Pre-, peri-, and postnatal death

Prenatal developmental toxicity studies (e.g. OECD Test Guideline 414) are very suitable for the demonstration of intrauterine death resorption after implantation. In studies where dosing is started before implantation, preimplantation loss may also be assessed by comparing the number of corpora lutea in the ovaries of the pregnant animals with the number of implantations. Uteri that appear non-gravid should be further examined. 

There are some limitations of generation studies concerning stillbirth and early postnatal death, since the commonly used laboratory animals may eat their dead or seriously malformed pups immediately after birth. An effect may, therefore, be indicated only indirectly by a smaller litter size. If only a few pups are affected, the reduction in litter size will be small compared with the normal variation in litter size and may, therefore, go undetected or not reach statistical significance. Preimplantation losses and resorption are also indicated in an indirect way as a decreased litter size, and the sensitivity for these effects may be rather low. 

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