Prenatal exposure to antipsychotic medication and use of primary health care system in childhood: a population-based cohort study in Denmark

Figures & data

Table 1 Characteristics of the children prenatally exposed and unexposed to AP medication and their mothers at the time of the index pregnancy; mean (SD) or proportion

	+AP medication (n=2,483)	−AP medication (n=960,527)
Characteristics of the children
Sex, %
Female	48	49
Male	52	51
Gestational age
Mean (SD), days	274 (15)	279 (13)
Preterm (<37 weeks), %	9	5
Term (≥37 weeks), %	91	95
Birth year, %
1997–2001	22	32
2002–2006	28	31
2007–2012	51	36
Apgar score at 5 min, %
0–7	3	1
8–10	97	98
Missing value	<1	<1
Characteristics of the mothers
Maternal age, years
Mean (SD)	31 (6)	30 (5)
<21, %	3	2
21–25, %	17	12
26–30, %	26	34
31–35, %	29	36
≥36, %	25	17
Parity, %
1 child	45	44
2 children	26	37
3 children	17	14
4+ children	12	5
Cohabitation, %
Married	43	60
Cohabiting	31	33
Single	25	7
Missing value	<1	<1
Income, %
Quartile 1	43	25
Quartile 2	31	25
Quartile 3	16	25
Quartile 4	9	25
Missing value	<1	<1
Education, %
<10 years	48	18
10–15 years	34	45
>15 years	13	33
Missing value	4	3
Smoking status, %
Nonsmoker	52	80
Smoker	39	15
Unknown	9	5
Diagnoses, %
Severe psychiatric disorders	27	<1
Substance abuse	22	3
Depression	36	2
Epilepsy	4	2
Concurrent drug use, %
Antiepileptic drugs	3	<1
Antidepressants	49	2
Benzodiazepines	19	<1
Insulin	1	1

Abbreviations: AP, antipsychotic; SD, standard deviation.

Figure 1 Type of GP contact by age of the children in 1-year intervals comparing prenatally AP-exposed and AP-unexposed children; unadjusted mean number of contacts in top panels and adjusted IRRs (95% CI) in bottom panels.

Notes: IRRs and 95% CIs were estimated using negative binomial regression applying cluster robust variance to account for correlations in the children’s use of GP services due to multiparity in the mothers. Adjusted for sex and date of birth of the children and for maternal age, parity, cohabitation status, income, education, smoking status, diagnosis of substance abuse, depression and epilepsy as well as use of antiepileptic drugs, antidepressants, benzodiazepines and insulin.
Abbreviations: AP, antipsychotic; CI, confidence interval; GP, general practitioner; IRR, incidence rate ratio.

Table 2 IRR (95% CI) for type of GP contact and services provided comparing prenatally AP-exposed children to AP-unexposed children

Contact	Crude IRR (95% CI)	Adjusted IRR (95% CI)a
Type of GP contact
Total contacts	1.32 (1.28–1.36)	1.07 (1.03–1.11)
Visits	1.27 (1.23–1.30)	1.06 (1.03–1.09)
Phone contacts	1.39 (1.34–1.45)	1.08 (1.04–1.13)
Email contacts (from 2004)	0.82 (0.68–0.99)	0.84 (0.68–1.01)
Service at GP contact
Blood sample	1.12 (0.97–1.29)	1.06 (0.92–1.23)
B-hemoglobin measurement	1.26 (1.10–1.45)	1.04 (0.89–1.20)
Peak flow/spirometry	1.08 (0.86–1.35)	1.14 (0.90–1.43)
Urinary stix	1.17 (1.04–1.32)	1.08 (0.94–1.24)
Streptococcal antigen test	1.21 (1.14–1.28)	1.11 (1.05–1.18)
CRP measurement	1.51 (1.38–1.64)	1.10 (1.00–1.21)

Notes:

a Adjusted for sex, date of birth of the child, maternal age, parity, cohabitation status, income, education, smoking status, diagnosis of substance abuse, severe psychiatric disorder, depression and epilepsy as well as use of antiepileptic drugs, antidepressants, benzodiazepines and insulin.

Abbreviations: AP, antipsychotic; CI, confidence interval; CRP, C-reactive protein; GP, general practitioner; IRR, incidence rate ratio.

Table 3 IRR (95% CI) for type of GP contact comparing prenatally AP-exposed children to AP-unexposed children stratified on maternal diagnosis of severe psychiatric disorder

	Contacts	Crude IRR (95% CI)	Adjusted IRR (95% CI)a
Maternal diagnosis of severe psychiatric disorderb	Total contacts	1.08 (1.01–1.16)	1.03 (0.96–1.11)
	Visits	1.06 (0.99–1.13)	1.02 (0.95–1.09)
	Phone contacts	1.11 (1.02–1.21)	1.05 (0.96–1.15)
	Email contacts (from 2004)	0.63 (0.44–0.91)	0.51 (0.34–0.77)
No maternal diagnosis of severe psychiatric disorderb	Total contacts	1.32 (1.27–1.37)	1.08 (1.04–1.13)
	Visits	1.28 (1.23–1.32)	1.08 (1.04–1.11)
	Phone contacts	1.38 (1.32–1.44)	1.09 (1.04–1.15)
	Email contacts (from 2004)	0.86 (0.69–1.09)	0.93 (0.74–1.16)

Notes:

a Adjusted for sex and date of birth of the children and for maternal age, parity, cohabitation status, income, education, smoking status, diagnosis of substance abuse, depression and epilepsy as well as use of antiepileptic drugs, antidepressants, benzodiazepines and insulin.

b Ever vs never maternal diagnosis of severe psychiatric disorder.

Abbreviations: AP, antipsychotic; CI, confidence interval; GP, general practitioner; IRR, incidence rate ratio.

Table 4 IRR (95% CI) for type of GP contact comparing prenatally AP-exposed children to children of mothers who used AP medication before, but not during pregnancy

Contacts	Crude IRR (95% CI)	Adjusted IRR (95% CI)a
Total contacts	0.96 (0.92–1.00)	0.95 (0.91–0.99)
Visits	0.96 (0.93–1.00)	0.96 (0.92–1.00)
Phone contacts	0.96 (0.91–1.00)	0.94 (0.89–0.99)
Email contacts (from 2004)	0.86 (0.67–1.10)	0.76 (0.59–0.98)

Notes:

a Adjusted for sex and date of birth of the children and for maternal age, parity, cohabitation status, income, education, smoking status, diagnosis of substance abuse, severe psychiatric disorder, depression and epilepsy as well as use of antiepileptic drugs, antidepressants, benzodiazepines and insulin.

Abbreviations: AP, antipsychotic; CI, confidence interval; GP, general practitioner; IRR, incidence rate ratio.

Figure 2 IRR (95% CI) for type of GP contact comparing children prenatally exposed to AP medication with their unexposed siblings.

Notes: IRRs and 95% CIs were estimated using a mixed-model analysis with separate strata for each mother and adjusted for sex and date of birth of the children and for maternal age, parity, cohabitation status, income, education, smoking status, diagnosis of substance abuse, depression and epilepsy as well as use of antiepileptic drugs, antidepressants, benzodiazepines and insulin.
Abbreviations: AP, antipsychotic; CI, confidence interval; GP, general practitioner; IRR, incidence rate ratio.

Figure 3 Type of AP medication and IRR (95% CI) for total GP contacts.

Notes: IRRs and 95% CIs were estimated using negative binomial regression applying cluster robust variance to account for correlations in the children’s use of GP services due to multiparity in the mothers. Adjusted for sex and date of birth of the children and for maternal age, parity, cohabitation status, income, education, smoking status, diagnosis of substance abuse, depression and epilepsy as well as use of antiepileptic drugs, antidepressants, benzodiazepines and insulin. ^aFirst-generation AP medication.^b Second-generation AP medication.
Abbreviations: AP, antipsychotic; CI, confidence interval; GP, general practitioner; IRR, incidence rate ratio.