Table 1: Evidence-based medicine and continuous subcutaneous terbutaline infusion review of efficacy literature.

StudyResearch designQuality of evidence PopulationComments

Lam et al. [11]
Observational cohortII-21,556RPTLInclusion criterion: tocolytic breakthrough in high-risk population subset. Results: PTD rate was reduced from 5.18% to 2.69% ( ).

Lam et al. [12]Descriptive case series III9RPTL Pregnancy prolongation 9.2 weeks, mean GAD 39 weeks.

Lam et al. [13]
Randomized controlled trial (RCT)I68CPTLWeeks of pregnancy prolongation and PPI were 8.6 (0.93) and 2.4 (0.34) in the pump versus oral groups, respectively.

Gianopoulos et al. [14]
Descriptive case series III31RPTLPregnancy prolongation 5.4 ± 4.5 weeks and weeks gestational age at delivery.

Jones et al. [15]
Descriptive case series III50RPTL Pregnancy prolongation 6.3 weeks.

Fischer and Kaatz [16]Descriptive case series III19CPTLSafe and effective in the treatment of preterm labor. Average GAD 35.6 weeks.

McGettigan et al. [17]
Observational cohortII-228RPTLAverage GAD 35.7 weeks. Terb pump prolongs tocolysis, reduces terb dose significantly ( ), reduces maternal side effects, and may reduce the newborns’ total exposure to β-mimetic dosage.

Wolfsen and Winn [18]Descriptive case seriesIII9Twins w/advanced cervical dilatation75% achieved >37 weeks or mature lung indices on amniocentesis

Allbert et al. [19]Descriptive case series III992C/RPTL
206 twins
786 singletons
Extended the gestation as mean of 38 ± 23 days and average GAD 36.3 ± 2.6 weeks.

Lindenbaum et al. [20]Observational
cohort
II-2725CPTLThe incidence of gestational diabetes is not increased in patients receiving terbutaline via the subcutaneous pump.

Moise et al. [21] Descriptive case series III13RPTL
10 singletons
2 triplets
1 twin
Average GAD 35.3 weeks, pregnancy prolongation 5.0 weeks.

Weinbaum and Olson [22]Descriptive case series III202CPTLContractions were arrested and the mean gestational age at delivery was 36.2 weeks. Only 9.6% of the patients were readmitted to the hospital.

Elliott and Radin [23]Observational case controlII-267 CPTL
67 quadruplets
Mean GAD 32.5 weeks. Mean infant birth weight 1534 ± 429 g.

Adkins et al. [24]Descriptive case series III51CPTL Average birth weight 3,000 g. Average GAD 37 weeks. Pregnancy prolongation 6.6 weeks.

Regenstein et al. [25]Observational case controlII-2151CPTLNo difference in the incidence of gestational diabetes or glucose intolerance between subcutaneous and oral groups

Allbert et al. [26]
Observational cohortII-264RPTLPregnancy prolongation index was 0.86 and 0.72 for the pump and oral groups, respectively.

Perry et al. [27]Descriptive case series III8,709CPTLContinuous terbutaline infusion is associated with much fewer adverse effects than the previously reported literature on intravenous terbutaline or ritodrine therapy would suggest.

Elliott et al. [28]Retrospective cohortII-221CPTL
15 triplets
6 quadruplets
Estimated $18,150 savings per pregnancy. Only 2 of the 15 triplets (13%) and 1 of the 6 quadruplets (17%) delivered because of tocolytic failure. Mean GAD 33.0 weeks for both groups.

Wenstrom et al. [29] Randomized control trial  (RCT) I 42 CPTL Three-arm study—15 terbutaline pump, 15 oral terbutaline, and 12 saline pump. Significant methodological flaw in those patients crossed over between groups while in study. Patients on oral terbutaline or saline pump were switched to terbutaline pump if therapy failed. No electronic contraction monitoring or daily nursing contact. Tocolytic therapy was not individualized for each patient. Study underpowered in that it did not contain enough patients to show a difference between groups. No difference in outcomes between groups.

Guinn et al. [30] Randomized control trial  (RCT) I 52 CPTL Overall dropout rate 38%. 13 patients in the terbutaline group completed this study and 19 patients in the placebo group. Advanced median cervical dilatation of 3 cm, effacement of 50% at start. Tocolytic therapy was not individualized for each patient. No electronic contraction monitoring or daily nursing contact. Study was underpowered and, therefore, showed no difference in outcomes between groups.

Lam et al. [31]
Observational cohortII-2256RPTL
Patients served as their own control. Subcutaneous terbutaline therapy prolonged pregnancy greater than oral terbutaline
4.4 ± 2.6 weeks compared to 2.7 ± 2.2 weeks.

Berkus et al. [32]
Descriptive case seriesIII7CPTLLow dose, continuous SQ terbutaline infusion had no effect on insulin sensitivity in nondiabetic patients, in contrast to oral terbutaline.

Hammersley et al. [33]Descriptive case series III70RPTL
52 singletons
11 twins
7 triplets
Inclusion criterion: preterm labor or cervical shortening <3 cm and/or 50% funneling. Mean cervical length 2.6 ± 0.9 cm at initiation of therapy. 76% of desired pregnancy prolongation was achieved.

Lam et al. [34]Observational cohort II-2386RPTL
386 twins
34.0 ± 19.8 versus 19.3 ± 15.3 days in utero gained with subcutaneous therapy compared to oral therapy.

Ambrose et al. [35]Observational case controlII-2180CPTL
76 twins
Outpatient-administered subcutaneous terbutaline shown to be a cost-effective and viable alternative versus inpatient-administered subcutaneous terbutaline.

Elliott et al. [36]
Observational case controlII-2144144 quadrupletsOutpatient therapy cost $30,270 less per patient and is associated with a statistically significant better chance of delivery >32 weeks than in patient.

Elliott et al. [37]Observational cohort II-2104RPTL
104 triplets
Mean pregnancy prolongation on pump 5.4 ± 3.4 weeks versus 2.8 ± 2.2 weeks for oral treatment.

Lam et al. [38] Observational case control II-2 706 RPTL  706 twins Total maternal and nursery charges were $17,109 less for patients treated with subcutaneous terbutaline compared to oral treatment.

Elliott et al. [39]Descriptive case seriesIII9,359CPTL
7,028 singletons
1,946 twins
385 triplets
Extremely low incidence of serious adverse events. GAD was 36.6 weeks in the singletons, 34.9 weeks in the twins, and 32.8 weeks in the triplets. Authors conclude that therapy is a viable and safe option for outpatient management.

Hamersley et al. [40]Descriptive case series III6Twins with delayed-interval deliveryThe median pregnancy prolongation achieved following delivery of the first-born nonviable twin was 93 days.

Viscarello et al. [41]
Observational case controlII-240CPTL
40 triplets
Proactive dose acceleration protocol achieved significantly better outcomes than standard dosing.

Viscarello et al. [42]
Observational case controlII-259Higher order multiples:
56 triplets
3 quadruplets
A comprehensive clinical pathway (CCP) including subcutaneous terbutaline proved significantly better outcomes (35.1 ± 1.6 versus 31.6 ± 3.1 weeks GAD) compared to concurrent local standard of care. Of the 12 patients whose GAD was <32 weeks, 1 received the CCP including subcutaneous terbutaline, compared to 11 who received the concurrent local standard of care.

Jones et al. [43]
Descriptive case seriesIII1420CPTLOne-third of singletons and 60% of twins delivered within 3 days of early discontinuation of SQT. Early discontinuation of SQT places a pregnancy at risk for PTD.

Morrison et al. [44] Observational case control II-2 60 RPTL Among patients with recurrent PTL, the use of SQT infusion significantly prolongs pregnancy while decreasing the likelihood of the rate of low birth weight (2500 g) infants, the need for admission to NICU, and duration of being hospitalized. For every dollar spent on SQT, there was a saving of $4.67 on the charges of newborns stay in the hospital.

Lam et al. [45] Observational case control II-2 558 RPTL 70.6% of subcutaneous therapy patients reached at least 36 weeks compared to 56.6% of oral therapy patients. Subcutaneous therapy patients cost $5,286 less.

Roman et al. [46]
Matched cohortII-2260Twins in CPTL>7 days prolongation of pregnancy in over 86% of cases

Gaziano et al. [47]Matched cohortII-21,079CPTLOutpatients obtained statistically better antepartum days, pregnancy prolongation, GAD, delivery <35 weeks, and cost. Total average cost outpatients were $17,375 versus $39,040 inpatient.

Rebarber et al. [48]
Matched cohortII-2783CPTL86% of patients had their pregnancy prolonged >7 days

Fleming et al. [49] Observational case control II-2 284 RPTL 37.3% of nifedipine patients delivered ≤35 weeks compared to 19.7% of subcutaneous terbutaline patients. Subcutaneous terbutaline patients cost $10,494 less per pregnancy.

Gaziano et al. [50]
Observational case controlII-2273CPTLTwin pregnancies discharged for outpatient management following i.v. treatment for PTL obtained significantly longer pregnancy prolongation, a greater gestational age at delivery, and delivered infants with fewer NICU admission.

Brown and Stanziano [51]
Observational case controlII-2840CPTLMedicaid versus commercial patients with singleton gestations and cervical dilatation of ≥2 cm at PTL. Medicaid patients experienced comparable pregnancy prolongation and gestational age at delivery as commercially insured. 96% of medicaid patients experienced pregnancy prolongation of at least 7 days after PTL. Incidence of discontinuation of SQT for noncompliance was 1.6% for medicaid versus 2.8% for commercially insured ( ).

Newman et al. [52]Observational case controlII-21839CPTLTwin pregnancies with PTL. Medicaid versus commercially insured. Similar pregnancy prolongation and GA at delivery. 97% of medicaid patients experienced >7 days of pregnancy prolongation after PTL. Incidence of discontinuation of SQT for noncompliance was 4.6% for medicaid versus 2.0% for commercially insured ( ).

McWeeney et al. [53]
DescriptiveIII3496CPTLSingleton gestations hospitalized with CPTL; all treated with SQT following stabilization. The degree of cervical dilatation and gestational age at initiation of treatment are predictive of subsequent pregnancy outcome. With each centimeter of cervical dilatation, the risk for delivery at <32 weeks almost doubles.

Rebarber et al. [54]Observational cohortII-24253CPTLSingleton gestations with elective discontinuation of tocolytic treatment that occurred at 33–36 weeks’ gestation were found to have a higher incidence of late preterm birth, with significantly greater rates of NICU admission and low birth weight, and significantly higher nursery charges. Tocolytic treatment should be continued through 36 weeks.

de la Torre et al. [55] Observational cohort II-2 1421 Twins with RPTL In twin pregnancies receiving nifedipine tocolysis, alteration of tocolytic treatment to subcutaneous terbutaline following hospitalization for recurrent preterm labor symptoms had a positive impact on pregnancy prolongation and neonatal outcomes.

Flick et al. [56] Observational cohort II-2 4748 Singletons with RPTL Alteration of tocolytic treatment following rehospitalization for PTL resulted in decreased antepartum hospital days, decreased nursery days and lower rates of higher level nursery admission and preterm birth, proving both to be clinical and cost effective.