Developmental Disorders and Medical Complications Among Infants with Subclinical Intrauterine Opioid Exposures

Abstract

The objective was to compare diagnosis rates representing developmental outcomes and medical complications between infants with intrauterine opioid exposures who did not receive pharmacologic treatment for neonatal abstinence syndrome at the time of birth and infants for whom no exposure to substances of abuse were detected. This retrospective, descriptive study included approximately 95% of Hamilton County, Ohio resident births in 2014 and 2015. Universal maternal drug test results, performed at the time of birth, were documented and linked to electronic health records representing pediatric primary and subspecialty follow-up care as well as urgent care, emergency care, and inpatient services provided by Cincinnati Children's Hospital Medical Center through 2017, when all children were at least 24 months old. Diagnosis rates were compared between drug exposure groups using chi-square tests. Among infants born at >34 weeks gestation and without other complex clinical conditions, infants with subclinical opioid exposures (N = 473) were more likely than infants with no drug exposures (N = 14,933) to be diagnosed with behavioral or emotional disorders (3.0% vs 1.1%, P = 0.0008), developmental delay (15.6% vs 7.6%, P < 0.0001), speech disorder (10.1% vs 6.5%, P = 0.001), or strabismus (3.4% vs 1.0%, P < 0.0001), and more likely to be exposed to the hepatitis C virus (6.8% vs 0.1%, P < 0.0001). Increased diagnosis rates among all opioid exposed infants, regardless of withdrawal severity, may warrant the additional allocation of resources for screening and follow-up. Awareness of the increased risk for certain developmental delays and medical conditions is critical to early intervention and treatment supporting improved outcomes.

Longitudinal Outcomes of Children Exposed to Opioids In‐utero: A Systematic Review

“…However, four studies found significantly higher rates of hospitalizations for exposed children through the first 5 years of life (Kelty & Hulse, 2017; Skurtveit et al, 2019; Uebel et al, 2015; Witt et al, 2017). Five studies examined morbidities using ICD codes (Hall, McAllister, & Wexelblatt, 2019; Kelty & Hulse, 2017; Skurtveit et al, 2019; Uebel et al, 2015; Witt et al, 2017), and found significantly higher morbidity among exposed children through the first 2, 3, 5, and 13 years of life, including diagnoses of infections and parasitic diseases, diseases of the digestive system, and diseases of the skin and subcutaneous tissue across all studies. Three studies (Kivistö, Tupola, & Kivitie‐Kallio, 2015; Uebel et al, 2015; Witt et al, 2017) also found significantly higher rates of abuse, neglect, and maltreatment in exposed children compared with unexposed children.…”

“…Four studies (Gill et al, 2003; Hall et al, 2019; Hamilton et al, 2010; Uebel et al, 2015) examined vision in children with in‐utero opioid exposure using ophthalmology assessment and ICD code analysis. All studies reported increased incidence of visual disorders, specifically strabismus and nystagmus in children with in‐utero opioid exposure.…”

Childhood Health and Educational Outcomes After Neonatal Abstinence Syndrome: A Systematic Review and Meta-analysis

“…Of the 5865 titles identified from searches, 581 full texts were assessed for eligibility, 15 eligible studies were identified, and six were amenable to meta-analysis (Figure 2). (11,(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42) This represented 10,907 children with a history of NAS and 1,730,213 unexposed children (Table 5; available at www.jpeds.com). (11,(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42) Multiple publications from the same cohort were clarified, to avoid duplication of cases in the statistical analysis.…”

“…(30-32, 34, 38, 41) Eight studies were deemed to be overall good quality, (11,(32)(33)(34)(35)(36)(37)39) 4 were deemed fair, (29)(30)(31)41) and three poor (Table 6; available at www.jpeds.com). (38,40,42) Included studies were published between 2003-2019 with infants born between 1998 and 2016. (11,(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42) The age range of included children was 0-16 years; ages for specific outcome assessments often were not provided (Table 5).…”

Neonatal abstinence syndrome practice variations across pediatric subspecialty

“…Our survey highlighted several knowledge gaps: (1) the variation across pediatric subspecialty in inpatient and post-discharge referral practices for infants with NAS, (2) the lack of follow-up for infants with NAS-No-Tx compared with NAS-Tx despite a similar risk of long-term complications in both groups [3], and (3) the short duration of follow-up for infants with NAS, raising concerns in light of the widening disparity and challenges for this population over time [4]. The low response rate in our study may reflect unfamiliarity with post-discharge practices among respondents.…”