1. CANNABIS USE DURING PREGNANCY AND RISK OF ADVERSE NEONATAL OUTCOMES: A LONGITUDINAL COHORT STUDY
Svetlana Skurtveit, Ingunn Olea Lund, Jørgen G. Bramness, Roman Gabrhelik, Randi Selmer, Eva Skovlund and Marte Handal
Norwegian Institute of Public Health, Norway
University of Oslo, Norway
Charles University, Czech Republic

2. Background
Cannabis is one of the most frequently used recreational drugs
Female use is increasing
Reviewsa suggest that in utero exposure to cannabis is associated with adverse neonatal outcomes
however
there are several methodological limitations in the studies included
a Gunn JK eta al. BMJ open
Huizink AC et al. P Prog Neuropsychopharmacol Biol Psychiatry
Metz TD et al. Am J Obstet Gynecol

3. Background
Liberalization and legalization of recreational cannabis use
Use of cannabis for medical purposes is increasing
Cannabis products contain more delta-9-tetrahydrocannabinol (THC)

4. Aim
To estimate the strength of the association between cannabis use during pregnancy and neonatal outcomes.
- The aim of this study was to examine whether there was an association between use of anxiolytics and hypnotics in pregnancy and language competence at 3 years of age

5. The Norwegian Mother and Child
Cohort Study (MoBa)
Prospective population-based pregnancy cohort
Pregnant women recruited from 1999 – 2008
40.6 % participation rate
Self-administered questionnaires during pregnancy and after birth (ongoing)
MoBa cohort
Number of individuals
Women
92 500
Men
75 200
Children
In this study we have used data from the norwegian mother and child cohort study (MoBa)
Prospective population-based pregnancy cohort
Pregnant woman recruited from 1999 – 2008
Data collection is based on self-administered questionnaires that the women receive both during pregnancy and after birth
The cohort study is still ongoing

6. MoBa Questionnaires Child Mother Father
Pregnancy start
to week 18
Week 19-29
Week 30
to birth Q1 Q3 Q4
Self-reported drug use in pregnancy
Week 18
Week 30
Birth
6 months Q1 Q3 Q4
Ultra-sound
Child
Mother
Father

7. Study population 74 641 pregnancies 65 412 women Exclusions:
Where the woman did not answer all questionnaires where cannabis
use during pregnancy was to be reported
Pregnancies with multiple fetuses
The study population consisted of pregnancies and women
The following individuals were excluded from the study…

8. Definition of exposure and outcome
Cannabis user: The women answered questions regarding illegal drug use at
pregnancy week 18 and 30, and 6 months postpartum.
Duration of cannabis use:
1: earlier in life
2: use the last month before pregnancy only
3: use during pregnancy
one period only
at least two periods
Individuals were defined as users of these drugs if they had reported use of any anxiolytic/hypnotic in at least one of the three periods
The individuals were divided into different categories based on duration of use
These categories are…
Birth outcomes
obtained from the Medical Birth Registry of Norway

9. Possible confounders, mediators and effect modifiers
Maternal education
Paternal education
Maternal age
Paternal age
Planned pregnancy
Maternal smoking
Alcohol intake in pregnancy
Analgesic opioids use in pregnancy
Benzodiazepines use in pregnancy
Parity
Marital status
Pre-pregnancy BMI
Maternal working status

10. Analysis strategy and Statistical methods
We chose to restrict the analyses to women with use of cannabis one month before pregnancy or in pregnancy and women smoking in pregnancy
Linear regression analysis was used to estimate crude effects on neonatal outcomes
We performed propensity score (PS) adjusted linear regression analyses.

11. No cannabis, but tobacco smoking in pregnancy
No cannabis, but tobacco smoking in pregnancy
Cannabis 1 month before pregnacy
Cannabis use one period in pregnancy only
Cannabis use at least two periods in pregnancy
N (%)
Number, N
4955 (6.6)
309 (0.4)
209 (0.3)
63 (0.1)
Maternal tobacco smoking in pregnancy % No
64.5
54.4
27.3
Sime times
61.4
23.2
30.9
36.4
Daily
38.6
12.3
14.8
Maternal use of illegal drugs %
99.8
27.7
14.7
4.4
Yes, earlier no pregnancy
0.2
70.0
55.9
84.4
Yes, in pregnancy
0.0
2.3
29.4
11.1
Paternal use of illegal drugs %
83.4
9.7
22.4
6.4
Yes, earlier
15.1
20.9
24.8
17.0
Yes, last 6 months before pregnancy
1.3
60.7
44.8
53.2
8.7
8.0
23.6
Maternal alcohol intake in pregnancy %
Never
46.6
21.3
20.3
19.0
sometimes
35.8
46.3
40.6
36.5
regularly/binge
17.6
32.3
39.1
44.4
Maternal benzodiazepines use in pregnancy %
98.7
95.8
92.3
90.5
Yes
1.2
4.2
7.7
9.5

12. Birth outcomes
We found that in 395 pregnancies, the women reported use of anxiolytics/hypnotics during pregnancy
Of these use during at least two periods was reported in 79 pregnancies
Use of these drugs before pregnancy only was reported in 258 pregnancies; these women stopped using the drugs when they got pregnant

13. Linear regression analysis. Unadjusted analysisB
95% CI
P value
Birth weight
Cannabis in pregnancy during one period 20
(-135, 175)
0.797
Cannabis in pregnancy during at least two periods
-269
(-485, -53)
0.015
Birth length
-0.4
(-1.0, 0.03)
0.288
Cannabis in pregnancy during at least two periods
-1.5
(-2.5, -0.6)
0.002
Head circumference
-0.2
(-0.6, 0.3)
0.528
-0.7
(-1.4, -0.0)
0.042

14. Linear regression analysis. Propensity score adjusted analysisB
95% CI
P value
Birth weight
Propensity score adjusted
Cannabis in pregnancy during one period 30
(-152,213)
0.743
Cannabis in pregnancy during at least two periods
-255
(-510, 0)
0.050
Birth length
-0.2
(-1.0, 0.6)
0.546
Cannabis in pregnancy during at least two periods
-1.4
(-2.6, -0.3)
0.015
Head circumference
-0.1
(-0.6, 0.5)
0.847
-0.6
(-1.3, 0.2)
0.172

15. Methodological consideration
Size of the cohort and the prospective design
Controlling for several important potential confounders is possible
Information about drug use in several periods
Information about dosage is not available
Selection bias
Under-reporting of drug use
Strengths are:
- Prospective design → data on exposure is collected before the outcome is measured
- Since the women received questionnares quite frequently during pregnancy the risk of recall bias was minimized
- Controlling for several important potential confounders is possible
- We have information about drug use in several periods;makes it possible to estimate duration and timing of treatment
- Information about dosage is not available
- From validity studies comparing data in MoBa and the norwegian prescription database it seems that there is a probability for under-reporting of use of these drugs in MoBa.
- This is often seen for drugs that are used sporadically
- Small study population; although MoBa is a large pregnancy cohort the number of exposures is very low compared to the number of pregnancies, so exposure is rare
- We did not have the power to study each drug separately

16. Conclusions
Short-term use did not indicate adverse effects on birth outcome.
Pregnant women reporting cannabis use in at least two time period during pregnancy delivered children with lower birth weight and birth length, even after adjusting for potential confounders
as for instance smoking.
Need further studies

17. Conclusions
Women reporting cannabis use during pregnancy had lower socioeconomic status, used more alcohol, tobacco and prescribed drugs, and had more psychiatric symptoms compared both to lifetime users, tobacco smokers and never users.
This illustrates the importance of adjusting for all possible confounders that could influence outcome.
Need further studies