms of OI is deeply
flawed. OI subtypes were developed
by using retrospective data such as
radiograph findings, genetics, and
clinical course. By these criteria,
OI type II was diagnosed when the
affected individual had died in utero
or shortly after birth. The criteria
were not developed to be predictive.
The sensitivity or specificity of
different findings as predictors of
prognosis has never been validated.
Nevertheless, these categories are
still used and type II is considered the
most severe type.
A significant limitation of these
diagnostic and prognostic criteria is
that they were developed without
taking into account the effect of
medical interventions. A recent
review stated that OI “type II is
lethal, usually because of respiratory
failure resulting from multiple rib
This is the case only if
one decides not to treat respiratory
failure due to rib fractures.
We did not find any respective study
that was not biased by self-fulfilling
prophecy or patient selection. In
one retrospective study of “lethal”
congenital anomalies, approximately
three-quarters of pregnancies were
terminated and 90% of the live-born
infants died before 4 months of
age. When the diagnosis was made
prenatally, the infants received less
intensive care compared with those
who were diagnosed postnatally.
Because aggressive treatment was
not associated with prolonged
survival, the authors concluded that
it should not be offered.
This is a
classic self-fulfilling prophecy. It is
hard to know what the mortality
rate would be with treatment if
current outcome statistics are based
on cohorts in which many affected
infants die after termination of
pregnancy and another large number
of infants receive palliative care after
8, 9
We believe that classification
is not useful today and that the
spectrum of clinical severity of OI
should be considered as continuous
rather than classified into discrete
With an explicit aim of preventing
early postnatal death, the treatment
of respiratory failure due to rib
fractures is likely to be effective.
However, death also may result
from an undersized thorax, overall
thoracic wall instability, and
pulmonary hypoplasia.
When such
features are present, they are likely
to be associated with high mortality,
even with treatment.
Genetic results are also problematic.
OI is a highly heterogeneous disorder
in which no reliable genotype-
phenotype correlation exists.
11, 12
Nevertheless, in cases of diagnostic
uncertainty, clinicians and especially
parents might be tempted to attach
high importance to a distinctive and
verifiable genetic feature. In any case,
parents should be counseled carefully
and the limitations of genetic test
results should be discussed in detail.
The most influential problem is
not specific to OI. It arises with
the concept of “lethal” congenital
malformations. The term “lethal”
is very imprecise.
However, a
common understanding is that
a “lethal” diagnosis implies an
irresistible progression of a disease
that inevitably leads to death in the
near future.
Such understanding
and usage of the terminology
“lethal” unavoidably implicates that
treatment of such a condition is futile
or even detrimental. As reported
previously and now observed in
our case, such “lethal” language
predetermines medical treatment,
because it predetermines parental
and medical anticipations on the
clinical course.
“Lethal” language
is harmful because it may distract
parents from unprejudiced decisions
between different treatment
options. When counseling in cases
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PEDIATRICS Volume 137 , number 5 , May 2016
of life-threatening fetal anomalies,
most physicians encourage a certain
treatment option. Furthermore,
significant discrepancies in
counseling can be observed
depending on whether a condition is
considered to be “uniformly lethal” or
“uniformly severe, commonly lethal.
Because of the inherent ambiguity
in such terms, we recommend
physicians to avoid the term “lethal”
in communication practice and,
even more importantly, in the
nomenclature of diseases.
With these considerations in mind,
we can examine the 3 options that
were offered in this case at the time
of the prenatal ethics consultation:
(1) carrying the child to full term and
perinatal palliative care, (2) feticide
and termination of pregnancy, and,
because the mother had already
rejected these options, (3) medical
induction of labor and perinatal
palliative care. Active intervention
by means of full intensive care was
not discussed as a treatment option.
Although options (1) and (2) were
identified as ethically most consistent
due to their clear consequential
effectuation of an either mother-
centered or child-centered
perspective, option (3) was finally
considered acceptable, although
concerns had been raised that this
approach might imply therapeutic
disadvantages to the infant and
neglect potential harm for the mother
at the same time. This may seem
like the worst of both worlds. We
In a case like this, it is permissible to
allow the mother to take some risks
as long as she understands those
risks and they are consistent with her
overall goals. Many parents want to
see and hold their living infant, even
if that infant is not likely to survive.
In such situations, both aggressive
and nonaggressive intrapartum
monitoring should be considered,
depending on parents’ preferences.
Parents and health care professionals
should be prepared for a situation
in which an infant with a life-
threatening congenital malformation
will not die immediately after birth
but will survive for days or more.
Significant outcome-relevant
discrepancies between the proposed
prenatal and the actual postnatal
diagnosis may occur.
One should also bear in mind that
palliative care does not per se limit
certain interventions. An infant with
a severe congenital OI might have
difficulties in respiratory adaption
like any other nonaffected infant. So
there might be a palliative indication
to give supplemental oxygen in
such a case or even to give some
additional respiratory support
if there is a reasonable prospect
that the infant can overcome this
temporary disturbance. In a pre-
as well as a postnatal setting of a
severe congenital malformation,
the consideration of all possible
treatment options and respectful
communication with the (future)
parents are essential prerequisites
to respect parental autonomy and
to ascertain the child’s and families’
best interests. Especially when
decision-making is informed by
prognostic concepts, the narrative
co-construction and negotiation
of therapeutic goals and strategies
between health care professionals
and parents and thus the influence
of subjective values and judgments
must be taken in account.
In this case, we decided to forego
palliative care and to start full life-
sustaining treatment. The parents
were fully aware of the anticipated
outcome of an infant with severe
OI. However, their decision to ask
for termination of pregnancy and
palliative care was likely based on
the assumption that their infant
would suffer and die shortly after
birth. We were wondering why the
outcome of our prenatal assessment
was that inaccurate and we are now
convinced that the use of the term
“lethal” distracted the parents and
the clinicians from an unprejudiced
assessment of the survival prognosis.
Jenni Linebarger, MD, Pediatric
Palliative Care Physician, Comments
Perinatal diagnosis comes with
inherent uncertainty. Providers rely
on imaging, genetic studies, and
experience (personal and published)
to formulate a prognosis before they
can truly “see” the infant. As such,
planning for care at delivery often
follows the mindset of “prepare for
the worst, hope for the best.” In this
case, the providers and the parents
prepared for the infant’s death based
on the genetic diagnosis of OI type
II and the thoracic hypoplasia noted
on ultrasound. Yet on day of life 1,
the infant is eupneic and breathing
in room air, leaving the providers
uncertain about how to proceed
and doubting whether to continue
palliative care.
Of course you provide palliative care!
Palliative care is not exclusive to the
end of life. Palliative care is provided
for patients with a wide range of
life-limiting and life-threatening
conditions; ideally beginning
when an illness is diagnosed and
continuing regardless of whether a
child receives treatment directed at
a cure or prolonging life. The role of
palliative care is to address physical,
psychological, and social stressors,
with a focus on improving the quality
of life.
The infant boy in this case has
genetically confirmed OI, and as
the OI Foundation Web site states,
“There is no cure for OI, but there
are ways to manage the symptoms.
So in one sense, all treatments for
patients with OI are “palliative, ” not
meant to cure, but meant to manage.
For patients with OI type II (and
severe type III), the life expectancy is
shortened. Although the infant boy in
this case appears to be breathing well
now, we do not know whether that
will continue over time. Given such
remaining uncertainty, a palliative
care team may aid the parents and
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the treatment team in outlining goals
for this infant’s care.
The parents in this case have been
given the gift of time with their
son that they did not anticipate.
How do they want to fill it? Using
a 4-quadrant decision-making tool
may help the family outline the
goals for their son’s care by taking
into account their values as well as
the medical indications (diagnosis,
symptoms, proposed interventions),
the infant’s current and anticipated
quality of life (important activities),
and contextual issues that make up
the nonmedical side of life. It may
be, for example, that an isolette and
intravenous fluids do not fit into their
goals, and that they would prefer to
have him room-in and breastfeed ad
Prenatal palliative care teams
are familiar with infants who
are delivered and do better than
expected, as well as infants who do
worse. In such cases, it is crucial to
talk to parents about uncertainties
and about their hopes, fears, goals,
and plans. In this case, they have
been given the gift of time with their
infant. We should help them figure
out how to best appreciate and use
that gift.
Jennifer K. Walter, MD, PhD, MS,
Pediatric Palliative Care Physician
and Clinical Ethicist, Comments
Pediatric patients with serious illness
sometimes defy expectations when
technologic support is withheld
or withdrawn, doing better than
anticipated. In such cases, clinicians
should explore 3 different potential
areas of concern: the facts of the
diagnosis and prognosis, the values
and goals of care of the family,
and the overall experience of how
to partner with families given
uncertainty. In doing so, clinical
teams can help families determine
a plan of care consistent with their
goals for their child.
In this case, let’s first focus on the
diagnostic and prognostic “facts”
and uncertainties. Prenatal genetic
testing has identified a “lethal”
type of OI. Infants with the this
genetic syndrome often do not
survive to birth and usually die in
the first 2 months, but others may
live until 1 year of age, usually
dying of respiratory infections and
The parents and
team chose to induce preterm labor
due to a concern that the infant
would suffer significantly in utero
and after birth. However, after
delivery, the child was found to be
comfortable: not demonstrating signs
of significant pain from fractures,
able to breathe without support, and
interested in feeding (although it
would be unusual for a 31-weeker to
adequately feed without help given
his gestational age).
The child’s healthy appearance at
birth raised questions about the
accuracy of the prenatal genetic
testing. Although there is growing
evidence that the phenotype-
genotype correlation is accurate
for the gene mutations found,
child’s condition could reasonably
lead the team and parents to question
the veracity of the diagnosis.
Confirmation of the diagnosis
with other physical examination
findings by geneticists, and even
repeat genetic testing, would not be
unreasonable while acknowledging
that the diagnosis is most likely
Although the exact progression of
this child’s disease is unknown,
his trajectory is very likely to
worsen in the coming months,
with increasing fractures requiring
pain management and the need to
balance comfort with respiratory
insufficiency. All prognostication
about what to expect should be
underscored with uncertainty
because he could decompensate
at any point. Many children with
OI type II will also suffer from
pneumonias and a progressive need
for positive pressure ventilation,
which can be painful due to mask
interfaces that result in further
fractures. Preparing families for
these declines and helping them
recognize that regardless of the
choice now, there may be a time in
the near future where the burdens
of interventions such as intubation,
continuous positive airway pressure,
or maintaining wakefulness in light
of difficult pain management may
warrant a primarily comfort-focused
approach with little or no respiratory
Second, let’s turn from facts to
consider values and goals of care.
Although the diagnosis is being
confirmed and the prognostic range
clarified, the medical team should
revisit the values of the parents. In
the case we learn that the parents are
“highly committed to care for their
infant” irrespective of the disorder
he may have, yet also want to protect
him from suffering. Coupled with the
child’s unexpected condition at birth,
the clinical team then questioned
whether palliative care was still
warranted, even if the genetic
diagnosis was correct.
Pediatric palliative care is often
described as an extra layer of
support in decision-making and
symptom management for children
with serious illness, often provided
in conjunction with life-prolonging
treatments. The team and family
do not need to make an either-or
decision. In fact, the clinical team
may have been asking whether they
should continue to recommend a
primarily comfort-focused approach
given the child’s well appearance and
likely need for support in feeding
with a nasogastric tube (NGT).
So how should the team weigh
whether a comfort-only approach
is warranted given the parents’
wishes to care for their child while
also preventing suffering? Given the
possibility that this infant would
live longer with some life-sustaining
treatments, such as artificial
nutrition, and at some point in the
future, will likely need noninvasive
by guest on May 24, 2016Downloaded from
PEDIATRICS Volume 137 , number 5 , May 2016
or invasive respiratory support,
the team must consider whether
withholding these treatments
now is ethically acceptable. Some
clinicians are reluctant to start any
life-sustaining therapy given the
potential psychological challenge of
withdrawing it in the future. That
is generally not the best approach.
When it is ethical to withhold a
treatment, it is generally also ethical
to withdraw that treatment.
The team and family should consider
what is in the best interest of this
child from the child’s perspective,
while weighing the risks of
each possible intervention. For
example, providing the child with
supplemental nutrition by NGT
carries low risk with the potential
benefit of extending his currently
good quality of life, one that does
not include intractable pain or
repeated interventions. The clinical
team should reengage the parents,
discuss the realities of the infant’s
current good status, and recommend
NGT placement with supplemental
feeds to offer him the possibility of
extending his life, and keeping him
from feeling hungry, as long as he
maintains a good quality of life.
In making this first recommendation
for NGT feeding, the care team must
further explore the family’s values
and assess the level of suffering that
they are willing to tolerate for their
child in the future to potentially
prolong his life. The team should
also recommend home hospice
services, given the dynamic nature of
the child’s disease. Concurrent care
insurance legislation has meant that
hospice can frequently be offered
simultaneously with life-sustaining
treatments for these types of
Third, let’s consider how we can
partner in the face of uncertainty.
Parents who have struggled to
make a decision to withhold or
withdraw life-sustaining treatments
may experience increasing distress
when their child appears to be doing
better than expected. Therefore,
the uncertainty regarding possible
outcomes should be part of the
discussion of any decision to limit
interventions. Clinical teams can
anticipate potential scenarios in
advance and agree on the kinds of
interventions that they would be
willing to offer to families given the
clear expression of their goals.
Primary clinical teams, working
with pediatric palliative care
specialists and ethics consultants,
can successfully navigate these
discussions by recognizing their
role in supporting the decision-
making of parents, learning what
is most important to families, and
then making recommendations
that are consistent with those
goals and values. Merely offering
families a menu of options can be
overwhelming and unfair given our
professional responsibility to guide
families through these difficult
decisions. With careful coordination
of care and clear communication,
teams can help families realize their
hopes for a comfortable quality of
life, or a peaceful death, for their
John D. Lantos, MD, Comments
This case illustrates the challenges
that pediatricians face as a result
of new technologies for prenatal
diagnosis. Although we can get much
more information about the health
and well-being of a fetus than ever
before, the wealth of new information
may be difficult to interpret.
Statisticians and epidemiologists
have long known that the availability
of more tests does not necessarily
increase the precision or the
accuracy of diagnosis. Instead, more
testing may lead to more uncertainty.
This can happen when tests give
conflicting results or when tests are
used in populations for which their
sensitivity and specificity have not
been evaluated.
more information can lead to less
certainty. Recognition of these
problems should lead to special
caution in discussing the results of
prenatal evaluations. There should
always be a caveat about confirming
the prenatal findings on postnatal
NGT:  nasogastric tube
OI:  osteogenesis imperfecta
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DOI: 10.1542/peds.2015-4514
; originally published online April 1, 2016;Pediatrics
Eva Mildenberger and John D. Lantos
André Kidszun, Jennifer Linebarger, Jennifer K. Walter, Norbert W. Paul, Anja Fruth,
What If the Prenatal Diagnosis of a Lethal Anomaly Turns Out to Be Wrong?
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DOI: 10.1542/peds.2015-4514
; originally published online April 1, 2016;Pediatrics
Eva Mildenberger and John D. Lantos
André Kidszun, Jennifer Linebarger, Jennifer K. Walter, Norbert W. Paul, Anja Fruth,
What If the Prenatal Diagnosis of a Lethal Anomaly Turns Out to Be Wrong?
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... Thirdly, the diverse expression of phenotypes and the absence of rigorous genotypephenotype correlations obscures PCS clinical validity [122]. The existence of both lethal and non-lethal OI cases caused by the same variant adds additional complexity to the prediction of the phenotype [62,63,123]. Other limitations with PCS relate to NGS methodology limitations, such as VUS variants, lack of genetic counselling and non-specific genetic findings. ...
... Empathetic and sensitive communication with parents is therefore a crucial part of care-provision. It has also been argued that, given the uncertainties involved in interpretation of tests, the articulation of a prognosis as lethal or as incompatible with life is inappropriate: such vocabulary may create additional stress for parents and tends to limit the clinical treatment options [123,179]. ...
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Background: Osteogenesis Imperfecta (OI) is a rare genetic disorder involving bone fragility. OI patients typically suffer from numerous fractures, skeletal deformities, shortness of stature and hearing loss. The disorder is characterised by genetic and clinical heterogeneity. Pathogenic variants in more than 20 different genes can lead to OI, and phenotypes can range from mild to lethal forms. As a genetic disorder which undoubtedly affects quality of life, OI significantly alters the reproductive confidence of families at risk. The current review describes a selection of the latest reproductive approaches which may be suitable for prospective parents faced with a risk of OI. The aim of the review is to alleviate suffering in relation to family planning around OI, by enabling prospective parents to make informed and independent decisions. Main body: The current review provides a comprehensive overview of possible reproductive options for people with OI and for unaffected carriers of OI pathogenic genetic variants. The review considers reproductive options across all phases of family planning, including pre-pregnancy, fertilisation, pregnancy, and post-pregnancy. Special attention is given to the more modern techniques of assisted reproduction, such as preconception carrier screening, preimplantation genetic testing for monogenic diseases and non-invasive prenatal testing. The review outlines the methodologies of the different reproductive approaches available to OI families and highlights their advantages and disadvantages. These are presented as a decision tree, which takes into account the autosomal dominant and autosomal recessive nature of the OI variants, and the OI-related risks of people without OI. The complex process of decision-making around OI reproductive options is also discussed from an ethical perspective. Conclusion: The rapid development of molecular techniques has led to the availability of a wide variety of reproductive options for prospective parents faced with a risk of OI. However, such options may raise ethical concerns in terms of methodologies, choice management and good clinical practice in reproductive care, which are yet to be fully addressed.
... This study will help to address the aforementioned challenges by rendering the lived experiences of children with OI visible. 1,8 Background Preliminary evidence suggests that children with OI confront a host of ethical concerns in their daily lives, such as unexplained injuries and unintended consequences associated with inconclusive genetic tests 9 ; social isolation, 3 feelings of "otherness," 10 and describing oneself as "mutants" 11 ; and being frequent recipients of larger societal discourses about genetic screening, 9,12 selective pregnancy termination, 13 and disparaging messages related to disability. 14 HCPs and other adults may perpetuate, exacerbate, or contribute to these ethical concerns by underestimating or disregarding children's competencies due to their status as minors or misconceptions about disability. ...
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Background Serious ethical problems have been anecdotally identified in the care of children with osteogenesis imperfecta (OI), which may negatively impact their moral experiences, defined as their sense of fulfillment towards personal values and beliefs. Research aims To explore children’s actual and desired participation in discussions, decisions, and actions in an OI hospital setting and their community using art-making to facilitate their self-expression. Research design A focused ethnography was conducted using the moral experiences framework with data from key informant interviews; participant observations, semi-structured interviews, and practice-based research (art-making) with 10 children with OI; and local documents. Participants and research context The study was conducted at a pediatric, orthopedic hospital. Ethical considerations This study was approved by McGill University Institutional Review Board. Findings/results Children expressed desires to participate in their care, but sometimes lacked the necessary resources and encouragement from healthcare providers. Art-making facilitated children’s voice and participation in health-related discussions. Conclusions Healthcare providers are recommended to consider the benefits of art-making and educational resources to reduce discrepancies between children’s actual and desired participation in care and promote positive moral experiences.
... Chorionic villus sampling (CVS), amniotic fluid (AF), and maternal plasma are the most referred samples and the most common reason for CVS or amniocentesis is to request for cytogenetic studies such as karyotype and FISH. Interpretation of the results from prenatal diagnosis (PND) testing contributes to critical decisions by the clinicians and parents such as terminating a pregnancy so that diagnostic errors can lead to serious consequences such as legal issues and a heavy emotional and financial burden on the family and the society especially when the error results in the birth of an affected child (178)(179)(180). Some specific general considerations should be taken into account when dealing with PND specimens in the clinical laboratory: 1-The laboratory should make sure that the patient has gone through proper consultation sessions and informed about the accuracy of the tests and potential treatments for the fetus. ...
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Molecular assays for detection of nucleic acids in biologic specimens are valuable diagnostic tools supporting clinical diagnoses and therapeutic decisions. Pre-analytical errors, which occur before or during processing of nucleic acid extraction, contribute a significant role in common errors that take place in molecular laboratories. Certain practices in specimen collection, transportation, and storage can affect the integrity of nucleic acids before analysis. Applying best practices in these steps, helps to minimize those errors and leads to better decisions in patient diagnosis and treatment. Widely acceptable recommendations, which are for optimal molecular assays associated with pre-analytic variables, are limited. In this article, we have reviewed most of the important issues in sample handling from bed to bench before starting molecular tests, which can be used in diagnostic as well as research laboratories. We have addressed the most important pre-analytical points in performing molecular analysis in fixed and unfixed solid tissues, whole blood, serum, plasma, as well as most of the body fluids including urine, fecal and bronchial samples, as well as prenatal diagnosis samples.
... However, for many so-called 'lethal malformations', long-term survival is possible, and so it is not clear that such fetuses lack a FLO. 8 Diagnoses of the severity of such conditions also can be inaccurate. 9 So granting Gillham's point is unlikely to affect the applicability of SIA to the vast majority of induced abortions. ...
Perry Hendricks' original impairment argument for the immorality of abortion is based on the impairment principle: if impairing an organism to some degree is immoral, then ceteris paribus, impairing it to a higher degree is also immoral. Since abortion impairs a fetus to a higher degree than fetal alcohol syndrome (FAS) and giving a fetus FAS is immoral, it follows that abortion is immoral. Critics have argued that the ceteris paribus is not met for FAS and abortion, and so we proposed the modified impairment principle (MIP) to avoid these difficulties. Dustin Crummett has responded, arguing that MIP is open to various counterexamples which show it to be false. He also shows that MIP can generate moral dilemmas. Here, we propose a modification to MIP that resolves the issues Crummett raises. Additionally, Alex Gillham has criticised our appropriation of Don Marquis' 'future like ours' reasoning about the wrongness of impairment. We show that his objections have minimal implications for our argument.
Background: Treatment of psychotic disorders in pregnancy is often ethically and clinically challenging, especially when psychotic symptoms impair decision-making capacity. There are several competing ethical obligations to consider: the ethical obligation to maternal autonomy, the maternal and fetal beneficence-based obligations to treat peripartum psychosis, and the fetal beneficence-based obligation to minimize teratogenic exposure. Objective: This article outlines an ethical framework for clinical decision-making for the management of chronic psychosis in pregnancy, with an emphasis on special considerations in the previable and periviable period. Case Presentation: A 31-year-old gravida 2, para 1 with intrauterine pregnancy at 12 weeks and 4 days gestation was brought to the emergency department by her husband seven months after delivering her first child, due to sudden onset of behavioral changes that included self-isolation, not eating, and not taking care of her child. Her past medical history included hypothyroidism and inflammatory bowel disease, but no prior psychiatric illness. After being admitted to the psychiatric hospital, she continued to have poor oral intake and weight loss despite initial inpatient treatment with antipsychotics, levothyroxine, and discontinuation of corticosteroids. Her pregnancy was also complicated by the diagnosis of multiple fetal anomalies at 20 weeks gestation, when the fetus was periviable. Conclusions: For previable or periviable pregnancies, the patient and/or surrogate should decide whether to pursue prenatal genetic screening and invasive diagnostic testing, as well as whether to continue or terminate the pregnancy. When the choice is made to continue the pregnancy, initiation of long-term psychiatric treatment (including medications with potential adverse fetal effects) should be based on shared decision-making between the physician and the patient and/or surrogate. Although some pharmacologic interventions may have potential adverse effects on the developing fetus, the use of psychotropic medications can be ethically justified, even if the patient herself does not have the capacity to consent and requires a surrogate, when the goal is to restore maternal autonomy and minimize the risks of maternal and fetal harm from untreated psychiatric illness.
Perinatal Palliative Care (PnPC) focuses on enhancing family and newborn quality-of-life in the setting of a life-limiting fetal condition while simultaneously ensuring medical care delivery that is soundly in line with the family's goals and values. The inclusion of PnPC in the multidisciplinary care of a family facing severe fetal neurologic diagnoses allows for skilled exploration of the values and experience that ultimately drive creation of goals of care. The parental experience of receiving a life-limiting fetal diagnosis pushes parents into an emotional journey, which typically follows a recognizable progression of stages. PnPC providers appreciate the significance of this experiential journey and the importance of parental movement toward readiness to simultaneously welcome and mourn their child. Through longitudinal supportive care, beginning early in the fetal diagnostic progress and continuing throughout pregnancy and into the newborn period, PnPC providers explore the uncharted parental experience alongside the family and support them in creating value-driven care plans for their child. They contribute greatly to the multidisciplinary fetal and neonatal care teams as the advocate for and promote insightful communication and assist in delivery and coordination of value-driven care.
Das Spektrum an lebenslimitierenden Erkrankungen im Kindesalter ist sehr breit gefächert. Es reicht von seltenen genetischen Erkrankungen, angeborenen/erworbenen Anomalien und (Mehrfach-) Behinderungen über neurologische Symptomenkomplexe bis hin zu Krebserkrankungen. Genauso weit sind auch das Altersspektrum pädiatrischer Palliativpatienten und so unterschiedlich sind die Versorgungsorte, an denen uns diese Patienten und ihre Familien begegnen. Das Kapitel beschreibt, wie eine gute palliative Versorgung gelingen kann - ob schon perinatal, in der Neonatologie, auf der pädiatrischen Intensivstation oder beim Übergang in das Erwachsenenleben. Zusätzlich bietet es viel Information zu den wichtigsten Themenkomplexen in der pädiatrischen Palliativversorgung, wie z. B. bei chromosomalen und metabolischen Störungen, neuro-muskulären Erkrankungen, schweren Mehrfachbehinderungen u. v. a. m. Der Fokus in diesem Kapitel liegt vermehrt auf den palliativ-psycho-sozialen Aspekten, detaillierte Angaben zur medikamentös-medizinischen Behandlung finden sich in der gesonderten Ausgabe Pädiatrische Palliativversorgung – Schmerzbehandlung und Symptomkontrolle.
Objective/methods: Pediatric Palliative Care (PPC) is a multidisciplinary medical subspecialty focused on the care of children with serious illnesses and terminal diagnoses. Providers impact the care of children from the perinatal stage through adolescence/young adulthood and help patients and families face diagnoses such as complex chronic disease and malignancy. This article describes these unique populations and distinct areas of current PPC research. Results: Unique aspects of PPC include a high level of prognostic uncertainty, symptom burden, pediatric, and surrogate advance care planning, hope in the face of prognostic challenges, care of children at end of life, concurrent care, staff support, sibling support, and bereavement. Conclusion: PPC's evolution from an extension of hospice into a continuum of support for families and staff caring for children with serious illnesses is exemplified in both qualitative and quantitative research. The literature proves the value that PPC can provide to families, hospitals, and communities. PPC is evolving from a supportive service into a uniquely beneficial, collaborative, educational, and interdisciplinary specialty that improves outcomes for all involved.Plain Language Summary (PLS)Pediatric Palliative Care (PPC) is a service provided to all children with serious illness as a way of addressing suffering. Populations served by PPC range from those not yet born to patients preparing for adulthood. The serious illnesses they face range from chronic disease to cancer. Over the last 20 years research has explored the unique aspects of the pediatric experience of serious illness, including prognostic uncertainty, concurrent care, symptom management, advance care planning, hope, family experience of illness, care at the end of life, staff support, and bereavement.As the number of patients who would benefit from PPC services rapidly expands nationally and worldwide, PPC teams provide education and skills training for their colleagues in primary and subspecialty fields. Hospitals benefit from PPC through improved patient experience, family-centered care, and staff support. Communities are served by PPC that occurs in and out of the hospital.Research in PPC provides guidance for challenging questions in care and has resulted in an increasingly robust body of work. PPC providers have skills of advanced communication training, hope in the face of uncertainty, targeted and personalized symptom management, and a diverse understanding of quality of life. These skills help support decision-making and establish strong connections between providers and families.The field of PPC has a distinct skillset to support families who face serious illness. This article helps medical and psychosocial providers visualize how PPC is evolving from what has often been explained to families as an added layer of support into a uniquely beneficial, collaborative, and interdisciplinary service.
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In case of extremely rare diseases, case reports are often the only experience to draw from for evidence-based management. Carmi syndrome is a rare, mostly lethal combination of junctional epidermolysis bullosa and pyloric atresia. During an ethical board, there were differences in perception of mortality rate. We tested the hypothesis that the cumulative mortality of single case reports is lower than that of multiple case series.CaseA baby girl was born at 33 weeks gestation with Carmi syndrome. The treatment options discussed in an interdisciplinary ethics board were a palliative approach versus surgical gastrojejunostomy. Because about one third of operated children described in case reports survived, we opted for surgical treatment. The patient died a painful death 4 weeks later.Methods The PubMed database was systematically searched for reports of Carmi syndrome. Single case reports were compared to case series in terms of outcome.ResultsA total of 102 cases of Carmi syndrome were identified in the literature. Mortality of single case reports was 17 out of 27 patients (63%), while that of case series was higher at 62 out of 74 patients (84%, p = 0.036).Conclusions Selection and publication bias may lead to inflation of survival rates in single case reports because successful cases are more likely to be published in the literature. These biases may lead to inappropriately aggressive treatment in futile cases. Clinicians should be cautious when discussing prognosis and making decisions based on the cumulative experience of case reports of extremely rare or novel diseases.
Easier access to prenatal diagnostic procedures led to its widespread use as a screening measure. Hence, today it is more common for life-limiting illnesses to be diagnosed during fetal life. The concept of Advance Care Planning (ACP) provides a framework for caregivers, families and their multidisciplinary teams to anticipate and plan ahead for potential future medical decisions so that the affected children are reliably treated according to their parents’ individual values and wishes. In the perinatal context, ACP also has the potential to tackle the needs of unborn or newborn children with life-limiting illnesses and their families better, avoid unnecessary and burdensome measures and focus upon goals that are valuable and meaningful to both child and family.
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Osteogenesis imperfecta (OI) is a rare hereditary bone fragility disorder, caused by collagen I mutations in 90% of cases. There are no comprehensive genotype-phenotype studies on >100 families outside North America, and no population-based studies determining the genetic epidemiology of OI. Here, detailed clinical phenotypes were recorded, and the COL1A1 and COL1A2 genes were analyzed in 164 Swedish OI families (223 individuals). Averages for bone mineral density (BMD), height and yearly fracture rate were calculated and related to OI and mutation type. N-terminal helical mutations in both the α1- and α2-chains were associated with the absence of dentinogenesis imperfecta (P<0.0001 vs 0.0049), while only those in the α1-chain were associated with blue sclera (P=0.0110). Comparing glycine with serine substitutions, α1-alterations were associated with more severe phenotype (P=0.0031). Individuals with type I OI caused by qualitative vs quantitative mutations were shorter (P<0.0001), but did not differ considering fractures or BMD. The children in this cohort were estimated to represent >95% of the complete Swedish pediatric OI population. The prevalence of OI types I, III, and IV was 5.16, 0.89, and 1.35/100 000, respectively (7.40/100 000 overall), corresponding to what has been estimated but not unequivocally proven in any population. Collagen I mutation analysis was performed in the family of 97% of known cases, with causative mutations found in 87%. Qualitative mutations caused 32% of OI type I. The data reported here may be helpful to predict phenotype, and describes for the first time the genetic epidemiology in >95% of an entire OI population.European Journal of Human Genetics advance online publication, 6 May 2015; doi:10.1038/ejhg.2015.81.
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In clinical practice, and in the medical literature, severe congenital malformations such as trisomy 18, anencephaly, and renal agenesis are frequently referred to as ‘lethal’ or as ‘incompatible with life’. However, there is no agreement about a definition of lethal malformations, nor which conditions should be included in this category. Review of outcomes for malformations commonly designated ‘lethal’ reveals that prolonged survival is possible, even if rare. This article analyses the concept of lethal malformations and compares it to the problematic concept of ‘futility’. We recommend avoiding the term ‘lethal’ and suggest that counseling should focus on salient prognostic features instead. For conditions with a high chance of early death or profound impairment in survivors despite treatment, perinatal and neonatal palliative care would be ethical. However, active obstetric and neonatal management, if desired, may also sometimes be appropriate.
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Objective: To describe the neonatal outcomes of a case series of infants who were prenatally diagnosed with potential life-limiting conditions and to whom individualized comfort measures were offered. Study design: This is a retrospective analysis of the postnatal outcomes of a selected population of 49 infants prenatally diagnosed with potential life-limiting conditions whose parents were prenatally referred for counseling to the comfort care team. Result: The prenatal diagnosis was confirmed postnatally in 45 infants. The only four survivors had a significant discrepancy between prenatal and postnatal diagnosis. Whether they were treated with individualized comfort measures (n=28) or intensive care (n=17), all the newborns died with similar median age at death (2 days). Conclusion: Diagnostic accuracy is the main determinant of outcomes. Provision of intensive care neither prevents the death of infants affected by life-limiting conditions nor prolongs life compared with that of infants treated with individualized comfort measures.
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Please cite this paper as: Wilkinson D, Thiele P, Watkins A, De Crespigny L. Fatally flawed? A review and ethical analysis of lethal congenital malformations. BJOG 2012;119:1302–1308. Prenatally diagnosed abnormalities that are associated with death in the newborn period are often referred to as ‘lethal malformations’. Yet, for many of the commonly described lethal malformations long-term survival is possible if supportive interventions are provided. In this paper we analyse and review fetal or congenital lethal abnormalities. The designation ‘lethal’ overlaps with the concept of ‘medical futility’. The term is used for a heterogenous group of conditions, and hinders clear communication and counselling. We argue that the term should be avoided, and propose in its place a set of key questions that should be addressed by counselling.
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Osteogenesis imperfecta, discussed in Baldridge et al. 2008 is an inherited bone fragility disorder with a wide range of clinical severity that in the majority of cases is caused by mutations in COL1A1 or COL1A2, the genes that encode the two collagen type I alpha chains. Here we describe genotype-phenotype correlations in OI patients who have mutations affecting collagen type I. This paper is based on findings in a large single-centre OI population and a review of the literature.
Hip and knee replacements are challenging in patients with OI. Brittle bone leads to higher rates of intraoperative fractures. Bone deformity and hardware lead to difficulty in placement of the implant. Osteotomy may be required for deformity correction and implant placement. Such procedures should be performed by a surgeon with extensive experience in revision techniques and fracture repair.
Osteogenesis imperfecta is a phenotypically and molecularly heterogeneous group of inherited connective tissue disorders that share similar skeletal abnormalities causing bone fragility and deformity. Previously, the disorder was thought to be an autosomal dominant bone dysplasia caused by defects in type I collagen, but in the past 10 years discoveries of novel (mainly recessive) causative genes have lent support to a predominantly collagen-related pathophysiology and have contributed to an improved understanding of normal bone development. Defects in proteins with very different functions, ranging from structural to enzymatic and from intracellular transport to chaperones, have been described in patients with osteogenesis imperfecta. Knowledge of the specific molecular basis of each form of the disorder will advance clinical diagnosis and potentially stimulate targeted therapeutic approaches. In this Seminar, together with diagnosis, management, and treatment, we describe the defects causing osteogenesis imperfecta and their mechanism and interrelations, and classify them into five groups on the basis of the metabolic pathway compromised, specifically those related to collagen synthesis, structure, and processing; post-translational modification; folding and cross-linking; mineralisation; and osteoblast differentiation.
AimTechnological and clinical advances have reduced neonatal deaths and this study explored how the mode and timing of neonatal deaths has changed in a tertiary neonatal intensive care unit (NICU) over ten yearsMethods We carried out a retrospective chart review on NICU deaths in 2000 to 2002 and 2007 to 2010, categorising deaths and compared the timing, cause and mode of death in the two cohortsResultsWe analysed 204 neonatal deaths and found that the average age at death doubled from 9.71 days in 2000-2002 to 18.8 days (p = 0.014) in 2007-2010 and that the number of deaths in the first 48-hours-of-life fell from 52% to 29% (p< 0.001). Mode of death and ethical decision-making was similar. In both cohorts, 26% of patients who died had a do not resuscitate order and 9% of the 151 patients without an order died while receiving cardiopulmonary resuscitation. Most neonates received medication to keep them comfortable and their use was similar in both cohortsConclusions Changes in neonatal management have led to a reduction in early deaths, and an increase in age at death. The impact of later deaths on families and healthcare providers deserves further researchThis article is protected by copyright. All rights reserved.
Heuser, Eller and Byrne provide important descriptive ethics data about how physicians counsel women on the clinical management of pregnancies complicated by severe fetal anomalies. The authors present an account of what such counselling ought to be based on, the ethical concept of the fetus as a patient and the professional responsibility model of obstetric ethics. When there is certainty about the diagnosis and either a very high probability of either death as the outcome of the anomaly or survival with severe and irreversible deficit of cognitive developmental capacity as a result of the anomaly diagnosed, the pregnant woman should be offered the alternatives of aggressive and non-aggressive obstetric management and induced abortion before viability. It is also ethically permissible to offer feticide followed by termination of pregnancy after viability in such cases. This ethically justified approach will reduce the variation in the actual practices of specialists in maternal-fetal medicine described by Heuser, Eller and Byrne.