Neonatal mortality rates and calculated risk ratios
| Intervention | Control | Mortality definition | Author (year) | Mortality outcome intervention, n (%) | Mortality outcome control, n (%) | RR | 95%CI | P value | GRADE quality of evidence | |
| ANTENATAL INTERVENTIONS | ||||||||||
| Four doses of dexamethasone 6 mg 12 hours apart | Standard care | Stillbirths | Althabe et al20 (2015) | 748 (22.9) | 739 (24.7) | 0.99 | 0.90–1.09 | 0.81 | ⨁⨁⨁⨁ High | |
| Perinatal mortality | Althabe et al20 (2015) | 1203 (36.8) | 1172 (39.1) | 0.97 | 0.91–1.04 | 0.46 | ⨁⨁⨁⨁ High | |||
| 7-day neonatal mortality | Althabe et al20 (2015) | 455 (13.9) | 433 (14.4) | 0.94 | 0.84–1.06 | 0.30 | ⨁⨁⨁⨁ High | |||
| 28-day neonatal mortality | Althabe et al20 (2015) | 566 (22.4) | 524 (23.2) | 0.96 | 0.87–1.06 | 0.65 | ⨁⨁⨁⨁ High | |||
| Garces et al36 (2016) | 36 (18.3) | 39 (23.5) | 0.74 | 0.68–0.81 | <0·0001 | ⨁⨁⨁⨁ High | ||||
| Klein et al39 (2016) | Belgaum, India | 133 (25) | 158 (25.6) | 0.96 | 0.75–1.22 | NA | ⨁⨁⨁◯ Moderate* | |||
| Nagpur, India | 109 (30.5) | 84 (32.9) | 0.94 | 0.72–1.23 | NA | ⨁⨁⨁◯ Moderate* | ||||
| Pakistan | 172 (22.6) | 172 (25) | 0.89 | 0.80–0.99 | NA | ⨁⨁⨁⨁ High | ||||
| Zambia | 30 (15.2) | 27 (12.7) | 1.43 | 0.90–2.28 | NA | ⨁⨁⨁◯ Moderate* | ||||
| Kenya | 45 (19.2) | 27 (14.3) | 1.30 | 0.94–1.81 | NA | ⨁⨁⨁◯ Moderate* | ||||
| Guatemala | 57 (16.5) | 39 (23.5) | 0.75 | 0.69–0.82 | NA | ⨁⨁⨁⨁ High | ||||
| Argentina | 20 (22) | 17 (13) | 1.60 | 0.99–2.58 | NA | ⨁⨁⨁◯ Moderate* | ||||
| Two doses of 12 mg of dexamethasone 24 hours apart | Rasool et al43 (2017) | 0 (0)† | 2 (8.4)† | 0.20 | 0.01–3.96 | 0.29 | ⨁◯◯◯ Very low‡§¶** | |||
| Maintenance tocolysis with nifedipine | Standard care | Perinatal mortality | Aggarwal et al21 (2018) | 2 (11.1) | 3 (13) | 0.85 | 0.16–4.57 | 0.85 | ⨁⨁◯◯ Low** | |
| POSTNATAL INTERVENTIONS | ||||||||||
| Feeding interventions | ||||||||||
| Fortified pasteurised donor human milk (PDHM) | Unfortified PDHM | 28-day neonatal mortality | Adhisivam et al25 (2018) | 3 (7.5) | 3 (7.5) | 1.00 | 0.21–4.66 | 1.00 | ⨁⨁◯◯ Low** | |
| Hybrid milk feeds | Mother’s milk alone | Nandakumar et al42 (2020) | 4 (6.4) | 5 (8.4) | 0.76 | 0.21–2.70 | 0.67 | ⨁◯◯◯ Very low¶††‡‡** | ||
| Infection prevention | ||||||||||
| Single cord cleansing with chlorhexidine | Dry cord care | 28-day neonatal mortality | Arifeenet al27 (2012) | LBW: 121 (3.8) | 145 (4.7) | 0.82 | 0.63–1.06 | NA | ⨁⨁⨁⨁ High | |
| Preterm: 78 (4.0) | 128 (6.2) | 0.65 | 0.50–0.86 | NA | ⨁⨁⨁⨁ High | |||||
| Multiple cord cleansing with chlorhexidine | LBW: 159 (4.7) | 145 (4.7) | 1.00 | 0.79–1.27 | NA | ⨁⨁⨁⨁ High | ||||
| Preterm: 119 (5.4) | 128 (6.2) | 0.88 | 0.69–1.12 | NA | ⨁⨁⨁⨁ High | |||||
| Skin cleansing with chlorhexidine | Placebo | Tielsch et al47 (2007) | 83 (3.4) | 117 (4.7) | 0.72 | 0.55–0.95 | NA | ⨁⨁⨁⨁ High | ||
| Topical ointment SSO | Standard skin care | Darmstadt et al34 (2004) | 12 (23.5) | 18 (34.6) | 0.68 | 0.37–1.26 | 0.29 | ⨁⨁◯◯ Low*§¶§§ | ||
| SSO and Aquaphor | Darmstadt et al35 (2008) | SSO: 105 (65.8) | 128 (70.6) | SSO: 0.93 | SSO: 0.81–1.08 | SSO: 0.36 | ⨁⨁◯◯ Low*§¶§§ | |||
| Aquaphor: 85 (54.2) | 128 (70.6) | Aquaphor: 0.77 | Aquaphor: 0.64–0.91 | Aquaphor: 0·0023 | ⨁⨁◯◯ Low*¶¶§§ | |||||
| Aquaphor | 21-day neonatal mortality | Erdemir et al23 (2015) | 10 (10) | 4 (4.1) | 2.43 | 0.79–7.47 | 0.12 | ⨁⨁◯◯ Low*¶¶§§ | ||
| Supplementation Selenium | Glucon-D powder alone | 28-day neonatal mortality | Aggarwal et al26 (2016) | 2 (4.4) | 3 (6.7) | 0.67 | 0.12–3.80 | 0.65 | ⨁◯◯◯ Very low***** | |
| Bovine lactoferrin | Placebo | Kaur et al37 (2015) | 0 (0) | 5 (7.5) | 0.10 | 0.01–1.71 | 0.11 | ⨁⨁◯◯ Low** | ||
| Early BCG vaccine | Late BCG | Aaby et al24 (2011) | 27 (2.3) | 48 (4.2) | 0.55 | 0.35–0.88 | 0.01 | ⨁⨁⨁⨁ High§§ | ||
| Biering Sorensen et al31 (2017) | 44 (2.1) | 62 (3.0) | 0.71 | 0.49–1.04 | 0.08 | ⨁⨁⨁⨁ High§§ | ||||
| Prophylactic fluconazole | Placebo | Kirpal et al38 (2016) | 7 (18.4) | 12 (32.4) | 0.57 | 0.25–1.28 | 0.17 | ⨁⨁⨁◯ Moderate* | ||
| Strategies of newborn care | ||||||||||
| Early KMC | Late KMC | 28-day neonatal mortality | Nagai et al41 (2010) | 2 (5.4) | 1 (2.8) | 1.95 | 0.18–20.53 | 0.58 | ⨁⨁◯◯ Low** | |
| Conventional care | Worku et al47 (2005) | 14 (22.5) | 24 (38) | 0.57 | 0.33–1.00 | 0.05 | ⨁⨁⨁◯ Moderate* | |||
| Community KMC | Standard home-based care | Sloan et al45 (2008) | ≤2500 g: 22 (5.4) | 20 (6) | 0.87††† | 0.43–1.74††† | 0.69††† | ⨁⨁⨁⨁ High§§ | ||
| ≤2000 g: 9 (9.5) | 16 (22.5) | 0.37††† | 0.16–0.86††† | 0.02††† | ⨁⨁⨁◯ Moderate* | |||||
| Mazumder et al40 (2019) | 73 (1.6) | 90 (2.3) | 0.71 | 0.52–0.96 | 0.03 | ⨁⨁⨁⨁ High§§ | ||||
| Home-based neonatal care | Preintervention period | Bang et al29 (1999) | LBW: 13 (4) | 36 (11.3) | 0.36 | 0.20–0.67 | 0·0011 | ⨁⨁⨁⨁ High | ||
| Preterm: 9 (9.7) | 25 (33.3) | 0.29 | 0.14–0.58 | 0·0005 | ⨁⨁⨁⨁ High | |||||
| Bang, Baitule et al28 (2005) | Preterm: 23 (10.2) | 25 (33.3) | 0.31 | 0.18–0.50 | 0.00 | ⨁⨁⨁⨁ High | ||||
| LBW: 39 (4.7) | 36 (11.3) | 0.42 | 0.27–0.65 | 0·0001 | ⨁⨁⨁⨁ High | |||||
| Bang, Reddy et al30 (2005) | 12 (8.5) | 25 (33.3) | 0.25 | 0.14–0.48 | 0·0000 | ⨁⨁⨁⨁ High | ||||
| Training of traditional birth attendants | ENC: preintervention period NRP: No additional training | Stillbirths | Carlo et al22 (2010) | ENC: 157 (43.7) | ENC: 72 (42.6) | ENC: 1.03 | ENC: 0.80–1.31 | NA | ⨁⨁⨁◯ Moderate* | |
| NRP: 91 (33.3) | NRP: 101 (34.2) | NRP: 0.97 | NRP: 0.57–1.67 | NA | ⨁⨁⨁◯ Moderate* | |||||
| Perinatal mortality | ENC: 283 (78.8) | ENC: 133 (78.7) | ENC: 1.02 | ENC: 0.91–1.14 | NA | ⨁⨁⨁⨁ High | ||||
| NRP: 198 (72.5) | NRP: 225 (76.3) | NRP: 0.95 | NRP: 0.84–1.07 | NA | ⨁⨁⨁⨁ High | |||||
| 7-day neonatal mortality | ENC: 126 (35.1) | ENC: 61 (36.1) | ENC: 1.03 | ENC: 0.83–1.27 | NA | ⨁⨁⨁⨁ High | ||||
| NRP: 107 (39.2) | NRP: 124 (42) | NRP: 0.92 | NRP: 0.77–1.09 | NA | ⨁⨁⨁⨁ High | |||||
| Others | ||||||||||
| Delayed cord clamping | Early cord clamping | 28-day neonatal mortality | Chopra et al33 (2018) | 1 (1.8) | 0 | 3.16 | 0.13–75.98 | 0.48 | ⨁◯◯◯ Very low**‡‡‡ | |
| Heated mattress | Air-heated incubators | Sarman et al44 (1989) | 6 (21.4) | 11 (34.4) | 0.62 | 0.26–1.47 | 0.28 | ⨁⨁⨁◯ Moderate* | ||
| Quality improvement intervention | Preintervention period | Cavicchiolo et al32 (2016) | 200 (33.0) | 192 (43.0) | 0.77 | 0.66–0.90 | 0.001 | ⨁⨁⨁◯ Moderate§§§ | ||
*Insufficient sample to meet optimal information size (OIS) criteria and/or 95% CI close to or crosses line of no effect or fails to exclude important benefit or harm.
†The mortality event rate is based on the number of women per study arm who received the intervention.
‡Identification and recruitment of individual participants occurred after randomisation.
§Method of randomisation is not reported, baseline differences suggest a problem with randomisation.
¶Information about blinding of participants and carers is not provided.
**Insufficient sample to meet OIS criteria with very few events and 95% CI fails to exclude important benefit or harm.
††Allocation concealment is not reported.
‡‡Method of ascertainment of mortality outcome measure is not reported.
§§Derived from the meta-analysis pooling the results of both studies.
¶¶I2 of 76%, p value of 0,04, minimal overlapping 95% CIs and one study showing benefit while the other study shows harm suggest serious inconsistency of results.
***Loss to follow-up and failure to conduct both analyses considering only those who adhered to treatment, and all patients for whom outcome data are available.
†††OR; adjusted for cluster design effect.
‡‡‡Substantial loss to follow-up in relation to the number of events and failure to adhere to the intention-to-treat principle.
§§§Confounding due to baseline differences cannot be excluded and is not controlled for in the study.