Scolaris Content Display Scolaris Content Display

Study flow diagram.
Figures and Tables -
Figure 1

Study flow diagram.

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
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Figure 2

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
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Figure 3

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

Forest plot of comparison: 1 Intravenous (IV) fluid supplementation versus no fluid supplementation, outcome: 1.2 Serum bilirubin (μmol/L).
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Figure 4

Forest plot of comparison: 1 Intravenous (IV) fluid supplementation versus no fluid supplementation, outcome: 1.2 Serum bilirubin (μmol/L).

Forest plot of comparison: 1 Intravenous (IV) fluid supplementation versus no fluid supplementation, outcome: 1.6 Number of infants who required exchange transfusion.
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Figure 5

Forest plot of comparison: 1 Intravenous (IV) fluid supplementation versus no fluid supplementation, outcome: 1.6 Number of infants who required exchange transfusion.

Forest plot of comparison: 1 Intravenous (IV) fluid supplementation versus no fluid supplementation, outcome: 1.7 Frequency of breastfeeding per day.
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Figure 6

Forest plot of comparison: 1 Intravenous (IV) fluid supplementation versus no fluid supplementation, outcome: 1.7 Frequency of breastfeeding per day.

Comparison 1 Intravenous (IV) fluid supplementation versus no fluid supplementation, Outcome 1 Number of infants with bilirubin encephalopathy.
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Analysis 1.1

Comparison 1 Intravenous (IV) fluid supplementation versus no fluid supplementation, Outcome 1 Number of infants with bilirubin encephalopathy.

Comparison 1 Intravenous (IV) fluid supplementation versus no fluid supplementation, Outcome 2 Serum bilirubin (μmol/L).
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Analysis 1.2

Comparison 1 Intravenous (IV) fluid supplementation versus no fluid supplementation, Outcome 2 Serum bilirubin (μmol/L).

Comparison 1 Intravenous (IV) fluid supplementation versus no fluid supplementation, Outcome 3 Difference in serum bilirubin (%).
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Analysis 1.3

Comparison 1 Intravenous (IV) fluid supplementation versus no fluid supplementation, Outcome 3 Difference in serum bilirubin (%).

Comparison 1 Intravenous (IV) fluid supplementation versus no fluid supplementation, Outcome 4 Rate of change of serum bilirubin (μmol/L/hour).
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Analysis 1.4

Comparison 1 Intravenous (IV) fluid supplementation versus no fluid supplementation, Outcome 4 Rate of change of serum bilirubin (μmol/L/hour).

Comparison 1 Intravenous (IV) fluid supplementation versus no fluid supplementation, Outcome 5 Duration of phototherapy (hours).
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Analysis 1.5

Comparison 1 Intravenous (IV) fluid supplementation versus no fluid supplementation, Outcome 5 Duration of phototherapy (hours).

Comparison 1 Intravenous (IV) fluid supplementation versus no fluid supplementation, Outcome 6 Number of infants who required exchange transfusion.
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Analysis 1.6

Comparison 1 Intravenous (IV) fluid supplementation versus no fluid supplementation, Outcome 6 Number of infants who required exchange transfusion.

Comparison 1 Intravenous (IV) fluid supplementation versus no fluid supplementation, Outcome 7 Frequency of breastfeeding per day.
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Analysis 1.7

Comparison 1 Intravenous (IV) fluid supplementation versus no fluid supplementation, Outcome 7 Frequency of breastfeeding per day.

Comparison 2 Intravenous (IV) fluid supplementation versus oral fluid supplementation, Outcome 1 Number of infants with abnormal neurological signs.
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Analysis 2.1

Comparison 2 Intravenous (IV) fluid supplementation versus oral fluid supplementation, Outcome 1 Number of infants with abnormal neurological signs.

Comparison 2 Intravenous (IV) fluid supplementation versus oral fluid supplementation, Outcome 2 Serum bilirubin (μmol/L).
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Analysis 2.2

Comparison 2 Intravenous (IV) fluid supplementation versus oral fluid supplementation, Outcome 2 Serum bilirubin (μmol/L).

Comparison 2 Intravenous (IV) fluid supplementation versus oral fluid supplementation, Outcome 3 Rate of change of serum bilirubin (μmol/L/hour).
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Analysis 2.3

Comparison 2 Intravenous (IV) fluid supplementation versus oral fluid supplementation, Outcome 3 Rate of change of serum bilirubin (μmol/L/hour).

Comparison 2 Intravenous (IV) fluid supplementation versus oral fluid supplementation, Outcome 4 Number of infants who required exchange transfusion.
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Analysis 2.4

Comparison 2 Intravenous (IV) fluid supplementation versus oral fluid supplementation, Outcome 4 Number of infants who required exchange transfusion.

Comparison 2 Intravenous (IV) fluid supplementation versus oral fluid supplementation, Outcome 5 Number of infants with feed intolerance: vomiting.
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Analysis 2.5

Comparison 2 Intravenous (IV) fluid supplementation versus oral fluid supplementation, Outcome 5 Number of infants with feed intolerance: vomiting.

Comparison 2 Intravenous (IV) fluid supplementation versus oral fluid supplementation, Outcome 6 Number of infants with feed intolerance: abdominal distension.
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Analysis 2.6

Comparison 2 Intravenous (IV) fluid supplementation versus oral fluid supplementation, Outcome 6 Number of infants with feed intolerance: abdominal distension.

Summary of findings for the main comparison. Intravenous fluid supplementation versus no fluid supplementation for neonatal unconjugated hyperbilirubinaemia

Intravenous fluid supplementation versus no fluid supplementation for neonatal unconjugated hyperbilirubinaemia

Patient or population: newborn infants with unconjugated hyperbilirubinaemia undergoing phototherapy

Setting: neonatal intensive care unit

Intervention: intravenous fluid supplementation

Comparison: no fluid supplementation

Outcomes

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

No of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Risk with no fluid supplementation

Risk with intravenous fluid supplementation

Incidence of acute bilirubin encephalopathy

Study population

Not estimable

74 (1 RCT)

Effects not estimable as there were no reported cases of bilirubin encephalopathy in either group.

0 per 1000

0 per 1000
(0 to 0)

Bilirubin level (μmol/L): 4 hours postintervention

The mean serum bilirubin 4 hours postintervention was 344 μmol/L

The mean serum bilirubin 4 hours postintervention in the intervention group was 34 μmol/L lower (52.29 lower to 15.71 lower)

67
(1 RCT)

⊕⊕⊝⊝
Low a,b

Proportion of infants who required exchange transfusion

Study population

RR 0.39
(0.21 to 0.71)

462
(6 RCTs)

⊕⊕⊝⊝
Lowc,d

147 per 1000

57 per 1000
(31 to 105)

Frequency of breastfeeding per day: day 3

The mean frequency of breastfeeding per day on day 3 was 9.5 times per day

The mean frequency of breastfeeding per day on day 3 in the intervention group was 0.9 more feeds (0.4 fewer to 2.2 more)

60
(1 RCT)

⊕⊕⊕⊝
Moderate e

Although the study had high risk of bias in blinding of personnel, breastfeeding frequency on‐demand was considered unlikely to be affected.

The study evaluated breastfeeding frequencies on days 1, 2, and 3. Data on day 3 were chosen because compared to the earlier period, it most closely reflected the breastfeeding frequency on discharge.

*The risk in the intervention group (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; RCT: randomised controlled trial; RR: risk ratio.

GRADE Working Group grades of evidence
High quality: We are very confident that the true effect lies close to that of the estimate of the effect.
Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.
Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect.
Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect.

a Although widely used, serum bilirubin is only a surrogate to the relevant clinical outcomes, namely, bilirubin encephalopathy or kernicterus. Quality of evidence downgraded one level on the basis of indirectness.

b There is at least one unpublished study that was registered in ClinicalTrials.gov that included similar outcomes (NCT01550627). Quality of evidence downgraded one level on the basis of suspected publication bias. This outcome was also assessed in a published study for which we are yet to acquire full‐text (Demirsoy 2011). Both of these studies are currently placed under Studies awaiting classification.

c Moderate degree of heterogeneity was present, as indicated by an I² statistic of 72%, which was mainly due to one included study with effect estimates in opposite direction to the other studies. Quality of evidence downgraded one level on the basis of inconsistency.

d There are two unpublished studies (NCT01550627; IRCT2013022711145N5) identified from ClinicalTrials.gov, and one published study that we are yet to acquire full‐text (Demirsoy 2011) that are likely to assess this outcome. All three studies are placed under Studies awaiting classification. Quality of evidence downgraded one level on the basis of suspected publication bias.

e Quality of evidence downgraded one level due to imprecision, as reflected by wide 95% CIs for the estimate.

Figures and Tables -
Summary of findings for the main comparison. Intravenous fluid supplementation versus no fluid supplementation for neonatal unconjugated hyperbilirubinaemia
Summary of findings 2. Intravenous fluid supplementation versus oral fluid supplementation for neonatal unconjugated hyperbilirubinaemia

Intravenous fluid versus oral fluid supplementation for neonatal unconjugated hyperbilirubinaemia

Patient or population: newborn infants with unconjugated hyperbilirubinaemia undergoing phototherapy

Setting: neonatal intensive care unit

Intervention: intravenous fluid supplementation

Comparison: oral fluid supplementation

Outcomes

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

No of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Risk with oral fluid supplementation

Risk with intravenous fluid supplementation

Number of infants with abnormal neurological signs

Study population

Not estimable

54
(1 RCT)

Not estimable as there were no cases reported in either group.

0 per 1000

0 per 1000
(0 to 0)

Bilirubin level (μmol/L): 4 hours postphototherapy

The mean serum bilirubin 4 hours postphototherapy was 332 μmol/L

The mean serum bilirubin 4 hours postphototherapy in the intervention group was 11 μmol/L higher (21.58 lower to 43.58 higher)

54
(1 RCT)

⊕⊕⊕⊝
Moderate a

Rate of change in bilirubin (μmol/L/hour): during the first 4 hours of admission

The mean rate of decrease of serum bilirubin (μmol/L/hour) during the first 4 hours of admission was 10.4 μmol/L/hour

The mean rate of decrease of serum bilirubin (μmol/L/hour) during the first 4 hours of admission in the intervention group was 0.8 μmol/L/hour higher (2.55 lower to 4.15 higher)

54
(1 RCT)

⊕⊕⊕⊝
Moderatea

*The risk in the intervention group (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; RCT: randomised controlled trial.

GRADE Working Group grades of evidence
High quality: We are very confident that the true effect lies close to that of the estimate of the effect.
Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.
Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect.
Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect.

a Although widely used, serum bilirubin is only a surrogate to the relevant clinical outcomes, namely, bilirubin encephalopathy or kernicterus. Quality of evidence downgraded one level on the basis of indirectness.

Figures and Tables -
Summary of findings 2. Intravenous fluid supplementation versus oral fluid supplementation for neonatal unconjugated hyperbilirubinaemia
Comparison 1. Intravenous (IV) fluid supplementation versus no fluid supplementation

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Number of infants with bilirubin encephalopathy Show forest plot

1

Risk Ratio (IV, Fixed, 95% CI)

Totals not selected

2 Serum bilirubin (μmol/L) Show forest plot

4

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

2.1 4 hours postintervention

1

67

Mean Difference (IV, Fixed, 95% CI)

‐34.0 [‐52.29, ‐15.71]

2.2 6 hours postintervention

1

80

Mean Difference (IV, Fixed, 95% CI)

1.70 [‐28.67, 32.07]

2.3 8 hours postintervention

1

49

Mean Difference (IV, Fixed, 95% CI)

‐44.0 [‐65.95, ‐22.05]

2.4 12 hours postintervention

3

204

Mean Difference (IV, Fixed, 95% CI)

‐10.21 [‐18.45, ‐1.97]

2.5 18 hours postintervention

1

80

Mean Difference (IV, Fixed, 95% CI)

‐5.20 [‐33.70, 23.30]

2.6 24 hours postintervention

4

252

Mean Difference (IV, Fixed, 95% CI)

‐6.06 [‐11.12, 1.00]

2.7 36 hours postintervention

3

204

Mean Difference (IV, Fixed, 95% CI)

‐4.25 [‐8.73, 0.23]

2.8 48 hours postintervention

3

204

Mean Difference (IV, Fixed, 95% CI)

‐7.86 [‐14.15, ‐1.57]

2.9 60 hours postintervention

2

140

Mean Difference (IV, Fixed, 95% CI)

‐9.16 [‐21.25, 2.93]

2.10 72 hours postintervention

2

140

Mean Difference (IV, Fixed, 95% CI)

‐0.96 [‐8.76, 6.83]

2.11 84 hours postintervention

1

60

Mean Difference (IV, Fixed, 95% CI)

7.40 [4.69, 10.11]

3 Difference in serum bilirubin (%) Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

3.1 0‐4 hours of study

1

67

Mean Difference (IV, Fixed, 95% CI)

10.5 [6.66, 14.34]

3.2 0‐8 hours of study

1

49

Mean Difference (IV, Fixed, 95% CI)

13.0 [7.49, 18.51]

3.3 0‐24 hours of study

1

48

Mean Difference (IV, Fixed, 95% CI)

8.0 [1.11, 14.89]

4 Rate of change of serum bilirubin (μmol/L/hour) Show forest plot

1

60

Mean Difference (IV, Fixed, 95% CI)

0.50 [‐0.21, 1.21]

4.1 During the first 12 hours of study

1

60

Mean Difference (IV, Fixed, 95% CI)

0.50 [‐0.21, 1.21]

5 Duration of phototherapy (hours) Show forest plot

3

218

Mean Difference (IV, Fixed, 95% CI)

‐10.70 [‐15.55, ‐5.85]

6 Number of infants who required exchange transfusion Show forest plot

6

462

Risk Ratio (IV, Fixed, 95% CI)

0.39 [0.21, 0.71]

7 Frequency of breastfeeding per day Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

7.1 Day 1

1

60

Mean Difference (IV, Fixed, 95% CI)

0.70 [‐0.62, 2.02]

7.2 Day 2

1

60

Mean Difference (IV, Fixed, 95% CI)

0.90 [‐0.43, 2.23]

7.3 Day 3

1

60

Mean Difference (IV, Fixed, 95% CI)

0.90 [‐0.40, 2.20]

Figures and Tables -
Comparison 1. Intravenous (IV) fluid supplementation versus no fluid supplementation
Comparison 2. Intravenous (IV) fluid supplementation versus oral fluid supplementation

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Number of infants with abnormal neurological signs Show forest plot

1

54

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

2 Serum bilirubin (μmol/L) Show forest plot

1

54

Mean Difference (IV, Fixed, 95% CI)

11.0 [‐21.58, 43.58]

2.1 4 hours postphototherapy

1

54

Mean Difference (IV, Fixed, 95% CI)

11.0 [‐21.58, 43.58]

3 Rate of change of serum bilirubin (μmol/L/hour) Show forest plot

1

54

Mean Difference (IV, Fixed, 95% CI)

0.80 [‐2.55, 4.15]

3.1 During first 4 hours of admission

1

54

Mean Difference (IV, Fixed, 95% CI)

0.80 [‐2.55, 4.15]

4 Number of infants who required exchange transfusion Show forest plot

1

54

Risk Difference (IV, Fixed, 95% CI)

0.11 [‐0.12, 0.34]

5 Number of infants with feed intolerance: vomiting Show forest plot

1

54

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

6 Number of infants with feed intolerance: abdominal distension Show forest plot

1

54

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

Figures and Tables -
Comparison 2. Intravenous (IV) fluid supplementation versus oral fluid supplementation