This work analyzed the incidence of risk factors in 138 cases presenti
ng two or more of five components defining VATERL, with no other recog
nized unrelated anomalies: vertebral anomalies, anal atresia, esophage
al atresia with or without tracheoesophageal fistula, renal anomalies,
and preaxial defects of the upper limbs, including polydactyly of the
thumb. The 138 infants were ascertained among 1,811,461 births examin
ed in the 1967-1994 period by the Latin-American Collaborative Study o
f Congenital Malformations: ECLAMC. One healthy and one malformed cont
rol newborn infant were matched to each VATERL case. The birth prevale
nce rates (per 100,000 births) for VATERL were significantly lower in
Venezuela (3.1) than in the other eight countries (8.8) (P < 0.001). V
enezuela also had lower rates for all five VATERL defects, even after
excluding the 138 VATERL cases. VATERL cases were preferentially males
(male proportion 0.6261) (P < 0.02), and, when compared with healthy
controls, they had a higher perinatal mortality rate (63.7%) (P < 0.00
5), a higher frequency of fetal losses in previous pregnancies (12.6%)
(P < 0.05), and lower mean birthweights (2,361.79 +/- 809.63 g) (P <
0.005). VATERL cases showed a higher rate than matched malformed contr
ols for prenatal exposures to drugs and physical agents (P < 0.02 and
P < 0.05, respectively), although no specific pharmacological or physi
cal group was involved. The lower birth prevalence rates found in Vene
zuela, for VATERL as well as for each of the five congenital anomalies
involved in this association, seem to be biologically meaningful. Sin
ce we could not identify a potential risk factor, nor a common cause o
f underascertainment unique to the Venezuelan subsample and common to
all six hospitals, no hypothesis can be advanced here for this phenome
non. Nevertheless, this unequal geographic distribution strongly sugge
sts a common etiopathogenicity for the five congenital anomalies invol
ved in the VATERL association. (C) 1997 Wiley-Liss, Inc.