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Flow diagram of the review process from our initial search to the final inclusion of studies
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Figure 1

Flow diagram of the review process from our initial search to the final inclusion of studies

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Methodological quality summary: review authors' judgements about each methodological quality item for each included study.
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Figure 2

Methodological quality summary: review authors' judgements about each methodological quality item for each included study.

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Methodological quality graph: review authors' judgements about each methodological quality item presented as percentages across all included studies.
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Figure 3

Methodological quality graph: review authors' judgements about each methodological quality item presented as percentages across all included studies.

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Forest plot of comparison: 1 Co‐bedding vs separate care, outcome: 1.1 Rate of weight gain (in gram/kg of baseline weight/day).
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Figure 4

Forest plot of comparison: 1 Co‐bedding vs separate care, outcome: 1.1 Rate of weight gain (in gram/kg of baseline weight/day).

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Forest plot of comparison: 1 Co‐bedding vs separate care, outcome: 1.6 Neurobehaviour: infant pain score following painful procedure.
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Figure 5

Forest plot of comparison: 1 Co‐bedding vs separate care, outcome: 1.6 Neurobehaviour: infant pain score following painful procedure.

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Forest plot of comparison: 1 Co‐bedding vs separate care, outcome: 1.7 Infections.
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Figure 6

Forest plot of comparison: 1 Co‐bedding vs separate care, outcome: 1.7 Infections.

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Comparison 1 Co‐bedding vs standard care, Outcome 1 Rate of weight gain (in gram/kg of baseline weight/day).
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Analysis 1.1

Comparison 1 Co‐bedding vs standard care, Outcome 1 Rate of weight gain (in gram/kg of baseline weight/day).

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Comparison 1 Co‐bedding vs standard care, Outcome 2 Apnoea, bradycardia or desaturation.
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Analysis 1.2

Comparison 1 Co‐bedding vs standard care, Outcome 2 Apnoea, bradycardia or desaturation.

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Comparison 1 Co‐bedding vs standard care, Outcome 3 Episodes in coregulated state (out of 20 observations).
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Analysis 1.3

Comparison 1 Co‐bedding vs standard care, Outcome 3 Episodes in coregulated state (out of 20 observations).

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Comparison 1 Co‐bedding vs standard care, Outcome 4 Episodes of crying (out of 20 observations).
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Analysis 1.4

Comparison 1 Co‐bedding vs standard care, Outcome 4 Episodes of crying (out of 20 observations).

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Comparison 1 Co‐bedding vs standard care, Outcome 5 Episodes in quiet sleep (out of 20 observations).
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Analysis 1.5

Comparison 1 Co‐bedding vs standard care, Outcome 5 Episodes in quiet sleep (out of 20 observations).

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Comparison 1 Co‐bedding vs standard care, Outcome 6 Neurobehaviour: infant pain score following painful procedure.
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Analysis 1.6

Comparison 1 Co‐bedding vs standard care, Outcome 6 Neurobehaviour: infant pain score following painful procedure.

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Comparison 1 Co‐bedding vs standard care, Outcome 7 Infections.
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Analysis 1.7

Comparison 1 Co‐bedding vs standard care, Outcome 7 Infections.

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Comparison 1 Co‐bedding vs standard care, Outcome 8 Length of hospital stay (Days).
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Analysis 1.8

Comparison 1 Co‐bedding vs standard care, Outcome 8 Length of hospital stay (Days).

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Comparison 1 Co‐bedding vs standard care, Outcome 9 Parental anxiety (Parental State Anxiety Inventory).
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Analysis 1.9

Comparison 1 Co‐bedding vs standard care, Outcome 9 Parental anxiety (Parental State Anxiety Inventory).

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Comparison 1 Co‐bedding vs standard care, Outcome 10 Parental attachment (Maternal Attachment Inventory).
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Analysis 1.10

Comparison 1 Co‐bedding vs standard care, Outcome 10 Parental attachment (Maternal Attachment Inventory).

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Comparison 1 Co‐bedding vs standard care, Outcome 11 Parental satisfaction.
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Analysis 1.11

Comparison 1 Co‐bedding vs standard care, Outcome 11 Parental satisfaction.

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Summary of findings for the main comparison. Co‐bedding compared to separate care for promoting growth and neurodevelopment in stable preterm twins

Co‐bedding compared to separate care for promoting growth and neurodevelopment in stable preterm twins

Patient or population: patients with promoting growth and neurodevelopment in stable preterm twins
Settings:
Intervention: Co‐bedding
Comparison: separate care

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No of Participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

Separate care

Co‐bedding

Rate of weight gain (in gram/kg of baseline weight/day) ‐ Average from study entry to week three
Grams per kilogram per day
Follow‐up: 7 weeks

The mean rate of weight gain (in gram/kg of baseline weight/day) ‐ average from study entry to week three in the control groups was
13.7 grams per kilogram per day

The mean rate of weight gain (in gram/kg of baseline weight/day) ‐ average from study entry to week three in the intervention groups was
0.2 higher
(1.6 lower to 2 higher)

18
(1 study)

⊕⊕⊝⊝
low1,2

Apnoea, bradycardia or desaturation
Number of twins with the episodes
Follow‐up: 10 days

Study population

RR 0.85
(0.18 to 4.05)

124
(1 study)

⊕⊕⊝⊝
low2,3

53 per 1000

45 per 1000
(9 to 213)

Moderate

53 per 1000

45 per 1000
(10 to 215)

Episodes in coregulated state (out of 20 observations)
Episodes observed (out of a total of 20 observations).

Scale from: 0 to 20.
Follow‐up: 2 months

The mean episodes in coregulated state (out of 20 observations) in the control groups was
13.94 episodes

The mean episodes in coregulated state (out of 20 observations) in the intervention groups was
0.96 higher
(3.44 lower to 5.36 higher)

6
(1 study)

⊕⊝⊝⊝
very low2,4

Neurobehaviour: infant pain score following painful procedure ‐ At 90 seconds post heel lance
Premature Infant Pain Profile (PIPP). Scale from: 0 to 21.
Follow‐up: 10 days

The mean PIPP score following painful procedure at 90 seconds post heel lance in the control groups was
5 points (out of 21)

The mean PIPP score following painful procedure at 90 seconds post heel lance in the intervention groups was
1 higher
(0.14 to 1.86 higher)

124
(1 study)

⊕⊕⊕⊕
high

Infections ‐ Suspected or proven infections (any)
Clinical and microbiological methods
Follow‐up: 2 months

Study population

RR 0.84
(0.3 to 2.31)

65
(3 studies)

⊕⊕⊝⊝
low1,2,4

182 per 1000

153 per 1000
(55 to 420)

Moderate

100 per 1000

84 per 1000
(30 to 231)

Length of hospital stay (Days)
Follow‐up: mean 2 months

The mean length of hospital stay (days) in the control groups was
52.7 days

The mean length of hospital stay (days) in the intervention groups was
4.9 lower
(35.23 lower to 25.43 higher)

6
(1 study)

⊕⊝⊝⊝
very low2,4

Parental satisfaction
Parental Satisfaction Survey. Scale from: 0 to 55
Follow‐up: 5 days

The mean parental satisfaction in the control groups was
51.13 points (out of 55)

The mean parental satisfaction in the intervention groups was
0.38 lower
(4.49 lower to 3.73 higher)

18
(1 study)

⊕⊕⊕⊝
moderate5

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval; RR: Risk ratio;

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

1 Unclear method of sequence generation, non‐blinding and selective outcome reporting present
2 Wide 95% confidence intervals
3 The study assessed specifically A/B/D episodes after a painful procedure in the form of a heel lance
4 A pilot study which was non‐blinded with high risk of bias for incomplete outcome data and selective outcome reporting,
5 Unclear sequence generation and allocation concealment, non‐blinded.

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Summary of findings for the main comparison. Co‐bedding compared to separate care for promoting growth and neurodevelopment in stable preterm twins
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Table 1. Matrix on outcome reporting by each study

Study ID

Outcomes listed in the methods

Additional key outcomes relevant to the study

Actual outcomes reported

Byers 2003a

1. Physiological measures including heart rate, respiratory rate and oxygen saturation.

2. Sleep‐wake synchrony.

3. Neuro behavioural observations using the Newborn Individualised Developmental Care and Assessment Programme (NIDCAP) guidelines.

4. Complicatons such as infections, intraventricular haemorrhage and patent ductus arteriosus.

5. Parental measures including anxiety, attachment and satisfaction.

This is a study that assessed specifically physiological measures in the short term. Growth parameters were reported, but as "mean daily weight", which was not suitable for meta‐analysis. Additionally, the physiological measures were reported in the form of average figures, such as the average "highest activity heart rate" and not the episodes of apnoea, bradycardia or desaturation which are more clinically relevant.

1. Physiological measures including heart rate, respiratory rate and oxygen saturation.

2. Sleep‐wake synchrony was reported narratively and only ranges were given in the paper

3. Neurobehavioural observations using the Newborn Individualised Developmental Care and Assessment Programme (NIDCAP) guidelines.

4. Complicatons such as care giver errors, intraventricular haemorrhage and patent ductus arteriosus.

5. Parental measures including anxiety, attachment and satisfaction.

6. Mean daily weight

Campbell‐Yeo 2012b

1. Pain response measured by the Premature Infant Pain Profile (PIPP).

2. Time for physiologic recovery in response to heel lance determined by the length of time for heart rate and oxygen saturation to return to baseline.

3. Need for additional pain relieve using 24% sucrose.

4. Adverse outcomes such as episodes of apnoea, bradycardia, infection and caregiver error.

This is a study that assessed specifically infants' response to pain, and growth‐related outcomes such as weight gain and length of hospital stay were not included in the outcomes. The only outcome that was relevant to this review was the pain response, which we considered as a form of neurobehaviour.

1. Pain response measured by the Premature Infant Pain Profile (PIPP).

2. Time for physiologic recovery in response to heel lance determined by the length of time for heart rate and oxygen saturation to return to baseline.

3. Need for additional pain relieve using 24% sucrose.

4. Adverse outcomes such as episodes of apnoea, bradycardia, infection and caregiver error.

Chin 2006

1. Weight gain

2. Apnoea/bradycardia/desaturation (A/B/D) episodes

3. Infections, including sepsis (positive blood culture), necrotising enterocolitis (clinical and radiological diagnosis) or conjunctivitis (positive eye culture)

1. Rate of weight gain

2. Length of hospital stay

3. Medication error

1. Weight

2. A/B/D episodes

3. Infections, including sepsis, necrotising enterocolitis or conjunctivitis

4. Medication error

Hayward 2007

1. Parental self efficacy (measured using the Infant Care Survey) and parental anxiety (measured using the Speilberger State‐Trait‐Anxiety Inventory) upon entry to the study, before discharge, and at 1‐month postdischarge

2. Coregulatory behaviour (measured using the Nursing Child Assessment Sleep/Activity Record which included the assessment of synchrony of infant state (e.g. in quiet sleep, alert or crying), heart rate, temperature, respirations, and oxygen saturation.

3. Infection rate ("incidence of septic workup, treatment with antibiotics, and confirmed incidence of sepsis")

4. Caregiver error

1. Length of hospital stay

2. Weight gain

3. Apnoea, bradycardia or desaturation episodes

1. Time in quiet sleep and crying

2. Time coregulated

3. Infection rate

4. Caregiver error

5. Length of hospital stay (as part of descriptive characteristics and not part of the results)

(The authors stated that "Data were insufficient to analyse
parental self‐efficacy and parental
stress"‐ Results, paragraph 1, lines 1‐3)

Lutes 2001

No outcome was listed in the Methods. However, there were three major outcomes stated in the Purpose and Hypotheses, as follows:

1. Weight gain

2. Head circumference growth

3. Longitudinal growth/length gain

1. Length of hospital stay

2. Apnoea, bradycardia or desaturation episodes

3. Infections

4. Medication error

1. Weekly weight gain

2. "Weekly mean kilocalories per kilogram"

3. Weekly head circumference growth

4. Weekly length growth

5. Medication error

6. Nosocomial infection

7. Sepsis work‐ups initiated

8. Thermal insults
Figuras y tablas -
Table 1. Matrix on outcome reporting by each study
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Table 2. Median combined apnoea, bradycardia and desaturation (A/B/D) episodes

Study ID

Study period

Median combined A/B/D episodes

P value

Co‐bedded group

Control group

Chin 2006

Week one

4.5

7

0.2

Week two

6

12

0.8

Week three

2.5

8

0.4
Figuras y tablas -
Table 2. Median combined apnoea, bradycardia and desaturation (A/B/D) episodes
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Comparison 1. Co‐bedding vs standard care

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Rate of weight gain (in gram/kg of baseline weight/day) Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

1.1 From study entry to week one

1

38

Mean Difference (IV, Fixed, 95% CI)

4.0 [‐0.96, 8.96]

1.2 From week one to week two

1

28

Mean Difference (IV, Fixed, 95% CI)

1.40 [‐2.27, 5.07]

1.3 From week two to week three

1

18

Mean Difference (IV, Fixed, 95% CI)

‐2.10 [‐4.33, 0.13]

1.4 Average from study entry to week three

1

18

Mean Difference (IV, Fixed, 95% CI)

0.20 [‐1.60, 2.00]

2 Apnoea, bradycardia or desaturation Show forest plot

1

124

Risk Ratio (M‐H, Fixed, 95% CI)

0.85 [0.18, 4.05]

3 Episodes in coregulated state (out of 20 observations) Show forest plot

1

6

Mean Difference (IV, Fixed, 95% CI)

0.96 [‐3.44, 5.36]

4 Episodes of crying (out of 20 observations) Show forest plot

1

6

Mean Difference (IV, Fixed, 95% CI)

4.43 [1.72, 7.14]

5 Episodes in quiet sleep (out of 20 observations) Show forest plot

1

6

Mean Difference (IV, Fixed, 95% CI)

4.58 [1.58, 7.58]

6 Neurobehaviour: infant pain score following painful procedure Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

6.1 At 30 seconds post heel lance

1

124

Mean Difference (IV, Fixed, 95% CI)

‐0.10 [‐1.21, 1.01]

6.2 At 90 seconds post heel lance

1

124

Mean Difference (IV, Fixed, 95% CI)

1.0 [0.14, 1.86]

7 Infections Show forest plot

3

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

7.1 Suspected or proven infections (any)

3

65

Risk Ratio (M‐H, Fixed, 95% CI)

0.84 [0.30, 2.31]

7.2 Necrotising enterocolitis

1

41

Risk Ratio (M‐H, Fixed, 95% CI)

1.90 [0.19, 19.40]

7.3 Conjunctivitis

1

41

Risk Ratio (M‐H, Fixed, 95% CI)

0.95 [0.15, 6.13]

7.4 Sepsis

2

59

Risk Ratio (M‐H, Fixed, 95% CI)

0.45 [0.07, 2.86]

8 Length of hospital stay (Days) Show forest plot

1

6

Mean Difference (IV, Fixed, 95% CI)

‐4.90 [‐35.23, 25.43]

9 Parental anxiety (Parental State Anxiety Inventory) Show forest plot

1

18

Mean Difference (IV, Fixed, 95% CI)

0.90 [‐2.13, 3.93]

10 Parental attachment (Maternal Attachment Inventory) Show forest plot

1

18

Mean Difference (IV, Fixed, 95% CI)

0.90 [‐2.02, 3.82]

11 Parental satisfaction Show forest plot

1

18

Mean Difference (IV, Fixed, 95% CI)

‐0.38 [‐4.49, 3.73]
Figuras y tablas -
Comparison 1. Co‐bedding vs standard care
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