Supplementary Table 3. Overview of observational studies on associations of triptan exposure during pregnancy and adverse pregnancy outcomes
Country
Data source
Time period
Multinational
Pregnancy registry
(1996–2012)
Norway
Prescription data base and
medical birth registry
(2004–2007)
Study design
Size
Exposure
Comparison group
CH
n = 904
T1:
Sumatriptan, n = 533
Naratriptan, n = 52
Any triptan, n = 1,465
T1:
Sumatriptan, n = 415
Rizatriptan, n = 310
Eletriptan, n = 189
Zolmitriptan, n = 144
Almotriptan, n = 67
Naratriptan, n = 16
None
Congenital malformations: NS
1
Disease comparison
group
(n = 1,095)
2
Any triptan§, n = 139:
Naratriptan
Rizatriptan
Sumatriptan
Zolmitriptan
Rizatriptan:
Any trimester, n = 71
T1, n = 40
Health controls,
differed in size for each
outcome
(n > 47,000)
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 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.
Spontaneous abortion:
For any triptan: OR 2.65; 95% CI 1.57–4.48
Congenital malformations: NS
Prematurity: NS
Low birth weight: NS
Congenital malformations: NS
Spontaneous abortion: NS
Elective abortion: NS
Fetal death: NS
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
CH
n = 181,125
Canada
Prescription data base and
medical birth registry
(1998–2007)
Nested CC
n = 59,707
USA
Pregnancy registry
(1998 to 2012)
CH
n = 161
Sweden
Medical birth registry
(1995–2008) and prescription
data base (2005–2008)
CH
n = 1,211,670
Population comparison
group
(n = 178,565)
None
Outcome
Main findings
Ref.
3
4
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)
Sweden
Registry of congenital
malformations and medical birth
registry
(1995–1999)
Denmark
Prescription data base and
medical birth registry
(1991–1996)
CH
n = 912
T1:
Sumatriptan, n = 658
Infants exposed in utero
to other anti-migraine
agents than triptans
(n = 254)
CH
n = 35,950
Sumatriptan†, n = 34
Healthy controls
(n = 15,955)
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
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)
Health controls
(n = 68,021)
Migraine controls
(n = 89
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
Congenital malformations: NS
6, 7
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
Congenital malformations: not reported in either group.
Still births: not reported in either group.
Spontaneous abortion: NS
Elective abortion: NS
Congenital malformations: NS
Miscarriage: NS
Elective abortion: NS
Gestational age: NS
Birth weight: NS
9
8
10
11
Non-teratogen controls
(n = 96
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.
1.
2.
3.
Ephross, S.A. & Sinclair, S.M. Final results from the 16-year sumatriptan, naratriptan, and treximet pregnancy registry. Headache 54, 1158-1172 (2014).
Nezvalová-Henriksen, K., Spigset, O. & Nordeng, H. Triptan safety during pregnancy: a Norwegian population registry study. Eur J Epidemiol 28, 759-769 (2013).
Berard, A. & Kori, S. Dihydroergotamine (DHE) use during gestation and the risk of adverse pregnancy outcomes. Headache 52, 1085-1093 (2012).
4.
5.
6.
7.
8.
9.
10.
11.
Merck & Co. Thirteenth/fourteenth annual report from the Merck Pregnancy Registry for Maxalt (rizatriptan benzoate): covering the period from approval (June 1998) through June
12, 2012. (2012).
Källén, B., Nilsson, E. & Otterblad Olausson, P. Delivery outcome after maternal use of drugs for migraine: a register study in Sweden. Drug Saf 34, 691-703 (2011).
Nezvalová-Henriksen, K., Spigset, O. & Nordeng, H. Triptan exposure during pregnancy and the risk of major congenital malformations and adverse pregnancy outcomes: results from
the Norwegian Mother and Child Cohort Study. Headache 50, 563-575 (2010).
Nezvalová-Henriksen, K., Spigset, O. & Nordeng, H. Errata in "Triptan exposure during pregnancy and the risk of major congenital malformations and adverse pregnancy outcomes:
results from the Norwegian Mother and Child Cohort Study". Headache 52, 1319-1320 (2012).
Källén, B. & Lygner, P.E. Delivery outcome in women who used drugs for migraine during pregnancy with special reference to sumatriptan. Headache 41, 351-356 (2001).
Olesen, C., Steffensen, F.H., Sørensen, H.T., Nielsen, G.L. & Olsen, J. Pregnancy outcome following prescription for sumatriptan. Headache 40, 20-24 (2000).
O'Quinn, S. et al. Pregnancy and perinatal outcomes in migraineurs using sumatriptan: a prospective study. Arch Gynecol Obstet 263, 7-12 (1999).
Shuhaiber, S.B. et al. Pregnancy outcome following first trimester exposure to sumatriptan. Neurology 51, 581-583 (1998).