Fragile X syndrome accounts for between one third and one half of all X-linked mental retardation. It is the most common cause of familial intellectual handicap and is second in prevalence only to Down’s syndrome among the mental retardations. The syndrome is known to affect about 1 in 2500 males and a similar number of females. It has been detected in all ethnic groups with access to modern medicine. The economic and social costs of this disorder made the determination of its molecular basis a high priority.

Recent studies have shown that babies who are small for dates at birth, or who fail to grow in infancy, have, in adult life, raised blood pressure, impaired glucose tolerance, abnormal serum lipids, raised fibrinogen and high death rates from coronary disease, stroke and obstructive lung disease. This has led to the hypothesis that these diseases are ‘programmed’ in utero in response to an adverse environment.

The childhood effects of antenatal exposure to cocaine are largely unknown. While several authors have evaluated the consequences of antenatal cocaine exposure during the neonatal period and early childhood, there are no large, blinded and systematic studies of the effects beyond early childhood and no data at early school age.

Asthma is the most common significant chronic medical condition affecting young adults and it is therefore often encountered in pregnancy. Approximately 3% of women of child-bearing age suffer some degree of asthma and this prevalence is increasing. Some of the apparent increase is due to heightened awareness of the condition, although air pollution and increased childhood exposure to house dust mite may also be contributing.

The haemoglobin disorders are a group of recessively inherited conditions of varying severity. In the homozygous state, alpha zero thalassaemia causes hydrops fetalis, beta thalassaemia usually causes a severe transfusion-dependent anaemia and sickle cell anaemia (HbSS), haemoglobin S/C disease, haemoglobin S/D disease and haemoglobin S/beta thalassaemia cause sickling disorders ranging from quite mild to very severe. Haemoglobin disorders are among the commonest inherited diseases in the UK. Management can be very burdensome, but produces good results in many cases. The disorders can also be prevented by a programme of carrier screening, genetic counselling and prenatal diagnosis in populations at risk. The WHO has defined a “haemoglobinopathy control programme” as an integral strategy combining optimal patient care with prevention based on community education, propective carrier diagnosis, genetic counselling and the offer of prenatal diagnosis. The services required for haemoglobin disorders in the UK have recently been reviewed in a report from the Standing Medical Advisory Committee of the Department of Health. This report focuses on genetic counselling and prenatal diagnosis for haemoglobin disorders.

Congenital diaphragmatic hernia (CDH) is a simple anatomical defect. The reported incidence is between 1:2000 and 1:5000 live births, with the majority affecting the left side. A defect in the diaphragm allows abdominal viscera to herniate into and stay within the thoracic cavity during crucial stages of lung development. This results in pulmonary hypoplasia, a reduction in pulmonary vascular branching and an alteration in the surfactant system.

In the Netherlands, approximately 30% of all women of reproductive age smoke, compared with 36% of men.

Cigarette smoking is associated in women with a dose-related reduction in fecundity and fertility and in men with a reduction in semen quality. Smoking has a negative effect on pregnancy: increased rates of antepartum bleeding and placenta praevia have been described. Smoking is also associated with increases in the rates of spontaneous abortion, low birth weight and perinatal death. Some tobacco-related perinatal deaths are due to an increased risk of serious malformation. Children of mothers who smoke are admitted twice as often to hospital for pulmonary problems. However, studies on maternal smoking and childhood cancer have proved inconclusive.

The fetus mounts a coordinated cardiovascular response to an insult of acute hypoxaemia which involves neural and endocrine components. During acute hypoxaemia in late pregnancy there is a transient bradycardia, a gradual increase in arterial blood pressure and an increase in heart rate variability. In addition, there is a redistribution of the combined ventricular output favouring the cerebral, myocardial and adrenal circulations by shunting blood away from the peripheral circulations. A component of the increase in peripheral vascular resistance and the increase in arterial blood pressure during acute hypoxaemia is mediated via increases in plasma concentrations of vasoconstrictor hormones such as vasopressin, angiotensin II and neuropeptide Y. Whilst an increase in plasma ACTH and cortisol is also seen during acute hypoxaemia, their contribution to cardiovascular control in fetal sheep is less clear.

Evidence has been presented to suggest that a number of these cardiovascular and endocrine responses to acute hypoxaemia are chemorefiex in nature, mediated principally by carotid chemoreceptor afferents. In addition, this reflex may be modifiable in terms of changes in magnitude and gain: first, by an influence of the intrauterine environment during chronic hypoxaemia and second, through genetic influences, in animals adapted to life at high altitude.

Although amniocentesis was first reported in 1882, the technique was not in widespread clinical practice until the 1970's. The reason for this slow uptake was that there were few indications for performing the procedure until fetal karyotyping from amniotic fluid cells became possible in 1966. Currently fetal karyotyping is the commonest indication for the technique and amniocentesis has become the mainstay of antenatal diagnosis.

A woman with heart disease may benefit from early obstetric counselling because it may help to reduce uncertainty or anxiety with regard to her ability to carry a pregnancy at some time in her life and may help her to prevent unwanted pregnancy or to avoid the need for an abortion. Pregnancy imposes an additional burden upon the circulation of a woman with heart disease and additional precautions may therefore be required during the antenatal period, labour, delivery and the puerperium. Nevertheless, with proper care, maternal and fetal outcome is good in most women with cardiac disease.

It is logical to deliver a distressed fetus as quickly as possible in the most appropriate way either abdominally or vaginally. Unfortunately, the diagnosis of fetal distress is not always precise compared with the diagnosis of placenta praevia or anaemia in pregnancy. By common usage and for want of a better term, the situation where the clinician feels that the baby might be hypoxic and acidotic is termed fetal distress. The fetus may also become distressed because of infection or injury associated with labour. Many babies are delivered operatively for fetal distress and are in excellent condition. One could argue that, in such cases, action had been taken long before the fetus actually became distressed and hence the baby was born in good condition.

The main function of the immune system is to protect the host from both pathogenic (ie. viruses, bacteria and foreign material) and neoplastic invasion. It is composed of both humoral and cellular factors. The humoral factors comprise the antibodies and the complement system, while the cellular factors comprise the lymphocytes and the phagocytes. These immunological factors remain in a relatively inactive state until activated by foreign molecules. Activation of the immune system under normal circumstances is beneficial to the host. In septic, multiply traumatized, critically ill surgical patients or severe preclamptic women, the host response to stress is more extensive and, as a result, extensive activation of immunological factors could create complications in the host like the adult respiratory distress syndrome (ARDS), multisystem organ failure (MOF) or the syndrome of haemolysis, elevated liver enzymes and low platelet count (HELLP) in preeclamptic women. In order to appreciate the later parts of this article regarding immunology and pregnancy, an understanding of the normal immune system is essential.

Severe pre-eclampsia is a common disorder in developing countries but still remains a significant problem in developed societies. The management of severe pre-eclampsia in developing countries is frequently hampered by lack of adequate facilities; paradoxically those countries with sufficient resources have a lower incidence of the disease and consequently lack experience in the treatment of severe pre-eclampsia. The management of these patients is further compromised because obstetricians generally lack the necessary knowledge and skills in critical care and conversely critical care specialists may lack appreciation and knowledge of pregnancy physiology and pathophysiology. Patients with severe pre-eclampsia therefore present an interdisciplinary challenge to obstetricians and physicians, who need to be familiar with pregnancy physiology and the current concepts in the pathogenesis and pathophysiology of severe pre-eclampsia. Patients who develop multisystem disease are most appropriately managed by an experienced obstetrician in an obstetric intensive care unit with a physician in consultation.

Hypertension is a common problem occuring in around 12–15% of all pregnancies. It remains one of the major causes of maternal death. Because of its perceived risk and the difficulty in deciding who has a problem and who does not, obstetricians often admit a patient found to be hypertensive to hospital for closer observation. This “play safe” approach can cause much inconvenience to the patient and her existing family. The result of this policy is that pregnancy hypertension is responsible for around 25% of all antenatal admissions. It is a major burden on health service resources in terms of manpower and hospital accommodation. Inpatient management may vary between different hospitals but the cornerstone is to keep the patient in hospital in order to allow serial monitoring of blood presure. Strict bedrest has been suggested to have therapeutic value but this has never been substantiated. As some of these patients will progress to more severe forms of the disease, it is important that there is early recognition of any signs of progression.

Prenatal diagnosis is one of the most rapidly expanding areas in medicine and now forms a significant part of Fetal Medicine subspecialization. With the introduction of new technologies in the areas of human genetics, fetal therapy and fetal pathology, those interested must work hard to keep abreast of the latest advances. General obstetricians and those involved in pregnancy counselling must now be aware of all diseases which can be transmitted and for which prenatal diagnosis and screening tests are available and appropriate. There is a plethora of reviews of current techniques and procedures and it would be repetitive for us to produce another such paper. Rather, this article aims to highlight those areas which by definition are changing and where we see future developments occurring. Those readers seeking in depth reviews of present methods are referred to standard texts.

Much of our understanding of uteroplacental insufficiency has been derived from animal research and the study of the pathology of human placental and uterine biopsies. These studies have shown how the placenta plays a major role in the development of normal pregnancy and how placental dysfunction is generally caused by factors interfering with the normal growth of the uteroplacental and/or fetoplacental circulations. These abnormalities lead to a deficient supply of oxygen and nutrients to the fetus and to several complications of pregnancy such as gestational hypertension, preeclampsia and intrauterine growth retardation (IUGR).

The developmental origins of the ability to hear have been the subject of much debate and speculation. Since time immemorial, there has been much anecdotal evidence that the fetus responds to sound. In contrast, until the late 19th Century, scientific evidence and opinion held that the newborn was deaf and only developed the ability to hear in the first weeks after birth. At the beginning of the 20th Century the prevailing scientific and clinical view changed and it was accepted that the newborn was able to hear at birth. This led to much speculation about, and limited experimental study of, when the individual first started to hear. Detailed study of the ontogency of auditory abilities had to wait until the 1980’s when scientific opinion regarding the abilities of the newborn changed and the ultrasound technology with which to observe the fetus in utero became widely available. Research thus commenced in earnest to investigate the response of the fetus to sound. Despite this increased interest in fetal hearing, experimental studies have concentrated upon the responsiveness to sound in late pregnancy and not on the developmental origine of auditory abilities. It is the aim of this review to examine the ontogenesis of hearing in the fetus.