Morphine exposure and neurodevelopmental outcome in extremely preterm infants (2024)

Abstract

Background: Opioids are the most common drugs used to treat pain and stress in infants receiving mechanical ventilation in the NICU. However, controversial data regarding their effects on long-term neurological outcome have been reported.

Methods: We conducted a retrospective study in extremely preterm infants (gestational age (GA) <28 weeks), admitted to the Wilhelmina Children’s Hospital NICU, Utrecht, between 2008 and 2011 with the aim to investigate the association between morphine exposure up to term age and neurodevelopmental outcome at 2 and 5 years. Morphine administration was expressed as cumulative dose (mg/kg) until term-equivalent age (TEA). Neurodevelopmental outcome was assessed at 2 years with the Bayley Scales of Infant and Toddler Development (BSID-III-NL) and at 5 years with the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-III-NL). Multivariable linear regression analysis was used to assess the association between morphine exposure and outcome. Analyses were adjusted for confounders: GA, patent ductus arteriosus, long-term mechanical ventilation (>7 days), postnatal corticosteroids, number of painful procedures, intraventricular hemorrhage (IVH), white matter injury (WMI), cerebellar hemorrhage and maternal education.

Results: 106 extremely preterm infants were included in the study, 64 received morphine (60.4%) at a mean dose 2.03 ± 2.09 mg/kg during their NICU admission. Infants exposed to morphine were more frequently male, had a lower GA and birth weight, longer mechanical ventilation, a higher incidence of IVH, bronchopulmonary dysplasia and WMI at TEA compared to not-exposed infants. Moreover, exposed subjects revealed a significantly worse motor performance at 2 years (p < 0.005), whereas no differences were observed in cognitive and language of Bayley-III-NL and in WPSSI-III-NL score, respectively. At regression analysis morphine exposure did not represent a risk factor for a worse Bayley-III-NL scores at 2 years. Nevertheless, morphine-exposure resulted a risk factor for a lower Fullscale-IQ scores (p = 0.008, B = −9.3, CI −15.6 −3.1) and Performance-IQ scores (p = 0.005, B = −17.5, CI −27.9 −7) at 5 years of age.

Conclusion: Morphine exposure in extremely preterm infants is not associated with neurological outcome at 2 years. However, an association is found with poorer Fullscale -IQ and Performance IQ at 5 years. Future, prospective studies with larger sample sizes are needed to confirm these findings.

Original languageEnglish
Article number478
Pages (from-to)8-8
JournalPediatric Research
Volume90
Issue numberSUPPL 1
DOIs
Publication statusPublished - Oct 2021

Access to Document

Fingerprint

Dive into the research topics of 'Morphine exposure and neurodevelopmental outcome in extremely preterm infants'. Together they form a unique fingerprint.

Cite this

  • APA
  • Author
  • BIBTEX
  • Harvard
  • Standard
  • RIS
  • Vancouver

Luzzati, M., Coviello, C., Swarenburg-Veye, H., Dudink, J., Dani, C., Koopmans, C., deVries, L. S., Groenendaal, F., Benders, M., & Tataranno, M. L. (2021). Morphine exposure and neurodevelopmental outcome in extremely preterm infants. Pediatric Research, 90(SUPPL 1), 8-8. Article 478. https://doi.org/10.1038/s41390-021-01757-3

Luzzati, Michele ; Coviello, Caterina ; Swarenburg-Veye, Henriette et al. / Morphine exposure and neurodevelopmental outcome in extremely preterm infants. In: Pediatric Research. 2021 ; Vol. 90, No. SUPPL 1. pp. 8-8.

@article{9fffcde5d2cb4826a7ad288c724bbedc,

title = "Morphine exposure and neurodevelopmental outcome in extremely preterm infants",

abstract = "Background: Opioids are the most common drugs used to treat pain and stress in infants receiving mechanical ventilation in the NICU. However, controversial data regarding their effects on long-term neurological outcome have been reported.Methods: We conducted a retrospective study in extremely preterm infants (gestational age (GA) <28 weeks), admitted to the Wilhelmina Children{\textquoteright}s Hospital NICU, Utrecht, between 2008 and 2011 with the aim to investigate the association between morphine exposure up to term age and neurodevelopmental outcome at 2 and 5 years. Morphine administration was expressed as cumulative dose (mg/kg) until term-equivalent age (TEA). Neurodevelopmental outcome was assessed at 2 years with the Bayley Scales of Infant and Toddler Development (BSID-III-NL) and at 5 years with the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-III-NL). Multivariable linear regression analysis was used to assess the association between morphine exposure and outcome. Analyses were adjusted for confounders: GA, patent ductus arteriosus, long-term mechanical ventilation (>7 days), postnatal corticosteroids, number of painful procedures, intraventricular hemorrhage (IVH), white matter injury (WMI), cerebellar hemorrhage and maternal education.Results: 106 extremely preterm infants were included in the study, 64 received morphine (60.4%) at a mean dose 2.03 ± 2.09 mg/kg during their NICU admission. Infants exposed to morphine were more frequently male, had a lower GA and birth weight, longer mechanical ventilation, a higher incidence of IVH, bronchopulmonary dysplasia and WMI at TEA compared to not-exposed infants. Moreover, exposed subjects revealed a significantly worse motor performance at 2 years (p < 0.005), whereas no differences were observed in cognitive and language of Bayley-III-NL and in WPSSI-III-NL score, respectively. At regression analysis morphine exposure did not represent a risk factor for a worse Bayley-III-NL scores at 2 years. Nevertheless, morphine-exposure resulted a risk factor for a lower Fullscale-IQ scores (p = 0.008, B = −9.3, CI −15.6 −3.1) and Performance-IQ scores (p = 0.005, B = −17.5, CI −27.9 −7) at 5 years of age.Conclusion: Morphine exposure in extremely preterm infants is not associated with neurological outcome at 2 years. However, an association is found with poorer Fullscale -IQ and Performance IQ at 5 years. Future, prospective studies with larger sample sizes are needed to confirm these findings.",

author = "Michele Luzzati and Caterina Coviello and Henriette Swarenburg-Veye and Jeroen Dudink and Carlo Dani and Corine Koopmans and deVries, {Linda S.} and Floris Groenendaal and Manon Benders and Tataranno, {Maria Luisa}",

year = "2021",

month = oct,

doi = "10.1038/s41390-021-01757-3",

language = "English",

volume = "90",

pages = "8--8",

journal = "Pediatric Research",

issn = "0031-3998",

publisher = "Lippincott Williams and Wilkins",

number = "SUPPL 1",

}

Luzzati, M, Coviello, C, Swarenburg-Veye, H, Dudink, J, Dani, C, Koopmans, C, deVries, LS, Groenendaal, F, Benders, M & Tataranno, ML 2021, 'Morphine exposure and neurodevelopmental outcome in extremely preterm infants', Pediatric Research, vol. 90, no. SUPPL 1, 478, pp. 8-8. https://doi.org/10.1038/s41390-021-01757-3

Morphine exposure and neurodevelopmental outcome in extremely preterm infants. / Luzzati, Michele; Coviello, Caterina; Swarenburg-Veye, Henriette et al.
In: Pediatric Research, Vol. 90, No. SUPPL 1, 478, 10.2021, p. 8-8.

Research output: Contribution to journalMeeting AbstractAcademic

TY - JOUR

T1 - Morphine exposure and neurodevelopmental outcome in extremely preterm infants

AU - Luzzati, Michele

AU - Coviello, Caterina

AU - Swarenburg-Veye, Henriette

AU - Dudink, Jeroen

AU - Dani, Carlo

AU - Koopmans, Corine

AU - deVries, Linda S.

AU - Groenendaal, Floris

AU - Benders, Manon

AU - Tataranno, Maria Luisa

PY - 2021/10

Y1 - 2021/10

N2 - Background: Opioids are the most common drugs used to treat pain and stress in infants receiving mechanical ventilation in the NICU. However, controversial data regarding their effects on long-term neurological outcome have been reported.Methods: We conducted a retrospective study in extremely preterm infants (gestational age (GA) <28 weeks), admitted to the Wilhelmina Children’s Hospital NICU, Utrecht, between 2008 and 2011 with the aim to investigate the association between morphine exposure up to term age and neurodevelopmental outcome at 2 and 5 years. Morphine administration was expressed as cumulative dose (mg/kg) until term-equivalent age (TEA). Neurodevelopmental outcome was assessed at 2 years with the Bayley Scales of Infant and Toddler Development (BSID-III-NL) and at 5 years with the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-III-NL). Multivariable linear regression analysis was used to assess the association between morphine exposure and outcome. Analyses were adjusted for confounders: GA, patent ductus arteriosus, long-term mechanical ventilation (>7 days), postnatal corticosteroids, number of painful procedures, intraventricular hemorrhage (IVH), white matter injury (WMI), cerebellar hemorrhage and maternal education.Results: 106 extremely preterm infants were included in the study, 64 received morphine (60.4%) at a mean dose 2.03 ± 2.09 mg/kg during their NICU admission. Infants exposed to morphine were more frequently male, had a lower GA and birth weight, longer mechanical ventilation, a higher incidence of IVH, bronchopulmonary dysplasia and WMI at TEA compared to not-exposed infants. Moreover, exposed subjects revealed a significantly worse motor performance at 2 years (p < 0.005), whereas no differences were observed in cognitive and language of Bayley-III-NL and in WPSSI-III-NL score, respectively. At regression analysis morphine exposure did not represent a risk factor for a worse Bayley-III-NL scores at 2 years. Nevertheless, morphine-exposure resulted a risk factor for a lower Fullscale-IQ scores (p = 0.008, B = −9.3, CI −15.6 −3.1) and Performance-IQ scores (p = 0.005, B = −17.5, CI −27.9 −7) at 5 years of age.Conclusion: Morphine exposure in extremely preterm infants is not associated with neurological outcome at 2 years. However, an association is found with poorer Fullscale -IQ and Performance IQ at 5 years. Future, prospective studies with larger sample sizes are needed to confirm these findings.

AB - Background: Opioids are the most common drugs used to treat pain and stress in infants receiving mechanical ventilation in the NICU. However, controversial data regarding their effects on long-term neurological outcome have been reported.Methods: We conducted a retrospective study in extremely preterm infants (gestational age (GA) <28 weeks), admitted to the Wilhelmina Children’s Hospital NICU, Utrecht, between 2008 and 2011 with the aim to investigate the association between morphine exposure up to term age and neurodevelopmental outcome at 2 and 5 years. Morphine administration was expressed as cumulative dose (mg/kg) until term-equivalent age (TEA). Neurodevelopmental outcome was assessed at 2 years with the Bayley Scales of Infant and Toddler Development (BSID-III-NL) and at 5 years with the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-III-NL). Multivariable linear regression analysis was used to assess the association between morphine exposure and outcome. Analyses were adjusted for confounders: GA, patent ductus arteriosus, long-term mechanical ventilation (>7 days), postnatal corticosteroids, number of painful procedures, intraventricular hemorrhage (IVH), white matter injury (WMI), cerebellar hemorrhage and maternal education.Results: 106 extremely preterm infants were included in the study, 64 received morphine (60.4%) at a mean dose 2.03 ± 2.09 mg/kg during their NICU admission. Infants exposed to morphine were more frequently male, had a lower GA and birth weight, longer mechanical ventilation, a higher incidence of IVH, bronchopulmonary dysplasia and WMI at TEA compared to not-exposed infants. Moreover, exposed subjects revealed a significantly worse motor performance at 2 years (p < 0.005), whereas no differences were observed in cognitive and language of Bayley-III-NL and in WPSSI-III-NL score, respectively. At regression analysis morphine exposure did not represent a risk factor for a worse Bayley-III-NL scores at 2 years. Nevertheless, morphine-exposure resulted a risk factor for a lower Fullscale-IQ scores (p = 0.008, B = −9.3, CI −15.6 −3.1) and Performance-IQ scores (p = 0.005, B = −17.5, CI −27.9 −7) at 5 years of age.Conclusion: Morphine exposure in extremely preterm infants is not associated with neurological outcome at 2 years. However, an association is found with poorer Fullscale -IQ and Performance IQ at 5 years. Future, prospective studies with larger sample sizes are needed to confirm these findings.

U2 - 10.1038/s41390-021-01757-3

DO - 10.1038/s41390-021-01757-3

M3 - Meeting Abstract

SN - 0031-3998

VL - 90

SP - 8

EP - 8

JO - Pediatric Research

JF - Pediatric Research

IS - SUPPL 1

M1 - 478

ER -

Luzzati M, Coviello C, Swarenburg-Veye H, Dudink J, Dani C, Koopmans C et al. Morphine exposure and neurodevelopmental outcome in extremely preterm infants. Pediatric Research. 2021 Oct;90(SUPPL 1):8-8. 478. doi: 10.1038/s41390-021-01757-3

Morphine exposure and neurodevelopmental outcome in extremely preterm infants (2024)

FAQs

Morphine exposure and neurodevelopmental outcome in extremely preterm infants? ›

Interpretation: Morphine exposure in infants born preterm is associated with poorer Full-Scale IQ and Performance IQ at 5 years. Individualized morphine administration is advised in infants born extremely preterm.

What is the neurodevelopmental impact of neonatal morphine administration? ›

Using amplitude-integrated electroencephalogram, Tataranno et al. demonstrated that early morphine administration caused reduction of spontaneous early brain activity in infants born preterm. In addition, the cumulative morphine dose was negatively correlated with total brain volume14 and cerebellar growth at TEA.

What are the neurodevelopmental outcomes after extreme prematurity? ›

Extremely preterm infants are at risk for neurodevelopmental impairment due to postnatal events such as intraventricular hemorrhage or periventricular leukomalacia,1 sepsis,2 necrotizing enterocolitis,3 bronchopulmonary dysplasia,4 and poor growth. Interventions to improve neurodevelopmental outcomes are needed.

What are the neurodevelopmental outcomes of preterm infants? ›

Preterm birth is a major cause of long-term neurodevelopmental disability1. Preterm infants at highest risk for neurodevelopmental disorders are those born before 28 weeks of gestational age (GA; extremely preterm [EP]), and the prevalence of mild-to-severe neurodevelopmental disorders at 2 years of age is > 50%2.

What are the neurodevelopmental outcomes of late preterm infants literature review? ›

The literature reviewed suggest that most late-preterm infants had typical neurodevelopment comparable with term infants. Some late-preterm infants showed 'catch up' growth with gross motor,14 speech milestones,6 cognitive scores12,13 by early childhood.

What are the side effects of morphine in NICU? ›

It is difficult, therefore, to measure the analgesic effect of morphine in neonates. Suggested adverse effects of morphine are hypotension,3-6 seizures,7 bradycardia, decreased gastrointestinal motility,8 intestinal obstruction, urinary retention, and respiratory depression.

What are the long term effects of neonatal opioid exposure? ›

Across 16 studies, defining POE to include any opioids including methadone and buprenorphine, this analysis found infants and young children with POE had significantly lower cognitive, psychom*otor, and language scores with also more parent-rated internalizing, externalizing, and attention problems.

What are the outcomes of very preterm infants? ›

Despite technological advances and efforts of child health experts during the last generation, the extremely premature infant (less than 28 weeks gestation) and extremely low birth weight infant (<1000 g) remain at high risk for death and disability with 30% to 50% mortality and, in survivors, at least 20% to 50% risk ...

What is neurodevelopmental care of the preterm infant? ›

Developmental care is an approach to individualise care of infants to maximise neurological development and reduce long-term cognitive and behavioural problems. While advances in perinatal care have resulted in decreased mortality rates in preterm neonates, morbidity rates remain significantly high.

What are the late preterm neurodevelopmental outcomes? ›

Outcome studies indicate that they are at increased risk of developmental disability, school failure, behavior problems, social and medical disabilities, and death. Many questions still remain regarding late preterm infant neurodevelopmental outcomes and future research should be done into this topic.

What are the neurodevelopmental problems in infants? ›

Examples of neurodevelopmental disorders in children include attention-deficit/hyperactivity disorder (ADHD), autism, learning disabilities, intellectual disability (also known as mental retardation), conduct disorders, cerebral palsy, and impairments in vision and hearing.

What are the developmental outcomes of preterm birth? ›

Crucial clinical outcomes for preterm infants encompass survival and normal long-term neurodevelopment for independent survival in the future. However, numerous preterm survivors encounter a range of disabilities, including cerebral palsy, sensory deficits, and learning disabilities [8,9].

What neurodevelopmental disorders are preterm? ›

2 Major neurodevelopmental morbidities in surviving preterm infants include cerebral palsy, deafness, blindness and cognitive delay, with scores of <2 standard deviations below the mean for age.

What are the neurodevelopmental implications of neonatal pain and morphine exposure? ›

A significant association between morphine exposure and neurodevelopmental impairment at 5 years was observed. Higher exposure to painful and stressful procedures during the neonatal period was associated with poorer abilities at 5 years of age.

Do late preterm infants have worse 24 month neurodevelopmental outcomes than term infants? ›

Another study of late preterm twins found that they were at increased risk for any neurological or neurodevelopmental delay (hazard ratio, 1.14; 95% CI, 1.07–1.21) compared to term twins.

What was the neurodevelopmental outcome at 2 years for preterm children born at 22 to 34 weeks gestation in France in 2011? ›

In this French population based cohort of neonates born at 22-34 weeks' gestation in 2011, rates of survival without severe or moderate neuromotor and sensory disabilities at 2 years corrected age of 48.5%, 90.0%, and 97.5% were observed for children born at 22-26, 27-31, and 32-34 weeks' gestation, respectively.

What are the developmental effects of neonatal abstinence syndrome? ›

Will my child have long-term symptoms of neonatal abstinence syndrome? Long-term symptoms vary depending on the severity of their diagnosis but neonatal abstinence syndrome (NAS) could affect your child as they get older by causing: Developmental delays and difficulty using their cognitive, social and motor skills.

What effect does morphine have on children? ›

Morphine is very effective for pain management and is used for both adults and children. Children are commonly given morphine to relieve pain, which can help them continue to move about and have a better quality of life. Side effects of morphine include constipation, nausea, drowsiness, slowed breathing or itching.

How does morphine affect cognition? ›

However, research suggests that morphine use can lead to cognitive impairment, which may manifest as difficulties in memory retention and recall. The exact nature and severity of memory impairment vary among individuals and depend on factors such as the dosage and duration of morphine use.

What is the impact of the neonatal intensive care unit on sensory and developmental outcomes in infants born preterm? ›

Preterm infants admitted to the Neonatal Intensive Care Unit are at higher risk of poor neurodevelopmental and sensory outcomes. There is interest in establishing whether elements of the Neonatal Intensive Care Unit sensory environment may influence the sensory and overall development of these infants.

Top Articles
Latest Posts
Article information

Author: Pres. Lawanda Wiegand

Last Updated:

Views: 5287

Rating: 4 / 5 (71 voted)

Reviews: 94% of readers found this page helpful

Author information

Name: Pres. Lawanda Wiegand

Birthday: 1993-01-10

Address: Suite 391 6963 Ullrich Shore, Bellefort, WI 01350-7893

Phone: +6806610432415

Job: Dynamic Manufacturing Assistant

Hobby: amateur radio, Taekwondo, Wood carving, Parkour, Skateboarding, Running, Rafting

Introduction: My name is Pres. Lawanda Wiegand, I am a inquisitive, helpful, glamorous, cheerful, open, clever, innocent person who loves writing and wants to share my knowledge and understanding with you.