Table 1 The identified studies and their characteristics
Author and year | Title | Na | Intervention arm | Comparator arm | Single/multiple centre trial | Age/ weight Inclusion criteria of participants | Infant age group | Disease area |
|---|---|---|---|---|---|---|---|---|
Azzopardi 2009 [18] | Moderate hypothermia to treat perinatal asphyxial encephalopathy | 325 | Total body cooling and intensive care | Intensive care | Multiple | ≥ 36 weeks’ gestation | Term | Neurological |
Azzopardi 2014 [19] | Effects of hypothermia for perinatal asphyxia on childhood outcomes | 325 | Standard care with hypothermia | Standard care | Multiple | ≥ 36 weeks | Term | Neurological |
Ballard 2006 [20] | Inhaled nitric oxide in preterm infants undergoing mechanical ventilation | 582 | Nitric oxide | Placebo | Multiple | < 32 weeks | Preterm | Respiratory |
Bassler 2015 [21] | Early inhaled budesonide for the prevention of bronchopulmonary dysplasia | 856 | Early inhaled budesonide | Placebo | Multiple | 23+ 0 to 27+ 6 weeks+days | Preterm | Respiratory |
Baud 2016 [22] | Effect of early low-dose hydrocortisone on survival without bronchopulmonary dysplasia in extremely preterm infants (PREMILOC): a double-blind, placebo-controlled, multicentre randomised trial | 521 | Hydrocortisone | Placebo | Multiple | 24+ 0 to 27+ 6 weeks+days | Term | Respiratory |
Beardsall 2008 [23] | Early insulin therapy in very-low-birth-weight infants | 386 | Early insulin | Standard neonatal care | Multiple | < 1500 g | Preterm | Other- metabolic/endocrine |
Benjamin 2014 [24] | Effect of fluconazole prophylaxis on candidiasis and mortality in premature infants, a randomized clinical trial | 361 | Fluconazole | Placebo | Multiple | < 750 g | Preterm | Infection |
Brocklehurst 2011 [25] | Treatment of neonatal sepsis with intravenously administered immune globulin | 3493 | Polyvalent IgG immune globulin | Placebo | Multiple | < 1500 g | Preterm | Infection |
Carlo 2010 [26] | Target ranges of oxygen saturation in extremely preterm infants | 1316 | Oxygen saturation 85–89% | Oxygen saturation 91–95% | Multiple | 24+ 0 to 27+ 6 weeks+days | Preterm | Respiratory |
Carr 2009 [27] | Granulocyte-macrophage colony stimulating factor administered as prophylaxis for reduction of sepsis in extremely preterm, small-for-gestational age neonates (PROGRAMS): a single-blind, multicentre randomised controlled trial | 280 | Granulocyte-macrophage colony stimulating factor | Standard care | Multiple | ≤ 31 weeks | Preterm | Infection |
Ceelie 2013 [28] | Effect of intravenously administered paracetamol on postoperative morphine requirements in neonates and infants undergoing major noncardiac surgery | 71 | Continuous morphine | Intermittent intravenously administered paracetamol | Single | > 36+ 1 week+days to 1 year | Term | Other- pain |
Costeloe 2016 [29] | Bifidobacterium breve BBG-001 in very preterm infants: a randomised controlled phase 3 trial | 1310 | Probiotic B breve BBG-001 | Placebo | Multiple | 23+ 0 to 30+ 6 weeks+days | Preterm | Infection |
Davidson 2016 [30] | Neurodevelopmental outcome at 2 years of age after general anaesthesia and awake-regional anaesthesia in infancy (GAS): an international multicentre, randomised controlled trial | 719 | Awake-regional anaesthesia | General anaesthesia | Multiple | ≥ 26 weeks to 60 weeks | Both | Other- sedation/anaesthesia |
Fergusson 2012 [31] | Effect of fresh red blood cell transfusions on clinical outcomes in premature, very-low-birth-weight infants | 377 | Fresh red blood cell transfusions | Standard red blood cell transfusions | Multiple | < 1250 g | Preterm | Other- haematological |
Finer 2010 [32] | Early continuous positive airway pressure (CPAP) versus surfactant in extremely preterm infants | 1316 | Intubation and surfactant | Continuous positive airway pressure | Multiple | 24+ 0 to 27+ 6 weeks+days | Preterm | Respiratory |
Fivez 2016 [33] | Early versus late parenteral nutrition in critically ill children | 1440 | Late parenteral nutrition | Early parenteral nutrition | Multiple | Term newborns to 17 years | Term | Other- nutrition |
Gopel 2011 [34] | Avoidance of mechanical ventilation by surfactant treatment of spontaneously breathing preterm infants: an open-label randomised, controlled trial | 220 | Surfactant without ventilation | Standard care | Multiple | 26 to 28+ 6 weeks+days | Preterm | Respiratory |
Harris 2013 [35] | Dextrose gel for neonatal hypoglycaemia (the Sugar Babies study): a randomised, double-blind, placebo-controlled trial | 237 | Dextrose gel | Placebo | Single | 35 to 42 weeks | Both | Other- metabolic/endocrine |
Hyttel-Sorenson 2015 [36] | Cerebral near infrared spectroscopy oximetry in extremely preterm infants: phase II randomised clinical trial | 166 | Cerebral near infrared spectroscopy monitoring | Blinded near infrared spectroscopy monitoring | Multiple | < 27+ 6 weeks+days | Preterm | Neurological |
Kelleher 2013 [37] | Oronasopharyngeal suction versus wiping of the mouth and nose at birth: a randomised equivalency trial | 488 | Gentle wiping of the face, mouth and nose with a towel | Suction with a bulb syringe of the mouth and nostrils | Single | ≥ 35 weeks | Both | Respiratory |
Kimberlin 2011 [38] | Orally administered acyclovir suppression and neurodevelopment after neonatal herpes | 74 | Oral acyclovir | Placebo | Multiple | > 800 g | Both | Infection |
Kimberlin 2015 [39] | Valganciclovir for symptomatic congenital cytomegalovirus disease | 96 | Valganciclovir therapy | Placebo | Multiple | ≥ 32 weeks | Both | Infection |
Kirpalani 2013 [40] | A trial comparing non-invasive ventilation strategies in preterm infants | 1007 | Nasal intermittent positive-pressure ventilation | Nasal continuous positive airway pressure | Multiple | < 30 weeks and < 1000 g | Preterm | Respiratory |
Leuchter 2014 [41] | Association between early administration of high-dose erythropoietin in preterm infants and brain magnetic resonance imaging (MRI) abnormality at term-equivalent age | 165 | Recombinant human erythropoietin | Placebo | Multiple | 26 weeks to 31+ 6 weeks+days | Preterm | Neurological |
Makrides 2009 [42] | Neurodevelopmental outcomes of preterm infants fed high-dose docosahexaenoic acid | 657 | High docosahexaenoic acid diet | Standard docosahexaenoic acid diet | Multiple | < 33 weeks | Preterm | Other- nutrition |
Manley 2013 [43] | High-flow nasal cannulae in very preterm infants after extubation | 303 | High-flow nasal cannulae | Nasal continuous positive airway pressure | Multiple | < 32 weeks | Preterm | Respiratory |
Manzoni 2007 [44] | A multicentre, randomized trial of prophylactic fluconazole in preterm neonates | 322 | Fluconazole | Placebo | Multiple | < 1500 g | Preterm | Infection |
Manzoni 2009 [45] | Bovine lactoferrin supplementation for prevention of late-onset sepsis in very-low-birth-weight neonates | 472 | Lactoferrin | Lactoferrin + Lactobacillus rhamnosus GG Placebo | Multiple | < 1500 g | Preterm | Infection |
Mercier 2010 [46] | Inhaled nitric oxide for prevention of bronchopulmonary dysplasia in premature babies (EUNO): a randomised controlled trial | 800 | Inhaled nitric oxide | Placebo | Multiple | 24+ 0 to 28+ 6 weeks+days | Preterm | Respiratory |
Morley 2008 [47] | Nasal CPAP or intubation at birth for very preterm infants | 610 | CPAP | Intubation and ventilation at 5 min | Multiple | 25+ 0 to 28+ 6 weeks+days | Preterm | Respiratory |
Morris 2008 [48] | Aggressive versus conservative phototherapy for infants with extremely low birth weight | 1974 | Aggressive phototherapy | Conservative phototherapy | Multiple | 501–1000 g | Preterm | Other- hepatic |
Morris 2013 [49] | Percutaneous vesicoamniotic shunting versus conservative management for fetal lower urinary tract obstruction (PLUTO): a randomised trial | 31 | Percutaneous vesicoamniotic shunting | Conservative management | Multiple | No age or weight criteria | Both | Genitourinary |
Moss 2006 [50] | Laparotomy versus peritoneal drainage for necrotising enterocolitis (NEC) and perforation | 117 | Primary peritoneal drainage | Laparotomy with bowel resection | Multiple | < 34 weeks, < 1500 g | Preterm | Gastrointestinal |
Natalucci 2016 [51] | Effect of early prophylactic high-dose recombinant human erythropoietin in very preterm infants on neurodevelopmental outcome at 2 years | 365 | Prophylactic early high-dose recombinant human erythropoietin (rhEPO) | Placebo | Multiple | 26+ 0 to 31+ 6 weeks+days | Preterm | Neurological |
Schmidt 2012 [52] | Survival without disability to age 5 years after neonatal caffeine therapy for apnea of prematurity | 1640 | Caffeine therapy | Placebo | Multiple | 500–1250 g | Preterm | Respiratory |
Schmidt 2013 [53] | Effects of targeting higher versus lower arterial oxygen saturations on death or disability in extremely preterm infants | 1201 | Oxygen saturation 85–89% | Oxygen saturation 91–95% | Multiple | 23+ 0 to 27+ 6 weeks+days | Preterm | Respiratory |
Shankaran 2012 [54] | Childhood outcomes after hypothermia for neonatal encephalopathy | 190 | Hypothermia | Usual care | Multiple | ≥ 36 weeks | Both | Neurological |
Shankaran 2014 [55] | Effect of depth and duration of cooling on deaths in the neonatal intensive care unit (NICU) among neonates with hypoxic ischemic encephalopathy, a randomised clinical trial | 364 | 32 °C for 72 h 33.5 °C for 120 h 32 °C for 120 h | 33.5 °C for 72 h | Multiple | ≥ 36 weeks | Both | Neurological |
Slater 2010 [56] | Orally administered sucrose as an analgesic drug for procedural pain in newborn infants: a randomised controlled trial | 44 | Sucrose solution | Sterile water | Single | 37–43 weeks | Term | Other- pain |
Stenson 2013 [57] | Oxygen saturation and outcomes in preterm infants | 2448 | Oxygen saturation of 85–89% | Oxygen saturation of 91–95% | Multiple | < 28 weeks | Preterm | Respiratory |
Taddio 2006 [58] | Intravenously administered morphine and topically administered tetracaine for treatment of pain in preterm neonates undergoing central-line placement | 132 | Tetracaine or morphine or both | Neither tetracaine nor morphine | Multiple | No age or weight criteria | Both | Other- pain |
Tarnow-Mordi 2016 [59] | Outcomes of two trials of oxygen-saturation targets in preterm infants | 1858 | Lower oxygen-saturation range | Higher oxygen-saturation range | Multiple | < 28 weeks | Preterm | Respiratory |
Vaucher 2012 [60] | Neurodevelopmental outcomes in the early CPAP and pulse oximetry trial | 990 | Early CPAP with a limited ventilation strategy | Early surfactant administration (2 × 2 factorial) Also to: 85–89% oxygen saturation or 91–95% oxygen saturation | Multiple | 24+ 0 to 27+ 6 weeks+days | Preterm | Respiratory |
Zivanovic 2014 [61] | Late outcomes of a randomized trial of high-frequency oscillation in neonates | 319 | High-frequency oscillatory ventilation | Conventional ventilation | Multiple | < 29 weeks | Preterm | Respiratory |