Scolaris Content Display Scolaris Content Display

Flow diagram of study selection process. IVIg: intravenous immunoglobulin; RCT: randomized controlled trial.
Figures and Tables -
Figure 1

Flow diagram of study selection process. IVIg: intravenous immunoglobulin; RCT: randomized controlled trial.

Risk of bias summary: review authors' judgments about each risk of bias item for each included study.
Figures and Tables -
Figure 2

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

Comparison 1 Intravenous immunoglobulin plus phototherapy versus phototherapy, Outcome 1 Use of exchange transfusion (≥ 1).
Figures and Tables -
Analysis 1.1

Comparison 1 Intravenous immunoglobulin plus phototherapy versus phototherapy, Outcome 1 Use of exchange transfusion (≥ 1).

Comparison 1 Intravenous immunoglobulin plus phototherapy versus phototherapy, Outcome 2 Exchange transfusions per infant, by study quality.
Figures and Tables -
Analysis 1.2

Comparison 1 Intravenous immunoglobulin plus phototherapy versus phototherapy, Outcome 2 Exchange transfusions per infant, by study quality.

Comparison 1 Intravenous immunoglobulin plus phototherapy versus phototherapy, Outcome 3 Use of top‐up transfusion in 1st week by study quality.
Figures and Tables -
Analysis 1.3

Comparison 1 Intravenous immunoglobulin plus phototherapy versus phototherapy, Outcome 3 Use of top‐up transfusion in 1st week by study quality.

Comparison 1 Intravenous immunoglobulin plus phototherapy versus phototherapy, Outcome 4 Top‐up transfusions in 1st week per infant by study quality.
Figures and Tables -
Analysis 1.4

Comparison 1 Intravenous immunoglobulin plus phototherapy versus phototherapy, Outcome 4 Top‐up transfusions in 1st week per infant by study quality.

Comparison 1 Intravenous immunoglobulin plus phototherapy versus phototherapy, Outcome 5 Use of top‐up transfusion after 1st week by study quality.
Figures and Tables -
Analysis 1.5

Comparison 1 Intravenous immunoglobulin plus phototherapy versus phototherapy, Outcome 5 Use of top‐up transfusion after 1st week by study quality.

Comparison 1 Intravenous immunoglobulin plus phototherapy versus phototherapy, Outcome 6 Top‐up transfusions after first week per infant, by study quality.
Figures and Tables -
Analysis 1.6

Comparison 1 Intravenous immunoglobulin plus phototherapy versus phototherapy, Outcome 6 Top‐up transfusions after first week per infant, by study quality.

Comparison 1 Intravenous immunoglobulin plus phototherapy versus phototherapy, Outcome 7 Maximum total serum bilirubin (µmol/L) by study quality.
Figures and Tables -
Analysis 1.7

Comparison 1 Intravenous immunoglobulin plus phototherapy versus phototherapy, Outcome 7 Maximum total serum bilirubin (µmol/L) by study quality.

Comparison 1 Intravenous immunoglobulin plus phototherapy versus phototherapy, Outcome 8 Duration of phototherapy (days) by study quality.
Figures and Tables -
Analysis 1.8

Comparison 1 Intravenous immunoglobulin plus phototherapy versus phototherapy, Outcome 8 Duration of phototherapy (days) by study quality.

Comparison 2 Intravenous immunoglobulin plus phototherapy versus phototherapy. Rh incompatibility only, Outcome 1 Use of exchange transfusion (≥ 1).
Figures and Tables -
Analysis 2.1

Comparison 2 Intravenous immunoglobulin plus phototherapy versus phototherapy. Rh incompatibility only, Outcome 1 Use of exchange transfusion (≥ 1).

Comparison 2 Intravenous immunoglobulin plus phototherapy versus phototherapy. Rh incompatibility only, Outcome 2 Exchange transfusions per infant.
Figures and Tables -
Analysis 2.2

Comparison 2 Intravenous immunoglobulin plus phototherapy versus phototherapy. Rh incompatibility only, Outcome 2 Exchange transfusions per infant.

Comparison 2 Intravenous immunoglobulin plus phototherapy versus phototherapy. Rh incompatibility only, Outcome 3 Use top‐up transfusion in 1st week.
Figures and Tables -
Analysis 2.3

Comparison 2 Intravenous immunoglobulin plus phototherapy versus phototherapy. Rh incompatibility only, Outcome 3 Use top‐up transfusion in 1st week.

Comparison 2 Intravenous immunoglobulin plus phototherapy versus phototherapy. Rh incompatibility only, Outcome 4 Top‐up transfusions in 1st week per infant.
Figures and Tables -
Analysis 2.4

Comparison 2 Intravenous immunoglobulin plus phototherapy versus phototherapy. Rh incompatibility only, Outcome 4 Top‐up transfusions in 1st week per infant.

Comparison 2 Intravenous immunoglobulin plus phototherapy versus phototherapy. Rh incompatibility only, Outcome 5 Use of top‐up transfusion after 1st week.
Figures and Tables -
Analysis 2.5

Comparison 2 Intravenous immunoglobulin plus phototherapy versus phototherapy. Rh incompatibility only, Outcome 5 Use of top‐up transfusion after 1st week.

Comparison 2 Intravenous immunoglobulin plus phototherapy versus phototherapy. Rh incompatibility only, Outcome 6 Top‐up transfusions after 1st week per infant.
Figures and Tables -
Analysis 2.6

Comparison 2 Intravenous immunoglobulin plus phototherapy versus phototherapy. Rh incompatibility only, Outcome 6 Top‐up transfusions after 1st week per infant.

Comparison 2 Intravenous immunoglobulin plus phototherapy versus phototherapy. Rh incompatibility only, Outcome 7 Maximum total serum bilirubin (µmol/L).
Figures and Tables -
Analysis 2.7

Comparison 2 Intravenous immunoglobulin plus phototherapy versus phototherapy. Rh incompatibility only, Outcome 7 Maximum total serum bilirubin (µmol/L).

Comparison 2 Intravenous immunoglobulin plus phototherapy versus phototherapy. Rh incompatibility only, Outcome 8 Duration of phototherapy (days).
Figures and Tables -
Analysis 2.8

Comparison 2 Intravenous immunoglobulin plus phototherapy versus phototherapy. Rh incompatibility only, Outcome 8 Duration of phototherapy (days).

Comparison 3 Intravenous immunoglobulin (IVIg) plus phototherapy versus phototherapy. IVIg administration ≤ 12 hours after birth, Outcome 1 Use of exchange transfusion (≥ 1).
Figures and Tables -
Analysis 3.1

Comparison 3 Intravenous immunoglobulin (IVIg) plus phototherapy versus phototherapy. IVIg administration ≤ 12 hours after birth, Outcome 1 Use of exchange transfusion (≥ 1).

Comparison 3 Intravenous immunoglobulin (IVIg) plus phototherapy versus phototherapy. IVIg administration ≤ 12 hours after birth, Outcome 2 Exchange transfusions per infant.
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Analysis 3.2

Comparison 3 Intravenous immunoglobulin (IVIg) plus phototherapy versus phototherapy. IVIg administration ≤ 12 hours after birth, Outcome 2 Exchange transfusions per infant.

Comparison 3 Intravenous immunoglobulin (IVIg) plus phototherapy versus phototherapy. IVIg administration ≤ 12 hours after birth, Outcome 3 Use of top‐up transfusion in 1st week.
Figures and Tables -
Analysis 3.3

Comparison 3 Intravenous immunoglobulin (IVIg) plus phototherapy versus phototherapy. IVIg administration ≤ 12 hours after birth, Outcome 3 Use of top‐up transfusion in 1st week.

Comparison 3 Intravenous immunoglobulin (IVIg) plus phototherapy versus phototherapy. IVIg administration ≤ 12 hours after birth, Outcome 4 Top‐up transfusions in 1st week per infant.
Figures and Tables -
Analysis 3.4

Comparison 3 Intravenous immunoglobulin (IVIg) plus phototherapy versus phototherapy. IVIg administration ≤ 12 hours after birth, Outcome 4 Top‐up transfusions in 1st week per infant.

Comparison 3 Intravenous immunoglobulin (IVIg) plus phototherapy versus phototherapy. IVIg administration ≤ 12 hours after birth, Outcome 5 Use of top‐up transfusions after 1st week.
Figures and Tables -
Analysis 3.5

Comparison 3 Intravenous immunoglobulin (IVIg) plus phototherapy versus phototherapy. IVIg administration ≤ 12 hours after birth, Outcome 5 Use of top‐up transfusions after 1st week.

Comparison 3 Intravenous immunoglobulin (IVIg) plus phototherapy versus phototherapy. IVIg administration ≤ 12 hours after birth, Outcome 6 Top‐up transfusions after 1st week per infant.
Figures and Tables -
Analysis 3.6

Comparison 3 Intravenous immunoglobulin (IVIg) plus phototherapy versus phototherapy. IVIg administration ≤ 12 hours after birth, Outcome 6 Top‐up transfusions after 1st week per infant.

Comparison 3 Intravenous immunoglobulin (IVIg) plus phototherapy versus phototherapy. IVIg administration ≤ 12 hours after birth, Outcome 7 Maximum total serum bilirubin (µmol/L).
Figures and Tables -
Analysis 3.7

Comparison 3 Intravenous immunoglobulin (IVIg) plus phototherapy versus phototherapy. IVIg administration ≤ 12 hours after birth, Outcome 7 Maximum total serum bilirubin (µmol/L).

Comparison 3 Intravenous immunoglobulin (IVIg) plus phototherapy versus phototherapy. IVIg administration ≤ 12 hours after birth, Outcome 8 Duration of phototherapy (days).
Figures and Tables -
Analysis 3.8

Comparison 3 Intravenous immunoglobulin (IVIg) plus phototherapy versus phototherapy. IVIg administration ≤ 12 hours after birth, Outcome 8 Duration of phototherapy (days).

Comparison 4 Intravenous immunoglobulin (IVIg) plus phototherapy versus phototherapy. Single dose of IVIg, Outcome 1 Use of exchange transfusion (≥ 1).
Figures and Tables -
Analysis 4.1

Comparison 4 Intravenous immunoglobulin (IVIg) plus phototherapy versus phototherapy. Single dose of IVIg, Outcome 1 Use of exchange transfusion (≥ 1).

Comparison 4 Intravenous immunoglobulin (IVIg) plus phototherapy versus phototherapy. Single dose of IVIg, Outcome 2 Exchange transfusions per infant.
Figures and Tables -
Analysis 4.2

Comparison 4 Intravenous immunoglobulin (IVIg) plus phototherapy versus phototherapy. Single dose of IVIg, Outcome 2 Exchange transfusions per infant.

Comparison 4 Intravenous immunoglobulin (IVIg) plus phototherapy versus phototherapy. Single dose of IVIg, Outcome 3 Use of top‐up transfusions in 1st week.
Figures and Tables -
Analysis 4.3

Comparison 4 Intravenous immunoglobulin (IVIg) plus phototherapy versus phototherapy. Single dose of IVIg, Outcome 3 Use of top‐up transfusions in 1st week.

Comparison 4 Intravenous immunoglobulin (IVIg) plus phototherapy versus phototherapy. Single dose of IVIg, Outcome 4 Top‐up transfusions in 1st week per infant.
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Analysis 4.4

Comparison 4 Intravenous immunoglobulin (IVIg) plus phototherapy versus phototherapy. Single dose of IVIg, Outcome 4 Top‐up transfusions in 1st week per infant.

Comparison 4 Intravenous immunoglobulin (IVIg) plus phototherapy versus phototherapy. Single dose of IVIg, Outcome 5 Use of top‐up transfusion after 1st week.
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Analysis 4.5

Comparison 4 Intravenous immunoglobulin (IVIg) plus phototherapy versus phototherapy. Single dose of IVIg, Outcome 5 Use of top‐up transfusion after 1st week.

Comparison 4 Intravenous immunoglobulin (IVIg) plus phototherapy versus phototherapy. Single dose of IVIg, Outcome 6 Top‐up transfusions after 1st week per infant.
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Analysis 4.6

Comparison 4 Intravenous immunoglobulin (IVIg) plus phototherapy versus phototherapy. Single dose of IVIg, Outcome 6 Top‐up transfusions after 1st week per infant.

Comparison 4 Intravenous immunoglobulin (IVIg) plus phototherapy versus phototherapy. Single dose of IVIg, Outcome 7 Maximum total serum bilirubin (µmol/L).
Figures and Tables -
Analysis 4.7

Comparison 4 Intravenous immunoglobulin (IVIg) plus phototherapy versus phototherapy. Single dose of IVIg, Outcome 7 Maximum total serum bilirubin (µmol/L).

Comparison 4 Intravenous immunoglobulin (IVIg) plus phototherapy versus phototherapy. Single dose of IVIg, Outcome 8 Duration of phototherapy (days).
Figures and Tables -
Analysis 4.8

Comparison 4 Intravenous immunoglobulin (IVIg) plus phototherapy versus phototherapy. Single dose of IVIg, Outcome 8 Duration of phototherapy (days).

Comparison 5 Intravenous immunoglobulin (IVIg) plus phototherapy versus phototherapy. Multiple doses of IVIg, Outcome 1 Use of exchange transfusion (≥ 1).
Figures and Tables -
Analysis 5.1

Comparison 5 Intravenous immunoglobulin (IVIg) plus phototherapy versus phototherapy. Multiple doses of IVIg, Outcome 1 Use of exchange transfusion (≥ 1).

Comparison 5 Intravenous immunoglobulin (IVIg) plus phototherapy versus phototherapy. Multiple doses of IVIg, Outcome 2 Exchange transfusions per infant.
Figures and Tables -
Analysis 5.2

Comparison 5 Intravenous immunoglobulin (IVIg) plus phototherapy versus phototherapy. Multiple doses of IVIg, Outcome 2 Exchange transfusions per infant.

Comparison 5 Intravenous immunoglobulin (IVIg) plus phototherapy versus phototherapy. Multiple doses of IVIg, Outcome 3 Use of top‐up transfusions after 1st week.
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Analysis 5.3

Comparison 5 Intravenous immunoglobulin (IVIg) plus phototherapy versus phototherapy. Multiple doses of IVIg, Outcome 3 Use of top‐up transfusions after 1st week.

Comparison 5 Intravenous immunoglobulin (IVIg) plus phototherapy versus phototherapy. Multiple doses of IVIg, Outcome 4 Duration of phototherapy (days).
Figures and Tables -
Analysis 5.4

Comparison 5 Intravenous immunoglobulin (IVIg) plus phototherapy versus phototherapy. Multiple doses of IVIg, Outcome 4 Duration of phototherapy (days).

Comparison 6 Intravenous immunoglobulin (IVIg) plus phototherapy versus phototherapy. Gestational age ≥ 37 weeks, Outcome 1 Use of exchange transfusion (≥ 1).
Figures and Tables -
Analysis 6.1

Comparison 6 Intravenous immunoglobulin (IVIg) plus phototherapy versus phototherapy. Gestational age ≥ 37 weeks, Outcome 1 Use of exchange transfusion (≥ 1).

Comparison 6 Intravenous immunoglobulin (IVIg) plus phototherapy versus phototherapy. Gestational age ≥ 37 weeks, Outcome 2 Exchange transfusions per infant.
Figures and Tables -
Analysis 6.2

Comparison 6 Intravenous immunoglobulin (IVIg) plus phototherapy versus phototherapy. Gestational age ≥ 37 weeks, Outcome 2 Exchange transfusions per infant.

Comparison 6 Intravenous immunoglobulin (IVIg) plus phototherapy versus phototherapy. Gestational age ≥ 37 weeks, Outcome 3 Use of top‐up transfusion in 1st week.
Figures and Tables -
Analysis 6.3

Comparison 6 Intravenous immunoglobulin (IVIg) plus phototherapy versus phototherapy. Gestational age ≥ 37 weeks, Outcome 3 Use of top‐up transfusion in 1st week.

Comparison 6 Intravenous immunoglobulin (IVIg) plus phototherapy versus phototherapy. Gestational age ≥ 37 weeks, Outcome 4 Top‐up transfusions in 1st week per infant.
Figures and Tables -
Analysis 6.4

Comparison 6 Intravenous immunoglobulin (IVIg) plus phototherapy versus phototherapy. Gestational age ≥ 37 weeks, Outcome 4 Top‐up transfusions in 1st week per infant.

Comparison 6 Intravenous immunoglobulin (IVIg) plus phototherapy versus phototherapy. Gestational age ≥ 37 weeks, Outcome 5 Use of top‐up transfusion after 1st week.
Figures and Tables -
Analysis 6.5

Comparison 6 Intravenous immunoglobulin (IVIg) plus phototherapy versus phototherapy. Gestational age ≥ 37 weeks, Outcome 5 Use of top‐up transfusion after 1st week.

Comparison 6 Intravenous immunoglobulin (IVIg) plus phototherapy versus phototherapy. Gestational age ≥ 37 weeks, Outcome 6 Top‐up transfusions after 1st week per infant.
Figures and Tables -
Analysis 6.6

Comparison 6 Intravenous immunoglobulin (IVIg) plus phototherapy versus phototherapy. Gestational age ≥ 37 weeks, Outcome 6 Top‐up transfusions after 1st week per infant.

Comparison 6 Intravenous immunoglobulin (IVIg) plus phototherapy versus phototherapy. Gestational age ≥ 37 weeks, Outcome 7 Maximum total serum bilirubin (µmol/L).
Figures and Tables -
Analysis 6.7

Comparison 6 Intravenous immunoglobulin (IVIg) plus phototherapy versus phototherapy. Gestational age ≥ 37 weeks, Outcome 7 Maximum total serum bilirubin (µmol/L).

Comparison 6 Intravenous immunoglobulin (IVIg) plus phototherapy versus phototherapy. Gestational age ≥ 37 weeks, Outcome 8 Duration of phototherapy (days).
Figures and Tables -
Analysis 6.8

Comparison 6 Intravenous immunoglobulin (IVIg) plus phototherapy versus phototherapy. Gestational age ≥ 37 weeks, Outcome 8 Duration of phototherapy (days).

Comparison 6 Intravenous immunoglobulin (IVIg) plus phototherapy versus phototherapy. Gestational age ≥ 37 weeks, Outcome 9 Duration of hospitalization (days).
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Analysis 6.9

Comparison 6 Intravenous immunoglobulin (IVIg) plus phototherapy versus phototherapy. Gestational age ≥ 37 weeks, Outcome 9 Duration of hospitalization (days).

Summary of findings for the main comparison. Intravenous immunoglobulin plus phototherapy compared to phototherapy alone for alloimmune hemolytic disease in neonates

Intravenous immunoglobulin plus phototherapy compared to phototherapy alone for alloimmune hemolytic disease in neonates

Patient or population: neonates with alloimmune hemolytic disease

Settings:

Intervention: IVIg + phototherapy

Comparison: phototherapy

Outcomes

№ of participants
(studies)

Quality of the evidence
(GRADE)

Relative effect
(95% CI)

Anticipated absolute effects* (95% CI)

Risk with phototherapy alone

Risk difference with IVIg + phototherapy

Use of ET (≥ 1); all studies

658
(9 RCTs)

⊕⊝⊝⊝
Very low1,2,3

RR 0.35
(0.25 to 0.49)

Study population

329 per 1000

214 fewer per 1000
(247 fewer to 168 fewer)

Use of ET (≥ 1); placebo‐controlled studies

172
(2 RCTs)

⊕⊕⊕⊝
Moderate4

RR 0.98
(0.48 to 1.98)

Study population

153 per 1000

3 fewer per 1000
(80 fewer to 150 more)

ETs performed per infant; all studies

658
(9 RCTs)

⊕⊝⊝⊝
Very low1,2,3,5

The mean ETs per infant for all studies was 0

MD 0.34 lower
(0.5 lower to 0.17 lower)

ETs performed per infant; placebo‐controlled studies

172
(2 RCTs)

⊕⊕⊕⊝
Moderate4,5

The mean ETs per infant for placebo‐controlled studies was 0

MD 0.04 lower
(0.18 lower to 0.1 higher)

Use of top‐up transfusion in 1st week of life; all studies

378
(4 RCTs)

⊕⊕⊝⊝
Low6,7

RR 1.05
(0.65 to 1.69)

Study population

130 per 1000

6 more per 1000
(45 fewer to 89 more)

Use of top‐up transfusion after 1st week of life; all studies

507
(7 RCTs)

⊕⊝⊝⊝
Very low1,8,9

RR 1.16
(0.97 to 1.38)

Study population

219 per 1000

35 more per 1000
(7 fewer to 83 more)

Maximum total serum bilirubin (µmol/L); all studies

451
(6 RCTs)

⊕⊝⊝⊝
Very low10,11,12

The mean maximum serum bilirubin (µmol/L) for all studies was 0

MD 25.39 lower
(34.07 lower to 16.7 lower)

*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; ET: exchange transfusion; IVIg: intravenous immunoglobulin; MD: mean difference; RCT: randomized 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.

1In three studies, the method of randomization was not stated and there was inadequate concealment of random sequence (selection bias). In seven studies, there was no blinding of personnel (performance bias) and in five studies, no blinding of outcome assessment (detection bias). Among other potential sources of bias were that mean bilirubin levels at study entry were already higher than the threshold for the outcome (ET) in one study, differences between study groups despite randomization (one study), postrandomization withdrawals or cross‐over between study groups (two studies) and criteria for ET differing between treatment arms (one study).

2Substantial heterogeneity: Chi2 = 34.63, df = 8 (P = 0.0003), I2 = 77%.

3Four studies did not clearly specify use of intensive phototherapy (which should be a routine intervention for infants at high risk of ET).

4Total number of participants in these two trials was low, increasing the risk of possible bias.

5Only a few infants needed a second ET.

6In one trial, the methods of randomization and allocation concealment were not stated. In two studies, there was no blinding of personnel (performance bias).

7Combined studies were underpowered for use of top‐up transfusion in 1st week. A total of 378 infants were enrolled in all four trials, and the overall frequency of top‐up transfusion was low (13.8%).

8Substantial heterogeneity: Chi2 = 15.60, df = 5 (P = 0.008); I2 = 68%.

9Due to small differences between treatment groups, the combined studies were underpowered for use of top‐up transfusion after 1st week.

10Four studies used no method of blinding the intervention.

11Substantial heterogeneity: Chi2 = 14.82, df = 5 (P = 0.01); I2 = 66%.

12Peak serum bilirubin in the control group varied 1.86‐fold between studies; there was considerably greater variation between studies than between groups within studies.

Figures and Tables -
Summary of findings for the main comparison. Intravenous immunoglobulin plus phototherapy compared to phototherapy alone for alloimmune hemolytic disease in neonates
Comparison 1. Intravenous immunoglobulin plus phototherapy versus phototherapy

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Use of exchange transfusion (≥ 1) Show forest plot

9

658

Risk Ratio (M‐H, Fixed, 95% CI)

0.35 [0.25, 0.49]

1.1 Studies without a placebo group

7

486

Risk Ratio (M‐H, Fixed, 95% CI)

0.26 [0.18, 0.39]

1.2 Placebo‐controlled studies

2

172

Risk Ratio (M‐H, Fixed, 95% CI)

0.98 [0.48, 1.98]

2 Exchange transfusions per infant, by study quality Show forest plot

9

658

Mean Difference (IV, Random, 95% CI)

‐0.34 [‐0.50, ‐0.17]

2.1 Studies without a placebo group

7

486

Mean Difference (IV, Random, 95% CI)

‐0.44 [‐0.64, ‐0.25]

2.2 Placebo‐controlled studies

2

172

Mean Difference (IV, Random, 95% CI)

‐0.04 [‐0.18, 0.10]

3 Use of top‐up transfusion in 1st week by study quality Show forest plot

4

378

Risk Ratio (M‐H, Fixed, 95% CI)

1.05 [0.65, 1.69]

3.1 Studies without a placebo group

2

206

Risk Ratio (M‐H, Fixed, 95% CI)

0.71 [0.24, 2.12]

3.2 Placebo‐controlled studies

2

172

Risk Ratio (M‐H, Fixed, 95% CI)

1.18 [0.70, 2.00]

4 Top‐up transfusions in 1st week per infant by study quality Show forest plot

3

262

Mean Difference (IV, Fixed, 95% CI)

0.05 [‐0.07, 0.17]

4.1 Studies without a placebo group

1

90

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

4.2 Placebo‐controlled studies

2

172

Mean Difference (IV, Fixed, 95% CI)

0.05 [‐0.07, 0.17]

5 Use of top‐up transfusion after 1st week by study quality Show forest plot

7

507

Risk Ratio (M‐H, Fixed, 95% CI)

1.16 [0.97, 1.38]

5.1 Studies without a placebo group

5

335

Risk Ratio (M‐H, Fixed, 95% CI)

1.40 [1.08, 1.82]

5.2 Placebo‐controlled studies

2

172

Risk Ratio (M‐H, Fixed, 95% CI)

1.01 [0.80, 1.27]

6 Top‐up transfusions after first week per infant, by study quality Show forest plot

4

316

Mean Difference (IV, Fixed, 95% CI)

‐0.00 [‐0.12, 0.12]

6.1 Studies without a placebo group

2

144

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

6.2 Placebo‐controlled studies

2

172

Mean Difference (IV, Fixed, 95% CI)

‐0.00 [‐0.12, 0.12]

7 Maximum total serum bilirubin (µmol/L) by study quality Show forest plot

6

451

Mean Difference (IV, Fixed, 95% CI)

‐25.39 [‐34.07, ‐16.70]

7.1 Studies without a placebo group

4

279

Mean Difference (IV, Fixed, 95% CI)

‐29.05 [‐38.32, ‐19.78]

7.2 Placebo‐controlled studies

2

172

Mean Difference (IV, Fixed, 95% CI)

0.93 [‐23.94, 25.79]

8 Duration of phototherapy (days) by study quality Show forest plot

7

585

Mean Difference (IV, Random, 95% CI)

‐0.98 [‐1.31, ‐0.66]

8.1 Studies without a placebo group

5

413

Mean Difference (IV, Random, 95% CI)

‐1.06 [‐1.41, ‐0.72]

8.2 Placebo‐controlled studies

2

172

Mean Difference (IV, Random, 95% CI)

‐0.50 [‐1.24, 0.24]

Figures and Tables -
Comparison 1. Intravenous immunoglobulin plus phototherapy versus phototherapy
Comparison 2. Intravenous immunoglobulin plus phototherapy versus phototherapy. Rh incompatibility only

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Use of exchange transfusion (≥ 1) Show forest plot

7

371

Risk Ratio (M‐H, Fixed, 95% CI)

0.38 [0.25, 0.58]

1.1 Studies without a placebo group

5

199

Risk Ratio (M‐H, Fixed, 95% CI)

0.23 [0.13, 0.40]

1.2 Placebo‐controlled studies

2

172

Risk Ratio (M‐H, Fixed, 95% CI)

0.98 [0.48, 1.98]

2 Exchange transfusions per infant Show forest plot

7

371

Mean Difference (IV, Fixed, 95% CI)

‐0.25 [‐0.34, ‐0.16]

2.1 Studies without a placebo group

5

199

Mean Difference (IV, Fixed, 95% CI)

‐0.39 [‐0.51, ‐0.28]

2.2 Placebo‐controlled studies

2

172

Mean Difference (IV, Fixed, 95% CI)

‐0.04 [‐0.18, 0.10]

3 Use top‐up transfusion in 1st week Show forest plot

4

285

Risk Ratio (M‐H, Fixed, 95% CI)

1.08 [0.65, 1.77]

3.1 Studies without a placebo group

2

113

Risk Ratio (M‐H, Fixed, 95% CI)

0.51 [0.10, 2.51]

3.2 Placebo‐controlled studies

2

172

Risk Ratio (M‐H, Fixed, 95% CI)

1.18 [0.70, 2.00]

4 Top‐up transfusions in 1st week per infant Show forest plot

3

262

Mean Difference (IV, Fixed, 95% CI)

0.05 [‐0.07, 0.17]

4.1 Studies without a placebo group

1

90

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

4.2 Placebo‐controlled studies

2

172

Mean Difference (IV, Fixed, 95% CI)

0.05 [‐0.07, 0.17]

5 Use of top‐up transfusion after 1st week Show forest plot

6

281

Risk Ratio (M‐H, Fixed, 95% CI)

1.09 [0.92, 1.28]

5.1 Studies without a placebo group

4

109

Risk Ratio (M‐H, Fixed, 95% CI)

1.21 [0.96, 1.53]

5.2 Placebo‐controlled studies

2

172

Risk Ratio (M‐H, Fixed, 95% CI)

1.01 [0.80, 1.27]

6 Top‐up transfusions after 1st week per infant Show forest plot

3

204

Mean Difference (IV, Fixed, 95% CI)

‐0.00 [‐0.12, 0.12]

7 Maximum total serum bilirubin (µmol/L) Show forest plot

6

358

Mean Difference (IV, Fixed, 95% CI)

‐21.77 [‐30.86, ‐12.67]

7.1 Studies without a placebo group

4

186

Mean Difference (IV, Fixed, 95% CI)

‐25.27 [‐35.04, ‐15.50]

7.2 Placebo‐controlled studies

2

172

Mean Difference (IV, Fixed, 95% CI)

0.92 [‐23.94, 25.79]

8 Duration of phototherapy (days) Show forest plot

5

298

Mean Difference (IV, Fixed, 95% CI)

‐1.23 [‐1.43, ‐1.02]

8.1 Studies without a placebo group

3

126

Mean Difference (IV, Fixed, 95% CI)

‐1.28 [‐1.49, ‐1.07]

8.2 Placebo‐controlled studies

2

172

Mean Difference (IV, Fixed, 95% CI)

‐0.50 [‐1.24, 0.24]

Figures and Tables -
Comparison 2. Intravenous immunoglobulin plus phototherapy versus phototherapy. Rh incompatibility only
Comparison 3. Intravenous immunoglobulin (IVIg) plus phototherapy versus phototherapy. IVIg administration ≤ 12 hours after birth

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Use of exchange transfusion (≥ 1) Show forest plot

5

335

Risk Ratio (M‐H, Fixed, 95% CI)

0.41 [0.26, 0.66]

1.1 Studies without a placebo group

3

163

Risk Ratio (M‐H, Fixed, 95% CI)

0.22 [0.11, 0.42]

1.2 Placebo‐controlled studies

2

172

Risk Ratio (M‐H, Fixed, 95% CI)

0.98 [0.48, 1.98]

2 Exchange transfusions per infant Show forest plot

5

335

Mean Difference (IV, Fixed, 95% CI)

‐0.19 [‐0.28, ‐0.10]

2.1 Studies without a placebo group

3

163

Mean Difference (IV, Fixed, 95% CI)

‐0.30 [‐0.42, ‐0.18]

2.2 Placebo‐controlled studies

2

172

Mean Difference (IV, Fixed, 95% CI)

‐0.04 [‐0.18, 0.10]

3 Use of top‐up transfusion in 1st week Show forest plot

3

262

Risk Ratio (M‐H, Fixed, 95% CI)

1.18 [0.70, 2.00]

4 Top‐up transfusions in 1st week per infant Show forest plot

3

262

Mean Difference (IV, Fixed, 95% CI)

0.05 [‐0.07, 0.17]

5 Use of top‐up transfusions after 1st week Show forest plot

4

245

Risk Ratio (M‐H, Fixed, 95% CI)

1.04 [0.89, 1.22]

6 Top‐up transfusions after 1st week per infant Show forest plot

3

204

Mean Difference (IV, Fixed, 95% CI)

‐0.00 [‐0.12, 0.12]

7 Maximum total serum bilirubin (µmol/L) Show forest plot

5

335

Mean Difference (IV, Fixed, 95% CI)

‐20.57 [‐29.81, ‐11.33]

7.1 Studies without a placebo group

3

163

Mean Difference (IV, Fixed, 95% CI)

‐24.01 [‐33.96, ‐14.06]

7.2 Placebo‐controlled studies

2

172

Mean Difference (IV, Fixed, 95% CI)

0.92 [‐23.94, 25.79]

8 Duration of phototherapy (days) Show forest plot

3

262

Mean Difference (IV, Fixed, 95% CI)

‐1.24 [‐1.44, ‐1.03]

8.1 Studies without a placebo group

1

90

Mean Difference (IV, Fixed, 95% CI)

‐1.30 [‐1.51, ‐1.09]

8.2 Placebo‐controlled studies

2

172

Mean Difference (IV, Fixed, 95% CI)

‐0.50 [‐1.24, 0.24]

Figures and Tables -
Comparison 3. Intravenous immunoglobulin (IVIg) plus phototherapy versus phototherapy. IVIg administration ≤ 12 hours after birth
Comparison 4. Intravenous immunoglobulin (IVIg) plus phototherapy versus phototherapy. Single dose of IVIg

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Use of exchange transfusion (≥ 1) Show forest plot

7

563

Risk Ratio (M‐H, Fixed, 95% CI)

0.37 [0.26, 0.53]

1.1 Studies without a placebo group

5

391

Risk Ratio (M‐H, Fixed, 95% CI)

0.27 [0.17, 0.42]

1.2 Placebo‐controlled studies

2

172

Risk Ratio (M‐H, Fixed, 95% CI)

0.98 [0.48, 1.98]

2 Exchange transfusions per infant Show forest plot

7

563

Mean Difference (IV, Fixed, 95% CI)

‐0.21 [‐0.28, ‐0.14]

2.1 Studies without a placebo group

5

391

Mean Difference (IV, Fixed, 95% CI)

‐0.27 [‐0.36, ‐0.19]

2.2 Placebo‐controlled studies

2

172

Mean Difference (IV, Fixed, 95% CI)

‐0.04 [‐0.18, 0.10]

3 Use of top‐up transfusions in 1st week Show forest plot

4

378

Risk Ratio (M‐H, Fixed, 95% CI)

1.05 [0.65, 1.69]

4 Top‐up transfusions in 1st week per infant Show forest plot

3

262

Mean Difference (IV, Fixed, 95% CI)

0.05 [‐0.07, 0.17]

5 Use of top‐up transfusion after 1st week Show forest plot

6

473

Risk Ratio (M‐H, Fixed, 95% CI)

1.13 [0.95, 1.33]

6 Top‐up transfusions after 1st week per infant Show forest plot

4

316

Mean Difference (IV, Fixed, 95% CI)

‐0.00 [‐0.12, 0.12]

7 Maximum total serum bilirubin (µmol/L) Show forest plot

6

451

Mean Difference (IV, Fixed, 95% CI)

‐25.39 [‐34.07, ‐16.70]

7.1 Studies without a placebo group

4

279

Mean Difference (IV, Fixed, 95% CI)

‐29.05 [‐38.32, ‐19.78]

7.2 Placebo‐controlled studies

2

172

Mean Difference (IV, Fixed, 95% CI)

0.92 [‐23.94, 25.79]

8 Duration of phototherapy (days) Show forest plot

5

490

Mean Difference (IV, Fixed, 95% CI)

‐1.12 [‐1.30, ‐0.94]

8.1 Studies without a placebo group

3

318

Mean Difference (IV, Fixed, 95% CI)

‐1.16 [‐1.34, ‐0.97]

8.2 Placebo‐controlled studies

2

172

Mean Difference (IV, Fixed, 95% CI)

‐0.50 [‐1.24, 0.24]

Figures and Tables -
Comparison 4. Intravenous immunoglobulin (IVIg) plus phototherapy versus phototherapy. Single dose of IVIg
Comparison 5. Intravenous immunoglobulin (IVIg) plus phototherapy versus phototherapy. Multiple doses of IVIg

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Use of exchange transfusion (≥ 1) Show forest plot

1

34

Risk Ratio (M‐H, Fixed, 95% CI)

0.27 [0.09, 0.81]

2 Exchange transfusions per infant Show forest plot

1

34

Mean Difference (IV, Fixed, 95% CI)

‐0.94 [‐1.45, ‐0.43]

3 Use of top‐up transfusions after 1st week Show forest plot

1

34

Odds Ratio (M‐H, Fixed, 95% CI)

5.65 [0.25, 126.87]

4 Duration of phototherapy (days) Show forest plot

1

34

Mean Difference (IV, Fixed, 95% CI)

‐1.47 [‐2.52, ‐0.42]

Figures and Tables -
Comparison 5. Intravenous immunoglobulin (IVIg) plus phototherapy versus phototherapy. Multiple doses of IVIg
Comparison 6. Intravenous immunoglobulin (IVIg) plus phototherapy versus phototherapy. Gestational age ≥ 37 weeks

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Use of exchange transfusion (≥ 1) Show forest plot

6

391

Risk Ratio (M‐H, Fixed, 95% CI)

0.39 [0.25, 0.61]

1.1 Studies without a placebo group

4

301

Risk Ratio (M‐H, Fixed, 95% CI)

0.29 [0.18, 0.49]

1.2 Placebo‐controlled studies

2

90

Risk Ratio (M‐H, Fixed, 95% CI)

1.78 [0.49, 6.42]

2 Exchange transfusions per infant Show forest plot

6

391

Mean Difference (IV, Fixed, 95% CI)

‐0.17 [‐0.26, ‐0.08]

2.1 Studies without a placebo group

4

301

Mean Difference (IV, Fixed, 95% CI)

‐0.25 [‐0.36, ‐0.15]

2.2 Placebo‐controlled studies

2

90

Mean Difference (IV, Fixed, 95% CI)

0.05 [‐0.12, 0.22]

3 Use of top‐up transfusion in 1st week Show forest plot

4

296

Risk Ratio (M‐H, Fixed, 95% CI)

0.91 [0.48, 1.74]

4 Top‐up transfusions in 1st week per infant Show forest plot

3

180

Mean Difference (IV, Fixed, 95% CI)

‐0.01 [‐0.35, 0.33]

5 Use of top‐up transfusion after 1st week Show forest plot

4

240

Risk Ratio (M‐H, Fixed, 95% CI)

1.18 [0.81, 1.71]

6 Top‐up transfusions after 1st week per infant Show forest plot

2

90

Mean Difference (IV, Fixed, 95% CI)

‐0.03 [‐0.20, 0.13]

7 Maximum total serum bilirubin (µmol/L) Show forest plot

4

296

Mean Difference (IV, Fixed, 95% CI)

‐26.81 [‐35.97, ‐17.65]

7.1 Studies without a placebo group

2

206

Mean Difference (IV, Fixed, 95% CI)

‐30.33 [‐39.83, ‐20.82]

7.2 Placebo‐controlled studies

2

90

Mean Difference (IV, Fixed, 95% CI)

19.47 [‐15.00, 53.94]

8 Duration of phototherapy (days) Show forest plot

6

391

Mean Difference (IV, Fixed, 95% CI)

‐1.20 [‐1.38, ‐1.01]

8.1 Studies without a placebo group

4

301

Mean Difference (IV, Fixed, 95% CI)

‐1.25 [‐1.44, ‐1.06]

8.2 Placebo‐controlled studies

2

90

Mean Difference (IV, Fixed, 95% CI)

0.18 [‐0.75, 1.12]

9 Duration of hospitalization (days) Show forest plot

5

330

Mean Difference (IV, Fixed, 95% CI)

‐1.33 [‐1.59, ‐1.07]

9.1 Studies without a placebo group

3

240

Mean Difference (IV, Fixed, 95% CI)

‐1.37 [‐1.63, ‐1.10]

9.2 Placebo‐controlled studies

2

90

Mean Difference (IV, Fixed, 95% CI)

‐0.32 [‐1.69, 1.05]

Figures and Tables -
Comparison 6. Intravenous immunoglobulin (IVIg) plus phototherapy versus phototherapy. Gestational age ≥ 37 weeks