Childhood neurodevelopment after prescription of maintenance methadone for opioid dependency in pregnancy: a systematic review and meta‐analysis
Aim To systematically review and meta‐analyse studies of neurodevelopmental outcome of children born to mothers prescribed methadone in pregnancy. Method MEDLINE, Embase, and PsycINFO were searched for studies published from 1975 to 2017 reporting neurodevelopmental outcomes in children with prenata...
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| Veröffentlicht in: | Developmental medicine and child neurology 2019-07, Vol.61 (7), p.750-760 |
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| creator | Monnelly, Victoria J Hamilton, Ruth Chappell, Francesca M Mactier, Helen Boardman, James P |
| description | Aim
To systematically review and meta‐analyse studies of neurodevelopmental outcome of children born to mothers prescribed methadone in pregnancy.
Method
MEDLINE, Embase, and PsycINFO were searched for studies published from 1975 to 2017 reporting neurodevelopmental outcomes in children with prenatal methadone exposure.
Results
Forty‐one studies were identified (2283 participants). Eight studies were amenable to meta‐analysis: at 2 years the Mental Development Index weighted mean difference of children with prenatal methadone exposure compared with unexposed infants was −4.3 (95% confidence interval [CI] −7.24 to −1.63), and the Psychomotor Development Index weighted mean difference was −5.42 (95% CI −10.55 to −0.28). Seven studies reported behavioural scores and six found scores to be lower among methadone‐exposed children. Twelve studies reported visual outcomes: nystagmus and strabismus were common; five studies reported visual evoked potentials of which four described abnormalities. Factors that limited the quality of some studies, and introduced risk of bias, included absence of blinding, small sample size, high attrition, uncertainty about polydrug exposure, and lack of comparison group validity.
Interpretation
Children born to mothers prescribed methadone in pregnancy are at risk of neurodevelopmental problems but risk of bias limits inference about harm. Research into management of opioid use disorder in pregnancy should include evaluation of childhood neurodevelopmental outcome.
What this paper adds
Children born to opioid‐dependent mothers prescribed methadone are at risk of neurodevelopmental impairment.
Exposed infants have lower Mental Development Index and Psychomotor Development Index scores than unexposed children.
Atypical visual evoked potentials, strabismus, and nystagmus have increased prevalence.
Estimates of impairment may be biased by intermediate to poor quality evidence.
Resumen
Desarrollo neurológico infantil tras la prescripción de metadona de mantenimiento para el tratamiento de la dependencia de opioides durante el embarazo: revisión sistemática y meta‐análisis
Objetivo
Revisar sistemáticamente y realizar un meta‐análisis de estudios sobre el resultado del desarrollo neurológico de los niños nacidos de madres a quienes se les recetó metadona durante el embarazo.
Metodología
Se realizó una búsqueda en MEDLINE, Embase, y PsycINFO de estudios publicados desde el año 1975 al 2017 que informaran sobre el resultado del desarrollo neu |
| doi_str_mv | 10.1111/dmcn.14117 |
| format | Article |
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To systematically review and meta‐analyse studies of neurodevelopmental outcome of children born to mothers prescribed methadone in pregnancy.
Method
MEDLINE, Embase, and PsycINFO were searched for studies published from 1975 to 2017 reporting neurodevelopmental outcomes in children with prenatal methadone exposure.
Results
Forty‐one studies were identified (2283 participants). Eight studies were amenable to meta‐analysis: at 2 years the Mental Development Index weighted mean difference of children with prenatal methadone exposure compared with unexposed infants was −4.3 (95% confidence interval [CI] −7.24 to −1.63), and the Psychomotor Development Index weighted mean difference was −5.42 (95% CI −10.55 to −0.28). Seven studies reported behavioural scores and six found scores to be lower among methadone‐exposed children. Twelve studies reported visual outcomes: nystagmus and strabismus were common; five studies reported visual evoked potentials of which four described abnormalities. Factors that limited the quality of some studies, and introduced risk of bias, included absence of blinding, small sample size, high attrition, uncertainty about polydrug exposure, and lack of comparison group validity.
Interpretation
Children born to mothers prescribed methadone in pregnancy are at risk of neurodevelopmental problems but risk of bias limits inference about harm. Research into management of opioid use disorder in pregnancy should include evaluation of childhood neurodevelopmental outcome.
What this paper adds
Children born to opioid‐dependent mothers prescribed methadone are at risk of neurodevelopmental impairment.
Exposed infants have lower Mental Development Index and Psychomotor Development Index scores than unexposed children.
Atypical visual evoked potentials, strabismus, and nystagmus have increased prevalence.
Estimates of impairment may be biased by intermediate to poor quality evidence.
Resumen
Desarrollo neurológico infantil tras la prescripción de metadona de mantenimiento para el tratamiento de la dependencia de opioides durante el embarazo: revisión sistemática y meta‐análisis
Objetivo
Revisar sistemáticamente y realizar un meta‐análisis de estudios sobre el resultado del desarrollo neurológico de los niños nacidos de madres a quienes se les recetó metadona durante el embarazo.
Metodología
Se realizó una búsqueda en MEDLINE, Embase, y PsycINFO de estudios publicados desde el año 1975 al 2017 que informaran sobre el resultado del desarrollo neurológico de niños que hubieran tenido exposición prenatal a la metadona.
Resultados
Se identificaron 41 estudios (2283 participantes). Ocho estudios se pudieron someter al meta‐análisis: a los dos años de edad los niños con exposición prenatal a la metadona mostraron una diferencia de medias ponderada de ‐4,3 (95% intervalo de confianza [IC] −7,24 to −1,63) en el Índice de Desarrollo Mental (Mental Development Index) en comparación con los niños no expuestos. En el Índice de Desarrollo Psicomotor (Psychomotor Development Index) la diferencia de medias ponderada fue −5,42 (95% CI −10,55 to −0,28). 7 estudios mostraron las puntuaciones comportamentales y 6 de ellos encontraron puntuaciones más bajas entre los niños expuestos a la metadona. Doce estudios informaron sobre los resultados a nivel visual: el nistagmo y el estrabismo fueron comunes; 5 estudios informaron sobre los potenciales evocados visuales, de los cuáles cuatro describieron anormalidades. Los factores que limitaron la calidad de algunos estudios e introdujeron el riesgo de sesgo, incluyeron la ausencia de cegamiento, el pequeño tamaño de la muestra, el alto desgaste, la incertidumbre acerca de la exposición a varias drogas y la falta de validez del grupo de comparación.
Interpretación
Los niños nacidos de madres a quienes se les recetó metadona durante el embarazo se encuentran en riesgo de sufrir problemas de desarrollo neurológico, pero el riesgo de sesgo limita la inferencia sobre el daño. La investigación sobre el manejo del trastorno por uso de opioides en el embarazo debe incluir la evaluación del resultado del desarrollo neurológico infantil.
Resumo
Neurodesenvolvimento infantil após prescrição de metadona de manutenção para dependência de opióides na gestação: uma revisão sistemática e metanálise
Objetivo
Revisar sistematicamente e metanalisar os estudos com resultados do neurodesenvolvimento de crianças nascidas de mães que tiveram prescrição de metadona na gestação.
Método
MEDLINE, Embase, e PsycINFO foram pesquisadas por estudos publicados de 1974 a 2017 relatando resultados do neurodesenvolvimento em crianças expostas a metadona no período pré‐natal.
Resultados
Quarenta e um estudos foram identificados (2.283 participantes). Oito estudos foram possíveis de incluir na metanálise: aos 2 anos a diferença na média ponderada do Índice de Desenvolvimento Mental de crianças expostas a metadona pré‐natal comparadas com as não expostas foi −4,3 (intervalo de confiança [IC a 95%] −7,24 a −1,63), e a diferença na média ponderada do Índice de Desenvolvimento Psicomotor foi −5,42 (IC 95% −10,55 a −0,28). Sete estudos relataram escores comportamentais e seis encontraram escores menores entre crianças expostas a metadona. Doze estudos relataram resultados visuais: nistagmo e estrabismo foram comuns; cinco estudos reportaram potenciais evocados visuais, dos quais quatro descreveram anormalidades. Fatores que limitaram a qualidade de alguns estudos e introduziram risco de viéis incluíram falta de cegamento, reduzido tamanho amostral, desgaste alto, incerteza sobre exposição a outras drogas, e falta de validade por grupo de comparação.
Interpretação
Crianças nascidas de mães que receberam prescrição de metadona na gestação apresentam risco para problemas neurodesenvolvimentais, mas o risco de viés limita as inferências sobre o dano. Pesquisas sobre o manejo do uso de opióides na gestação devem incluir a avaliação do resultado do neurodesenvolvimento na infância.
What this paper adds
Children born to opioid‐dependent mothers prescribed methadone are at risk of neurodevelopmental impairment.
Exposed infants have lower Mental Development Index and Psychomotor Development Index scores than unexposed children.
Atypical visual evoked potentials, strabismus, and nystagmus have increased prevalence.
Estimates of impairment may be biased by intermediate to poor quality evidence.
Editor's Choice
My Editor's Choice for the July 2019 issue is this systematic review. It highlights neurodevelopmental outcomes of children who had antenatal exposure to methadone given to their mother as maintenance treatment (as well as other, less documented risk factors). The surge in opiod dependence in the USA and other countries, particularly in young adults, raises specific concerns for the children's development.
This article is commented on by Skranes on page 738 of this issue.
This article's has been translated into Spanish and Portuguese.
Follow the links from the to view the translations.
Video Podcast: https://www.youtube.com/watch?v=Ixo12Fg0FJs</description><identifier>ISSN: 0012-1622</identifier><identifier>EISSN: 1469-8749</identifier><identifier>DOI: 10.1111/dmcn.14117</identifier><identifier>PMID: 30511742</identifier><language>eng</language><publisher>England: John Wiley and Sons Inc</publisher><subject>Child ; Child Development - drug effects ; Child, Preschool ; Female ; Humans ; Infant ; Methadone - therapeutic use ; Narcotics - therapeutic use ; Opioid-Related Disorders - complications ; Opioid-Related Disorders - drug therapy ; Opioid-Related Disorders - epidemiology ; Pregnancy ; Pregnancy Complications - drug therapy ; Pregnancy Complications - epidemiology ; Prenatal Exposure Delayed Effects ; Reviews ; Systematic Review</subject><ispartof>Developmental medicine and child neurology, 2019-07, Vol.61 (7), p.750-760</ispartof><rights>2018 The Authors. published by John Wiley & Sons Ltd on behalf of Mac Keith Press</rights><rights>2018 The Authors. Developmental Medicine & Child Neurology published by John Wiley & Sons Ltd on behalf of Mac Keith Press.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4207-92cfb570484e36dfe9a2b215c9d7bdc78d91f92f72aede0006f5da822d6a99cc3</citedby><cites>FETCH-LOGICAL-c4207-92cfb570484e36dfe9a2b215c9d7bdc78d91f92f72aede0006f5da822d6a99cc3</cites><orcidid>0000-0003-3904-8960</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fdmcn.14117$$EPDF$$P50$$Gwiley$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fdmcn.14117$$EHTML$$P50$$Gwiley$$Hfree_for_read</linktohtml><link.rule.ids>230,314,780,784,885,1417,1433,27924,27925,45574,45575,46409,46833</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30511742$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Monnelly, Victoria J</creatorcontrib><creatorcontrib>Hamilton, Ruth</creatorcontrib><creatorcontrib>Chappell, Francesca M</creatorcontrib><creatorcontrib>Mactier, Helen</creatorcontrib><creatorcontrib>Boardman, James P</creatorcontrib><title>Childhood neurodevelopment after prescription of maintenance methadone for opioid dependency in pregnancy: a systematic review and meta‐analysis</title><title>Developmental medicine and child neurology</title><addtitle>Dev Med Child Neurol</addtitle><description>Aim
To systematically review and meta‐analyse studies of neurodevelopmental outcome of children born to mothers prescribed methadone in pregnancy.
Method
MEDLINE, Embase, and PsycINFO were searched for studies published from 1975 to 2017 reporting neurodevelopmental outcomes in children with prenatal methadone exposure.
Results
Forty‐one studies were identified (2283 participants). Eight studies were amenable to meta‐analysis: at 2 years the Mental Development Index weighted mean difference of children with prenatal methadone exposure compared with unexposed infants was −4.3 (95% confidence interval [CI] −7.24 to −1.63), and the Psychomotor Development Index weighted mean difference was −5.42 (95% CI −10.55 to −0.28). Seven studies reported behavioural scores and six found scores to be lower among methadone‐exposed children. Twelve studies reported visual outcomes: nystagmus and strabismus were common; five studies reported visual evoked potentials of which four described abnormalities. Factors that limited the quality of some studies, and introduced risk of bias, included absence of blinding, small sample size, high attrition, uncertainty about polydrug exposure, and lack of comparison group validity.
Interpretation
Children born to mothers prescribed methadone in pregnancy are at risk of neurodevelopmental problems but risk of bias limits inference about harm. Research into management of opioid use disorder in pregnancy should include evaluation of childhood neurodevelopmental outcome.
What this paper adds
Children born to opioid‐dependent mothers prescribed methadone are at risk of neurodevelopmental impairment.
Exposed infants have lower Mental Development Index and Psychomotor Development Index scores than unexposed children.
Atypical visual evoked potentials, strabismus, and nystagmus have increased prevalence.
Estimates of impairment may be biased by intermediate to poor quality evidence.
Resumen
Desarrollo neurológico infantil tras la prescripción de metadona de mantenimiento para el tratamiento de la dependencia de opioides durante el embarazo: revisión sistemática y meta‐análisis
Objetivo
Revisar sistemáticamente y realizar un meta‐análisis de estudios sobre el resultado del desarrollo neurológico de los niños nacidos de madres a quienes se les recetó metadona durante el embarazo.
Metodología
Se realizó una búsqueda en MEDLINE, Embase, y PsycINFO de estudios publicados desde el año 1975 al 2017 que informaran sobre el resultado del desarrollo neurológico de niños que hubieran tenido exposición prenatal a la metadona.
Resultados
Se identificaron 41 estudios (2283 participantes). Ocho estudios se pudieron someter al meta‐análisis: a los dos años de edad los niños con exposición prenatal a la metadona mostraron una diferencia de medias ponderada de ‐4,3 (95% intervalo de confianza [IC] −7,24 to −1,63) en el Índice de Desarrollo Mental (Mental Development Index) en comparación con los niños no expuestos. En el Índice de Desarrollo Psicomotor (Psychomotor Development Index) la diferencia de medias ponderada fue −5,42 (95% CI −10,55 to −0,28). 7 estudios mostraron las puntuaciones comportamentales y 6 de ellos encontraron puntuaciones más bajas entre los niños expuestos a la metadona. Doce estudios informaron sobre los resultados a nivel visual: el nistagmo y el estrabismo fueron comunes; 5 estudios informaron sobre los potenciales evocados visuales, de los cuáles cuatro describieron anormalidades. Los factores que limitaron la calidad de algunos estudios e introdujeron el riesgo de sesgo, incluyeron la ausencia de cegamiento, el pequeño tamaño de la muestra, el alto desgaste, la incertidumbre acerca de la exposición a varias drogas y la falta de validez del grupo de comparación.
Interpretación
Los niños nacidos de madres a quienes se les recetó metadona durante el embarazo se encuentran en riesgo de sufrir problemas de desarrollo neurológico, pero el riesgo de sesgo limita la inferencia sobre el daño. La investigación sobre el manejo del trastorno por uso de opioides en el embarazo debe incluir la evaluación del resultado del desarrollo neurológico infantil.
Resumo
Neurodesenvolvimento infantil após prescrição de metadona de manutenção para dependência de opióides na gestação: uma revisão sistemática e metanálise
Objetivo
Revisar sistematicamente e metanalisar os estudos com resultados do neurodesenvolvimento de crianças nascidas de mães que tiveram prescrição de metadona na gestação.
Método
MEDLINE, Embase, e PsycINFO foram pesquisadas por estudos publicados de 1974 a 2017 relatando resultados do neurodesenvolvimento em crianças expostas a metadona no período pré‐natal.
Resultados
Quarenta e um estudos foram identificados (2.283 participantes). Oito estudos foram possíveis de incluir na metanálise: aos 2 anos a diferença na média ponderada do Índice de Desenvolvimento Mental de crianças expostas a metadona pré‐natal comparadas com as não expostas foi −4,3 (intervalo de confiança [IC a 95%] −7,24 a −1,63), e a diferença na média ponderada do Índice de Desenvolvimento Psicomotor foi −5,42 (IC 95% −10,55 a −0,28). Sete estudos relataram escores comportamentais e seis encontraram escores menores entre crianças expostas a metadona. Doze estudos relataram resultados visuais: nistagmo e estrabismo foram comuns; cinco estudos reportaram potenciais evocados visuais, dos quais quatro descreveram anormalidades. Fatores que limitaram a qualidade de alguns estudos e introduziram risco de viéis incluíram falta de cegamento, reduzido tamanho amostral, desgaste alto, incerteza sobre exposição a outras drogas, e falta de validade por grupo de comparação.
Interpretação
Crianças nascidas de mães que receberam prescrição de metadona na gestação apresentam risco para problemas neurodesenvolvimentais, mas o risco de viés limita as inferências sobre o dano. Pesquisas sobre o manejo do uso de opióides na gestação devem incluir a avaliação do resultado do neurodesenvolvimento na infância.
What this paper adds
Children born to opioid‐dependent mothers prescribed methadone are at risk of neurodevelopmental impairment.
Exposed infants have lower Mental Development Index and Psychomotor Development Index scores than unexposed children.
Atypical visual evoked potentials, strabismus, and nystagmus have increased prevalence.
Estimates of impairment may be biased by intermediate to poor quality evidence.
Editor's Choice
My Editor's Choice for the July 2019 issue is this systematic review. It highlights neurodevelopmental outcomes of children who had antenatal exposure to methadone given to their mother as maintenance treatment (as well as other, less documented risk factors). The surge in opiod dependence in the USA and other countries, particularly in young adults, raises specific concerns for the children's development.
This article is commented on by Skranes on page 738 of this issue.
This article's has been translated into Spanish and Portuguese.
Follow the links from the to view the translations.
Video Podcast: https://www.youtube.com/watch?v=Ixo12Fg0FJs</description><subject>Child</subject><subject>Child Development - drug effects</subject><subject>Child, Preschool</subject><subject>Female</subject><subject>Humans</subject><subject>Infant</subject><subject>Methadone - therapeutic use</subject><subject>Narcotics - therapeutic use</subject><subject>Opioid-Related Disorders - complications</subject><subject>Opioid-Related Disorders - drug therapy</subject><subject>Opioid-Related Disorders - epidemiology</subject><subject>Pregnancy</subject><subject>Pregnancy Complications - drug therapy</subject><subject>Pregnancy Complications - epidemiology</subject><subject>Prenatal Exposure Delayed Effects</subject><subject>Reviews</subject><subject>Systematic Review</subject><issn>0012-1622</issn><issn>1469-8749</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>WIN</sourceid><sourceid>EIF</sourceid><recordid>eNp9kc9uFDEMhyMEotvChQdAOSNNSbLzLxyQqi0FpAIXOEfe2OkGzSSjZHarufEIiEfkSZhhoaIXfPHBnz_L-jH2TIpzOddL7G04l6WUzQO2kmWti7Yp9UO2EkKqQtZKnbDTnL8KIdZ1VT5mJ2tRzXSpVuzHZuc73MWIPNA-RaQDdXHoKYwc3EiJD4myTX4YfQw8Ot6DDyMFCJZ4T-MOMAbiLiYeBx89cqSBAlKwE_dhWb9Z4OkVB56nPFIPo7c80cHTLYeAiwV-fvsOAbop-_yEPXLQZXr6p5-xL1dvPm_eFdef3r7fXFwXtlSiKbSybls1omxLWtfoSIPaKllZjc0WbdOilk4r1yggpPn32lUIrVJYg9bWrs_Y66N32G97Qju_nKAzQ_I9pMlE8Ob-JPiduYkHU9eyaUU7C14cBTbFnBO5u10pzJKMWZIxv5OZ4ef_XrtD_0YxA_II3PqOpv-ozOWHzcej9BdH36CX</recordid><startdate>201907</startdate><enddate>201907</enddate><creator>Monnelly, Victoria J</creator><creator>Hamilton, Ruth</creator><creator>Chappell, Francesca M</creator><creator>Mactier, Helen</creator><creator>Boardman, James P</creator><general>John Wiley and Sons Inc</general><scope>24P</scope><scope>WIN</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-3904-8960</orcidid></search><sort><creationdate>201907</creationdate><title>Childhood neurodevelopment after prescription of maintenance methadone for opioid dependency in pregnancy: a systematic review and meta‐analysis</title><author>Monnelly, Victoria J ; Hamilton, Ruth ; Chappell, Francesca M ; Mactier, Helen ; Boardman, James P</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4207-92cfb570484e36dfe9a2b215c9d7bdc78d91f92f72aede0006f5da822d6a99cc3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Child</topic><topic>Child Development - drug effects</topic><topic>Child, Preschool</topic><topic>Female</topic><topic>Humans</topic><topic>Infant</topic><topic>Methadone - therapeutic use</topic><topic>Narcotics - therapeutic use</topic><topic>Opioid-Related Disorders - complications</topic><topic>Opioid-Related Disorders - drug therapy</topic><topic>Opioid-Related Disorders - epidemiology</topic><topic>Pregnancy</topic><topic>Pregnancy Complications - drug therapy</topic><topic>Pregnancy Complications - epidemiology</topic><topic>Prenatal Exposure Delayed Effects</topic><topic>Reviews</topic><topic>Systematic Review</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Monnelly, Victoria J</creatorcontrib><creatorcontrib>Hamilton, Ruth</creatorcontrib><creatorcontrib>Chappell, Francesca M</creatorcontrib><creatorcontrib>Mactier, Helen</creatorcontrib><creatorcontrib>Boardman, James P</creatorcontrib><collection>Wiley Online Library (Open Access Collection)</collection><collection>Wiley Online Library (Open Access Collection)</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Developmental medicine and child neurology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Monnelly, Victoria J</au><au>Hamilton, Ruth</au><au>Chappell, Francesca M</au><au>Mactier, Helen</au><au>Boardman, James P</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Childhood neurodevelopment after prescription of maintenance methadone for opioid dependency in pregnancy: a systematic review and meta‐analysis</atitle><jtitle>Developmental medicine and child neurology</jtitle><addtitle>Dev Med Child Neurol</addtitle><date>2019-07</date><risdate>2019</risdate><volume>61</volume><issue>7</issue><spage>750</spage><epage>760</epage><pages>750-760</pages><issn>0012-1622</issn><eissn>1469-8749</eissn><abstract>Aim
To systematically review and meta‐analyse studies of neurodevelopmental outcome of children born to mothers prescribed methadone in pregnancy.
Method
MEDLINE, Embase, and PsycINFO were searched for studies published from 1975 to 2017 reporting neurodevelopmental outcomes in children with prenatal methadone exposure.
Results
Forty‐one studies were identified (2283 participants). Eight studies were amenable to meta‐analysis: at 2 years the Mental Development Index weighted mean difference of children with prenatal methadone exposure compared with unexposed infants was −4.3 (95% confidence interval [CI] −7.24 to −1.63), and the Psychomotor Development Index weighted mean difference was −5.42 (95% CI −10.55 to −0.28). Seven studies reported behavioural scores and six found scores to be lower among methadone‐exposed children. Twelve studies reported visual outcomes: nystagmus and strabismus were common; five studies reported visual evoked potentials of which four described abnormalities. Factors that limited the quality of some studies, and introduced risk of bias, included absence of blinding, small sample size, high attrition, uncertainty about polydrug exposure, and lack of comparison group validity.
Interpretation
Children born to mothers prescribed methadone in pregnancy are at risk of neurodevelopmental problems but risk of bias limits inference about harm. Research into management of opioid use disorder in pregnancy should include evaluation of childhood neurodevelopmental outcome.
What this paper adds
Children born to opioid‐dependent mothers prescribed methadone are at risk of neurodevelopmental impairment.
Exposed infants have lower Mental Development Index and Psychomotor Development Index scores than unexposed children.
Atypical visual evoked potentials, strabismus, and nystagmus have increased prevalence.
Estimates of impairment may be biased by intermediate to poor quality evidence.
Resumen
Desarrollo neurológico infantil tras la prescripción de metadona de mantenimiento para el tratamiento de la dependencia de opioides durante el embarazo: revisión sistemática y meta‐análisis
Objetivo
Revisar sistemáticamente y realizar un meta‐análisis de estudios sobre el resultado del desarrollo neurológico de los niños nacidos de madres a quienes se les recetó metadona durante el embarazo.
Metodología
Se realizó una búsqueda en MEDLINE, Embase, y PsycINFO de estudios publicados desde el año 1975 al 2017 que informaran sobre el resultado del desarrollo neurológico de niños que hubieran tenido exposición prenatal a la metadona.
Resultados
Se identificaron 41 estudios (2283 participantes). Ocho estudios se pudieron someter al meta‐análisis: a los dos años de edad los niños con exposición prenatal a la metadona mostraron una diferencia de medias ponderada de ‐4,3 (95% intervalo de confianza [IC] −7,24 to −1,63) en el Índice de Desarrollo Mental (Mental Development Index) en comparación con los niños no expuestos. En el Índice de Desarrollo Psicomotor (Psychomotor Development Index) la diferencia de medias ponderada fue −5,42 (95% CI −10,55 to −0,28). 7 estudios mostraron las puntuaciones comportamentales y 6 de ellos encontraron puntuaciones más bajas entre los niños expuestos a la metadona. Doce estudios informaron sobre los resultados a nivel visual: el nistagmo y el estrabismo fueron comunes; 5 estudios informaron sobre los potenciales evocados visuales, de los cuáles cuatro describieron anormalidades. Los factores que limitaron la calidad de algunos estudios e introdujeron el riesgo de sesgo, incluyeron la ausencia de cegamiento, el pequeño tamaño de la muestra, el alto desgaste, la incertidumbre acerca de la exposición a varias drogas y la falta de validez del grupo de comparación.
Interpretación
Los niños nacidos de madres a quienes se les recetó metadona durante el embarazo se encuentran en riesgo de sufrir problemas de desarrollo neurológico, pero el riesgo de sesgo limita la inferencia sobre el daño. La investigación sobre el manejo del trastorno por uso de opioides en el embarazo debe incluir la evaluación del resultado del desarrollo neurológico infantil.
Resumo
Neurodesenvolvimento infantil após prescrição de metadona de manutenção para dependência de opióides na gestação: uma revisão sistemática e metanálise
Objetivo
Revisar sistematicamente e metanalisar os estudos com resultados do neurodesenvolvimento de crianças nascidas de mães que tiveram prescrição de metadona na gestação.
Método
MEDLINE, Embase, e PsycINFO foram pesquisadas por estudos publicados de 1974 a 2017 relatando resultados do neurodesenvolvimento em crianças expostas a metadona no período pré‐natal.
Resultados
Quarenta e um estudos foram identificados (2.283 participantes). Oito estudos foram possíveis de incluir na metanálise: aos 2 anos a diferença na média ponderada do Índice de Desenvolvimento Mental de crianças expostas a metadona pré‐natal comparadas com as não expostas foi −4,3 (intervalo de confiança [IC a 95%] −7,24 a −1,63), e a diferença na média ponderada do Índice de Desenvolvimento Psicomotor foi −5,42 (IC 95% −10,55 a −0,28). Sete estudos relataram escores comportamentais e seis encontraram escores menores entre crianças expostas a metadona. Doze estudos relataram resultados visuais: nistagmo e estrabismo foram comuns; cinco estudos reportaram potenciais evocados visuais, dos quais quatro descreveram anormalidades. Fatores que limitaram a qualidade de alguns estudos e introduziram risco de viéis incluíram falta de cegamento, reduzido tamanho amostral, desgaste alto, incerteza sobre exposição a outras drogas, e falta de validade por grupo de comparação.
Interpretação
Crianças nascidas de mães que receberam prescrição de metadona na gestação apresentam risco para problemas neurodesenvolvimentais, mas o risco de viés limita as inferências sobre o dano. Pesquisas sobre o manejo do uso de opióides na gestação devem incluir a avaliação do resultado do neurodesenvolvimento na infância.
What this paper adds
Children born to opioid‐dependent mothers prescribed methadone are at risk of neurodevelopmental impairment.
Exposed infants have lower Mental Development Index and Psychomotor Development Index scores than unexposed children.
Atypical visual evoked potentials, strabismus, and nystagmus have increased prevalence.
Estimates of impairment may be biased by intermediate to poor quality evidence.
Editor's Choice
My Editor's Choice for the July 2019 issue is this systematic review. It highlights neurodevelopmental outcomes of children who had antenatal exposure to methadone given to their mother as maintenance treatment (as well as other, less documented risk factors). The surge in opiod dependence in the USA and other countries, particularly in young adults, raises specific concerns for the children's development.
This article is commented on by Skranes on page 738 of this issue.
This article's has been translated into Spanish and Portuguese.
Follow the links from the to view the translations.
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| fulltext | fulltext |
| identifier | ISSN: 0012-1622 |
| ispartof | Developmental medicine and child neurology, 2019-07, Vol.61 (7), p.750-760 |
| issn | 0012-1622 1469-8749 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6617808 |
| source | MEDLINE; Access via Wiley Online Library; Wiley Online Library (Open Access Collection) |
| subjects | Child Child Development - drug effects Child, Preschool Female Humans Infant Methadone - therapeutic use Narcotics - therapeutic use Opioid-Related Disorders - complications Opioid-Related Disorders - drug therapy Opioid-Related Disorders - epidemiology Pregnancy Pregnancy Complications - drug therapy Pregnancy Complications - epidemiology Prenatal Exposure Delayed Effects Reviews Systematic Review |
| title | Childhood neurodevelopment after prescription of maintenance methadone for opioid dependency in pregnancy: a systematic review and meta‐analysis |
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