Thomas McKeown and RG Record were colleagues in Birmingham, England, f
rom 1947 to 1977. During their first decade together, they laid the fo
undations of epidemiological research on malformations with a series o
f case-control studies of the commoner major defects. They found evide
nce of numerous trends of birth prevalence with variables such as seas
on and year of birth, maternal age, birth rank, and socioeconomic stat
us, suggesting that environmental factors played an important part in
causation. The work that has led recently to the use of folate to redu
ce the risk of neural tube defects is among the lines of research that
can be traced back to these case-control studies. McKeown and Record
also initiated, in Birmingham, the first population-based register of
malformations to be set up as an on-going activity. As well as paving
the way for the international networks of registers that now exist, th
e Birmingham register has been used in a variety of cohort studies. Th
is work has confirmed many of the case-control study findings and cont
inues to yield new observations, including evidence that enteroviruses
are involved in aetiology.