Table 2

Study characteristics of studies assessing in-hospital mortality

Author (year)+CountryStudy designDuration of study (months)Study participants and sample sizeSettingInterventionControlMortality as primary outcomeDuration of hospital stay in days (mean±SD)
Feeding interventions
Feeding scheduleTali et al67 (2016)
RCTNANeonates weighing 501–1500 g/intervention: 60, control: 60Level III NICU3-hour feeding schedule (eight feeds daily)2-hour feeding schedule (12 feeds daily)NoIntervention: 46±21.5, control: 43.7±20.2
Infection prevention
Granulocyte stimulationAktas et al48 (2015)
RCT24Neutropenic preterm neonates* with culture-proven or suspected sepsis/intervention: 33, control: 23Teaching hospitalRecombinant human granulocyte-macrophage colony-stimulating factor (rhG-CSF) 10 mg/kg/day in 5% dextrose until absolute neutrophil count reached >1.0×109/LEmpirical antibiotics aloneYesNot reported
Pro/synbiotic supplementsNandhini et al62 (2016)
RCTNAEnterally fed preterm neonates with gestational age 28–34 weeks and birth weight >1000 g/intervention: 110 (analysed: 108), control: 110Paediatrics department of a tertiary hospitalSynbiotics 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 careNoIntervention: 8.3±4.5, control: 8.4±5.1
Sari et al64 (2011)
RCT9Preterm 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 hospitalFeeding with oral probiotic Lactobacillus sporogenes 350 000 000 colony-forming unit once a dayBreast milk or formula aloneYesDeath >7 days intervention: 43.5, control: 30
Prevention and treatment of respiratory morbidity
CPAPBhatti et al52 (2015)
RCT19Preterm neonates <34 weeks of gestation with respiratory distress within 6 hours of life/intervention: 80, control: 90Two level III NICU’sNasal-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 interfaceBubble CPAPNoNot reported
Mazmanyan et al60 (2016)
RCTNAPreterm neonates/ intervention: 66, control: 59Neonatal unitBubble CPAPFlow driver CPAPNoNot reported
Okello et al63 (2019)
Pre–post intervention trial32VLBW† neonates/preintervention: 158, postintervention: 219Neonatal unit of a regional referral hospitalBubble CPAPPreintervention periodYesMedian (IQR) preintervention: 8 (2, 17), postintervention: 9.5 (4, 19)
Say et al65 (2016)
RCT7Preterm infants with gestation 26–32 weeks and IRDS/intervention: 75, control: 74NICU of a teaching hospitalBinasal prong for applying CPAPNasal mask for applying nasal CPAPNoMedian (IQR) intervention: 18 (10–21), control: 25 (20–28)
Tagare et al66 (2013)
RCT13Preterm neonates with IRDS and oxygen requirement >30% within first 6 hours of life/intervention: 57, control: 57NICU of a tertiary hospitalBubble CPAPVentilator-derived CPAPNot reportedNoNot reported
Exogenous surfactant replacement therapyGharehbaghi et al54 (2010)
RCT13Preterm infants with IRDS that required exogenous surfactant replacement therapy/intervention: 79, control: 71Level III NICU of a university hospitalPoractant alfa 200 mg/kg in two divided dosesBeractant 100 mg/kg in four divided dosesNoIntervention: 24.9±26.4, control: 29.1±23.5
Halim et al56 (2018)
RCT8Preterm neonates at <34 weeks of gestation with IRDS/intervention: 50, control: 50Neonatal unit of a tertiary hospitalLess invasive surfactant administration (LISA) method: surfactant was administered at a dose of 100 mg/kg of Survanta with the help of size 6Fr nasogastric tubeConventional INSURE method: INtubation SURfactant administration and ExtubationNoMedian (IQR) intervention: 7 (5), control: 6 (4)
Jain et al57 (2019)
RCT19Preterm 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 centresGoat lung surfactant extractBeractantYesIntervention: 31.6±32.0, control: 31.7±21.9
Feeding supplementationBasu et al51 (2019)
RCT20VLBW 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: 98NICU of a tertiary care teaching hospitalOral vitamin A 1 mL of syrup (10 000 IU of retinol/dose) on alternate day for 28 days, starting at 24 hours of lifePlaceboNoDeath was recorded at 36 weeks post menstrual age
Oxygen systems other than CPAPGraham et al55 (2019)
Stepped-wedge cluster RCT44All children (aged <15 years), admitted to participating hospitals. LBW‡, preterm/ preintervention: 1883, pulse oximetry: 688, full O2 system: 1137Twelve general, paediatric, and maternity hospitals in southwest Nigeria
  • Pulse oximetry to improve clinical use of oxygen targeting hypoxaemic neonates

  • Full O2 system involving (1) a standardised oxygen equipment package, (2) clinical education and support, (3) technical training and support, and (4) infrastructure and systems support

Preintervention periodYesNot reported
Krishna et al58 (2019)
RCT17Preterm neonates with gestational age of 27–34 weeks, ventilated within the first week of life for IRDS/intervention: 40, control: 41Level III NICU of a tertiary hospitalVolume-guaranteed ventilation (VGV)Pressure-controlled ventilationNoNot reported
Murki et al61 (2018)
RCT13Preterm infants with gestational age of ≥28 weeks and birth weight ≥1000 g, with respiratory distress/intervention: 133, control: 139NICUs of two tertiary care hospitalsHigh-flow nasal cannula (HFNC) as a primary non-invasive respiratory supportNasal CPAPNoIntervention: 18±13, control: 17±14
Prophylactic methylxanthinesKumar et al59 (2017)
RCT24Preterm 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 hospitalAminophylline: 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 theophyllineCaffeine: 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)NoDuration of NICU stay median (25th percentile, 75th percentile)/intervention: 34 (14.8, 48.3), control: 38 (21, 55)
Strategies of newborn care
Maternal nursing careArif et al49 (1999)
RCT6Babies 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 hospitalMaternal nursing careSpecial care baby unit, looked after entirely by nursesYesNot reported
Bhutta et al53 (2004)
Pre–post intervention trial98VLBW infants/intervention: 318, control: 191Neonatal unit of a tertiary hospitalA stepdown unit (involvement of maternal nursing care)Preintervention periodYesIntervention: 15.4±15.7, control: 22.2±21.7
Strategies for PDA closureBalachander et al50 (2018)
RCT16Preterm neonates with PDA of size ≥1.5 mm and left to right shunt after 24 hours of life/intervention: 55, control: 55Neonatal unit of a tertiary hospitalOral paracetamol for PDA closure: 15 mg/kg/dose 6-hourly by oro-gastric tube or paladai for 2 daysOral ibuprofen: 10 mg/kg stat on day 1 followed by 5 mg/kg 24 hours for 2 daysNoIntervention: 21.4±11.8, control: 25.7±15.1
Hypothermia preventionVan Den Bosch et al68 (1996)
RCT4Neonates 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 hospitalPolythene tobacco-wrap folded double with one thickness above and two thicknesses tucked below the babyStandard nursing procedureNoIntervention: 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.