Prenatal opioid exposure could have long-term impact on immune system

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Prenatal opioid exposure (POE) could have long-term impacts on the immune system and health of the child, as POE was associated with an increased risk of infection, eczema and dermatitis, and asthma in a study published in JAMA Network Open.¹

Investigators aimed to assess associations between POE and risk of immune-related conditions, which could influence long-term health of the child.¹

The use of exogenous opioids during pregnancy could interfere with fetal development. In the clinical setting, evidence of POE influence on the immune system has been observed in umbilical cord samples. Exposed neonates have had lower levels of neutrophils, inflammatory cytokines, and chemokines compared to neonates without POE.¹

Opioid use disorder is a significant public health concern in the United States, according to the Centers for Disease Control and Prevention, as the number of pregnant women with opioid use disorder at labor and delivery more than quadrupled from 1999 to 2014.²

In the retrospective, population-based cohort study, the investigators used linked administrative health records of all children born in Western Australia between January 1, 2003 and December 31, 2018 (n = 401,462).¹

Outcomes were grouped into 3 types of immune system-related conditions¹:

• Infective diseases (overall and by type-specific conditions)
• Conditions associated with an overactive immune system and inflammation (asthma, eczema, and allergies and anaphylaxis)
• Autoimmune diseases (rheumatoid conditions [juvenile idiopathic arthritis and systemic lupus erythematosus], inflammatory bowel disease, and type 1 diabetes)

The main outcome of the study was hospital admissions and emergency department (ED) presentations during which the child was diagnosed with the above system-related conditions.¹

The study consisted of 401,462 children, including 1656 with POE (0.4%; mean [SD] gestational age, 37.1 weeks; 50.5% females) and 399,806 without POE (99.6%; mean [SD] gestational age, 38.6 [1.9] weeks; 48.7% female).¹

Neonates with POE were more likely to be born preterm, have low birth weight for gestational age, and be co-exposed to cigarette smoke compared to those not exposed. POE was associated with an increased risk of perinatal infection (adjusted odds ratio [AOR], 1.62; 95% CI, 1.38-1.90). Common perinatal infections in neonates with POE include sepsis, urinary tract infection, conjunctivitis, and candidiasis. Compared to non-exposure, neonates with POE were also associated with an increased risk of eczema and dermatitis (AOR, 11.91; 95% CI, 9.84-14.41). Neonatal abstinence syndrome (NAS) was also associated with eczema and dermatitis (AOR, 2.91 [95% CI, 2.36-3.57] and 31.11 [95% CI, 24.64-39.28], respectively), the study authors found.¹

Related to immune sensitivity, POE was associated with an increased risk of hospitalization and/or ED presentations for asthma, compared to those non-exposed (adjusted hazard ratio [AHR], 1.44; 95% CI, 1.16-1.79). In addition, increased risk of hospitalization or ED presentation for eczema and dermatitis was observed in children with POE compared to non-exposed children (AHR, 1.35; 95% CI, 1.05-1.74).¹

For childhood infections, POE was linked to an increased risk of infection overall, and by trimester of exposure, though the increased risk was "modest (8%-18%)," wrote the study authors. Prenatal opioid exposure as a result of opioids used to treat pain was linked to a 45% increase in risk of infection (AHR, 1.44; 95% CI, 1.32-1.58). POE associated with opioids used to treat opioid use disorder was associated with a 4% increase of infection (AHR, 1.04; 95% CI, 0.96-1.12).¹

For autoimmune conditions, POE was not associated with an increased risk, though the authors noted that autoimmune conditions were uncommon in the patient population, as fewer than 5 children in the POE group (<0.3%) were hospitalized or presented to the ED before 5 years of age with an autoimmune disease.¹

Overall, POE was associated with an increased risk of infection, eczema and dermatitis, and asthma in the cohort study. Allergies and anaphylaxis or autoimmune conditions were not. Results demonstrate the importance for further study of opioid-induced immune changes during pregnancy, potential impact on long-term health, and the mechanisms of opioid-induced dysregulation, according to the investigators.¹

References:

1. Kelty E, Rae K, Jantzie LL, Wyrwoll CS, Preen DB. Prenatal Opioid Exposure and Immune-Related Conditions in Children. JAMA Netw Open. 2024;7(1):e2351933. doi:10.1001/jamanetworkopen.2023.51933
2. Substance use during pregnancy. Centers for Disease Control and Prevention. Accessed May 13, 2024. https://www.cdc.gov/reproductivehealth/maternalinfanthealth/substance-abuse/substance-abuse-during-pregnancy.htm#:~:text=Opioid%20use%20disorder%20during%20pregnancy,neonatal%20abstinence%20syndrome%20(NAS).