The effect of drugs on fetal development is heavily dependent therefore on the gestation at the time of administration as well as the actual potential for teratogenicity of the agent concerned. This will be discussed later.
| Organ | Differentiation | Complete Formation |
|---|---|---|
| Spinal cord | 3–4 weeks | 20 weeks |
| Brain | 3 | 28 |
| Eyes | 3 | 20–24 |
| Olfactory apparatus | 4–5 | 8 |
| Auditory apparatus | 3–4 | 24–28 |
| Respiratory system | 5 | 24–28 |
| Heart | 3 | 6 |
| Gastro-intestinal system | 3 | 24 |
| Liver | 3–4 | 12 |
| Renal system | 4–5 | 12 |
| Genital system | 5 | 7 |
| Face | 3–4 | 8 |
| Limbs | 4–5 | 8 |
Fetal Cardiovascular Development
The respiratory function of the placenta requires that oxygenated blood be returned via the umbilical vein and into the fetal circulation. The changes which then occur at birth are dramatic.
Oxygenated blood from the placenta returns to the fetus via the umbilical vein. This vessel penetrates the liver and gives off small branches to that organ. Most of the blood is directed via the ductus venosus into the inferior vena cava which is carrying the returning non-oxygenated blood from the lower limbs, kidneys, liver, etc. There is only partial mixing of the two streams and most of the oxygenated blood is directed to the crista dividens at the upper end of the inferior vena cava through the foramen ovale into the left atrium and thence to the left ventricle and aorta.
CARDIOVASCULAR SYSTEM
This relatively well-oxygenated blood supplies the head and upper extremities. The remainder of the blood from the superior vena cava mixes with that of the inferior vena cava, passes to the right ventricle and thence to the pulmonary artery. A small amount of blood goes to the lungs. Most of it passes on via the ductus arteriosus into the aorta beyond the vessels supplying the head and upper extremities. Thereafter it passes down the aorta to supply the viscera and lower limbs. Little blood actually goes to the lower limbs. Most at this level passes into the umbilical arteries which arise as branches of the right and left internal iliac arteries. At birth the umbilical vessels contract. Breathing helps to create a negative thoracic pressure thus sucking more blood from the pulmonary artery into the lungs and diverting it from the ductus arteriosus which gradually closes. The foramen ovale is a valvular opening, the valve functioning from right to left. The left atrial pressure rises and closes this valve.
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The greatest volume of cardiac output from both ventricles, around 40%, goes to the placenta. The organ which receives the greatest flow is the brain which receives about 13%.
The autonomic nervous system is the principal control mechanism for fetal heart rate, stroke volume and blood pressure. In the first half of pregnancy control is chiefly by the sympathetic system. In the second half the parasympathetic system becomes increasingly dominant. It is this development which explains the reduction in fetal heart rate with advancing gestation.
FETAL HAEMATOLOGY
The fetus is hypoxic relative to the maternal oxygen state yet does not become acidotic. There are three factors accounting for this: fetal haemoglobin concentration is high, around 180 g/l, the cardiac output is greater, and finally, the oxygen affinity of fetal haemoglobin is greater. Fetal haemoglobin is composed of two α and two γ chains. The presence of γ chains increases oxygen affinity beyond that of adult haemoglobin so that for a given oxygen tension in the blood a greater percentage oxygen saturation is obtained. This is seen in comparisons of the oxygen dissociation curves for fetal and maternal haemoglobin.
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FETAL LUNG DEVELOPMENT
The placenta is the organ of respiration for the fetus but adaptation to extra-uterine life requires that the lungs go through four recognised phases of development. The last of these, the terminal sac period, is when alveolar development occurs from 24 weeks gestation to term. Fetal breathing movements are established even before this and are required for proper anatomical development of the lungs. Absence of fetal breathing movements in later pregnancy may be a sign of fetal acidosis and its identification can be used to assess fetal well being. This will be discussed later.
During this time development of pneumocytes occurs and production of surface acting phospholipids is established. These components of surfactant are required to enable lung function to occur postnatally. Surfactant deficiency, a consequence of prematurity, causes respiratory distress syndrome in the newborn and is the greatest determinant of outcome in babies born preterm.
MATERNAL PHYSIOLOGY
Enormous physiological changes occur throughout pregnancy and may not be clinically obvious. Thus, alterations in metabolic rate are more apparent than, for example, changes in the renin angiotensin system.
Nevertheless the alterations in the physiology require changes in energy consumption and use.
The energy demands of pregnancy derive from:
a) Basic physiological processes such as respiration, circulation, digestion, secretion, thermoregulation, growth and repair. These account for 66% of the total energy requirements in the non-pregnant female and amount to 1440 kcal/day. It is these processes which undergo greatest increase in pregnancy due to the demands of the fetus and placenta, uterus, breast growth, etc.
b) Activities of daily living. These account for 17% of the total energy use in the non-pregnant state, approximately 360 kcal/day. Advancing pregnancy usually entails some reduction in activity though there is great individual variation in this.
c) Work. The requirements associated with work differ with occupation but comprise around 10% for most women or 150–200kcal/day. This contribution to energy requirements generally reduces with advancing gestation, notably in the third trimester.
d) Specific dynamic action of food. Metabolism appears to be stimulated by food intake and comprises around 7% of the total or 150kcal/day. This should be met by increased consumption during pregnancy.
Overall there is a 14% increase in energy requirement during pregnancy.
During lactation a further increase is required for milk production and the total requirements will be in the region of 3000 kcal/day.
WEIGHT INCREASE
These metabolic changes, accompanied by fetal growth, result in an increase in weight of around 25% of the non-pregnant weight: approximately 12.5kg in the average woman. There is marked variation in normal women but the main increase occurs in the second half of pregnancy and is usually around 0.5kg per week. Towards term the rate of gain diminishes and weight may fall after 40weeks.
The increase is due to the growth of the conceptus, enlargement of maternal organs, maternal storage of fat and protein and increase in maternal blood volume and interstitial fluid.
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The increased metabolic rate is largely due to the fetus and leads to an increase in maternal oxygen consumption of around 20%. The factors governing this are chiefly endocrine. The pituitary gland enlarges and there is a 13% increase in size of the thyroid.
The fundamental hypothalamic–pituitary–thyroid relationships remain intact.
CARBOHYDRATE METABOLISM
In the non-pregnant state ingested glucose is dealt with in four ways. Under the influence of insulin it may be deposited in the liver as glycogen. Some escapes into the general circulation and a proportion of this is metabolised directly by the tissues: some is converted to depot fat and a further portion is stored as muscle glycogen again with the aid of insulin.
The blood sugar is maintained between 4.5 and 5.5mmol/litre (80–100mg/dl). Sugar which passes out in the renal glomerular filtrate is never in excess of the amount which can be reabsorbed by the tubules, and none appears in the urine.
A marked alteration in carbohydrate metabolism occurs in pregnancy.
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