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Public Health Surveillance of Prenatal Exposure in Mothers and Infants Margaret A. Honein, PhD, MPH, Coleen Boyle, PhD, MS hyg, Robert R. Redfield, MD

The US opioid crisis is the public health emergency of our time and requires urgent public health action to monitor and protect the most vulnerable Americans. We have witnessed a startling toll in 2017 with 70 237 overdose in the , of which two-thirds involved .1 The devastating consequences of this Centers for Disease Control and Prevention, Atlanta, Georgia epidemic for mothers and infants have received less attention. Increases Dr Honein conceptualized and drafted the initial manuscript in opioid use and misuse in pregnancy have paralleled the increases in and reviewed and revised the manuscript; Drs Boyle and the general population; at delivery hospitalization, there were 4 times Redfield critically reviewed the manuscript for important as many women with an in 2014 compared with intellectual content; and all authors approved the final manuscript as submitted and agree to be accountable for 1999.2 One of the most immediate and visible impacts of the opioid all aspects of the work. crisis on infants is the in the newborn period, termed The findings and conclusions in this report are those of the neonatal syndrome (NAS). On the basis of 2014 data, 1 authors and do not necessarily represent the official position newborn was diagnosed with NAS every 15 minutes in the United of the Centers for Disease Control and Prevention. States, totaling about 32 000 infants annually with associated DOI: https://doi.org/10.1542/peds.2018-3801 hospital costs estimated at $563 million.3 Accepted for publication Dec 20, 2018 Address correspondence to Margaret A. Honein, PhD, MPH, INFORMING CLINICAL CARE AND LINKAGE TO SERVICES FOR PREGNANT National Center on Birth Defects and Developmental WOMEN AND INFANTS Disabilities, Centers for Disease Control and Prevention, 4770 Buford Hwy NE, Mailstop S106-3, Atlanta, GA 30341. E-mail: Because prevention and treatment of opioid use disorder in pregnancy [email protected] is important to both maternal and infant health, there is an urgent need PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098- to expand prevention efforts and reduce barriers for - 4275). assisted treatment before, during, and after pregnancy. The stigma of Copyright © 2019 by the American Academy of Pediatrics substance exposure during pregnancy and fears of punitive FINANCIAL DISCLOSURE: The authors have indicated they have consequences can be obstacles to women receiving the treatment and no financial relationships relevant to this article to disclose. care they need, and studies with inadequate control of cofactors can FUNDING: All authors completed this work as full-time exaggerate the specific effects of an individual substance as occurred government employees; no other specific funding support was with prenatal exposure.4 Opioid use disorder during pregnancy provided. is a medical condition that requires care and treatment and can have POTENTIAL CONFLICT OF INTEREST: The authors have adverse consequences for the infant, much like pregestational diabetes, indicated they have no potential conflicts of interest to which increases the risk of birth defects and other adverse pregnancy disclose. outcomes.5 Current recommendations for pregnant women with opioid use disorder are to avoid withdrawal during pregnancy and be To cite: Honein MA, Boyle C, Redfield RR. Public Health provided appropriate opioid agonist treatment.6 Increasing and Surveillance of Prenatal Opioid Exposure in Mothers and Infants. Pediatrics. 2019;143(3):e20183801 targeting prevention efforts and providing appropriate treatment and

Downloaded from www.aappublications.org/news by guest on September 27, 2021 PEDIATRICS Volume 143, number 3, March 2019:e20183801 PEDIATRICS PERSPECTIVES adequate access to care could exposure to these psychoactive affects children with improve both maternal and infant on the developing fetus prenatal exposure to opioids. As was health in the midst of this public and particularly the fetal brain is true in evaluating prenatal cocaine health crisis. unknown; the effects might extend far exposure, full consideration must be beyond diagnoses that are apparent given to the postnatal environment Public health surveillance is needed in the first days and weeks of life. Of of children with prenatal opioid to fill critical knowledge gaps and significant concern is that exposures, which might include social inform clinical guidance for the care polysubstance exposure during and economic complexities that of pregnant women with a treated or pregnancy can include , adversely impact . untreated opioid use disorder and a known human teratogen. The their infants. Updated, evidence- lessons learned from prenatal alcohol The full impact of opioid exposure based clinical guidance might help exposure might be relevant for during pregnancy on the health of our mitigate adverse infant and childhood opioids. Although there is no known nation’s children, including the outcomes by providing treatment safe level of alcohol exposure in impact on birth defects, is not yet that is tailored to the specific pregnancy, sustained and heavy use known. The birth prevalence of prenatal exposures, including of alcohol in pregnancy can cause gastroschisis, a severe defect of the both pharmacologic and fetal alcohol spectrum disorders. abdominal wall, has been increasing nonpharmacologic treatments for Fetal alcohol spectrum disorders can for more than a decade with no clear infants who are exposed. Progress include a range of physical problems explanation. Young maternal age is could be monitored by using (eg, facial features, central nervous the strongest and most consistent a cascade of care model (Table 1) system abnormalities) as well as risk factor for gastroschisis. with metrics obtained from neurologic (eg, executive functioning Prescription opioid exposure in early longitudinal linked public deficits), behavioral (eg, emotional pregnancy has been associated with health surveillance. lability), and learning disabilities, several structural birth defects, which are lifelong and influenced by including gastroschisis, and authors UNDERSTANDING THE FULL IMPACT OF timing and extent of exposure in of 1 recent study suggested a possible PRENATAL OPIOID EXPOSURE ON pregnancy.7 We are concerned that association between preconception INFANTS AND CHILDREN – fetal opioid exposure (and fetal opioid use and .10 12 The Understanding the effects of prenatal polysubstance exposure) might also Centers for Disease Control and opioid and polysubstance exposure result in a range of adverse outcomes Prevention released a report linking requires assessing the multiple forms and that not all will be readily county-level opioid prescribing data and combinations in which exposure apparent at birth. Prenatal alcohol with population-based birth defects can occur. Prenatal opioid exposure exposure has been associated with surveillance data of gastroschisis can include opioid medications for onset of alcohol use disorders when from 20 states that include nearly management or treatment of the prenatally exposed children reach 50% of US births.13 Although the opioid use disorder, misuse of adolescence and young adulthood,8 authors of the report use an prescription or illicit opioid , and it is suggested in animal studies ecological design with appropriate and polysubstance exposure to both that prenatal alcohol can also cautions for not overinterpreting this opioids and other potentially harmful increase the risk of addiction to other association, the prevalence of substances. Although NAS is a well- drugs of abuse.9 Public health gastroschisis was 1.6 times higher recognized consequence of prenatal surveillance could help inform in counties with high opioid opioid exposure, the full impact of whether a similar risk of future prescribing rates (5.1 per 10 000 live births; 95% confidence interval: 4.9–5.3) compared with counties with TABLE 1 Proposed Cascade of Care for Prenatal Opioid Exposure and the Impact on Mothers and low opioid prescribing rates (3.2 per Infants 10 000 live births; 95% confidence Cascade of Care interval: 3.1–3.4). The report sounds Reproductive-aged women with opioid use disorder at risk for pregnancy an early alarm for the need to Pregnant women with opioid use disorder increase our public health Pregnant women with opioid use disorder linked to treatment surveillance on the full range of fetal, Pregnant women with opioid use disorder in treatment throughout pregnancy and postpartum period Women with opioid use disorder in a previous pregnancy who are receiving appropriate treatment and infant, and childhood outcomes care preconceptionally potentially related to these exposures. Infants with prenatal opioid exposure receiving appropriate neonatal assessment and care More research is needed to better Infants with prenatal opioid exposure linked to early intervention services understand the possible role of Infants with prenatal opioid exposure monitored for behavioral and learning disabilities opioid exposure or related substance

Downloaded from www.aappublications.org/news by guest on September 27, 2021 2 HONEIN et al exposure on the occurrence of clinical guidance.15 We are committed Pediatr Adolesc Health Care. 2014;44(4): gastroschisis and other birth defects to building on this model to continue 88–95 and the underlying mechanisms for to address the health threats to and 8. Alati R, Al Mamun A, Williams GM, these potential effects. Areas of the needs of mothers and infants through O’Callaghan M, Najman JM, Bor W. United States with high opioid use a network of public health In utero alcohol exposure and might need to plan for services for surveillance. prediction of alcohol disorders in infants and children impacted with early adulthood: a birth cohort study. a broader range of adverse outcomes, Arch Gen . 2006;63(9): far beyond the impact of NAS. Current ABBREVIATION 1009–1016 surveillance efforts are limited to NAS: neonatal abstinence 9. Wang R, Shen YL, Hausknecht KA, et al. monitoring prenatal opioid use, Prenatal exposure increases syndrome opioid use disorder at delivery, and risk of psychostimulant addiction. diagnosis of NAS; these efforts lack Behav Brain Res. 2019;356:51–61 information on the full range of 10. Rubenstein E, Young JC, Croen LA, et al. outcomes that could be obtained from REFERENCES Brief report: maternal opioid longitudinal mother-infant linked 1. Hedegaard H, Miniño AM, Warner M. prescription from preconception surveillance approaches. Drug Overdose Deaths in the United through pregnancy and the odds of States, 1999–2017. NCHS Data Brief, No disorder and autism 329. Hyattsville, MD: National Center for features in children [published online A PUBLIC HEALTH CALL TO ACTION Health Statistics; 2018 ahead of print August 21, 2018] There is an urgent need to build the [published correction appears in 2. Haight SC, Ko JY, Tong VT, Bohm MK, J Autism Dev Disord. 2018]. 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Downloaded from www.aappublications.org/news by guest on September 27, 2021 PEDIATRICS Volume 143, number 3, March 2019 3 Public Health Surveillance of Prenatal Opioid Exposure in Mothers and Infants Margaret A. Honein, Coleen Boyle and Robert R. Redfield Pediatrics 2019;143; DOI: 10.1542/peds.2018-3801 originally published online January 17, 2019;

Updated Information & including high resolution figures, can be found at: Services http://pediatrics.aappublications.org/content/143/3/e20183801 References This article cites 12 articles, 3 of which you can access for free at: http://pediatrics.aappublications.org/content/143/3/e20183801#BIBL Subspecialty Collections This article, along with others on similar topics, appears in the following collection(s): Fetus/Newborn Infant http://www.aappublications.org/cgi/collection/fetus:newborn_infant_ sub Birth Defects http://www.aappublications.org/cgi/collection/birth_defects_sub Gynecology http://www.aappublications.org/cgi/collection/gynecology_sub Maternal and Fetal Medicine http://www.aappublications.org/cgi/collection/maternal_fetal_medici ne_sub Permissions & Licensing Information about reproducing this article in parts (figures, tables) or in its entirety can be found online at: http://www.aappublications.org/site/misc/Permissions.xhtml Reprints Information about ordering reprints can be found online: http://www.aappublications.org/site/misc/reprints.xhtml

Downloaded from www.aappublications.org/news by guest on September 27, 2021 Public Health Surveillance of Prenatal Opioid Exposure in Mothers and Infants Margaret A. Honein, Coleen Boyle and Robert R. Redfield Pediatrics 2019;143; DOI: 10.1542/peds.2018-3801 originally published online January 17, 2019;

The online version of this article, along with updated information and services, is located on the World Wide Web at: http://pediatrics.aappublications.org/content/143/3/e20183801

Pediatrics is the official journal of the American Academy of Pediatrics. A monthly publication, it has been published continuously since 1948. Pediatrics is owned, published, and trademarked by the American Academy of Pediatrics, 345 Park Avenue, Itasca, Illinois, 60143. Copyright © 2019 by the American Academy of Pediatrics. All rights reserved. Print ISSN: 1073-0397.

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