Substance use and abuse among pregnant women in Denmark

Background
Substance use during pregnancy can pose risks to both maternal and fetal health, underscoring the crucial importance of early intervention. Despite this urgency, the true extent of substance use during pregnancy remains inadequately understood in Denmark. In the United States, recent estimates from 2020 indicate that 8-11% of pregnant women aged 15-44 used illegal drugs, tobacco products, or alcohol in the past month (7). Cannabis emerged as the most prevalent illegal substance. In Denmark, while 2% of pregnant women receive treatment for substance use including alcohol (8, 9), estimations suggest that around 6% of pregnant women may be using substances, including alcohol (10, 11). Our pilot study has brought to light compelling evidence suggesting a notable underestimation of pregnant women with substance use. This disparity in reported numbers underscores the need for a comprehensive examination of the true prevalence of sub-stance use including alcohol, nicotine, and addictive medications among pregnant women. In pursuit of such insight, dipstick screening emerges as a direct method to promptly identify substance use. This approach offers immediate results, expediting the crucial process of identification and intervention.

Methods
In collaboration with the Family Outpatient Care Clinics and the Substance Abuse Treatment Facilities, we decided on the substances to identify. This decision was informed by their clinical experiences with substances commonly encountered in practice. We partnered with a leading manufacturer of urine dipsticks, Ferle ApS, and with the laboratory to set up confirmatory analyses (LC-MS/MS) for our findings from the urine dipsticks. We then validated the alcohol component in the new urine dipsticks (Study I), as this alcohol marker was entirely novel. Afterwards, we conducted an opioid drug utilization study, extracting data from Danish registers on prescribed and filled opioid prescriptions among pregnant women in Denmark (Study II). Lastly, we employed the urine dipsticks, - capable of detecting 15 sub-stances including alcohol, nicotine, and pharmaceuticals (prescription or OTC) - in a nationwide screening among almost 2000 pregnant women across Denmark (Study III).

Results
In the validation study (Study I), we observed that the dipsticks were capable of detecting low to moderate alcohol intake for up to 24 hours, whereas LC-MS/MS-analyses revealed isolated cases of alcohol detection for up to 72 hours. In the register study (Study II), we found that total estimated opioid use remained stable at 19.8 per 1000 pregnancies from 2007 to 2016. This involved a decline in codeine use but a notable threefold increase in tramadol use. Interestingly, this trend was not in line with recommendations suggesting a reduced prioritization of tramadol. In the nationwide urine screening (Study III), we identified an overall prevalence proportion of sub-stance use of 10.8%. This prevalence was predominantly driven by nicotine use, accounting for 10.1%. Other substances exhibited prevalence proportions of less than half a percent each. The self-reporting of use demonstrated generally high validity, except for alcohol and cannabis, where validity was comparatively lower. The overall validity of the dipstick was deemed poor, exhibiting a confirmation rate of 44.0%.

Discussion
The trend in tramadol use appears to have regressed in the years following our study signifying a positive shift in prescription practices (Sundhedsdatastyrelsen, publicly available aggregated data from the Danish Medical Birth Register). This is further underscored by the national screening conducted from 2019 to 2020, which showed minimal levels of opioid use among pregnant women and furthermore that the prevalence of sub-stance use among pregnant women was overwhelmingly attributed to nicotine. Although this result was not surprising, nicotine constitutes one of the best characterized teratogenic substances, highlighting the need for further intervention.

Our results did not uncover indications suggesting that the current antenatal care program overlooks pregnant women with substance use, but we identified several challenges within the program related to the self-reporting approach and the guidelines regarding preventive measures for substance use in pregnancy. Our results raise significant doubts on the reliability of dip-sticks, particularly in terms of risks of both false positives and false negatives, underlining the necessity of confirmatory analyses. Given the evolving landscape of substance use, including nicotine products, maintaining a consistent focus on updating guidelines to support healthcare professionals, and employing methods for secure identification of all substances remain pertinent, ultimately safeguarding the well-being of both mothers and their unborn children.