Antiepileptic drugs prescribed in pregnancy and prevalence of major congenital malformations: comparative prevalence studies

Figures & data

Table 1 Characteristics of women in the four treatment cohorts

Characteristics	Treatment status in first trimester
	Valproate		Carbamazepine		Lamotrigine		Not treated with AEDs
	n	%	n	%	n	%	n	%
Total	229	100	334	100	357	100	239,151	100
Age (years)
Mean (SD)	30 (5.6)	–	31 (5.5)	–	30 (5.3)	–	31 (5.9)	–
12–19	7	3.1	4	1.2	14	3.9	9,048	3.8
20–29	94	41	113	33.8	147	41.2	89,162	37.3
30–39	117	51.1	196	58.7	188	52.7	128,333	53.7
40–49	11	4.8	21	6.3	8	2.2	12,608	5.3
Year of delivery
1995–1999	34	14.8	47	14.1	7	2	18,626	7.8
2000–2004	65	28.4	98	29.3	50	14	59,706	25
2005–2009	78	34.1	106	31.7	154	43.1	86,303	36.1
2010–2014	52	22.7	83	24.9	146	40.9	74,516	31.2
Lifestyle variables
Obesity	25	10.9	35	10.5	38	10.6	14,697	6.1
Illicit drug use	9	3.9	11	3.3	5	1.4	1,560	0.7
Alcohol problems	3	1.3	5	1.5	4	1.1	1,252	0.5
Smoker	69	30.1	63	18.9	82	23	47,069	19.7
Townsend score
1	31	13.5	71	21.3	65	18.2	54,674	22.9
2	29	12.7	59	17.7	67	18.8	46,081	19.3
3	38	16.6	73	21.9	66	18.5	48,922	20.5
4	66	28.8	58	17.4	79	22.1	45,599	19.1
5	55	24	63	18.9	62	17.4	33,739	14.1
Missing	10	4.4	10	3	18	5	10,136	4.2
Indication
Unknown indication	8	3.5	17	5.1	7	2	219,849	91.9
Severe mental illness or depression	14	6.1	19	5.7	6	1.7	16,458	6.9
Epilepsy	207	90.4	298	89.2	344	96.4	2,844	1.2
Child characteristics
Male	111	48.5	186	55.7	180	50.4	122,091	51.1

Abbreviations: AEDs, antiepileptic drugs; SD, standard deviation.

Table 2 Prevalence and results from unadjusted and adjusted analyses of PRs and 95% CIs of MCM

Comparisons made between	Total (N)	MCM (n)	Prevalence per 100 live births (95% CI)	PRunadj	95% CI	PRadj*	95% CI No AED
No AED	239,151	5,315	2.22 (2.16–2.28)	1	–	1	–
Valproate	229	15	6.55 (3.71–10.57)	2.95	(1.81–4.81)	2.19	(1.32–3.64)
No AED	239,151	5,315	2.22 (2.16–2.28)	1	–	1	–
Valproate polytherapy	53	5	9.43 (3.13–20.66)	4.24	(1.86–9.69)	2.98	(1.29–6.88)
No AED	239,151	5,315	2.22 (2.16–2.28)	1	–	1	–
Valproate monotherapy	176	10	5.68 (2.76–10.20)	2.56	(1.40–4.67)	1.94	(1.05–3.61)
No AED	239,151	5,315	2.22 (2.16–2.28)	1	–	1	–
Carbamazepine	334	11	3.29 (1.66–5.82)	1.48	(0.80–2.74)	1.09	(0.57–2.09)
No AED	239,151	5,315	2.22 (2.16–2.28)	1	–	1	–
Lamotrigine	357	10	2.80 (1.35–5.09)	1.26	(0.69–2.31)	0.95	(0.51–1.79)
Lamotrigine/carbamazepine	691	21	3.04 (1.89–4.61)	1	–	1	–
Valproate	229	15	6.55 (3.71–10.57)	2.16	(1.15–4.04)	2.33	(1.21–4.50)

Note:

* Adjusted analyses include adjustments for maternal age, sex of child, quintiles of Townsend deprivation score and indication for treatment.

Abbreviations: PR, prevalence ratio; CI, confidence interval; PR_unadj, unadjusted PR; PR_adj, adjusted PR; AEDs, antiepileptic drugs; MCM, major congenital malformations.

Table 3 Prevalence and results from unadjusted and adjusted analyses of PRs and 95% CI of MCM in children of women with a record of epilepsy

Comparisons made between	Total (N)	MCM (n)	Prevalence per 100 live births (95% CI)	PRunadj	95% CI	PRadj	95% CI No AED
No AED	2,844	86	3.02 (2.42–3.73)	1	–	1	–
Valproate	207	15	7.25 (4.06–11.95)	2.40	(1.38–4.14)	2.33	(1.34–4.04)
No AED	2,844	86	3.02 (2.42–3.73)	1	–	1	–
Valproate polytherapy	50	5	10.00 (3.25–23.33)	3.31	(1.34–8.15)	2.81	(1.13–7.01)
No AED	2,844	86	3.02 (2.42–3.73)	1	–	1	–
Valproate monotherapy	157	10	6.37 (3.05–11.71)	2.11	(1.09–4.05)	2.14	(1.11–4.13)
No AED	2,844	86	3.02 (2.42–3.73)	1	–	1	–
Carbamazepine	298	10	3.36 (1.61–6.17)	1.11	(0.58–2.14)	1.09	(0.56–2.10)
No AED	2,844	86	3.02 (2.42–3.73)	1	–	1	–
Lamotrigine	344	9	2.61 (1.20–4.97)	0.87	(0.44–1.72)	0.88	(0.44–1.75)
Lamotrigine/carbamazepine	642	19	2.96 (1.78–4.62)	1	–	1	–
Valproate	207	15	7.25 (4.06–11.95)	2.59	(1.24–4.82)	2.65	(1.32–5.30)

Abbreviations: PR, prevalence ratio; CI, confidence interval; PR_unadj, unadjusted PR; PR_adj, adjusted PR; MCM, major congenital malformations; AEDs, antiepileptic drugs.

Table S1 The 50 most commonly recorded Read codes for major congenital malformations

Read codes	Description
P54..00	Ventricular septal defect
PC60.00	Hypospadias
PA5..00	Congenital hypertrophic pyloric stenosis
P550.00	Atrial septal defect NOS
P90..00	Cleft palate
PD23.11	Congenital dilated renal pelvis
PE1..12	Sternomastoid tumor
P71..00	Coarctation of aorta
PD34.11	Duplex kidneys
P52..00	Tetralogy of Fallot
PF0..00	Polydactyly – supernumerary digits
PG0y000	Brachycephaly
P92..00	Cleft palate with cleft lip
PD23.00	Congenital hydronephrosis
P55..00	Ostium secundum atrial septal defect
PG0z.11	Dysmorphic features
PB26.00	Imperforate anus
PF1..00	Syndactyly – webbing of digits
PG71.00	Gastroschisis
P6y2.00	Pulmonary infundibular stenosis
PB30.00	Hirschsprung’s disease
PC33.00	Bicornuate uterus
PF13.11	Webbed toes
P9…00	Cleft palate and lip
PF01.00	Accessory fingers
P21..00	Microcephalus
P91..00	Cleft lip (harelip)
PD11.00	Polycystic kidney disease
P360.00	Congenital ptosis
PG03.00	Craniosynostosis
P1…00	Spina bifida
PD02.00	Congenital absence of kidney
PG0C.00	Pierre–Robin syndrome
PD13.11	Multicystic kidney
P6z..00	Congenital heart anomaly NOS
PH3y200	Epidermolysis bullosa
P51..00	Transposition of great vessels
PKy9300	Prader–Willi syndrome
P641.00	Bicuspid aortic valve
P67..00	Hypoplastic left heart syndrome
P602.00	Congenital pulmonary stenosis
PK5..00	Tuberous sclerosis
P31..00	Microphthalmos
P63..00	Congenital aortic valve stenosis
PH1..00	Ichthyosis congenital
P344200	Coloboma of iris
P3y0.00	Ocular albinism
P80..00	Choanal atresia
PA30.00	Atresia of esophagus
PC60312	Hypospadias, glandular

Abbreviation: NOS, not otherwise specified.