Assessment of tobacco, alcohol and cannabinoid metabolites in 645 meconium samples of newborns compared to maternal self-reports

https://doi.org/10.1016/j.jpsychires.2017.02.012Get rights and content

Abstract

Prenatal psychoactive substance exposure has significant impact on neonatal health and child development and the development of reliable biomarkers is critical. Meconium presents several advantages for detecting prenatal exposure to psychoactive substances, as it is easy to collect and provides a broad time frame of exposure (third trimester). The aim of our study was to compare the prevalence of alcohol, tobacco and/or cannabis use during the third trimester of pregnancy (using maternal self-reports) with the results of meconium testing of their metabolites in newborns (cotinine, ethyl-glucuronide (EtG) and cannabinoid metabolites).

Among all deliveries (993) that occurred in all maternities in Rouen (Normandy) during a defined time period (5 consecutive weeks in August, 2010 and August, 2011), 724 mothers were included and 645 meconium samples were collected. Maternal self-reports, using the Addiction Severity Index (5th edition), and meconium samples were collected within 72 h of delivery.

Cotinine detection appears highly correlated to maternal self-reports (Kappa value: 0.79; [95%CI: 0.73–0.85]). Moreover, detection in meconium seems more accurate in the prediction of neonatal consequences of prenatal tobacco exposure as compared to maternal self-reports. In contrast, we have found a lower concordance between maternal self-reports and meconium testing for EtG and cannabinoid metabolites (Kappa value: 0.13; [95%CI: 0.04–0.22] and: 0.30; [95%CI: −0.03–0.63], respectively); however the total number of EtG- and cannabinoid-positive meconium samples was small. Interestingly, meconium samples with the highest levels of EtG mainly corresponded to negative maternal self-reports. Fetal exposure to alcohol, tobacco or cannabis may also considerably differ as displayed in our pairs of dizygotic twins. Finally, a polyconsumption of these psychoactive substances was not frequently observed according to meconium testing.

In conclusion, cotinine detection appears as a valuable meconium biomarker. EtG measurement in meconium samples seems interesting if there is any risk of high fetal exposure, whereas assessment of prenatal cannabis exposure, using meconium testing, needs to be improved.

Introduction

Prenatal psychoactive substance exposure is an ongoing major concern, with significant impact on neonatal health and neurodevelopment (Lamy and Thibaut, 2010, Płotka et al., 2014, Lamy et al., 2015, Del Campo and Jones, 2016, Cornelius et al., 2016). It is estimated that 20–30% of pregnant women use tobacco, 3.5–54% use alcohol, 3–10% use cannabis in European countries (Goecke et al., 2014) and 16.4%, 8.5% and 5.3%, respectively in the USA, according to the National Survey on Drug Use and Health (2014) (https://www.samhsa.gov/data/sites/default/files/NSDUH-DetTabs2014/NSDUH-DetTabs2014.pdf). Lange et al., (2014) reported that maternal self-report underestimates alcohol use by 4-fold, compared to biomarker analyses in meconium.

Alcohol, tobacco and cannabinoid metabolites have the ability to accumulate in meconium and their measurements reflect fetal psychoactive substance exposure. Meconium accumulates in the fetal gut from around the 20th week of gestation until birth and the great majority of the meconium is created during the last trimester of pregnancy (Eichler et al., 2016). The use of meconium as a matrix for assessing prenatal drug exposure has yielded a method exhibiting higher sensitivity, easier collection, than other traditional matrices and a window of detection corresponding to the 3rd trimester (Gareri et al., 2006, Gray and Huestis, 2007, Wright, 2015).

Among alcohol biomarkers, ethyl-glucuronide (EtG) may be superior to fatty acid ethyl esters (FAEEs) due to better stability in meconium and insensivity to maternal diet variation; unlike FAEEs, in meconium, EtG is primarily of maternal origin. Moreover, according to Himes et al. (2015), EtG (using a cut off > 30 ng/g) is the meconium marker with the highest concordance with maternal self-report of alcohol use. EtG has been established in several studies as a biomarker of fetal ethanol exposure during the third trimester of pregnancy (see for review Burd and Hofer, 2008, Joya et al., 2016). Cotinine, a major nicotine metabolite is a relatively stable biomarker for both active and passive tobacco exposure (Gray et al., 2008). Assessment of fetal exposure to cannabis can be performed via the detection of 11-nor-Delta-tetrahydrocannabinol-9-carboxylic acid (THC-COOH), the main metabolite of tetrahydrocannabinol (THC), as it is the most abundant metabolite identified in meconium samples from cannabis-exposed newborns (Marchei et al., 2006).

The aim of our study was to compare the prevalence of tobacco, alcohol and/or cannabis use during the third trimester of pregnancy (using maternal self-reports) with the results of meconium testing of their metabolites in newborns (cotinine, ethyl-glucuronide and THC-COOH were assessed, respectively).

Section snippets

Clinical data

This study was conducted in all maternity hospitals of Rouen (a city with a population of 350 000 people, located in Normandy, North West of France), namely Rouen University Hospital (public hospital, about 2700 deliveries per year), Mathilde Clinic (private clinic, about 3100 deliveries per year) and Le Belvédère Hospital (public hospital, 3600 deliveries per year). Any pregnant women aged 18 or over and living in our catchment area that delivered a child in one of these maternity hospitals,

Results

In total, 993 deliveries occurred during the inclusion timeframe and 724 deliveries fulfilled the inclusion criteria; 676 meconium samples were collected (mean weight ± S.D.: 4.17 g ± 3.5 [minimum-maximum: 0.002–22.8]) and 645 were included in the final analyses (Fig. 1). In fact, 269 deliveries were not included for the following reasons (sometimes for several reasons): 61 mothers refused to participate, 48 did not speak and/or understand French language, 6 were younger than 18 years, 145 were

Discussion

So far, studies conducted on large cohorts of pregnant women and studying concordance between maternal self-reports of psychoactive substance use (alcohol, tobacco and cannabis) and meconium testing of their metabolites, are scarce.

Maternal self-report is the most widely used method to evaluate ethanol, tobacco or cannabis prenatal exposure (Falcon et al., 2010). Yet, health care professionals should be aware of maternal under-reporting when self-reports are used (Himes et al., 2015). In our

Conclusion

Maternal psychoactive substance use is an ongoing concern and detecting its use when suspected during pregnancy is a crucial component of early diagnosis of fetal alcohol syndrome and neonatal care. For this purpose, the development of reliable biomarkers is a critical step. Meconium is the preferred specimen as it is easy to collect and provides a broad time frame of exposure (third trimester).

In fact, tobacco is less associated to social stigma as compared to alcohol or cannabis; so maternal

Conflicts of interest

F Thibaut is Editor-in-Chief of Dialogues in Clinical Neurosciences (grant Servier).

Acknowledgments

Mothers and children who participated in the study; the Perinatal network of Upper-Normandy coordinated by C. Levèque, L. Marpeau (M.D., Ph.D., Department of Gynaecology-Obstetrics, Rouen University Hospital); P. Fournet (M.D ., Department of Gynaecology-Obstetrics, Belvédère Hospital); M. Durand-Réville (M.D., Department of Gynaecology-Obstetrics, Mathilde Hospital); Association of Midwives of Upper-Normandie; INSERM CIC-CRB 1404, Rouen (J. Weber, A. Cailleux, M. Vasse); FEDER (Fonds Européens

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