The entire period of growth can be divided into two major phases, i.e., Prenatal (before birth) and Postnatal (after birth). The prenatal phase is further divided in three distinct stages – the fertiized egg (ovum) or Zygote, the Embryo and the Foetus. The stages of postnatal phase are – infancy, childhood, adolescence, maturity and senescence.
Prenatal Growth
The period of prenatal growth is significantly important to the child’s future well-being; the fact remains that it is the period about which, certainly, we do not have much knowledge. For the first and second trimesters of pregnancy we have to depend on cross-sectional studies. In the second trimester we also have to rely almost completely on foetuses expelled from the uterus because one or the other was abnormal, whereas during the earliest weeks of pregnancy we have mostly normal products of social abortions. For later foetal life we can study infants born prematurely, making the conjecture that these children have grown before birth and will grow after it in exactly the same way as children who remain in the uterus the average length of time, which is in normal cases.
Period of Egg: Fertilized Egg (ovum) or Zygote (first 2 weeks): We do not know what forces are responsible for selecting one out of millions of sperm (i.e. male gamete) which fertilizes the ovum (i.e. female gamete). Fertilization take splace in one of the tubes which lead from the ovaries to the uterus. The fertilized egg spends some four to five days drifting down the tube and floating in the uterine cavity before it implants into the wall of the uterus (the female organ in which embryo/foetus develops). During this time the cells divide steadily so that at the time of implantation, the blastocyst as it is called consists of around 150 cells. After implantation, the outer layer of the blastocyst undergoes a series of changes which culminate in the formation of the placenta which gives nourishment to embryo/foetus. A small proportion of the inner layer develops into the embryo.
Period of the Embryo (2 to 8 weeks): The period of the embryo is considered to begin 2 weeks after fertilization and ends 8 weeks after fertilization. The child now is recognisably human, with arms and legs, a heart that beats, and a nervous system that shows the beginning of reflex responses to tactile stimuli, is called a foetus. At this stage it is about 3 cm long.
This is a hazardous period, and many more ova are fertilized than come to fruition. It is estimated that 10% fail to implant and of those that implant and become embryos half of them are spontaneously aborted, usually without the mother’s knowledge. Such abortion is in most cases due to developmental abnormalities, either of the embryo or of its protective and nutritive surrounding structures. 5% to 10% of fertilized ova have abnormalities of the chromosomes but amongst newborns it is only 0.5%. Spontaneous abortions take care of this situation when 90% to 95% of all conceptions with these abnormalities are rejected.
The counting of age in the prenatal period remains problematic. Traditionally, and because we have no better way, age tends to be counted from the first day of the last menstrual period. This occurs on an average 2 weeks before fertilization. Thus the most frequent age at birth is 280 days or 40 weeks, reckoned as ‘postmenstrual age’, but this represents only 38 weeks of true foetal age. However, there are difficulties in individual cases. The interval from menstruation to fertilization varies considerably; and again, menstrual bleeding may continue in some women for 1 or even 2 months after fertilization.
The velocity is not pronounced in the embryonic period. Initially, during the first 2 months differentiation of the originally homogeneous whole into regions, such as head, arms take place. Histogenesis which is the differentiation of cells into specialised tissues such as muscle and nerve also occurs same time. Each region transforms into a definite shape, by differential growth of cells or by cell migration due to the process called morphogenesis. This carries on until adulthood and in some parts of the body, into old age, though the major part of it is completed by the 8th postmenstrual week.
Period of the Foetus (9 to 40 weeks): As has already been explained reliable growth curves of the foetus are hard to come by. There are reliable data available for body length of foetuses from about 10 to 18 weeks of postmenstrual age, and for infants born prematurely from about 28 weeks onwards. No useful data is available for 18 and 28 weeks. Figure 1.1 shows the distance and velocity curves of body length in prenatal life, and for the first year after birth. The peak velocity is experienced at about 4 month’s postmenstrual age. The solid lines shows the actual length and length velocity; the interrupted lines interpret the theoretical curve which is expected if no uterine restriction takes place in the last weeks of pregnancy, followed by a compensating catch-up after birth.
Due to the continuing cellular multiplication the high rate of growth of the foetus takes place compared with that of the child. As the foetus gets older, the proportion of cells undergoing division in any tissue becomes gradually less and it is normally few new nerve cells and only a small proportion of new muscle cells appear after 30 postmenstrual weeks. By this time the velocity in linear dimensions drops sharply. There is however considerable difference in appearance of muscle and nerve cells of the foetus as compared those of the child or adult, due to the fact that early in development there is little cytoplasm around the nuclei. Great deal of intracellular substance and a much higher proportion of water compared to mature muscle are found in foetal muscles, while the later foetal and postnatal growth of muscle comprises primarily of building up the cytoplasm of the muscle cells. Then again salts are incorporated and the contractile proteins are formed as a result the cells become bigger in size, the intracellular substance mainly disappears and the concentration of water drops. This continues fairly vigorously till 3 years and slows down subsequently. It briefly speeds up again in adolescence, particularly in boys, under the influence of androgenic (male determining) hormones. In the foetal nerve cells cytoplasm is added, and the cell processes grow. Postnatal growth for most tissues is significant as a period of development and enlargement of existing cells, while in early foetal life cell division and the addition of new cells takes place.
It is also to be noted that growth in weight in the foetus follows the same general pattern as that of height, except that the peak velocity is reached later, usually at the 34th postmenstrual week. During the last 10 weeks in the uterus, the foetus stores considerable amounts of energy in the form of fat. Up till about 26 weeks postmenstrual age, most of the increase in foetal weight is due to accumulation of protein as the main cells of the body are built up. From then on fat begins to accumulate, both deep in the body and subcutaneously. It has been found that from about 30 to 40 postmenstrual weeks’ fat increases from nearly 30g to 430g. Since fat contains much more energy than protein or carbohydrate per unit volume this represents a large reserve of energy available for the first, perhaps critical, period after birth. Conversely, the creation of such a store represents a considerable drain on the energy resources of the mother in the last weeks of pregnancy.
The Effect of the Uterine Environment on Prenatal Growth: Evidence ascertains that, beginning at 34 to 36 weeks, the growth of the foetus slows down owing to the influence of the uterus, whose available space by that time becomes fully occupied. Twins slow down earlier, when their combined weight is approximately the 36-week weight of the singleton foetus (Tanner 2011). In Figure1.2, a velocity curve is plotted, created before birth from the differences between weight means of singleton babies born alive at periods from 24 to 40 weeks and after birth from differences in weight means in a mixed longitudinal study of a similar population in the U.K. A curve comparable in shape with usual growth curves could be constructed by joining the top, 32-week prenatal point with the first, 8-week postnatal point. Such a hypothetical curve would predict a peak weight velocity reached at about 34 weeks. However, between then and 40 weeks, growth is held up; and the increase in velocity in the first 8 weeks after birth represents a catch-up, on the part of those newborns that have been most delayed in the uterus. Thus, there is a significant negative correlation between length at birth and length gain in the first 6 months after birth, and also between weight at birth and weight gain in the first 6 months. The smaller the baby, on average, the more it grows at this time (Tanner, 1978).
In man it is observed that the correlation coefficient between length at birth and adult height is only about 0·3. Again, the coefficient rises sharply during the first year, and between length at age 2 and adult height the correlation coefficient is nearly 0·8. These figures also reflect maternal control of newborn size. However, it is not clear, how this control is exercised. The placenta grows at first more rapidly than the foetus, but from about 30 weeks onwards its growth rate becomes less than that of the foetus and the placenta/foetus ratio falls. The possibility could be that the placenta simply cannot increase its capacity to supply enough food to sustain the rapid 34-week foetal velocity. In animals like mice and guinea pigs it seems likely that the limiting factor is blood flow, the size of the placenta depending on the pressure at which the maternal blood reaches it, and the size of the foetus depending, in turn, on the size of the placenta. Whether this is also important in man is not yet known.
Poor environmental circumstances, especially of nutrition (inappropriate or low nutrition), result in lowered birth weight in the human being. This seems chiefly to be due to a reduced rate of growth in the last 2 to 4 weeks of foetal life, for mean weights of babies born at 36 weeks to 38 weeks in various parts of the world under various circumstances are rather similar. Mothers who, because of adverse socio-economic circumstances in their own childhood, have not achieved their full growth potential may produce smaller foetuses than they would have done had they grown up under better conditions. Thus, two consecutive generations or even more may be needed to reverse the effect of poor environment on birth weight. In Guatemalan villages, for example, mothers of short stature had babies of lower birth weight than did mothers of medium stature. A food supplement given to the mothers during pregnancy had more effect on the birth weight of children born to short mothers than on those born to medium-sized mothers, but it did not wholly eliminate the difference as observed by Tanner.
So-called ‘Premature’ Babies: The average length of gestation is 280 days or 40 weeks measured on an average from the beginning of the first day of the last menstrual period. Nonetheless considerable individual variation has also been observed. An international agreement deliberates lengths of gestation from 259 days (or 37 completed weeks) to 293 days (or 42 completed weeks). Babies born within these period are called term babies, earlier to it are called pre-term babies and those born later are post-term babies. Latest studies conclude that the limits of normal term should be between 38 and 41 completed weeks rather than between 37 and 42 weeks.
Until a few years ago all babies who weighed less than 2500 g (5½lb.) at birth were designated ‘premature’ irrespective of their length of gestation or physiological state. This definition as promulgated by World Health Organization in 1948 caused much confusion and has now been dropped; the word ‘premature’ has disappeared from scientific use. Babies less than 2,500 g at birth according to World Health Organization in 1961 are called ‘low birth weight’ babies. This low birth weight may be due either to their being born early, or to their being babies who are pathologically small for their length of gestation. The distinction is made by the use of standards such as the one shown in Figure 1.3, which gives the centiles for first-born girls only; children subsequent to the first one are heavier on average by 110 g and boys are heavier than girls on average by 150 g. The baby marked A weighed 2,500 g but was born a month early, at 36 weeks. She is at the 25th centile for first-born girls of this gestational age, thus perfectly normally grown. The baby B, also of 2.500 g, born at 40 weeks (full-term), is below the 5th centile and thus of very questionable normality. Such a baby is known colloquially as ‘small-for-dates’.
There exists a tendency for some mothers always to have relatively small babies and other mothers relatively large ones. Therefore, a more critical standard can be constructed in which the weight of the new baby is compared with the birth weight of his brothers and sisters with an allowance given for length of gestation. To a great extent this trait of size at birth runs in families and therefore, is inherited, possibly through characteristics of the maternal uterus rather than of the foetus itself. This variation between families, however, remains strictly within the normal range of birth weights. When we talk about small-for-dates babies we mean those who are beyond these limits. A small overlap exists, for a very few normal babies are necessarily below the arbitrary limit set for the upper bound of smallfor-dates infants.
The distinction between pre-term babies of normal weight for length of gestation and babies who are light for their often normal length of gestation is an important one. The purely pre-term infants catch up reasonably well and seem little worse for their earlier experience of the outside world. Even those born as early as 28 weeks weighing 1000 g can be seen these days to grow at the very rapid rate appropriate to their age and sent home 8 to 10 weeks later at the normal weight for a full-term infant. This is possible providing nutritional supplements enriched in nutrients in appropriate quantities.
On the other hand, babies who are light for length of gestation, i.e. small-fordates, do not on average catch up to normal, although they diminish the gap a little. It is noted that the average small-for-dates child reaches about the 25th centile for height, which implies that a considerable proportion of such children remain below the 3rd centile limits of normal. A substantial proportion fails also to develop the same level of mental ability as normal children.
Children can of course be both pre-term and small-for-dates. About one-third of pre-term babies in the U.K. appear to be so. Such children fall clearly in the small-for-dates category. The deficits in later size and ability get worse as the birthweight decreases. Children between 2,000 and 2,500 g at birth having fullterm show little impairment of ability and only a slight size deficit. A considerable proportion of those under 2,000 g, however, have some mental or neurological defect. The chance of perinatal death (i.e. death-within -24-hours after birth) increases. In a study of 44,000 consecutive births in the Royal Victoria Hospital in Montreal, Usher and McLean found that the preinatal mortality was 54 per 1,000 births in babies born at term i.e.37 to 42 weeks with weights under the 3rd centile for gestational age compared with 6 per 1,000 in babies with weights between the 30th and 70th centiles. In babies of all lengths of gestation, perinatal mortality was 16 per 1,000 amongst babies whose weights were between the 3rd and 97th centiles for gestational age, but 189 per 1,000 for those whose weights were under the 3rd centile for gestational age (Tanner, 1978).
Thus, it is documented that the prognosis for a small child born after a normallength gestation is very different from the prediction for an equally small child born after a shortened gestation. Coming out of the uterus early is not in itself harmful, while growing less than normally during a full uterine stay implies pathology of foetus, placenta or mother.
It is a demonstrated fact that small-for-dates babies are a heterogeneous group, produced by several different causes. In countries where severe maternal malnutrition occurs a proportion of small-for-dates babies are definitely due to maternal malnutrition. But the malnutrition has to be fairly severe, for in this situation the foetus is protected at the expense of the mother. In well-nourished mothers disorders of the placenta may be responsible. Smoking in pregnancy is seen to cause, a reduction of 180 g on average, in full-term foetal weight and a 30% increase in perinatal mortality. The size of reduction persists throughout childhood. This reduction of weight brings some babies into the small-for-dates category. Alcohol appears also to reduce foetal weight, and a large consumption of alcohol may affect the foetus directly. This may cause a recognisable disorder known as the foetal alcohol syndrome. Because of this syndrome, the face of the baby has a characteristic appearance, due to insufficient development of parts around the eyes, nose and upper lip. Some maternal diseases cause smallnessfor-dates, in particular rubella (German measles), which also may cause specific deformities and deafness. In other instances it seems the foetus itself is disordered and lacks the capacity to grow properly. According to some studies, mothers of small-for-dates babies have a higher proportion of abnormal outcomes in other conceptions (miscarriages, etc.) than do mothers of normal-sized babies.
Since the worst period for the small-for-dates baby seems to be the last part of pregnancy, when she is, or should be, growing most, many doctors are now advocating removal of these foetuses at 36 weeks, or even at 34 weeks in severe cases. This is done by straightforward induction of labour and vaginal delivery. Much research is therefore in progress to devise means of recognising these foetuses in time for this action to be taken. To date, the most helpful guide to intra-uterine growth insufficiency is measurement of the foetus by ultrasonic means (Tanner, 1978). Ultrasound may be used early in pregnancy to measure the length of the foetus’s back from crown of head to rump, and from about 13 postmenstrual weeks to measure the width of the head and the circumference of the abdomen. It seems that screening all babies for crown to rump length between 6 and 12 weeks, for head width between 13 and 20 weeks, and for abdominal circumference at 32 weeks, would detect over 90% of all small-for-dates babies, with a negligible number of false positives (i.e. babies so diagnosed who were really normal). Such a screening programme is well within the capabilities of the medical services of industrialised countries.
Postnatal Growth (birth to maturity)
The amount of growth achieved obviously depends on the time for which growth proceeds and on the speed of growth per unit time. Measurements taken on a single individual at intervals can be plotted against time to produce a graph of progress, whether they are derived from the whole body (e.g. height) or from one of its components (e.g. leg length).
Figure 1.4 shows the most famous of all records of postnatal human growth. It demonstrates the height of a single boy, measured every 6 months from birth to 18 years. This is the oldest longitudinal record in existence, and it remains, one of the best for the necessary illustration. It was made during the years 1759-77 by Count Philibert de Montbeillard on his son and it was published by Buffon in a supplement to the Histoire Naturelle.
In Figure 1.4a is plotted the height attained at successive ages while in Figure 4b the increments in height from one age to the next, expressed as the rate of growth per year. If we think of growth as a form of motion and considered analogous to the journey of a train then the upper curve is one of distance traveled and the lower curve, one of velocity. The velocity, or rate of growth, naturally reflects the child’s state at any particular time better than does the distance achieved, which depends largely on how much the child has grown in all the preceding years. Thus, for those substances which change in amount with age, the concentrations in blood and tissues are more likely to run parallel to the velocity than to the distance curve. In some circumstances, it is the acceleration rather than the velocity curves which best reflect physiological events (Tanner, 1978).
Figure 1.4b shows that in general the velocity of growth decreases from birth. From 13 to 15 years in this particular boy, there is a marked acceleration of growth, called the adolescent growth spurt. Some writers although distinguish sharply the terms ‘adolescence’ and ‘puberty”. Some use puberty to refer to physical changes, and adolescence to refer to psychosocial ones. From birth until age 4 or 5 the rate of growth in height declines rapidly, and then the decline, or in other words deceleration gets gradually less, so that in some children the velocity is practically constant from 5 or 6 up to the beginning of the adolescent spurt. A slight increase in velocity is sometimes seen to occur between about 6 and 8 years. This phenomenon provides a second wave on the general velocity curve, sometimes called as ‘pre-adolescent’ spurt (Tanner, 1978).
The Adolescent Growth Spurt: The adolescent growth spurt is a constant phenomenon and occurs in all children, though it varies in intensity and duration from one child to another. The difference in size in men and women is to a large degree due to differences in timing and intensity of the adolescent spurt. Before adolescent spurt boys and girls differ only by about 2% in height, but after it by an average of about 8%. The difference is partly because of later occurrence of the male spurt allowing an extra period of growth, and partly because of a greater intensity of the spurt (Tanner, 1978).
Figure 1.5 shows the typical girl as slightly shorter than the typical boy at all ages until adolescence. She becomes taller shortly after 11·0 years because her adolescent spurt takes place two years earlier than the boys. At age 14·0 she is surpassed again in height by the typical boy, whose adolescent spurt has now started, whereas her adolescence is nearly finished. In the same way, the typical girl weighs a little less than the boy at birth, equals him at age 8·0, becomes heavier at age 9 or 10 and remains so till about age 14·5 (Tanner, 1978).
The velocity curves given in Figure 1.6 show these processes more clearly. At birth the typical boy is growing slightly faster than the typical girl but the velocities become equal at about 7 months and then the girl grows faster until about age 4·0. From then till adolescence no difference in velocity can be detected. The sex difference is best thought of, perhaps, in terms of acceleration, the boy decelerating harder than the girl over the first four years. The typical girl begins her adolescent spurt in height at about 10·5 and reaches peak height velocity at approximately 12·0 in the UK, and about three months earlier in the U.S.A. The boy begins his spurt and reaches his peak just two years later. The boys’ peak is higher than the girls’, on an average by 10.3 centimeters a year compared with the girls’ 9·0 cm/yr as observed in U.K. It is noted that girls are always in advance of boys (i.e. closer to their final mature status), even at birth (Tanner, 1978).