It is a rather simple fact, in biological terms, that the unborn child develops continuously in a continuum. There are no particularly arbitrary points in it where anything dramatic or different happens. It is just part of an ongoing stream and although one uses terms like zygote or morular or blastocyst or embryo or fetus, one uses these no more technically or no more self-consciously than you would talk about someone being a newborn or an infant or a toddler or an adolescent or a septuagenarian. These are simply names given to particular stages or ages of development.
The other feature which is quite apparent on this development scale or view, is that the units of time used to describe or chronicle these events has to change with the events.
In the earliest time of development, hours are the appropriate unit. There is a difference between an eighteen and a twenty-two hour zygote.
Then days become an appropriate unit. One can talk about a nineteen or twenty-two day embryo and there are quite obvious differences to an experienced embryologist between such babies.
Then you reach a time where weeks are an appropriate unit and this is satisfactory for most of the pregnancy thereafter. Then of course after birth months are adequate – we talk about a child being six months old or eight months old.
Then you reach a stage where years are satisfactory units, you are sixteen or seventeen or eighteen years old; and then most of us reach a time where decades are quite good enough. We would rather not note the passing of those either. In other words, the scale on which one chronicles the events of a human life does change.
We spend nine months, three-quarters of a year in the uterus; and three score years and ten, (approximately three-quarters of a century), out of it. In those terms, intrauterine life occupies about one percent of our earthly existence. But if we look on intrauterine life, not simply on a chronological scale, (in which it seems rather insignificant), but on a developmental scale, we get a rather different picture.
We each began life as a single cell and as an adult we each have about thirty million million cells in our body. And the question is, how do you get from the one to the thirty million million? Well the one cell divides into two and that is the first generation of cell division. The two cells divide into four and that is the second generation; and the four into eight, the third; and so on. And the question is, how many generations of such cell multiplication or replication divisions do you need to get to thirty million million? The answer is approximately forty-five.
Now of those forty-five generations of growth or multiplication divisions, eight have occurred by the time we are implanted in the walls of our mother’s uterus: nearly one-fifth. Thirty, or two-thirds of them, have occurred by eight weeks gestation; thirty-nine of them have occurred by seven months, or twenty-eight weeks gestation; forty-one by the time we are born and the remaining tedious four occupy the whole of childhood and adolescence, and then there are no more.
Looking at things on a developmental scale, forty-one of those forty-five generations of cell division have occurred by the time of birth: in developmental terms we spend ninety percent of our life in utero, and indeed the die is very far cast as to the type of person we are going to be – (physically that is, our intellectual capacities, and all manner of body functions).
This concept or view of things is very important. Of course it underpins the importance of prenatal medicine, the medicine of the unborn child, since events going wrong during that dramatic period of development can then cast a shadow so far into our chronological future. It is important to bear in mind the clinical fact that the early divisions are not only concerned with increase in number of cells but increase in complexity with formation of body organs. And insofar as rapidly multiplying cells are vulnerable to a variety of insults, this does explain the susceptibility of the unborn child, particularly in the early stages of pregnancy to noxious influences two of which particularly – say thalidomide and rubella – are good examples.
After we have finished our adolescent growth spurt beyond puberty, probably somewhere in the range of the fifteenth to the eighteenth year, the only remaining cell divisions are cell replacement or repair divisions. There are no more growth divisions. Even that scale should be modified because not all structures develop at the same rate.
In particular, the precocious growth of the human brain and major sense organs means that we have completed forty-three or nearly forty-four of them by the time we are born. In other words, these are even more accelerated than the scale shows.
The brain is practically complete then on birth. Our eyeballs are three-fifths adult size. Our brain does not grow. It is very large in proportion to our body weight at birth; it subsequently declines as a proportion of it. So our brains are even further down the road than the scale suggests, at birth.
The brain is the most dramatic and early-developing of all the body systems. It predominates in determining the anatomical confirmation of the early embryo and is ahead of development of other body structures and functions by birth. That fact provides the child with the ability, as it were, to dictate the time of its birth. Such processes as these all depend on two things in maturation or ‘maturifying’ as it were, of body structures. And it also depends on coordinating a number of different parts of the body, and the two great integrating systems in the body are the circulation and the nervous system. They average out, they accumulate and take in, coordinate information from different parts of the body. So it is not just a biological fact that this growth has accelerated, it would appear an organizational necessity.
Clearly, life begins considerably before birth. A number of teaching films showing the fusion of the genetic material that derived from the mother (carried in the ovum); and that derived from the father (carried in the sperm): have considered the moment of fusion of those two paired amounts of nuclear material as being the instant when a new life begins.
Interestingly, there is now evidence that even before that fusion has occurred, information has been communicated between those nuclei that determines subsequent development. The one cell divides into two and this continues and a multiplying ball of cells (apparently at that stage with little to distinguish one cell from the other), and in fact with one total bulk of cells not much increasing, so the individual cells get smaller until you have a ball of two or three hundred of them, the so-called morula (from the Latin word meaning “a mulberry”) – an accumulation of cells that just look like a common blackberry or such compartmentalized fruit.
An experienced geneticist can tell the sex of an unborn child at that stage from an examination of the nuclei in the cells, although not from ordinary external appearances. At that stage the zygote, the conceptus, is still free-living. It is contained inside a membrane, a clear membrane, the zona pellucida, which seems to serve the very useful function of stopping the conceptus sticking, arresting and starting development in places it should not. In other words, the surface of the ball of cells is itself very sticky so it is, as it were, to have a plastic wrap around it to stop it sticking until it is in the right place. And in that manner this free living ball of cells progresses down mother’s fallopian tubes for some six to eight days, when it loses its protective plactic sheath as it were, and attaches to the wall of the uterus.
At this stage there is starting to appear a distinction within the assemblage of cells, a cleft appears so that one has a nubbin or body of cells on the inside (called the inner cell mass which is going to mainly form baby); and an outer cell mass which is going to essentially form placenta. It is not the only structure which contributes to the placenta. And at this stage the conceptus, burrowing into the receptive wall of mother’s uterus, now has available to it nutrient materials from mother’s blood stream which it encounters, and not just the fluids which it found in the fallopian tube and uterine cavity.
From there on, events are very rapid indeed. The outer cell mass develops communications; it erodes the wall of maternal blood vessels (the uterine wall), so that the cells are actually hosed down by maternal blood as it were. It comes into very close acquisition with the maternal blood stream. The inner cell mass first of all develops two more cavities within it and it is only the small plaque of tissue in between those two cavities which is actually going to form the future baby.
The rest are all additional, extracorporeal structures, which are necessary to the baby in its early life. One of these on what will be the underside of the baby, the so-called yolk sac, never achieves any great biological significance in the human except that it is the site of earliest formation of tissue which is going to form blood vessels, blood cells, and the heart. The other cavity on the back of the baby is going to enlarge more and more and is going to form the eventual amniotic cavity containing its amniotic fluid. That is, the amniotic fluid, the sac and all of its contents, are part of baby. The fluid is very complex in its origin. Its different constituents come from different points: some of the fluid crosses the membranes, some arrives in the baby’s kidneys, and so on; so it is quite complex in its formation and disposal.
Meanwhile the layer of cells in between these two cavities which is going to form the definitive baby, first of all develops a striking ridge along its back. It starts off as a proliferation of two ridges of cells with a trough between them. The walls of those ridges grow up until they meet and close off a tube and that tube is the future nervous system: the spinal cord, and the brain. And the anterior or cephalic end of that tube early in human fetal life or embryonic life, begins to expand enormously so that again it dominates the appearance of say, the three week embryo.
At the same time the primitive heart is beginning to develop. By three and a half weeks, as we said before, twenty-four to twenty-five days from conception, the heart begins beating. At that stage it is simply a tube with no valves in it, so the first circulation the baby has isn’t, in fact, circulation at all. It is an ebb and flow system as physiologists before Harvey imagined. But very soon valves develop and then, with a pump to give pressure and valves to give direction, the baby has circulation. At about four weeks, mother, normally, would be two weeks past her period and would suspect she was pregnant.
Over the next ten days, between twenty-four and thirty-five days, there is rapid development of all organ systems so that by twenty-eight days, four weeks from conception, the baby (about one-quarter of an inch long), has a brain, a liver, eyes structures of the inner ear, kidney rudiments and a heart pumping blood that he has made himself.
By thirty-five days there is extensive proliferation of nervous tissue, muscle box are appearing and brain wave electrical activity can be recorded for the first time. By forty-five days, about the time of mother’s second missed period, the baby’s skeleton is complete and cartilage initially, not bone. The buds of the milk teeth appear, baby has grown arms and legs and has sprouted fingers and toes on the end of them, and for a few days has been making the first movements of his trunk and new grown limbs.
By six weeks our baby is about half an inch long and by eight weeks, its length which is now very rapidly increasing, is an inch and a half or more. By nine weeks the early, rather marionette-like movements of the baby are becoming much more graceful and by sixty-three days the baby will squint if his face is stroked and can attempt to grasp an object placed in his palm and make a fist (not a very tight one), but can in fact make a fist. Thumb sucking has also been photographed in the nine-week abortions.
By twelve weeks there is simply further refinement of structures that are already present. By sixteen weeks for instance, the baby now has his own individual fingerprints and has developed eyelashes and eyebrows. At this stage also it is quite apparent from amniocentesis for instance, pricking the babies with needles, that they are quite responsive to external stimuli. It is also from now on that mother will begin to feel movements because they are strong enough to be felt through her uterus. This is the point traditionally referred to as “quickening,” although of course the movements are detectable much earlier.
Somewhere about the nineteen to twenty week mark, one first can usefully monitor fetal responses to sound. We have constructed audiometric curves on fetuses as early as twenty-two weeks. For instance, to reassure deaf mute mothers that their babies could hear. And you can also at this stage demonstrate quite refined modifications of, for instance, a response to sound. We can demonstrate both habituation and the fact that the baby gets bored with repeated signals and after a while will ignore them, and we can also demonstrate conditioning, — classical Pavlovian conditioning by which the baby may be alerted by a first signal to a second different one. You can train a baby to predict or expect a stimulus: such learning has been recorded as early as twenty-two weeks.
Earliest responses to external light have been demonstrated by twenty-four weeks but again that may depend on just the technology available to us. The baby at this stage is very slim. While the muscle box are present there is very little in the way of subcutaneous fat, which normally gives the body its nice rounded out appearance.
The baby is also still a minority party in a kingdom of its own making. The membranes, placenta and fluid make up a greater bulk than the actual baby does himself. But, as I have remarked, the structures are necessary to the baby in its environment-his placenta with all its many functions, and the amniotic cavity which gives the baby room to move, and movement is necessary for the proper development of bones and muscles and joints. The placenta, along with the fetal membranes and fluid, are formed entirely by the conceptus. The placenta represents a frontier through which nutrient, waste, and other materials may be exchanged between the tissues of mother and baby. The umbilical cord connects the baby, not to its mother, but, you see, to its own organ, the placenta.
From the time of about twenty-four weeks, there is actually a slim chance of fetal survival, if delivered, and that steadily improves as time goes on. So that at twenty-six weeks one gets a regular trickle of survivors and in better prenatal units, by twenty-eight weeks, one is expecting a survival better than eighty, usually around ninety percent.
But progressively the baby is being better and better prepared for extrauterine life and normally the main thing that happens in the last ten or twelve weeks of pregnancy is a laying down of subcutaneous fat which is an important food reserve for the baby so that it loses its scraggly look; and also increasingly glycogen, which is a manner in which glucose is stored, is laid down in fetal liver. Up until about twenty-eight weeks that fuel has been mainly stored in the placenta; from twenty-eight weeks on it is increasingly stored within the baby, so the baby delivered at term has quite extensive fuel resources which would be denied to the baby delivered very prematurely.
In general, one is forced to recognize that the fetus, not the mother, is in command of the pregnancy. This is a conclusion forced on one physiologically in that it is the conceptus who organizes his own development and environs in terms of the things we have already mentioned – his fluid and placenta. The baby develops and grows these all himself. It is the baby who solves his important environmental problems, particularly preventing the mother’s next menstrual period. And this is a remarkable performance when you realize that at this stage the conceptus is little more than the size of a grain of sugar measured in micrograms, and yet must influence a mother weighing over a thousand million times more.
It is the baby, or the conceptus, who produces all the hormones necessary for the success of pregnancy; who induces all the physical or physiological changes and adjustments necessary in mother’s body in pregnancy. These are all induced by the unborn child. He further determines which way he will lie in pregnancy and which way he will present in labour.
And finally, it is the baby who decides, the unilateral decision generally, when he will be born. When he is done – brown on both sides, as it were, — time to be born. If these are simple physiological facts of life, they also have an important bearing in clinical obstetrics in that all the problems in obstetrics which can be solved by pulling, and pushing and cutting (and I say that without any denigration of the great and famous, the mechanical obstetricians who have contributed so much to the safety of pregnancy for women), that nevertheless the major unsolved problems in prematurity – like toxemia, premature labour and so on – are unsolvable until we have a better understanding of fetal physiology.
