Screening of substance use in pregnancy: A Danish cross-sectional study.

INTRODUCTION: There is a paucity of objectively verified data on substance use among Danish pregnant women. We estimated the prevalence of substance use including alcohol and nicotine among the general population of Danish pregnant women. MATERIAL AND METHODS: In this anonymous, national, cross-sectional, descriptive study, pregnant women were invited when attending an ultrasound scan between November 2019 and December 2020 at nine Danish hospitals. Women submitted a urine sample and filled out a questionnaire. Urine samples were screened on-site with a qualitative urine dipstick for 15 substances including alcohol, nicotine, opioids, amphetamines, cannabis, and benzodiazepines. All screen-positive urine samples underwent secondary quantitative analyses with gold standard, liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. Results were compared to questionnaire information to analyze the validity of self-reporting and to examine possible cross-reactions. RESULTS: A total of 1903 of 2154 invited pregnant women participated (88.3%). The prevalence of dipstick-positive urine samples was 25.0%. 44.0% of these were confirmed positive, resulting in a total confirmed prevalence of 10.8%. The prevalence of nicotine use was 10.1%-and for all other substances, <0.5%. Nicotine use was more prevalent among younger pregnant women, while other substance use appeared evenly distributed over age groups. Self-reporting of use of nicotine products was high (71.1%), but low for cannabis and alcohol intake (0% and 33.3%, respectively). Prescription medication explained almost all cases of oxycodone, methylphenidate, and benzodiazepine use. CONCLUSIONS: Substance use among pregnant women consisted mainly of nicotine. Dipstick screening involved risks of false negatives and false positives. Except for alcohol intake and cannabis use, dipstick analyses did not seem to provide further information than self-reporting. LC-MS/MS analyses remain gold standard, and future role of dipstick screenings should be discussed.

Use of opioids among pregnant women 1997-2016: A Danish drug utilization study.

OBJECTIVE: Use of opioids in pregnancy is of concern yet little is known on opioid prescription patterns in Denmark. The aim of this drug utilization study was to describe prescription patterns for opioids during pregnancy in Denmark from 1997 to 2016. STUDY DESIGN: Using the nationwide health care registers, we obtained information on all women with a registered pregnancy in the period 1 January 1997 to 31 December 2016. Opioids were grouped in four: opioids (N02A except codeines), opioid dependency medications (N07BC), cough medications (R05DA except codeines), and codeines (N02AJ06, N02AJ07, N02BA75, and R05DA04). We used logistic regression analyses to identify factors associated with opioid use in pregnancy and cumulative oral morphine equivalent (OMEQ) to estimate volume of use in pregnancy. RESULTS: Prescription patterns were similar for women with live births, non-live births, and terminations. Total use of opioids among women with live born deliveries remained stable at 19.8 per 1000 pregnancies from 1997 to 2016. Codeine use declined from 2008 onwards, while use of other opioids increased from 2007 onwards. This was dominated by a threefold increase in tramadol use (2.0-7.6 per 1000 pregnancies with live births). Codeine was the most used opioid, followed by tramadol and codeine combined with paracetamol. The number of women, who used opioids before pregnancy and continued into their pregnancy, was reduced as the pregnancy progressed. The cumulative oral morphine equivalent during pregnancy was stable until 2007, after which, use prior to pregnancy and during the first two trimesters increased. The odds ratios for opioid use were higher in pregnancies of women of lower socioeconomic status or older age. For live births, odds ratios for opioid use in pregnancy were higher among women with obesity or smoking. CONCLUSIONS: Overall use of opioids was stable from 2007 to 2016. This covers a decline in the use of codeine, but a 3-fold increase in tramadol. The number of pregnant women who continued use throughout pregnancy decreased, while OMEQ among persistent users increased. The real-world data suggest an unmet need of specific focus in local Danish Outpatient Clinics and Multidisciplinary Pain Centers both pre-conceptionally and during pregnancy.

Clinical usefulness of a urine dipstick to detect ethyl glucuronide (EtG): A quantitative clinical study in healthy young female volunteers.

The metabolite of ethanol, ethyl glucuronide (EtG), reflects alcohol intake longer than ethanol and is used as a biomarker in clinical settings to detect alcohol use. We aimed to assess the clinical usefulness in a low-to-moderate alcohol intake setting and validate a new urine EtG dipstick. A three-way, open, cross-over trial was conducted. Data were collected from January to June 2019. Among 12 healthy female volunteers, we quantified urine EtG and used a dipstick following intake of either one, two or four units of alcohol. Main outcomes were concentrations of EtG in urine and serum, and creatinine and ethanol in serum. EtG in urine was determined dichotomously by dipsticks at two different thresholds and by mass spectrometry used as gold standard. EtG in urine was quantifiable up to 24 hours after alcohol intake. In some individual cases, EtG was quantifiable up to 72 hours at low concentrations. The dipstick detected EtG in urine up to 24 hours. At thresholds of 1000 and 1500 ng/mL, the dipsticks had a specificity of 100% (both), while sensitivity was 84% and 69%, respectively. The sensitivity of the dipsticks was insufficient to support a screening purpose in this setting of low-to-moderate alcohol intake.

Sex Differences in Early Cognitive Development After Prenatal Exposure to Opioids.

OBJECTIVE: Prenatal opioid exposure has been linked with impaired cognitive development, with boys potentially at elevated risk. In the present study, we examined cognitive and language development of children prenatally exposed to opioids, with an additional focus on sex differences. METHODS: A sample of 378 children (n = 194 girls and n = 184 boys) aged 1.2-42.8 months was drawn from the Danish Family Outpatient Clinic database. Developmental outcomes were assessed using the Bayley-III cognitive and language scales, and substance exposure was determined with urine screening and/or verbal report. Children exposed to opioids (n = 94) were compared to children with no prenatal substance exposure (n = 38), and children exposed to alcohol (n = 131) or tobacco (n = 115). Group and sex differences were investigated with separate linear mixed models for each Bayley scale, controlling for concurrent cannabis exposure. RESULTS: There were significantly reduced scores in opioid-exposed boys compared to boys with no prenatal substance exposure, but no difference between opioid-exposed and nonexposed girls. Additionally, alcohol-exposed boys had lower cognitive scores than nonexposed boys, and alcohol-exposed girls had lower scores on both scales compared to opioid-exposed girls. There were otherwise no significant differences according to group, sex, or scale. CONCLUSIONS: The present findings indicate poorer cognitive and language development in boys after prenatal opioid exposure. As academic performance is rooted in cognitive functioning, long-term follow-up might be necessary for exposed children.

Identification of Alcohol Risk Drinking Behaviour in Pregnancy Using a Web-Based Questionnaire: Large-Scale Implementation in Antenatal Care.

AIMS: This study aimed to examine the feasibility of a web-based questionnaire when collecting information on alcohol consumption in pregnancy to identify women with risk drinking behaviour, and to describe factors associated with risk drinking behaviour, and the use of specialized care for prenatal risk drinking. METHODS: In 2413 women referred to antenatal care at Odense University Hospital, Denmark, April-October 2018, self-reported alcohol intake was retrieved from a web-based questionnaire. Replies were screened for risk drinking behaviour: current intake of ≥7 drinks/week, ≥3 binge drinking episodes (intake of ≥5 drinks on a single occasion) in pregnancy, binge drinking after recognition of pregnancy and/or a TWEAK-score ≥ 2 points. Women with risk drinking behaviour were called to clarify the need for specialized care. A summary of the interview was obtained from the medical records. RESULTS: Overall, 2168 (90%) completed the questionnaire. Of 2097 women providing information on alcohol intake, 77 (4%) had risk drinking behaviour. Risk drinking was associated with higher alcohol intake prior to pregnancy, spontaneous conception, younger age, nulliparity and higher level of physical activity in pregnancy. Amongst 47 women with risk drinking behaviour reached by phone, five (11%, 95% CI 4-23%) accepted examinations of the child by paediatrician and child psychologist, and <3 (not further specified due to small numbers) were referred to specialized antenatal care. CONCLUSIONS: A web-based questionnaire was feasible when collecting information on alcohol consumption in pregnancy to identify risk drinking behaviour. Women with risk drinking behaviour had a low acceptance of referral to specialized care.

Management and monitoring of opioid use in pregnancy.

Opioid use during pregnancy has serious consequences for mother and baby. The true extent of the problem is unknown and there is a need for better screening. Existing guidelines with respect to the management of pregnant women with opioid use are based on limited evidence. To improve recommendations for optimal identification, management, and treatment, publications on opioids in pregnancy were reviewed. Published literature from 2007 to 2017 was searched in PubMed, Cochrane and Embase databases. The review employed 60 publications from 210 studies identified, that were of varying quality and included randomized controlled trials, systematic reviews, meta-analyses, and Cochrane reviews. The prevalence of opioid use in pregnancy is underestimated. Screening by urine testing and self-reporting is acceptable to identify fetal exposure. To minimize risk, opioid agonist pharmacotherapy should replace the continued use of opioids or detoxification. Current guidelines recommend methadone and buprenorphine equally. However, recent studies indicate that buprenorphine has advantages over methadone. Accordingly, we suggest buprenorphine as first-line therapy. Future studies should elaborate on better objective screening methods to prevent the consequences of fetomaternal opioid exposure.