Clara cell protein (CC16) is a 16-kD protein secreted at the surface o
f respiratory airways by nonciliated bronchial and bronchiolar cells,
including Clara cells. Using the same immunoassay as that recently dev
eloped for CC16 in lung lavage, we have measured CC16 in amniotic flui
d samples from 100 normal fetuses and 51 fetuses with various patholog
ies. Ouchterlony immunodiffusion analysis showed a complete identity b
etween CC16 in amniotic fluid and the protein in lung lavages of adult
s. CC16 was detectable in amniotic fluid from about the 15th wk of pre
gnancy, then progressively increased until delivery, with a tendency t
o reach a plateau after the 30th wk. Between the 15th and the 39th wk
of pregnancy, the concentration of CC16 in amniotic fluid increased on
average 25 times. The sex of the fetus did not influence the concentr
ation of CC16 in amniotic fluid. Compared with expected values, levels
of CC16 in amniotic fluid were on average not significantly altered i
n cases of spina bifida (n = 9), anencephaly (n = 7), and trisomy 21 (
n = 6). In contrast, CC16 was on average significantly decreased in ca
ses of diaphragmatic hernia (n = 6), trisomy 18 (n = 14), Turner syndr
ome (n = 4), and diabetic pregnancy (n = 5). In cases of diaphragmatic
hernia, a relation emerged between the concentration of CC16 in amnio
tic fluid and both the weight of the lungs and the survivorship of the
fetuses. The time course of CC16 in amniotic fluid during normal preg
nancy and its reduction in pathologies associated with lung hypoplasia
suggest that CC16 in amniotic fluid might serve as a marker of bronch
ial epithelium growth.