Supplementary Table 3. Overview of Observational Studies on Associations of Triptan Exposure

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.

1.Ephross, S.A. & Sinclair, S.M. Final results from the 16-year sumatriptan, naratriptan, and treximet pregnancy registry. Headache 54, 1158-1172 (2014).

2.Nezvalová-Henriksen, K., Spigset, O. & Nordeng, H. Triptan safety during pregnancy: a Norwegian population registry study. Eur J Epidemiol 28, 759-769 (2013).

3.Berard, A. & Kori, S. Dihydroergotamine (DHE) use during gestation and the risk of adverse pregnancy outcomes. Headache 52, 1085-1093 (2012).

4.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).

5.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).

6.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).

7.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).

8.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).

9.Olesen, C., Steffensen, F.H., Sørensen, H.T., Nielsen, G.L. & Olsen, J. Pregnancy outcome following prescription for sumatriptan. Headache 40, 20-24 (2000).

10.O'Quinn, S. et al. Pregnancy and perinatal outcomes in migraineurs using sumatriptan: a prospective study. Arch Gynecol Obstet 263, 7-12 (1999).

11.Shuhaiber, S.B. et al. Pregnancy outcome following first trimester exposure to sumatriptan. Neurology 51, 581-583 (1998).