1.1.1. Introduction

Neonatal infection is a significant cause of mortality and morbidity in newborn babies. It can lead to life-threatening sepsis, which accounts for 10% of all neonatal deaths. For the purpose of this guideline, late-onset neonatal infection is defined as infection which occurs between 72 hours of birth and 28 days of age (corrected for gestational age).

Predicting which babies are most at risk of late-onset neonatal infection is important to help determine who should receive antibiotic treatment. A culture taken from blood or cerebrospinal fluid which tests positive for the organisms associated with infection is the gold-standard for identifying which babies should receive treatment. However, waiting for the results of these tests may delay treatment. A tool which can predict which babies are most at risk of late-onset neonatal infection is therefore important to help identify those who will benefit from early treatment, whilst reducing the number of babies who receive unnecessary treatment. This will also reduce other associated risks such as antimicrobial resistance. The aim of this review is therefore to evaluate existing clinical prediction models for late-onset neonatal infection and determine their effectiveness in guiding management of the baby.

1.1.2. Summary of the protocol

The review was divided into 2 parts. Part A aimed to identify studies assessing the accuracy of clinical prediction models in identifying babies with late onset infection. Part B aimed to identify ‘test and treat’ randomised controlled trials that assessed the effectiveness of clinical prediction models in guiding management.

Table

Part A.

Table

Part B.

1.1.3. Methods and process

This evidence review was developed using the methods and process described in Developing NICE guidelines: the manual. Methods specific to this review question are described in the review protocol in Appendix A. For full details of the methods used see the methods document.

Declarations of interest were recorded according to NICE’s 2018 conflicts of interest policy.

Prospective and retrospective observational cohort or cross-sectional studies (part A) and test and treat randomised controlled trials (part B) were considered in addition to systematic reviews. The review protocol specified that, where possible, subgroup analyses would be conducted for gestational age of the baby (preterm vs term) and for babies who had been admitted to the hospital from home. However, this was not possible as most studies included both preterm and term babies, and the results were not separated by gestational age. Studies did not state the admission route of the babies. No studies matched the protocol for Part B of the review (RCTs for different risk predictor tools).

1.1.4. Prognostic evidence

1.1.5. Summary of studies included in the prognostic evidence

Table 2

Summary of included clinical studies.

See appendix D for full evidence tables.

1.1.6. Model summaries

1.1.7. Summary of the prognostic evidence

1.1.8. Economic evidence

1.1.9. Economic model

This question was not prioritised for original economic analysis.

2.1.1. Introduction

Neonatal infection is a significant cause of mortality and morbidity. It can lead to life-threatening sepsis, which accounts for 10% of all neonatal deaths. For the purpose of this guideline, late-onset neonatal infection is defined as infection which occurs between 72 hours of birth and 28 days of age (corrected for gestational age).

Predicting which babies are most at risk of late-onset neonatal infection is important to help determine who should receive antibiotic treatment. A culture taken from blood or cerebrospinal fluid which tests positive for the organisms associated with infection is the gold-standard for identifying which babies should receive treatment. However, waiting for the results of these tests may delay treatment. Identifying the factors which can put a baby at high risk of neonatal infection is therefore important to help determine whether a baby should be given antibiotics while waiting for the results of a blood culture to confirm infection. The aim of this review is therefore to evaluate potential risk factors in the mother and determine how well they can guide management of the baby.

2.1.2. Summary of the protocol

2.1.3. Methods and process

This evidence review was developed using the methods and process described in Developing NICE guidelines: the manual. Methods specific to this review question are described in the review protocol in Appendix A. For full details of the methods used see the methods document.

Declarations of interest were recorded according to NICE’s 2018 conflicts of interest policy.

Predictive accuracy studies were considered in addition to systematic reviews. For outcomes where no predictive accuracy studies were available, multivariate cohort studies that reported adjusted measures of association were included. The review protocol specified that, where possible, subgroup analyses would be conducted for gestational age of the baby (preterm vs term), multiple births, age of the baby (72 hours to 6 days vs 7+ days) and for babies who had been admitted to the hospital from home. However, no evidence was available for any of the specified subgroup analyses.

Some studies reported outcomes that matched the protocol but were only reported as part of univariate analysis. These outcomes were not included in the analysis as they did not meet the inclusion criteria for multivariate analyses methods.

2.1.4. Prognostic evidence

2.1.5. Summary of studies included in the prognostic evidence

Table 3

Summary of included clinical studies.

See appendix D for full evidence tables.

2.1.6. Summary of the prognostic evidence

2.1.7. Economic evidence

2.1.8. Economic model

No economic modelling was undertaken for this review because of a lack of economic evidence and because the committee agreed that other topics were higher priorities for economic evaluation.

3.1.1. Introduction

Neonatal infection is a significant cause of mortality and morbidity in newborn babies. It can lead to life-threatening sepsis, which accounts for 10% of all neonatal deaths. For the purpose of this guideline, late-onset neonatal infection is defined as infection which occurs between 72 hours of birth and 28 days of age (corrected for gestational age).

Predicting which babies are most at risk of late-onset neonatal infection is important to help determine who should receive antibiotic treatment. A culture taken from blood or cerebrospinal fluid which tests positive for the organisms associated with infection is the gold-standard for identifying which babies should receive treatment. However, waiting for the results of these tests may delay treatment. Identifying the factors which can put a baby at high risk of neonatal infection is therefore important to help determine whether a baby should be given antibiotics while waiting for the results of a blood culture to confirm infection. The aim of this review is therefore to evaluate potential risk factors as well as signs and symptoms in the baby to determine how they can guide management of the baby.

3.1.2. Summary of the protocol

3.1.3. Methods and process

This evidence review was developed using the methods and process described in Developing NICE guidelines: the manual. Methods specific to this review question are described in the review protocol Error! Reference source not found.. For full details of the methods used see the methods document.

Declarations of interest were recorded according to NICE’s 2018 conflicts of interest policy.

Predictive accuracy studies were considered in addition to systematic reviews. For outcomes where no predictive accuracy studies were available, multivariate cohort studies that reported adjusted measures of association were included. The review protocol specified that, where possible, subgroup analyses would be conducted for gestational age of the baby (preterm vs term), multiple births, age of the baby (72 hours to 6 days vs 7+ days) and for babies who had been admitted to the hospital from home. Data was available for gestational age and, in some cases, multiple births, but no data was reported for the other subgroups.

3.1.4. Prognostic and diagnostic evidence

3.1.5. Summary of studies included in the prognostic evidence

Table 3

Summary of included clinical studies.

See appendix D for full evidence tables.

3.1.6. Summary of the prognostic and diagnostic evidence

3.1.7. Economic evidence

3.1.8. Economic model

No economic modelling was undertaken for this review because of a lack of economic evidence and because the committee agreed that other topics were higher priorities for economic evaluation.

4.1.1. The outcomes that matter most

The committee discussed the potential effects of true positive, true negative, false positive and false negative outcomes from tools designed to predict risk of late-onset neonatal infection. A model that correctly identifies all those with infection (true positives) would result in antibiotics being prescribed to all those who need treatment, reducing the serious harms associated with neonatal infection. If a model correctly identifies all those without infection (true negatives) then it will avoid over-prescribing of antibiotics. This is a particular concern when evaluating neonatal infection as it is difficult to diagnose and can therefore result in all, or most, babies being prescribed antibiotics to avoid any infections being missed and being left untreated.

If a model does not accurately predict true positives and true negatives, then there are a number of potential harms. False positive results will result in babies being given antibiotics unnecessarily, and admission to hospital will lead to separation of the mother and baby, potentially causing anxiety and distress to the family. False positive results will also incur the costs associated with a hospital stay and can contribute to the development of antibiotic resistance. However, a false negative result is the biggest concern for parents and clinicians as there can be serious consequences if neonatal infection is left untreated. The most serious consequence is death of the baby, but delayed treatment can also have long-term health consequences, such as neuro-disability, which can have both emotional and financial impacts on the family as well as downstream treatment costs for the healthcare system. Consequently, the committee prioritised negative likelihood ratios over positive likelihood ratios – the committee believed that it was important that negative test results were accurate, and that neonatal infection was not incorrectly ruled out.

Some studies only reported c-statistics and did not include data which allowed sensitivity, specificity or likelihood ratios to be calculated. The committee agreed that this outcome was less useful as it weighs false negatives and false positives as equally important, which the committee agreed was not appropriate.

No evidence was available on the sensitivity, specificity and likelihood ratios for risk factors and signs of infection. Instead, the committee decided that information about the associations between potential risk factors and infection was useful, provided it were from multivariate analyses that adjusted for potential confounding variables. Adjusted risk ratios, odds ratios and hazard ratios were therefore considered important.

4.1.2. The quality of the evidence

Eight studies investigated the use of clinical prediction models for late-onset neonatal infection, with quality the of the outcome measures ranging from high to very low quality. Most of the evidence was moderate or low quality, with outcomes most commonly downgraded for imprecision and for studies being at moderate risk of bias. Some of the results for the models had wide confidence intervals, raising questions over the imprecision of the results. Others, such as the demographics and heart rate model and the nearest neighbour model, reported very limited information on the statistical outcomes. These studies only reported c-statistics with no confidence intervals, and there was insufficient information to allow for the calculation of sensitivity or specificity. The models developed by Mani 2014 had low specificity, and had negative likelihood ratios that crossed 1, suggesting that a negative test outcome could indicate both a decrease and an increase in the probability of a baby having an infection. None of the studies were based in the UK and all but two of the models had only been evaluated by one study with no evidence of external validation. The committee still considered these relevant to the review and they were not downgraded for indirectness.

Two models (RALIS and NOSEP) did include evidence of external validation. However, the studies which investigated the use of the NOSEP model were published in 2000 and 2002, with no further evidence available since that time. Three studies published between 2014 and 2016 assessed the use of the RALIS model. However, the model does not appear to be available as a tool outside of the hospitals where it was evaluated. Given the age and location of some of the studies the committee agreed that any tool would need to be re-evaluated to reflect changes in clinical practice, and the differences in practice between the UK and the countries in which the research took place. The quality of outcomes from these studies were not downgraded, as they met the inclusion criteria for the protocol, but the committee decided that the issues with location and age of the research meant that the evidence was not sufficient for these models to be recommended. Instead it supported the need for a research recommendation to validate new or existing prognostic models for late-onset infection (Appendix K).

The majority of the evidence for the risk factors and signs of infection was of moderate or low quality. Evidence was sparse, with no information about some well-known clinical signs and symptoms of sepsis, such as abnormal heart rate, temperature abnormalities, and altered muscle tone. In addition, many of the studies only reported results when there was a significant association between sepsis and a risk factor or symptom of infection. The evidence base is therefore likely to be biased as evidence reporting no significant association between risk factors or symptoms and neonatal infection is likely to have been under-reported. Where studies reported limited information about the analysis methods, or did not report non-significant associations, their outcomes were downgraded for risk of bias. There was very limited evidence for maternal risk factors for late-onset infection, and although some of the studies reported diagnostic accuracy measures, such as sensitivity and specificity, much of this was low quality. The committee therefore focused on the risk factors and signs and symptoms in the baby when developing the recommendations.

The committee discussed the methodological limitations of the studies, as most reported limited or no information on the multivariate analysis, particularly which variables were adjusted for in the model. Most studies were therefore downgraded for risk of bias. Some studies did not report whether blood cultures were taken before or after babies were given antibiotics, and so these were also downgraded for risk of bias. The applicability of the studies was also discussed as many stated that they were investigating sepsis, late-onset infection or nosocomial infection but did not state a maximum age at which their definition of infection ended. It was therefore unclear whether the studies matched the definition in the protocol of infection up to 28 days of age. However, as the studies were based in neonatal units the committee decided that they were likely to be applicable to the research question. Studies were therefore not downgraded for indirectness.

Some of the studies had limited information about the risk factors that were investigated. This was a particular issue for the 3 studies that compared babies with a central venous catheter (CVC) to babies who were not given a catheter. Some of the studies did not specify whether the catheters inserted were umbilical arterial, umbilical venous or peripherally inserted central catheters (PICCs). The committee thought that this information was important as each type of catheter has a different use, is inserted at a different time, and can remain in place for different lengths of time. However, it decided that the evidence was sufficient to support current clinical consensus that the insertion of a central catheter can increase a baby’s risk of developing late-onset neonatal infection.

All of the evidence was based in neonatal units, meaning that it reflected some of the risk factors faced by babies who are being cared for in hospital. However, the committee highlighted that babies who are admitted to hospital from home are usually admitted to a paediatric, rather than neonatal ward. Consequently, there was no evidence available for the risk factors for a baby who is being cared for at home. The committee agreed that there is a big difference between an infection which occurs in hospital and infection in the community. Although some of the findings, such as those related to gestational age, could be applied to these group of babies, many were not relevant, supporting the need for a research recommendation (Appendix K).

4.1.3. Benefits and harms

A tool that can accurately predict whether a baby is at high or low risk of late-onset neonatal infection would help to ensure that only babies who were likely to develop an infection would be given antibiotics. This would also reduce the adverse effects associated with unnecessary treatment for both the baby and the baby’s family as well as reducing the costs associated with treatment. A model based on clinical signs and symptoms would help to make this decision more quickly than current practice whereby babies are screened for infection and treated with antibiotics until culture results are available. However, although some of the models that have been investigated, such as the Celik models, showed high sensitivity and specificity and likelihood ratios that were beyond the clinical decision threshold, they also included factors that would require substantial changes to clinical practice, such as the need to run tests that are not currently part of routine practice. Using these models would therefore involve resource implications such as training for clinicians prior to their implementation. The committee also had concerns over the age of some of the studies and the reasons why some of the models, despite showing good sensitivity and specificity, had not been investigated in more recent studies. The risk factors for late-onset neonatal infection may have changed in the last 10 years, and so more recent studies are needed to ensure the safety of these models and allow a particular clinical prediction model to be recommended.

Given the limited evidence for prognostic models for late-onset infection, the committee decided that recommendations should be based on the risk factors and signs and symptoms of late-onset neonatal infection. Evidence was found on a small subset of the risk factors and signs and symptoms specified in the review protocol, and was limited to association studies, rather than studies reporting predictive accuracy. Consequently, the committee were unable to make specific recommendations about when late-onset infection should be suspected and investigated further. However, the committee agreed that it was important that clinicians were aware of the risk factors for infection. The signs identified in the clinical indicators table were thought to be useful for clinicians in both a specialist and non-specialist setting. Some were more relevant to babies being treated in a hospital, and these were stated as risk factors in a separate recommendation. Given the potentially serious consequences of late-onset neonatal infection, the committee agreed that it was important that more research into the factors associated with late-onset infection should take place. However, it decided that this should be in relation to prognostic models for late-onset neonatal infection as these consider a range of potential risk factors and use them to predict a baby’s risk of infection. This was considered more useful in clinical practice than a list of individual risk factors, and so a research recommendation was made in relation to the development and validation of prognostic models (Appendix K).

The evidence showed that late-onset infection was associated with lower gestational age. When comparing the results for gestational age, the committee noted that there was a variety of comparisons. Some of these were preterm compared to term babies, as stated in the protocol, but many comparisons were based on the number of weeks’ gestation (such as extremely preterm compared to very preterm babies). With this lack of consistency in comparisons, and the low or moderate quality of many of the outcomes, the committee could not be specific about which babies were most at risk of infection based on gestational age. However, it agreed that the results indicated that the more pre-term a baby is, the greater their risk of developing infection. This was therefore included as one of the additional risk factors in the recommendations.

There was some conflict in the results for the use of catheters. When results were reported for central venous catheters, with no specific type of catheter stated, they indicated that the presence of a catheter may increase the risk of infection. In contrast, results for umbilical catheters suggested there was no clear difference in the risk of infection compared to when a baby does not have a catheter. However, with no other evidence on specific types of central catheters, the committee decided that it should report central catheters as a risk factor without specifying which type is most associated with infection.

There were also conflicting results for the association between history of surgery and late-onset infection. While one study indicated that a history of surgery could increase a baby’s chance of infection the other suggested that surgery did not alter the risk of infection. The study which suggested history was a risk factory had a much larger sample size than the study which reported no clear effect on infection rates. This, in addition to the clinical experience of the committee, led them to include history of surgery as a potential risk factor for late-onset infection.

The evidence available on the signs and symptoms of late-onset infection was limited and likely to be biased, due to the limited reporting of non-significant outcomes in many of the studies. The amount of evidence available for many of the risk factors and signs and symptoms was also very limited. Many of the outcomes (such as lethargy, capillary refill time, Apgar scores, hypotension, intraventricular haemorrhage and various outcomes for respiratory difficulties) had only one study to evaluate whether they are a risk factor or sign of infection, and so the committee did not think this was sufficient to justify including them in the recommendations. The committee therefore did not use the evidence directly to formulate a list of clinical indicators of late-onset infection. However, the high-risk criteria listed in the NICE sepsis guideline (NG51 - Section 1.4, Table 3) matched those that the committee considered important based on clinical experience. All of the risk factors included in the high-risk criteria from the sepsis guideline were therefore used as the important indicators of infection, with the exception of ‘no response to social cues’. The sepsis guidelines are based on all children under 5 and the committee did not think that this factor was applicable to a neonate population. Instead, they replaced ‘no response to social cues’ with ‘parental or carer concern over changes in behaviour’. Concern over changes in behaviour was highlighted as an important indicator of infection for newborn babies in the community. This was consistent with the knowledge and experience of the committee, who agreed that late-onset infection should be considered whenever a baby (under 28 days, corrected age) presented with altered behaviour that was causing concern, particularly in a non-specialist setting where a baby would not already be undergoing monitoring. Four other factors were also added to the clinical indicators (alterations in feeding pattern, abdominal distension, seizures and bulging fontanelle). These factors are specific to neonates and so are not part of the sepsis guidelines for children under 5 years. However, the committee decided that these were important factors that need to be considered when deciding on whether a baby is at risk of late-onset infection. The committee noted that babies with late-onset infection often deteriorate quickly, so it is important for non-specialist clinicians to have a low threshold for suspecting late-onset infection, and to seek specialist advice quickly.

Given the limited evidence on the signs and symptoms of late-onset infection, the committee discussed a number of other potential clinical indicators that were not included in the recommendations. However, the committee were concerned about the risk of over-treatment if too many clinical indicators were listed in the recommendations, especially if some of those indicators could have causes other than neonatal infection. The committee decided that the signs included in the recommendation were those that were most likely to indicate infection and therefore the most important to consider when assessing whether a baby may need treatment.

A benefit of increasing awareness of the risk factors for late-onset neonatal infection in non-specialist settings is that babies at risk of infection may be identified sooner and receive early treatment to avoid the negative effects of infection. Increasing the number of babies receiving treatment could potentially increase the development of antibiotic resistance. However, the recommendations are not expected to cause a major change in practice and so this was not seen as a major concern.

4.1.4. Cost effectiveness and resource use

For risk factors and signs of infection, the committee agreed that, while there are good reasons to be judicious about prescribing antibiotics, the costs of the medicines themselves are negligible. In contrast, the costs and consequences associated with infection, including but not limited to death and lifelong morbidity, are potentially very high. The committee agreed that increasing awareness of the risk factors for late-onset neonatal infection may result in cases of late-onset neonatal infection being identified sooner and receiving treatment earlier. This could be important in decreasing hospital stays and is bound to be cost-saving at the population level.

4.1.5. Other factors the committee took into account

A key issue when discussing the prognostic models was the lack of general availability of the models. The committee agreed that it could not recommend a model that was based purely on statistical modelling and did not have a user-friendly design, such as a web-based tool, that could be easily used by clinicians in a neonatal unit.

When considering risk factors, the committee discussed the differences in knowledge between clinicians working in specialist (for example neonatal and paediatric units) and non-specialist (for example community settings and A&E) settings. For instance, while factors such as gestational age are commonly considered risk factors by people working in neonatal units, a baby who is born at a low gestational age would not necessarily be flagged as being at greater risk of infection to community workers, such as GPs. This supported the committee’s decision to include prematurity as a risk factor alongside other issues, such as mechanical ventilation and presence of a catheter, both of which were identified as risk factors from the evidence, that are primarily risk factors for babies who are already in hospital. The committee also decided to highlight that suspected or confirmed infection in another baby in the case of a multiple birth should be a reason to consider the possibility of infection in siblings. Although this is a rare event, the committee decided that it was important to include this in the recommendations as it is something that would not necessarily be considered when evaluating a baby for risk of infection.

The committee discussed whether there should be a recommendation to begin antibiotic treatment based on the presence of a particular number of risk factors and clinical indicators.

However, because of the low quality of evidence identified for this question and the lack of an appropriate prediction model, the committee agreed that a prescriptive recommendation for antibiotic treatment was not appropriate. Instead the committee specified risk factors and clinical indicators that clinicians should be aware of when considering late-onset neonatal infection. As there are high risks associated with delayed treatment of neonatal infection, the committee decided that clinicians should begin treatment if late-onset neonatal infection is suspected, based on clinical judgement. This is in line with current practice, where a baby will be given antibiotics until blood culture results are available, and so it was agreed that an additional recommendation for this was not required.

The committee considered also equality issues. It noted that the risk of having a premature baby was higher in some ethnic groups, such as people of Black African family origin (Puthussery et al. 2019). It also noted that the likelihood of having a baby who is preterm also increased with maternal age (Fuchs et al 2018. Prematurity is noted as a factor in table 1 that can increase the risk of neonatal infection that clinicians should be particularly aware of.

4.1.6. Recommendations supported by this evidence review

This evidence review supports recommendations 1.4.1-1.4.2 and the research recommendation on clinical prediction models for late-onset infection.

4.1.7. References – included studies

4.3.2. Other citations

• Fuchs, F., Monet, B., Ducruet, T., Chaillet, N. and Audibert, F., 2018. Effect of maternal age on the risk of preterm birth: A large cohort study. PloS one, 13(1), p.e0191002. [PMC free article: PMC5791955] [PubMed: 29385154]
• Puthussery, S., Li, L., Tseng, P.C., Kilby, L., Kapadia, J., Puthusserry, T. and Thind, A., 2019. Ethnic variations in risk of preterm birth in an ethnically dense socially disadvantaged area in the UK: a retrospective cross-sectional study. BMJ open, 9(3), p.e023570. [PMC free article: PMC6429724] [PubMed: 30852531]

B.1. Clinical search: Clinical prediction models

The search was conducted on 14th August 2019. Given the broad range of publication types included in the review protocol, no in-house publication type filters were used. The following databases were searched: Medline, Medline In Process, Medline E-pub Ahead of print, Embase, (all via the Ovid platform), Cochrane Database of Systematic Reviews, CENTRAL (all via the Wiley platform), and the DARE database (via the CRD platform).

Medline. Medline In Process, Medline E-pub

1. exp Infant, Newborn/
2. Term Birth/
3. Infant Care/
4. Perinatal Care/
5. Intensive Care Units, Neonatal/
6. Intensive Care, Neonatal/
7. Infant Health/
8. (newborn* or new born* or neonat* or neo-nat* or perinat* or peri-nat*).tw.
9. ((premature or pre-mature* or preterm or pre-term) adj4 (child* or infant* or baby* or babies* or offspring)).tw.
10. or/1-9
11. exp Bacterial Infections/
12. ((bacter* or strep* or staph* or GNB) adj4 (infect* or diseas* or contaminat* or mening* or pneumon* or nosocomial*)).tw.
13. exp Sepsis/
14. (sepsis or septic?emia* or py?emia* or pyho?emia*).tw.
15. (septic* adj4 shock*).tw.
16. or/11-15
17. exp Streptococcus/
18. exp Staphylococcus/
19. (streptococc* or staphylococc*).tw.
20. (GBS or MRSA or NRCS-A or MSSA).tw.
21. (met?icillin-resistant adj3 aureus).tw.
22. exp Escherichia coli/
23. ((Escheric* or E) adj2 coli).tw.
24. exp Listeria/
25. listeria*.tw.
26. exp Klebsiella/
27. klebsiella*.tw.
28. exp Pseudomonas/
29. (pseudomonas or chryseomonas or flavimonas).tw.
30. Enterobacteriaceae/
31. (enterobact* or sodalis or paracolobactrum or ewingella or leclercia).tw.
32. ((enteric or coliform) adj2 bac*).tw.
33. exp Neisseria/
34. neisseria*.tw.
35. exp Haemophilus influenzae/
36. ((h?emophil* or H or bacter* or bacill* or mycobacter* or coccobac*) adj2 (influenz* or pfeiffer* or meningitidis)).tw.
37. exp Serratia/
38. serratia*.tw.
39. exp Cronobacter/
40. (cronobact* or sakazaki* or malonatic*).tw.
41. exp Acinetobacter/
42. (acinetobact* or herellea* or mima or baumanni* or genomosp* or calcoacetic*).tw.
43. exp Fusobacterium/
44. (fusobact* or sphaerophor* or necrophorum or nucleatum).tw.
45. exp Enterococcus/
46. enterococc*.tw.
47. or/17-46
48. 16 or 47
49. 10 and 48
50. ((newborn* or new born* or neonat* or neo-nat* or perinat* or peri-nat*) adj4 infect*).tw.
51. ((premature or pre-mature* or preterm or pre-term) adj4 (child* or infant* or baby* or babies* or offspring) adj4 infect*).tw.
52. 50 or 51
53. 49 or 52
54. (bacter?emia* or bacill?emia*).tw.
55. (blood* adj4 (infect* or contamin* or invas* or invad*)).tw.
56. 54 or 55
57. 10 and 56
58. 53 or 57
59. Risk Assessment/mt [Methods]
60. ((risk* or predict* or probab* or prognos* or quantitativ*) adj2 (model* or tool* or algorithm* or rul*)).tw.
61. (diagnos* adj2 (model* or algorithm*)).tw.
62. ((sepsis* or septic* or Bayes* or EOS or LOS) adj4 calculator*).tw.
63. (NEOSC or EOSCAL* or SRC).tw.
64. (Kaiser adj2 Permanente).tw.
65. (Kaiser adj10 calculator*).tw.
66. ((sepsis or septic*) adj4 risk* adj4 scor*).tw.
67. SRS.tw.
68. ((sepsis* or septic*) adj4 (metascore* or meta-score*)).tw.
69. Diagnosis, Computer-Assisted/
70. Algorithms/
71. ((computer* or vital signs* or math* or manag* or clinic* or medic* or stratif* or prevent* or therap*) adj4 algorithm*).tw.
72. RALIS.tw.
73. (computer* adj4 (analys* or template*)).tw.
74. Decision Support Techniques/
75. (decision* adj4 (aid* or analys* or support* or assist*)).tw.
76. CDSS*.tw.
77. or/59-76
78. 58 and 77
79. Animals/ not Humans/
80. 78 not 79
81. limit 80 to english language

Embase

1. newborn/
2. term birth/
3. infant care/
4. perinatal care/
5. neonatal intensive care unit/
6. newborn intensive care/
7. child health/
8. (newborn* or new born* or neonat* or neo-nat* or perinat* or peri-nat*).tw.
9. ((premature or pre-mature* or preterm or pre-term) adj4 (child* or infant* or baby* or babies* or offspring)).tw.
10. or/1-9
11. exp bacterial infection/
12. ((bacter* or strep* or staph* or GNB) adj4 (infect* or diseas* or contaminat* or mening* or pneumon* or nosocomial*)).tw.
13. exp sepsis/
14. (sepsis or septic?emia* or py?emia* or pyho?emia*).tw.
15. (septic* adj4 shock*).tw.
16. or/11-15
17. exp Streptococcus/
18. exp Staphylococcus/
19. (streptococc* or staphylococc*).tw.
20. (GBS or MRSA or NRCS-A or MSSA).tw.
21. (met?icillin-resistant adj3 aureus).tw.
22. exp Escherichia coli/
23. ((Escheric* or E) adj2 coli).tw.
24. exp Listeria/
25. listeria*.tw.
26. exp Klebsiella/
27. klebsiella*.tw.
28. exp Pseudomonas/
29. (pseudomonas or chryseomonas or flavimonas).tw.
30. Enterobacteriaceae/
31. (enterobact* or sodalis or paracolobactrum or ewingella or leclercia).tw.
32. ((enteric or coliform) adj2 bac*).tw.
33. exp Neisseria/
34. neisseria*.tw.
35. exp Haemophilus influenzae/
36. ((h?emophil* or H or bacter* or bacill* or mycobacter* or coccobac*) adj2 (influenz* or pfeiffer* or meningitidis)).tw.
37. exp Serratia/
38. serratia*.tw.
39. exp cronobacter/
40. (cronobact* or sakazaki* or malonatic*).tw.
41. exp Acinetobacter/
42. (acinetobact* or herellea* or mima or baumanni* or genomosp* or calcoacetic*).tw.
43. exp Fusobacterium/
44. (fusobact* or sphaerophor* or necrophorum or nucleatum).tw.
45. exp Enterococcus/
46. enterococc*.tw.
47. or/17-46
48. 16 or 47
49. 10 and 48
50. ((newborn* or new born* or neonat* or neo-nat* or perinat* or peri-nat*) adj4 infect*).tw.
51. ((premature or pre-mature* or preterm or pre-term) adj4 (child* or infant* or baby* or babies* or offspring) adj4 infect*).tw.
52. 50 or 51
53. 49 or 52
54. (bacter?emia* or bacill?emia*).tw.
55. (blood* adj4 (infect* or contamin* or invas* or invad*)).tw.
56. 54 or 55
57. 10 and 56
58. 53 or 57
59. *risk assessment/
60. ((risk* or predict* or probab* or prognos* or quantitativ*) adj2 (model* or tool* or algorithm* or rul*)).tw.
61. (diagnos* adj2 (model* or algorithm*)).tw.
62. ((sepsis* or septic* or Bayes* or EOS or LOS) adj4 calculator*).tw.
63. (NEOSC or EOSCAL* or SRC).tw.
64. (Kaiser adj2 Permanente).tw.
65. (Kaiser adj10 calculator*).tw.
66. ((sepsis or septic*) adj4 risk* adj4 scor*).tw.
67. SRS.tw.
68. ((sepsis* or septic*) adj4 (metascore* or meta-score*)).tw.
69. computer assisted diagnosis/
70. algorithm/
71. ((computer* or vital signs* or math* or manag* or clinic* or medic* or stratif* or prevent* or therap*) adj4 algorithm*).tw.
72. RALIS.tw.
73. (computer* adj4 (analys* or template*)).tw.
74. exp decision support system/
75. (decision* adj4 (aid* or analys* or support* or assist*)).tw.
76. CDSS*.tw.
77. or/59-76
78. 58 and 77
79. nonhuman/ not human/
80. 78 not 79
81. limit 80 to english language
82. limit 81 to (conference abstract or conference paper or “conference review”)
83. 81 not 82

Cochrane Database of Systematic Reviews, CENTRAL

#1.

MeSH descriptor: [Infant, Newborn] explode all trees

#2.

MeSH descriptor: [Term Birth] this term only

#3.

MeSH descriptor: [Infant Care] this term only

#4.

MeSH descriptor: [Perinatal Care] this term only

#5.

MeSH descriptor: [Intensive Care Units, Neonatal] this term only

#6.

MeSH descriptor: [Intensive Care, Neonatal] this term only

#7.

MeSH descriptor: [Infant Health] this term only

#8.

((newborn* or new born* or new-born or neonat* or neo-nat* or perinat* or peri-nat*)):ti,ab,kw

#9.

((premature or pre-mature* or preterm or pre-term) near/4 (child* or infant* or baby* or babies* or offspring)):ti,ab,kw

#10.

{or #1-#9}

#11.

MeSH descriptor: [Bacterial Infections] explode all trees

#12.

((bacter* or strep* or staph* or GNB) near/4 (infect* or diseas* or contaminat* or mening* or pneumon* or nosocomial*)):ti,ab,kw

#13.

MeSH descriptor: [Sepsis] explode all trees

#14.

((sepsis or septic?emia* or py?emia* or pyho?emia*)):ti,ab,kw

#15.

((septic* near/4 shock*)):ti,ab,kw

#16.

{or #11-#15}

#17.

MeSH descriptor: [Streptococcus] explode all trees

#18.

MeSH descriptor: [Staphylococcus] explode all trees

#19.

((streptococc* or staphylococc*)):ti,ab,kw

#20.

((GBS or MRSA or NRCS-A or MSSA)):ti,ab,kw

#21.

((met?icillin-resistant near/3 aureus)):ti,ab,kw

#22.

MeSH descriptor: [Escherichia coli] explode all trees

#23.

((Escheric* or E) near/2 (coli)):ti,ab,kw

#24.

MeSH descriptor: [Listeria] explode all trees

#25.

(Listeria*):ti,ab,kw

#26.

MeSH descriptor: [Klebsiella] explode all trees

#27.

(klebsiella*):ti,ab,kw

#28.

MeSH descriptor: [Pseudomonas] explode all trees

#29.

((pseudomonas or chryseomonas or flavimonas)):ti,ab,kw

#30.

MeSH descriptor: [Enterobacteriaceae] this term only

#31.

((enterobact* or sodalis or paracolobactrum or ewingella or leclercia)):ti,ab,kw

#32.

((enteric or coliform) near/2 (bac*)):ti,ab,kw

#33.

MeSH descriptor: [Neisseria] explode all trees

#34.

(neisseria*):ti,ab,kw

#35.

MeSH descriptor: [Haemophilus influenzae] explode all trees

#36.

((h?emophil* or H or bacter* or bacill* or mycobacter* or coccobac*) near/2 (influenz* or pfeiffer* or meningitidis)):ti,ab,kw

#37.

MeSH descriptor: [Serratia] explode all trees

#38.

(serratia*):ti,ab,kw

#39.

MeSH descriptor: [Cronobacter] explode all trees

#40.

((cronobact* or sakazaki* or malonatic*)):ti,ab,kw

#41.

MeSH descriptor: [Acinetobacter] explode all trees

#42.

((acinetobact* or herellea* or mima or baumanni* or genomosp* or calcoacetic*)):ti,ab,kw

#43.

MeSH descriptor: [Fusobacterium] explode all trees

#44.

((fusobact* or sphaerophor* or necrophorum or nucleatum)):ti,ab,kw

#45.

MeSH descriptor: [Enterococcus] explode all trees

#46.

(enterococc*):ti,ab,kw

#47.

{or #17-#46}

#48.

#16 or #47

#49.

#10 and #48

#50.

((newborn* or new born* or new-born* or neonat* or neo-nat* or perinat* or peri-nat*) near/4 (infect*)):ti,ab,kw

#51.

((premature or pre-mature* or preterm or pre-term) near/4 (child* or infant* or baby* or babies* or offspring) near/4 (infect*)):ti,ab,kw

#52.

#50 or #51

#53.

#49 or #52

#54.

((bacter?emia* or bacill?emia*)):ti,ab,kw

#55.

((blood*) near/4 (infect* or contamin* or invas* or invad*)):ti,ab,kw

#56.

#54 or #55

#57.

#10 and #56

#58.

#53 or #57

#59.

MeSH descriptor: [Risk Assessment] this term only and with qualifier(s): [methods - MT]

#60.

((risk* or predict* or probab* or prognos* or quantitativ*) near/2 (model* or tool* or algorithm* or rul*)):ti,ab,kw

#61.

((diagnos*) near/2 (model* or algorithm*)):ti,ab,kw

#62.

((sepsis* or septic* or Bayes* or EOS or LOS) near/4 (calculator*)):ti,ab,kw

#63.

((NEOSC or EOSCAL* or SRC)):ti,ab,kw

#64.

((Kaiser) near/2 (Permanente)):ti,ab,kw

#65.

((Kaiser) near/10 (calculator*)):ti,ab,kw

#66.

((sepsis or septic*) near/4 (risk*) near/4 (scor*)):ti,ab,kw

#67.

(SRS):ti,ab,kw

#68.

((sepsis* or septic*) near/4 (metascore* or meta-score*)):ti,ab,kw

#69.

MeSH descriptor: [Diagnosis, Computer-Assisted] this term only

#70.

MeSH descriptor: [Algorithms] this term only

#71.

((computer* or vital signs* or math* or manag* or clinic* or medic* or stratif* or prevent* or therap*) near/4 (algorithm*)):ti,ab,kw

#72.

(RALIS):ti,ab,kw

#73.

((computer*) near/4 (analys* or template*)):ti,ab,kw

#74.

MeSH descriptor: [Decision Support Techniques] this term only

#75.

((decision*) near/4 (aid* or analys* or support* or assist*)):ti,ab,kw

#76.

(CDSS*):ti,ab,kw

#77.

{or #59-#76}

#78.

#58 and #77

#79.

(conference):pt

#80.

((clinicaltrials or trialsearch)):so

#81.

#79 or #80

#82.

#78 not #81

DARE

1. MeSH DESCRIPTOR Infant, Newborn EXPLODE ALL TREES
2. MeSH DESCRIPTOR Term Birth
3. MeSH DESCRIPTOR Infant Care
4. MeSH DESCRIPTOR Perinatal Care
5. MeSH DESCRIPTOR Intensive Care Units, Neonatal
6. MeSH DESCRIPTOR Intensive Care, Neonatal
7. MeSH DESCRIPTOR Infant Health
8. (((newborn* or new born* or neonat* or neo-nat* or perinat* or peri-nat*)))
9. (((premature or pre-mature* or preterm or pre-term) NEAR4 (child* or infant* or baby* or babies* or offspring)))
10. #1 OR #2 OR #3 OR #4 OR #5 OR #6 OR #7 OR #8 OR #9
11. MeSH DESCRIPTOR Bacterial Infections EXPLODE ALL TREE
12. (((bacter* or strep* or staph* or GNB) NEAR4 (infect* or diseas* or contaminat* or mening* or pneumon* or nosocomial*)))
13. MeSH DESCRIPTOR Sepsis EXPLODE ALL TREES
14. (((sepsis or septic?emia* or py?emia* or pyho?emia*)))
15. (((septic* NEAR4 shock*)))
16. #11 OR #12 OR #13 OR #14 OR #15
17. MeSH DESCRIPTOR Streptococcus EXPLODE ALL TREES
18. MeSH DESCRIPTOR Staphylococcus EXPLODE ALL TREES
19. (((streptococc* or staphylococc*)))
20. (((GBS or MRSA or NRCS-A or MSSA)))
21. (((met?icillin-resistant NEAR3 aureus)))
22. MeSH DESCRIPTOR Escherichia coli EXPLODE ALL TREES
23. (((Escheric* or E) NEAR2 (coli)))
24. MeSH DESCRIPTOR Listeria EXPLODE ALL TREES
25. ((listeria*))
26. MeSH DESCRIPTOR Klebsiella EXPLODE ALL TREES
27. ((klebsiella*))
28. MeSH DESCRIPTOR Pseudomonas EXPLODE ALL TREES
29. ((pseudomonas or chryseomonas or flavimonas))
30. MeSH DESCRIPTOR Enterobacteriaceae EXPLODE ALL TREES
31. (enterobact* or sodalis or paracolobactrum or ewingella or leclercia)
32. ((enteric or coliform) NEAR2 (bac*))
33. MeSH DESCRIPTOR Neisseria EXPLODE ALL TREES
34. (neisseria*)
35. MeSH DESCRIPTOR Haemophilus influenzae EXPLODE ALL TREES
36. ((h?emophil* or H or bacter* or bacill* or mycobacter* or coccobac*) NEAR2 (influenz* or pfeiffer* or meningitidis))
37. MeSH DESCRIPTOR Serratia EXPLODE ALL TREES
38. (serratia*)
39. MeSH DESCRIPTOR Cronobacter EXPLODE ALL TREES
40. (cronobact* or sakazaki* or malonatic*)
41. MeSH DESCRIPTOR Acinetobacter EXPLODE ALL TREES
42. ((acinetobact* or herellea* or mima or baumanni* or genomosp* or calcoacetic*))
43. MeSH DESCRIPTOR Fusobacterium EXPLODE ALL TREES
44. ((fusobact* or sphaerophor* or necrophorum or nucleatum))
45. MeSH DESCRIPTOR Enterococcus EXPLODE ALL TREES
46. (enterococc*)
47. #17 OR #18 OR #19 OR #20 OR #21 OR #22 OR #23 OR #24 OR #25 OR #26 OR #27 OR #28 OR #29 OR #30 OR #31 OR #32 OR #33 OR #34 OR #35 OR #36 OR #37 OR #38 OR #39 OR #40 OR #41 OR #42 OR #43 OR #44 OR #45 OR #46
48. #16 OR #47
49. #10 AND #48
50. ((newborn* or new born* or neonat* or neo-nat* or perinat* or peri-nat*) NEAR4 (infect*))
51. ((premature or pre-mature* or preterm or pre-term) NEAR4 (child* or infant* or baby* or babies* or offspring) NEAR4 (infect*))
52. #50 OR #51
53. #49 OR #52
54. ((bacter?emia* or bacill?emia*))
55. ((blood*) NEAR4 (infect* or contamin* or invas* or invad*))
56. #54 OR #55
57. #10 AND #56
58. #53 OR #57
59. MeSH DESCRIPTOR Risk Assessment WITH QUALIFIER MT
60. ((risk* or predict* or probab* or prognos* or quantitativ*) NEAR2 (model* or tool* or algorithm* or rul*))
61. ((diagnos*) NEAR2 (model* or algorithm*))
62. ((sepsis* or septic* or Bayes* or EOS or LOS) NEAR4 (calculator*))
63. (NEOSC or EOSCAL* or SRC)
64. ((Kaiser) NEAR2 (Permanente))
65. ((Kaiser) NEAR10 (calculator*))
66. ((sepsis or septic*) NEAR4 (risk*) NEAR4 (scor*))
67. (SRS)
68. ((sepsis* or septic*) NEAR4 (metascore* or meta-score*))
69. MeSH DESCRIPTOR Diagnosis, Computer-Assisted
70. MeSH DESCRIPTOR Algorithms
71. ((computer* or vital signs* or math* or manag* or clinic* or medic* or stratif* or prevent* or therap*) NEAR4 (algorithm*))
72. (RALIS)
73. ((computer*) NEAR4 (analys* or template*))
74. MeSH DESCRIPTOR Decision Support Techniques
75. ((decision*) NEAR4 (aid* or analys* or support* or assist*))
76. (CDSS)
77. #59 OR #60 OR #61 OR #62 OR #63 OR #64 OR #65 OR #66 OR #67 OR #68 OR #69 OR #70 OR #71 OR #72 OR #73 OR #74 OR #75 OR #76
78. #58 AND #77
79. * IN DARE
80. #78 AND #79

B.2. Clinical search: Maternal and neonatal risk factors

The search was conducted on 23rd September 2019. A single search strategy was developed for questions 5.1 and 5.2. The following databases were searched: Medline, Medline In Process, Medline E-pub Ahead of print, Embase, (all via the Ovid platform), Cochrane Database of Systematic Reviews, (via the Wiley platform), and the DARE database (via the CRD platform).

Population and risk factor terms

The search terms used to identify information on population and risk factors are reproduced below for all databases. The population and risk factor terms were combined as ‘And’ to identify papers that discussed both.

Medline, Medline in Process & Medline E-pub Ahead of Print

1. exp Infant, Newborn/
2. Term Birth/
3. Infant Care/
4. Perinatal Care/
5. Intensive Care Units, Neonatal/
6. Intensive Care, Neonatal/
7. Infant Health/
8. (newborn* or new born* or neonat* or neo-nat* or perinat* or peri-nat*).tw.
9. ((premature* or pre-mature* or preterm* or pre-term*) adj4 (child* or infant* or baby* or babies* or offspring)).tw.
10. or/1-9
11. exp Bacterial Infections/
12. ((bacter* or strep* or staph* or GNB) adj4 (infect* or diseas* or contaminat* or mening* or pneumon* or nosocomial*)).tw.
13. exp Sepsis/
14. (sepsis or septic?emia* or py?emia* or pyho?emia*).tw.
15. (septic* adj4 shock*).tw.
16. (bacter?emia* or bacill?emia*).tw.
17. (blood* adj4 (infect* or contamin* or invas* or invad*)).tw.
18. or/11-17
19. exp Streptococcus/
20. exp Staphylococcus/
21. (streptococc* or staphylococc*).tw.
22. (GBS or MRSA or NRCS-A or MSSA).tw.
23. (met?icillin-resistant adj3 aureus).tw.
24. exp Escherichia coli/
25. ((Escheric* or E) adj2 coli).tw.
26. exp Listeria/
27. listeria*.tw.
28. exp Klebsiella/
29. klebsiella*.tw.
30. exp Pseudomonas/
31. (pseudomonas or chryseomonas or flavimonas).tw.
32. Enterobacteriaceae/
33. (enterobact* or sodalis or paracolobactrum or ewingella or leclercia).tw.
34. ((enteric or coliform) adj2 bac*).tw.
35. exp Neisseria/
36. neisseria*.tw.
37. exp Haemophilus influenzae/
38. ((h?emophil* or H or bacter* or bacill* or mycobacter* or coccobac*) adj2 (influenz* or pfeiffer* or meningitidis)).tw.
39. exp Serratia/
40. serratia*.tw.
41. exp Cronobacter/
42. (cronobact* or sakazaki* or malonatic*).tw.
43. exp Acinetobacter/
44. (acinetobact* or herellea* or mima or baumanni* or genomosp* or calcoacetic*).tw.
45. exp Fusobacterium/
46. (fusobact* or sphaerophor* or necrophorum or nucleatum).tw.
47. exp Enterococcus/
48. enterococc*.tw.
49. or/19-48
50. 18 or 49
51. 10 and 50
52. ((newborn* or new born* or neonat* or neo-nat* or perinat* or peri-nat*) adj4 infect*).tw.
53. ((premature or pre-mature* or preterm or pre-term) adj4 (child* or infant* or baby* or babies* or offspring) adj4 infect*).tw.
54. 52 or 53
55. 51 or 54
56. ((previous or preceding or earlier or prior or antecedent) adj4 (child* or infant* or baby* or babies* or offspring or delivery or deliveries)).tw.
57. ((later or next or succeeding) adj4 (child* or infant* or baby* or babies* or offspring or delivery or deliveries)).tw.
58. (Infectious Disease Transmission, Vertical/ or Carrier State/) and (Streptococcal Infections/ or Methicillin-Resistant Staphylococcus aureus/)
59. ((vertical* or maternal* or mother* or mum* or mom* or parental* or fetomaternal* or feto-maternal* or woman* or women* or pregnan* or gestat* or parturition* or birth* or childbirth* or labo?r*) adj4 (GBS* or group B* or MRSA* or met?icillin-resist*) adj4 (transmission* or transmit* or transfer* or infect* or diseas* or contaminat* or coloni?ation* or contagio* or bacteriuria* or carrier* or carriage or heterozygo*)).tw.
60. exp Pregnancy, Multiple/
61. ((multiple or twin or triplet or quadruplet or quintuplet or superfetation) adj4 (pregnan* or gestat* or parturition* or birth* or childbirth* or labo?r* or delivery or deliveries)).tw.
62. Wound Infection/
63. (wound* adj4 (infect* or diseas* or contaminat* or coloni?ation* or contagio* or sepsis)).tw.
64. Postpartum Period/
65. (postpartum or post-partum or puerperium or puerperal).tw.
66. ((perineal or perineum) adj4 (infect* or diseas* or contaminat* or coloni?ation* or contagio*)).tw.
67. exp Obesity/
68. ((obesity or obese or overweight or over-weight) adj8 risk*).tw.
69. exp Hygiene/
70. exp Sanitation/
71. (hygien* or saniti?e* or sanitation* or sanitary*).tw.
72. exp Maternal Behavior/
73. ((behavio?r* or attitud*) adj4 (factor* or aspect* or consider* or circumstanc* or component* or influenc* or feature*)).tw.
74. Illness Behavior/
75. ((alter* or chang* or illness*) adj4 (behavio?r* or respons* or feedback*) adj8 risk*).tw.
76. Muscle Hypotonia/
77. (flop* or flaccid* or hypoton* or hypomyotoni*).tw.
78. ((alter* or chang* or poor* or decreas* or atonic* or feeble or insuffic* or meag* or weak* or unsatisfact* or imperfect* or impair* or declin* or reduc* or diminish*) adj4 musc*).tw.
79. Feeding Behavior/
80. ((feed* or bottle* or breast*) adj4 (behavio?r* or difficult* or refus* or intoleran* or declin* or ignor* or withdraw* or problem*)).tw.
81. exp Vomiting/
82. (vomit* or emesis*).tw.
83. ((gastric* or nasogastric* or naso-gastric*) adj4 (aspirat* or suction*)).tw.
84. (abdom?n* adj4 disten*).tw.
85. Arrhythmias, Cardiac/ or Atrial Fibrillation/ or Atrial Flutter/ or Cardiac Complexes, Premature/ or Parasystole/ or Ventricular Fibrillation/ or Ventricular Flutter/
86. (arr?ythmia* or dysrhythmia*).tw.
87. ((abnormal* or anomal* or atypical* or irregular* or uncommon* or unexpect*) adj4 (heart* or cardiac* or vascular*) adj2 (rate* or pace* or measure* or rhythm* or beat*)).tw.
88. Bradycardia/ or Tachycardia/
89. (bradycardia* or bradyarrhythmia* or tachycardia* or tachyarrhythmia*).tw.
90. Respiratory Distress Syndrome, Newborn/
91. ((respirat* or breath*) adj4 (distres* or troubl* or discomfort*)).tw.
92. exp Hypoxia/
93. (hypoxia* or hypoxic* or hypoxem* or anoxia* or anoxem*).tw.
94. (oxygen* adj4 (deficien* or reduc* or suturat* or concentrat* or measur*)).tw.
95. exp Cyanosis/
96. exp Oximetry/
97. (cyanos?s* or cyanotic* or oximet*).tw.
98. exp Jaundice, Neonatal/
99. (jaundice* or icterus*).tw.
100. exp Apnea/
101. apn?ea*.tw.
102. Seizures/
103. ((seizure* or convuls* or paroxysm*) adj8 risk*).tw.
104. exp Cardiopulmonary Resuscitation/
105. (((cardiopulmon* or cardio-pulmon* or mouth-to-mouth*) adj4 resuscitat*) or CPR).tw.
106. exp Respiration, Artificial/
107. ((artificial* or mechanic* or automat* or machine* or control*) adj4 (respirat* or ventilat* or breath* or oxygenat*)).tw.
108. exp Body Temperature/
109. ((body* or organ* or skin* or high* or low* or excess* or reduc*) adj4 temperat*).tw.
110. ((“36*” or “38*”) adj2 (C or celsius)).tw.
111. ((“96*” or “100*”) adj2 (F or fahrenheit)).tw.
112. exp Shock/
113. (shock not (septic or sepsis)).tw.
114. (circulat* adj4 (collaps* or fail*)).tw.
115. ((pale* or cold* or clammy or chill* or blanch*) adj4 skin*).tw.
116. Sweat/ or Sweating/
117. (sweat* or perspir*).tw.
118. ((rapid* or shallow* or accelarat* or hollow* or flat*) adj4 (breath* or respirat*)).tw.
119. (weakness* or fragilit*).tw.
120. Dizziness/
121. (dizz* or orthostas* or lighthead* or light-head*).tw.
122. Thirst/
123. thirst*.tw.
124. Yawning/
125. (yawn* or sigh or sighs).tw.
126. exp Hemorrhage/
127. (bleed* or h?emorrhag*).tw.
128. (blood* adj4 (loss or effus* or excess*)).tw.
129. exp Thrombocytopenia/
130. (thrombocytop?enia* or thrombop?enia*).tw.
131. Blood Coagulation/
132. ((coagulat* or clot or clott*) adj8 risk*).tw.
133. Oliguria/
134. oliguria*.tw.
135. ((decreas* or diminish* or dwindl* or reduc* or wane) adj4 urin*).tw.
136. Homeostasis/
137. (homeostas* or homeostat* or autoregulat* or auto-regulat*).tw.
138. exp Hypoglycemia/
139. exp Hyperglycemia/
140. (hypoglyc?emi* or hyperglyc?emi*).tw.
141. ((low* or high*) adj4 blood* adj4 (sugar* or glucose*)).tw.
142. exp Acidosis/
143. acidos?s*.tw.
144. ((local* or region* or limit*) adj4 (infect* or contamin* or invas*)).tw.
145. ((previous* or preced* or earlier or prior* or anteceden* or histor* or past*) adj4 (surg* or operat*)).tw.
146. exp Catheters/ or Catheterization/ or Catheterization, Central Venous/ or exp Catheterization, Peripheral/
147. ((catheter* or cannula*) adj4 (present* or presence* or exist* or attend* or current*)).tw.
148. ((indwell* or in-dwell*) adj4 (devic* or apparat* or applianc* or equip* or gadget* or machine* or mechanism*)).tw.
149. (prematur* adj8 risk*).tw.
150. ((newborn* or new born* or neonat* or neo-nat* or perinat* or peri-nat*) adj4 (admiss* or admit*)).tw.
151. ((previous* or preced* or earlier or prior* or anteceden* or histor* or past*) adj4 (GBS* or group B*) adj4 (infect* or contamin* or invas*)).tw.
152. ((newborn* or new born* or neonat* or neo-nat* or perinat* or peri-nat* or infant* or baby* or babies*) adj4 (GBS* or group B* or MRSA* or met?icillin-resist*) adj4 (contaminat* or coloni?ation* or contagio*)).tw.
153. or/56-152
154. 55 and 153
155. Animals/ not Humans/
156. 154 not 155
157. limit 156 to english language

Embase

1. newborn/
2. term birth/
3. infant care/
4. perinatal care/
5. neonatal intensive care unit/
6. newborn intensive care/
7. child health/
8. (newborn* or new born* or neonat* or neo-nat* or perinat* or peri-nat*).tw.
9. ((premature* or pre-mature* or preterm* or pre-term*) adj4 (child* or infant* or baby* or babies* or offspring)).tw.
10. or/1-9
11. exp bacterial infection/
12. ((bacter* or strep* or staph* or GNB) adj4 (infect* or diseas* or contaminat* or mening* or pneumon* or nosocomial*)).tw.
13. exp sepsis/
14. (sepsis or septic?emia* or py?emia* or pyho?emia*).tw.
15. (septic* adj4 shock*).tw.
16. (bacter?emia* or bacill?emia*).tw.
17. (blood* adj4 (infect* or contamin* or invas* or invad*)).tw.
18. or/11-17
19. exp Streptococcus/
20. exp Staphylococcus/
21. (streptococc* or staphylococc*).tw.
22. (GBS or MRSA or NRCS-A or MSSA).tw.
23. (met?icillin-resistant adj3 aureus).tw.
24. exp Escherichia coli/
25. ((Escheric* or E) adj2 coli).tw.
26. exp Listeria/
27. listeria*.tw.
28. exp Klebsiella/
29. klebsiella*.tw.
30. exp Pseudomonas/
31. (pseudomonas or chryseomonas or flavimonas).tw.
32. Enterobacteriaceae/
33. (enterobact* or sodalis or paracolobactrum or ewingella or leclercia).tw.
34. ((enteric or coliform) adj2 bac*).tw.
35. exp Neisseria/
36. neisseria*.tw.
37. exp Haemophilus influenzae/
38. ((h?emophil* or H or bacter* or bacill* or mycobacter* or coccobac*) adj2 (influenz* or pfeiffer* or meningitidis)).tw.
39. exp Serratia/
40. serratia*.tw.
41. exp cronobacter/
42. (cronobact* or sakazaki* or malonatic*).tw.
43. exp Acinetobacter/
44. (acinetobact* or herellea* or mima or baumanni* or genomosp* or calcoacetic*).tw
45. exp Fusobacterium/
46. (fusobact* or sphaerophor* or necrophorum or nucleatum).tw.
47. exp Enterococcus/
48. enterococc*.tw.
49. or/19-48
50. 18 or 49
51. 10 and 50
52. ((newborn* or new born* or neonat* or neo-nat* or perinat* or peri-nat*) adj4 infect*).tw.
53. ((premature or pre-mature* or preterm or pre-term) adj4 (child* or infant* or baby* or babies* or offspring) adj4 infect*).tw.
54. 52 or 53
55. 51 or 54
56. ((previous or preceding or earlier or prior or antecedent) adj4 (child* or infant* or baby* or babies* or offspring or delivery or deliveries)).tw.
57. ((later or next or succeeding) adj4 (child* or infant* or baby* or babies* or offspring or delivery or deliveries)).tw.
58. (vertical transmission/ or heterozygote/) and (exp group B streptococcal infection/ or methicillin resistant Staphylococcus aureus/)
59. ((vertical* or maternal* or mother* or mum* or mom* or parental* or fetomaternal* or feto-maternal* or woman* or women* or pregnan* or gestat* or parturition* or birth* or childbirth* or labo?r*) adj4 (GBS* or group B* or MRSA* or met?icillin-resist*) adj4 (transmission* or transmit* or transfer* or infect* or diseas* or contaminat* or coloni?ation* or contagio* or bacteriuria* or carrier* or carriage or heterozygo*)).tw.
60. exp multiple pregnancy/
61. ((multiple or twin or triplet or quadruplet or quintuplet or superfetation) adj4 (pregnan* or gestat* or parturition* or birth* or childbirth* or labo?r* or delivery or deliveries)).tw.
62. wound infection/
63. (wound* adj4 (infect* or diseas* or contaminat* or coloni?ation* or contagio* or sepsis)).tw.
64. puerperium/
65. (postpartum or post-partum or puerperium or puerperal).tw.
66. ((perineal or perineum) adj4 (infect* or diseas* or contaminat* or coloni?ation* or contagio*)).tw.
67. exp obesity/
68. ((obesity or obese or overweight or over-weight) adj8 risk*).tw.
69. exp hygiene/
70. exp sanitation/
71. (hygien* or saniti?e* or sanitation* or sanitary*).tw.
72. maternal behavior/
73. ((behavio?r* or attitud*) adj4 (factor* or aspect* or consider* or circumstanc* or component* or influenc* or feature*)).tw.
74. illness behavior/
75. ((alter* or chang* or illness*) adj4 (behavio?r* or respons* or feedback*) adj8 risk*).tw.
76. exp muscle hypotonia/
77. (flop* or flaccid* or hypoton* or hypomyotoni*).tw.
78. ((alter* or chang* or poor* or decreas* or atonic* or feeble or insuffic* or meag* or weak* or unsatisfact* or imperfect* or impair* or declin* or reduc* or diminish*) adj4 musc*).tw.
79. feeding behavior/
80. ((feed* or bottle* or breast*) adj4 (behavio?r* or difficult* or refus* or intoleran* or declin* or ignor* or withdraw* or problem*)).tw.
81. exp vomiting/
82. (vomit* or emesis*).tw.
83. gastric suction/
84. ((gastric* or nasogastric* or naso-gastric*) adj4 (aspirat* or suction*)).tw.
85. abdominal distension/
86. (abdom?n* adj4 disten*).tw.
87. heart arrhythmia/ or heart atrium arrhythmia/ or heart fibrillation/ or heart palpitation/ or heart proarrhythmia/ or heart ventricle arrhythmia/ or parasystole/
88. (arr?ythmia* or dysrhythmia*).tw.
89. ((abnormal* or anomal* or atypical* or irregular* or uncommon* or unexpect*) adj4 (heart* or cardiac* or vascular*) adj2 (rate* or pace* or measure* or rhythm* or beat*)).tw.
90. exp bradycardia/ or exp tachycardia/
91. (bradycardia* or bradyarrhythmia* or tachycardia* or tachyarrhythmia*).tw.
92. neonatal respiratory distress syndrome/
93. ((respirat* or breath*) adj4 (distres* or troubl* or discomfort*)).tw.
94. exp hypoxia/
95. (hypoxia* or hypoxic* or hypoxem* or anoxia* or anoxem*).tw.
96. (oxygen* adj4 (deficien* or suturat* or concentrat* or measur* or reduc*)).tw.
97. exp cyanosis/
98. exp oximetry/
99. (cyanos?s* or cyanotic* or oximet*).tw.
100. newborn jaundice/
101. (jaundice* or icterus*).tw.
102. exp apnea/
103. apn?ea*.tw.
104. exp seizure/
105. ((seizure* or convuls* or paroxysm*) adj8 risk*).tw.
106. resuscitation/
107. (((cardiopulmon* or cardio-pulmon* or mouth-to-mouth*) adj4 resuscitat*) or CPR).tw.
108. exp artificial ventilation/
109. ((artificial* or mechanic* or automat* or machine* or control*) adj4 (respirat* or ventilat* or breath* or oxygenat*)).tw.
110. exp body temperature/
111. skin temperature/
112. ((body* or organ* or skin* or high* or low* or excess* or reduc*) adj4 temperat*).tw.
113. ((“36*” or “38*”) adj2 (C or celsius)).tw.
114. ((“96*” or “100*”) adj2 (F or fahrenheit)).tw.
115. exp shock/
116. (shock not (septic or sepsis)).tw.
117. (circulat* adj4 (collaps* or fail*)).tw.
118. ((pale* or cold* or clammy or chill* or blanch*) adj4 skin*).tw.
119. Sweat/ or exp Sweating/
120. (sweat* or perspir*).tw.
121. ((rapid* or shallow* or accelarat* or hollow* or flat*) adj4 (breath* or respirat*)).tw.
122. (weakness* or fragilit*).tw.
123. dizziness/
124. (dizz* or orthostas* or lighthead* or light-head*).tw.
125. thirst/
126. thirst*.tw.
127. yawning/
128. (yawn* or sigh or sighs).tw.
129. exp bleeding/
130. (bleed* or h?emorrhag*).tw.
131. (blood* adj4 (loss or effus* or excess*)).tw.
132. exp thrombocytopenia/
133. (thrombocytop?enia* or thrombop?enia*).tw.
134. exp blood clotting/
135. ((coagulat* or clot or clott*) adj8 risk*).tw.
136. oliguria/
137. oliguria*.tw.
138. ((decreas* or diminish* or dwindl* or reduc* or wane) adj4 urin*).tw.
139. homeostasis/
140. (homeostas* or homeostat* or autoregulat* or auto-regulat*).tw.
141. exp hypoglycemia/
142. exp hyperglycemia/
143. (hypoglyc?emi* or hyperglyc?emi*).tw.
144. ((low* or high*) adj4 blood* adj4 (sugar* or glucose*)).tw.
145. exp acidosis/
146. acidos?s*.tw.
147. ((local* or region* or limit*) adj4 (infect* or contamin* or invas*)).tw.
148. ((previous* or preced* or earlier or prior* or anteceden* or histor* or past*) adj4 (surg* or operat*)).tw.
149. catheter/ or exp indwelling catheter/ or catheterization/ or central venous catheterization/
150. ((catheter* or cannula*) adj4 (present* or presence* or exist* or attend* or current*)).tw.
151. ((indwell* or in-dwell*) adj4 (devic* or apparat* or applianc* or equip* or gadget* or machine* or mechanism*)).tw.
152. (prematur* adj8 risk*).tw.
153. ((newborn* or new born* or neonat* or neo-nat* or perinat* or peri-nat*) adj4 (admiss* or admit*)).tw.
154. ((previous* or preced* or earlier or prior* or anteceden* or histor* or past*) adj4 (GBS* or group B*) adj4 (infect* or contamin* or invas*)).tw.
155. ((newborn* or new born* or neonat* or neo-nat* or perinat* or peri-nat* or infant* or baby* or babies*) adj4 (GBS* or group B* or MRSA* or met?icillin-resist*) adj4 (contaminat* or coloni?ation* or contagio*)).tw.
156. or/56-155
157. 55 and 156
158. nonhuman/ not human/
159. 157 not 158
160. limit 159 to english language

CDSR

#1.

MeSH descriptor: [Infant, Newborn] explode all trees

#2.

MeSH descriptor: [Term Birth] this term only

#3.

MeSH descriptor: [Infant Care] this term only

#4.

MeSH descriptor: [Perinatal Care] this term only

#5.

MeSH descriptor: [Intensive Care Units, Neonatal] this term only

#6.

MeSH descriptor: [Intensive Care, Neonatal] this term only

#7.

MeSH descriptor: [Infant Health] this term only

#8.

((newborn* or new born* or neonat* or neo-nat* or perinat* or peri-nat*)):ti,ab,kw

#9.

((premature* or pre-mature* or preterm* or pre-term*) near/4 (child* or infant* or baby* or babies* or offspring)):ti,ab,kw

#10.

{or #1-#9}

#11.

MeSH descriptor: [Bacterial Infections] explode all trees

#12.

((bacter* or strep* or staph* or GNB) near/4 (infect* or diseas* or contaminat* or mening* or pneumon* or nosocomial*)):ti,ab,kw

#13.

MeSH descriptor: [Sepsis] explode all trees

#14.

(sepsis or septic?emia* or py?emia* or pyho?emia*):ti,ab,kw

#15.

(septic* near/4 shock*):ti,ab,kw

#16.

(bacter?emia* or bacill?emia*):ti,ab,kw

#17.

((blood*) near/4 (infect* or contamin* or invas* or invad*)):ti,ab,kw

#18.

{or #11-#17}

#19.

MeSH descriptor: [Streptococcus] explode all trees

#20.

MeSH descriptor: [Staphylococcus] explode all trees

#21.

(streptococc* or staphylococc*):ti,ab,kw

#22.

(GBS or MRSA or NRCS-A or MSSA):ti,ab,kw

#23.

(met?icillin-resistant near/3 aureus):ti,ab,kw

#24.

MeSH descriptor: [Escherichia coli] explode all trees

#25.

((Escheric* or E) near/2 (coli)):ti,ab,kw

#26.

MeSH descriptor: [Listeria] explode all trees

#27.

(listeria*):ti,ab,kw

#28.

MeSH descriptor: [Klebsiella] explode all trees

#29.

(klebsiella*):ti,ab,kw

#30.

MeSH descriptor: [Pseudomonas] explode all trees

#31.

(pseudomonas or chryseomonas or flavimonas):ti,ab,kw

#32.

MeSH descriptor: [Enterobacteriaceae] explode all trees

#33.

(enterobact* or sodalis or paracolobactrum or ewingella or leclercia):ti,ab,kw

#34.

((enteric or coliform) near/2 (bac*)):ti,ab,kw

#35.

MeSH descriptor: [Neisseria] explode all trees

#36.

(neisseria*):ti,ab,kw

#37.

MeSH descriptor: [Haemophilus influenzae] explode all trees

#38.

((h?emophil* or H or bacter* or bacill* or mycobacter* or coccobac*) near/2 (influenz* or pfeiffer* or meningitidis)):ti,ab,kw

#39.

MeSH descriptor: [Serratia] explode all trees

#40.

(serratia*):ti,ab,kw

#41.

MeSH descriptor: [Cronobacter] explode all trees

#42.

(cronobact* or sakazaki* or malonatic*):ti,ab,kw

#43.

MeSH descriptor: [Acinetobacter] explode all trees

#44.

(acinetobact* or herellea* or mima or baumanni* or genomosp* or calcoacetic*):ti,ab,kw

#45.

MeSH descriptor: [Fusobacterium] explode all trees

#46.

(fusobact* or sphaerophor* or necrophorum or nucleatum):ti,ab,kw

#47.

MeSH descriptor: [Enterococcus] explode all trees

#48.

(enterococc*):ti,ab,kw

#49.

{or #19-#48}

#50.

#18 or #49

#51.

#10 and #50

#52.

((newborn* or new born* or neonat* or neo-nat* or perinat* or peri-nat*) near/4 (infect*)):ti,ab,kw

#53.

((premature or pre-mature* or “preterm” or “pre-term”) near/4 (child* or infant* or baby* or babies* or offspring) near/4 (infect*)):ti,ab,kw

#54.

#52 or #53

#55.

#51 or #54

#56.

((previous or preceding or earlier or prior or antecedent) near/4 (child* or infant* or baby* or babies* or offspring or delivery or deliveries)):ti,ab,kw

#57.

((later or “next” or succeeding) near/4 (child* or infant* or baby* or babies* or offspring or delivery or deliveries)):ti,ab,kw

#58.

MeSH descriptor: [Infectious Disease Transmission, Vertical] this term only

#59.

MeSH descriptor: [Carrier State] this term only

#60.

((vertical* or maternal* or mother* or mum* or mom* or parental* or fetomaternal* or feto-maternal* or woman* or women* or pregnan* or gestat* or parturition* or birth* or childbirth* or labo?r*) near/4 (GBS* or group B* or MRSA* or met?icillin-resist*) near/4 (transmission* or transmit* or transfer* or infect* or diseas* or contaminat* or coloni?ation* or contagio* or bacteriuria* or carrier* or carriage or heterozygo*)):ti,ab,kw

#61.

MeSH descriptor: [Pregnancy, Multiple] explode all trees

#62.

((multiple or twin or triplet or quadruplet or quintuplet or superfetation) near/4 (pregnan* or gestat* or parturition* or birth* or childbirth* or labo?r* or delivery or deliveries)):ti,ab,kw

#63.

MeSH descriptor: [Wound Infection] this term only

#64.

((wound*) near/4 (infect* or diseas* or contaminat* or coloni?ation* or contagio* or sepsis)):ti,ab,kw

#65.

MeSH descriptor: [Postpartum Period] this term only

#66.

(postpartum or post-partum or puerperium or puerperal):ti,ab,kw

#67.

((perineal or perineum) near/4 (infect* or diseas* or contaminat* or coloni?ation* or contagio*)):ti,ab,kw

#68.

MeSH descriptor: [Obesity] explode all trees

#69.

((obesity or obese or overweight or over-weight) near/8 (risk*)):ti,ab,kw

#70.

MeSH descriptor: [Hygiene] explode all trees

#71.

MeSH descriptor: [Sanitation] explode all trees

#72.

(hygien* or saniti?e* or sanitation* or sanitary*):ti,ab,kw

#73.

MeSH descriptor: [Maternal Behavior] explode all trees

#74.

((behavio?r* or attitud*) near/4 (factor* or aspect* or consider* or circumstanc* or component* or influenc* or feature*)):ti,ab,kw

#75.

MeSH descriptor: [Illness Behavior] this term only

#76.

((alter* or chang* or illness*) near/4 (behavio?r* or respons* or feedback*) near/8 (risk*)):ti,ab,kw

#77.

MeSH descriptor: [Muscle Hypotonia] this term only

#78.

(flop* or flaccid* or hypoton* or hypomyotoni*):ti,ab,kw

#79.

((alter* or chang* or poor* or decreas* or atonic* or feeble or insuffic* or meag* or weak* or unsatisfact* or imperfect* or impair* or declin* or reduc* or diminish*) near/4 (musc*)):ti,ab,kw

#80.

MeSH descriptor: [Feeding Behavior] this term only

#81.

((feed* or bottle* or breast*) near/4 (behavio?r* or difficult* or refus* or intoleran* or declin* or ignor* or withdraw* or problem)):ti,ab,kw

#82.

MeSH descriptor: [Vomiting] explode all trees

#83.

(vomit* or emesis*):ti,ab,kw

#84.

((gastric* or nasogastric* or naso-gastric*) near/4 (aspirat* or suction*)):ti,ab,kw

#85.

((abdom?n* near/4 disten*)):ti,ab,kw

#86.

MeSH descriptor: [Arrhythmias, Cardiac] explode all trees

#87.

(arr?ythmia* or dysrhythmia*):ti,ab,kw

#88.

((abnormal* or anomal* or atypical* or irregular* or uncommon* or unexpect*) near/4 (heart* or cardiac* or vascular*) near/2 (rate* or pace* or measure* or rhythm* or beat*)):ti,ab,kw

#89.

(bradycardia* or bradyarrhythmia* or tachycardia* or tachyarrhythmia*):ti,ab,kw

#90.

MeSH descriptor: [Respiratory Distress Syndrome, Newborn] this term only

#91.

((respirat* or breath*) near/4 (distres* or troubl* or discomfort*)):ti,ab,kw

#92.

MeSH descriptor: [Hypoxia] explode all trees

#93.

(hypoxia* or hypoxic* or hypoxem* or anoxia* or anoxem*):ti,ab,kw

#94.

((oxygen*) near/4 (deficien* or reduc* or suturat* or concentrat* or measur*)):ti,ab,kw

#95.

MeSH descriptor: [Cyanosis] explode all trees

#96.

MeSH descriptor: [Oximetry] explode all trees

#97.

(cyanos?s* or cyanotic* or oximet*):ti,ab,kw

#98.

MeSH descriptor: [Jaundice, Neonatal] explode all trees

#99.

(jaundice* or icterus*):ti,ab,kw

#100.

MeSH descriptor: [Apnea] explode all trees

#101.

(apn?ea*):ti,ab,kw

#102.

MeSH descriptor: [Seizures] this term only

#103.

((seizure* or convuls* or paroxysm*) near/8 (risk*)):ti,ab,kw 647

#104.

MeSH descriptor: [Cardiopulmonary Resuscitation] explode all trees

#105.

((cardiopulmon* or cardio-pulmon* or mouth-to-mouth*) near/4 (resuscitat*)):ti,ab,kw

#106.

(CPR):ti,ab,kw

#107.

MeSH descriptor: [Respiration, Artificial] explode all trees

#108.

((artificial* or mechanic* or automat* or machine* or control*) near/4 (respirat* or ventilat* or breath* or oxygenat*)):ti,ab,kw

#109.

MeSH descriptor: [Body Temperature] explode all trees

#110.

((body* or organ* or skin* or high* or low* or excess* or reduc*) near/4 (temperat*)):ti,ab,kw

#111.

((“36*” or “38*”) near/2 (C or celsius)):ti,ab,kw

#112.

((“96*” or “100*”) near/2 (F or fahrenheit)):ti,ab,kw

#113.

MeSH descriptor: [Shock] explode all trees

#114.

((shock) not (septic or sepsis)):ti,ab,kw

#115.

((circulat*) near/4 (collaps* or fail*)):ti,ab,kw

#116.

((pale* or cold* or clammy or chill* or blanch*) near/4 (skin*)):ti,ab,kw

#117.

MeSH descriptor: [Sweat] this term only

#118.

MeSH descriptor: [Sweating] this term only

#119.

(sweat* or perspir*):ti,ab,kw

#120.

((rapid* or shallow* or accelarat* or hollow* or flat*) near/4 (breath* or respirat*)):ti,ab,kw

#121.

(weakness* or fragilit*):ti,ab,kw

#122.

MeSH descriptor: [Dizziness] this term only

#123.

(dizz* or orthostas* or lighthead* or light-head*):ti,ab,kw

#124.

MeSH descriptor: [Thirst] this term only

#125.

(thirst*):ti,ab,kw

#126.

MeSH descriptor: [Yawning] this term only

#127.

(yawn* or sigh or sighs):ti,ab,kw

#128.

MeSH descriptor: [Hemorrhage] explode all trees

#129.

(bleed* or h?emorrhag*):ti,ab,kw

#130.

((blood*) near/4 (loss or effus* or excess*)):ti,ab,kw

#131.

MeSH descriptor: [Thrombocytopenia] explode all trees

#132.

(thrombocytop?enia* or thrombop?enia*):ti,ab,kw

#133.

MeSH descriptor: [Blood Coagulation] this term only

#134.

((coagulat* or clot or clott*) near/8 (risk*)):ti,ab,kw

#135.

MeSH descriptor: [Oliguria] this term only

#136.

(oliguria*):ti,ab,kw

#137.

((decreas* or diminish* or dwindl* or reduc* or wane) near/4 (urin*)):ti,ab,kw

#138.

MeSH descriptor: [Homeostasis] this term only

#139.

(homeostas* or homeostat* or autoregulat* or auto-regulat*):ti,ab,kw

#140.

MeSH descriptor: [Hypoglycemia] explode all trees

#141.

MeSH descriptor: [Hyperglycemia] explode all trees

#142.

(hypoglyc?emi* or hyperglyc?emi*):ti,ab,kw

#143.

((low* or high*) near/4 (blood*) near/4 (sugar* or glucose*)):ti,ab,kw

#144.

MeSH descriptor: [Acidosis] explode all trees

#145.

(acidos?s*):ti,ab,kw

#146.

((local* or region* or limit*) near/4 (infect* or contamin* or invas*)):ti,ab,kw

#147.

((previous* or preced* or earlier or prior* or anteceden* or histor* or past*) near/4 (surg* or operat*)):ti,ab,kw

#148.

MeSH descriptor: [Catheters] explode all trees

#149.

MeSH descriptor: [Catheterization] this term only

#150.

MeSH descriptor: [Catheterization, Central Venous] this term only

#151.

MeSH descriptor: [Catheterization, Peripheral] explode all trees

#152.

((catheter* or cannula*) near/4 (present* or presence* or exist* or attend* or current*)):ti,ab,kw

#153.

((indwell* or in-dwell*) near/4 (devic* or apparat* or applianc* or equip* or gadget* or machine* or mechanism*)):ti,ab,kw

#154.

(prematur* near/8 risk*):ti,ab,kw

#155.

((newborn* or new born* or neonat* or neo-nat* or perinat* or peri-nat*) near/4 (admiss* or admit*)):ti,ab,kw

#156.

((previous* or preced* or earlier or prior* or anteceden* or histor* or past*) near/4 (GBS* or group B*) near/4 (infect* or contamin* or invas*)):ti,ab,kw

#157.

((newborn* or new born* or neonat* or neo-nat* or perinat* or peri-nat* or infant* or baby* or babies*) near/4 (GBS* or group B* or MRSA* or met?icillin-resist*) near/4 (contaminat* or coloni?ation* or contagio*)):ti,ab,kw

#158.

{or #56-#157}

#159.

#55 and #158

DARE

1. MeSH DESCRIPTOR Infant, Newborn EXPLODE ALL TREES
2. MeSH DESCRIPTOR Term Birth
3. MeSH DESCRIPTOR Infant Care
4. MeSH DESCRIPTOR Perinatal Care
5. MeSH DESCRIPTOR Intensive Care Units, Neonatal
6. MeSH DESCRIPTOR Intensive Care, Neonatal
7. MeSH DESCRIPTOR Infant Health
8. (newborn* or new born* or neonat* or neo-nat* or perinat* or peri-nat*)
9. ((premature or pre-mature* or preterm or pre-term) NEAR4 (child* or infant* or baby* or babies* or offspring))
10. #1 OR #2 OR #3 OR #4 OR #5 OR #6 OR #7 OR #8 OR #9
11. MeSH DESCRIPTOR Bacterial Infections EXPLODE ALL TREES
12. ((bacter* or strep* or staph* or GNB) NEAR4 (infect* or diseas* or contaminat* or mening* or pneumon* or nosocomial*))
13. MeSH DESCRIPTOR Sepsis EXPLODE ALL TREES
14. (sepsis or septic?emia* or py?emia* or pyho?emia*)
15. ((septic* NEAR4 shock*))
16. (bacter?emia* or bacill?emia)
17. ((blood*) NEAR4 (infect* or contamin* or invas* or invad*))
18. #11 OR #12 OR #13 OR #14 OR #15 OR #16 OR #17
19. MeSH DESCRIPTOR Streptococcus EXPLODE ALL TREES
20. MeSH DESCRIPTOR Staphylococcus EXPLODE ALL TREES
21. (streptococc* or staphylococc*)
22. (GBS or MRSA or NRCS-A or MSSA)
23. ((met?icillin-resistant NEAR3 aureus))
24. MeSH DESCRIPTOR Escherichia coli EXPLODE ALL TREES
25. ((Escheric* or E) NEAR2 (coli))
26. MeSH DESCRIPTOR Listeria EXPLODE ALL TREES
27. (listeria*)
28. MeSH DESCRIPTOR Klebsiella EXPLODE ALL TREES
29. (klebsiella*)
30. MeSH DESCRIPTOR Pseudomonas EXPLODE ALL TREES
31. (pseudomonas or chryseomonas or flavimonas)
32. MeSH DESCRIPTOR Enterobacteriaceae EXPLODE ALL TREES
33. (enterobact* or sodalis or paracolobactrum or ewingella or leclercia)
34. ((enteric or coliform) NEAR2 (bac*))
35. MeSH DESCRIPTOR Neisseria EXPLODE ALL TREES
36. (neisseria*)
37. MeSH DESCRIPTOR Haemophilus influenzae EXPLODE ALL TREES
38. ((h?emophil* or H or bacter* or bacill* or mycobacter* or coccobac*) NEAR2 (influenz* or pfeiffer* or meningitidis))
39. MeSH DESCRIPTOR Serratia EXPLODE ALL TREES
40. (serratia*)
41. MeSH DESCRIPTOR Cronobacter EXPLODE ALL TREES
42. (cronobact* or sakazaki* or malonatic*)
43. MeSH DESCRIPTOR Acinetobacter EXPLODE ALL TREES
44. ((acinetobact* or herellea* or mima or baumanni* or genomosp* or calcoacetic*))
45. MeSH DESCRIPTOR Fusobacterium EXPLODE ALL TREES
46. (fusobact* or sphaerophor* or necrophorum or nucleatum)
47. MeSH DESCRIPTOR Enterococcus EXPLODE ALL TREES
48. (enterococc*)
49. #19 OR #20 OR #21 OR #22 OR #23 OR #24 OR #25 OR #26 OR #27 OR #28 OR #29 OR #30 OR #31 OR #32 OR #33 OR #34 OR #35 OR #36 OR #37 OR #38 OR #39 OR #40 OR #41 OR #42 OR #43 OR #44 OR #45 OR #46 OR #47 OR #48
50. #18 OR #49
51. #10 AND #50
52. ((newborn* or new born* or neonat* or neo-nat* or perinat* or peri-nat*) NEAR4 (infect*))
53. ((premature or pre-mature* or preterm or pre-term) NEAR4 (child* or infant* or baby* or babies* or offspring) NEAR4 (infect*))
54. #52 OR #53
55. #51 OR #54
56. ((previous or preceding or earlier or prior or antecedent) NEAR4 (child* or infant* or baby* or babies* or offspring or delivery or deliveries))
57. ((later or ‘next’ or succeeding) NEAR4 (child* or infant* or baby* or babies* or offspring or delivery or deliveries))
58. MeSH DESCRIPTOR Infectious Disease Transmission, Vertical EXPLODE ALL TREES
59. MeSH DESCRIPTOR Carrier State EXPLODE ALL TREES
60. ((vertical* or maternal* or mother* or mum* or mom* or parental* or fetomaternal* or feto-maternal* or woman* or women* or pregnan* or gestat* or parturition* or birth* or childbirth* or labo?r*) NEAR4 (GBS* or group B* or MRSA* or met?icillin-resist*) NEAR4 (transmission* or transmit* or transfer* or infect* or diseas* or contaminat* or coloni?ation* or contagio* or bacteriuria* or carrier* or carriage or heterozygo))
61. MeSH DESCRIPTOR Pregnancy, Multiple EXPLODE ALL TREES
62. ((multiple or twin or triplet or quadruplet or quintuplet or superfetation) NEAR4 (pregnan* or gestat* or parturition* or birth* or childbirth* or labo?r* or delivery or deliveries)
63. MeSH DESCRIPTOR Wound Infection
64. ((wound*) NEAR4 (infect* or diseas* or contaminat* or coloni?ation* or contagio* or sepsis))
65. MeSH DESCRIPTOR Postpartum Period
66. (postpartum or post-partum or puerperium or puerperal)
67. ((perineal or perineum) NEAR4 (infect* or diseas* or contaminat* or coloni?ation* or contagio*))
68. MeSH DESCRIPTOR Obesity EXPLODE ALL TREES
69. ((obesity or obese or overweight or over-weight) NEAR8 (risk*))
70. MeSH DESCRIPTOR Hygiene EXPLODE ALL TREES
71. MeSH DESCRIPTOR Sanitation EXPLODE ALL TREES
72. (hygien* or saniti?e* or sanitation* or sanitary*)
73. MeSH DESCRIPTOR Maternal Behavior EXPLODE ALL TREES
74. ((behavio?r* or attitud*) NEAR4 (factor* or aspect* or consider* or circumstanc* or component* or influenc* or feature*))
75. MeSH DESCRIPTOR Illness Behavior
76. ((alter* or chang* or illness*) NEAR4 (behavio?r* or respons* or feedback*) NEAR8 (risk*))
77. MeSH DESCRIPTOR Muscle Hypotonia
78. (flop* or flaccid* or hypoton* or hypomyotoni*)
79. ((alter* or chang* or poor* or decreas* or atonic* or feeble or insuffic* or meag* or weak* or unsatisfact* or imperfect* or impair* or declin* or reduc* or diminish*) NEAR4 (musc*))
80. MeSH DESCRIPTOR Feeding Behavior
81. ((feed* or bottle* or breast*) NEAR4 (behavio?r* or difficult* or refus* or intoleran* or declin* or ignor* or withdraw* or problem*))
82. MeSH DESCRIPTOR Vomiting EXPLODE ALL TREES
83. (vomit* or emesis*)
84. ((gastric* or nasogastric* or naso-gastric*) NEAR4 (aspirat* or suction*)
85. ((abdom?n* NEAR4 disten*))
86. MeSH DESCRIPTOR Arrhythmias, Cardiac EXPLODE ALL TREES
87. (arr?ythmia* or dysrhythmia*) 566 Delete
88. ((abnormal* or anomal* or atypical* or irregular* or uncommon* or unexpect*) NEAR4 (heart* or cardiac* or vascular*) NEAR2 (rate* or pace* or measure* or rhythm* or beat*)
89. (bradycardia* or bradyarrhythmia* or tachycardia* or tachyarrhythmia*)
90. MeSH DESCRIPTOR Respiratory Distress Syndrome, Newborn
91. ((respirat* or breath*) NEAR4 (distres* or troubl* or discomfort*))
92. MeSH DESCRIPTOR Hypoxia EXPLODE ALL TREES
93. (hypoxia* or hypoxic* or hypoxem* or anoxia* or anoxem*)
94. ((oxygen*) NEAR4 (deficien* or reduc* or suturat* or concentrat* or measur*))
95. MeSH DESCRIPTOR Cyanosis EXPLODE ALL TREES
96. MeSH DESCRIPTOR Oximetry EXPLODE ALL TREES
97. (cyanos?s* or cyanotic* or oximet*)
98. MeSH DESCRIPTOR Jaundice, Neonatal EXPLODE ALL TREES
99. (jaundice* or icterus*)
100. MeSH DESCRIPTOR Apnea EXPLODE ALL TREES
101. (apn?ea*)
102. MeSH DESCRIPTOR Seizures
103. ((seizure* or convuls* or paroxysm*) NEAR8 (risk*))
104. MeSH DESCRIPTOR Cardiopulmonary Resuscitation EXPLODE ALL TREES
105. ((cardiopulmon* or cardio-pulmon* or mouth-to-mouth*) NEAR4 (resuscitat*))
106. (CPR) 133
107. MeSH DESCRIPTOR Respiration, Artificial EXPLODE ALL TREES
108. ((artificial* or mechanic* or automat* or machine* or control*) NEAR4 (respirat* or ventilat* or breath* or oxygenat*))
109. MeSH DESCRIPTOR Body Temperature EXPLODE ALL TREES
110. ((body* or organ* or skin* or high* or low* or excess* or reduc*) NEAR4 (temperat*))
111. ((‘36*’ or ‘38*’) NEAR2 (C or celsius))
112. ((‘96*’ or ‘100*’) NEAR2 (F or fahrenheit))
113. MeSH DESCRIPTOR Shock EXPLODE ALL TREES
114. ((shock) NOT (septic or sepsis))
115. ((circulat*) NEAR4 (collaps* or fail*))
116. ((pale* or cold* or clammy or chill* or blanch*) NEAR4 (skin*))
117. MeSH DESCRIPTOR Sweat
118. MeSH DESCRIPTOR Sweating
119. (sweat* or perspir*)
120. ((rapid* or shallow* or accelarat* or hollow* or flat*) NEAR4 (breath* or respirat*))
121. (weakness* or fragilit*)
122. MeSH DESCRIPTOR Dizziness
123. (dizz* or orthostas* or lighthead* or light-head*)
124. MeSH DESCRIPTOR Thirst
125. (thirst*)
126. MeSH DESCRIPTOR Yawning
127. (yawn* or sigh or sighs)
128. MeSH DESCRIPTOR Hemorrhage EXPLODE ALL TREES
129. (bleed* or hemorrhag*)
130. ((blood*) NEAR4 (loss or effus* or excess*))
131. MeSH DESCRIPTOR Thrombocytopenia EXPLODE ALL TREES
132. (thrombocytop?enia* or thrombop?enia*)
133. MeSH DESCRIPTOR Blood Coagulation
134. ((coagulat* or clot or clott*) NEAR8 (risk*))
135. MeSH DESCRIPTOR Oliguria
136. (oliguria*)
137. ((decreas* or diminish* or dwindl* or reduc* or wane) NEAR4 (urin*))
138. MeSH DESCRIPTOR Homeostasis
139. (homeostas* or homeostat* or autoregulat* or auto-regulat*)
140. MeSH DESCRIPTOR Hypoglycemia EXPLODE ALL TREES
141. MeSH DESCRIPTOR Hyperglycemia EXPLODE ALL TREES
142. (hypoglyc?emi* or hyperglyc?emi*)
143. MeSH DESCRIPTOR Acidosis EXPlODE ALL TREES
144. (acidos?s*)
145. ((local* or region* or limit*) NEAR4 (infect* or contamin* or invas*))
146. ((previous* or preced* or earlier or prior* or anteceden* or histor* or past*) NEAR4 (surg* or operat*))
147. MeSH DESCRIPTOR Catheters EXPLODE ALL TREES
148. MeSH DESCRIPTOR Catheterization
149. MeSH DESCRIPTOR Catheterization, Central Venous
150. MeSH DESCRIPTOR Catheterization, Peripheral EXPLODE ALL TREES
151. ((catheter* or cannula*) NEAR4 (present* or presence* or exist* or attend* or current*))
152. ((indwell* or in-dwell*) NEAR4 (devic* or apparat* or applianc* or equip* or gadget* or machine* or mechanism*))
153. ((prematur* NEAR8 risk*))
154. ((newborn* or new born* or neonat* or neo-nat* or perinat* or peri-nat*) NEAR4 (admiss* or admit*))
155. ((previous* or preced* or earlier or prior* or anteceden* or histor* or past*) NEAR4 (GBS* or group B*) NEAR4 (infect* or contamin* or invas*))
156. ((newborn* or new born* or neonat* or neo-nat* or perinat* or peri-nat* or infant* or baby* or babies*) NEAR4 (GBS* or group B* or MRSA* or met?icillin-resist*) NEAR4 (contaminat* or coloni?ation* or contagio*))
157. #56 OR #57 OR #58 OR #59 OR #60 OR #61 OR #62 OR #63 OR #64 OR #65 OR #66 OR #67 OR #68 OR #69 OR #70 OR #71 OR #72 OR #73 OR #74 OR #75 OR #76 OR #77 OR #78 OR #79 OR #80 OR #81 OR #82 OR #83 OR #84 OR #85 OR #86 OR #87 OR #88 OR #89 OR #90 OR #91 OR #92 OR #93 OR #94 OR #95 OR #96 OR #97 OR #98 OR #99 OR #100 OR #101 OR #102 OR #103 OR #104 OR #105 OR #106 OR #107 OR #108 OR #109 OR #110 OR #111 OR #112 OR #113 OR #114 OR #115 OR #116 OR #117 OR #118 OR #119 OR #120 OR #121 OR #122 OR #123 OR #124 OR #125 OR #126 OR #127 OR #128 OR #129 OR #130 OR #131 OR #132 OR #133 OR #134 OR #135 OR #136 OR #137 OR #138 OR #139 OR #140 OR #141 OR #142 OR #143 OR #144 OR #145 OR #146 OR #147 OR #148 OR #149 OR #150 OR #151 OR #152 OR #153 OR #154 OR #155 OR #156
158. #55 AND #157

Search Filters

The following search filters were combined as ‘And’ with the population and risk factor terms for the Medline databases and Embase. CDSR and DARE are systematic review databases so did not require the addition of a filter.

The Medline versions of the filters are reproduced below. Embase has validated translations of these that were used in the search.

Systematic Review

1. MEDLINE or pubmed).tw.
2. systematic review.tw.
3. systematic review.pt.
4. meta-analysis.pt.
5. intervention$.ti.
6. or/1-5

Observational studies

The in-house observational studies filter was adapted to focus on cross-sectional studies this was then supplemented with the McMaster diagnostic and prognostic filters.

1. Cohort Studies/
2. Prospective Studies/
3. Retrospective Studies/
4. Cross-Sectional Studies/
5. cohort:.mp.
6. predictor:.tw.
7. cross sectional.tw.
8. prospective*.tw.
9. retrospective*.tw.
10. sensitiv:.mp.
11. predictive value:.mp.
12. accurac:.tw.
13. prognosis.sh.
14. diagnosed.tw.
15. death.tw.
16. exp models, statistical/
17. or/1-16

Risk terms

Following combination of population, risk factor and filter terms (if an appropriate database) the number of results were still considered too high. Additional risk terms were combined as ‘And’ with the other sections of the search strategy to reduce numbers.

The Medline risk terms are listed below. These were translated across all databases used in the search:

1. exp Risk/
2. exp Risk Management/
3. Pregnancy, High Risk/
4. risk*.tw.
5. exp Health Status Indicators/
6. ((health* or illness* or wellness* or wellbeing* or well-being*) adj4 (indicat* or index* or indices* or apprais* or barometer* or gaug* or mark* or warn* or ratio or ratios)).tw.
7. (sever* adj4 illness*).tw.
8. exp “Signs and Symptoms”/
9. ((symptom* or sign or signs or manifest* or phenomenon*) adj8 (infect* or diseas* or contaminat* or mening* or pneumon* or nosocomial*)).tw.
10. or/1-9

Virus terms

The following terms were combined as ‘Not’ with the other sections of the search strategy to remove any papers focused on viral illness.

The Medline virus terms are listed below. These were translated across all databases used in the search:

1. exp Virus Diseases/
2. exp Viruses/
3. (virus* or viral* or retrovir* or arbovir* or lentivir* or deltaretrovir*).tw.
4. HIV*.tw.
5. (cytomegalovir* or CMV*).tw.
6. herpes*.tw.
7. (papillomavir* or HPV*).tw.
8. ((hepatitis* or hepatitid*) adj2 (A or B or C or D or E)).tw.
9. (parechovir* or echovir*).tw.
10. (yellow* adj2 fever*).tw.
11. rhinovir*.tw.
12. (coronavir* or deltacoronavir*).tw.
13. rotavir*.tw.
14. (enterovir* or coxsackie*).tw.
15. exp Malaria/
16. (malaria* or paludism*).tw.
17. exp Syphilis/
18. (syphili* or neurosyphili* or neuro-syphili*).tw.
19. or/1-18

B.3. Economics search: Health Economics literature search strategy

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K.1.1. Research recommendation

What is the accuracy of new or existing clinical prediction models for late-onset neonatal infection in the UK and what is their effectiveness in guiding management?

• for babies already on a neonatal unit
• for babies admitted from home

K.1.2. Why this is important

Eight studies were identified which evaluated the accuracy of clinical prediction models for late-onset neonatal infection, none of which were based in the UK and none which provided evidence of external validation. There was no evidence for the use of clinical prediction models for babies who were admitted to hospital from home.

Further research is needed using a robust study design such as prospective cohort studies, parallel RCTs or cluster RCTs to either examine the effectiveness of existing clinical prediction models for late-onset neonatal infection, or to develop new clinical prediction models designed for use in UK clinical practice. Research in this area is essential to help develop accurate methods of identifying babies most at risk of developing late-onset neonatal infection whilst avoiding over-prescribing of antibiotics.

K.1.3. Rationale for research recommendation

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K.1.4. Modified PICO table (Part A – prognostic accuracy)

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K.1.5. Modified PICO table (Part B – clinical effectiveness)

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