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Discussion not so unexpected in any adult population—pregnant
women may experience these adverse events in the
In this small review of 14 studies, most data came from absence of terbutaline therapy due to other reasons.
observational designs, and several studies analyzed data
Observational studies of medium to high risk of bias,
from the Matria database. Aside from two RCTs, the
primarily from the Matria database, showed benefit of
studies exhibited considerable clinical and
SQ terbutaline pump compared with oral tocolytics or
methodological heterogeneity. For the gradable
no treatment for other surrogate outcomes, such as birth
outcomes, the available evidence addressed only two
weight and NICU admission, for women with twin
specific populations of interest—women with RPTL or
gestation and/or RPTL. In contrast, two small RCTs that
those additionally with twin gestation. The strength of
did not address any of the populations of interest,
evidence favoring the SQ terbutaline pump compared
reported nonsignificant differences for several surrogate
with oral tocolytics for neonatal death in women with
outcomes.
twin gestation and RPTL is low (OR = 0.09, 95% CI:
0.01, 0.70). While this result is striking in the presence The evidence base for this review contained several
of insufficient findings on other neonatal health limitations. Most evidence came from observational
outcomes summarized below, it is apparent that it stems designs of medium to high risk of bias. Several
from the largest of studies contributing data on neonatal outcomes revealed nonsignificant results that could be
health outcomes with more than 700 patients. As such, it attributed to type II error. Type II error is a statistical
is the only outcome that appears to be adequately term that implies inability of studies to find a difference
powered to reach statistical significance. Strength of when it might truly exist because of their small sample
evidence favoring terbutaline pump compared to oral size (false negative). Many important variables, such as
tocolytics or no treatment is also low for women with race, socioeconomic status, and fetal fibronectin level
twin gestation and/or RPTL for the surrogate outcomes were not reported. Furthermore, cointerventions, such as
of pregnancy prolongation. For bronchopulmonary administration of corticosteroids, were rarely described.
dysplasia, significant intraventricular hemorrhage, death None of the included studies assessed long-term
within initial hospitalization, and Withdrawal-AE, childhood outcomes, such as childhood development,
strength of evidence is insufficient. The evidence was neurobehavioral testing, long-term lung function, and
inconclusive for all other neonatal health outcomes, long-term vision. Our review comprehensively reviewed
neonatal harms, maternal harms, and pump-related the literature and selected reports based on well-defined
outcomes. inclusion and exclusion criteria. However, one potential
limitation of our review process is that we excluded
Based on postmarketing surveillance data, the FDA has
potentially relevant non-English publications. Also, we
issued a new warning against the use of terbutaline in
could not investigate the impact of publication bias.
general, and as an injection in particular, as maintenance
However, in completing this review, we undertook an
tocolysis (i.e., beyond 48–72 hours) in pregnant
extensive grey literature search. Further, we requested
women. Although meriting transparent disclosure in the
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relevant scientific information from the industry and had
form of a warning, evidence emerging from case reports
many experts in the field participate in the review
is usually regarded as noncomparative and hypothesis
process. Despite this thorough process, the number of
generating signal rather than a hypothesis testing
identified studies was very small—we had too few
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confirmation. Furthermore, case reports are useful in
studies per outcome to perform statistical assessment of
identifying rare and unexpected adverse events—the
publication bias. We believe that all relevant data
rarer the adverse event, the stronger is the effect size,
regarding the use of subcutaneous terbutaline for the
and the magnitude of effect size is an important criterion
prevention of preterm labor is captured in this review.
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that increases our confidence in an estimate. However,
Any exaggerated positive findings are more likely due to
adverse events such as death, hypertension, myocardial
the medium to high risk of bias detected in
infarction, tachycardia, arrhythmias, and pulmonary
observational studies than publication bias.
edema that were reported with the use of terbutaline are
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