In utero opioid exposure and risk of infections in childhood: A multinational Nordic cohort study

Abstract

Purpose: There is an increasing number of children with in utero exposure to opioids. Knowledge about opioid safety in pregnancy, particularly for outcomes later in childhood is scarce. It has been suggested that opioids can modulate immune system and increase the risk of infections. Our goal was to study the impact of in utero opioid exposure on the immune system and the risk of infections in childhood. Methods: This population-based cohort study used nationwide registers from Denmark, Norway, and Sweden. Among pregnant women we identified users of opioids for two different indications, opioids used in opioid maintenance therapy (OMT) and opioids used for treatment of pain. We followed the exposed children and studied susceptibility for infections measured as number of antibiotic prescriptions expressed as Incidence rate ratios (IRRs) and diagnoses in specialist health care expressed as hazard ratios (HRs). Results: After adjustment we did not observe increased risk for filling antibiotic prescriptions in children exposed to OMT opioids compared with OMT discontinuers (IRR, 1.08; 95% CI 0.81-1.44 in Norway and Sweden, and IRR, 0.74; 95% CI 0.63-0.88 in Denmark), or for diagnosis of infection in specialist health care (HR 0.83; 95% CI 0.55-1.26 in Norway and Sweden, and 0.82; 95% CI 0.62-1.10 in Denmark). Conclusions: In this population-based cohort study, we did not observe increased risk of infections among children prenatally exposed to OMT opioids when compared to OMT discontinuers, nor long-term analgesic opioids exposed when compared to short-term analgesic opioids exposed.

Analysis of Prenatal Exposure to Opioid Analgesics and Scholastic Skills in Children in Fifth Grade in Norway

“…Most previous studies were conducted with women who used opioids for opioid maintenance therapy or for illicit purposes . However, those results are not generalizable to women who use opioid analgesics for pain management owing to differences in sociodemographic characteristics and lifestyle factors . Moreover, neurodevelopment includes a wide range of domains .…”

“… 59 , 60 However, those results are not generalizable to women who use opioid analgesics for pain management owing to differences in sociodemographic characteristics and lifestyle factors. 61 , 62 Moreover, neurodevelopment includes a wide range of domains. 57 Thus, further studies are needed to examine other domains of neurodevelopment.…”

Prenatal opioid exposure and risk of asthma in childhood: a population-based study from Denmark, Norway, and Sweden

“…In contrast, evidence on long-term consequences of prenatal opioid exposure on immune reactions is scarce. A recent study found no evidence for an association between prenatal opioid exposure and risk of infections in the offspring (Mahic et al, 2020). Some epidemiological studies have investigated the association between prenatal exposure to analgesics and risk of childhood asthma with conflicting results (Källén et al, 2013;Cheelo et al, 2015;Magnus et al, 2016;Fan et al, 2017;Shaheen et al, 2019).…”

Opioid maintenance treatment in the Czech Republic, Norway and Denmark: a study protocol of a comparative registry linkage study

“…Therefore, use of data from multiple nationwide health and population registers is an important new approach with great potential to further improve the knowledge base. [30][31][32] Further, use of multiple national data prevents potential confounding and classification bias in comparison with mortality risk between OMT, including periods of cycling in and out of treatment. 25 28 Finally, linking data from multiple registers allows for large unselected study populations, and for identification of relevant comparison groups and comparable outcome indicators.…”