Table 2.

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	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 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.