Introduction
Methods
Literature search
Eligibility criteria
Types of trials
Types of participants
Types of interventions
Types of outcome measures
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Algorithm 1: Moderate or severe redness
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Algorithm 2: Moderate redness with pus, or severe redness (without regard to pus)
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Algorithm 3: Severe redness with pus
Data abstraction and risk of bias assessment
Quantitative data synthesis
Recommendations for LiST
Results
Trial flow
Study characteristics
Study ID | Study groups | Any CHX vs. No CHX |
---|---|---|
Nepal trial 2006 [11] | Group A: Multiple cleansing of cord stump with 4 % CHX. Group B: Cleansing of cord with Soap and water Group C: Dry cord care | Group A vs. Group B +C |
Bangladesh trial 2012 [12] | Group A: Multiple cleansing of cord stump with 4 % CHX. Group B: Single cleansing of cord stump with 4 % CHX. Group C: Dry cord care |
Group A + B vs. Group C
|
Pakistan trial 2012 [13] | Group A: Multiple cleansing of cord stump with 4 % CHX and promotion of handwashing among caregivers. Group B: Promotion of handwashing only. Group C: Multiple cleansing of cord stump with 4 % CHX only Group D: Dry cord care |
Group A +C vs. Group B +D
|
Study characteristics | Nepal trial* | Bangladesh trial | Pakistan trial |
---|---|---|---|
Type of study
| Cluster RCT | Cluster RCT | 2 × 2 factorial design cluster RCT |
No. clusters (average size)
| 413 (700) | 133 (4100) | 187 (1000) |
Sample size total
| 15,123 | 29,760 | 9,741 |
Average sample size per group
| ~ 5,050 | ~ 9,900 | ~ 4,850 |
Duration of trial
| Nov 2002 to Mar 2005 | Jun 2007 to Sep 2009 | Jan 2008 to Jun 2009 |
Overall NMR
| 32/1000 | 36/1000 | 30/1000 |
% of home births
| 92 % | 93 % | 80 % |
Inclusion criteria
| All live births in the study area | All live births in the study area | All live births in the study area were included except those who were born in hospitals. |
Exclusion criteria
| Not met within 10 days after birth | Didn’t receive intervention within 7 days after birth | Not met within 3 days after birth. Babies with congenital anomalies |
Comparison group
| Dry cord care | Dry cord care | Dry cord care |
Intervention groups
| 1.Multiple CHX 2.Soap/H2O | 1.Multiple CHX 2.Single CHX | 1.Multiple CHX 2.Handwashing (HW) 3.CHX + HW |
CHX concentration
| 4.0 % | 4.0 % | 4.0 % |
Participants recruiters
| Local female worker | CHWs | CHWs |
Intervention providers
| Local project staff | Village health worker | TBA to caretaker |
Outcome assessors
| (Nonmedical) field workers | CHWs | CHWs |
Basic interventions to all babies/mothers
| CDK, FE/FA, TT, promotion of ANC/ENC | CDK. FE/FA, promotion of TT, ANC, birth preparedness, ENC | Basic component of ENC as promoted by Ministry of Health |
Primary outcomes
| Omphalitis, neonatal mortality | Omphalitis, neonatal mortality | Omphalitis, neonatal mortality |
Follow up days
| 1, 2, 3, 4, 6, 8, 10, 12, 14, 21, 28 | 1,3,6,9,15,28 | 1,3,5,7,14,28 |
Quantitative data synthesis
Effect on sepsis specific mortality
Quality Assessment | Summary of findings | |||||||
---|---|---|---|---|---|---|---|---|
Generalizability | Number of cases | Pooled effect | ||||||
No. of studies | Design | Limitations | Consistency | Generalizability to Population of Interest | Generalizability to intervention of Interest | CHX | Control | Relative risk (95 % CI) |
Sepsis Specific mortality: GRADE quality: Low | ||||||||
1 | RCT | None | Only one trial reported data | All the participants were neonates | 4.0% chlorhexidine solution. | Only RR was reported in the published manuscript. | 0.69 (0.40-1.18) | |
All-Cause neonatal mortality: GRADE quality: Moderate | ||||||||
3 | RCT | All three included studies are well conducted community randomized trials. Intervention was not masked in two studies. | Direction of effect in favor of intervention in all three studies. There was moderate statistical heterogeneity (I2 =50%). | All the participants were neonates | All the studies used 4.0% chlorhexidine solution. Frequency of application was different in different study groups. | 670/29543 | 655/25072 | 0.77 (0.63-0.94) |
Incidence of omphalitis: Algorithm 1 GRADE quality: Moderate | ||||||||
3 | RCT | All three included studies are well conducted community randomized trials. Intervention was not masked in two studies. | Direction of effect in favor of intervention in all three studies. There was moderate statistical heterogeneity (I2 =34%). | All the participants were neonates | All the studies used 4.0% chlorhexidine solution. Frequency of application was different in different study groups. | Not applicable as data was pooled by generic inverse variance | Not applicable as data was pooled by generic inverse variance | 0.73 (0.64-00.83) |
Incidence of omphalitis: Algorithm 2 GRADE quality: High | ||||||||
3 | RCT | All three included studies are well conducted community randomized trials. Intervention was not masked in two studies. | Direction of effect in favor of intervention in all three studies. No statistical heterogeneity (I2 =0%). | All the participants were neonates | All the studies used 4.0% chlorhexidine solution. Frequency of application was different in different study groups. | Not applicable as data was pooled by generic inverse variance | Not applicable as data was pooled by generic inverse variance | 0.69 (0.60-0.79) |
Incidence of omphalitis: Algorithm 3 GRADE quality: High | ||||||||
3 | RCT | All three included studies are well conducted community randomized trials. Intervention was not masked in two studies. | Direction of effect in favor of intervention in all three studies. Small statistical heterogeneity (I2 =19 %). | All the participants were neonates | All the studies used 4.0% chlorhexidine solution. Frequency of application was different in different study groups. | Not applicable as data was pooled by generic inverse variance | Not applicable as data was pooled by generic inverse variance | 0.46 (0.32-0.66) |
Effect on all-cause mortality
Omphalitis
Cord separation time
Application of CHERG rules
Outcome measure | Studies | Total Events | Effect size | GRADE quality of pooled estimate | Application of standard rules |
---|---|---|---|---|---|
Sepsis specific neonatal mortality | (n=1) | Not reported | 31 % reduction, statistically non-significant (RR=0.69, 95 % CI 0.40-1.18) | Low | Effect size for sepsis specific mortality was not used for inclusion in LiST model as results were not statistically significant and overall quality grade was “low” |
All cause neonatal mortality | (n=3) | 838 | 23% reduction, Statistically significant (RR=0.77, 95 % CI 0.63 - 0.94) | Moderate → Low | Effect size for all-cause mortality was used for inclusion to LiST model. This was based on rule 1 that says that if there is no evidence for cause specific mortality and there is evidence for all-cause mortality, use the effect size for all-cause and down grade quality grade by one. |