naloxone and Premature-Birth

Evidence on the perinatal health of mother-infant dyads affected by opioids is limited. Elevated risks of opioid-related harms for people with opioid use disorder (OUD) increase the urgency to identify protective factors for mothers and infants. Our objectives were to determine perinatal outcomes after an OUD diagnosis and associations between opioid agonist treatment and birth outcomes.. We conducted a population-based retrospective study among all women with diagnosed OUD before delivery and within the puerperium period in British Columbia, Canada, between 2000 and 2019 from provincial health administrative data. Controlling for demographic and clinical characteristics, we determined associations of opioid agonist treatment on birth weight, gestational age, infant disorders related to gestational age and birth weight, and neonatal abstinence syndrome via logistic regression.. The population included 4574 women and 6720 live births. Incidence of perinatal OUD increased from 166 in 2000 to 513 in 2019. Compared with discontinuing opioid agonist treatment during pregnancy, continuous opioid agonist treatment reduced odds of preterm birth (adjusted odds ratio: 0.6; 95% confidence interval: 0.4-0.8) and low birth weight (adjusted odds ratio: 0.4; 95% confidence interval: 0.2-0.7). Treatment with buprenorphine-naloxone (compared with methadone) reduced odds of each outcome including neonatal abstinence syndrome (adjusted odds ratio: 0.6; 95% confidence interval: 0.4-0.9).. Perinatal OUD in British Columbia tripled in incidence over a 20-year period. Sustained opioid agonist treatment during pregnancy reduced the risk of adverse birth outcomes, highlighting the need for expanded services, including opioid agonist treatment to support mothers and infants.

Topics: Adult; Analgesics, Opioid; British Columbia; Buprenorphine; Female; Humans; Incidence; Infant, Newborn; Logistic Models; Longitudinal Studies; Methadone; Naloxone; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Premature Birth; Retrospective Studies

Toll-like receptor 4 (TLR4) activation by bacterial infection, or by sterile inflammatory insult is a primary trigger of spontaneous preterm birth. Here we utilize mouse models to investigate the efficacy of a novel small molecule TLR4 antagonist, (+)-naloxone, the non-opioid isomer of the opioid receptor antagonist (-)-naloxone, in infection-associated preterm birth. Treatment with (+)-naloxone prevented preterm delivery and alleviated fetal demise in utero elicited by i.p. LPS administration in late gestation. A similar effect with protection from preterm birth and perinatal death, and partial correction of reduced birth weight and postnatal mortality, was conferred by (+)-naloxone administration after intrauterine administration of heat-killed E. coli. Local induction by E. coli of inflammatory cytokine genes Il1b, Il6, Tnf and Il10 in fetal membranes was suppressed by (+)-naloxone, and cytokine expression in the placenta, and uterine myometrium and decidua, was also attenuated. These data demonstrate that inhibition of TLR4 signaling with the novel TLR4 antagonist (+)-naloxone can suppress the inflammatory cascade of preterm parturition, to prevent preterm birth and perinatal death. Further studies are warranted to investigate the utility of small molecule inhibition of TLR-driven inflammation as a component of strategies for fetal protection and delaying preterm birth in the clinical setting.

Topics: Animals; Cytokines; Female; Inflammation; Lipopolysaccharides; Mice; Naloxone; Pregnancy; Premature Birth; Toll-Like Receptor 4