CAPITULO I. PROCESO DE EVALUACIÓN AUTOMÁTICA
1.6 VENTAJAS DE LA TRI RESPECTO CON LA TEORÍA CLÁSICA
Patterns o f fetal and infant body growth
2.1) Aims o f chapter
This chapters deals w ith general patterns o f grow th in fetal and infant life. It also
includes a com parison o f growth betw een hum ans and non-hum an prim ates and
describes the data used to quantify growth in this thesis.
The chapter is divided into 3 m ain sections. The first includes a description o f grow th
in fetal and infant life. H ere changes in the body’s chem ical com position during
grow th are discussed and sex differences in grow th velocity are discussed, as are
factors w hich influence growth. The costs o f grow th in the fetus and infant are also
shown.
In the next section, established m ethods for quantifying grow th are discussed and the
data used in the thesis are described. These include fetal ultrasound and infant
anthropom etric m easures in humans, rhesus monkeys, baboons and com m on
m arm osets. The m ethods used in the thesis for quantifying grow th are described in
detail.
In the final section o f the chapter, growth and grow th velocity curves are constructed
and sex differences assessed. In addition, hum an and non-hum an prim ate grow th
curves are com pared, after controlling for gestation length differences betw een
species. Finally, the degree o f variability in grow th trajectories betw een individuals is
investigated.
SECTIO N I : Fetal and infant growth
2.2) B odv growth
G row th is the result o f a com plex pattern o f genetic, horm onal and environm ental
2.2a) Fetal growth
D uring the course o f 280 days o f gestation, the hum an zygote increases in w eight by a
factor o f several billion. From a single cell o f about 1/10 o f a m illim eter, the com plex
organism develops. The first m ajor developm ental period begins during the first p ost
conception w eek w ith the form ation and im plantation o f the blastocyst w hich consists
o f about 100 cells. The em bryonic period occurs during the second w eek and lasts
until about 56 post-conception days. G astrulation (laying dow n o f germ layers) and
the form ulation o f the neurula (neural plate and neural tube) occur during this period,
follow ed by differentiation o f the embryo. A fter the com pletion o f embryo
m etam orphosis, the fetal period begins and lasts from about 56 post-conception days
to term. This period is m arked by a very high rate o f grow th com pared to that o f the
child, due largely to the rate o f cell division and the fact that the proportion o f cells
undergoing division decreases w ith increasing age (Tanner 1989). Betw een 56-70
days after conception, the eyelids form, the gut is w ithdraw n into the fetus and the
external genitalia differentiate.
In the second stage o f fetal developm ent, lasting from 70-140 days, the eyelids
becom e sealed, the vertebral colum n starts to ossify and hair follicles are formed. The
final stage o f the fetal period occupies the entire second h a lf o f gestation (140-280
post-conception days), during w hich the fetus increases in w eight from about 45 to
3500 grams. This period is one o f growth and m aturation o f function (Southgate and
H ay 1976).
D uring the first trim ester, crow n-heel length doubles approxim ately every 10 days
from 6 to 10 gestation weeks. D uring this tim e, grow th is linear and velocity
increases by - 1 .4 m m /w eek (M eire 1986).
G row th in biparietal diam eter is alm ost linear throughout the first two trim esters o f
pregnancy, but during the third trim ester there is a progressive reduction in biparietal
diam eter growth. The same is true o f head volum e w hich undergoes a m arked
w eeks. This sudden and significant slowing down o f head grow th does not appear to
be due to placental insufficiency as abdom inal growth is not affected in the sam e w ay
(M eire 1986).
Briend (1979) suggested that brain growth in late gestation slows dow n in order to
allow for passage through the birth canal in upright hum ans. H e postulated that the
pressure o f the fetal head in the m aternal pelvis produces grow th reduction by
im pairing uterine blood supply. However, there is no clear physiological evidence to
support his case. N o reduction in uterine blood supply has been detected w ith m odem
D oppler m ethods in late pregnancy (M eire 1986). Therefore, it appears that the
slow ing dow n in brain grow th after 30 gestation weeks m ay be a natural ontogenetic
phenom enon in hum ans.
A bdom inal circum ference grow th is sim ilar to that o f the biparietal diameter, although
its reduction in late gestation is m uch less marked than that o f the biparietal diameter.
A bdom inal grow th velocity increases rapidly until about 30 gestation weeks, after
which, in synchronism w ith head circumference, it slows down. A t no tim e is the
trend in abdom inal circum ference grow th velocity negative (M eire 1986). This slight
reduction in abdom inal circum ference growth in late pregnancy is probably due to
uterine restriction (M eire 1981, D obbing and Sands 1978, Tanner 1978).
D uring the last 10 w eeks o f intrauterine growth, the fetus lays dow n fat both
subcutaneously and deep in the body (Catalano et al. 1998). M ost o f the fetal w eight
gain up to about 26 post-m enstm ation weeks is, how ever, due to protein accretion
(Tanner 1989).
2.2b) Changes in chem ical com position during fetal growth
The literature describing the chem ical com position o f the hum an fetus is far m ore
com prehensive than at any other age. Zeigler et al. (1976) sum m arised body
com position values for hum an fetuses and constructed a reference fetus o f ‘average’
data on w ater, lipid, protein and m ajor m ineral com position. The authors show ed that
concentrations o f w ater, sodium and chloride per unit o f body w eight decrease w ith
increasing gestational age, w hile concentrations o f protein, lipid, calcium , phosphorus,
m agnesium and potassium increase w ith age. Ziegler et al. (1976) then used estim ates
o f body com position as a function o f age and w eight gain to determ ine daily
increm ents in these body com ponents. Table 2.1 lists the w eekly increm ent in water,
protein, lipid, m inerals, carbohydrates and other undeterm ined body constituents in
the reference fetus.
These values reveal that during the last 4 m onths o f pregnancy, the fetus is com prised
o f 79, 74, 69.9 and 62.5 % w ater, respectively. The fetus, therefore, undergoes a
steady decrease in w ater content. D uring the sam e period, the fetus is com prised o f
7.8, 11.4, 13.9 and 19.8% lipid. An increase in protein also occurs during this period
T able 2.1 W eekly increm ent in water, lipid, protein and carbohydrates and other undeterm ined body constituents
ag e in te rv a l (w eeks) w a te r (g) p ro te in (g) lip id (g) o th e r (g) 24-25 82.1 10.9 4.7 2.3 25-26 79.6 10.6 7.6 2.3 26-27 78.5 10.8 8.4 2.3 27-28 77.5 11.1 9.1 2.3 28-29 76.1 11.5 10.1 2.3 29-30 74.5 12.0 11.1 2.4 30-31 73.3 12.4 11.8 2.5 31-32 72.2 12.7 12.4 2.6 32-33 71.2 13.1 13.1 2.7 33-34 70.5 13.2 13.4 2.8 34-35 69.5 13.4 14.1 3.0 35-36 68.7 13.5 14.8 3.1 36-37 67.6 13.5 15.6 3.3 37-38 64.7 13.8 18.0 3.5 38-39 59.7 14.2 22.1 4.0 39-40 51.7 14.6 2&9 4.8
Taken from Ziegler et al. (1976)
W hen considering the rate o f protein and lipid deposition in the fetus, W iddow son and
Spray (1951) show ed that protein deposition is m ost rapid before the fetus reaches a
w eight o f 1 kg, thereafter, the rate o f deposition decreases slowly. The rate o f fat
synthesis in early fetal life is very low and appears to be confined to the synthesis o f
structural lipids involved in cell m em branes and related structures. H owever, by the
m iddle o f gestation, the proportion o f fat in the body tissues increases in an
exponential m anner. D ugdale (1975) show ed that fat and lean tissue deposition is
cyclical in nature, w ith early and m id-fetal life m arked by lean tissue deposition.
N earer term fat deposition is, however, favored and predom inates during the first few
m onths o f postnatal life. The fact that both fetal tissue solids and fat increase
differentially and m arkedly during the third stage o f gestation and infancy has clear
im plications for the nutritional requirem ents o f the developing fetus (Southgate 1976).
2.2c) Infant growth
D uring the first year o f postnatal life, body length increases by about 50% o f birth
values. D uring this tim e grow th is episodic, increasing at tim es by about 0.5 to 2.5 cm
in a few days or rem aining stagnant for som e tim e (Sinclair and D angerfield 1998).
Average w eight at birth is 3.4 kg but is m ore variable than that o f length. In the first
two days o f life, neonates generally lose up to 6.5% o f their birth w eight (due to the
energetic costs o f therm oregulation, respiration and gravity), w hich is com pletely
recovered by 7 to 8 postnatal days (Fritz et al. 1985, A m it et al. 1993). W eight
velocity increase is highest shortly after birth, slow ing dow n m arkedly thereafter.
D uring the first year o f life, w eight reaches about 3 tim es that at birth and 4 tim es that
at birth b y the end o f the second year, thereafter slow ing down. B ody length follow s a
sim ilar grow th pattern to body w eight (Sinclair and D angerfield 1998), although there
are subtle differences in w hen peak grow th rate is achieved.
A large num ber o f studies have described head grow th in the infant. These include
studies by M eredith (1971), Fujim ura and Seryu (1977), B randt (1976), Fescina and
M artell (1983), Boryslaw ski (1988), Tsuzaki et al. (1990), C abana et al. (1993) and
H ead circum ference velocity peaks at about 31 gestation w eeks (Brandt 1976,
Fujim ura and Seryu 1977), at about the sam e tim e as does brain w eight (C heek 1975).
H ead circum ference grow th then slows dow n steadily during the last 9 w eeks o f
gestation, rising abruptly following birth. In fact, m axim um head grow th velocity is
attained shortly after birth, perhaps in response to release from uterine restriction at
birth (Fujim ura and Seryu 1977). Shortly thereafter, velocity decelerates to about 2.4
cm per week. B y one year-of-age, head circum ference velocity is only about 0.2 cm
per w eek (Brandt 1976).
It should be noted that although growth is often described in term s o f sm oothed
grow th curves, norm al soft tissue grow th fluctuates during developm ent and
progresses in cyclicities and pulsatilities, w ith periodic spurts and troughs in growth
(Bogin 1998, H artm an et al. 1993). It is not unusual for m ini grow th spurts to occur
from w eek to w eek in low er leg length, for exam ple (H erm anussen 1988) or as a
function o f season (Bogin 1998). This is due principally to fluctuations in growth
horm one release (H artm an et al. 1993).
2.2d) Changes in chem ical com position during infant growth
Like the fetus, grow th in the infant is accom panied by changes in the b o dy ’s chem ical
com position. Fom on (1966) and Fom on et al. (1982) have described these changes in
chem ical com position in the infant during the first year o f life by establishing
reference values for infant body com position. Infant chem ical com position values
w ere based on individual tissues.
These m easures are listed in Tables 2.2 and 2.3 and show that together m inerals,
carbohydrates and non-protein nitrogenous com pounds com prise about 2.5% o f body
m ass in the infant throughout the first year o f life. Clearly, w ater com prises a m uch
sm aller percentage o f postnatal rather than prenatal body mass, w hile protein and fat
com prise a greater proportion, particularly in the case o f protein after 6 postnatal
m uscle, adipose tissue, skin, bone, liver and heart, there are clear changes in the
com position o f these com ponents during infant grow th as show n in Table 2.3.
P rotein content o f skeletal m uscle approaches that o f the adult value by about 4 to 7
m onths o f age. A dipose tissue, on the other hand, exceeds that o f the adult during
infancy, w hile skin protein com position is approxim ately that o f the adult by 3 to 6
m onths. The protein com position o f neonatal bone, liver and heart in the first year o f
life, on the other hand, is relatively low. It should b e noted that extracellular fluid
decreases rapidly during the early months o f life (Cheek 1961) w hile fat-free adipose
tissue and skeletal m uscle change relatively little in w ater content during this period
(Fom on 1966). B y about 4 postnatal months, the chem ical m aturation o f fat-ffee
tissue (in term s o f w ater content) is 25% that o f the adult value, and 50% o f the adult
value by about 12 months. Thus, changes in the body com position w ith grow th relate
Table 2.2 Body com position o f the reference m ale infant
A ge (mo) w eight (kg)
Percentage com position (g/lOOg)
W hole body fat-free body m ass
water protein lipid other* w ater protein
birth 3.50 75.1 11.4 11.0 2.5 84.3 12.8 2 5.45 63.7 11.4 22.4 2.5 8 2 ^ 14.7 4 7.00 60.2 11.4 25.9 2.5 81.0 15.4 6 8.28 59.9 12.3 25.3 2.5 80.0 16.5 8 9.08 59.6 13.1 24.8 2.5 79.2 17.4 10 9.82 59.3 13.7 24.5 2.5 78.5 18.1 12 10.50 59.0 14.6 23.9 2.5 77.5 19.4
* includes m inerals, carbohydrate and non-protein nitrogenous com pounds
Table 2.3 Ratio o f protein w eight to w ater w eight in a num ber o f body com ponents_____________________________________________________
R atio w eight o f protein to w eight o f w ater
tissue neonate infant adult
skeletal m uscle 0.16 0.23 (4-7 m onths) 0.27
adipose 0.11 0.14 (2-9 m onths) 0.05
skin 0.20 0.51 (3-6 m onths) 0.48
bone 0.27 0.30 (2-4.5 m onths) 1.10
liver 0.18 0.20 (4-7 m onths) 0.25
heart 0.15 0.16 (5-7 m onths) 0.17
Taken from Fom on (1966) who used m ean values given by W iddow son and D ickerson (1960) for the skin, bone, liver, heart, D ickerson and W iddow son (1960) for the skeletal m uscle and B aker (1969) for the adipose tissue. A dult values based on individuals betw een 16-86 years o f age
B utte et al. (2000), in an updated body com position reference, show ed that m ales have
significantly m ore potassium than do females. Increased potassium is generally
associated w ith decreased nitrogen balance in response catabolising protein during
energy stress (Blackburn and Loper 1992: 362). The fact that m ale infants have
relatively m ore potassium than females m ay im ply that they undergo a greater degree
o f protein catabolis perhaps in response to their decreased fat stores, relative to
females. Bone m ineral content and total body w ater are also higher in boys, w ith the
difference betw een the sexes generally increasing w ith age.
2.3) Sex differences in growth patterns
A num ber o f com ponents differ in their growth betw een the sexes. Fatness, size and
shape differ betw een m ales and females. Subcutaneous fat begins to be laid dow n in
the last trim ester o f pregnancy (from about 34 post-m enstruation w eeks) and peaks at
about 9 postnatal m onths. M ale neonates display a greater proportion o f centralised
fat, w hile fem ales display a greater proportion o f peripheral fat (Cam eron, 1998).
Full-term fem ales are, on average, about 140 g lighter than m ales at birth (Sinclair and
D angerfield 1998). Girls, how ever, generally grow relatively faster than boys,
reaching 50% o f their adult height at about 1.75 years w hile boys reach their adult
height m idpoint at about 2 years (Tanner 1989). The difference in grow th rate starts
about h a lf w ay through the fetal period w hen the skeleton is about 3 w eeks m ore
advanced in fem ales (Tanner 1989). By birth, girls are about 4 to 6 w eeks m ore
m ature than boys in term s o f skeletal growth. A lthough boys are slightly larger than
girls at birth, the difference is sm all and remains so until puberty.
D ifferences in body shape betw een the sexes begin in utero. For exam ple, during the
fetal period m ales have longer forearms relative to the upper arm than do females.
This difference becom es m ore exaggerated as developm ent progresses. This differs
from leg length sexual dim orphism , w here longer leg length relative to height in m ales
is associated w ith a delayed grow th spurt (Tanner 1986, Johnston 1998). Betw een
birth and about 10 years o f age, m ales and females are fairly sim ilar in term s o f their
differ in their fat/lean tissue ratio, having proportionately m ore lean tissue than
fem ales (W ells 2000).
2.4) Influences on growth and body com position in fetal life
G row th is largely the outcom e o f m any genetic, horm onal, nutritional and
environm ental factors. It is particularly difficult to tease out the relative roles played
by each o f these com ponents in growth as they often w ork in concert. H ere some o f
the m ajor factors influencing grow th in general are sum m arised and those influences
w hich have a stronger influence either during the fetal or infancy periods are
discussed.
2.4a) Genetic and horm onal factors
Genetic factors play a crucial role in growth from the point o f conception through to
m aturation. In hum ans, height and w eight are highly correlated w ith parental height
and w eight (Tanner 1978, Byard et al. 1993). Indeed, body size and shape, deposition
o f fat and patterns o f growth are m ore strongly influenced by genetics than external
factors (M ueller 1986, Tanner 1989, H auspie et al. 1994, Sinclair and D angerfield
1998). G row th tem po, for exam ple, is highly influenced b y that o f the parents, w here