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. Author manuscript; available in PMC: 2019 Dec 1.
Published in final edited form as: JAMA Psychiatry. 2018 Dec 1;75(12):1217–1224. doi: 10.1001/jamapsychiatry.2018.2728

Table 2.

Top Associations Between Prenatal Exposure to Medications and Subsequent Diagnosis of ASD

Medication Group Model 1a Model 2b Model 3c Model 4d
HR (95% CI) P Value HR (95% CI) P Value HR (95% CI) P Value HR (95% CI) P Value
Serotonin transporter inhibitor 1.35 (0.96–1.89) .08 1.37 (0.97–1.91)  .07  1.26 (0.90–1.76) .17  1.06 (0.76–1.48)  .73
Serotonin receptor 1B and 1D agonist 0.72 (0.10–5.20) .75 0.76 (0.11–5.43)  .78  0.72 (0.10–5.21) .75  0.57 (0.08–4.14)  .58
Serotonin receptor 2A antagonist 1.07 (0.15–7.69) .95 1.10 (0.15–7.93)  .92  0.87 (0.12–6.30) .89  0.79 (0.11–5.76)  .82
Serotonin receptor 2B antagonist 3.56 (0.48–26.27) .22 3.70 (0.50–27.48)  .20  2.57 (0.34–19.42) .36  2.43 (0.32–18.77)  .39
GABA transaminase inhibitor 4.09 (1.01–16.60)e .05 4.06 (1.00–16.46)e  .05  3.36 (0.86–13.22) .08  3.15 (0.82–12.06)  .09
GABA A receptor agonist 1.47 (0.91–2.38) .11 1.53 (0.95–2.48)  .08  1.32 (0.82–2.11) .25  1.17 (0.73–1.86)  .52
GluR 3 agonist 3.32 (0.47–23.52) .23 3.27 (0.46–23.51)  .24  2.42 (0.33–17.60) .39  2.67 (0.36–19.68)  .34
NMDAR 1, 2D, and 3B antagonists 0.80 (0.25–2.49) .70 0.80 (0.26–2.51)  .71  0.79 (0.25–2.48) .69  0.57 (0.18–1.81)  .34
NMDAR 3A antagonist 0.63 (0.26–1.51) .30 0.63 (0.26–1.52)  .30  0.62 (0.26–1.49) .28  0.48 (0.20–1.15)  .10
nAChR α antagonist 5.83 (0.77–44.27) .09 6.15 (0.82–46.11)  .08 10.01 (1.08–92.87)e .04 12.94 (1.35–124.25)e  .03
mAChR 1 agonist 1.01 (0.78–1.30) .96 1.00 (0.77–1.29) >.99  0.99 (0.76–1.28) .92  0.80 (0.62–1.03)  .09
mAChR 1 antagonist 0.42 (0.14–1.31) .14 0.43 (0.14–1.34)  .14  0.42 (0.14–1.32) .14  0.33 (0.11–1.03)  .06
mAChR 2 antagonist 0.61 (0.30–1.23) .17 0.62 (0.31–1.24)  .18  0.62 (0.31–1.24) .18  0.49 (0.24–0.98)e  .04
CBR 1 and 2 agonists/FAAH inhibitor 0.89 (0.68–1.17) .40 0.81 (0.68–1.17)  .40  0.89 (0.68–1.16) .38  0.72 (0.55–0.95)e  .02
OR κ and ε agonists 0.84 (0.57–1.25) .40 0.85 (0.57–1.27)  .42  0.85 (0.57–1.26) .41  0.67 (0.45–0.99)e  .045
OR μ agonist 0.86 (0.58–1.28) .46 0.87 (0.59–1.29)  .49  0.87 (0.59–1.28) .48  0.69 (0.46–1.01)  .06
Dopamine transporter inhibitor 1.15 (0.78–1.70) .49 1.16 (0.78–1.71)  .47  1.14 (0.77–1.69) .51  0.93 (0.63–1.38)  .73
Dopamine receptor D2 agonist 1.22 (0.58–2.58) .60 1.24 (0.59–2.61)  .58  1.22 (0.58–2.58) .61  1.08 (0.51–2.29)  .83
Dopamine receptor D2 antagonist 0.97 (0.76–1.26) .84 0.97 (0.75–1.25)  .80  0.96 (0.74–1.23) .73  0.78 (0.60–1.00)  .052
Dopamine receptor D3 agonist 1.48 (0.55–4.00) .44 1.46 (0.54–3.95)  .46  1.42 (0.52–3.86) .49  1.22 (0.45–3.31)  .69
Adrenergic transporter inhibitor 1.08 (0.76–1.51) .68 1.08 (0.77–1.53)  .65  1.07 (0.76–1.50) .71  0.86 (0.61–1.21)  .38
α1A-ADR agonist 1.18 (0.94–1.47) .15 1.18 (0.95–1.48)  .14  1.17 (0.94–1.46) .16  0.96 (0.77–1.20)  .71
α1B-ADR agonist 1.27 (0.90–1.80) .18 1.27 (0.90–1.80)  .18  1.26 (0.89–1.79) .20  1.05 (0.74–1.48)  .80
α1D-ADR agonist 1.24 (0.87–1.76) .24 1.24 (0.87–1.76)  .24  1.23 (0.86–1.75) .26  1.02 (0.72–1.45)  .91
α2A-ADR agonist 1.06 (0.81–1.39) .69 1.06 (0.81–1.39)  .66  1.06 (0.81–1.38) .69  0.86 (0.66–1.13)  .28
α2B-ADR agonist 0.59 (0.28–1.25) .17 0.59 (0.28–1.24)  .16  0.59 (0.28–1.24) .16  0.50 (0.24–1.04)  .06
α2C-ADR agonist 0.51 (0.23–1.15) .10 0.51 (0.23–1.14)  .10  0.51 (0.23–1.14) .10  0.43 (0.19–0.96)  .04
β1-ADR agonist 1.28 (0.41–4.00) .68 1.31 (0.42–4.10)  .65  1.32 (0.42–4.13) .64  1.05 (0.34–3.29)  .93
β2-ADR agonist 0.75 (0.38–1.49) .42 0.77 (0.39–1.53)  .46  0.76 (0.39–1.51) .44  0.59 (0.30–1.18)  .14
β1-ADR antagonist 1.12 (0.53–2.37) .76 1.21 (0.57–2.56)  .62  1.18 (0.56–2.49) .67  0.87 (0.41–1.84)  .71
β2-ADR antagonist 1.57 (0.58–4.24) .37 1.65 (0.61–4.45)  .32  1.56 (0.58–4.24) .38  1.14 (0.42–3.08)  .80
Histamine receptor 1 antagonist 1.09 (0.85–1.40) .50 1.10 (0.86–1.41)  .46  1.09 (0.85–1.40) .51  0.89 (0.69–1.14)  .35
Histamine receptor 2 antagonist 1.17 (0.72–1.90) .52 1.19 (0.73–1.93)  .49  1.16 (0.72–1.89) .54  0.86 (0.53–1.39)  .53
VAT inhibitor 1.19 (0.49–2.89) .70 1.20 (0.50–2.91)  .68  1.20 (0.50–2.90) .69  1.00 (0.42–2.41) >.99

Abbreviations: ADR, adrenergic receptor; ASD, autism spectrum disorders; CBR, cannabinoid receptor; FAAH, fatty acid amide hydrolase; GABA, γ-aminobutyric acid; GluR, glutamate receptor; HR, hazard ratio; mAChR, muscarinic acetylcholine receptor; nAChR, neuronal nicotinic acetylcholine receptor; NMDAR, N-methyl-D-aspartate receptor; OR, opioid receptor; VAT, vesicular amine transporter.

a

Adjusted for exposure and year of birth

b

Adjustedforcovariatesinmodel1, maternal age at birth, and paternal age at birth.

c

Adjusted for covariates in model 2, maternal affective disorders, maternal anxiety disorders, maternal psychotic disorders, and maternal neurologic disorders.

d

Adjusted for covariates in model 3 and number of maternal diagnoses.

e

Indicates statistically significant.