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Neurodevelopmental effects of opioids in preterm infants - A systematic review and meta-analysis of randomised and observational studies

Forfatter(e)
Rakshasbhuvankar, M., Rath, C., Agrawal, S., Patole, S.
År
2025
DOI
10.1016/j.earlhumdev.2025.106357
Tidsskrift
Early Human Development
Volum
210
Sider
106357
Kategori(er)
Rus (alkohol, illegale rusmidler) For tidlig fødsel
Tiltakstype(r)
Beroligende medikamenter
Abstract

BACKGROUND

Opioids are commonly used to reduce pain and distress in preterm infants in neonatal intensive care units. However, there is a concern that exposure to opioids may adversely affect their neurodevelopment.

METHODS

We conducted a systematic review of randomised controlled trials (RCTs) and observational studies (OSs) to investigate the effect of opioids on neurodevelopmental outcomes in preterm infants. We followed the Cochrane Collaboration guidelines and those for the synthesis of OSs. Results were pooled when at least two studies reported the outcome. We performed a qualitative synthesis for data not suitable for pooling.

RESULTS

The systematic review included 21 records of 16 studies (13 OSs [n = 2993] and three RCTs [n = 180]). Quantitative analysis was possible for ten studies. The certainty of evidence was 'very low' for all outcomes. The risk of neurodevelopmental impairment, the primary outcome, was not increased in opioid exposed preterm infants (OR: 1.15, 95 % CIs: 0.64, 2.08, 5 OSs, n = 697 and OR: 1.29, 95 % CIs: 0.56, 3.01, 2 RCTs, n = 151). There was no increase in adverse secondary outcomes apart from lower motor scores at 2-3 years of age (MD: -6.19, 85 % CI: -11.26, -1.11, 4 OSs, n = 692) in the opioid group. On qualitative analysis of adjusted data, opioids showed variable effects: ten reports suggested harm, two suggested benefit and two suggested no impact, while the results were inconsistent in three reports.

CONCLUSION

The current evidence for the effect of opioids on neurodevelopmental outcomes of preterm infants is inconclusive and of very low certainty.