Table 1 Evidence on interventions to improve inpatient neonatal morbidity and mortality in a selection of existing systematic reviews

Chlorhexidine skin or cord care for prevention of mortality and infections in neonates born in the community and in facility births

4 (4) cluster RCT in community

72909 (72909)

There is high-quality evidence that chlorhexidine skin or cord care in the community setting results in a 50 % reduction in the incidence of omphalitis and a 12 % reduction in neonatal mortality. There is some uncertainty as to the effect of chlorhexidine applied to the umbilical cords of newborns in hospital settings on neonatal mortality [11].

4 (1) RCT in hospital settings

1451 (146)

Effect of plastic wrappers to prevent mortality in preterm and/or low birthweight infants or to prevent hypothermia on admission to newborn units

4 (0) RCT for mortality

264 (0)

Plastic wraps or bags lead to higher temperatures on admission to neonatal units and less hypothermia. However, the small numbers of infants and studies and the absence of long-term follow-up mean that firm recommendations for clinical practice cannot be given [18, 32]. A more recent trial of 104 babies in Malawi suggested plastic wrappers prevent hypothermia but there was no effect on mortality [32].

2 (0) RCT for hypothermia

152 (0)

Total volume of water (fluid) intake in early life in preterm infants and optimum initial glucose supply rates when intravenous fluids must be used

5 (0) RCT

582 (0)

Restricted water intake significantly increases postnatal weight loss but significantly reduces the risks of patent ductus arteriosus and necrotizing enterocolitis. With restricted water intake, there were trends toward increased risk of dehydration and reduced risks of bronchopulmonary dysplasia, intracranial hemorrhage, and death [21].

Optimum initial glucose supply rates when intravenous fluids must be used

2 (0) RCT

51 (0)

There is insufficient evidence from trials comparing lower with higher glucose infusion rates to inform clinical practice [20].

Early trophic feeding versus enteral fasting for very preterm or very low birth weight infants (effect on mortality)

8 (0) RCT

558 (0)

Early trophic feeding is associated with a non-significant reduction in mortality 0.66 [0.41, 1.07] [33]

Delayed introduction of progressive enteral feeds and slow or rapid advancement of feeds to prevent necrotising enterocolitis (NEC) in very low birth weight infants

8 (0) RCT Delayed introduction

1092 (0)

Delaying introduction of progressive enteral feeds to four days or more after birth did not reduce the risk of NEC (typical RR 0.93, 95 % CI 0.64 to 1.34; 8 trials; 1092 infants) [22]. There were no statistically significant effects on the risk of NEC of fast rates of feed advancement (typical risk ratio (RR) 0.96, 95 % confidence interval (CI) 0.55 to 1.70) or all-cause mortality (typical RR 1.57, 95 % CI 0.92 to 2.70) [23].

6 (3) RCT Rate of advancement

618 (183)

Effect of nasogastric or orogastric feeding tubes on time to establish full enteral feeding in preterms who have respiratory distress

1 (0) RCT

46 (0)

There are insufficient data available to inform practice [25].

Whether continuous, slow feeding is safer or more effective than bolus feeding in preterm infants

5 (0)

424 (0)

There were no differences in time to achieve full enteral feeds in studies comparing continuous nasogastric versus intermittent bolus nasogastric milk feedings (WMD 2 days, 95 % CI -0.3 to 3.9) [24].

Alternatives to phenobarbitone as first line treatment for convulsing newborns and optimal second line treatment for continued convulsions in a newborn after receiving phenobarbitone

1 (0) RCT and 5 (1) observational studies for first line treatment

59 (0) in RCT and 717 (101) in observational studies

There is very low quality evidence comparing phenobarbitone with phenytoin as first line treatment and very low quality evidence informing decisions on second line treatment. There is a similar deficit in evidence to inform duration of therapy, whether to use anticonvulsant prophylaxis in babies with hypoxic ischaemic encephalopathy and strategies to stop treatment. There is no evidence to inform decisions on empiric treatment for hypoglycaemia in convulsing newborns and so testing blood glucose in convulsing newborns is recommended prior to starting anticonvulsants [26].

1 (0) RCT and 1 (0) observational study for second line treatment

8 (0) in RCT and 45 (0) in observational study

Kangaroo Mother Care (KMC)

8 (7) RCT; 1 (1) of these RCT in babies pre-stabilisation

1736 (1676); 123 in a trial of babies pre-stabilisation

The evidence from this updated review supports the use of KMC in LBW infants as an alternative to conventional neonatal care mainly in resource-limited settings. Further information is required concerning effectiveness and safety of early onset continuous KMC in unstabilized or relatively stabilized LBW infants, long term neurodevelopmental outcomes, and costs of care [10].

Topical emollient therapy

8 (2) RCT

2086 (535)

There is no clear evidence that use of emollient therapy prevents invasive infection (RR 1.13, 95 % CI 0.97-1.31) or mortality (RR 0.87 95 % CI 0.75-1.03) [27].

Safety and efficacy of CPAP (particularly bubble CPAP) as a primary respiratory support to improve survival, compared with standard oxygen therapy in low and middle income countries.

(4) RCT plus (5) case control and cohort studies

(450) in RCT and (1408) in observational studies

There is evidence that CPAP is safe and may reduce the need for mechanical ventilation. However more studies are recommended to compare CPAP and existing standard oxygen therapy in low and middle income countries [28].

Comparisons of alternative empiric antibiotic regimens for early onset neonatal sepsis

2 (0) RCT

127 (0)

There is no evidence from randomised trials to suggest that any antibiotic regimen may be better than any other in the treatment of presumed early neonatal sepsis. More studies are needed to resolve this issue [16]. There is inadequate evidence from randomised trials in favour of any particular antibiotic regimen for the treatment of suspected late onset neonatal sepsis [15]. There was insufficient evidence to recommend a particular antibiotic regimen for the treatment of NEC [17]. In guidance WHO updated in 2012 on empiric treatment of neonatal sepsis the quality of evidence was judged to be low [14].

Comparisons of alternative empiric antibiotic regimens for late onset neonatal sepsis

1 (0)

28 (0)

Comparisons of alternative empiric antibiotic regimens for necrotising enterocolitis

2 (0)

62 (0)

Use of prophylactic phototherapy to prevent cerebral palsy or all-cause mortality in preterm infants (<37 weeks or <2500 g)

2 (0) RCT Cerebral palsy

756 (0)

Prophylactic phototherapy helps to maintain a lower serum bilirubin concentration and may have an effect on the rate of exchange transfusion and the risk of neurodevelopmental impairment. However, further well-designed studies are needed to determine the efficacy and safety of prophylactic phototherapy on long-term outcomes including neurodevelopmental outcomes [30].

4 (1) RCT Mortality

3044 (50)

Single versus double volume exchange transfusion in treatment of ABO incompatibility

1 (0)

20 (0)

There was insufficient evidence to support or refute the use of single volume exchange transfusion as opposed to double volume exchange transfusion in jaundiced newborns [29].