Study reference

Study characteristics

Patient characteristics ²

Intervention (I)

Comparison / control (C) ³

Follow-up

Outcome measures and effect size ⁴

Comments

Bremerich, 2005

Type of study: RCT

Setting:

Johann Wolfgang Goethe- University Hospital

Country: Germany

Source of funding: not reported

Inclusion criteria:

1. older than 18 years;

2. requesting epidural analgesia;

3. ASA physical status I or II;

4. >37 weeks of gestation;

5. singleton pregnancy;

6. cephalad presentation;

7. conversational fluency in German;

8. minimum cervical dilation before initiation of epidural

analgesia was 3–4 cm with uterine contractions at regular intervals of 2–3 min.

Exclusion criteria:

Common contraindications to epidural analgesia and the need for cesarean section during the study

N total at baseline:

Intervention: 40

Control: 40

Important prognostic factors²:

age (SD):

I: 30 (6)

C:30 (5)

Primiparae (%)

I: 70

C: 52

Groups are comparable at baseline

Describe intervention (treatment/procedure/test):

Initial bolus containing ropivacaine 16 mg and sufentanil 10 µg

4 mL/h plus an hourly maximum of three 4-mL boluses on demand (lock-out time 20 min) of ropivacaine 0.16% plus sufentanil 0.5 µg /mL

Describe control (treatment/procedure/test):

Initial bolus containing ropivacaine 16 mg and sufentanil 10 µg

An hourly maximum of four 4-mL boluses (lock-out time 15 min) of ropivacaine 0.16% plus sufentanil 0.5 µg /mL

Length of follow-up: 48 hours after delivery

Loss-to-follow-up:

Intervention:

7 (17.5%)

Reasons

Cesarean delivery during study

Control:

7 (17.5%)

Reasons

Cesarean delivery during study

Incomplete outcome data:

Intervention: none

Control: none

Outcome measures and effect size (include 95%CI and p-value if available):

Pain (VAS) >40

Measured every 5 min for the first 30 min after catheter insertion, after 60 min and subsequently every hour until delivery

I: 12 (7.5%) of the 161 time points

C: 33 (22.4%) of the 147 time points

P=0.0003

Maximum motor block Bromage 1, n

I: 2

C: 1

No statistically significant difference between groups (p-value not reported)

Adverse events

Nausea, n (n time points)

I: 2 (3)

C: 1 (2)

Pruritus

I: 3 (6)

C: 3(6)

No statistically significant difference between groups (p-value not reported)

Umbilical artery pH, mean (SD)

I: 7.27 (0.07)

C: 7.28 (0.06)

Okutomi, 2009

Type of study: RCT

Setting:

Kitasato University

Country: Japan

Source of funding: not reported

Inclusion criteria: Nulliparous patients undergoing full-term elective induction of labor with a singleton

fetus in the vertex presentation who desired neuraxial

anesthesia for childbirth.

Exclusion criteria:

Cesarean section

N total at baseline:

Intervention: 33

Control: 33

Important prognostic factors²:

age ± SD:

I: 31 (5)

C: 32 (4)

Groups are comparable at baseline

Describe intervention (treatment/procedure/test):

Bupivacaine 2.5 mg with fentanyl 25 µg

Continuous infusion of 6 mL/h with an hourly demand maximum of five 5-mL boluses of 0.1% ropivacaine with fentanyl 2 µg /mL

Describe control (treatment/procedure/test):

Bupivacaine 2.5 mg with fentanyl 25 µg

5-mL demand dose of 0.1% ropivacaine with fentanyl 2 µg /mL with a 10-min lockout interval and a dose limit of 30 mL/h

Length of follow-up: until delivery

Loss-to-follow-up:

none

Incomplete outcome data:

none

Outcome measures and effect size (include 95%CI and p-value if available):

Labour duration (h)

First stage, mean SD

I: 7.2 ± 2.4

C: 8.7 ± 3.0

P<0.05

Second stage, mean SD

I: 2.1 ± 1.5

C: 1.9 ± 1.2

33

No statistically significant difference between groups (p-value not reported)

Mode of delivery (n)

Spontaneous

I: 10

C: 9

Vacuum extraction

I: 17

C: 17

Forceps extraction

I: 6

C:7

Maternal adverse events, n (%)

Hypotension

I: 0 (0%)

C: 0 (0%)

Nausea

I: 0 (0%)

C: 1 (3%)

Pruritus

I: 20 (61%)

C: 24 (73%)

No statistically significant difference between groups (p-value not reported)

Umbilical artery pH, mean (SD)

I: 7.29 ± 0.04

C: 7.28 ± 0.03

Pain was assessed according to the method section, but results were not reported.

Srivastava, 2009

Type of study: RCT

Setting: Research scholar Agra University

Country: India

Source of funding: not reported

Inclusion criteria:

ASA status I and II of mixed parity

who were willing for epidural analgesia during labor, a singleton pregnancy

with vertex presentation, no contraindication

to epidural analgesia and who were able to use

PCA pump.

Exclusion criteria:

N total at baseline:

Intervention: 25

Control: 30

Important prognostic factors²:

age ± SD:

I: 24±5

C: 25±6

Primi/multi

I: 11/14

C: 14/16

Groups are comparable at baseline

Describe intervention (treatment/procedure/test):

Initial bolus dose of

a 10 ml solution containing 0.125% bupivacaine + 2

mcg.ml^-1 of fentanyl

Continuous epidural infusion of above solution at the rate of 10 ml/hr with demand bolus of 3 ml of above solution with lockout interval of 10 minutes with a maximum upper limit of epidural solution of 25ml/ hour

Describe control (treatment/procedure/test):

Initial bolus dose of

a 10 ml solution containing 0.125% bupivacaine + 2

mcg.ml^-1 of fentanyl

8ml bolus of the above solution on demand

with lockout interval of 20 minutes with a maximum upper limit of epidural solution of 25ml/ hour

Length of follow-up: until delivery

Loss-to-follow-up:

None

Incomplete outcome data:

Not described

Outcome measures and effect size (include 95%CI and p-value if available):

Duration of labour (minutes), mean SD

I: 342±91

C: 349±78

Vaginal/caesarean delivery, mean SD

I: 21/4

C: 24/6

Pain

Mean VAS during labour, mean SD

I: 1.89±1.03

C: 1.96±1.08

p=0.32

Highest VAS, median (range)

I: 5 (0 – 7)

C: 6 (0 – 6)

p<0.05

Rescue boluses, n patients

I: 2 (8%)

C: 8 (27%)

P<0.05

Paech, 1992

Type of study: RCT

Setting: King Edward Memorial Hospital for Woman, Perth

Country: Australia

Source of funding: non-commercial

Inclusion criteria: Women at term with a singleton cephalic fetus, no major medical or obstetric complications and in established labour were enrolled.

Exclusion criteria:

Women delivering within two hours of attaching the PCA pump

N total at baseline:

Intervention: 26

Control: 26

Important prognostic factors²:

age ± SD:

I: 26±6

C: 28±4

Primiparity,n (%):

I: 18 (72%)

C: 17 (68%)

Groups comparable at baseline? Yes

Describe intervention (treatment/procedure/test):

Epidural solution of 10 ml bolus of 0.125% bupivacaine (12.5 mg) containing fentanyl 5 mcg per ml. Allowance was made for an additional 4 ml bolus of 0.5% bupivacaine (20 mg).

PCEA

4 ml incremental bolus dose on demand of 0.125% plain bupivacaine plus fentanyl 3 mcg per ml (62.5 mg of bupivacaine and 150 mcg of fentanyl diluted to 50 ml with normal saline) with a lockout interval of 15 minutes.

CI

4 ml continuous infusion

Describe control (treatment/procedure/test):

Epidural solution of 10 ml bolus of 0.125% bupivacaine (12.5 mg) containing fentanyl 5 mcg per ml. Allowance was made for an additional 4 ml bolus of 0.5% bupivacaine (20 mg).

PCEA

4 ml incremental bolus dose on demand of 0.125% plain bupivacaine plus fentanyl 3 mcg per ml (62.5 mg of bupivacaine and 150 mcg of fentanyl diluted to 50 ml with normal saline) with a lockout interval of 15 minutes.

Length of follow-up: within 24 hours after delivery

Loss-to-follow-up:

Intervention:

None

Control:

None

Incomplete outcome data:

Intervention:

2 (4%)

Reasons:

1 woman delivered within two hours of attaching the PCA pump, 1 woman was included in analysis until the time of her withdrawal due to cephalad sensory block exceeding T6.

Control:

1 (2%)

Reasons:

1 woman delivered within two hours of attaching the PCA pump

Outcome measures and effect size (include 95%CI and p-value if available):

Pain score

 (0-100), median (range)

I: 7 (0-86)

C: 11 (0-77)

Satisfaction with pain relief During the first stage (Excellent/ good/ fair/ unsatisfactory)

I: 20/ 4/ 1/ 0

C: 18/ 7/ 0/ 0

During the expulsion phase (Excellent/ good/ fair/ unsatisfactory)

I: 6/ 6/ 2/ 2

C: 5/ 10/ 3/ 1

(no significant differences between groups, p-value not reported)

Mode of delivery (n)

Spontaneous

I: 7/ 25

C: 10/ 25

Instrumental

I: 13/ 25

C: 9/ 25

Caesarean

I: 5/ 25

C:6/ 25

Duration of labour (hour), mean SD

I: 5.6 (2.2)

C: 5.8 (2.6)

Maternal adverse events, n (%)

Hypotension:

I: 4/ 25

C: 2/ 25

Pruritus

I: 4/ 25

C: 5/ 25

Grade 2/3 motor block

I: 8/ 25

C: 9/ 25

(no significant differences between groups, p-value not reported)

Staff administered boluses, n patients

I: 7 (28%)

C: 10 (40%)

P<0.55

Petry, 2000

Type of study: RCT

Setting: University hospital Antwerp

Country: Belgium

Source of funding: not reported

Inclusion criteria: parturients requesting epidural analgesia during labor.

Exclusion criteria: Those presenting with cervical dilatation exceeding 5cm (for which intrathecal analgesia was selected) or those scheduled for trial of labor were excluded.

N total at baseline:

Intervention: 40

Control: 40

Important prognostic factors²:

Groups comparable at baseline? Yes

Describe intervention (treatment/procedure/test):

A 10 ml loading dose consisting of bupicacaine 0.125% with sufentanil 0.75 µg/ml and epinephrine 1/800.000 was administered without a test does. If after 10 minutes initial VAS scores (0-10) were not below 2 or were not reduced by 50%, additional increments of 2 ml of the same mixture were administerd.

PCEA

3 ml (of the same mixture as described above) with a lock-out time of 12 minutes and a 1 hour limit of 10 ml.

CI:

Basal rate of 3 ml/h.

Describe control (treatment/procedure/test):

A 10 ml loading dose consisting of bupicacaine 0.125% with sufentanil 0.75 µg/ml and epinephrine 1/800.000 was administered without a test does. If after 10 minutes initial VAS scores (0-10) were not below 2 or were not reduced by 50%, additional increments of 2 ml of the same mixture were administerd.

PCEA

3 ml (of the same mixture as described above) with a lock-out time of 12 minutes and a 1 hour limit of 10 ml.

Length of follow-up:

Until delivery

Loss-to-follow-up:

Intervention:

None

Control:

None

Incomplete outcome data:

Intervention:

3 (7.5%)

Reasons

2 patients delivered within the first hour after epidural catheter placement, 1 patient was not considered for statistical analysis because of technicalpump problems.

Control:

3 (7.5%)

Reasons

2 patients delivered within the first hour after epidural catheter placement, 1 patient was not considered for statistical analysis because of technicalpump problems.

Outcome measures and effect size (include 95%CI and p-value if available):

Pain score (VAS) 2^nd stage

I: 2.4 (SD 0.4)

C: 2.9 (SD 0.5)

Mode of delivery (n)

Instrumental

I: 3/ 37

C: 1/ 37

Caesarean

I: 1/ 37

C:1/ 37

Maternal adverse events, n (%)

Hypotension:

I: 0

C: 0

Pruritus

I: 12/ 37

C: 10/ 37

Motor block, defined as difficulty to flex knee

I: 2/ 37

C: 1/ 37

Apgarscores

All neonates had Apgarscores equal to or exceeding ≥9 at five minutes.

Rescue boluses, n patients

I: 1

C: 1

Study reference

Study characteristics

Patient characteristics

Intervention (I)

Comparison / control (C)

Follow-up

Outcome measures and effect size

Comments

Heesen,

2015

(individual study characteristics deduced from Heesen,

2015 (unless stated otherwise))

SR and meta-analysis of (RCTs / cohort / case-control studies)

Literature search up to November 1, 2014

A: Ferrante, 1994

B: Boselli, 2004

C: Missant, 2005

D: Vallejo, 2007

E: Lim, 2008

F: Brogly, 2011

G: Haydon, 2011

Study design: RCT

Setting and Country: Germany

Source of funding:

non-commercial

Inclusion criteria SR:

RCTs comparing PCEA combined with a continuous (basal) infusion with PCEA-only with:

1. adequate method of randomization

2. blinding of patient and outcome assessor

3. at least 6 of the 12 domains assessed to determine the methodological study quality had to be scored as “yes.”

7 studies included

Important patient characteristics at baseline:

N (I/C)

A: 30/15

B: 99/34

C: 40/38

D: 64/63

E: 200/100

F: 20/17

G: 87/84

According to the authors groups were similar at baseline for all included studies, except for Vallejo 2007.

The following information was deducted from Vallejo 2007:

There was a significant difference (p=0.03) in age different between the groups.

Mean age (SD):

I1 (CI) 27.8 (5.7)

I2 (CI+PCEA): 29.6 (6.6)

C (PCEA): 28.7 (5.6)

Describe intervention:

A: Epidural solution: Bupivacaine 0.125% + 2 μg/mL fentanyl;

Basal infusion: 12 mL/h (CI only); 3 mL/h (PCEA); 6 mL/h (PCEA)

PCEA: bolus 3 mL, lock-out time 10 min

B: Epidural solution: Ropivacaine 0.1% + sufentanil 0.5 μg/mL

Initial bolus: 12 mL

Basal infusion: 3, 6 and 9 mL/h

PCEA: bolus 5 mL lock-out time 5 min, dose limit 22 mL/h

C: Epidural solution: Ropivacaine 0.15% + sufentanil 0.75 μg/mL

Basal infusion: 2 mL/h

D: Epidural solution: Bupivacaine 0.1% + fentanyl 2 μg/mL

Initial bolus: 10 mL

Bupivacaine 0.1% + fentanyl 100 μg

Basal infusion: 0.5 mL/h

PCEA: bolus 5 mL, lock-out time 20 min

E: Epidural solution: Ropivacaine 0.1% + fentanyl 2 μg/mL

Basal infusion: 5 or 10 mL/h

PCEA: bolus 5 mL,

lock-out time 12 or 10

min, maximal dose 20 mL/h

F: Epidural solution:

Levobupivacaine 0.125% + fentanyl 1.5 μg/mL

Initial bolus: 10 mL

Basal infusion: 10 mL/h

PCEA: bolus 10 mL, lock-out time 20 min

G: Epidural solution: Bupivacaine 0.1% + fentanyl 2 μg/mL

Basal infusion:

10 mL/h

PCEA: bolus 10 mL, lock-out time 20 min

Describe control:

A: Epidural solution: Bupivacaine 0.125% + 2 μg/mL fentanyl;

PCEA: bolus 3 mL, lock-out time 10 min

B: Epidural solution: Ropivacaine 0.1% + sufentanil 0.5 μg/mL

Initial bolus: 12 mL

PCEA: bolus 5 mL lock-out time 5 min, dose limit 22 mL/h

C: Epidural solution: Ropivacaine 0.15% + sufentanil 0.75 μg/mL

PCEA: bolus 4 mL, lock-out time 15 min

D: Epidural solution: Bupivacaine 0.1% + fentanyl 2 μg/mL

Initial bolus: 10 mL

Bupivacaine 0.1% + fentanyl 100 μg

PCEA: bolus 5 mL, lock-out time 15 min

E: Epidural solution: Ropivacaine 0.1% + fentanyl 2 μg/mL

PCEA: bolus 5 mL,

lock-out time 15 min, maximal dose 20 mL/h

F: Epidural solution:

Levobupivacaine 0.125% + fentanyl 1.5 μg/mL

Initial bolus: 10 mL

PCEA: bolus 10 mL, lock-out time 20 min

G: Epidural solution: Bupivacaine 0.1% + fentanyl 2 μg/mL

PCEA: bolus 10 mL, lock-out time 20 min

End-point of follow-up:

A: not reported

B: 2 hours after delivery

C: not reported

D: removal of the epidural

E: 24 hours after delivery

F: 24 hours after delivery

G: after delivery

For how many participants were no complete outcome data available?

(intervention/control)

Not reported.

Outcome measure-1

Defined as rate of instrumental deliveries

Effect measure: RR (95% CI):

A: 1.50 (0.17, 13.23)

B: 1.20 (0.42, 3.40)

C: 1.90 (0.51, 7.06)

D: 0.98 (0.21, 4.69)

E: 1.80 (0.93, 3.48)

F: 3.40 (0.42, 27.59)

G: 1.93 (0.60, 6.17)

Pooled effect (random effects model):

1.66 (95% CI 1.88 to 2.56) favoring PCEA without CI

Heterogeneity (I²): 0%

Outcome measure-2

Defined as rate of caesarean deliveries

Effect measure: RR (95% CI):

A: 1.50 (0.17, 13.23)

B: 1.03 (0.30, 3.59)

C: 0.47 (0.09, 2.44)

D: 0.98 (0.42, 2.32)

E: 0.68 (0.40, 1.14)

F: 0.28 (0.07, 1.22)

G: 1.05 (0.64, 1.73)

Pooled effect (random effects model):

0.83 (95% CI 0.61 to 1.13) favoring PCEA with CI

Heterogeneity (I²): 0%

Outcome measure-3

Defined as rate of spontaneous vaginal deliveries

Effect measure: RR (95% CI):

A: 0.92 (0.71, 1.21)

B: 0.97 (0.79, 1.18)

C: 0.98 (0.79, 1.22)

D: 1.00 (0.85, 1.19)

E: 0.98 (0.83, 1.15)

F: 1.19 (0.73, 1.94)

G: 0.90 (0.72, 1.12)

Pooled effect (random effects model):

0.97 (95% CI 0.90 to 1.05) favoring PCEA with CI

Heterogeneity (I²): 0%

Outcome measure-4

Defined as duration of labour

Overall duration

Effect measure: weighted mean difference (minutes) (95% CI):

A: -19.00 (-62.18, 24.18)

B: 23.00 (-17.53, 63.53)

C: -50.00 (-125.32, 25.32)

D: 15.00 (-48.29, 78.29)

E: 5.00 (-37.20, 47.20)

F: 30.00 (-71.14, 131.14)

G: 12.00 (-54.72, 78.72)

Pooled effect (random effects model):

2.92 (95% CI -17.26 to 23.11) favoring PCEA without CI

Heterogeneity (I²): 0%

Duration of the first stage

Effect measure: weighted mean difference (minutes) (95% CI):

A: -45.00 (-61.49, -28.51)

B: 28.00 (-5.69, 61.69)

D: 4.00 (-51.39, 59.39)

Pooled effect (random effects model):

-6.47 (95% CI -59.89 to 46.96) favoring PCEA with CI

Heterogeneity (I²): 87%

Duration of the second stage

Effect measure: weighted mean difference (minutes) (95% CI):

A: 6.00 (-6.77, 18.77)

B: 20.00 (0.46, 39.54)

D: 10.00 (-5.15, 25.15)

E: 17.00 (4.15, 29.85)

Pooled effect (random effects model):

12.30 (95% CI 5.07 to 19.52) favoring PCEA with CI

Heterogeneity (I²): 0%

Outcome measure-5

Defined as maternal adverse events

Nausea (B, E)*:

B: I: 8/ C: 3

E: I: 26/ C: 7

Pooled effect (random effects model):

RR 0.80 (95% CI 0.31 to 2.10) favoring PCEA with CI, I²=0%

Pruritus (B, E):

B: I: 21 C: 9

E: I: 79/ C: 38

Pooled effect (random effects model):

RR 1.00 (95% CI 0.75 to 1.31), I²=0%

Hypotension (E):

E: I: 4/ C: 3

Outcome measure-6

Defined as neonatal outcome parameters

Umbilical arterial pH (C)*, mean:

I: 7.27 (SD 0.06)

C: 7.25 (SD 0.07)

Number of infants with Apgarscore <7 at 5 min (B)*:

I: 2

C: 1

Outcome measure-7

Defined as patients with no motor weakness (A, B, C)

Only pooled estimate reported:

RR 0.98 (95% CI 0.92 to 1.06) favoring PCEA with CI

The following outcomes (not pooled) were only described qualitatively in the SR due to heterogeneity among studies regarding timing of and assessment of different outcomes. Quantitative data were deducted from individual studies.

Outcome measure-8

Defined as pain (I/C)*

No differences in VAS

pain scores between the 2 treatment arms were seen in 5

studies (A, B, C, D, F).

A: VAS at 1 h, median (range) (I1 (CI+demand dose 3 mL/h)/ I2 (CI+demand dose 6 mL/h)/ C)

1 (0-7) / 1 (0.1-3.4) / 0.5 (0-1.5), no significant differences (p-value not reported)

B: Verbal Pain Score, mean

(I1 (3 mL/h)/ I2 (6 mL/h)/ I3 (9 mL/ h) / C)

Time 30 minutes: 3.2/ 2.7/ 2.6/ 2.0

Time 1 h: 1.8/ 1.7/ 1.3/ 1.1

No significant differences exist (p-value not reported)

C: VAS ^ꝉ

Time 15: 1.3/ 1.2

Time 30: 1.6/ 1.0

Time 60: 1.1/ 1.1

No significant differences exist (p-value not reported)

D: median VAS (max)

Time 15: 1 (7.9)/ 1 (7.9)

E: maximum VAS, median (range) (I1 (5 mL/h)/ I2 (10 mL/h)/ C

2.0 (0-10)/ 0 (0-10)/ 3.5 (0-10) (p<0.01)

F: Verbal Rating Scale, mean (SD) (

Time 30 minutes: 2.0 (2.4)/ 2.8 (2.7) (p=0.39)

G: median VAS (range)

Pain after delivery: 0 (0-10)/ 0 (0-5) (p=0.65)

Outcome measure-9

Defined as rate of patients requiring physician-delivered boluses (unless stated otherwise)

Effect measure: RR (95% CI):

A: Mean (SEM) initial physician-administered bolus:

I (3): 48.3 (1.5)/ I (6): 44.3 (1.7)/ C: 54.3 (1.7), p<0.004^¥

B: One or two supplemental boluses, n (%)

First stage of labor:

I: 16 (16%)/ C: 5 (15%), p=0.979

Second stage of labor:

I: 4 (4%)/ C: 1 (3%)^¥

C: 0.35 (0.20, 0.62)

D: Staff interventions (n) median (range) (I/C) 0 (0-8)/ 0 (0-6), p=0.57^¥

E: 0.33 (0.22, 0.49)

F: 0.57 (0.11, 3.01)

G: 0.40 (0.15, 1.09)

Pooled effect (random effects model):

0.35 (95% CI 0.25 to 1.09) favoring PCEA with CI

Heterogeneity (I²): 0%

Outcome measure-10*

Defined as maternal satisfaction (B, C, D, E, F, G) (I/C)

No trial reported a difference between the treatment arms.

B: mean VAS (95% CI) (I1 (3 mL/h)/ I2 (6 mL/h)/ I3 (9 mL/ h) / C)

9(9-10)/ 10(9-10)/ 9(9-10)/ 9(9-10), no significant differences (p-value not reported)

C: median VAS

9.1/ 8.7

no significant differences (p-value not reported)

D: mean VAS (range)

10 (3-10)/ 10 (5-10) (p=0.30)

E: Verbal Rating Scale, median (range) (I1 (5 mL/h)/ I2 (10 mL/h)/ C (PCEA)

9 (5-10)/ 9 (6-10)/ 9 (5-10), (p=0.06)

F: VAS 10(8-10)/ 10(7-10)^ꝉ (p=0.11)

G: median (0 best – 100 worst) 0/ 0 (p=0.23)

*Data derived from individual study

^ꝉ not specified which values were reported

^¥ No absolute numbers for the total duration of delivery were reported, therefore data of these studies were not included in the pooled analysis.

Facultative:

Author’s conclusion: On the basis of current evidence, no conclusion can be drawn regarding the risks or benefits of adding a continuous background infusion to PCEA compared with PCEA-only epidural labor analgesia.

Other comments:

The authors sometimes referred incorrectly. This was adjusted if noticed;

Nausea and pruritus: Heesen incorrectly referred to F and an excluded study (Bremerich 2005) instead of B and E.

Hypotension: Heesen incorrectly referred to F instead of E

Umbilical arterial pH: Heesen incorrectly referred to A instead of C

Number of infants with Apgarscore <7 at 5 min: Heesen incorrectly referred to an excluded study (Bremerich 2005) instead of B.

Level of evidence: not reported in SR.

Study reference

(first author, publication year)

Describe method of randomisation¹

Bias due to inadequate concealment of allocation?²

(unlikely/likely/unclear)

Bias due to inadequate blinding of participants to treatment allocation?³

(unlikely/likely/unclear)

Bias due to inadequate blinding of care providers to treatment allocation?³

(unlikely/likely/unclear)

Bias due to inadequate blinding of outcome assessors to treatment allocation?³

(unlikely/likely/unclear)

Bias due to selective outcome reporting on basis of the results?⁴

(unlikely/likely/unclear)

Bias due to loss to follow-up?⁵

(unlikely/likely/unclear)

Bias due to violation of

intention to treat analysis?⁶

(unlikely/likely/unclear)

Bremerich 2005

Closed opaque

envelope allocation

Unlikely

Unlikely

Likely

Likely

Unlikely

Unlikely

Unlikely

Okutomi 2009

Not descibed

Unclear

Unlikely

Unclear

Unlikely

Unlikely

Unlikely

Unlikely

Srivastava 2009

Computer generated randomization

Unclear

Unclear

Likely

Likely

Unlikely

Unlikely

Unlikely

Paech 1992

Computer-derived random number sequence

Unclear

Unlikely

Likely

Likely

Unlikely

Unlikely

Unlikely

Petry 2000

Not described

Unclear

Likely

Likely

Likely

Unlikely

Unlikely

Likely

Study

First author, year

Appropriate and clearly focused question?¹

Yes/no/unclear

Comprehensive and systematic literature search?²

Yes/no/unclear

Description of included and excluded studies?³

Yes/no/unclear

Description of relevant characteristics of included studies?⁴

Yes/no/unclear

Appropriate adjustment for potential confounders in observational studies?⁵

Yes/no/unclear/not applicable

Assessment of scientific quality of included studies?⁶

Yes/no/unclear

Enough similarities between studies to make combining them reasonable?⁷

Yes/no/unclear

Potential risk of publication bias taken into account?⁸

Yes/no/unclear

Potential conflicts of interest reported?⁹

Yes/no/unclear

Heesen 2015

Yes

Yes

Yes

No, patient characteristics were not described

Not applicable

Yes

Yes

Unclear, source of funding for the included studies was not reported