appendix 1. flow diagram of studies identified in the

Saccone G, Ciardulli A, Baxter JK, Quinones JN, Diven LC, Pinar B, Maruotti GM, et al. Discontinuing oxytocin infusion in active phase of labor: a systematic review and meta-analysis. Obstet Gynecol 2017; 130. The authors provided this information as a supplement to their article. ©2017 American College of Obstetricians and Gynecologists. of 14

Appendix 1. Flow diagram of studies identified in the systematic review.


Appendix 2. Assessment of risk of bias. A. Summary of risk of bias for each trial. Plus sign indicates low risk of bias, minus sign indicates high risk of bias, and question mark indicates unclear risk of bias. B. Risk of bias graph about each risk of bias item presented as percentages across all included studies.


Appendix 3. Characteristics of the Included Studies Study

location Sample size*

Inclusion criteria

Augmentation vs induction of labor**

Exclusion criteria

Daniel-Spiegel 200412

Israel 104 (52 vs 52)

Singleton gestations with ≥41 weeks, or PROM >24 hours, or IUGR, or diabetes

Induction of labor

More than one prior cesarean delivery, estimated fetal weight >4,250 grams, or fetal distress at the time of randomization

Ustunyurt 200713

Turkey 342 (168 vs 174)

Singleton gestations ≥ 37 weeks

Induction of labor

Prior cesarean delivery, estimated fetal weight >4,000 grams, or fetal distress at the time of randomization

Bahadoran 20105

Iran 104 (50 vs 54)

Singleton gestations ≥ 37 weeks Bishop <5 BMI <26

Induction of labor

Hypertonic contraction, or fetal distress at the time of randomization

Rashwan 201011

Egypt 200 (100 vs 100)

Singleton gestations ≥ 37 weeks Bishop >4

Induction of labor

Hypertonic contraction, or fetal distress at the time of randomization, maternal or fetal disease

Diven 20129

USA 252 (125 vs 127)


Induction of labor

Hypertonic contraction, or fetal distress at the time of randomization.

Begum 20136

Bangladesh 100 (50 vs 50)


Induction of labor

Hypertonic contraction, or fetal distress at the time of randomization,


maternal or fetal disease

Ozturk 201410

Turkey 130 (66 vs 64)

Nulliparous singleton gestations ≥ 36 weeks

Induction of labor

Hypertonic contraction, or fetal distress at the time of randomization, maternal or fetal disease

Bor 20157 Denmark 200 (100 vs 100)

Singleton gestations ≥ 37 weeks cervical dilation ≤4cm

Induction of labor

More than one prior cesarean delivery, estimated fetal weight >4,250 grams, fetal distress at the time of randomization, maternal or fetal disease

Chopra 20158

India 106 (53 vs 53)


Induction of labor

Prior cesarean delivery, estimated fetal weight >4,250 grams, fetal distress at the time of randomization, maternal or fetal disease

*Data are presented as total number (number in the discontinue oxytocin protocol group vs number in the continuous oxytocin protocol group). **Use of the oxytocin within the trial ***Data are presented as number in the discontinue oxytocin protocol group vs number in the continuous oxytocin protocol group IUGR, intrauterine growth restriction


Appendix 4. Intervention Group and Control Group of the Included Trials Definition of

active phase Definition of uterine tachysystole

Intervention group

Control group


Cervical dilatation of 5 cm

>5 contractions in 10 minutes

Infusion of oxytocin was discontinued when active phase was reached

Infusion of oxytocin was continued until delivery on the same dose

Ustunyurt 200713

Cervical dilatation of 5 cm, and regular contractions at 3 min intervals


Infusion of oxytocin was discontinued when active phase was reached, and infusion was continued with 500 mL of 0.9% of NaCl solution.


Bahadoran 20105

Dilatation of 4 cm and 80% effacement, or 5 cm without considering effacement.


Infusion of oxytocin was discontinued when active phase was reached, and infusion was continued with 500 cc of Ringer’s solution

Infusion of oxytocin was continued with 500 cc of Ringer’s solution with 5 units of oxytocin until delivery

Rashwan 201011





Diven 20129 Cervical dilatation of ≥4 cm, and regular contractions

>5 contractions in 10 minutes*


Infusion of oxytocin titrated to target 3-5 contractions in a 10- minute period was continued until delivery


Begum 20136 Cervical dilatation of 5 cm

Not reported Infusion of oxytocin was discontinued when active phase was reached


Ozturk 201410


Not reported Infusion of oxytocin was discontinued when active phase was reached


Bor 20157 Cervical dilatation of 5 cm




Chopra 2015 8

Cervical dilatation of 4-6 cm


Infusion of oxytocin was discontinued when active phase was reached, and infusion was continued with 500 mL of 0.9% of NaCl solution.


*Additional unpublished data kindly provided by the authors of the original trials


Appendix 5. Protocol Adherence in Intervention (Discontinuation of Oxytocin) and Control (Continuation of Oxytocin) Groups Intervention

group failure protocol

N (%) with failure protocol in the intervention group

Control group failure protocol

N (%) with failure protocol in the control group


Inadequate uterine contractions for two hours or more, or if cervical dilation did not improve

4/52 (7.7%) had oxytocin restarted

Non-reassuring fetal heart rate tracing

4/52 (7.7%) had oxytocin discontinued

Ustunyurt 200713

No cervical change for two hours despite adequate contractions

11/168 (6.5%) had oxytocin restarted

Non-reassuring fetal heart rate tracing

8/174 (4.6%) had oxytocin discontinued

Bahadoran 20105

Not reported Not reported Not reported Not reported

Rashwan 201011

Not reported Not reported Not reported Not reported

Diven 20129 Lack of cervical change, or decrease in contraction frequency

89/125 (71.2%): - 31/125 not

discontinued despite randomization

- 58/125 had oxytocin restarted

Non-reassuring fetal heart rate tracing, or other indication to stop the infusion

0/127

Begum 20136 Not reported 0/50 Not reported 0/50 Ozturk 201410 Lack of

cervical change, or decrease in contraction frequency

0/66* Non-reassuring fetal heart rate tracing, or other indication to stop the infusion

0/64

Bor 20157 No cervical dilatation in two hours**

36/100 (36.0%) had oxytocin restarted**

Non-reassuring fetal heart rate tracing, or other indication to stop the infusion**

3/100 (3.0%) had oxytocin discontinued**

Chopra 2015 8 Inadequate uterine

Not reported Non-reassuring fetal heart rate

Not reported


contractions (<3/10min) for two hours or more, or if cervical dilation did not improve

tracing, or other indication to stop the infusion

*Two women had oxytocin restarted and were excluded after randomization **Additional unpublished data kindly provided by the authors of the original trials


Appendix 6. Oxytocin Infusion Management of the Included Trials Oxytocin

dilution Starting dose Increasing dose Maximal

allowed dose Daniel-Spiegel 200412

5 UI in 500 mL of 0.9% NaCl

1 mIU/minute 1 mIU/20 min until regular contractions*

20 mIU/min

Ustunyurt 200713

5 UI in 500 mL of 0.9% NaCl


Not reported

Bahadoran 20105

5 UI in 500 mL of Ringer’s solution

6 mIU/minute 6 mIU/30 min until regular contractions

Not reported

Rashwan 201011 5 UI in 500 mL of 0.9% NaCl


20 mIU/min

Diven 20129 30 UI in 500 mL of 0.9% NaCl**

1 mIU/minute**

1 or 2 mIU/15 min until regular contractions**

40 mIU/min**

Begum 20136 5 UI in 500 mL of Ringer’s solution or 5% dextrose

Not reported Until regular contractions*

20 mIU/min

Ozturk 201410 5 UI in 500 mL of 0.9% NaCl

1-2 mIU/minute

2 mIU/15 min until regular contractions*

40 mIU/min

Bor 20157 5 UI in 500 mL of Ringer’s solution or 5% dextrose

3.3 mIU/minute

3.3 mIU/20 min until regular contractions*

30 mIU/min

Chopra 20158 Not reported 3 mIU/minute 3.3 mIU/30 min until regular contractions*

42 mIU/min

*Regular contractions, defined as a rate of 3-5 per 10 min **Additional unpublished data kindly provided by the authors of the original trials


Appendix 7. Characteristics of the Included Women Nulliparous* Bishop score at time of

randomization* Cervical ripening used before induction (first method of induction)


Not reported Not reported Not reported

Ustunyurt 200713

114/168 (67.9%) vs 110/174 (63.2%)

Bishop <6: 47/168 (28.0%) vs 50/174 (28.7%)

Not reported

Bahadoran 20105

Not reported 5.7±0.9 vs 5.6±0.8 Not reported

Rashwan 201011

60/100 (60.0%) vs 60/100 (60.0%)

Not reported Not reported

Diven 20129 64/125 (51.2%) vs 63/127 (49.6%)

5 (0-10) vs 5 (0-10) Misoprostol, or Foley balloon in case of unfavorable Bishop score

Begum 20136 100 (50 vs 50) 6.72±0.11 vs 6.50±0.11 Not reported

Ozturk 201410 66/66 (100%) vs 64/64 (100%)

5.5±1.4 vs 5.2±1.7 Not reported

Bor 20157 46/100 (46.0%) vs 45/100 (45.0%)

Not reported 5/100 vs 7/100* Misoprostol, or Foley balloon in case of unfavorable Bishop score

Chopra 20158 26/53 (49.1%) vs 25/53 (49.2%)

Not reported Dinoprostone 0.5 Gel in case of unfavorable Bishop score

*Data are presented as number in the intervention group vs number in the control group, as number (percentage) or as mean ± standard deviation, or as median (range)


Appendix 8. Forest plot for the mean difference in duration of second stage of labor in minutes. SD, standard deviation; IV, independent variable; df, degrees of freedom.


Appendix 9. Forest plot for the risk of abnormal fetal heart rate in labor. M-H, Mantel-Haenszel test; df, degrees of freedom.


Appendix 10. Neonatal Outcomes Birth weight (grams) Admission to NICU APGAR <7 at 5 min Daniel-Spiegel 200412

3391±513 vs 3299±525 Not reported Not reported

Ustunyurt 200713

3289±388 vs 3242±397 12/168 (7.1%) vs 17/174 (9.8%)

4/168 (2.4%) vs 6/174 (3.4%)

Bahadoran 20105

3198±288 vs 3172±266 Not reported Not reported

Rashwan 201011 Not reported 4/100 (4.0%) vs 10/100 (10.0%)

Not reported

Diven 20129 3475 (2715-4650) vs 3475 (2345-4495)*

9/125 (7.2%) vs 10/127 (7.9%)

0/125 vs 1/127 (0.8%)

Begum 20136 3340 vs 3400** 2/50 (4.0%) vs 6/50 (12.0%)

Not reported

Ozturk 201410 Not reported Not reported Not reported

Bor 20157 3705(3347-4000) vs 3600 (3212-4055)

4/100 (4.0%) vs 5/100 (5.0%)

0/100 vs 0/100

Chopra 20158 2870 vs 2850** Not reported Not reported

Total - 31/543 (5.7%) vs 48/551 (8.7%)

4/393 (1.0%) vs 7/401 (1.7%)

I2 0% 0% 0%

RR or MD (95% CI)

44.24 grams (-18.11 to 106.58)

0.67 (0.43 to 1.04) 0.63 (0.20 to 2.01)

MD, mean difference; RR, relative risk; CI, confidence interval; NICU, neonatal intensive care unit Data are presented as number in the intervention group vs number in the control group, as number (percentage) or as mean ± standard deviation, or as median (range) *Median (range) was not included in the meta-analysis **Mean without standard deviation was not included in the meta-analysis


Appendix 11. Forest plot for the risk of cesarean delivery in sensitivity analysis according to the quality of the trials. M-H, Mantel-Haenszel test; df, degrees of freedom.

appendix 1. flow diagram of studies identified in the

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