Inmunoglobulina para la enfermedad hemolítica aloinmune en los recién nacidos
Appendices
Appendix 1. Complete search strategy
| Database | Search strategy | Number of unique references |
| PubMed | Strategy 1: limited to RCTs or Systematic Reviews (immunoglobulin OR gammaglobulin or immunoglobulins OR gammaglobulins OR "Immunoglobulins"[Mesh] OR "Immunoglobulins, Intravenous"[mesh] OR "Intravenous Immune Globulin" OR "Intravenous Immune Globulins" OR IVIG OR "Intravenous IG" OR "Intravenous Immunoglobulins" OR "Intravenous Immunoglobulin" OR "IV Immunoglobulins" OR "Intravenous Antibodies" OR "Intravenous Antibody" OR "Venoglobulin‐I" OR "Venoglobulin I" OR VenoglobulinI OR Gamimune OR Gamimmune OR "Gamimune N" OR "Gamimmune N" OR Gammagard OR Gammonativ OR "Globulin‐N" OR "Globulin N" OR GlobulinN OR Intraglobin OR Iveegam OR "Modified Immune Globulin" OR Sandoglobulin OR Venimmune OR Venoglobulin OR Alphaglobin OR Endobulin) AND (((isoimmune haemolytic jaundice OR alloimmune haemolytic jaundice OR isoimmune haemolytic jaundice OR alloimmune haemolytic jaundice OR jaundice OR hyperbilirubinemia OR hyperbilirubinemi* OR haemolysis OR haemolytic OR haemolytic OR haemolysis OR hyperbilirubinemia OR hyperbilirubinaemi* OR rhesus OR isoimmune OR "Anemia, Hemolytic"[mesh] OR "Jaundice"[mesh] OR "Hyperbilirubinemia"[mesh] OR "Hemolysis"[mesh]) AND ("Infant, Newborn"[mesh] OR newborn OR newborns OR neon* OR neonate OR neonates OR neonat* OR neonatal OR "Low Birth Weight Infant" OR "Small for Gestational Age Infant" OR "Very Low Birth Weight Infant" OR "Postmature Infant" OR "Premature Infant" OR "Low Birth Weight Infants" OR "Small for Gestational Age Infants" OR "Very Low Birth Weight Infants" OR "Postmature Infants" OR "Premature Infants" OR premature OR low birth weight OR VLBW OR LBW)) OR "Anemia, Neonatal" OR "Jaundice, Neonatal") AND (randomised controlled trial [pt] OR controlled clinical trial [pt] OR randomised [tiab] OR placebo [tiab] OR clinical trials as topic [mesh: noexp] OR randomly [tiab] OR trial [ti] OR RCT OR RCTS OR randomized [tiab] OR systematic[sb]) Strategy 2: focus on Immunoglobulin infusion and isoimmune haemolytic jaundice, no other limits applied immunoglobulin[ti] OR gammaglobulin[ti] or immunoglobulins[ti] OR gammaglobulins[ti] OR "Immunoglobulins"[majr] OR "Immunoglobulins, Intravenous"[majr] OR "Intravenous Immune Globulin"[ti] OR "Intravenous Immune Globulins"[ti] OR IVIG[ti] OR "Intravenous IG"[ti] OR "Intravenous Immunoglobulins"[ti] OR "Intravenous Immunoglobulin"[ti] OR "IV Immunoglobulins"[ti] OR (Intravenous[ti] AND Antibodies[ti]) OR "Intravenous Antibody"[ti] OR "Venoglobulin‐I"[ti] OR "Venoglobulin I"[ti] OR VenoglobulinI[ti] OR Gamimune[ti] OR Gamimmune[ti] OR "Gamimune N"[ti] OR "Gamimmune N"[ti] OR Gammagard[ti] OR Gammonativ[ti] OR "Globulin‐N"[ti] OR "Globulin N"[ti] OR GlobulinN[ti] OR Intraglobin[ti] OR Iveegam[ti] OR "Modified Immune Globulin"[ti] OR Sandoglobulin[ti] OR Venimmune[ti] OR Venoglobulin[ti] OR Alphaglobin[ti] OR Endobulin[ti]) AND ((((isoimmune[ti] AND haemolytic[ti] AND jaundice[ti]) OR (alloimmune[ti] AND haemolytic[ti] AND jaundice[ti]) OR (isoimmune[ti] AND haemolytic[ti] AND jaundice[ti]) OR (alloimmune[ti] AND haemolytic[ti] AND jaundice[ti]) OR jaundice[ti] OR hyperbilirubinemia[ti] OR hyperbilirubinemi*[ti] OR haemolysis[ti] OR haemolytic[ti] OR haemolytic[ti] OR haemolysis[ti] OR hyperbilirubinemia[ti] OR hyperbilirubinaemi*[ti] OR rhesus[ti] OR isoimmune[ti] OR "Anemia, Hemolytic"[majr] OR "Jaundice"[majr] OR "Hyperbilirubinemia"[majr] OR "Hemolysis"[majr]) AND ("Infant, Newborn"[mesh] OR newborn OR newborns OR neon* OR neonate OR neonates OR neonat* OR neonatal OR "Low Birth Weight Infant" OR "Small for Gestational Age Infant" OR "Very Low Birth Weight Infant" OR "Postmature Infant" OR "Premature Infant" OR "Low Birth Weight Infants" OR "Small for Gestational Age Infants" OR "Very Low Birth Weight Infants" OR "Postmature Infants" OR "Premature Infants" OR premature OR low birth weight OR VLBW OR LBW)) OR "Anemia, Neonatal" OR "Jaundice, Neonatal") NOT (animals [mh] NOT humans [mh]) | 873 |
| Embase (Ovid) | Strategy 1: limited to RCTs or Systematic Reviews (exp immunoglobulin/ OR (gammaglobulin* or immunoglobulin* OR "Immune Globulin*" OR IVIG OR "Intravenous IG" OR "Intravenous Antibod*" OR "Venoglobulin‐I" OR "Venoglobulin I" OR VenoglobulinI OR Gamimune OR Gamimmune OR "Gamimune N" OR "Gamimmune N" OR Gammagard OR Gammonativ OR "Globulin‐N" OR "Globulin N" OR GlobulinN OR Intraglobin OR Iveegam OR "Modified Immune Globulin" OR Sandoglobulin OR Venimmune OR Venoglobulin OR Alphaglobin OR Endobulin).mp) AND ((((isoimmune haemolytic jaundice OR alloimmune haemolytic jaundice OR isoimmune haemolytic jaundice OR alloimmune haemolytic jaundice OR jaundice OR hyperbilirubinemia OR hyperbilirubinemi* OR haemolysis OR haemolytic OR haemolytic OR haemolysis OR hyperbilirubinemia OR hyperbilirubinaemi* OR rhesus OR isoimmune).mp OR exp haemolytic anemia/ OR exp Jaundice/ OR exp hyperbilirubinemia/ OR exp haemolysis/) AND (exp Newborn/ OR (newborn OR newborns OR neon* OR neonate OR neonates OR neonat* OR neonatal OR "Low Birth Weight Infant" OR "Small for Gestational Age Infant" OR "Very Low Birth Weight Infant" OR "Postmature Infant" OR "Premature Infant" OR "Low Birth Weight Infants" OR "Small for Gestational Age Infants" OR "Very Low Birth Weight Infants" OR "Postmature Infants" OR "Premature Infants" OR premature OR low birth weight OR VLBW OR LBW).mp)) OR newborn jaundice/ or newborn anemia/) AND (exp randomised controlled trial/ OR exp controlled clinical trial/ OR random*.ti,ab OR placebo*.ti,ab OR exp "clinical trial (topic)"/ OR trial*.ti OR RCT.ti,ab OR RCTS.ti,ab OR exp evidence based medicine/) Strategy 2: focus on Immunoglobulin infusion and isoimmune haemolytic jaundice, no other limits applied (exp *immunoglobulin/ OR (gammaglobulin* OR immunoglobulin* OR "Immune Globulin*" OR IVIG OR "Intravenous IG" OR "Intravenous Antibod*" OR "Venoglobulin‐I" OR "Venoglobulin I" OR VenoglobulinI OR Gamimune OR Gamimmune OR "Gamimune N" OR "Gamimmune N" OR Gammagard OR Gammonativ OR "Globulin‐N" OR "Globulin N" OR GlobulinN OR Intraglobin OR Iveegam OR "Modified Immune Globulin" OR Sandoglobulin OR Venimmune OR Venoglobulin OR Alphaglobin OR Endobulin).ti) AND ((((isoimmune haemolytic jaundice OR alloimmune haemolytic jaundice OR isoimmune haemolytic jaundice OR alloimmune haemolytic jaundice OR jaundice OR hyperbilirubinemia OR hyperbilirubinemi* OR haemolysis OR haemolytic OR haemolytic OR haemolysis OR hyperbilirubinemia OR hyperbilirubinaemi* OR rhesus OR isoimmune).ti OR exp *haemolytic anemia/ OR exp *Jaundice/ OR exp *hyperbilirubinemia/ OR exp *haemolysis/) AND (exp Newborn/ OR (newborn OR newborns OR neon* OR neonate OR neonates OR neonat* OR neonatal OR "Low Birth Weight Infant" OR "Small for Gestational Age Infant" OR "Very Low Birth Weight Infant" OR "Postmature Infant" OR "Premature Infant" OR "Low Birth Weight Infants" OR "Small for Gestational Age Infants" OR "Very Low Birth Weight Infants" OR "Postmature Infants" OR "Premature Infants" OR premature OR low birth weight OR VLBW OR LBW).mp)) OR *newborn jaundice/ or *newborn anemia/) AND exp human/ | 530 |
| The Cochrane Library (including CENTRAL) | (immunoglobulin OR gammaglobulin or immunoglobulins OR gammaglobulins OR Intravenous Immune Globulin OR Intravenous Immune Globulins OR IVIG OR Intravenous IG OR Intravenous Immunoglobulins OR Intravenous Immunoglobulin OR IV Immunoglobulins OR Intravenous Antibodies OR Intravenous Antibody OR Venoglobulin‐I OR Venoglobulin I OR VenoglobulinI OR Gamimune OR Gamimmune OR Gamimune N OR Gamimmune N OR Gammagard OR Gammonativ OR Globulin‐N OR Globulin N OR GlobulinN OR Intraglobin OR Iveegam OR Modified Immune Globulin OR Sandoglobulin OR Venimmune OR Venoglobulin OR Alphaglobin OR Endobulin) AND (isoimmune haemolytic jaundice OR alloimmune haemolytic jaundice OR isoimmune haemolytic jaundice OR alloimmune haemolytic jaundice OR jaundice OR hyperbilirubinemia OR hyperbilirubinemi* OR haemolysis OR haemolytic OR haemolytic OR haemolysis OR hyperbilirubinemia OR hyperbilirubinaemi* OR rhesus OR isoimmune) AND (newborn OR newborns OR neon* OR neonate OR neonates OR neonat* OR neonatal OR Low Birth Weight Infant OR Small for Gestational Age Infant OR Very Low Birth Weight Infant OR Postmature Infant OR Premature Infant OR Low Birth Weight Infants OR Small for Gestational Age Infants OR Very Low Birth Weight Infants OR Postmature Infants OR Premature Infants OR premature OR low birth weight OR VLBW OR LBW) | 19 |
| Web of Science | TS=((immunoglobulin OR gammaglobulin or immunoglobulins OR gammaglobulins OR Intravenous Immune Globulin OR Intravenous Immune Globulins OR IVIG OR Intravenous IG OR Intravenous Immunoglobulins OR Intravenous Immunoglobulin OR IV Immunoglobulins OR Intravenous Antibodies OR Intravenous Antibody OR Venoglobulin‐I OR Venoglobulin I OR VenoglobulinI OR Gamimune OR Gamimmune OR Gamimune N OR Gamimmune N OR Gammagard OR Gammonativ OR Globulin‐N OR Globulin N OR GlobulinN OR Intraglobin OR Iveegam OR Modified Immune Globulin OR Sandoglobulin OR Venimmune OR Venoglobulin OR Alphaglobin OR Endobulin) AND (isoimmune haemolytic jaundice OR alloimmune haemolytic jaundice OR isoimmune haemolytic jaundice OR alloimmune haemolytic jaundice OR jaundice OR hyperbilirubinemia OR hyperbilirubinemi* OR haemolysis OR haemolytic OR haemolytic OR haemolysis OR hyperbilirubinemia OR hyperbilirubinaemi* OR rhesus OR isoimmune) AND (newborn OR newborns OR neon* OR neonate OR neonates OR neonat* OR neonatal OR Low Birth Weight Infant OR Small for Gestational Age Infant OR Very Low Birth Weight Infant OR Postmature Infant OR Premature Infant OR Low Birth Weight Infants OR Small for Gestational Age Infants OR Very Low Birth Weight Infants OR Postmature Infants OR Premature Infants OR premature OR low birth weight OR VLBW OR LBW) AND (trial* OR RCT* OR random* OR placebo* OR eviden* OR systematic*)) | 68 |
| CINAHL (EBSCOhost), replaced by Emcare per 1 January 2017 | ((immunoglobulin OR gammaglobulin or immunoglobulins OR gammaglobulins OR Intravenous Immune Globulin OR Intravenous Immune Globulins OR IVIG OR Intravenous IG OR Intravenous Immunoglobulins OR Intravenous Immunoglobulin OR IV Immunoglobulins OR Intravenous Antibodies OR Intravenous Antibody OR Venoglobulin‐I OR Venoglobulin I OR VenoglobulinI OR Gamimune OR Gamimmune OR Gamimune N OR Gamimmune N OR Gammagard OR Gammonativ OR Globulin‐N OR Globulin N OR GlobulinN OR Intraglobin OR Iveegam OR Modified Immune Globulin OR Sandoglobulin OR Venimmune OR Venoglobulin OR Alphaglobin OR Endobulin) AND (isoimmune haemolytic jaundice OR alloimmune haemolytic jaundice OR isoimmune haemolytic jaundice OR alloimmune haemolytic jaundice OR jaundice OR hyperbilirubinemia OR hyperbilirubinemi* OR haemolysis OR haemolytic OR haemolytic OR haemolysis OR hyperbilirubinemia OR hyperbilirubinaemi* OR rhesus OR isoimmune) AND (newborn OR newborns OR neon* OR neonate OR neonates OR neonat* OR neonatal OR Low Birth Weight Infant OR Small for Gestational Age Infant OR Very Low Birth Weight Infant OR Postmature Infant OR Premature Infant OR Low Birth Weight Infants OR Small for Gestational Age Infants OR Very Low Birth Weight Infants OR Postmature Infants OR Premature Infants OR premature OR low birth weight OR VLBW OR LBW)) | 45 |
| Academic Search Premier | ((immunoglobulin OR gammaglobulin or immunoglobulins OR gammaglobulins OR Intravenous Immune Globulin OR Intravenous Immune Globulins OR IVIG OR Intravenous IG OR Intravenous Immunoglobulins OR Intravenous Immunoglobulin OR IV Immunoglobulins OR Intravenous Antibodies OR Intravenous Antibody OR Venoglobulin‐I OR Venoglobulin I OR VenoglobulinI OR Gamimune OR Gamimmune OR Gamimune N OR Gamimmune N OR Gammagard OR Gammonativ OR Globulin‐N OR Globulin N OR GlobulinN OR Intraglobin OR Iveegam OR Modified Immune Globulin OR Sandoglobulin OR Venimmune OR Venoglobulin OR Alphaglobin OR Endobulin) AND (isoimmune haemolytic jaundice OR alloimmune haemolytic jaundice OR isoimmune haemolytic jaundice OR alloimmune haemolytic jaundice OR jaundice OR hyperbilirubinemia OR hyperbilirubinemi* OR haemolysis OR haemolytic OR haemolytic OR haemolysis OR hyperbilirubinemia OR hyperbilirubinaemi* OR rhesus OR isoimmune) AND (newborn OR newborns OR neon* OR neonate OR neonates OR neonat* OR neonatal OR Low Birth Weight Infant OR Small for Gestational Age Infant OR Very Low Birth Weight Infant OR Postmature Infant OR Premature Infant OR Low Birth Weight Infants OR Small for Gestational Age Infants OR Very Low Birth Weight Infants OR Postmature Infants OR Premature Infants OR premature OR low birth weight OR VLBW OR LBW)) | 30 |
| Emcare | Strategy 1: limited to RCTs or Systematic Reviews (exp immunoglobulin/ OR (gammaglobulin* or immunoglobulin* OR "Immune Globulin*" OR IVIG OR "Intravenous IG" OR "Intravenous Antibod*" OR "Venoglobulin‐I" OR "Venoglobulin I" OR VenoglobulinI OR Gamimune OR Gamimmune OR "Gamimune N" OR "Gamimmune N" OR Gammagard OR Gammonativ OR "Globulin‐N" OR "Globulin N" OR GlobulinN OR Intraglobin OR Iveegam OR "Modified Immune Globulin" OR Sandoglobulin OR Venimmune OR Venoglobulin OR Alphaglobin OR Endobulin).mp) AND ((((isoimmune haemolytic jaundice OR alloimmune haemolytic jaundice OR isoimmune haemolytic jaundice OR alloimmune haemolytic jaundice OR jaundice OR hyperbilirubinaemia OR hyperbilirubinemi* OR haemolysis OR haemolytic OR haemolytic OR haemolysis OR hyperbilirubinemia OR hyperbilirubinaemi* OR rhesus OR isoimmune).mp OR exp haemolytic anemia/ OR exp Jaundice/ OR exp hyperbilirubinemia/ OR exp haemolysis/) AND (exp Newborn/ OR (newborn OR newborns OR neon* OR neonate OR neonates OR neonat* OR neonatal OR "Low Birth Weight Infant" OR "Small for Gestational Age Infant" OR "Very Low Birth Weight Infant" OR "Postmature Infant" OR "Premature Infant" OR "Low Birth Weight Infants" OR "Small for Gestational Age Infants" OR "Very Low Birth Weight Infants" OR "Postmature Infants" OR "Premature Infants" OR premature OR low birth weight OR VLBW OR LBW).mp)) OR newborn jaundice/ or newborn anemia/) AND (exp randomised controlled trial/ OR exp controlled clinical trial/ OR random*.ti,ab OR placebo*.ti,ab OR exp "clinical trial (topic)"/ OR trial*.ti OR RCT.ti,ab OR RCTS.ti,ab OR exp evidence based medicine/) Strategy 2: focus on Immunoglobulin infusion and isoimmune haemolytic jaundice, no other limits applied (exp *immunoglobulin/ OR (gammaglobulin* OR immunoglobulin* OR "Immune Globulin*" OR IVIG OR "Intravenous IG" OR "Intravenous Antibod*" OR "Venoglobulin‐I" OR "Venoglobulin I" OR VenoglobulinI OR Gamimune OR Gamimmune OR "Gamimune N" OR "Gamimmune N" OR Gammagard OR Gammonativ OR "Globulin‐N" OR "Globulin N" OR GlobulinN OR Intraglobin OR Iveegam OR "Modified Immune Globulin" OR Sandoglobulin OR Venimmune OR Venoglobulin OR Alphaglobin OR Endobulin).ti) AND ((((isoimmune haemolytic jaundice OR alloimmune haemolytic jaundice OR isoimmune haemolytic jaundice OR alloimmune haemolytic jaundice OR jaundice OR hyperbilirubinemia OR hyperbilirubinemi* OR haemolysis OR haemolytic OR haemolytic OR haemolysis OR hyperbilirubinemia OR hyperbilirubinaemi* OR rhesus OR isoimmune).ti OR exp *haemolytic anemia/ OR exp *Jaundice/ OR exp *hyperbilirubinemia/ OR exp *haemolysis/) AND (exp Newborn/ OR (newborn OR newborns OR neon* OR neonate OR neonates OR neonat* OR neonatal OR "Low Birth Weight Infant" OR "Small for Gestational Age Infant" OR "Very Low Birth Weight Infant" OR "Postmature Infant" OR "Premature Infant" OR "Low Birth Weight Infants" OR "Small for Gestational Age Infants" OR "Very Low Birth Weight Infants" OR "Postmature Infants" OR "Premature Infants" OR premature OR low birth weight OR VLBW OR LBW).mp)) OR *newborn jaundice/ or *newborn anemia/) AND exp human/ | 0 |
| Total | 1565 |
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.
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.
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.
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.
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.
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.
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.
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.
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).
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.
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.
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.
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).
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.
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.
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.
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).
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.
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).
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.
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.
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.
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).
Comparison 6 Intravenous immunoglobulin (IVIg) plus phototherapy versus phototherapy. Gestational age ≥ 37 weeks, Outcome 9 Duration of hospitalization (days).
| 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 | Quality of the evidence | Relative effect | Anticipated absolute effects* (95% CI) | |
| Risk with phototherapy alone | Risk difference with IVIg + phototherapy | ||||
| Use of ET (≥ 1); all studies | 658 | ⊕⊝⊝⊝ | RR 0.35 | Study population | |
| 329 per 1000 | 214 fewer per 1000 | ||||
| Use of ET (≥ 1); placebo‐controlled studies | 172 | ⊕⊕⊕⊝ | RR 0.98 | Study population | |
| 153 per 1000 | 3 fewer per 1000 | ||||
| ETs performed per infant; all studies | 658 | ⊕⊝⊝⊝ | ‐ | The mean ETs per infant for all studies was 0 | MD 0.34 lower |
| ETs performed per infant; placebo‐controlled studies | 172 | ⊕⊕⊕⊝ | ‐ | The mean ETs per infant for placebo‐controlled studies was 0 | MD 0.04 lower |
| Use of top‐up transfusion in 1st week of life; all studies | 378 | ⊕⊕⊝⊝ | RR 1.05 | Study population | |
| 130 per 1000 | 6 more per 1000 | ||||
| Use of top‐up transfusion after 1st week of life; all studies | 507 | ⊕⊝⊝⊝ | RR 1.16 | Study population | |
| 219 per 1000 | 35 more per 1000 | ||||
| Maximum total serum bilirubin (µmol/L); all studies | 451 | ⊕⊝⊝⊝ | ‐ | The mean maximum serum bilirubin (µmol/L) for all studies was 0 | MD 25.39 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 | |||||
| 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. | |||||
| 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] |
| 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] |
| 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] |
| 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] |
| 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] |
| 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] |
