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Invited Commentary
Pediatrics
June 28, 2019

Maternal and Child Health After Prenatal Opioid Exposure

Author Affiliations
  • 1Department of Surgery, Queen’s University, Kingston, Ontario, Canada
JAMA Netw Open. 2019;2(6):e196428. doi:10.1001/jamanetworkopen.2019.6428

The study of mother-infant pairs from the Boston Birth Cohort by Azuine et al1 adds to the growing body of evidence that children prenatally exposed to opioids or with a history of neonatal abstinence syndrome (NAS) may have poorer developmental outcomes than children with no exposure to opioids. The Boston Birth Cohort included 8509 mother-infant pairs enrolled at delivery starting in 1998. The 454 infants (5.3%) with NAS or exposed to opioids had 2-fold increased risk of preterm birth, low birth weight, and small-for-gestational-age (SGA) birth compared with infants with no NAS and not exposed to opioids.1 Longer-term outcomes were observed in 3153 children (37.1%) who continued to be cared for at Boston Medical Center. Children with opioid exposure or NAS, compared with children with no opioid exposure, had greater risks of conduct disorder/emotional disturbance (odds ratio, 2.13; 95% CI, 1.20-3.77) and physiological development below expected normal levels (odds ratio, 1.80; 95% CI, 1.17-2.79) before the age of 6 years.1

Although not all studies have observed significant impairments in neurobehavioral outcomes among children prenatally exposed to opioids compared with peers with no exposure, there appears to be a trend toward poorer outcomes.2 A 2010 study from the United States3 suggested visual impairments, including nystagmus, strabismus, reduced visual acuity, delayed visual maturation, impaired voluntary eye movements, and absent binocular vision, in children prenatally exposed to opioids vs children with no exposure. There are less data on the association of NAS with longer-term child outcomes. In an Australian study of children matched on gestational age at birth, socioeconomic status, and sex,4 those with a history of NAS scored significantly lower on curriculum-based testing than those without a history of NAS. In another population-based study of children 13 years and younger in Australia,5 children with a history of NAS were more likely to be hospitalized for assault, maltreatment, poisoning, mental or behavioral disorders, and visual disorders than children without a history of NAS.

The causal mechanisms of opioids and of NAS on these adverse long-term outcomes in childhood has not been delineated. In the study by Azuine et al,1 the exposed group combined children with documented prenatal opioid exposure and children with a history of NAS (ie, those without documentation of prenatal opioid exposure who were presumably exposed to opioids). Evidence of the direct effect of opioids was not estimated. Neonatal abstinence syndrome would be part of the total effect of prenatal opioid exposure on longer-term child outcomes. If there is interest in the direct effect of opioids on child development (ie, a causal effect that is not mediated by other variables), then NAS should be taken into account along with preterm birth, low birth weight, and SGA birth. In contrast, preterm birth, low birth weight, and SGA birth are antecedent to NAS and therefore are potential confounders of the association of NAS with childhood health outcomes. Further, the home environment during childhood may modify the effect of prenatal opioid exposure and of NAS on longer-term outcomes. It has been shown that the harmful effect of in utero heroin exposure on the developmental outcomes of children is reduced in the presence of healthy home environments.6 While there may be scientific interest in further delineating the effects of opioids and NAS on child health—and such knowledge may benefit some mothers—it can perhaps be argued that the more pertinent research concerns interventions to improve health outcomes in this rapidly growing population of children, regardless of the causal mechanism of impairment.

Among the 8509 mothers in the Boston Birth Cohort, those who used opioids were more likely to be non-Hispanic white, to be unmarried, to be multiparous, and to have a history of polysubstance use. These characteristics were similar to those previously reported in a cohort of pregnant women with opioid dependence or opioid use disorder recruited from the Project Recovery, Empowerment, Social Services, Prenatal Care, Education, Community, and Treatment (RESPECT) clinic, a high-risk obstetric and addiction recovery clinic of Boston Medical Center.7 Of the 113 patients enrolled in the RESPECT cohort from 2014 to 2016, 58 (51.3%) had been incarcerated, 17 (15.0%) generally had unstable housing, and 80 (70.8%) had hepatitis C infection. Histories of sexual abuse (64 women [56.6%]) and physical abuse (74 women [65.5%]) were prevalent.7 The complexity of the issues faced by women with opioid use disorder cannot be addressed in pregnancy alone. Pregnancy and continuing postpartum interventions for employment, financial security, and safe housing should be considered. Incorporating the experiences, perceptions, and needs of these women and children in developing interventions will facilitate effective, relevant, and feasible programs. Supportive communities of women and children may be an important part of maintaining healthy mothers and children in the long term.8

The risks of poor pregnancy and child outcomes in cases of maternal opioid exposure are not because of prenatal opioid exposure alone; ongoing difficult social and environmental circumstances have an important role. While results from the study by Azuine et al1 may be based on data from a select sample of children from the Boston Birth Cohort who continued to be cared for at Boston Medical Center, the findings of poor outcomes importantly adds to available evidence. Rather than additional studies to delineate etiology, future research should focus on innovative interventions for the long-term health of these women and their children.

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Article Information

Published: June 28, 2019. doi:10.1001/jamanetworkopen.2019.6428

Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2019 Brogly S. JAMA Network Open.

Corresponding Author: Susan Brogly, PhD, MSc, Department of Surgery, Queen’s University, Kingston Health Science Center, Victory 3, 76 Stuart St, Kingston, ON K7L 2V7, Canada (susan.brogly@queensu.ca).

Conflict of Interest Disclosures: Dr Brogly reported receiving grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development outside the submitted work.

References
1.
Azuine  RE, Ji  Y, Chang  H-Y,  et al.  Prenatal risk factors and perinatal and postnatal outcomes associated with maternal opioid exposure in an urban, low-income, multiethnic US population.  JAMA Netw Open. 2019;2(6):e196405. doi:10.1001/jamanetworkopen.2019.6405Google Scholar
2.
Baldacchino  A, Arbuckle  K, Petrie  DJ, McCowan  C.  Neurobehavioral consequences of chronic intrauterine opioid exposure in infants and preschool children: a systematic review and meta-analysis.  BMC Psychiatry. 2014;14:104. doi:10.1186/1471-244X-14-104PubMedGoogle ScholarCrossref
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Hamilton  R, McGlone  L, MacKinnon  JR, Russell  HC, Bradnam  MS, Mactier  H.  Ophthalmic, clinical and visual electrophysiological findings in children born to mothers prescribed substitute methadone in pregnancy.  Br J Ophthalmol. 2010;94(6):696-700. doi:10.1136/bjo.2009.169284PubMedGoogle ScholarCrossref
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Oei  JL, Melhuish  E, Uebel  H,  et al.  Neonatal abstinence syndrome and high school performance.  Pediatrics. 2017;139(2):2016-2651. doi:10.1542/peds.2016-2651PubMedGoogle ScholarCrossref
5.
Uebel  H, Wright  IM, Burns  L,  et al.  Reasons for rehospitalization in children who had neonatal abstinence syndrome.  Pediatrics. 2015;136(4):e811-e820. doi:10.1542/peds.2014-2767PubMedGoogle ScholarCrossref
6.
Ornoy  A, Michailevskaya  V, Lukashov  I, Bar-Hamburger  R, Harel  S.  The developmental outcome of children born to heroin-dependent mothers, raised at home or adopted.  Child Abuse Negl. 1996;20(5):385-396. doi:10.1016/0145-2134(96)00014-2PubMedGoogle ScholarCrossref
7.
Brogly  SB, Saia  KE, Werler  MM, Regan  E, Hernández-Díaz  S.  Prenatal treatment and outcomes of women with opioid use disorder.  Obstet Gynecol. 2018;132(4):916-922. doi:10.1097/AOG.0000000000002881PubMedGoogle ScholarCrossref
8.
Kuo  C, Schonbrun  YC, Zlotnick  C,  et al.  A qualitative study of treatment needs among pregnant and postpartum women with substance use and depression.  Subst Use Misuse. 2013;48(14):1498-1508. doi:10.3109/10826084.2013.800116PubMedGoogle ScholarCrossref
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