Drugs which Cross the Placenta
All the material that the foetus requires for its growth and survival must be supplied to it from the mother by way of the placenta. Everything is passed in a comparatively simple chemical form for the foetus to manufacture into complex proteins and other substances. Similarly all the excreted products from the foetus are passed back to the mother across the placenta as simple chemical compounds. Most drugs are simple chemicals which when introduced into the mother will pass from her circulation to that of the foetus because of a lower concentration on the foetal side of the placenta. Some of these may be beneficial to the foetus while others may cause harm and those that are harmful are usually only capable of causing damage or trouble at a specific time during pregnancy.
The most important chemical passed to the foetus is oxygen. The red blood cells of the foetus contain a haemoglobin, slightly different to that present in ordinary adult cells, which has the ability to absorb readily from the maternal blood and transfer it to its own tissues easily. Occasionally, therefore, if the foetus becomes distressed, or short of oxygen, the mother may be given extra oxygen.
The majority of substances which are present in the maternal circulation cross to the foetal circulation. The ability of a drug to cross the placenta depends on the exact size of the drug molecule. Those chemicals with small molecules will pass easily into the circulation of the baby whereas those with large molecules will not. The commonly used drugs such as aspirin, codeine and barbiturates (sleeping pills) do cross to the baby but cause no damage. Nearly all the antibiotics cross the placental barrier and are present in the foetal circulation very shortly after administration to the mother, and in fact some of these are actually used to treat the foetus either during pregnancy or during labour when some obstetricians consider that the administration of antibiotics is advisable after a woman has had ruptured membranes for 24 hours.
During recent years there have been some tragedies when the administration of drugs to the mother had led to mild, or even severe, congenital abnormalities in the foetus. This has happened because the drugs have crossed the placental barrier and affected the foetus during its most formative time. It is for this reason that no drugs should be taken during pregnancy except with the permission of the doctor or midwife. The vast majority of congenital abnormalities are caused during the first 12 weeks of pregnancy so the pregnant woman must be particularly careful about taking drugs during this time, and should avoid them if possible.
Thalidomide has demonstrated to the world the potential danger of drug administration during pregnancy. Thalidomide and similar substances are, of course, absolutely forbidden at any stage of pregnancy. The catastrophe of children so severely maimed and handicapped due to the administration of a drug to their mothers has, however, brought an appreciation and awareness of the dangers of administering drugs to pregnant women. Today any new drug marketed into this country has to have official approval of a special committee established to ensure that no such similar tragedy should occur. Very rigid regulations have to be adhered to before drugs can be sold to the public and particularly those that might be administered to women during pregnancy, and all new drugs are tested specifically in animals in order to assess their action upon the growing foetus.
The problem of knowing what drugs can safely be taken in pregnancy is that a variety of drugs may be given for any one condition and, conversely, that any one drug may be given for a variety of conditions. Added to this is the fact that a drug, potentially harmful at one stage of pregnancy, may be completely safe at a different time in pregnancy.
Drugs have to be used correctly. Just as a motor-car is potentially lethal or dangerous, being perfectly capable of killing somebody if it is not used correctly, so are drugs safe when used in their correct dose but potentially dangerous or even lethal if that dose is exceeded or given at the wrong time or in the wrong manner. When discussing the use of drugs during pregnancy, one assumes that the drugs are being given in their correct and proper dosage in the correct manner at the proper time. Perhaps the easiest way to simplify the problem is to consider the classes or types of drugs that may be used and then to consider the different times or stages of pregnancy during which harm may come to the foetus as a result of drug administration. A very simple example is as follows. Should you have the extreme misfortune to injure yourself and perhaps break a leg in the earlier part of your pregnancy you may be given a very large dose of pethidine or morphine in order to relieve the pain until your leg can be treated. Such a large dose of pethidine or morphine will certainly do your baby no harm. If, on the other hand, you are given a similar large dose of pethidine or morphine about half an hour before your baby is to be delivered then its breathing might easily be depressed when it is born, to such an extent that it has considerable trouble in establishing satisfactory respiration.
Groups of Drugs
Alkalis are taken for the relief of indigestion and heartburn. If taken in the prescribed dose even in the early stages of pregnancy they will certainly cause no harm to either the mother or her baby.
Analgesics such as aspirin, codeine and paracetamol are taken for the relief of simple aches and pains or for the relief of headache and may be taken in early pregnancy quite safely. It is very strongly advised, however, that only tablets that contain aspirin, codeine and paracetamol should be used. Some proprietary tablets contain other chemicals or compounds some of which are very powerful analgesic agents but which are not recommended at any stage of pregnancy. Always drink lots of fluid when taking analgesics.
Purgatives should, ideally, never be required. Unfortunately, however, constipation is one of the main problems of pregnancy so that purgative drugs may have to be taken by women while they are pregnant. The best measures are adequate control of the diet together with a satisfactory water intake, but if purgatives are necessary the simplest possible drug should be used. Strong purges that cause violent diarrhoea are obviously to be avoided. Ordinary lubricants and preparations containing derivatives of senna are satisfactory but preparations containing phenolphthalein are better avoided.
Antibiotics. There are so many new and very powerful antibiotics on the market today that it is very difficult to state categorically which ones are safe and which ones should be avoided. As a matter of principle, therefore, the more recently introduced antibiotics are better not taken during pregnancy. Some antibiotics may have an unfortunate side effect on the growing foetus. Tetracyclines taken in early pregnancy are unlikely to have any deleterious effect but later in pregnancy they may be stored in the teeth and bones of the unborn baby and result in yellow discoloration of the teeth. This only applies to the first dentition, or milk teeth, that are in fact growing at the time of the administration of the drug. This does not seem to do the teeth any actual harm but it is decidedly unsightly when a baby is otherwise in perfect health. Streptomycin, even when given to adults, occasionally causes damage to the nerves supplying the ear, resulting in deafness or deficiency in balance. Although it has never been conclusively shown that streptomycin taken by a pregnant woman causes any damage to the hearing or balance of her unborn child, it is considered inadvisable to take streptomycin or its associated drugs during pregnancy. It is accepted at present that penicillin and its derivatives and nitrofurantoin may be safely administered but sulphonamides are better avoided in the last few weeks of pregnancy.
Tranquillizers. There are so many tranquillizers at present on the market that it is absolutely impossible to generalize regarding their saftey or the advisability of taking them during pregnancy. Certainly the more simple tranquillizers such as Valium or Equanil may be taken in the correct dosage through pregnancy by permission of your doctor but dosage should be a minimum in the last few weeks to avoid excessive sleepiness in the newborn child.
Antihistamines are mainly used to treat nausea and early morning sickness. A group of these drugs has been specially developed and tested for use in early pregnancy, and providing they have been prescribed by your doctor they can be taken in the correct dose without any fear of their causing harm.
Sedatives are sleeping pills. The simpler forms such as the mild barbiturates and the simple derivatives of chloral hydrate may be taken if advised by your doctor. The more complicated types of sleeping pill or sedative are better avoided.
Antidepressant drugs especially mono-amine oxidase inhibitors should never be taken during pregnancy except by permission of your doctor and with the knowledge of your midwife.
Under the heading of special drugs are those drugs taken by a woman for some underlying disease or condition either daily or intermittently according to the demands of her illness. These conditions may vary from arthritis to kidney disease or epilepsy. In the vast majority of instances the drugs so prescribed are perfectly harmless during pregnancy but if you do happen to be taking drugs regularly or intermittently for some chronic condition, you should discuss the whole question of pregnancy with your doctor beforehand. If you have not done this, you should consult your doctor as soon as you realize you are pregnant in order to confirm that you may continue taking the drugs.
Cortisone and all its derivatives are to be avoided during pregnancy if possible. Certain circumstances, however, may make their administration essential and if a woman is taking a daily dose when she becomes pregnant then this should be gradually reduced and the drug discontinued as soon as it is practicable; the body automatically increases its cortisone production during pregnancy so the sooner the dose can be discontinued the better. Very large doses of cortisone administered to pregnant rats do occasionally cause congenital abnormality. When cortisone is administered to humans throughout pregnancy it may not cause abnormality but it can cause a deficiency in cortisone production in the foetus so that the newly delivered infant has to receive cortisone treatment.
Thyroid drugs. Anti-thyroid drugs are frequently prescribed for the condition known as thyrotoxicosis due to an over-active thyroid gland. If such drugs are given during the last three months of pregnancy it may result in an overgrowth of the thyroid gland in the foetus. Anti-thyroid drugs are much better avoided altogether during pregnancy but some women require them during at least the first half, and they should then be discontinued at about the 28th week. Thyroid itself is given to women who are suffering from a deficiency in the thyroid gland and here again the drug is best discontinued during the last two months of pregnancy, if this is possible, to avoid its deficiency in the baby. Any pregnant woman who is taking either thyroid or anti-thyroid drugs will receive specific instructions regarding their administration and if she has been asked to continue taking them she can rest assured that her thyroid balance is sufficiently well controlled to have no effect on her baby.
Diabetes during pregnancy is discussed in this article. Women who suffer from diabetes usually know a great deal about their disease and its control because they are members of a diabetic association. It requires very careful management during pregnancy. A very high blood sugar or an overdose of insulin can prove harmful to the foetus just as it can to the pregnant woman herself. The rigid control of blood sugar levels during pregnancy is absolutely essential because it is well known that the unstable diabetic woman has a slightly higher incidence of congenital abnormality in her child than the non-diabetic woman. It is also known that the diabetic woman whose blood sugar is carefully controlled and who does not allow her blood sugar to fluctuate into the wild limits of abnormality does not have a higher incidence of congenital abnormality amongst her children, neither does she suffer from all the other problems that beset the pregnancy of the unstable diabetic.
Cytotoxic drugs are used in the treatment of some types of cancer and malignant disease of the bone marrow and, because of the damaging effect they exert upon dividing cells, they are absolutely forbidden at any stage during pregnancy.
There is no evidence that alcohol taken in moderation causes any harm during pregnancy either to the woman or to her baby. The majority of women ‘go off’ alcohol at the onset of pregnancy so the problem does not arise, but those who wish to continue drinking alcohol during pregnancy should avoid hard spirits if possible but can otherwise continue to drink alcohol in moderation, for it will certainly do them no harm. One of the medical methods by which premature labour can be stopped or averted is by giving a calculated dose of alcohol into a vein over a period of hours or days. This induces a state of intoxication in the woman and causes relaxation of the uterus.
Women should not smoke during pregnancy. Smoking itself is now considered to be generally antisocial and damaging to the health. Women who smoke more than 10 cigarettes a day do have smaller babies than they would have if they did not smoke during pregnancy. Even more important is the implication that carbon monoxide, nicotine and other substances in cigarettes reduce the blood supply to the placenta and the oxygen supply to the foetus. There are many things about a baby that cannot be assessed, such as its liver function, its kidney function, its heart condition or its intellect. Its weight, however, can be measured. Many people have an unhappy feeling that when medical science has advanced sufficiently to measure the physiological and mental powers of the new-born infant it might well be found that the babies of women who smoke do in fact suffer from deficiencies other than just a simple reduction in size. There is evidence today that smoking after the 16th week of pregnancy causes mental and physical retardation in later childhood.
Hormones are often given in early pregnancy for one of two reasons. Firstly, to try and confirm the diagnosis of pregnancy, a small amount of oestrogen and progesterone is given for one, two or even three days and if the woman is not pregnant then a period will follow. If she is pregnant there will be no bleeding. Such hormones are probably harmless but are not recommended. Secondly, hormone is given either by mouth or by injection over a fairly prolonged period to treat a threatened abortion or to treat women who have previously miscarried or who are shown to be deficient in progesterone. Oestrogen used to be administered for this purpose but has now been discontinued because there is some evidence that it may eventually prove harmful to the baby. Some preparations of progesterone have also caused congenital changes in female babies but these are not prescribed today and the hormone preparations that are at present in use are, so far as is known, safe, though they may cause nausea in the mother.
Local anaesthetics in the prescribed dose may be administered during pregnancy without any harm coming to the pregnant woman or to her baby. This is particularly applicable to dental anaesthesia.
General anaesthetics and operations are better avoided during pregnancy if possible. If general anaesthesia is necessary, do not worry; you will be perfectly safe. None of the drugs that are used are in any way harmful to yourself or to your baby and you may rest assured that the supply of oxygen that your baby will receive during your anaesthetic will be just as good as when you are awake, if not better. Do tell the anaesthetist that you are pregnant.
Drugs normally administered during Pregnancy
Iron and simple iron preparations are essential for the mother’s welfare and the prevention of anaemia during pregnancy. The majority of iron tablets available for pregnant women have been specifically prepared for the purpose and also contain the various trace elements required such as copper, manganese, magnesium and cobalt. Even iron, however, should not be given to women who suffer from a very rare disease called thalassaemia until fairly extensive blood tests have been carried out. Thalassaemia is extremely rare in Great Britain and the routine tests performed on a woman’s blood at the very commencement of pregnancy automatically ensure that this disease is diagnosed. Do not worry about taking your iron pills.
Vitamin supplements have now become a part of normal antenatal care. They are perfectly safe and should be taken as prescribed.
Calcium supplements are frequently prescribed during pregnancy especially to those people who suffer from muscular cramps. In many countries calcium supplements are given as a routine together with iron and vitamin preparations. It it not true that excess calcium will cause a baby’s bones to become brittle or its skull to be unduly hard so that delivery is difficult.
Fluoride. The role of fluoride in preventing dental decay is generally accepted and some dentists do support the routine administration of fluoride to women in late pregnancy on the principle that their children will therefore have less dental decay.
Drugs at Different Stages of Pregnancy
The first trimester is the first 14 weeks of pregnancy and it is during this stage that drugs or other factors may lead to the formation of congenital abnormalities in the rapidly developing foetus. Drugs administered after the end of the 12th week of pregnancy should not result in any developmental abnormality of the baby because by that time all its organs are properly formed and cannot, therefore, be damaged.
The second trimester is from the 14th to the 28th week of pregnancy and is the stage of the main physiological growth of the foetus as well as the development of its enzyme systems and other highly complex endocrinological processes. Abnormalities in the development of these processes would not be immediately obvious at birth but discoloration of the teeth by the administration of tetracycline, damage to nerves of the car by the administration of streptomycin or hidden damage to the baby by overdose of insulin can all occur during this stage of pregnancy.
The third trimester is from the 28th week until delivery. It is during this time that thyroid drugs may cause abnormal growth of the thyroid gland and other drugs such as anticoagulants may adversely affect the baby. Cigarette smoking is thought to exert its main effect after the 16th week of pregnancy. Sulphonamides taken late in pregnancy may prevent the newborn baby’s liver from dealing quickly with jaundice. Valium in moderate doses for some weeks before delivery may make the baby sleepy, slow to cry and poor to feed after delivery.
Labour. The administration of hypnotic, analgesic and anaesthetic drugs during labour is very carefully controlled because nearly all, if not all, of these drugs do in fact cross the placenta to the foetus. A woman who is sedated too heavily during labour may give birth to a baby so heavily sedated that it may be slow to breathe spontaneously.