Prenatal opioid use linked to greater risk of immune-related conditions
A new study has found that exposing babies to prescription opioids, such as oxycodone, methadone and codeine, while they’re in the womb can increase their risk of developing immune-related conditions – particularly infections, eczema and asthma – in early childhood.
When used during pregnancy, opioids have the potential to interfere with fetal development, affecting a wide range of body systems, including the immune system. Research using rat models suggests that opioid exposure during critical periods of fetal immune development may cause the immune system to overreact to subsequent immune activation.
In humans, clinical evidence suggests that prenatal opioid exposure (POE) may make a child more susceptible to immune-related conditions, but data is limited. So, researchers at the University of Western Australia (UWA) have examined the association between POE caused by prescribed opioids and immune-related conditions in childhood.
“Opioids had been found in animal studies to alter the developing immune system, potentially impacting its ability to respond appropriately to infections and other challenges, but we didn’t know if this similarly occurred in humans and what role the timing and type of exposure played,” said Erin Kelty, lead author of the study.
The retrospective, population-based cohort study used the health records of 401,462 children born in Western Australia between 2003 and 2018. Data were obtained for the mothers of the children from the Monitoring of Drugs of Dependence System, which contains information on the dispensing of all Schedule 8 medicines – ‘controlled drugs’ – in Western Australia, including methadone, buprenorphine, oxycodone, fentanyl, morphine, pethidine, hydromorphone, and high-dose codeine. Newborns were classified as having POE if two or more prescriptions were dispensed during pregnancy.
The primary outcome was hospital admissions and emergency department (ED) presentations during which a child was diagnosed with an immune-related condition before the age of five. Outcomes were grouped into three types: infections; conditions associated with an over-active immune system such as asthma, eczema, allergy, and anaphylaxis; and autoimmune diseases.
Out of all the children, 0.4% were classified as having POE. Compared to those without POE, children with POE were more likely to have been born prematurely (18.7% vs 8.4%) and at a low birth weight for gestational age (15.1% vs 8.0%). Of the children with POE, 70.8% were exposed during trimester one, 73.7% during trimester two, and 76.4% during the third trimester. Neonatal abstinence syndrome (NAS), which occurs when a newborn withdraws from opioids they’ve been exposed to in the womb, was diagnosed in 40.2% of children, 41.0% had POE associated with opioids used for the treatment of pain, while 60.8% were exposed to an opioid used for the treatment of opioid use disorder (OUD).
The researchers found that POE was associated with an increased risk of infection, eczema and dermatitis in the perinatal period (within 28 days of birth). NAS appeared to be a major driver of perinatal eczema and dermatitis in newborns with POE. The risk of being diagnosed with a perinatal infection was 2.91 times greater in newborns with POE who were also diagnosed with NAS.
A modest (18%) increase in infection was found in newborns with POE compared with unexposed newborns, but this was associated with exposure to opioids used to treat pain (45% increase) rather than opioids to treat OUD (4% increase). Exposure to opioids used to treat pain was associated with a significant increase in the risk of gut, neurologic, eye, and upper and lower respiratory infections. By comparison, POE associated with OUD medications was not associated with an increased risk of type-specific infection.
Beyond the perinatal period – after age 29 days to five years – POE was associated with a 35% increase in the odds of being diagnosed with eczema and dermatitis, modest compared with the more than 11-fold increase in the perinatal period. However, the increases did not appear to be linked to NAS as they were in that period.
The risk of eczema and dermatitis was significantly higher in children with POE associated with opioids used for OUD treatment (methadone or buprenorphine) compared with non-exposed children. Whereas the same was not found for POE associated with opioids used to treat pain (predominantly oxycodone, codeine, and morphine).
POE was associated with an increased risk of hospitalization and ED presentation for asthma compared to non-exposure. The association was not seen to be modified by the trimester of exposure, NAS diagnosis, or the type of opioids involved. Despite the increased risk for asthma, POE was not associated with an increased risk of hospitalization and ED presentation for allergies and anaphylaxis. There was no association found between POE and autoimmune conditions.
“We found there were significant differences in outcomes depending on the specific opioid and its intended use, such as for pain treatment or opioid use disorder,” Kelty said. “The findings highlight the importance of further study into opioid-induced immune changes during pregnancy and the potential impact on long-term health in exposed children.”
The study was published in the journal JAMA Network Open.