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In conclusion, the available evidence suggests that should be placebo controlled and include blinding of
pump therapy is beneficial as maintenance tocolysis. study participants, care providers, and study personnel.
However, our confidence in the validity and Consideration should be given to employing multiple
reproducibility of this evidence is low. While treatment arms in order to evaluate the pump against
postmarketing surveillance has detected cases of serious other tocolytic agents and conservative management.
harms, safety of the therapy remains unclear. Furthermore, the level of care provided to participants
(i.e., nursing assessments, home uterine monitoring,
Future Research
education, telephone support, and restriction of
activities) should be practical, feasible, and likely to be
Although cohort studies have provided a glimpse of the
adopted in routine practice. Important cointerventions,
potential for the SQ terbutaline pump to improve short-
such as administration of corticosteroids, should be
term neonatal outcomes for fetuses at risk for preterm
reported. A full accounting of the number of women
birth, the answers to several important questions remain
approached but not enrolled should be included to
unanswered. Most importantly, it remains to be seen
allow users to assess the impact of respondent bias. The
whether SQ terbutaline pump therapy alters long-term
analysis should be “intent to treat,” where all
development or systemic impairment of offspring, and
participants assigned by randomization to each group
neonatal/maternal morbidity and mortality. The
are included in the primary comparisons, regardless of
limitations of the available data must also be
whether the assigned medication was received.
recognized. Most of the cohort studies were medium to
Outcomes to be examined should go beyond those of
high risk of bias. In addition, several of the cohort
prolongation of pregnancy and birth weight to hard
studies investigated participants from a single
clinical endpoints of neonatal morbidity, such as
proprietary database (Matria), which raises concerns
bronchopulmonary dysplasia, necrotizing enterocolitis,
regarding double-counting of patients and common
significant intraventricular hemorrhage (grade III/IV),
biases. Therefore, results showing effectiveness should
retinopathy of prematurity, sepsis, stillbirth, and
be interpreted with caution, especially in light of the
neonatal death. Lastly, there should be long-term
most recent FDA warning recommending against the
followup to assess subsequent childhood outcomes.
use of terbutaline for maintenance tocolysis.
Pharmacodynamic and pharmacokinetic outcome
Information is lacking on the effectiveness and safety of measures can additionally be studied to understand
SQ terbutaline pump as a maintenance tocolytic inter-individual differences in effectiveness and toxicity
treatment in specific populations, including women and avoidance of ß-agonist related tachyphylaxis.
who deliver at specific gestational ages, women of
Conducting RCTs to assess the efficacy of tocolytics in
different racial or ethnic backgrounds, and women with
general is notoriously difficult. A definitive trial in this
previous preterm birth or preeclampsia. Future studies,
domain must include a focus on accurate diagnosis of
whether observational or experimental in design, should
preterm labor (perhaps combining stringent clinical
focus on garnering evidence for these specific
criteria with factors such as positive fetal fibronectin
populations.
and shortened transvaginal cervical length). Emphasis
Below we provide some specific recommendations for must also be placed on securing funding and
the conduct of RCTs and observational studies to maintaining followup for an appropriate duration of
further elucidate the potential benefits and harms of SQ time to allow assessment of long-term childhood
terbutaline pump for maintenance tocolysis. outcomes, including neurobehavioral testing and
Randomized trials. We recommend that an adequately developmental assessment.
powered randomized controlled and pragmatic clinical Observational studies. Although the RCT is the ideal
trial that assesses the SQ terbutaline pump as a study design for evaluating the efficacy of
maintenance tocolytic be conducted. A pragmatic RCT interventions, it may not be feasible for a number of
is designed to have broad applicability so that the reasons, such as a prohibitive sample size requirements
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results can guide decisions about practice. Such a trial and ethical considerations. We realize that collecting

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