Methodological approaches to evaluate teratogenic risk using birth defect registries: advantages and disadvantages

Area of Science:

• Epidemiology
• Teratology
• Biostatistics

Background:

• Case-control studies are crucial for assessing medication exposure and birth defect risks.
• Previous evaluations of these methods have not utilized birth defect surveillance programs.
• Understanding the performance of different control group strategies is essential for accurate teratogenic risk assessment.

Purpose of the Study:

• To evaluate the scope and limitations of three case-control approaches.
• To assess the teratogenic risk of birth defects in mothers exposed to antiepileptic medications, insulin, or acetaminophen.
• To compare the odds ratio (OR) estimates derived from different control group designs.

Main Methods:

• Utilized data from the Latin American Collaborative Study of Congenital Anomalies (ECLAMC) from 1967-2008.
• Included 110,814 non-malformed newborns and 58,514 newborns with birth defects.
• Employed three control groups: non-malformed (HEALTHY), malformed (SICK), and a subgroup of only-exposed cases (OECA).

Main Results:

• The HEALTHY design showed no concordance with OECA and produced average OR differences of 3.0-11.5, overestimating risks.
• Overestimation in the HEALTHY design correlated significantly with higher OR values.
• SICK and OECA designs demonstrated good concordance and no significant differences in average risks.

Conclusions:

• The HEALTHY design, while estimating true population OR, yields high false-positive rates due to bias, which decreases with more exposed controls.
• SICK and OECA ORs are not direct estimates of true population ORs unless specific conditions are met.
• SICK and OECA designs are valuable for generating hypotheses about potential teratogens.