Naloxone for opioid-exposed newborn infants

Review question

Does naloxone (a drug that counters the negative effects of opioids on breathing) help newborn babies whose mothers have received opioid pain relief during birth?


When a woman receives opioid medicines for pain relief during labour (for example, pethidine, morphine, and similar drugs), the opioid can cross over to the baby inside the womb and then reduce the newborn baby's breathing rate. Naloxone, a drug that counters the effects of opioids, can be given to the newborn baby to try to prevent or treat problems with breathing. This may reduce the chance of the baby needing to go to a neonatal unit for help with breathing, and reduce the need for separating mother and baby (and so help with establishing breastfeeding). Concern exists, however, that naloxone may cause side effects, including possible long-term developmental problems.

Study characteristics

We found nine completed trials that compared giving to newborn babies, whose mothers had received opioids during labour, either naloxone or a placebo ('dummy drug'). These trials were conducted more than 30 years ago and they were generally very small including only about 300 infants in total. Most of the trials did not use reliable methods consistently. Evidence is up-to-date as of February 2018.

Key results

The trials reported the effects of naloxone on the baby's breathing but did not assess the effect on the need for babies to be cared for in a neonatal unit (separated from their mother), whether they needed help with breathing, or on breastfeeding success. None of the trials assessed long-term development. We did not find any trials including babies born to mothers who had used opioids (whether prescribed or non-prescribed) during pregnancy.

Quality of evidence

The available evidence was not sufficient to determine whether giving naloxone to babies whose mothers received opioids during birth was helpful or harmful.

Authors' conclusions: 

The existing evidence from randomised controlled trials is insufficient to determine whether naloxone confers any important benefits to newborn infants with cardiorespiratory or neurological depression that may be due to intrauterine exposure to opioid. Given concerns about the safety of naloxone in this context, it may be appropriate to limit its use to randomised controlled trials that aim to resolve these uncertainties.

Read the full abstract...

Naloxone, a specific opioid antagonist, is available for the treatment of newborn infants with cardiorespiratory or neurological depression that may be due to intrauterine exposure to opioid. It is unclear whether newborn infants may benefit from this therapy and whether naloxone has any harmful effects.


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

Search strategy: 

We searched the following databases in February 2018: the Cochrane Central Register of Controlled Trials (the Cochrane Library 2018, Issue 1), MEDLINE (OvidSP), MEDLINE In process & Other Non-Indexed Citations (OvidSP), Embase (OvidSP), CINAHL (EBSCO), Maternity and Infant Care (OvidSP), and PubMed. We searched for ongoing and completed trials in the WHO International Clinical Trials Registry Platform and the EU Clinical Trials Register. We checked the reference lists of relevant articles to identify further potentially relevant studies.

Selection criteria: 

Randomised controlled trials comparing the administration of naloxone versus placebo, or no drug, or another dose of naloxone to newborn infants with suspected or confirmed in utero exposure to opioid.

Data collection and analysis: 

We extracted data using the standard methods of Cochrane Neonatal with separate evaluation of trial quality and data extraction by two review authors and synthesis of data using risk ratio, risk difference, and mean difference.

Main results: 

We included nine trials, with 316 participants in total, that compared the effects of naloxone versus placebo or no drug in newborn infants exposed to maternal opioid analgesia prior to delivery. None of the included trials investigated infants born to mothers who had used a prescribed or non-prescribed opioid during pregnancy. None of these trials specifically recruited infants with cardiorespiratory or neurological depression. The main outcomes reported were measures of respiratory function in the first six hours after birth. There is some evidence that naloxone increases alveolar ventilation. The trials did not assess the effect on the primary outcomes of this review (admission to a neonatal unit and failure to establish breastfeeding).