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Naloxone for opiate-exposed newborn infants

  1. Thirimon Moe-Byrne1,
  2. Jennifer VE Brown1,
  3. William McGuire2,*

Editorial Group: Cochrane Neonatal Group

Published Online: 28 FEB 2013

Assessed as up-to-date: 31 JUL 2012

DOI: 10.1002/14651858.CD003483.pub2


How to Cite

Moe-Byrne T, Brown JVE, McGuire W. Naloxone for opiate-exposed newborn infants. Cochrane Database of Systematic Reviews 2013, Issue 2. Art. No.: CD003483. DOI: 10.1002/14651858.CD003483.pub2.

Author Information

  1. 1

    Centre for Reviews and Dissemination, University of York, York, UK

  2. 2

    Hull York Medical School & Centre for Reviews and Dissemination, University of York, York, Y010 5DD, UK

*William McGuire, Hull York Medical School & Centre for Reviews and Dissemination, University of York, York, Y010 5DD, UK. William.McGuire@hyms.ac.uk.

Publication History

  1. Publication Status: New search for studies and content updated (no change to conclusions)
  2. Published Online: 28 FEB 2013

SEARCH

 

Background

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Index terms
 

Description of the condition

Opioid analgesics are available, recommended and commonly used for relief of maternal pain during labour in most delivery units in middle- and high-income settings (NICE 2007; Jones 2012). Estimates suggest that about one-third to one-half of women receives opiate analgesia in labour. The extent of use in low-income settings is less certain (Redshaw 2007; Ullman 2010).

The commonly used opiates (pethidine, diamorphine, morphine, fentanyl) are highly lipid soluble and transplacental transfer to the fetus occurs rapidly. Intrauterine exposure to maternal opiates within about four hours of birth may be associated with neurological and cardiorespiratory depression and feeding-behaviour problems in newborn infants (Kumar 2003; Mercer 2007; Reynolds 2010). Concern exists that these adverse effects may delay neonatal physiological transition and postnatal adaptation and result in neonatal intensive or special care unit admission. Delay in establishment of effective breastfeeding is an important potential consequence of this maternal-infant separation (Nissen 1995; Ransjo-Arvidson 2001).

 

Description of the intervention

Naloxone, a specific opiate antagonist, is available for the treatment of neurological and cardiorespiratory depression in opiate-exposed newborn infants. The International Liaison Committee on Resuscitation (ILCOR) has provided guidance on the use of naloxone for newborn infants (Niermeyer 2001). The advice follows the long-standing recommendation of the American Academy of Pediatrics (AAP) Committee on Drugs that naloxone should not be used routinely in opiate-exposed newborn infants but should be "reserved for adjunctive therapy in selected infants who have not initiated or established independent respiration following ventilation, are significantly depressed, and have a high probability of being narcotized" (AAP 1980). These recommendations refer to infants of mothers who have received opiate for analgesia up to four hours prior to delivery. The dose of naloxone recommended in 1980, 0.01 mg/kg, was later revised to 0.1 mg/kg (AAP 1990). In 2010, an ILCOR Consensus on Science and Treatment Recommendations statement updated this advice and suggested that naloxone should only be given to infants with severe respiratory depression after positive-pressure ventilation has restored a normal heart rate and colour (Kattwinkel 2010; Perlman 2010). However, despite these guidelines, surveys of policy and practice indicate that clinicians continue to administer naloxone to opiate-exposed newborn infants in the first few minutes after birth even in the absence of neurological or cardiorespiratory depression or before effective supported ventilation is established (Herschel 2000; Gill 2007).

 
Opiate-dependent mothers

The AAP Committee on Drugs has advised that naloxone should not be administered to infants of opiate-dependent mothers as naloxone may precipitate acute withdrawal and seizures in opiate-habituated infants (Gibbs 1989; AAP 1998). However, there are few data on significant adverse events due to naloxone in infants of opiate-dependent mothers and some authors have recommended a small dose of naloxone (0.01 mg/kg) as a part of the resuscitation of such infants (Maas 1990).

 

Why it is important to do this review

Naloxone should not be regarded as harmless. Concern exists that naloxone may interfere with the role of endogenous opioids in neuroendocrine programming and behaviour (Smotherman 1992; de Castro 1993; Szeto 1995). Given these questions of appropriateness of use and potential long-term effects, it is important to evaluate the available data on the use of naloxone in opiate-exposed newborn infants.

 

Objectives

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Index terms

To determine the effect of naloxone on the need for and duration of neonatal unit stay in infants of mothers who received opiate analgesia prior to delivery or of mothers who have used a prescribed or non-prescribed opiate during pregnancy.

 

Methods

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Index terms
 

Criteria for considering studies for this review

 

Types of studies

Controlled trials using either random or quasi-random patient allocation.

 

Types of participants

Newborn infants with suspected or confirmed exposure to opiates, either:

  1. as maternal pain relief prior to delivery;
  2. as a result of use during pregnancy.

 

Types of interventions

Trials comparing naloxone with placebo or no drug, or comparing more than one dose of naloxone, as part of the management of newborn infants.

 

Types of outcome measures

 

Primary outcomes

 
Mother-infant separation and effect on breastfeeding

  1. Admission to neonatal intensive or special care unit.
  2. Duration of neonatal intensive or special care unit stay.
  3. Failure to establish breastfeeding by hospital discharge.

 

Secondary outcomes

 
Cardio-respiratory function, need for support, and neurobehavioural outcomes

  1. Measures of respiratory function, such as Apgar score, or arterial blood pH or arterial or alveolar carbon dioxide tension measured within the first six hours after birth.
  2. Receipt of assisted ventilation (any form of mechanical ventilation including continuous positive airway pressure) in the neonatal period.
  3. Receipt of endotracheal intubation for respiratory support.
  4. Duration of assisted ventilation (days).
  5. Duration of endotracheal intubation (days).
  6. Days from birth to establish full oral feeds independently of parenteral fluids or nutrition or of enteral tube feeding.
  7. Features of opiate withdrawal, using validated behavioural assessment measures in the neonatal period.
  8. Seizures in the neonatal period.
  9. Neurodevelopmental outcomes beyond infancy assessed using validated assessment.

 

Search methods for identification of studies

We used the standard search strategy of the Cochrane Neonatal Review Group.

 

Electronic searches

We updated the searches in June 2012 to identify reports of trials available since the date of the previous searches in February 2007. The original search strategy was duplicated as far as possible. We searched the original set of databases for this review:

  • Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 6, 2012);
  • MEDLINE (OvidSP, 1946 to June week 1 2012);
  • MEDLINE In process & Other Non-Indexed Citations (OvidSP, June 15, 2012);
  • EMBASE (OvidSP, 1974 to 2012 June 15).

 In addition, we searched the following databases: 

  • CINAHL (EBSCO, inception to June 2012);
  • Maternity and Infant Care (OvidSP, 1971 to June 2012);
  • PubMed.

We limited searches to references added to the databases since January 2007 where possible. We did not apply any language restrictions. A search filter was applied in MEDLINE and PubMed (Lefebvre 2011), and in EMBASE (Lefebvre 2008) to limit retrieval to randomised controlled trials. 

We searched clinicaltrials.gov/, metaRegister of Controlled Trials (mRCT; www.controlled-trials.com/mrct/), WHO International Clinical Trials Registry Platform (ICTRP; www.who.int/ictrp/en/), and the EU Clinical Trials Register (www.clinicaltrialsregister.eu/) to locate ongoing and completed trials.

The full search strategies for each database can be found in Appendix 1.

 

Searching other resources

We examined the references in studies identified as potentially relevant. We also searched the abstracts from the annual meetings of the Pediatric Academic Societies (1993 to 2012), the European Society for Pediatric Research (1995 to 2011), the UK Royal College of Paediatrics and Child Health (2000 to 2012) and the Perinatal Society of Australia and New Zealand (2000 to 2012). We considered trials reported only as abstracts to be eligible if sufficient information was available from the report, or from contact with the authors, to fulfil the inclusion criteria.

 

Data collection and analysis

We used the standard methods of the Cochrane Neonatal Review Group.

 

Selection of studies

Two review authors independently screened the title and abstract of all studies identified by the above search strategy. We assessed the full text of any potentially eligible reports and excluded those studies that did not meet all of the inclusion criteria. We discussed any disagreements until consensus was achieved.

 

Data extraction and management

We used a data collection form to extract relevant information from each included study. Two review authors extracted the data separately. We discussed any disagreements with the third review author until we reached consensus.

 

Assessment of risk of bias in included studies

We used the criteria and standard methods of the Cochrane Neonatal Review Group to assess the methodological quality of any included trials. We evaluated and reported the following issues in the 'Risk of bias' tables:

  1. Sequence generation: we categorised the method used to generate the allocation sequence as:
    1. low risk (any random process, e.g. random number table; computer random number generator);
    2. high risk (any non-random process, e.g. odd or even date of birth; patient case-record number);
    3. unclear.
  2. Allocation concealment: we categorised the method used to conceal the allocation sequence as:
    1. low risk (e.g. telephone or central randomisation; consecutively numbered sealed opaque envelopes);
    2. high risk (open random allocation; unsealed or non-opaque envelopes, alternation; date of birth);
    3. unclear.
  3. Blinding: we assessed blinding separately for different outcomes and categorised the methods as low, high or unclear risk for:
    1. participants;
    2. clinicians and caregivers;
    3. outcome assessors.
  4. Incomplete outcome data: we described the completeness of data including attrition and exclusions from the analysis for each outcome and any reasons for attrition or exclusion where reported. We assessed whether missing data were balanced across groups or were related to outcomes. Where sufficient information was reported or supplied by the trial authors, we re-included missing data in the analyses. We categorised completeness as:
    1. low risk (< 20% missing data);
    2. high risk (> 20% missing data);
    3. unclear.

 

Measures of treatment effect

We calculated risk ratio (RR) and risk difference (RD) for dichotomous data and weighted mean difference (WMD) for continuous data, with respective 95% confidence intervals (CI).

 

Dealing with missing data

We requested outcome data from the trial investigators when these were unavailable in the report.

 

Assessment of heterogeneity

We examined the treatment effects of individual trials and heterogeneity between trial results by inspecting the forest plots if more than one trial was included in a meta-analysis. We calculated the I2 statistic for statistical heterogeneity. We explored the possible causes (e.g. differences in study design, participants, interventions, or completeness of outcome assessments) in sensitivity analyses if substantial (I2 > 50%) heterogeneity was detected.

 

Assessment of reporting biases

We intended to conduct a funnel-plot analysis if there were data from more than five trials included in a meta-analysis.

 

Data synthesis

We used a fixed-effect model for meta-analyses.

 

Subgroup analysis and investigation of heterogeneity

We planned the following subgroup analyses:

  1. dose of naloxone < 0.1 mg/kg body weight;
  2. dose of naloxone ≥ 0.1 mg/kg body weight.

 

Results

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Index terms
 

Description of studies

See: Characteristics of included studies; Characteristics of excluded studies.

 

Included studies

We included nine trials in the review and these are described in the table 'Characteristics of included studies'. Two of these studies were reported in the same article (Dick 1978a; Dick 1978b).

A total of 316 infants participated in the included trials. All were undertaken in the 1970s or early 1980s. The participants were term newborn infants whose mothers had received pethidine (meperidine) for pain relief up to six hours prior to delivery. None of the trials specifically restricted participation to infants with cardiorespiratory or neurological depression following opiate exposure. In most trials, the intervention appears to have been given in the first five minutes after birth. In two trials, naloxone was given later; at 30 minutes (Gerhardt 1977) or at one hour (Welles 1984) after birth. Naloxone was administered via the intramuscular route in four trials, and in the other five via the umbilical venous route. The dose of naloxone used ranged from 0.01 to 0.07 mg/kg with the exception of one study in which a total dose of 0.2 mg was given (Wiener 1977b). The outcomes most commonly assessed were measures of respiratory effort such as Apgar scores, blood gases values, or other measures of alveolar ventilation.

None of the trials examined the effects of naloxone in infants of mothers who had used a prescribed or non-prescribed narcotic during pregnancy.

 

Excluded studies

We excluded two studies (Martin 1972; Brice 1979b; Characteristics of excluded studies).

 

Risk of bias in included studies

All of the trials were small and none presented a sample size calculation.

 

Allocation

Most reports did not provide any details of measures to ensure allocation concealment.

 

Blinding

Caregivers or assessors were likely to have been blinded in five of the trials. Three trials reported the outcome assessors were unblinded and in one trial it is unclear whether outcome assessors were blinded.

 

Incomplete outcome data

All of the trials appear to have achieved complete or near-complete follow-up of infants recruited although none of the trials undertook follow-up beyond the first three days after birth.

 

Effects of interventions

 

Primary outcomes  

  1. Admission to neonatal intensive or special care unit: not reported.
  2. Duration of neonatal intensive or special care unit stay: not reported.
  3. Failure to establish breastfeeding by hospital discharge: not reported.

 

Secondary outcomes  

  1. Measures of respiratory function: eight of the trials presented data on measures of respiratory function measured within the first six hours after birth. There were no statistically significant differences in the Apgar score (Bonta 1979), ventilation rate (Evans 1976), time to sustained respiration (Brice 1979a), minute ventilation (Gerhardt 1977) or blood gas parameters (Dick 1978a; Dick 1978b; Bonta 1979). Four trials assessed measures of alveolar ventilation (Evans 1976; Wiener 1977a; Wiener 1977b; Brice 1979a). There was evidence that, at 30 minutes and four hours post intervention, the expired carbon dioxide output and alveolar ventilation rate were statistically significantly higher, and the alveolar carbon dioxide tension lower, in the naloxone group (analyses 01.01 to 01.03; Figure 1). We detected statistical heterogeneity in these meta-analyses, in each case arising from one study (Wiener 1977b). This study used a larger dose of naloxone, and naloxone was given intramuscularly compared with intravenously in the other studies.
     FigureFigure 1. Forest plot of comparison: 1 Naloxone versus placebo or no drug, outcome: 1.1 Expired carbon dioxide output (mL/kg/min).

  2. Receipt of assisted ventilation in the neonatal period: not reported.
  3. Receipt of endotracheal intubation for respiratory support: not reported.
  4. Duration of assisted ventilation: not reported.
  5. Duration of endotracheal intubation: not reported.
  6. Days from birth to establish full oral feeds independently of parenteral fluids or nutrition or of enteral tube feeding: not reported.
  7. Features of opiate withdrawal: the studies that reported the Scanlon Behavioural Score (Bonta 1979; Brice 1979a) and the Brazelton Neonatal Behavioural Assessment Score (Brice 1979a; Welles 1984) did not find any statistically significant differences. One trial reported the Broussard Neonatal Perception Inventory at 72 hours and found statistically significantly "less optimal behaviour" in the naloxone group (Welles 1984). However, standard deviations were not reported in any of these studies. Wiener 1977b found that the time taken to habituate to a sound-specific stimulus within the first 48 hours was statistically significantly lower in infants who received intramuscular naloxone versus placebo. Wiener 1977a stated that there were no 'important differences' in habituation to auditory stimulus between infants who received intravenous naloxone versus placebo.
  8. Seizures in the neonatal period: not reported.
  9. Neurodevelopmental outcomes beyond infancy assessed using validated assessment: not reported.

Subgroup analyses

  1. Dose of naloxone < 0.1 mg/kg body weight: all of the included trials used this dose.
  2. Dose of naloxone ≥ 0.1 mg/kg body weight: none of the included trials used this dose.

 

Discussion

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Index terms
 

Summary of main results

We identified nine small trials that compared naloxone versus placebo or no drug for treating newborn infants who had been exposed to maternal opiate analgesia prior to delivery. The trials evaluated the effect of naloxone on infants exposed to opiate analgesia in labour. None examined the use of naloxone in infants who had been exposed to opiate in utero during pregnancy, for example due to maternal opiate-dependence.

None of the included trials provided any data on any of the primary outcomes of this review, that is maternal separation (need for neonatal unit admission) and effect on breastfeeding. With regard to secondary outcome measures, most trials only reported measures of respiratory function and neurological behaviour in the first 48 hours after birth. We did not find any data on the incidence of seizures in the neonatal period, or long-term neurodevelopmental outcomes.

 

Overall completeness and applicability of evidence

The trials provided some evidence that infants who received naloxone had higher indices of alveolar ventilation, higher expired carbon dioxide levels and lower alveolar carbon dioxide tensions than control infants. However, the clinical significance of these findings is unclear since the infants recruited to the trials did not appear to have been selected because of cardiorespiratory depression. Infants with low Apgar scores up to five minutes were not eligible for inclusion in two trials (Bonta 1979; Welles 1984). There are no trial data that assess whether treatment with naloxone affects the need for, or the duration of, mechanical respiratory support including positive-pressure ventilation. All of the included trials were conducted over 25 years ago. The evidence is likely to be of limited relevance in the clinical context for which naloxone is recommended by the ILCOR, that is, for opiate-exposed newborn infants with respiratory depression despite appropriate ventilation (Niermeyer 2001; Kattwinkel 2010; Perlman 2010).

 

Quality of the evidence

All of the trials were small and had various methodological weaknesses including uncertain allocation concealment that may have biased their findings and the findings of this review (Figure 2). Ascertainment or surveillance biases may also be present since caregivers and clinicians in some of the trials were aware of the allocated intervention. Although follow-up assessment was complete in the trials, none assessed outcomes beyond the first few days after birth.

 FigureFigure 2. Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

 

Authors' conclusions

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Index terms

 

Implications for practice

The available trial data do not provide any evidence that administration of naloxone to infants exposed in utero to opiate during delivery affects any important outcomes.

 
Implications for research

Clinicians and service-users may consider it appropriate to undertake a randomised controlled trial to determine if naloxone confers any important benefits to newborn infants with cardiorespiratory or neurological depression that may be due to intrauterine exposure to opiate. This trial should assess outcomes that are relevant to the infant, family, and caregivers, such as the need for admission to a neonatal unit for ongoing respiratory support. In view of the concerns that naloxone may interfere with the role of endogenous opioids in neuroendocrine programming and on behaviour (Smotherman 1992; de Castro 1993; Szeto 1995), follow-up assessment beyond infancy should determine neurodevelopmental outcomes.

 

Acknowledgements

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Index terms

This review was funded by the UK National Institute for Health Research (NIHR) under its Programme Grants for Applied Research funding scheme (RP-PG-0609-10107). The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the UK Department of Health.

Melissa Harden, Information Specialist, provided invaluable assistance in devising and running the electronic search.

 

Data and analyses

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Index terms
Download statistical data

 
Comparison 1. Naloxone versus placebo or no drug

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Expired carbon dioxide output (mL/kg/min)3Mean Difference (IV, Fixed, 95% CI)Subtotals only

    1.1 At 15 minutes
150Mean Difference (IV, Fixed, 95% CI)1.30 [0.15, 2.45]

    1.2 At 30 minutes
3108Mean Difference (IV, Fixed, 95% CI)0.90 [0.39, 1.40]

    1.3 At 90 minutes
150Mean Difference (IV, Fixed, 95% CI)0.50 [-0.17, 1.17]

    1.4 At 4 hours
258Mean Difference (IV, Fixed, 95% CI)0.86 [0.12, 1.59]

 2 Alveolar carbon dioxide tension (kPa)4Mean Difference (IV, Fixed, 95% CI)Subtotals only

    2.1 At 10 minutes
144Mean Difference (IV, Fixed, 95% CI)-0.60 [-1.01, -0.19]

    2.2 At 30 minutes
3102Mean Difference (IV, Fixed, 95% CI)-0.87 [-1.16, -0.59]

    2.3 At about 35 minutes
120Mean Difference (IV, Fixed, 95% CI)-0.10 [-0.90, 0.70]

    2.4 At 4 hours
258Mean Difference (IV, Fixed, 95% CI)-0.87 [-1.25, -0.50]

 3 Alveolar ventilation (mL/kg/minute)4Mean Difference (IV, Fixed, 95% CI)Subtotals only

    3.1 At 10 minutes
144Mean Difference (IV, Fixed, 95% CI)13.0 [-16.88, 42.88]

    3.2 At 15 minutes
150Mean Difference (IV, Fixed, 95% CI)16.0 [-8.53, 40.53]

    3.3 At 30 minutes
4152Mean Difference (IV, Fixed, 95% CI)36.03 [21.92, 50.14]

    3.4 At 90 minutes
150Mean Difference (IV, Fixed, 95% CI)14.0 [-6.30, 34.30]

    3.5 At 4 hours
258Mean Difference (IV, Fixed, 95% CI)55.30 [33.92, 76.69]

 

Appendices

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Index terms
 

Appendix 1. Electronic search strategy

Cochrane Central Register of Controlled Trials (CENTRAL)

Wiley onlinelibrary.wiley.com/

Issue 6 of 12, June 2012 

Searched on 18th June 2012. 8 records were retrieved.

#1    MeSH descriptor Infant, Newborn explode all trees (11587)

#2    MeSH descriptor Premature Birth, this term only (256)

#3    (neonat* or neo NEXT nat*):ti,ab (7180)

#4    (newborn* or new NEXT born* or newly NEXT born*):ti,ab (3515)

#5    (preterm or preterms or pre NEXT term or pre NEXT terms):ti,ab (4596)

#6    (preemie* or premie or premies):ti,ab (13)

#7    (prematur* NEAR/3 (birth* or born or deliver*)):ti,ab (569)

#8    (low NEAR/3 (birthweight* or birth NEXT weight*)):ti,ab (2132)

#9    (lbw or vlbw or elbw):ti,ab (676)

#10  infan*:ti,ab (15933)

#11  (baby or babies):ti,ab (2647)

#12  (#1 OR #2 OR #3 OR #4 OR #5 OR #6 OR #7 OR #8 OR #9 OR #10 OR #11) (25692)

#13  MeSH descriptor Naloxone explode all trees (1412)

#14  naloxone:ti,ab (1378)

#15  narcan:ti,ab (4)

#16  MeSH descriptor Narcotic Antagonists, this term only (773)

#17  ((narcotic or opiate or opioid) NEAR/3 antagonist*):ti,ab (701)

#18  (#13 OR #14 OR #15 OR #16 OR #17) (2301)

#19  (#12 AND #18) (66)

#20  (#12 AND #18), from 2007 to 2012 (8)

Line #20 shows the number of hits in CENTRAL only.

MEDLINE

OvidSP http://ovidsp.ovid.com/

1946 to June Week 1 2012 

Searched on 18 June 2012. 50 records were retrieved. The Cochrane highly sensitive search strategy for identifying randomised trials in MEDLINE (sensitivity-maximising version) was used to limit retrieval to clinical trials (lines 19-29).(Lefebvre 2011)

 

1     exp Infant, Newborn/ (465,198)

2     Premature Birth/ (4515)

3     (neonat$ or neo nat$).ti,ab. (169,877)

4     (newborn$ or new born$ or newly born$).ti,ab. (117,264)

5     (preterm or preterms or pre term or pre terms).ti,ab. (37,614)

6     (preemie$ or premie or premies).ti,ab. (95)

7     (prematur$ adj3 (birth$ or born or deliver$)).ti,ab. (10,057)

8     (low adj3 (birthweight$ or birth weight$)).ti,ab. (21,501)

9     (lbw or vlbw or elbw).ti,ab. (4342)

10     infan$.ti,ab. (292,199)

11     (baby or babies).ti,ab. (45,426)

12     or/1-11 (743,233)

13     exp Naloxone/ (21,647)

14     naloxone.ti,ab,rn. (22,762)

15     narcan.ti,ab,rn. (53)

16     Narcotic Antagonists/ (9514)

17     ((narcotic or opiate or opioid) adj3 antagonist$).ti,ab. (10,032)

18     or/13-17 (31,443)

19     randomized controlled trial.pt. (329,386)

20     controlled clinical trial.pt. (84,300)

21     randomized.ab. (233,146)

22     placebo.ab. (131,984)

23     drug therapy.fs. (1,540,302)

24     randomly.ab. (168,067)

25     trial.ab. (241,338)

26     groups.ab. (1,104,185)

27     or/19-26 (2,861,506)

28     exp animals/ not humans/ (3,732,613)

29     27 not 28 (2,429,876)

30     12 and 18 and 29 (192)

31     (2007$ or 2008$ or 2009$ or 2010$ or 2011$ or 2012$).ed. (4,122,936)

32     30 and 31 (50)

  

MEDLINE In-Process & Other Non-Indexed Citations

OvidSP ovidsp.ovid.com/

June 15, 2012 

Searched on 18 June 2012. 16 records were retrieved.

 

1     exp Infant, Newborn/ (0)

2     Premature Birth/ (0)

3     (neonat$ or neo nat$).ti,ab. (5414)

4     (newborn$ or new born$ or newly born$).ti,ab. (3154)

5     (preterm or preterms or pre term or pre terms).ti,ab. (1633)

6     (preemie$ or premie or premies).ti,ab. (2)

7     (prematur$ adj3 (birth$ or born or deliver$)).ti,ab. (320)

8     (low adj3 (birthweight$ or birth weight$)).ti,ab. (765)

9     (lbw or vlbw or elbw).ti,ab. (193)

10     infan$.ti,ab. (9274)

11     (baby or babies).ti,ab. (1838)

12     or/1-11 (16650)

13     exp Naloxone/ (0)

14     naloxone.ti,ab,rn. (336)

15     narcan.ti,ab,rn. (1)

16     Narcotic Antagonists/ (0)

17     ((narcotic or opiate or opioid) adj3 antagonist$).ti,ab. (215)

18     or/13-17 (451)

19     12 and 18 (16)

EMBASE

OvidSP http://ovidsp.ovid.com/

1974 to 2012 June 15 

Searched on 18 June 2012. 35 records were retrieved. A search strategy developed by Lefebvre et al. to identify randomised trials in EMBASE was used to limit retrieval to clinical trials (lines 23-37). (Lefebvre 2008

 

1     exp infant/ (504,798)

2     newborn/ (468,937)

3     prematurity/ (64,713)

4     premature labor/ (23,169)

5     exp low birth weight/ (33,807)

6     (neonat$ or neo nat$).ti,ab. (215,584)

7     (newborn$ or new born$ or newly born$).ti,ab. (145,479)

8     (preterm or preterms or pre term or pre terms).ti,ab. (49,475)

9     (preemie$ or premie or premies).ti,ab. (121)

10     (prematur$ adj3 (birth$ or born or deliver$)).ti,ab. (13,359)

11     (low adj3 (birthweight$ or birth weight$)).ti,ab. (26,452)

12     (lbw or vlbw or elbw).ti,ab. (5518)

13     infan$.ti,ab. (357,113)

14     (baby or babies).ti,ab. (59,494)

15     or/1-14 (1,124,362)

16     naloxone/ (35,742)

17     naltrexone/ (10,356)

18     naloxone.ti,ab. (22,967)

19     narcan.ti,ab. (89)

20     narcotic antagonist/ (2331)

21     ((narcotic or opiate or opioid) adj3 antagonist$).ti,ab. (11,952)

22     16 or 17 or 18 or 19 or 20 or 21 (50,309)

23     random$.ti,ab. (743,113)

24     factorial$.ti,ab. (19,445)

25     crossover$.ti,ab. (44,206)

26     cross-over$.ti,ab. (20,134)

27     placebo$.ti,ab. (180,615)

28     (doubl$ adj blind$).ti,ab. (134,615)

29     (singl$ adj blind$).ti,ab. (12,482)

30     assign$.ti,ab. (207,848)

31     allocat$.ti,ab. (69,955)

32     volunteer$.ti,ab. (162,807)

33     Crossover Procedure/ (34,089)

34     double blind procedure/ (111,697)

35     Randomized Controlled Trial/ (325,738)

36     single blind procedure/ (15,977)

37     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 (1,237,026)

38     15 and 22 and 37 (119)

39     animal/ (1,784,081)

40     exp animal experiment/ (1,622,232)

41     nonhuman/ (3,857,480)

42     (rat or rats or mouse or mice or hamster or hamsters or animal or animals or dog or dogs or cat or cats or bovine or sheep).ti,ab,sh. (4,684,524)

43     39 or 40 or 41 or 42 (6,628,324)

44     exp human/ (13,638,715)

45     human experiment/ (301,557)

46     44 or 45 (13,640,150)

47     43 not (43 and 46) (5,231,569)

48     38 not 47 (99)

49     (2007$ or 2008$ or 2009$ or 2010$ or 2011$ or 2012$).em. (5,769,628)

50     48 and 49 (35) 

 

CINAHL

via EBSCO www.ebsco.com/

Inception to 15 June 2012 

Searched on 25 June 2012. 33 records were retrieved.

 

S23       S21 and S22 (33)

S22       EM 200701- (1338056)

S21       S14 and S20 (69)

S20       S15 or S16 or S17 or S18 or S19 (1755)

S19       TI ( ((narcotic or opiate or opioid) N3 antagonist*) ) OR AB ( ((narcotic or opiate or opioid) N3 antagonist*) ) (296)

S18       (MH "Narcotic Antagonists") (553)

S17       TI narcan OR AB narcan (22)

S16       TI naloxone OR AB naloxone (537)

S15       (MH "Naloxone+") (1236)

S14       (S1 or S2 or S3 or S4 or S5 or S6 or S7 or S8 or S9 or S10 or S11 or S12 or S13) (90103)

S13       TI ( baby or babies ) OR AB ( baby or babies ) (12769)

S12       TI infan* OR AB infan* (36205)

S11       TI ( lbw or vlbw or elbw ) OR AB ( lbw or vlbw or elbw ) (1111)

S10       TI ( low N3 (birthweight* or birth-weight*) ) OR AB ( low N3 (birthweight* or birth-weight*) ) (4435)

S9         TI ( prematur* N3 (birth* or born or deliver*) ) OR AB ( prematur* N3 (birth* or born or deliver*) ) (1457)

S8         TI ( preemie* or premie or premies ) OR AB ( preemie* or premie or premies ) (152)

S7         TI ( preterm or preterms or pre-term or pre-terms ) OR AB ( preterm or preterms or pre-term or pre-terms ) (8849)

S6         TI ( newborn* or new-born* or "newly born*" ) OR AB ( newborn* or new-born* or "newly born*" ) (9626)

S5         TI ( neonat* or neo-nat* ) OR AB ( neonat* or neo-nat* ) (19333)

S4         (MH "Childbirth, Premature") (2837)

S3         (MH "Infant, Premature") (9120)

S2         (MH "Infant, Low Birth Weight+") (5567)

S1         (MH "Infant, Newborn+") (56780)

Maternity and Infant Care

OvidSP ovidsp.ovid.com/

1971 to June 2012 

Searched on 18 June 2012. 50 records were retrieved.

 

1     infant.de. (7000)

2     Infant - newborn.de. (23,180)

3     Infant - premature.de. (7126)

4     infant - very premature.de. (731)

5     Infant - low birth weight.de. (2354)

6     Infant - very low birth weight.de. (2132)

7     Premature birth - aetiology.de. (725)

8     Infant - small for gestational age.de. (881)

9     (neonat$ or neo nat$).ti,ab. (27614)

10     (newborn$ or new born$ or newly born$).ti,ab. (12,931)

11     (preterm or preterms or pre term or pre terms).ti,ab. (15,364)

12     (preemie$ or premie or premies).ti,ab. (33)

13     (prematur$ adj3 (birth$ or born or deliver$)).ti,ab. (2771)

14     (low adj3 (birthweight$ or birth weight$)).ti,ab. (7467)

15     (lbw or vlbw or elbw).ti,ab. (1891)

16     infan$.ti,ab. (41,734)

17     (baby or babies).ti,ab. (21,094)

18     or/1-17 (82513)

19     Naloxone.de. (12)

20     "Naloxone - administration and dosage".de. (3)

21     Naloxone - adverse effects.de. (4)

22     Naltrexone.de. (3)

23     naloxone.ti,ab. (57)

24     narcan.ti,ab. (1)

25     ((narcotic or opiate or opioid) adj3 antagonist$).ti,ab. (13)

26     19 or 20 or 21 or 22 or 23 or 24 or 25 (66)

27     18 and 26 (50)

  

PubMed

www.ncbi.nlm.nih.gov/pubmed/

Searched on 27 June 2012 using the PubMed advanced search builder. 195 records were retrieved. The Cochrane highly sensitive search strategy for identifying randomised trials in PubMed (sensitivity-maximizing version) was used to limit retrieval to clinical trials (lines 16-27). (Lefebvre 2011)

#28            Search (#15) AND #27 (195)

#27            Search (#25) NOT #26 (2567074)

#26            Search animals [mh] NOT humans [mh] (3683980)

#25            Search (((((((#16) OR #17) OR #18) OR #19) OR #21) OR #22) OR #23) OR #24 (2997189)

#24            Search groups[Title/Abstract] (1205973)

#23            Search trial[Title/Abstract] (306478)

#22            Search randomly[Title/Abstract] (182400)

#21            Search drug therapy[MeSH Subheading] (1525535)

#19            Search placebo[Title/Abstract] (141339)

#18            Search randomized[Title/Abstract] (265625)

#17            Search controlled clinical trial[Publication Type] (83926)

#16            Search randomized controlled trial[Publication Type] (325861)

#15            Search (#1) AND #14 (847)

#14            Search ((((((#4) OR #5) OR #6) OR #11) OR #13) OR #10) OR #12 (34499)

#13            Search (opioid[Title/Abstract]) AND antagonist*[Title/Abstract] (11829)

#12            Search (opiate[Title/Abstract]) AND antagonist*[Title/Abstract] (4385)

#11            Search (narcotic[Title/Abstract]) AND antagonist*[Title/Abstract] (1057)

#10            Search "Narcotic Antagonists"[Mesh:NoExp] (9354)

#6              Search narcan (27518)

#5              Search naloxone (27515)

#4              Search "Naloxone"[Mesh] (21432)

#1              Search ((((((((((((((("Infant, Newborn"[Mesh])) OR ("Premature Birth"[Mesh])) OR (((neonat*[Title/Abstract]) OR neo nat*[Title/Abstract]) OR neo-nat*[Title/Abstract])) OR (((((newborn*[Title/Abstract]) OR new born*[Title/Abstract]) OR new-born*[Title/Abstract]) OR newly born*[Title/Abstract]) OR newly-born*[Title/Abstract])) OR ((((((preterm[Title/Abstract]) OR preterms[Title/Abstract]) OR pre term[Title/Abstract]) OR pre-term[Title/Abstract]) OR pre terms[Title/Abstract]) OR pre-terms[Title/Abstract])) OR (((preemie*[Title/Abstract]) OR premie[Title/Abstract]) OR premies[Title/Abstract])) OR ((prematur*[Title/Abstract]) AND birth*[Title/Abstract])) OR ((prematur*[Title/Abstract]) AND born[Title/Abstract])) OR ((prematur*[Title/Abstract]) AND deliver*[Title/Abstract])) OR ((low[Title/Abstract]) AND birthweight*[Title/Abstract])) OR ((low[Title/Abstract]) AND birth weight*[Title/Abstract])) OR ((low[Title/Abstract]) AND birth-weight*[Title/Abstract])) OR (((lbw[Title/Abstract]) OR vlbw[Title/Abstract]) OR elbw[Title/Abstract])) OR (infan*[Title/Abstract])) OR ((baby[Title/Abstract]) OR babies[Title/Abstract]) (768278)

 

Trial registers

 

ClinicalTrials.gov

www.clinicaltrials.gov/

 Searched on 26 June 2012. 2 studies found.

 1. Naloxone AND (infant OR infants OR newborn OR newborns OR premature OR prematurity OR neonate OR neonates OR neonatal OR preterm OR preterms OR preemie OR preemies OR premie OR premies OR birthweight OR baby OR babies) – 1 result

 2. Narcan AND (infant OR infants OR newborn OR newborns OR premature OR prematurity OR neonate OR neonates OR neonatal OR preterm OR preterms OR preemie OR preemies OR premie OR premies OR birthweight OR baby OR babies) – 1 result 

 

metaRegister of Controlled Trials (mRCT)

www.controlled-trials.com/mrct/searchform

 Searched on 26th June 2012. 6 studies found.

 1. Naloxone AND (infant OR infants OR newborn OR newborns OR premature OR prematurity OR neonate OR neonates or neonatal OR preterm OR preterms OR  preemie OR preemies  OR premie OR premies OR birthweight OR  baby OR  babies) – 5 results

2. Narcan AND (infant OR infants OR newborn OR newborns OR premature OR prematurity OR neonate OR neonates or neonatal OR preterm OR preterms OR  preemie OR preemies  OR premie OR premies OR birthweight OR  baby OR  babies) – 1 result

 

WHO International Clinical Trials Registry Platform

apps.who.int/trialsearch/AdvSearch.aspx

 Searched on 26 June 2012. 12 studies found.

 1. Naloxone in title, clinical trials in children – 4 results

2. Naloxone in intervention field, clinical trials in children – 4 results

3. Narcan in title, clinical trials in children – 0

4. Narcan in intervention field, clinical trials in children – 4 results

  

EU Clinical Trials Register

www.clinicaltrialsregister.eu/ctr-search/search

 Searched on 26th June 2012 using the advance search page. No studies were found. 

1. naloxone textword search, limited to newborn or preterm new born infants age filter – 0 results 

2. narcan textword search, limited to newborn or preterm new born infants age filter – 0 results

 

 

What's new

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Index terms

Last assessed as up-to-date: 31 July 2012.


DateEventDescription

31 July 2012New search has been performedThis updates the review "Naloxone for opiate-exposed newborn infants" (McGuire 2002).

31 July 2012New citation required but conclusions have not changedSearch updated in June 2012.
No new trials added.

Background and discussion updated.



 

History

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Index terms

Protocol first published: Issue 1, 2002
Review first published: Issue 4, 2002


DateEventDescription

10 June 2008AmendedConverted to new review format.

14 March 2007New search has been performedThis review updates "Naloxone for narcotic-exposed newborn infants", published in the Cochrane Database of Systematic Reviews, The Cochrane Library, Issue 4, 2002 (McGuire 2002).

Our electronic search was updated in February 2007. No new trials that fulfilled eligibility criteria were identified.

We re-categorised studies that were previously listed as "studies awaiting assessment". Four of these were abstracts presenting data that was also presented in included substantive publications. These are now listed as secondary publications. One study was excluded.

18 June 2002New citation required and conclusions have changedSubstantive amendment



 

Contributions of authors

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Index terms

Thirimon Moe-Byrne and Jennifer Brown searched and screened the studies for inclusion, assessed the methodological quality of the trials and extracted and entered the relevant information and data from each included study independently.
All authors completed the final review.

 

Declarations of interest

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Index terms

None.

 

Sources of support

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. Appendices
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Index terms
 

Internal sources

  • Hull York Medical School & Centre for Reviews and Dissemination, University of York, UK.

 

External sources

  • NIHR Programme: Improving quality of care and outcome at preterm birth, UK.
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development National Institutes of Health, Department of Health and Human Services, USA.
    Editorial support of the Cochrane Neonatal Review Group has been funded with Federal funds from the Eunice Kennedy Shriver National Institute of Child Health and Human Development National Institutes of Health, Department of Health and Human Services, USA, under Contract No. HHSN275201100016C.

* Indicates the major publication for the study

References

References to studies included in this review

  1. Top of page
  2. AbstractRésumé
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Characteristics of studies
  18. References to studies included in this review
  19. References to studies excluded from this review
  20. Additional references
  21. References to other published versions of this review
Bonta 1979 {published data only}
  • Bonta BW, Gagliardi JV, Williams V, Warshaw JB. Naloxone reversal of mild neurobehavioral depression in normal newborn infants after routine obstetric analgesia. Journal of Pediatrics 1979;94(1):102-5.
Brice 1979a {published data only}
  • Brice JE, Moreland TA, Walker CH. Effects of pethidine and its antagonists on the newborn. Archives of Disease in Childhood 1979;54(5):356-61.
Dick 1978a {published data only}
Dick 1978b {published data only}
Evans 1976 {published data only}
  • Evans JM. The effect of naloxone on the early respiratory depressant effect of maternal pethidine analgesia. European Congress of Anaesthesiology. Madrid, 1974.
  • Evans JM, Hogg MI, Rosen M. Reversal of narcotic depression in the neonate by naloxone. BMJ 1976;2(6044):1098-100.
  • Evans JM, Hogg MIJ, Rosen M. The effect of naloxone on the depression of the early respiratory activity of neonates produced by maternal pethidine analgesia. In: Arias A editor(s). Recent Progress in Anaesthesiology and Resuscitation. Amsterdam: Excerpta Medica, 1975:72.
Gerhardt 1977 {published data only}
  • Gerhardt T, Bancalari E, Cohen H, Rocha LF. Use of naloxone to reverse narcotic respiratory depression in the newborn infant. Journal of Pediatrics 1977;90(6):1009-12.
  • Gerhardt T, Bancalari E, Cohen H, Rocha LF, Holsinger K. Reversal of narcotic respiratory depression in the newborn with naloxone. American Society of Anesthesiologists Annual Meeting. Chicago, 1975.
Welles 1984 {published data only}
  • Welles B, Belfrage P, de Chateau P. Effects of naloxone on newborn infant behavior after maternal analgesia with pethidine during labor. Acta Obstetricia et Gynecologica Scandinavica 1984;63(7):617-9.
Wiener 1977a {published data only}
  • Wiener PC, Hogg MI, Rosen M. Effects of naloxone on pethidine-induced neonatal depression. Part 1. Intravenous naloxone. BMJ 1977;2(6081):228-9.
Wiener 1977b {published data only}
  • Wiener PC, Hogg MI, Rosen M. Effects of naloxone on pethidine-induced neonatal depression. Part 2. Intramuscular naloxone. BMJ 1977;2:229-31.
  • Wiener PC, Hogg MI, Rosen M. Neonatal respiration, feeding and neurobehavioural state. Effects of intrapartum bupivacaine, pethidine and pethidine reversed by naloxone. Anaesthesia 1979;34(10):996-1004.

References to studies excluded from this review

  1. Top of page
  2. AbstractRésumé
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Characteristics of studies
  18. References to studies included in this review
  19. References to studies excluded from this review
  20. Additional references
  21. References to other published versions of this review
Brice 1979b {published data only}
  • Brice JEH, Moreland TA, Parija AC, Walker CHM. Plasma naloxone levels in the newborn after intravenous or intramuscular administration. British Journal of Clinical Pharmacology 1979;8(4):412P-3P.
Martin 1972 {published data only}
  • Martin K, Knapstein PG, Melchert F, Schafer H, Tietze KW. Clinical experiences with the opiate antagonist naloxone in newborns [Klinische Erfahrungen mit dem Opiat-Antagonisten naloxone beim Neugeborenen]. Tagung der Mittelrheinischen gesellschaft fur Geburtshilfe und Gynakologie 1972;143:10-11.

Additional references

  1. Top of page
  2. AbstractRésumé
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Characteristics of studies
  18. References to studies included in this review
  19. References to studies excluded from this review
  20. Additional references
  21. References to other published versions of this review
AAP 1980
  • American Academy of Pediatrics Committee on Drugs. Naloxone use in newborns. Pediatrics 1980;65(3):667-9.
AAP 1990
  • American Academy of Pediatrics Committee on Drugs. Naloxone dosage and route of administration for infants and children: addendum to emergency drug doses for infants and children. Pediatrics 1990;86(3):484-5.
AAP 1998
  • American Academy of Pediatrics Committee on Drugs. Neonatal drug withdrawal. Pediatrics 1998;101(6):1079-88.
de Castro 1993
  • de Castro RM, Cabral-Filho JE, Costa JA, Costa FB, Gallindo MA, Hecksher CA. Neonatal treatment with naloxone causes permanent hyperalgesia in rats. Brazilian Journal of Medical & Biological Research 1993;26(7):747-51.
Gibbs 1989
  • Gibbs J, Newson T, Williams J, Davidson DC. Naloxone hazard in infant of opioid abuser. Lancet 1989;2(8655):159-60.
Gill 2007
Herschel 2000
Jones 2012
Kattwinkel 2010
  • Kattwinkel J, Perlman JM, Aziz K, Colby C, Fairchild K, Gallagher J, et al. Part 15: neonatal resuscitation: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2010;122(18 Suppl 3):S909-19. [PUBMED: 20956231]
Kumar 2003
  • Kumar M, Paes B. Epidural opioid analgesia and neonatal respiratory depression. Journal of Perinatology 2003;23(5):425-7. [PUBMED: 12847541]
Lefebvre 2008
  • Lefebvre C, Eisinga A, McDonald S, Paul N. Enhancing access to reports of randomized trials published world-wide - the contribution of EMBASE records to the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library. Emerging Themes in Epidemiology 2008;5:13. [DOI: 10.1186/1742-7622-5-13]
Lefebvre 2011
  • Lefebvre C, Manheimer E, Glanville J. Chapter 6: Searching for studies. In: Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from www.cochrane-handbook.org.
Maas 1990
  • Maas U, Kattner E, Weingart-Jesse B, Schafer A, Obladen, M. Infrequent neonatal opiate withdrawal following maternal methadone detoxification during pregnancy. Journal of Perinatal Medicine 1990;18(2):111-8.
Mercer 2007
NICE 2007
  • National Institute for Health and Clinical Excellence. Intrapartum care: care of healthy women and their babies during childbirth. Clinical Guideline 55. London: NICE, 2007.
Niermeyer 2001
Nissen 1995
Perlman 2010
  • Perlman JM, Wyllie J, Kattwinkel J, Atkins DL, Chameides L, Goldsmith JP, et al. Neonatal resuscitation: 2010 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science with Treatment Recommendations. Pediatrics 2010;126(5):e1319-44. [PUBMED: 20956431]
Ransjo-Arvidson 2001
Redshaw 2007
  • Redshaw M, Rowe R, Hockley C, Brocklehurst P. Recorded Delivery: a National Survey of Women's Experience of Maternity Care 2006. Oxford: National Perinatal Epidemiology Unit, University of Oxford, 2007.
Reynolds 2010
  • Reynolds F. The effects of maternal labour analgesia on the fetus. Best Practice & Research. Clinical Obstetrics & Gynaecology 2010;24(3):289-302. [PUBMED: 20005180]
Smotherman 1992
Szeto 1995
  • Szeto HH, Soong Y, Wu DL, Cheng PY. Opioid modulation of fetal glucose homeostasis: role of receptor subtypes. Journal of Pharmacology & Experimental Therapeutics 1995;275(1):334-9.
Ullman 2010