Statistical evidence for shared transient causes of anatomically distinct birth defects.

Certain pairs of anatomically distinct birth defects co-occur in the same baby more often than predicted under independence. Such an excess might reflects either the fact that some subpopulations of parents have inherently increased risk for both, or that certain pregnancies are at increased risk for both, even within the same couple, perhaps, due to transient exposures specific to the pregnancy. We focus on the latter possibility in the context of a large birth registry and two relatively common types of defects, by testing the null hypothesis that within sibships the two defects occur independently. Focusing on sibships where both defects occurred, we propose a test based on the total number of 'co-incidences', sibships where both occurred in the same baby. Such a test can be carried out either with or without allowance for possible dependence of risk on birth order. Applying this to club foot and sex organ defects among sibships from the Medical Birth Registry of Norway, we find strong evidence for excess within-family co-incidence, suggesting that there are shared, time-varying (hence perhaps modifiable) causal components in their aetiology.