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

Flow diagram of the review process from initial search to 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/d).
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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/d).

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Forest plot of comparison: 1 Co‐bedding vs separate care, outcome: 1.6 Neurobehavior: 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 Neurobehavior: 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/d).
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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/d).

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

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

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

Comparison 1 Co‐bedding vs standard care, Outcome 3 Episodes in co‐regulated 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 Neurobehavior: infant pain score following painful procedure.
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Analysis 1.6

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

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

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

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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 versus separate care for promoting growth and neurodevelopment in stable preterm twins

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

Patient or population: stable preterm twins with growth and neurodevelopment promoted
Settings: neonatal nursery at the hospital
Intervention: co‐bedding
Comparison: separate care

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

Number of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

Separate care

Co‐bedding

Rate of weight gain (in grams/kg of baseline weight/d) ‐ average from study entry to week 3
Grams per kilogram per day
Follow‐up: 7 weeks

Mean rate of weight gain (in grams/kg of baseline weight/d) ‐ average from study entry to week 3 in control groups was
13.7 grams per kilogram per day

Mean rate of weight gain (in grams/kg of baseline weight/d) ‐ average from study entry to week 3 in intervention groups was
0.2 higher
(1.6 lower to 2 higher)

18
(1 study)

⊕⊕⊝⊝
Lowa,b

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

Study population

RR 0.85
(0.18 to 4.05)

124
(1 study)

⊕⊕⊝⊝
Lowb,c

53 per 1000

45 per 1000
(9 to 213)

Moderate

53 per 1000

45 per 1000
(10 to 215)

Episodes in co‐regulated state (out of 20 observations)
Episodes observed (out of a total of 20 observations)

Scale from 0 to 20
Follow‐up: 2 months

Mean number of episodes in co‐regulated state (out of 20 observations) in control groups was
13.94 episodes

Mean number of episodes in co‐regulated state (out of 20 observations) in intervention groups was
0.96 higher
(3.44 lower to 5.36 higher)

6
(1 study)

⊕⊝⊝⊝
Very lowb,d

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)

⊕⊝⊝⊝
Very lowa,b,d

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

Mean length of hospital stay (days) in control groups was
52.7 days

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

6
(1 study)

⊕⊝⊝⊝
Very lowa,b,d

Parental satisfaction
Parental satisfaction survey

Scale from 0 to 55
Follow‐up: 5 days

Mean parental satisfaction in control groups was
51.13 points (out of 55)

Mean parental satisfaction in intervention groups was
0.38 lower
(4.49 lower to 3.73 higher)

18
(1 study)

⊕⊕⊕⊝
Moderatee

Neurobehavior: infant pain score following painful procedure ‐ at 30 seconds post heel lance
Premature Infant Pain Profile (PIPP)

Scale from 0 to 21

Mean neurobehavior: infant pain score after painful procedure ‐ at 30 seconds post heel lance in control groups was
PIPP scale (0 to 21)

Mean neurobehavior: infant pain score after painful procedure ‐ at 30 seconds post heel lance in intervention groups was
0.96 lower
(1.68 to 0.23 lower)

224
(2 studies)

⊕⊕⊝⊝
Lowf,g

*The basis for the assumed risk (e.g. 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

aDowngraded 1 level for study limitations (owing to unclear method of sequence generation, non‐blinding, and presence of selective outcome reporting)
bDowngraded 1 level for imprecision (owing to wide 95% confidence interval, which encompassed effect sizes ranging from a clear and/or up to a moderately large benefit for the co‐bedded group to a clear and/or up to a moderately large benefit for the control group)
cDowngraded 1 level for indirectness (as the study assessed specifically A/B/D episodes after a painful procedure in the form of a heel lance)
dDowngraded 2 levels for serious study limitations (as this was a pilot study that was non‐blinded, with high risk of bias for incomplete outcome data and selective outcome reporting)
eDowngraded 1 level for study limitations (owing to unclear sequence generation and allocation concealment and non‐blinding)

fDowngraded 1 level for study limitations (owing to non‐blinding of care personnel and outcome assessors)
gDowngraded 1 level for inconsistency (owing to differing direction of results between the 2 included studies, with I2 = 75%)

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Summary of findings for the main comparison. Co‐bedding versus 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

  • Physiological measures including heart rate, respiratory rate, and oxygen saturation

  • Sleep‐wake synchrony

  • Neurobehavioral observations using Newborn Individualized Developmental Care and Assessment Program (NIDCAP) guidelines

  • Complicatons such as infection, intraventricular hemorrhage, and patent ductus arteriosus

  • Parental measures including anxiety, attachment, and satisfaction

This study 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, physiological measures were reported in the form of average figures, such as average "highest activity heart rate," not as episodes of apnea, bradycardia, or desaturation, which are more clinically relevant

  • Physiological measures including heart rate, respiratory rate, and oxygen saturation

  • Sleep‐wake synchrony was reported narratively; only ranges were given in the article

  • Neurobehavioral observations based on Newborn Individualized Developmental Care and Assessment Program (NIDCAP) guidelines

  • Complicatons such as caregiver error, intraventricular hemorrhage, and patent ductus arteriosus

  • Parental measures including anxiety, attachment, and satisfaction

  • Mean daily weight

Campbell‐Yeo 2012b

  • Pain response measured by the Premature Infant Pain Profile (PIPP)

  • Time for physiological recovery in response to heel lance determined by length of time for heart rate and oxygen saturation to return to baseline

  • Need for additional pain relief with 24% sucrose

  • Adverse outcomes such as episodes of apnea, bradycardia, infection, and caregiver error

This study assessed specifically infants' response to pain; 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 neurobehavior

  • Pain response measured by the Premature Infant Pain Profile (PIPP)

  • Time for physiological recovery in response to heel lance determined by length of time for heart rate and oxygen saturation to return to baseline

  • Need for additional pain relief with 24% sucrose

  • Adverse outcomes such as episodes of apnea, bradycardia, infection, and caregiver error

Chin 2006

  • Weight gain

  • Apnea/bradycardia/desaturation (A/B/D) episodes

  • Infection, including sepsis (positive blood culture), necrotizing enterocolitis (clinical and radiological diagnosis), or conjunctivitis (positive eye culture)

  • Rate of weight gain

  • Length of hospital stay

  • Medication error

  • Weight

  • A/B/D episodes

  • Infection, including sepsis, necrotizing enterocolitis, or conjunctivitis

  • Medication error

Hayward 2007

  • 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 post discharge

  • Co‐regulatory behavior (measured using the Nursing Child Assessment Sleep/Activity Record, which included assessment of synchrony of infant state (e.g. in quiet sleep, alert, crying), heart rate, temperature, respirations, and oxygen saturation

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

  • Caregiver error

  • Length of hospital stay

  • Weight gain

  • Apnea, bradycardia, or desaturation episodes

  • Time in quiet sleep and crying

  • Time co‐regulated

  • Infection rate

  • Caregiver error

  • Length of hospital stay (as part of descriptive characteristics, not part of results)

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

Lutes 2001

No outcome was listed in the methods. However, the following 3 major outcomes were stated in the purpose and hypothesis section

  • Weight gain

  • Head circumference growth

  • Longitudinal growth/length gain

  • Length of hospital stay

  • Apnea, bradycardia, or desaturation episodes

  • Infection

  • Medication error

  • Weekly weight gain

  • "Weekly mean kilocalories per kilogram"

  • Weekly head circumference growth

  • Weekly length growth

  • Medication error

  • Nosocomial infection

  • Sepsis workups initiated

  • Thermal insults

Badiee 2014

  • Pain response to heel prick measured by the Premature Infant Pain Profile (PIPP)

  • Infant salivary cortisol level before and after heel prick procedure

Like Campbell‐Yeo 2012b, this study assessed specifically infant response to pain; growth‐related outcomes were not assessed

The only outcome included in this review is PIPP score
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Table 1. Matrix on outcome reporting by each study
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Table 2. Median combined apnea, 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 1

4.5

7

0.2

Week 2

6

12

0.8

Week 3

2.5

8

0.4
Figuras y tablas -
Table 2. Median combined apnea, 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/d) Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

1.1 From study entry to week 1

1

38

Mean Difference (IV, Fixed, 95% CI)

4.0 [‐0.96, 8.96]

1.2 From week 1 to week 2

1

28

Mean Difference (IV, Fixed, 95% CI)

1.40 [‐2.27, 5.07]

1.3 From week 2 to week 3

1

18

Mean Difference (IV, Fixed, 95% CI)

‐2.10 [‐4.33, 0.13]

1.4 Average from study entry to week 3

1

18

Mean Difference (IV, Fixed, 95% CI)

0.20 [‐1.60, 2.00]

2 Apnea, bradycardia, or desaturation Show forest plot

1

124

Risk Ratio (M‐H, Fixed, 95% CI)

0.85 [0.18, 4.05]

3 Episodes in co‐regulated 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 Neurobehavior: infant pain score following painful procedure Show forest plot

2

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

6.1 At 30 seconds post heel lance

2

224

Mean Difference (IV, Fixed, 95% CI)

‐0.96 [‐1.68, ‐0.23]

6.2 At 90 seconds post heel lance

1

124

Mean Difference (IV, Fixed, 95% CI)

1.0 [0.14, 1.86]

7 Infection Show forest plot

3

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

7.1 Suspected or proven infection (any)

3

65

Risk Ratio (M‐H, Fixed, 95% CI)

0.84 [0.30, 2.31]

7.2 Necrotizing 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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