Table 2.

Shepard's amalgamation of criteria for proof of human teratogenicity (Source: shepard, 1994 [51]) applied to SSRIs.

Criterion	Fulfillment by SSRIs
(1) Proven exposure to agent at critical time(s) in prenatal development.	No
(2) Consistent findings by two or more epidemiologic studies of high quality:
(a) Control of confounding factors
(b) Sufficient numbers
(c) Exclusion of positive or negative bias factors	No
(d) Prospective studies, if possible
(e) Relative risk of six or more (?)
(3) Careful delineation of the clinical cases. A specific defect or syndrome, if present, is very helpful	No
(4) Rare environmental exposure associated with rare defect	Not applicable
(5) Teratogenicity in experimental animals	No
(6) The association should make biological sense	No
(7) Proof in an experimental system that the agent acts in an unaltered state	Evidence of placental transfer

Note: items (1), (2), and (3) or (1), (3), and (4) are essential criteria. Items (5), (6), and (7) are helpful but not essential.