Study characteristics of studies assessing in-hospital mortality
| Author (year)+Country | Study design | Duration of study (months) | Study participants and sample size | Setting | Intervention | Control | Mortality as primary outcome | Duration of hospital stay in days (mean±SD) | |
| POSTNATAL INTERVENTIONS | |||||||||
| Feeding interventions | |||||||||
| Feeding schedule | Tali et al67 (2016) India | RCT | NA | Neonates weighing 501–1500 g/intervention: 60, control: 60 | Level III NICU | 3-hour feeding schedule (eight feeds daily) | 2-hour feeding schedule (12 feeds daily) | No | Intervention: 46±21.5, control: 43.7±20.2 |
| Infection prevention | |||||||||
| Granulocyte stimulation | Aktas et al48 (2015) Turkey | RCT | 24 | Neutropenic preterm neonates* with culture-proven or suspected sepsis/intervention: 33, control: 23 | Teaching hospital | Recombinant human granulocyte-macrophage colony-stimulating factor (rhG-CSF) 10 mg/kg/day in 5% dextrose until absolute neutrophil count reached >1.0×109/L | Empirical antibiotics alone | Yes | Not reported |
| Pro/synbiotic supplements | Nandhini et al62 (2016) India | RCT | NA | Enterally fed preterm neonates with gestational age 28–34 weeks and birth weight >1000 g/intervention: 110 (analysed: 108), control: 110 | Paediatrics department of a tertiary hospital | Synbiotics supplement: Lactobacillus acidophilus, Bifidobacterium longum, Lactobacillus rhamnosus, Lactobacillus plantaris, Lactobacillus casei, Lactobacillus bulgaricus, Bifidobacterium infantis, Bifidobacterium breve and 100 mg of fructo-oligosaccharide (prebiotic) | Standard care | No | Intervention: 8.3±4.5, control: 8.4±5.1 |
| Sari et al64 (2011) Turkey | RCT | 9 | Preterm neonates with a gestational age <33 weeks or birth weight <1500 g, who survived to feed enterally/intervention: 121 (analysed: 110), control: 121 (analysed: 111) | NICU of a training hospital | Feeding with oral probiotic Lactobacillus sporogenes 350 000 000 colony-forming unit once a day | Breast milk or formula alone | Yes | Death >7 days intervention: 43.5, control: 30 | |
| Prevention and treatment of respiratory morbidity | |||||||||
| CPAP | Bhatti et al52 (2015) India | RCT | 19 | Preterm neonates <34 weeks of gestation with respiratory distress within 6 hours of life/intervention: 80, control: 90 | Two level III NICU’s | Nasal-jet CPAP device: a variable flow CPAP device with a Benveniste valve that generates CPAP at the level of the nostril with a short binasal prong as nasal interface | Bubble CPAP | No | Not reported |
| Mazmanyan et al60 (2016) Armenia | RCT | NA | Preterm neonates/ intervention: 66, control: 59 | Neonatal unit | Bubble CPAP | Flow driver CPAP | No | Not reported | |
| Okello et al63 (2019) Uganda | Pre–post intervention trial | 32 | VLBW† neonates/preintervention: 158, postintervention: 219 | Neonatal unit of a regional referral hospital | Bubble CPAP | Preintervention period | Yes | Median (IQR) preintervention: 8 (2, 17), postintervention: 9.5 (4, 19) | |
| Say et al65 (2016) Turkey | RCT | 7 | Preterm infants with gestation 26–32 weeks and IRDS/intervention: 75, control: 74 | NICU of a teaching hospital | Binasal prong for applying CPAP | Nasal mask for applying nasal CPAP | No | Median (IQR) intervention: 18 (10–21), control: 25 (20–28) | |
| Tagare et al66 (2013) India | RCT | 13 | Preterm neonates with IRDS and oxygen requirement >30% within first 6 hours of life/intervention: 57, control: 57 | NICU of a tertiary hospital | Bubble CPAP | Ventilator-derived CPAPNot reported | No | Not reported | |
| Exogenous surfactant replacement therapy | Gharehbaghi et al54 (2010) Iran | RCT | 13 | Preterm infants with IRDS that required exogenous surfactant replacement therapy/intervention: 79, control: 71 | Level III NICU of a university hospital | Poractant alfa 200 mg/kg in two divided doses | Beractant 100 mg/kg in four divided doses | No | Intervention: 24.9±26.4, control: 29.1±23.5 |
| Halim et al56 (2018) Pakistan | RCT | 8 | Preterm neonates at <34 weeks of gestation with IRDS/intervention: 50, control: 50 | Neonatal unit of a tertiary hospital | Less invasive surfactant administration (LISA) method: surfactant was administered at a dose of 100 mg/kg of Survanta with the help of size 6Fr nasogastric tube | Conventional INSURE method: INtubation SURfactant administration and Extubation | No | Median (IQR) intervention: 7 (5), control: 6 (4) | |
| Jain et al57 (2019) India | RCT | 19 | Preterm neonates born at 26–32 weeks’ gestation with clinical features of IRDS ≤6 hours of birth and fulfilled criteria for surfactant therapy ≤24 hours of birth/intervention: 53 (analysed: 52), control: 48 (analysed: 46) | NICUs of seven tertiary care centres | Goat lung surfactant extract | Beractant | Yes | Intervention: 31.6±32.0, control: 31.7±21.9 | |
| Feeding supplementation | Basu et al51 (2019) India | RCT | 20 | VLBW neonates requiring respiratory support in the form of oxygen inhalation, CPAP, high flow nasal cannula (HFNC), or mechanical ventilation at the age of 24 hours/ intervention: 98, control: 98 | NICU of a tertiary care teaching hospital | Oral vitamin A 1 mL of syrup (10 000 IU of retinol/dose) on alternate day for 28 days, starting at 24 hours of life | Placebo | No | Death was recorded at 36 weeks post menstrual age |
| Oxygen systems other than CPAP | Graham et al55 (2019) Nigeria | Stepped-wedge cluster RCT | 44 | All children (aged <15 years), admitted to participating hospitals. LBW‡, preterm/ preintervention: 1883, pulse oximetry: 688, full O2 system: 1137 | Twelve general, paediatric, and maternity hospitals in southwest Nigeria |
| Preintervention period | Yes | Not reported |
| Krishna et al58 (2019) India | RCT | 17 | Preterm neonates with gestational age of 27–34 weeks, ventilated within the first week of life for IRDS/intervention: 40, control: 41 | Level III NICU of a tertiary hospital | Volume-guaranteed ventilation (VGV) | Pressure-controlled ventilation | No | Not reported | |
| Murki et al61 (2018) India | RCT | 13 | Preterm infants with gestational age of ≥28 weeks and birth weight ≥1000 g, with respiratory distress/intervention: 133, control: 139 | NICUs of two tertiary care hospitals | High-flow nasal cannula (HFNC) as a primary non-invasive respiratory support | Nasal CPAP | No | Intervention: 18±13, control: 17±14 | |
| Prophylactic methylxanthines | Kumar et al59 (2017) India | RCT | 24 | Preterm neonates with gestational age of ≤30 weeks, who were intubated for ≥24 hours/intervention: 78 (analysed: 70), control: 78 (analysed: 73) | NICU of a tertiary hospital | Aminophylline: loading dose of 5 mg/kg, followed by a maintenance dose of 1.5 mg/kg Q8h via injection and oral preparation of 10 mg/mL of theophylline | Caffeine: a loading dose of 20 mg/kg of caffeine citrate and continued on a maintenance dose of 5 mg/kg Q24h via (IV or oral) | No | Duration of NICU stay median (25th percentile, 75th percentile)/intervention: 34 (14.8, 48.3), control: 38 (21, 55) |
| Strategies of newborn care | |||||||||
| Maternal nursing care | Arif et al49 (1999) Pakistan | RCT | 6 | Babies weighing 1000–2000 g on admission irrespective of sex or age/intervention: 160 (analysed: 151), control: 240 (analysed: 211) | Neonatal ward of a government children’s hospital | Maternal nursing care | Special care baby unit, looked after entirely by nurses | Yes | Not reported |
| Bhutta et al53 (2004) Pakistan | Pre–post intervention trial | 98 | VLBW infants/intervention: 318, control: 191 | Neonatal unit of a tertiary hospital | A stepdown unit (involvement of maternal nursing care) | Preintervention period | Yes | Intervention: 15.4±15.7, control: 22.2±21.7 | |
| Others | |||||||||
| Strategies for PDA closure | Balachander et al50 (2018) India | RCT | 16 | Preterm neonates with PDA of size ≥1.5 mm and left to right shunt after 24 hours of life/intervention: 55, control: 55 | Neonatal unit of a tertiary hospital | Oral paracetamol for PDA closure: 15 mg/kg/dose 6-hourly by oro-gastric tube or paladai for 2 days | Oral ibuprofen: 10 mg/kg stat on day 1 followed by 5 mg/kg 24 hours for 2 days | No | Intervention: 21.4±11.8, control: 25.7±15.1 |
| Hypothermia prevention | Van Den Bosch et al68 (1996) Malawi | RCT | 4 | Neonates with a birth weight of 800–1500 g and Apgar score >7/intervention: 33 (analysed: 15), control: 32 (analysed: 11) | Neonatal nursery of a tertiary hospital | Polythene tobacco-wrap folded double with one thickness above and two thicknesses tucked below the baby | Standard nursing procedure | No | Intervention: 29.4 (95% CI 1.0 to 57.8), control: 14 (–9.6 to 37.6) |
*Preterm neonate=<37 weeks of gestation.
†VLBW=very low birth weight (<1500 g).
‡LBW=low birth weight (<2500 g).
CPAP, continuous positive airway pressure; HFNC, high flow nasal cannula; INSURE, INtubation SURfactant administration and Extubation; IRDS, infant respiratory distress syndrome; IV, intravenous; LISA, less invasive surfactant administration; NICU, neonatal intensive care unit; PDA, patent ductus arteriosus; RCT, randomised controlled trial; rhG-CSF, recombinant human granulocyte-macrophage colony-stimulating factor; VGV, volume-guaranteed ventilation.