Clinics in obstetrics and gynaecology最新文献

The response of mother and fetus/neonate to drugs administered to the pregnant woman is determined largely by drug disposition and elimination within and between mother and fetus. Physiological changes occurring in pregnancy may result in reduced plasma protein binding, an increase in the apparent volume of distribution, and more rapid metabolic and renal clearance of certain drugs than are usually found in non-pregnant women. The consequences are relevant for the peak concentration of drug achieved after a single dose, the half-life of the drug, and the drug concentration to which the fetus is exposed via the placenta. Drugs whose dosage may need to be altered in pregnancy include most anticonvulsants, lithium, digoxin, certain beta-blockers, ampicillin and cefuroxime; for drugs which have not been specifically investigated, no generalizations are possible. Very few drugs given in pregnancy fail to cross the placenta and, as a rule, drug molecules not bound to plasma protein diffuse along a concentration gradient to establish and maintain an equilibrium. Because movement of drug molecules is bidirectional, the placenta is the main portal of exit from, as well as entry to, the fetus. The pharmacological response of the fetus to drugs which it receives depends mainly on the unbound concentration of drug in fetal blood--unwanted effects seldom occur if the maternal dose is correct; exceptions include tetracycline, antithyroid drugs, coumarin anticoagulants, aspirin, indomethacin and cerebral depressant drugs (opiates, barbiturates and phenothiazines). The total (bound plus unbound) drug concentration on the fetal side of the placenta is usually lower than on the maternal side except where differences in blood pH and/or protein binding lead to 'trapping' of drug in the fetus; the latter phenomenon may prove hazardous after birth because of the neonate's limited capacity to eliminate drugs by metabolism and excretion.

Preterm labour is a major cause of perinatal mortality and morbidity. The aetiology is multifactorial and attempts to predict preterm labour are unsuccessful. At the present time prophylaxis is unhelpful and the obstetrician must manage preterm labour as it arises. The management of preterm labour remains controversial because of the difficulty in conducting good clinical trials. Antepartum glucocorticoids are effective in reducing the incidence and severity of respiratory distress syndrome. The effect is dependent upon a number of factors such as race, fetal sex, gestational age, state of the membranes, fetal asphyxia and timing of delivery in relation to therapy. Tocolytics are effective in stopping contractions but this does not produce a significant prolongation of pregnancy or reduce perinatal mortality or morbidity. It is because they can suppress contractions and delay delivery for a short time that great care should be taken that this short delay is used beneficially, e.g. in-utero transfer, or steroid therapy. It is also important that this suppression does not result in an inappropriate delay where early delivery is indicated because of infection or fetal distress. Steroids, tocolytics and antibiotics are potentially hazardous although all may benefit the fetus. The particular risks versus benefits of each form of therapy should be carefully considered for the particular presentation of each individual patient. While all these agents given antenatally are of potential benefit to the fetus and neonate, prolongation of pregnancy for its own sake or for the sake of allowing time to administer such agents is no substitute for delivery of an infant in optimum condition.

Hypertensive diseases are among the most common of all pregnancy complications. Significant elevations of blood pressure can be missed if inflexible criteria are used. There is now very strong evidence to support the use of antihypertensive agents in all forms of hypertension. The antihypertensive drugs in current use have a good safety record with regard to both mother and baby. The management of hypertension during pregnancy ideally requires the close cooperation of obstetrician and physician.

In women with epilepsy, seizure control during pregnancy can be improved by maintaining the serum anticonvulsant drug concentration within the therapeutic range. Treatment with one anticonvulsant drug plus folic acid supplementation 5 mg per day seems appropriate in most cases. This should be achieved before conception whenever possible. No anticonvulsant drug seems free of teratogenic risk. With the commonly used anticonvulsant drugs-phenytoin, phenobarbitone, carbamazepine and sodium valproate-the risk is relatively low and represents less potential harm to the fetus than might occur with uncontrolled seizures.

When treating thyroid disease, as with other conditions in pregnancy, one is concerned with the welfare of both mother and developing child. Thyroid disease causes few maternal problems; thyrotoxicosis in fact tends to improve in pregnancy, allowing medical management with lower drug doses than usual. Relapse of thyroid disease may occur postpartum, when transient hypo- and hyperthyroidism are relatively common. In contrast, the fetus and neonate are threatened in a number of ways by drugs given to the mother and by transplacental passage of maternal antibodies capable of inducing thyroid disease. Antithyroid drugs may cause fetal goitre with airway obstruction, and are associated with mild neonatal hypothyroidism. Thyroid antibodies in primary myxoedema and Hashimoto's thyroiditis are occasionally implicated in neonatal hypothyroidism and may even cause thyroid dysgenesis. Neonatal hyperthyroidism has a high morbidity and mortality and may have long-term skeletal effects such as craniosynostosis. Fetal problems may not be apparent at birth but may emerge in the next eight to ten days, especially in hyperthyroidism when the mother has been on treatment. Close monitoring throughout pregnancy and for the first ten days postpartum is required to minimize risks to the fetus and neonate. Most pregnancies associated with thyroid disease will have a successful outcome. If the occasional at-risk fetus is to be identified and treated successfully there should ideally be close cooperation between obstetrician, endocrinologist and paediatrician.