This concentration changes over the course of a
pregnancy requiring that study results be interpreted
within the context of the age of the fetus at the time
the study is performed. One way this is accom-
plished is by arranging for the screening procedure
to be done at the same gestational interval in every
pregnant mother, such as at 16 to 18 weeks of gesta-
tion for the investigation of neural tube defects
(Wald and Cuckle 1982). Then all the results can be
analyzed using the same gestational age-specific
reference frequency distributions.
The majority of the laboratory studies performed
late in the fetal period are concerned with the deter-
mination of fetal maturity. Regardless of the fetus’
gestational age, the state of maturity of the individ-
ual fetus, especially the maturity of the pulmonary
epithelium, is paramount. The laboratory studies
that are used in this setting are ones for which there
is a known relationship between the study result and
the probability of post natal difficulties arising from
prematurity. The innate or therapeutically acceler-
ated maturation of the fetus is usually followed for
some period of time by serial monitoring before
study results indicate that it is safe to deliver the
baby.
The newborn period is marked by tumultuous
physiologic changes. These changes are accompa-
nied by rapid alterations in many laboratory study
results. Childhood and adolescence is a period of
growth, development, and maturation. The fre-
quency distributions of most laboratory studies
undergo changes during at least some portion of this
period. The changes may be fairly abrupt, such as
the increases in plasma sex hormone concentration
that occur with puberty, or they may be gradual,
lasting most or all of the period, as is shown in
Figure 6.6 for plasma creatinine concentration
(Schwartz
et al.
1976).
Because of the profound effects of age through-
out the pediatric periods, pediatric age-specific refer-
ence frequency distributions have been established
for most laboratory analytes. These distributions
can be found in textbooks devoted to pediatric clini-
cal practice and pediatric laboratory medicine.
Although adulthood and old age are generally
considered to be separate periods of life with distinct
physiologic differences, aging actually occurs
throughout adulthood (Bafitis and Sargent 1977); the
changes found in old age are, in general, cumulative
not distinctive. Figure 6.7 shows the aging behavior
of the lungs and kidneys. The lungs complete their
growth and development in late adolescence after
which they immediately begin to undergo a progres-
sive decline in functional capacity throughout adult-
hood. The kidneys mature a few years sooner than
the lungs but, like the lungs, they begin aging in
early adulthood.
The effects of age-related changes in organ
function may be evident throughout adulthood or
they may only become manifest late in life, often
after a critical functional reserve has been lost.
Creatinine clearance rate falls throughout life, for
Biologic Variability
6-7
Figure 6.6
Plasma creatinine concentration in children as a function of age. Mean concentrations for each sex binned by
year and fit by a linear model (solid lines). The error bars represent standard errors of the mean not standard deviations and
hence cannot be used to calculate the width of the distributions. Reprinted from Schwartz GJ, Haycock GB, and Spitzer A.
1976. Plasma creatinine and urea concentration in children: normal values for age and sex. J Pediatr 88:828.
