1. In a cohort study in South Korea, prenatal opioid use did not significantly increase the risk of neuropsychiatric disorders in infants. 

2. The risk of a neuropsychiatric disorder was increased by long-term opioid use, greater doses, and use during the first trimester. 

Evidence Rating Level: 2 (Good) 

Prenatal opioid exposure is generally contraindicated in pregnancy, though chronic pain and addiction can still lead to exposure.  Currently, the association between opioid exposure and subsequent neuropsychiatric disorders in infants is poorly characterized. To assess this, a nationwide cohort study was conducted using 98% of the South Korean population. To ensure confidentiality, all patient data was anonymized where possible. The participants included 3 251 594 children who were paired with 2 369 322 mothers according to their unique identification numbers. Mothers who received two or more opioid prescriptions each trimester were defined as having opioid exposure for the study classification. The extent of opioid use had three categories. The first was based on pregnancy trimester (first, second, third trimester, more than 1 trimester). The second based on total opioid intake which was calculated using morphine milligram equivalents. The third was classified based on number of opioid prescriptions received (0-1, 2, or ≥3) and exposure time (<30, 30-59, or ≥ 60 days) of opioids throughout their pregnancy. To understand the effects of opioid use on infants of prenatal use, the onset of neuropsychiatric disorders in children was studied as the primary outcome. Of the participants, 93.1% (n=2 912 559) of infants had no associated with prenatal opioid exposure (51.3% male, 48.7% female) while 6.9% (n=216 012) of infants were associated with prenatal opioid exposure (51.2% male, 48.8% female). Opioid exposure during pregnancy was associated with a greater risk of neuropsychiatric disorders in infants (fully adjusted hazard ratio 1.07 (95% CI 1.05 to 1.10). Specifically, opioid exposure in the first trimester was related to a higher risk of neuropsychiatric disorders in infants compared to infants in the non-exposed group (1.11 (1.07 to 1.15)). Interestingly, neuropsychiatric disorder risk increased in a dose-dependent manner (low dose 1.06 (1.03 to 1.09); high dose, 1.15 (1.09 to 1.21)). Overall, prenatal opioid use was not associated with a substantial increased risk of neuropsychiatric disorders in opioid-exposed infants. Even though there was a slightly higher risk of developing a neuropsychiatric disorder, these results were observational and thus not clinically significant. Opioid exposure during the first trimester, higher exposure doses, and long-term use were associated with a greater risk of neuropsychiatric disorders. 

Click to read the study in BMJ

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