Effects of opioid use in pregnancy on pediatric development and behaviour in children older than age 2: Systematic review

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WEB EXCLUSIVE R E S E A R C H

Editor’s key points

} The effect of illicit or prescribed opioid use on child development is unclear. Maintenance with opioid agonist therapy is commonly instituted in pregnancy to stabilize drug intake and encourage a healthier pregnancy. While neonatal abstinence syndrome is well documented, opioid effects beyond the newborn period are unknown and might affect the child’s and family’s primary care needs. This systematic review considers the evidence on cognitive and behavioural development in children older than age 2 following in utero opioid exposure.

} The effect of in utero opioid exposure on subsequent pediatric development is unclear and the evidence inconsistent.

Socioenvironmental factors might have more influence than opioid exposure does. Following the systematic review of the evidence, the authors note the importance of monitoring of childhood cognitive, motor, visual, language, and behavioural development. Family physicians should be aware of early intervention pediatric services, as well as allied health professional services, available to these at-risk children.

Effects of opioid use in pregnancy on pediatric

development and behaviour in children older than age 2

Systematic review

Stephanie Welton MSc Brittany Blakelock RN

Sharen Madden MD MSc FCFP Len Kelly MD MClinSci FCFP FRRM

Abstract

Objective To summarize information on the effects of opioid use in pregnancy on subsequent pediatric development and behaviour.

Data sources Searches were performed in EMBASE, MEDLINE, and PsycINFO for peer-reviewed, English articles, including a manual search of their references, that were published between January 1, 2000, and May 1, 2018.

Study selection Of the 543 articles reviewed, 19 relevant articles that focused on developmental effects of opioid exposure in utero were identified. Most of the studies provided level II evidence. One level I meta-analysis and 1 level III expert committee report were included.

Synthesis The literature was divided between documenting some level of impairment or normalization of early development deficits over time. Often no opioid effect was found once researchers controlled for socioenvironmental factors. The degree to which environmental factors, opioid exposure, or both affect pediatric development remains to be determined.

Conclusion The effect of maternal opioid use on pediatric development is unclear and the evidence is inconsistent. However, opioid exposure in pregnancy does define these children as a population at risk. They might experience developmental delays compared with their peers, yet remain within population norms in cognition, fine-motor skills, hand-eye coordination, executive function, and attention and impulsivity levels.

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Résumé

Objectif Résumer l’information concernant les effets de l’utilisation d’opioïdes durant la grossesse sur le développement et les comportements pédiatriques subséquents.

Sources des données Des recherches documentaires ont été effectuées dans EMBASE, MEDLINE et PsycINFO en quête d’articles en anglais révisés par des pairs, de même qu’une recension manuelle dans leurs références, dont les dates de publication se situaient entre le 1^er janvier 2000 et le 1^er mai 2018.

Sélection des études Parmi les 543 articles passés en revue, nous avons cerné 19 articles pertinents qui portaient sur les effets d’une exposition in utero aux opioïdes. La plupart des études ont présenté des données probantes de niveau II. Nous avons aussi inclus 1 méta-analyse de niveau I et 1 rapport d’un comité d’experts de niveau III.

Synthèse Les conclusions des ouvrages scientifiques étaient divisées entre la documentation d’un certain degré de déficience ou la normalisation des déficits du développement précoces avec le temps. Souvent, aucun effet des opioïdes n’a été constaté après rajustements par les chercheurs pour tenir compte des facteurs socio-environnementaux. Il reste à déterminer la mesure dans laquelle les facteurs environnementaux, l’exposition aux opioïdes ou les 2 nuisent au développement pédiatrique.

Conclusion Les effets de l’utilisation d’opioïdes par la mère sur le

développement pédiatrique demeurent incertains, et les données factuelles ne sont pas cohérentes. Par contre, les enfants exposés aux opioïdes pendant la grossesse de leur mère sont effectivement désignés comme une population à risque. Ils pourraient connaître des retards du développement par rapport à leurs pairs, mais demeurent quand même dans la norme populationnelle sur les plans de la cognition, de la motricité fine, de la coordination œil-main, de la fonction exécutive, ainsi que des degrés d’attention et d’impulsivité.

Points de repère du rédacteur

} Les effets de l’utilisation d’opioïdes illicites ou prescrits sur le développement des enfants demeurent nébuleux. Durant la grossesse, il est courant d’amorcer une thérapie de maintien aux agonistes opioïdes pour stabiliser la consommation de drogues et favoriser une grossesse plus saine.

Même si le syndrome d’abstinence néonatale est bien documenté, les effets des opioïdes au-delà de la période néonatale sont inconnus et pourraient avoir une influence sur les besoins en soins primaires de l’enfant et de la famille. Cette revue systématique examine les données probantes concernant le développement cognitif et comportemental chez les enfants de plus de 2 ans à la suite d’une exposition in utero aux opioïdes.

} Les répercussions d’une exposition in utero aux opioïdes sur le développement pédiatrique subséquent ne sont pas bien connues, et les données factuelles manquent de cohérence. Les facteurs socio-environnementaux pourraient avoir une plus grande influence que l’exposition aux opioïdes. À la suite de la revue systématique des données probantes, les auteurs ont fait remarquer l’importance de surveiller le développement cognitif, moteur, visuel, langagier et comportemental durant l’enfance. Les médecins de famille devraient connaître les services pédiatriques d’intervention précoce, de même que les services offerts par d’autres professionnels de la santé qui sont à la disposition de ces enfants à risque.

Effets de l’utilisation d’opioïdes durant la grossesse sur

le développement et les

comportements pédiatriques chez les enfants de plus de 2 ans

Revue systématique

Stephanie Welton MSc Brittany Blakelock RN

Sharen Madden MD MSc FCFP Len Kelly MD MClinSci FCFP FRRM

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RESEARCH

Effects of opioid use in pregnancy on pediatric development and behaviour in children older than age 2

O

pioid use in Canada poses an increasing health risk. Canadian hospitalizations from opioid overdoses increased by 53% between 2007 and 2017.¹ Opioid-related deaths increased in 1 year by 40%

in 2017.²

This opioid crisis extends to pregnancy: 6.7% of Canadian mothers reported using street drugs in the 3 months before conception, with 1% to 4% continu- ing to use throughout the pregnancy.^3,4 Opioid use in pregnancy is more prevalent in certain regions of the country, particularly in the remote First Nations com- munities of northwestern Ontario, where up to 30% of pregnancies include opioid exposure.⁵ Neonates are also affected; the national incidence of neonatal abstinence syndrome (NAS) increased 17% from 4.3 to 5.2 per 1000 live births from 2013 to 2017.⁶

The effect of illicit or prescribed opioid use on child development is unclear. Maintenance with opioid agonist therapy (OAT) is commonly instituted in pregnancy to stabilize drug intake and encourage a healthier pregnancy.^7,8 While NAS is well documented, opioid effects beyond the newborn period are unknown and might affect the child’s and family’s primary care needs. This systematic review considers the evidence on cognitive and behavioural development in children older than age 2 following in utero opioid exposure.

—— Data sources ——

Searches were performed in EMBASE, MEDLINE, and PsycINFO for peer-reviewed, English articles, including a manual search of their references, that were published between January 1, 2000, and May 1, 2018. We chose studies published since 2000 to cover a time frame with more recent types of drug use and pediatric assessment strategies.

Study selection

Search terms combined opioids and opiates and opi- oid and opiate agonists with pregnancy and maternal exposure, child development, and pediatrics, and with a variety of child development characteristics (cognition, memory, learning, language, intellectual, fine-motor skills, and behaviour). We excluded studies if they included subjects who had widespread concurrent alcohol use (if among > 25% of mothers) or polysubstance use (if

> 50% of mothers used a nonopioid substance). Evidence was categorized using the Canadian Task Force on Preventive Health Care guidelines.

—— Synthesis ——

Literature search results

We identified 543 unique papers whose abstracts were screened for children older than age 2 and who

Nineteen research studies^9-27 met these criteria (Figure 1). Twelve of these took place in Scandinavian countries where the primary opioid exposure was heroin or methadone.^9-18,20,24 A set of 6 Norwegian studies ini- tially followed 78 participants over the course of their childhood, some into adulthood.^9-14 Studies were small;

5 of them had fewer than 35 subjects.16,18,20,23,24 One study was population-based with 892 subjects.¹⁵

Seventeen studies were prospective, of which 15 included multivariate analysis.^9-14,16-24 Methodology was mainly case-control studies,^9-14,16-23 accompanied by a case series²⁴ and a 2014 meta-analysis of 4 studies that provided the only level 1 evidence.²⁵ Most evidence was level II. One well-informed expert committee report (level III evidence) was also included.²⁶

The 19 studies reviewed here examine the effect of opioid exposure in pregnancy on pediatric development, including cognition, motor skills, language, and attention and behaviour outcomes (Table 1).^9-27 The studies had limitations and variable findings. The studies are broadly distributed in their scope and findings.

A 2017 American expert consensus workshop by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and several pediatric and obstetric societies concluded that there is a lack of evidence regarding the long-term effects of prenatal opioid exposure. The executive summary noted that exist- ing study results were inconsistent, were of small sample size, were conducted before the current opioid epidemic, and had multiple confounders (level III evidence).²⁶

A 2014 systematic review and meta-analysis identified 4 of 200 studies (3 of which are included in our review^10,22,23; 1 predates our time frame) that quantita- tively reported on neurobehavioural development after maternal opioid use in pregnancy (level I evidence).²⁵

The largest study (N = 892) examined only language and communication skills in 892 Norwegian children exposed to opioids and found no difference from the general pediatric population.¹⁵ The most recent 2018 study (N = 96) found no deleterious effects on physical and mental development by 3 years of age and concluded that opioid use in pregnancy was safe (level II evidence).²⁷

Studies that documented specific developmental delay in exposed children acknowledged the difficulty in distin- guishing specific opioid exposure effects from the influence of growing up in a home environment where addiction was present.16-20,22,23 This socioenvironmental setting might include unstable relationships and bonding, poverty, poor nutrition, and increased stress (level II evidence).

These factors limit the ability to ascribe any documented delays specifically to the effects of opioid exposure. The likelihood of undocumented maternal polysubstance use also compromises accurate ascrib- ing of any developmental concerns specifically to opioid

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Figure 1. Search strategy and results

Papers identified through database searches

N = 543

Additional papers identified through other sources

n = 6

Full-text assessed for eligibility

n = 35 16 articles excluded

• 6 with nonopioid use • 5 with children aged ≤ 6 mo • 2 addressed maternal behaviour • 2 addressed alcohol use • 1 was a project proposal Primary articles

included in the review n = 19 Papers after duplicates removed

n = 547

512 excluded after reading title or abstract

that carry their own development considerations and are not uncommon in opioid-exposed pregnancy.

Findings from the studies

The effect of in utero opioid exposure on subsequent pediatric development is unclear and the evidence inconsistent. While no definitive opioid effect has been established, these children can be considered a population at risk, with fetal exposure to illicit drugs as a marker of socioenvironmental risk (Figure 2).

Cognitive development. Nine studies assessed cognitive development in the preschool years, one of which followed the exposed cohort into adolescence.9,10,13,17,20-23,27

Observed cognitive deficits were more strongly associated with socioenvironmental influences than with drug use. In a series of Norwegian studies of 78 children at 1, 3, 4.5, and 8.5 years, general cognitive development and perceptual abilities were lower than nonexposed children but remained within population norms.^9-11,13 In these studies, cognitive deficits built throughout childhood until 8 years of age, after which deficits remained stable with exposed children at a slight deficit compared with their peers.^11,12 Forty-five of the original 78 children were followed into adulthood; among them, small cognitive deficits persisted at ages 17 to 21, despite having been adopted before the age of 1.¹² The study found that by age 4.5, parental socioeconomic status substantially affected perceptual performance (level II evidence).¹⁰

An environmental effect on cognitive development was also supported by a 2001 study of 33 American

opioid-exposed children; it found that initial differences in mental development were no longer significant once environmental risk was controlled for (level II evidence).²³

Studies from Norway¹⁰ and Sweden²⁴ that considered parents’ socioeconomic levels found memory deficits at ages 4.5 to 6, while 2 other unrelated studies found no deficits when controlling for socioeconomic status¹⁹ or maternal education¹⁷ (level II evidence).

Language. Five studies that measured language development found that children with prenatal opioid exposure experience a delay in language development that improves over time.19,20,22,24,27 Two of these studies controlled for home environment^19,20 and again identified an environmental, with a strongly positive “adoption-related,”

effect on language development (N = 86) (level II evidence).

An international randomized controlled study comparing treatment with methadone versus buprenorphine followed 37 exposed children from birth to age 3 as a subset of the MOTHER (Maternal Opioid Treatment:

Human Experimental Research) study. The study found similar outcomes (level I evidence).²⁷ Effects include early deficits in language, physical growth, cognitive development, sensory processing, and temperament, which normalized by age 3; the authors concluded that prenatal opioid exposure was not deleterious to normal development (level III evidence).²⁷ This contrasts with the findings of 3 other studies that showed ongo- ing impaired language and verbal skills at ages 3 and 6 (level II evidence).^20,22,24

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Table 1. Summary of studies on childhood development following prenatal opioid exposure

STUDY NO. OF

PARTICIPANTS AGE AT

EVALUATION MAIN EXPOSURE FINDINGS LEVEL OF

EVIDENCE Most recent

• Kaltenbach et al,²⁷

2018 96 Birth to 3 y Methadone or

buprenorphine Normal physical, cognitive, language,

sensory, and behavioural development III Population-based

• Skovlund et al,¹⁵ 2017 Cohort of 892 3 y Opioids Trend toward effect of analgesic opioid use during pregnancy on childhood language development and communication

II

Longitudinal case series* 45 to 78 Opioids

(mainly heroin)

• Nygaard et al,¹² 2017 17-21 y Cognitive and fine-motor functions below

those of peers II

• Nygaard et al,¹¹ 2015 1-8.5 y Cognition below peers II

• Walhovd et al,¹⁴ 2007 11.3 y Lower neuroanatomical volumes than

those of peers II

• Slinning, 2004¹³ 1-4.5 y Cognitive and motor deficits compared

with peers; impulsivity and attention- related problems

II

• Moe, 2002¹⁰ 1-4.5 y Development assessments scored below

peers; specific weakness in visual-motor abilities

II

• Moe and Slinning,⁹

2001 1-3 y Development assessments scored

below peers II

Case-control studies

• Konijnenberg and

Melinder,¹⁷ 2015 35 4 y OMT Short-term memory, inhibition, and

executive function below peers II

• Konijnenberg and

Melinder,¹⁶ 2013 15 4 y OMT Difficulty using proactive goal-directed

eye movements II

• Melinder et al,¹⁸ 2013 26 4 y OMT Behavioural and visual-motor deficits

compared with peers II

• Wahlsten and

Sarman,²⁴2013 25 6 y Opioids Problems with motor skills, memory,

hyperactivity, impulsivity, and attention III

• Salo et al,²⁰ 2009 21 Birth to 3 y Buprenorphine Developmental deficits compared

with peers II

• Hunt et al,²² 2008 133 18 mo and 3 y Methadone Delays in mental, motor, and social

development compared with peers II

• Messinger et al,²¹ 2004 50 3 y Opioids No cognitive delay at 3 y II

• Hans and Jeremy,²³

2001 33 Birth to 2 y Opioids (mainly

methadone) Delay in mental development and motor functioning compared with peers II

• Ornoy et al,¹⁹ 2001 65 5 to 12 y Heroin, OMT Higher levels of inattention, hyperactivity, and behaviour problems than peers II Meta-analysis

• Baldacchino et al,²⁵

2014 NA Birth to 12 y Opioids Impairments in cognitive, psychomotor,

and behavioural development compared with peers

I

Expert panel

• Reddy et al,²⁶ 2017 NA From birth throughout childhood

Opioids No consensus on the long-term effects of in utero opioid exposure on

development; evidence is inconsistent

III

NA—not applicable, OMT—opioid maintenance therapy.

*These 6 studies comprise a longitudinal case series following the same cohort from birth to 17-21 years of age.

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Motor and visual skills. Visual and fine-motor skills were often assessed simultaneously. A range of motor skills are variably affected in young children with in utero opioid exposure. Three studies showed an early delay in motor skills in infancy that reached population norms by ages 2 to 3.^9,23,27 Moe and Slinning’s 2001 study found a delay in psychomotor development (general coordination, finer manipulation of the hands, and rec- ognizing objects by sense of touch) in exposed children during their first year of age that had reached the level of their peers by ages 2 to 3 (level II evidence).⁹

Kaltenbach and colleagues’ MOTHER study findings included early delays in motor skills; these delays improved by the age of 3 to being within population norms, but exposed children remained below unexposed peers matched for similar socioeconomic status.^22,27 In contrast, Wahlsten and Sarman’s 2013 study of 25 children’s motor development (coordination, imi- tating actions, and drawing specific objects) remained below normal at ages 5 to 6 (level II evidence).²⁴

Four-year-olds who were exposed to opioid maintenance therapy had specific fine-motor issues in the Konijnenberg et al and the Melinder et al studies.^16,18 In the first study the deficit disappeared when controlling for maternal education,¹⁶ but it remained in the latter study.¹⁸ Both studies found impaired goal-directed eye movement,^16,18 suggesting issues with visually track- ing objects (level II evidence)¹⁸ that contributed to fine- motor control and coordination performance.^16,18 When participants were followed into adulthood, Nygaard and colleagues found fine-motor skills had not caught up to the skills of peers by age 17 to 21 (n = 45) and pro- posed a contributing effect of impaired executive function (level II evidence).¹²

Behaviour and attention deficit hyperactivity disorder (ADHD). A longitudinal Norwegian study included assessments of behaviour and impulsivity; behaviour typically measured in the normal population range but below the level of the study control group. The range of behaviour issues examined included attention, impulsivity deficits, ADHD diagnoses, and executive function.

The first series of measurements at age 2 and 4 indicated increased impulsivity and attention problems in heroin-exposed children.¹³ The authors found attention deficits and hyperactivity presented as early as age 2 and worsened by age 4.5 (n = 42) (level II evidence).¹³ These deficits were associated with perceptual performance and motor abilities. Those children with more behaviour issues also tended to score lower in intel- ligence, memory, and motor tests.¹³ In school-aged Swedish children (aged 5 to 6), teacher questionnaires indicated ADHD in all the subset of 16 children tested, as well as issues with hyperactivity and conduct problems (level II evidence).²⁴ Behavioural deficits were present regardless of whether children had been adopted at an early age.²⁴ In contrast, the participants in these studies performed best in neuropsychological testing if they had been placed in an adoptive family at an early

age^12,24 and were born to a mother who used the low-

est drug dosage.¹² By adulthood, executive function was now within the population norm but still below that of the control group. Again, those who performed the best were born to mothers who used the lowest opioid dosage and were placed with foster or adoptive parents at an early age (level II evidence).¹²

Parental ADHD might contribute to the attention problems in the children,^19,24 and parents with opioid use disorder have a high prevalence of ADHD.¹⁹ In Ornoy and colleagues’ 2001 study, an increased prevalence of ADHD in exposed children was associated with concurrent maternal ADHD (level II evidence).¹⁹ Attention deficit hyperactivity disorder was also implicated among parents and family members in a Swedish study of pregnancies exposed to opiate maintenance treatment with buprenorphine.²⁴ Wahlsten and Sarman studied 25 buprenorphine-OAT pregnancies and performed development and behavioural testing in children aged 5 to 6. Exposed children showed signs of problems with motor skills and hyperactivity, and a high frequency of ADHD was seen in parents and other family members (level II evidence).²⁴

Socioeconomic status also affects behaviour and attention. Kaltenbach and colleagues’ 2018 study found children of low socioeconomic status differed in attention regardless of prenatal opioid exposure.²⁷ Boys seemed to be more adversely affected. Two studies found they performed worse on tasks related to development, cognition, memory, motor skills, and attention (level II and III evidence).^9,10,13,24

Deficits in one area might have broad effects.

Konijnenberg and Melinder suggest that opioid exposure Figure 2. Effects of environmental and opioid exposure on

pediatric development

Opioids used in utero

• Opioid agonist therapy

• Illicit opioids Environmental factors

• Socioeconomic status

• Parental education

• Family employment

• Drug use in the home

• Mother-child bond

Effects on pediatric development

• Cognitive development

• Language development

• Motor and visual skills

• Behaviour and impulsivity

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in pregnancy might change neurotransmitter levels in the developing brain, affecting social, motor, and cognitive development.¹⁶ The affected processes are inter- related. Visual deficits affect cognitive scores, hand-eye coordination, and executive function.^12,16,18 Behaviour issues are coincident with cognition and memory problems.¹³ Attention issues affect cognitive and motor performance, and children with impaired cognition, memory, and motor skills had more difficulties with attention in Slinning’s 2004 Norwegian study (level II evidence).¹³ Environmental factors and development. Numerous studies recognized the role of socioeconomic status, maternal education, employment, drug use in the house- hold, and emotional attachment in pediatric development.16,17,19,20 The bond between mother and child is particularly important for development in drug-exposed children.²⁸ The Salo et al and Kaltenbach et al studies documented low self-esteem and self-assessed maternal ability in mothers with opioid use disorder.^20,27 In Salo and colleagues’ study of 21 buprenorphine-exposed Finnish children, childhood emotional responsiveness at 3 years of age mirrored measured maternal emotional capacity and was lower than controls.²⁰ Mothers included in most studies had lower educational levels than the general population^9,16-19,21 and nearly 50%

unemployment rates (level II evidence).^9,16-18

Some studies controlled for environment effects by comparing exposed children who were adopted or fos- tered to those remaining in the care of their birth mothers.^13,19,20 Norwegian young adults (n = 45) who had been placed in permanent foster or adoptive homes at a young age still experienced slight deficits in cognition, memory, fine-motor skills, and executive function that remained into adulthood.¹² In exposed Finnish (n = 14) and Israeli children (n = 34) aged 5 to 12, adoption mitigated cognitive differences relative to peers (level II evidence).^19,20

Adoptive status had a substantial effect on intellectual performance in the Ornoy et al study of 160 Israeli children exposed to prenatal heroin and methadone replacement therapy.¹⁹ The 34 adopted, exposed children had better intellectual performance than those who remained with birth parents.¹⁹ Ornoy and colleagues commented that Israeli adoptions are often to affluent families,¹⁹ and Nygaard and colleagues similarly noted the socioeconomic status of adoptive Norwegian families was relatively high.¹²

Children in families with opioid exposure experience more upheaval in living circumstances. In Hunt and colleagues’ study of children of 133 mothers using methadone maintenance therapy, 28% had been adopted or placed in foster care at 18 months, rising to 32% by age 3; 10 mothers had died from opioid-related causes as well as 3 fathers.²² The unexposed comparison group

In Moe’s study of exposed children aged 1 to 4.5, both maternal opioid use and socioeconomic status made independent contributions to observed deficits in cognitive development (n = 64).¹⁰ Similarly, in Salo and colleagues’ study, no cognitive deficits were found when subjects were compared with peers of similar socioeconomic status.²⁰ Moe and Slinning also found adoption status to be protective. The 66% (of 78) of adopted, exposed children experienced a “catch up” in cognitive function by age 3 (level II evidence).⁹

The dose of maternal opioid use was not predictive of any developmental delay in 4 separate studies; nor was the presence or severity of NAS at birth (level II evidence).16,17,24,27

Detection and follow-up

These studies note the importance of monitoring of childhood cognitive, motor, visual, language, and behavioural development.^13,17,24 Family physicians should be aware of early intervention pediatric services and allied health professionals’ services available to these at-risk children.

Postpartum support for mothers should include con- sistent follow-up, breastfeeding support, education, and mental health care for parents, as well as social services assessments of care to the newborns and other children.²⁶ Interventions at the environmental level can affect development to some degree; however, there is evidence that the children might not be able to fully

“catch up” to their peers (level II evidence).¹²

The Parent-Child Assistance Program developed in Washington State in 1991 led to the institution of Alberta’s Parent Child Assistance Program in 2006.

These programs provide comprehensive family services to families dealing with addiction. Postpartum case management and home visits for a 3-year period have demonstrated improved health for at-risk mothers and their children, with a decrease in subsequent affected pregnancies and child protective custody referrals.^29,30 Programs targeting caregiver stability and mother-child bonding are difficult to provide.^17,19,20 More focused group and one-on-one psychotherapy and psychosocial support targeting mother-child interaction and prac- tical counseling are even more resource intense but succeed in improving the relationship between child and mother.³¹ Mothers with opioid use disorder have also been shown to benefit from long-term confidential relationships with a small number of clinicians,³² a role suited for the family physician (level II evidence).

Limitations

The main limitation in this review is the heterogeneity of both the study participants and the variety of assessment tools used. It was challenging to isolate relevant

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Conclusion

The effect of maternal opioid use on pediatric development is unclear. However, studies on opioid exposure in pregnancy define these children as a population at risk.

These children might experience developmental delays compared with their peers, yet remain within population norms in cognition, fine-motor skills, hand-eye coordination, executive function, and attention and impulsivity levels. The literature was divided between documenting some level of impairment or normalization of early deficits over time. Often no opioid effect was found once researchers controlled for socioenvironmental factors. The degree to which environmental factors, opioid exposure, or both affect pediatric development remains

to be determined.

Ms Welton and Ms Blakelock are researchers for the Anishinaabe Bimaadiziwin Research Program in Sioux Lookout, Ont. Dr Madden is Associate Professor in the Division of Clinical Sciences at the Northern Ontario School of Medicine in Sioux Lookout. Dr Kelly is a research consultant for the Sioux Lookout Meno Ya Win Health Centre.

Contributors

All authors contributed to the concept and design of the study; data gathering, analysis, and interpretation; and preparing the manuscript for submission.

Competing interests None declared Correspondence

Dr Len Kelly; e-mail [email protected] References

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This article has been peer reviewed.

Cet article a fait l’objet d’une révision par des pairs.

Can Fam Physician 2019;65:e544-51