Thirty studies were included in the review (22 case control studies, seven cohort studies and one RCT). Sample sizes ranged from 22 to 582,745.
Overall congenital malformation:
Aspirin (11 studies). Three studies found that use of aspirin in the first trimester of pregnancy was associated with a statistically significant increased risk of overall congenital malformation. Eight studies found no statistically significant association between the use of aspirin and risk of overall congenital malformations. Only case control studies (two studies) showed a statistically significant association between the use of aspirin and the risk of overall congenital malformations (OR 1.64, 95% CI 1.30 to 2.04).
NSAIDs (three studies). One study found that use of NSAIDs in the first trimester of pregnancy was associated with a statistically significant increased risk of overall congenital malformations. Two studies found no association between the use of NSAIDs and the risk of overall congenital malformations.
Gastroschisis:
Aspirin (eight studies). Six studies found that the use of aspirin during the first trimester of pregnancy was associated with a statistically significant increased risk of gastroschisis. Two studies found no association between the use of aspirin and the risk of gastroschisis.
NSAIDs (three studies). All three studies found no association between the use of the NSAID ibuprofen during the first trimester of pregnancy and the risk of gastroschisis.
Cardiac malformations:
Aspirin (eight studies). All eight studies found no association between the use of aspirin during the first trimester of pregnancy and the risk of cardiac malformations.
NSAIDs (eight studies). Three studies found that the use of NSAIDs during the first trimester of pregnancy was associated with an increased risk of cardiac malformations. Five studies found no association between the use of NSAIDs and the risk of cardiac malformations.
Orofacial malformations:
Aspirin (three studies). All three studies found no association between the use of aspirin during the first trimester of pregnancy and the risk of orofacial malformation.
NSAIDs (two studies). Both studies found a statistically significant association between the use of NSAIDs (including naproxen, ibuprofen and diclofenac) during the first trimester of pregnancy and the risk of orofacial malformations.