antenatal development

The embryonic period

of human antenatal development starts with fusion of the sperm and egg. Fertilization occurs in the Fallopian tube, usually within 12 hours of the release of the egg from the ovary (‘ovulation’). The chromosomes of mother and father intermingle, and shortly afterwards, the first cell division takes place. By the time that implantation takes place in the uterus a week later, the ‘conceptus’ contains around 100 cells and is called a ‘blastocyst’. Following implantation, an ‘embryonic disk’ becomes distinct from the other cells, and at 3 weeks after conception, or one week after the first missed menstrual period, this becomes a definable embryo. (Other cellular components of the conceptus will form the amniotic sac, the umbilical cord, and part of the placenta). The early embryo contains a notochord from which the spine develops, and the three germ layers from which all tissues and organs develop: the ectoderm, which gives rise to skin and nervous tissue; the mesoderm, which gives rise to muscles, muscular coats of the various tubular structures, connective tissues, and blood vessels; and the endoderm, which gives rise to the linings of the lungs and digestive tract and the glandular parts of organs like the liver and pancreas.

As the notochord develops, the overlying ectoderm thickens to form the neural plate which subsequently folds and fuses to form the neural tube: this will become the brain and spinal cord. Disturbances in this process may produce some of the more common congenital abnormalities: the neural tube defects. These include anencephaly, in which the brain and skull are missing, and spina bifida, in which the spinal cord is both abnormal and usually uncovered by skin. Neural tube defects are most common in Celtic populations of Western Europe and it is now known that the risk of these serious defects can be minimized if the mother takes the vitamin, folic acid, before and during early pregnancy. They can also be diagnosed by ultrasound examination later during pregnancy.

Between the fourth and eighth week after conception, most of the major organ systems start to form in the embryo, although it is very much later before these start to function properly. The process of embryogenesis is highly complex. Major advances are now taking place in our understanding of the genetic control of the cell migrations, cell proliferation, and programmed cell death (‘apoptosis’) that need to happen in a highly co-ordinated fashion over a short time-scale for the successful development of an individual. Many of these insights have emerged from study of the fruitfly, Drosophila.

From around 5 weeks after conception and 7 weeks after the mother's last menstrual period, it becomes possible to identify the embryo on an ultrasound scan. As the pregnancy advances, more and more detail can be seen so that, by 18 weeks, normality can be confirmed — or many subtle abnormalities can be identified. Around 15% of pregnancies miscarry, usually in the early weeks of pregnancy. The majority of these unsuccessful pregnancies have abnormal numbers of chromosomes, notably one extra, one too few, or a full extra complement. Many of these pregnancies are clearly abnormal on ultrasound examination long before the miscarriage occurs. Conversely, many women who have bled in early pregnancy can be reassured by normal ultrasound findings that their pregnancy is likely to continue.

Ultrasound has been a pivotal development in our ability to study the unborn child. The technique developed from the pioneering studies, in the 1950s and 1960s, of Ian Donald, Professor of Obstetrics and Gynaecology in Glasgow. He applied to human imaging the technology used to detect flaws in metal in engineering works. Now all maternity units in developed countries rely extensively on ultrasound imaging to monitor the growth and development of the fetus.

The fetal period

of antenatal development starts 9 weeks after fertilization, when the major organs have been formed and the embryo has reached 33 mm length from the crown of the head to the rump. It is characterized by rapid growth and, in the later stages, by maturing function of the different organ systems.

Throughout the pregnancy the fetus obtains nutrients and oxygen from the mother's blood, by transfer in the placenta to its own umbilical cord blood, and it excretes waste products of metabolism by the same route in reverse. In the great majority of instances, the fetus progresses normally to maturity, and is born at full term with fully functional organs, becoming a healthy neonate and infant.

There can, however, be damage during development due to a variety of teratogens, collectively defined as any agent or factor that when present during prenatal life produces a permanent alteration in form or function in the offspring. This can be a chemical, drug, infectious, or physical agent, or a maternal condition.

The fetus is less vulnerable than the embryo to these extraneous damaging agents, although infections such as syphilis or toxoplasmosis can cause serious damage in later pregnancy.

Fetal alcohol syndrome

The effects on the fetus of maternal ingestion of alcohol were first described in Europe in 1968. World-wide studies have now revealed a consistent picture of prenatal and postnatal growth deficiency with microcephaly (undersized head), mental handicap, a characteristic facial appearance, and heart abnormalities. The microcephaly is secondary to the disordered brain development resulting from alcohol exposure. Typical facial features include narrow eyes, flat nasal bridge, underdeveloped jaw, and thin upper lip. Speech, language, and behavioural problems, including severe hyperactivity and attention deficit disorders, contribute to the learning disabilities characteristically found in these children. Fetal alcohol syndrome (FAS) is estimated to occur in 30–40% of pregnant women who consume 3 oz (85 ml) of absolute alcohol per day. Large but lesser degrees of alcohol consumption are associated with intrauterine growth retardation, learning difficulties, and hyperactive behaviour. During the neonatal period the infant may show jitteriness and poor feeding similar to those features found with misuse of other substances. The term ‘alcohol-related birth defects’ is now used to reflect the range of anomalies associated with alcohol consumption during pregnancy.

Drug addiction

has effects in pregnancy that include miscarriage, fetal malformation (genito-urinary), fetal growth retardation, liver damage, ante-partum haemorrhage, fetal distress in labour, prematurity, and brain damage. After birth the infant is difficult to feed, jittery, and may have long-term problems from defective development of the nervous system. Cocaine usage is an increasing problem world-wide, resulting in vasoconstriction and hypertension in both the mother and the fetus. Attributed effects on the fetus include limb reduction, cerebrovascular accidents, and long-term neuro-behavioural disorders.

Amphetamines, like cocaine, are psychomotor stimulants, previously used primarily by those involved in sports and entertainment to enhance performance. They potentiate the action of noradrenaline, dopamine, and serotonin but, unlike cocaine, they appear to exert their central nervous system effects primarily by enhancing the release of neurotransmitters from pre-synaptic neurones. In children born to addicted mothers cardiovascular malformations have been described, and these children subsequently exhibit disturbed behaviour including hyperactivity, aggressiveness, and sleep disturbances. In New York city the proportion of women in the known addicted population rose from 14% in 1968 to 25% in 1973 and was expected to be 40% in 1995. In the US women make up approximately 30% of the drug treatment hospital admissions and 25% of the alcohol treatment admissions. In addition to the side effects produced by alcohol, nicotine, and prescription drugs, there are major problems now arising from the abuse of amphetamines, heroin, and cocaine. With the emergence of cocaine, especially in its ‘crack’ or smoked form, there has been an alarming increase in the incidence of fetal exposure to the drug. Studies in the US indicate that 10–15% of major urban area newborn births are affected by cocaine use. A majority of women who use cocaine during pregnancy are ‘poly drug’ users and take alcohol, marijuana, and heroin in addition to the cocaine.

Premature labour

is a major threat to the fetus, when it is born before its organs have matured sufficiently to ensure survival outside the uterus. However, modern neonatal intensive care does allow the survival of many premature babies that would have perished in the past. The lungs are the most critical organs. Their maturity can be accelerated by giving the mother high doses of corticosteroids if premature delivery can be anticipated — a highly effective treatment that emerged from the pioneering work of Liggins in New Zealand to explore the mechanisms of labour in sheep. After birth, the very premature baby usually requires artificial ventilation, and with intensive care some 90% of babies survive after delivery as early as 28 weeks. Survival may occur even from birth at 24 weeks, but this is uncommon.

Other low birthweight babies are not premature, but are small because of poor growth, usually as result of poor function of the placenta. The babies may be born to women who are heavy smokers, or who have disorders of their blood vessels, notably high blood pressure. These babies are malnourished and are prone to asphyxia before and during labour. They often require to be delivered before the time that natural labour would occur.

Jim Neilson, and Forrester Cockburn

See also abortion; congenital abnormalities; placenta; pregnancy.