Morphine exposure in preterm infants correlates with impaired cerebellar growth and poorer neurodevelopmental outcome

McPherson, Christopher

doi:10.1136/ebmed-2016-110511

Cited by 3 publications

(3 citation statements)

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“…Tolerance has also been described requiring increased doses and problems with withdrawal on discontinuation. [48][49][50] Therefore, it seems logical that a randomised trial of TH in infants with mild HIE is now required. 51 However, consensus must be reached on how we identify these infants.…”

Section: Discussionmentioning

confidence: 99%

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Multichannel EEG abnormalities during the first 6 hours in infants with mild hypoxic–ischaemic encephalopathy

et al. 2021

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Background Infants with mild HIE are at risk of significant disability at follow-up. In the pre-therapeutic hypothermia (TH) era, electroencephalography (EEG) within 6 hours of birth was most predictive of outcome. This study aims to identify and describe features of early EEG and heart rate variability (HRV) (<6 hours of age) in infants with mild HIE compared to healthy term infants. Methods Infants >36 weeks with mild HIE, not undergoing TH, with EEG before 6 hours of age were identified from 4 prospective cohort studies conducted in the Cork University Maternity Services, Ireland (2003–2019). Control infants were taken from a contemporaneous study examining brain activity in healthy term infants. EEGs were qualitatively analysed by two neonatal neurophysiologists and quantitatively assessed using multiple features of amplitude, spectral shape and inter-hemispheric connectivity. Quantitative features of HRV were assessed in both the groups. Results Fifty-eight infants with mild HIE and sixteen healthy term infants were included. Seventy-two percent of infants with mild HIE had at least one abnormal EEG feature on qualitative analysis and quantitative EEG analysis revealed significant differences in spectral features between the two groups. HRV analysis did not differentiate between the groups. Conclusions Qualitative and quantitative analysis of the EEG before 6 hours of age identified abnormal EEG features in mild HIE, which could aid in the objective identification of cases for future TH trials in mild HIE. Impact Infants with mild HIE currently do not meet selection criteria for TH yet may be at risk of significant disability at follow-up. In the pre-TH era, EEG within 6 hours of birth was most predictive of outcome; however, TH has delayed this predictive value. 72% of infants with mild HIE had at least one abnormal EEG feature in the first 6 hours on qualitative assessment. Quantitative EEG analysis revealed significant differences in spectral features between infants with mild HIE and healthy term infants. Quantitative EEG features may aid in the objective identification of cases for future TH trials in mild HIE.

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Section: Discussionmentioning

confidence: 99%

“…Tolerance has also been described requiring increased doses and problems with withdrawal on discontinuation. 48 – 50 …”

Section: Discussionmentioning

confidence: 99%

Multichannel EEG abnormalities during the first 6 hours in infants with mild hypoxic–ischaemic encephalopathy

et al. 2021

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“…Morphine analgesia in preterm neonates was associated with impaired cellular growth in the neonatal period and smaller head circumference/cerebellar volume and poorer neurodevelopmental outcome in early childhood (Ferguson et al., ; Steinhorn et al., ; Kocek et al., ; Zwicker et al., ; McPherson, ). Opioid receptors are expressed early in the developing brain.…”

Section: Assessmentmentioning

confidence: 99%

Update of the Scientific Opinion on opium alkaloids in poppy seeds

Knutsen¹,

Alexander²,

Barregård³

et al. 2018

EFS2

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Poppy seeds are obtained from the opium poppy (Papaver somniferum L.). They are used as food and to produce edible oil. The opium poppy plant contains narcotic alkaloids such as morphine and codeine. Poppy seeds do not contain the opium alkaloids, but can become contaminated with alkaloids as a result of pest damage and during harvesting. The European Commission asked EFSA to provide an update of the Scientific Opinion on opium alkaloids in poppy seeds. The assessment is based on data on morphine, codeine, thebaine, oripavine, noscapine and papaverine in poppy seed samples. The CONTAM Panel confirms the acute reference dose (ARfD) of 10 lg morphine/kg body weight (bw) and concluded that the concentration of codeine in the poppy seed samples should be taken into account by converting codeine to morphine equivalents, using a factor of 0.2. The ARfD is therefore a group ARfD for morphine and codeine, expressed in morphine equivalents. Mean and high levels of dietary exposure to morphine equivalents from poppy seeds considered to have high levels of opium alkaloids (i.e. poppy seeds from varieties primarily grown for pharmaceutical use) exceed the ARfD in most age groups. For poppy seeds considered to have relatively low concentrations of opium alkaloids (i.e. primarily varieties for food use), some exceedance of the ARfD is also seen at high levels of dietary exposure in most surveys. For noscapine and papaverine, the available data do not allow making a hazard characterisation. However, comparison of the dietary exposure to the recommended therapeutical doses does not suggest a health concern for these alkaloids. For thebaine and oripavine, no risk characterisation was done due to insufficient data. However, for thebaine, limited evidence indicates a higher acute lethality than for morphine and the estimated exposure could present a health risk.

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