Keywords
qualitative - preterm birth - progesterone - 17-OHP - decision
The United States ranks 27th among nations worldwide for infant mortality with a rate
of 6.1 deaths per 1,000 live births.[1] The majority of perinatal morbidity and mortality is related to preterm birth, defined
as delivery prior to 37 weeks' gestation. In the United States, one in eight deliveries
occurs prematurely, and these births contribute 85% of the neonatal morbidity and
35% of infant mortality (deaths in the first year of life).[2]
[3] The cost of providing care to these infants exceeds $26 billion annually.
Only 50% of all preterm births occur in women with risk factors that are identifiable
before the preterm birth occurs, making screening and surveillance difficult. The
risk factor having the greatest predictive value is a history of preterm delivery,
which is associated with a 1.5- to 2.0-fold increase in risk. Attempts to treat premature
labor once it occurs have been largely ineffective resulting in only a 2- to 7-day
extension of pregnancy.[4] The most effective intervention has been prevention of premature labor utilizing
progestins.[4] In a large multi-institutional study conducted in the National Institute of Child
Health and Human Development (NICHD) Maternal-Fetal Medicine Units Network, Meis et
al demonstrated that 17-α-hydroxyprogesterone caproate (17-OHP) given intramuscularly
decreased recurrent preterm birth by 30%.[5] Patients who were strongly adherent to this regimen decreased their risk of recurrent
preterm birth with a relative risk of 0.66 (confidence interval: 0.54–0.81).[6]
In contemporary practice, when a pregnant patient presents with a history of prior
spontaneous premature delivery or preterm premature rupture of membranes, she is offered
intramuscular progesterone (17-OHP) once weekly, beginning at 16 to 20 weeks' gestation
and continuing until 36 weeks' gestation, in the hope of preventing a recurrence in
her current pregnancy. Despite the absence of other Food and Drug Administration (FDA)
approved treatments for the prevention of preterm birth, many pregnant patients decline
this therapy. In some populations, this approximates 50% and appears to be most pronounced
among non-Hispanic black women.[4] This is distressing given the lack of significant side effects associated with the
administration of 17-OHP and the high premature birth rate experienced in the United
States. Summit County, Ohio—the location of this study—ranked as one of the worse
counties in the nation for preterm births from 2010 to 2012, with a rate of 13.5%
compared with Ohio's and national rates of 12.3 and 11.7%, respectively.[7]
There have been many studies exploring patient refusal of appropriate treatment among
the pregnant population. Ribak et al (2011) reported that women with a previous history
of perinatal morbidity and mortality more frequently refused the indicated intervention
of emergent cesarean section in the face of nonreassuring fetal heart tracings as
compared with women with parity less than 5, and maternal age less than 31 years.[8] Ohel et al[9] also found that increased maternal comorbidities, pregnancy complications, maternal
age, and parity of more than 5 were associated with patient refusal of indicated cesarean
sections and/or blood transfusions.[8] One prior study examined the issue of progesterone refusal. Ransom et al demonstrated
that those patients who had a previous delivery at an early gestational age (mean
28.7 weeks) were more likely to accept treatment with 17-OHP compared with those with
later deliveries (mean 34 weeks).[9] This finding is distressing as 80% of preterm birth occurs in the late preterm period
(32–36 weeks), and these infants often still experience difficulties with respiration,
thermoregulation, feeding, health complications, and death in childhood.[10]
While all the aforementioned studies find commonalities within the groups of patients
who refuse treatment, none has taken the next step and directly asked patients, “Why
are you refusing this proven beneficial treatment?” The goal of this study was to
address and clarify the reasoning patients utilize to make their decisions to accept
or decline 17-OHP administration while pregnant.
Methods
This was a prospective study using both qualitative and quantitative techniques over
a 12-month period (May 2016–May 2017) to assess patient decision making regarding
17-OHP treatment to prevent preterm delivery. To be eligible for the study women needed
to be currently pregnant, 18 years of age or older, and have a history of noniatrogenic
preterm birth between 20 and 366/7 weeks. Exclusion criteria included patients with only iatrogenic preterm births,
as well as those without a history of preterm birth. Patients who were candidates
for 17-OHP treatment were identified at their first obstetric visit and asked to complete
a 5-minute survey regarding their history of preterm birth. This study was granted
expedited approval by the Cleveland Clinic Akron General and Akron Children's Hospital
Institutional Research Review Board.
Items included in the questionnaire were developed based on a review of the literature,
discussions with patients similar to those included in the study, and suggestions
based on the clinical experience of a licensed social worker and registered nurse
(both attached to a federally qualified health center specializing in obstetrics and
gynecology), and a practicing maternal–fetal medicine physician. Items centered on
factors that were thought likely to influence patients' decisions regarding 17-OHP
use in pregnancy. Questionnaires such as the one used in this study have been found
helpful in past qualitative studies evaluating treatment refusal in pregnancy.[9] The surveys included a request for contact information from those willing to be
telephoned for follow-up questions and/or participation in a focus group. An interview
guide for use in the focus groups was developed in the same manner as the questionnaire
(see [Table 1]). The focus groups were led by the primary authors of this article with this preset
list of questions and lasted ∼90 minutes, with time for introductions, discussions,
and conclusions. These discussions were audio recorded and then transcribed. Focus
group participants were reimbursed $50 to cover time and transportation expenses associated
with attendance.
Table 1
Focus group interview layout
|
Rapport building stage—10 min
• Tell us what happened with your first preterm birth.
• How did that interaction with the medical system make you feel?
|
|
In-depth discussion—40–60 min
• What do you know about progesterone?
• What things about this medication make you nervous or scared?
• What things about progesterone do you feel comfortable with?
• What do you wish was different in the medical system to make the process of accepting
treatment for preterm birth easier?
• What are things in your personal lives do you think make it difficult to receive
care that doctors do not know about?
• What are things that we can change in the doctors' office to make your care easier?
• Has anyone used progesterone in the past? What was your overall experience with
it?
• When you interact with your OB/GYN, how does it make you feel?
• If you could say one thing about our group today that has not been addressed, what
would it be?
|
|
Wrap-up/closure—5–10 min
• Summarize impressions or conclusions gathered and participants clarify, confirm,
or elaborate on the information.
|
Results
During the 1-year study period, 55 progesterone candidates were identified, 43 accepted
treatment, 7 refused, and 5 either initiated prenatal care too late to receive injections
or did not follow-up. Average age of the patients in the sample was 27.8 years (±5.7)
with no significant difference between the groups who accepted versus declined treatment,
28.4 and 23.6 (p = 0.076), respectively. Those who accepted treatment were 23% African American (10
of 43) versus 29% (2 of 7) of those who declined treatment, and 70% Caucasian (30
of 43) compared with 29% (2 of 7) in the declined treatment group. Fifty-eight per
cent (25 of 43) of the acceptors were covered by public insurance, whereas 86% (6
of 7) of the treatment decliners had public insurance. [Table 2] summarizes the preterm delivery history by treatment acceptance status. Those who
accepted 17-OHP treatment had previously delivered infants at an earlier mean gestational
age who required longer hospitalizations after birth and experienced more frequent
infant mortality secondary to prematurity, although these differences were not statistically
significant. Only 7 of the 50 participants (14%) declined treatment, providing insufficient
sample size for adequate power to detect statistically significant differences between
the groups.
Table 2
Prior preterm delivery history by 17-OHP treatment status
|
Accepted treatment
(n = 43)
|
Declined treatment
(n = 7)
|
p-Value
|
|
Gestational age previous preterm delivery
|
|
|
Mean
|
31 wk
|
33 wk
|
0.139
|
|
Median
|
34 wk
|
34 wk
|
|
|
Mode
|
16–36 wk
|
21–26 wk
|
|
|
Duration of infant's hospitalization
|
16.2 d
(95% CI: −3.1 to 19.1)
|
9.8 d
(95% CI: 1.6 to 18.0)
|
0.084
|
|
Infant mortality secondary to prematurity
|
8 (19%)
|
1 (14%)
|
–
|
Abbreviations: CI, confidence interval; 17-OHP, 17-α-hydroxyprogesterone caproate.
A brief overview of interesting trends between these populations is as follows: 100%
of decliners (n = 7/7) felt well educated by their providers regarding progesterone and its potential
benefits and indication for the prevention of recurrent premature birth. Eighty-six
per cent of decliners (n = 6/7) had not received progesterone in the past, suggesting that their refusal was
not based on bad experiences with previous use. In contrast, 85% of acceptors were
past users and indicated they would use it again. Eighty-six per cent of decliners
were publicly insured and were aware that their insurance would cover the 17-OHP–associated
costs.
Separate focus groups were held for those who accepted treatment (n = 4) versus those who declined treatment (n = 2). Various themes were identified regarding women's acceptance or refusal of treatment.
These include their perception of education regarding treatment, their coping mechanisms
surrounding painful or perceived painful stimuli, a patient's participatory view versus
fatalism, the presence of traumatic birth processes, and the timing of patient education.
Acceptors
As described earlier, four volunteers identified through the initial surveys participated
within a focus group held for those who had accepted progesterone therapy. Of these,
three had delivered their subsequent pregnancies at term and the fourth had recently
reached 36 weeks of gestation and finished her injections. All reported an overall
positive experience with progesterone therapy. Three participants had children who
required neonatal intensive care unit (NICU) admission and would like to use 17-OHP
in the future, and one delivered a late preterm infant at 36 weeks who was discharged
without a NICU stay. The themes which emerged regarding patients who accept treatment
are further described as follows.
Theme 1: Education
Within the medical profession, consent and explanation of care are a pillar of patient
treatment. Surprisingly, focus group members accepting progesterone felt less educated
regarding their treatment process than those who had refused. Within the surveys,
all refusals answered “Yes” when asked if their physician had explained the purpose
of progesterone and had answered all their questions. Paradoxically, those who accepted progesterone
felt as if their questions regarding side effects were not addressed as serious, and
many felt frustrated with the paternalistic nature of their care.
“I looked it [the side effects] up online because my doctor didn't say anything when
I asked.” “…..The physician [he] didn't really even have anything for me. I researched
myself.” “I just got blown off.” “Honestly with the side effects that I had, I called
Makena because they knew more about it than my doctor's office.”
“ ‘Oh yeah we’re just gonna start these for you.' How do you know that I want this?
How do you know that I don't have different questions this time? Yeah, they do need
to have more information available for patients.”
While most women with preterm birth proceed with prophylactic therapy, it is important
to note that those who decide to accept care still require ardent support and explanation
of their care. Every focus group member requested additional materials to support
them in their decision making, going as far as to provide examples, such as a pharmacy
helpline or YouTube video.
Theme 2: Pain
Both groups cited pain, or perception of pain, as a side effect of injectable 17-OHP.
However, the interpretation of that pain was dissimilar between the groups. Progesterone
acceptors described injection-associated pain as a means to a healthy child, and often
as a nuisance rather than an absolute barrier to care. They also described all other
side effects as acceptable given the increased likelihood for a positive outcome.
“… the chances of having a healthy baby are higher. It does get, again, annoying,
like by 30 weeks, I'm like, for real, we've got to be done with this. I have six more
weeks of this? But, the comfort in knowing, OK, this will increase my chances of having
a full term healthy baby is enough in itself to continue on with it.”
“That while weekly injections may not be comfortable, they are better than a sick
or lost baby.”
Although pain may be cited as a contributing factor for treatment refusal, those who
accept progesterone frame the discomfort as a part of the narrative toward achieving
a term delivery.
Theme 3: Belief Systems
This constructive perception of a painful stimulus may well encompass acceptors' overall
belief systems, in that they demonstrate participatory responses and positivity regarding
their care. All focus group acceptors endorsed this readiness to alter their future
prenatal care to increase the odds of term delivery.
“You do all the research, you see all the side effects, but even if it give my baby
a 1% chance of even making it to 35 weeks, let's go, we can do this. So, for me, it
was a no brainer.”
Her participatory role is exemplified here by her acceptance of the treatment side
effects, and her willingness to engage and overcome them in exchange for a healthy
infant. Open-ended survey responses from acceptors further perpetuate this theme:
“I decided to [take progesterone] because I wanted to avoid the risk of losing my
baby again.” All participants were hopeful that their odds of delivering a premature infant would
be reduced with 17-OH-P, and were ready and willing to play an active role in their
future care.
Theme 4: Traumatic Birth Processes
The majority of women who accepted progesterone within the focus group endorsed a
personal experience of traumatic birth and recovery. Two participants had infants
spend significant time in the NICU, and one experienced a perinatal demise. They independently
use the word “traumatic” and cite it is a major nisus for their decisions in future
care, stating that they would continue to use progesterone during their subsequent
pregnancies.
“Because it is traumatizing, I had him and I didn't even get to see him because they
took him straight to the NICU...it's a pain in the butt literally, but it's worth
it. It's definitely worth it, when you've gone through that NICU experience and everything,
you just don't want to go through that ever again, and if there's something that can
make that avoidable, then you should really weigh out your options.”
“I had him living, and then he died afterwards, and it was pretty traumatic for me.
Like the whole process of, what do you even do? How do you even approach this?”
Interestingly, the focus group participant who delivered a late preterm infant not
requiring NICU admission felt as if she did not need progesterone in the future to
maintain a healthy future pregnancy—“my daughter was born at 36 weeks and we stayed the normal 2 days and then we went
home, no problems, nothing… ‘cause honestly I was wondering if I need it.”
Theme 5: Timing of Candidate Identification
The temporal association of the principal premature birth and counseling from a health
care professional appears to impact the decision-making process for progesterone candidates.
All focus group members were approached by health care providers during their admission
for delivery of their first premature infant.
“My doctor, my son was born at 34 weeks, and we were in the NICU and it's something
he brought up to me and he knew how strongly I felt about that not wanting that to
happen again.”
“My doctors were very thorough with it. They were on top of it,” states one candidate regarding her recovery process after delivery of a previable
fetus.
Perhaps discussing preventative measures while the gravity of premature birth is fresh
within the patient's experience has a more lasting implication for future consideration
of their care.
Additionally, this approach may continue to build rapport within the medical field,
especially if the patient travels between various care providers. The repetitive nature
of this medical advice may also sway the decision-making process, and so early introduction
of the topic begins this process. All focus group participants also mentioned that
progesterone was discussed at their first prenatal visit as well in the subsequent
pregnancy.
“He [the doctor] did bring it up my first visit as well.”
Decliners
Two volunteers identified from the initial surveys participated in a focus group for
women who did not receive progesterone. They both delivered premature infants at 36
weeks who did not require NICU admission. One volunteer had subsequently given birth
to two term pregnancies. The first subsequent infant delivered at term without progesterone
because the woman was mistakenly not identified as a candidate. She accepted progesterone
briefly in her third pregnancy but refused shortly thereafter secondary to pain. The
second volunteer was currently pregnant with her subsequent pregnancy.
Theme 1: Education
When asked on a survey, “Do you feel your healthcare professional explained progesterone
to you and answered your questions?” and, “has anyone explained the risk of premature
birth?” all seven women who declined progesterone marked “Yes.” This is in sharp comparison
to the discussion had with those accepting progesterone, who often felt undereducated
with regard to their treatment. There may be many explanations for this. By declining
progesterone, the health care professional is obligated to addresses those consequences
and potential use with each prenatal visit, and so those who decline truly are receiving
more education. Those who accept progesterone may receive less education in the office
because the goal of “convincing” someone to receive care is less driven. Alternatively,
those who refuse progesterone may feel compelled to project that their decision is
informed and defensible, and therefore will display their confidence with the subject
matter. It is also possible that those who accept treatment are also more integrated
into their care and have more questions. Regardless of cause, integrating more education
within the treatment curriculum regardless of a patient's decision seems integral
to closing the perceived knowledge gap for those actively pursuing treatment.
Theme 2: Pain
Pain, whether physically experienced or potentially experienced, was an active deterrent
for members of the focus group of treatment decliners. When asked to identify their
largest concern for treatment, both members cited, “Just only pain.” The physical pain also generated an emotional deterrent—“but I’m scared of shots.” This discomfort from injections infiltrated beyond the isolated events of medication
administration. It generated a pervasive concern for maintaining everyday life and
caring for their families while being both pregnant and acutely uncomfortable.
“Because I had to take care of 2 babies, with the pregnancy. So, it's really hard.
My leg is painful, so I cannot go anywhere.”
The theme of pain was also applied by women when discussing the ramifications of carrying
a gestation to full term, and justified their refusal as preventing the potential
for pregnancy-related pain or complications.
“My biggest scare is having a uterine rupture from where my cesarean section is…..I
really don't want a big baby or have a rupture. I'm just uncomfortable. When I put
my legs together I feel like I'm smashing her head.”
“I have little babies, [I'm] scared if I carry full term the baby would be too big
for me to deliver natural. I'm tiny.”
Health care professionals naturally interact with patients on the provider's terms
within their offices. This may prevent the providers from adequately understanding
the patients' more complex life stressors or concerns. It may be important to be aware
that pain directly associated with therapy refusal may have broader implications in
the patient's day-to-day life. The mention of pain as a reason for treatment rejection
may be a point with which to start a conversation regarding the wider implications
of the pain and to initiate a search for solutions to those problems.
Theme 3: Belief Systems
Women who declined progesterone often voiced the belief that all events are predetermined
and therefore inevitable. Within the surveys, an open-ended question asked for a generalized
statement regarding progesterone therapy. Many of these responses aligned with this
fatalistic belief system:
“I wouldn't use it, rather things run its course.”
“I have faith that my baby is going to make it. And I'm going to love him or her with
every flaw.”
“I believe in fate, because what's going to happen is going to happened regardless
of what we take…. if the baby does not survive it wasn't that babies time.”
These statements stand in stark contrast to patients who actively demonstrate a participatory
role in their care. This situation may be the most difficult for a clinician to navigate,
as the decision making for these patients is rooted in their belief systems, and not
from an evidence-based process. Personalized approaches, such as motivational interviewing,
which is a patient-centered counseling style designed to elicit behavioral changes,
may be more effective with these cases.
Theme 4: Traumatic Birth Processes
Neither focus group participant not receiving progesterone had previous birth outcomes
which required NICU admission. Both had late premature births, which were not described
as traumatic, and therefore, these women did not feel that their future pregnancies
warranted treatment.
“He went home—because he was at the baby shower a week later… I just didn't ever look
at it as [premature]—because he was almost 37 weeks.”
Many women cite a following uncomplicated term birth, without treatment, as further
cause for their refusal.
“Not sure its 100% necessary because my 2nd pregnancy was full term without it”
“I had my first son at 33 weeks. My second pregnancy I refused progesterone and baby
was born at a perfect 38 weeks. My third pregnancy-chance of preterm baby is even
lower.”
Theme 5: Timing of Candidate Identification
Neither woman in the refusal focus group was approached at the time of their premature
birth to discuss plans for progesterone use in their future pregnancies. One participant
had not been properly identified during her second pregnancy as a candidate but was
correctly identified in her third. Within the medical field, it has been demonstrated
that consistent repetition of appropriate treatment recommendations by the treatment
team is extremely important to patient treatment acceptance and compliance. The lack
of consistent education/identification between providers may also prove a jarring
experience for patients and may serve to generate distrust. The commitment of weekly
injections—which require time away from work and inflict pain (among other side effects)—is
potentially a difficult conversation and expectation to thrust upon a patient. Establishing
a framework at the outset of a premature delivery helps establish patient trust and
establishes an expected plan of care.
Women who refused treatment were asked what could be done to improve their care within
the medical field—each listed having multiple different care providers, and, being
distracted by their children in the office, as barriers to their care.
“I know my children [are] quieter if they're distracted with coloring or a movie…
I'm more focused on what the doctor is saying and telling me. I can remember and absorb
more information...”
They both endorsed the support from a counselor as being critical step toward their
emotional health and well-being.
“The 2 times that I did talk to her, it was very soothing, kind of stopped the tears
and stuff. She's very concerned about what's going on my life. And make sure that
nothing progressed to something that would put me in danger. So, I think it's real
good that she's there.”
Small changes in office management may make the environment more approachable for
patients who remain initially closed regarding their care.
Discussion
The primary objective of this study was to examine the decision-making process for
women who were candidates for intramuscular 17-OHP, based on a past history of noniatrogenic
preterm birth. This process is multifactorial, and different women approach this decision
with different backgrounds. While the initial surveys sent out did not generate enough
data to achieve statistical significance, the open-ended questions and focus groups
generated enlightening qualitative information. Themes identified from the study would
suggest that those who accept progesterone are more likely to have had traumatic birth
processes, an active interest in their medical care, were identified as candidates
at their index preterm birth, were undeterred by pain, and wanted more education regarding
their care. Women who declined progesterone were more likely to be deterred by pain,
felt that their decision was well informed, were less likely to have had traumatic
birth processes, were not identified at their initial preterm birth as progesterone
candidates, and were more likely to have a fatalistic belief system.
A literature search failed to identify other current research examining the reasoning
patients use to decide whether to accept or decline progesterone that employed a qualitative
process. Quantitative studies are consistent with results in this article. Ransom
et al determined with a retrospective cohort study that those refusing progesterone
had a median gestational age of 5 weeks earlier than those accepting treatment, likely
correlating to more traumatic birth and recovery processes.[9] Iris et al identified other risk factors for overall treatment refusal, such as
higher parity and increasing maternal age.[11]
Medical decision making is by nature a multifactorial process. This is complicated
further by the physical and emotional changes of pregnancy. Drawing from this study,
several approaches to the patient who delivers a premature infant may be employed.
Maternal health care providers should always discuss the prematurity of the index
pregnancy and the associated implications for future pregnancies at the time of delivery,
or while admitted for recovery, and again at the first prenatal visit of the subsequent
pregnancy. Providers need to be prepared to employ various techniques for patient
counseling and education. These tools may include using motivational interviewing
and having handouts readily available. Interestingly, all members of both focus groups
were asked which modes of information delivery they prefer, and all participants advocated
for a brief video. Development of such a video might also engender patient acceptance
and compliance. For women who cite pain as their primary concern, it may be appropriate
to explore the wider implications of that statement. Additionally, it may be reasonable
to consider the use of vaginal progesterone, which although not FDA approved for this
indication, several studies have shown to be effective for prevention of premature
birth. Barriers to accessible care should also be addressed, such as limiting the
number of providers and providing distractions for children.
The major limitation of this study was sample size. In Summit County, the 2016 rate
of premature births was 10.4% according to the March of Dimes. Those refusing treatment
are a small subset of these pregnancies. Future studies may prove more significant
if data can be collected over the course of more than 1 year. Interestingly, most
progesterone candidates were from the Federally Qualified Health Center (FQHC), where
16 women with a history of premature birth were identified as candidates; however,
only 10 received progesterone therapy. Three of the six women who refused 17-OHP treatment
also declined to participate in this study. This suggests that the motivations of
women who refuse therapy may be underrepresented and that novel approaches may need
to be employed to recruit such women in futures studies.
Qualitative research such as this, where women are invited to participate in a setting
free of judgment with like-minded peers, in support of their individual opinions,
gives privileged insight into the medical decision-making process.[12] Understanding the various narratives of human experience may flesh out and ground
our approaches to patient care and hopefully provide a basis to develop new approaches
to encourage patient acceptance of 17-OHP therapy and other appropriate therapies
during pregnancy.
