Opioid use during pregnancy for pain or opioid use disorder (OUD) was associated with an increased risk for hospitalizations and emergency department (ED) visits for immune-related conditions in exposed offspring, a retrospective population-based cohort study showed.
Of more than 400,000 kids born in Western Australia, those with perinatal opioid exposure had an increased risk of perinatal infection (adjusted OR 1.62, 95% CI 1.38-1.90) and eczema and dermatitis (aOR 11.91, 95% CI 9.84-14.41) compared with non-exposed children, reported Erin Kelty, PhD, of the University of Western Australia, and co-authors.
Prenatal opioid exposure was also linked to an increased risk of childhood asthma (aHR 1.44, 95% CI 1.16-1.79), but not allergies and anaphylaxis, according to findings in .
The authors also observed an association between neonatal abstinence syndrome (NAS) and perinatal infection (aOR 2.91, 95% CI 2.36-3.57) and eczema and dermatitis (aOR 31.11, 95% CI 24.64-39.28). Having both NAS and prenatal opioid exposure led to the risk increasing "additively," said Kelty.
Of note, the association between prenatal opioid exposure and the elevated risk of eczema and dermatitis was seen only in children whose exposure resulted from opioids used to treat OUD, such as buprenorphine or methadone (aHR 1.47, 95% CI 1.08-1.99), rather than pain.
While prenatal opioid exposure from opioids used to treat pain was associated with an increased risk of infection (aHR 1.44, 95% CI 1.32-1.58), exposure from OUD treatment was not.
Kelty and team highlighted studies in mouse models suggesting that prenatal opioid exposure during fetal immune development may lead to "immune priming," in which the immune system overreacts to subsequent triggers.
Curiously, autoimmune conditions, such as rheumatoid conditions (juvenile idiopathic arthritis and systemic lupus erythematosus), inflammatory bowel disease, and type 1 diabetes, were "rare and were not observed to be associated with" prenatal opioid exposure, the authors reported.
Jonathan Tam, MD, of Children's Hospital Los Angeles, told in an email that "opioids have wide ranging effects on the immune system," and suggested that "children with prenatal opioid exposure have been shown to have reduced numbers of immune cells."
"Which opioids are most likely to cause this effect, and when pregnant women are most susceptible, is still unanswered from this study," Tam added.
Kelty told that the big takeaway is that lumping all opioids together is "not particularly helpful for patients," and knowing which ones may have "slightly different effects" can improve care.
"Being dismissive of pain, or being dismissive of an opioid use disorder in pregnancy isn't going to result in having healthier children," she said.
For this study, Kelty and team used linked administrative health records for all children born in Western Australia from 2003 through 2018 -- approximately 401,462 neonates. They used medication data to track exposures of interest: prenatal exposure to prescription opioids, NAS, and opioid indication.
The study population included 1,656 neonates (mean gestational age 37.7 weeks, 50.5% girls) with prenatal opioid exposure. This population was more likely to be born preterm, have low birth weight for gestational age, and be co-exposed to cigarette smoke compared with those without exposure.
One limitation cited by the authors was the study only tracked diagnoses in a hospital or ED visit. Furthermore, neonates diagnosed with NAS may have longer hospital stays, making it easier to identify certain conditions, Kelty said.
Kelty and team stressed that more research on "opioid-induced immune changes during pregnancy" are needed. They are also currently studying the impact of keeping mothers on or off psychiatric medications during pregnancy.
Disclosures
This study was supported by a fellowship from the National and Health Medical Research Council and partially funded by a merit award from the Department of Health, Western Australia.
Kelty and a co-author reported receiving research funding from Mundipharma. Another co-author reported receiving grants from the National Institutes of Health and a patent for Therapeutic Composition and Methods Application.
Primary Source
JAMA Network Open
Kelty E, et al "Prenatal opioid exposure and immune-related conditions in children" JAMA Netw Open 2024; DOI: 10.1001/jamanetworkopen.2023.51933.