Supplementary Table 3. Overview of observational studies on associations of triptan exposure during pregnancy and adverse pregnancy outcomes

Country
Data source
Time period / Study design
Size / Exposure / Comparison group / Outcome
Main findings / Ref.
Multinational
Pregnancy registry
(1996–2012) / CH
n = 904 / T1:
Sumatriptan, n = 533
Naratriptan, n = 52 / None / Congenital malformations: NS / 1
Norway
Prescription data base and medical birth registry
(2004–2007) / CH
n = 181,125 / Any triptan, n = 1,465
T1:
Sumatriptan, n = 415 Rizatriptan, n = 310
Eletriptan, n = 189 Zolmitriptan, n = 144
Almotriptan, n = 67
Naratriptan, n = 16 / Disease comparison group
(n = 1,095)
Population comparison group
(n = 178,565) / Congenital malformations:
Disease comparison group (compared to population comparison group): aOR 1.48; 95% CI 1.11–1.97.
Miscarriage/stillbirth: NS
Maternal postpartum haemorrhage:
For any triptan in 2nd trimester:
aOR 1.57; 95% CI 1.19–2.07.
Prematurity:
Disease comparison group (compared to population comparison group): aOR 1.30; 95% CI 1.06–1.60.
Apgar score: NS
Low birth weight:
Disease comparison group (compared to population comparison group): aOR 1.39; 95% CI 1.08–1.81. / 2
Canada
Prescription data base and medical birth registry
(1998–2007) / Nested CC
n = 59,707 / Any triptan§, n = 139:
Naratriptan
Rizatriptan
Sumatriptan
Zolmitriptan / Health controls,
differed in size for each outcome
(n > 47,000) / Spontaneous abortion:
For any triptan: OR 2.65; 95% CI 1.57–4.48
Congenital malformations: NS
Prematurity: NS
Low birth weight: NS / 3
USA
Pregnancy registry
(1998 to 2012) / CH
n = 161 / Rizatriptan:
Any trimester, n = 71
T1, n = 40 / None / Congenital malformations: NS
Spontaneous abortion: NS
Elective abortion: NS
Fetal death: NS / 4
Sweden
Medical birth registry
(1995–2008) and prescription data base (2005–2008) / CH
n = 1,211,670 / Any triptan,
T1, n = 2,742
T2/3, n = 1,215:
Sumatriptan
Zolmitriptan
Rizatriptan
Naratriptan
Eletriptan
Almotriptan / Unexposed to antimigraine drugs
(n > 1,200,000) / Congenital malformation (any):
Eletriptan in 1st trimester: RR 5.17; 95% CI 1.07–15.1
Preterm birth:
For any triptan in 2nd and/or 3rd trimester:
RR 1.31; 95% CI 1.03–1.67
Pregnancy duration: NS
Pregnancy complications: NS
Neonatal morbidity and mortality: NS
Birth weight: NS / 5
Norway
Norwegian Mother and Child Cohort Study database and medical birth registry
(1999–2008) / CH
n = 69,929 / Any triptan, n = 1,535
T1:
Sumatriptan, n = 653
Rizatriptan, n = 328
Zolmitriptan, n = 243
Eletriptan, n = 179
Naratriptan, n = 31
Almotriptan, n = 29 / Disease comparison group
(n = 373)
Health controls
(n = 68,021) / Congenital malformations: NS
Miscarriage/stillbirth: NS
Perinatal death: NS
Low birth weight: NS
Prematurity: NS
Apgar score: NS
Atonic uterus:
Exposure during 2nd and/or 3rd trimester:
aOR 2.0; 95% CI 1.3–3.1 / 6, 7
Sweden
Registry of congenital malformations and medical birth registry
(1995–1999) / CH
n = 912 / T1:
Sumatriptan, n = 658 / Infants exposed in utero to other anti-migraine agents than triptans
(n = 254) / Congenital malformations: NS / 8
Denmark
Prescription data base and medical birth registry
(1991–1996) / CH
n = 35,950 / Sumatriptan†, n = 34 / Healthy controls
(n = 15,955)
Migraine controls
(n = 89 / Congenital malformations: not reported in exposed group.
Still birth: not reported in exposed group.
Prematurity:
For exposed group (compared with migraine controls):
OR 6.3; 95% CI 1.2–32.0
For exposed group (compared with healthy controls):
OR 3.3; 95% CI 1.3–8.5
Low birth weight: NS / 9
USA
Clinic visits, telephone interviews
(Time period not specified) / CH
n = 12,339 / T1:
Sumatriptan, n = 76 / Sumatriptan users prior to conception only
(n = 92 / Congenital malformations: not reported in either group.
Still births: not reported in either group.
Spontaneous abortion: NS
Elective abortion: NS / 10
Multinational
Teratology Information Services database
(Time period not specified) / CH
n = 288 / Sumatriptan:
Any trimester, n = 96
T1, n = 95 / Disease-matched controls
(n = 96)
Non-teratogen controls
(n = 96 / Congenital malformations: NS
Miscarriage: NS
Elective abortion: NS
Gestational age: NS
Birth weight: NS / 11

Abbreviations: CH, cohort; CC, case–control; T1, 1st trimester; T2, 2nd trimester; T3, 3rd trimester; NS, no excess risk (statistically not significant); aOR = adjusted OR. §Numbers not specified by triptan; †Trimester not specified.

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