Related Experiment Video
Updated: Nov 18, 2025
Preclinical Model of Prenatal Delta-9-Tetrahydrocannabinol Exposure to Assess Its Impact on Neurodevelopmental Outcomes
Published on: February 28, 2025
Association of first trimester prescription opioid use with congenital malformations in the offspring: population
Brian T Bateman1,2, Sonia Hernandez-Diaz3, Loreen Straub4
1Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 1620 Tremont Street, Suite 3030, Boston, MA 02120, USA bbateman@bwh.harvard.edu.
Insights
First trimester prescription opioid use in pregnant women was not linked to a significant increase in major birth defect risks. However, a potential small rise in oral cleft malformations was observed.
Area of Science:
- Obstetrics and Gynecology
- Teratology
- Pharmacoepidemiology
Background:
- First trimester exposure to prescription opioids has been previously linked to major congenital malformations.
- Understanding this association is crucial for maternal and child health.
- Accurate risk assessment is needed to guide clinical practice.
Purpose of the Study:
- To evaluate the association between first-trimester prescription opioid exposure and major congenital malformations.
- To assess the risk across various malformation types, including cardiac, neural tube, and oral clefts.
- To provide evidence-based information for healthcare providers and expectant mothers.
Main Methods:
- A population-based cohort study utilizing nationwide data from the Medicaid Analytic eXtract (MAX) and MarketScan Research Database.
- Inclusion of over 1.6 million publicly insured and 1.1 million commercially insured pregnant women.
- Opioid use defined by two or more dispensations in the first trimester; malformations identified via validated algorithms; propensity score stratification and meta-analysis used for adjustment.
Main Results:
- Opioid exposure was identified in 4.4% of publicly insured and 1.1% of commercially insured pregnant women.
- Adjusted analyses showed minimal increased risks for most malformations, with relative risks near the null.
- A statistically significant increased risk was observed for oral clefts (RR 1.21), particularly cleft palate (RR 1.62).
Conclusions:
- First-trimester prescription opioid use is not associated with a substantial increase in the risk of most major congenital malformations.
- A possible small increase in the risk of oral clefts, especially cleft palate, warrants further investigation.
- These findings contribute to a more nuanced understanding of opioid use during early pregnancy.
Objective:
To evaluate the risk of first trimester exposure to prescription opioids for major congenital malformations, previously reported to be associated with such exposure.
Design:
Population based cohort study.
Setting:
Nationwide sample of publicly and commercially insured pregnant women linked to their liveborn infants, nested in the Medicaid Analytic eXtract (MAX, 2000-14) and the MarketScan Research Database (MarketScan, 2003-15).
Participants:
1 602 580 publicly insured (MAX) and 1 177 676 commercially insured (MarketScan) pregnant women with eligibility from at least three months before pregnancy to one month after delivery; infants with eligibility for at least three months after birth.
Interventions:
Use of prescription opioids was ascertained by requiring two or more dispensations of any opioid during the first trimester.
Main Outcomes Measures:
Major malformations overall, cardiac malformations overall, ventricular septal defect, secundum atrial septal defect/patent foramen ovale, neural tube defect, clubfoot, and oral cleft, defined based on validated algorithms. Propensity score stratification was used to adjust for potential confounders and/or proxies for confounders. Estimates from each database were combined using meta-analysis.
Results:
70 447 (4.4%) of 1 602 580 publicly insured and 12 454 (1.1%) of 1 177 676 commercially insured pregnant women had two or more dispensations of an opioid during the first trimester. Absolute risk of malformations overall was 41.0 (95% confidence interval 39.5 to 42.5) per 1000 pregnancies exposed to opioids versus 32.0 (31.7 to 32.3) per 1000 unexposed pregnancies in the MAX cohort, and 42.6 (39.0 to 46.1) and 37.3 (37.0 to 37.7) per 1000, respectively, in the MarketScan cohort. Pooled unadjusted relative risk estimates were raised for all outcomes but shifted substantially toward the null after adjustment; for malformations overall (relative risk 1.06, 95% confidence interval 1.02 to 1.10), cardiovascular malformations (1.09, 1.00 to 1.18), ventricular septal defect (1.07, 0.95 to 1.21), atrial septal defect/patent foramen ovale (1.04, 0.88 to 1.24), neural tube defect (0.82, 0.53 to 1.27), and clubfoot (1.06, 0.88 to 1.28). The relative risk for oral clefts remained raised after adjustment (1.21, 0.98 to 1.50), with a higher risk of cleft palate (1.62, 1.23 to 2.14).
Conclusions:
Prescription opioids used in early pregnancy are not associated with a substantial increase in risk for most of the malformation types considered, although a small increase in the risk of oral clefts associated with their use is possible.
More Related Videos
Related Concept Videos
01:07Teratogenicity
01:20Opioid Analgesics: Morphine and Other Natural Cogeners
01:02Prescription, Nonprescription and Orphan Drugs
The misuse and addiction to prescription drugs is a growing problem that can affect people of all age groups, specifically teenagers. This can happen when prescription medications are used in ways not intended by the prescriber, such as taking someone else's prescription or using medication for...
01:15Opioid Analgesics: Synthetic and Semisynthetic Opioids
01:25Analgesia and Pain Management
01:21Factors Affecting Drug Response: Overview