Bovine lung lavage surfactant extract compared with modified bovine minced lung surfactant extract in preterm infants for prevention of RDS (Comparision 1: Prevention studies)

Patient or population: Preterm infants for prevention of RDS
Setting: Hospital
Intervention: Bovine lung lavage surfactant extract
Comparison: Modified bovine minced lung surfactant extract

Mortality prior to discharge (from any cause)

RR 1.24
(0.90 to 1.71)

1123
(2 RCTs)

⨁⨁⨁◯
MODERATE ¹

Downgraded one level due to imprecision (95% CI includes both no effect and appreciable harm) and and the total number of events does not meet the optimal information size (OIS).

Oxygen requirement at 36 weeks' postmenstrual age

RR 0.97
(0.79 to 1.19)

749
(1 RCT)

⨁⨁⨁◯
MODERATE ²

Downgraded one level due to imprecision (95% CI includes both no effect and appreciable harm).

Death or oxygen requirement at 36 weeks' postmenstrual age

RR 1.02
(0.89 to 1.17)

1133
(2 RCTs)

⨁⨁⨁⨁
HIGH

We did not downgrade evidence for imprecision as it was considered that 95% CI is narrow and precise around the no effect. The total number of events meets the OIS

Pneumothorax.

RR 0.76
(0.43 to 1.36)

749
(1 RCT)

⨁⨁⨁◯
MODERATE ²

Downgraded one level due to imprecision (95% CI includes both no effect and appreciable harm)

Pulmonary hemorrhage

RR 1.44
(0.88 to 2.39)

1123
(2 RCTs)

⨁⨁◯◯
LOW ³

Downgraded two levels due to very serious imprecision: 1) the 95% CI includes both no effect and appreciable harm. 2) the total number of events does not meet the optimal information size (OIS to detect a clinically beneficial effect if there is one is > 3000)

Severe IVH in infants receiving neuroimaging

RR 1.28
(0.89 to 1.83)

1087
(2 RCTs)

⨁⨁◯◯
LOW ⁴

Downgraded two levels due to very serious imprecision: 1) 95% CI includes both no effect and appreciable harm.2) The total number of events does not meet the optimal information size (OIS to detect a clinically beneficial effect if there is one is > 2000).

Neurodevelopmental outcome at approximately two years’ corrected age

Not reported in any of the studies

*The risk in the intervention group (and its 95% CI) 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; OR: Odds 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

Bovine lung lavage surfactant extract compared with modified bovine minced lung surfactant extract in preterm infants for treatment of RDS

Patient or population: Preterm infants for treatment of RDS
Setting: Hospital
Intervention: Bovine lung lavage surfactant extract
Comparison: Modified bovine minced lung surfactant extract

Mortality prior to discharge

RR 0.98
(0.79 to 1.21)

2231
(6 RCTs)

⨁⨁⨁◯
MODERATE ¹

Downgraded one level due to imprecision (95% CI includes both no effect and appreciable harm) and the total number of events does not meet the OIS.

Oxygen requirement at 36 weeks' postmenstrual age (all infants)

RR 0.95
(0.82 to 1.11)

1564
(5 RCTs)

⨁⨁⨁⨁
HIGH

We did not downgrade evidence for imprecision as it was considered that 95% CI is narrow and precise around the probability of no effect. Estimations are based in more than 300 events in each arm.

Death or oxygen requirement at 36 weeks' postmenstrual age

RR 0.95
(0.86 to 1.06)

2009
(3 RCTs)

⨁⨁⨁⨁
HIGH

We did not downgrade evidence for imprecision as it was considered that 95% CI is narrow and precise around the probability of no effect. Estimations are based in more than 300 events in each arm.

Pneumothorax

RR 1.14
(0.85 to 1.51)

2224
(6 RCTs)

⨁⨁◯◯
LOW ^{1 2}

Downgraded two levels due to:

1) Serious imprecision (95% CI includes both no effect and appreciable harm).

2) Inconsistency: Unexplained heterogeneity, with point estimates widely different; 95% CI not overlapping and leading to different conclusions (P value 0.03, Chi² 10.66, I² = 62%)

Pulmonary hemorrhage

RR 1.08
(0.74 to 1.59)

2138
(4 RCTs)

⨁⨁⨁◯
MODERATE ¹

Downgraded one level due to imprecision (95% CI includes both no effect and appreciable harm)

Severe IVH in infants receiving neuroimaging

RR 0.86
(0.68 to 1.09)

2040
(5 RCTs)

⨁⨁⨁◯
MODERATE ³

Downgraded one level due to imprecision (95% CI includes benefits, no effect and appreciable harm). The optimal information size to reliably detect a clinically beneficial effect if there is one is > 7000

Neurodevelopmental outcome at approximately two years’ corrected age

Not reported in any of the studies

*The risk in the intervention group (and its 95% CI) 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; OR: Odds 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

Bovine lung lavage surfactant extract compared with porcine minced lung surfactant extract in preterm infants for treatment of RDS

Patient or population: Preterm infants for treatment of RDS
Setting: Hospital
Intervention: Bovine lung lavage surfactant extract
Comparison: Porcine minced lung surfactant extract

Mortality prior to discharge

RR 1.40
(0.51 to 3.87)

54
(1 RCT)

⨁⨁◯◯
LOW ¹

Downgraded two levels due to very serious imprecision: 1) the 95% CI includes both no effect and appreciable harm.

2) the total number of events does not meet the optimal information size (OIS to detect a clinically beneficial effect if there is one is > 1000)

Oxygen requirement at 36 weeks' postmenstrual age

RR 0.75
(0.19 to 3.04)

54
(1 RCT)

⨁⨁◯◯
LOW ¹

Downgraded two levels due to:

1. Serious imprecision (95% CI includes both no effect and appreciable harm).

2. Total number of events does not meet the optimal information size (OIS to detect a clinically beneficial effect if there is one is > 1000)

Death or oxygen requirement at 36 weeks' postmenstrual age

Not reported in any of the studies

Pneumothorax

Not reported in any of the studies

Pulmonary hemorrhage

Not reported in any of the studies

Severe intraventricular hemorrhage in infants who received neuroimaging

RR 0.83
(0.29 to 2.41)

54
(1 RCT)

⨁◯◯◯
VERY LOW ^{2 3}

Downgraded three levels due to:

1. potential risk of bias (lack of blinding of outcome assessment)

2. very serious imprecision: (95% CI includes both no effect and appreciable harm) and the total number of events does not meet the optimal information size (OIS to detect a clinically beneficial effect if there is one is > 1000)

Neurodevelopmental outcome at approximately two years’ corrected age

Not reported in any of the studies

*The risk in the intervention group (and its 95% CI) 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; OR: Odds 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

Modified bovine minced lung surfactant extract compared with porcine minced lung surfactant extract in preterm infants for treatment of RDS

Patient or population: Preterm infants for treatment of RDS
Setting: Hospital
Intervention: Modified bovine minced lung surfactant extract
Comparison: Porcine minced lung surfactant extract

Mortality prior to hospital discharge (from any cause)

RR 1.44
(1.04 to 2.00)

901
(9 RCTs)

⨁⨁⨁◯
MODERATE ¹

Downgraded one level due to imprecision (95% CI includes both no effect and appreciable harm).

Despite the high risk of bias⁴ we did not downgrade the quality because of its lower impact on this outcome.

Oxygen requirement at 36 weeks' postmenstrual age

RR 1.04 (0.83 to 1.31)

773
(8RCTs)

⨁⨁⨁◯
MODERATE ²

Downgraded one level due to imprecision (95% CI includes both no effect and appreciable harm).

Despite the high risk of bias⁴ we did not downgrade the quality because of its lower impact on this outcome.

Death or oxygen requirement at 36 weeks' postmenstrual age

RR 1.30
(1.04 to 1.64)

448
(3 RCTs)

⨁⨁⨁◯
MODERATE ¹

Downgraded one level due to imprecision (total number of events does not meet the OIS)

Pneumothorax

RR 1.24
(0.71 to 2.17)

669
(6 RCTs)

⨁⨁◯◯
LOW ³

Downgraded two levels due to very serious imprecision:

1) the 95% CI includes both no effect and appreciable harm.

2) The total number of events does not meet the optimal information size (OIS to detect a clinically beneficial effect if there is one is > 5000)

Pulmonary hemorrhage

RR 1.28
(0.81 to 2.02)

871
(8 RCTs)

⨁⨁◯◯
LOW ³

Downgraded two levels due to very serious imprecision:

1) the 95% CI includes both no effect and appreciable harm.

2) The total number of events does not meet the optimal information size (OIS to detect a clinically beneficial effect if there is one is > 5000)

Severe intraventricular hemorrhage in infants who received neuroimaging

RR 1.28
(0.83 to 1.97)

705
(7 RCTs)

⨁◯◯◯
VERY LOW ^{4 5}

Downgraded three levels due to:

1. Potential risk of bias and 2. serious imprecision: 1) the 95% CI includes both no effect and appreciable harm; and 2) Total number of events does not meet the optimal information size (OIS to detect a clinically beneficial effect if there is one is > 3000)

Neurodevelopmental outcome at approximately two years’ corrected age

Not reported in any studies

*The risk in the intervention group (and its 95% CI) 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; OR: Odds 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

Modified bovine minced lung surfactant extract compared with porcine lung lavage surfactant in preterm infants for treatment of RDS

Patient or population: Preterm infants for treatment of RDS
Setting: Hospital
Intervention: Modified bovine minced lung surfactant extract
Comparison: Porcine lung lavage surfactant

Mortality prior to hospital discharge (from any cause)

RR 1.10
(0.60 to 1.99)

44
(1 RCT)

⨁⨁◯◯
LOW ¹

Downgraded two levels due to serious imprecision:

1) The 95% CI includes both no effect and appreciable harm.

2) Total number of events does not meet the optimal information size (OIS to detect a clinically beneficial effect if there is one is > 700).

Oxygen requirement at 36 weeks' postmenstrual age

Not reported in any of the studies

Death or oxygen requirement at 36 weeks' postmenstrual age

Not reported in any of the studies

Pneumothorax

RR 0.10
(0.01 to 0.73)

44
(1 RCT)

⨁⨁⨁⨁
HIGH

Pulmonary hemorrhage

Not reported in any of the studies

Severe intraventricular hemorrhage in infants who received neuroimaging

Not reported in any of the studies

Neurodevelopmental outcome at approximately two years corrected age

Not reported in any of the studies

*The risk in the intervention group (and its 95% CI) 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; OR: Odds 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