Table 3.

Pre and perinatal factors associated with tic severity and severity of co-morbid ADHD, OCD, and other disorders

Factors	Results (exposed vs. Non-exposed)	P value	Directions of association	Case Number	Scales of measurements	Reference
Pre-natal period
Pregnancy complications	Current YGTSS 22.3+/-9.4 vs. 17.3+/-8.4	p = 0.03	↑	70	YGTSS	Bos-Veneman 2010 [27]
	2.0 + -3.7 vs. 3.9 + -4.9	p = 0.05	↓	110	CYBOCS	Bos-Veneman 2010 [27]
	No difference in worst ever tic severity	p = 0.68	-	70	YGTSS	Bos-Veneman 2010 [27]
	No difference in ADHD severity	p = 0.45	-	65	ADHD rating scale	Bos-Veneman 2010 [27]
	No difference in tic severity	NS	-	110	YGTSS	Bos-Veneman 2010 [27]
	No difference in social behaviours	NS	-	110	CSBQ	Bos-Veneman 2010 [27]
	No difference in anxiety and depression	NS	-	110	RCADS	Bos-Veneman 2010 [27]
Severity of nausea/vomiting	Associated with current tic severity	p = 0.01	↑	31	TS Global scale and C-GAS (adjusted for gender)	Leckman 1990 [24]
Number of medications exposed in utero	Associated with increased global tic severity	p < 0.00001	↑	180	YGTSS	Mathews 2006 [26]
	Interference of OCS	p = 0.08	↑	180		Mathews 2006 [26]
Maternal smoking	ADHD Severity 26.4 + -10.1 vs. 19.1 + -10.9	p = 0.05	↑	70	ADHD rating scale	Bos-Veneman 2010 [27]
	Associated with more severe ADHD symptoms modified by positive family history of mental disorders	p = 0.04	↑	70	ADHD rating scale	Bos-Veneman 2010 [27]
	9.1 + -4.1 vs. 6.1 + -4.1	p = 0.05	↑	110	MDD RCADS	Bos-Veneman 2010 [27]
	6.6 + -3.8 vs. 4.4 + -3.7	p = 0.05	↑	110	CSBQ subscale orientation ratings	Bos-Veneman 2010 [27]
	Positive association with tic severity	p < 0.00001	↑	180	YGTSS	Mathews 2006 [26]
	Interference of OCS	p = 0.03	↑	180		Mathews 2006 [26]
	No difference in current tic severity	p = 0.38	-	70	YGTSS	Bos-Veneman 2010 [27]
	No difference in worst ever tic severity	p = 0.86	-	65	YGTSS	Bos-Veneman 2010 [27]
	No difference in tic severity	NS	-	110	YGTSS	Bos-Veneman 2010 [27]
	No difference in obsessive compulsive severity	NS	-	110	CYBOCS	Bos-Veneman 2010 [27]
	No difference in social behaviours other than orientation ratings	NS	-	110	CSBQ	Bos-Veneman 2010 [27]
	No difference in anxiety and total scale of RCADS	NS	-	110	RCADS	Bos-Veneman 2010 [27]
Maternal alcohol drinking	No difference in current tic severity	p = 0.13	-	70	YGTSS	Bos-Veneman 2010 [27]
	No difference in worst ever tic severity	p = 0.10	-	70	YGTSS	Bos-Veneman 2010 [27]
	No difference in ADHD severity	p = 0.71	-	65	ADHD rating scale	Bos-Veneman 2010 [27]
Psychological stress	Associated with current tic severity	p = 0.03	↑	31	TS Global scale and C-GAS	Leckman 1990 [24]
Perinatal period
Delivery complications	Worst ever YGTSS 28.7+/-9.1 vs. 23.4+/-7.3	p = 0.01	↑	70	YGTSS	Bos-Veneman 2010 [27]
	Associated with lesser total YGTSS ratings after adjusting for age and gender modified by DRD4 3R allele	p = 0.02	↓	110	YGTSS	Bos-Veneman 2010 [27]
	Associated with higher total anxiety ratings and total RCADS after adjusting for age and gender modified by DRD4 2R allele	p = 0.004 and 0.006	↑	110	RCADS	Bos-Veneman 2010 [27]
	No difference in current tic severity	p = 0.82	-	70	YGTSS	Bos-Veneman 2010 [27]
	No difference in ADHD severity	P = 0.13	-	65	ADHD rating scale	Bos-Veneman 2010 [27]
	No difference in tic severity	NS	-	110	YGTSS	Bos-Veneman 2010 [27]
	No difference in obsessive compulsive severity	NS	-	110	CYBOCS	Bos-Veneman 2010 [27]
	No difference in social behaviours	NS	-	110	CSBQ	Bos-Veneman 2010 [27]
	No difference in anxiety and depression	NS	-	110	RCADS	Bos-Veneman 2010 [27]
Delivery complications and other perinatal adversities	No difference in tic severity between TS twins	NS	-	13 pairs	Shapiro scales	Hyde 1992 [25]
Severity of perinatal complications	Borderline associated with the tic severity	p = 0.07	↑	31	TS Global scale and C-GAS (adjusted for gender)	Leckman 1990 [24]
Number of perinatal complications	No association with the tic severity	NS	-	31	TS Global scale and C-GAS (adjusted for gender)	Leckman 1990 [24]
Neonatal factors
Birth Weight	Higher tic scores in lighter body weight twin on both Shapiro and YGTSS scales	p = 0.001 and 0.01	↓	13 pairs	Shapiro scales and YGTSS	Hyde 1992 [25]
	Within-pair body weight difference is correlated with within-pair tic score difference (rho = 0.72)	p < 0.005	↓	13 pairs	Shapiro scale	Hyde 1992 [25]
Birth order in TS twins	Mean first-born tic score vs. mean second-born tic score: 7.1 + -6.5 vs. 8.4 + -5.6	p = 0.57	-	8 pairs	Shapiro scales and YGTSS	Hyde 1992 [25]
Handedness in TS twins	Tic score in right-handed vs. left-handed: 10.6 + -4.7 vs. 6.1 + -4.6	p = 0.13	-	7 pairs	Shapiro scales and YGTSS	Hyde 1992 [25]
Postnatal period
First-week postnatal complications	No difference in current tic severity	p = 0.87	-	69	YGTSS	Bos-Veneman 2010 [27]
	No difference in worst ever tic severity	p = 0.74	-	69	YGTSS	Bos-Veneman 2010 [27]
	No difference in ADHD severity	p = 0.83	-	64	ADHD rating scale	Bos-Veneman 2010 [27]

ADHD: Attention Deficit Hyperactive disorder; C-GAS: Children's Global Severity Scale; CI: confidence interval; CSBQ: Children's Social Behavior Questionnaire; CYBOCS: Children's Yale-Brown Obsessive-Compulsive scale; DRD4: Dopamine receptor D4; MDD; Major Depression Disorder; NS: non-significant; OCD: Obsessive Compulsive Disorder; OCS: Obsessive-Compulsive Symptoms; OR: odds ratio; RCADS: Revised Child Anxiety and Depression Scale; TS Tourette’s syndrome; YGTSS: Yale Global Tic Severity Scale; Borderline (0.05 < = p <0.10) or significant (p < 0.05) results are marked with the association directions, statistically significant results shown in bold.