Most drugs whether therapeutic or recreational, when taken during pregnancy are able to pass the placental barrier and possible effects of those drugs on the fetus must always be considered when they are prescribed or administered during pregnancy. It is not all cases of deformity in the fetus that is due to drug effects, therefore Care is necessary before attributing any solitary case of fetal deformity to a particular drug. A great majority of fetal malformations occur as a result of genetic disturbance or pathological events entirely unrelated to any drugs which the mother may have taken during pregnancy.
The study of harmful effects of drugs on fetus is called teratology and drug which has been identified as harmful to the fetus is referred to as a teratogen or teratogenic agent. An important principle of teratology claims that it is not so much as the nature of the harmful agent taken, but rather the time in embryonic or fetal development at which the drug was taken that chiefly determines the abnormality produced. So generally, the earlier in pregnancy that a teratogenic agent acts, the more severe the malformation will be. Furthermore, there is a particular period in the embryonic and fetal development that each developing structure is most vulnerable to malformation and this must also be considered.
It should be a general principle to avoid the administration of any drug during the early weeks of pregnancy unless it is clearly necessary for the treatment of a maternal condition. There are several therapeutic and recreational drugs that have been shown to have harmful effects during pregnancy and so many more are still being studied. The following are just a few out of the long list.
SOME DRUGS AND THEIR EFFECTS IN PREGNANCY
Sedatives and analgesics
- Morphine or pethidine : given within 2 or 3 hours before delivery will depress the fetal respiratory centre. This effect can however be counteracted by an injection of naloxone.
- Heroin : If the mother is a heroin addict, the baby may show withdrawal symptoms after delivery with restlessness and failure to feed which will consequently lead to loss of weight.
- Aspirin : NSAIDs like aspirin may inhibit prostaglandin synthesis and produce premature closure of the fetal ductus arteriosis.
- Diazepam : When administered in large doses before delivery, diazepam will depress fetal medullary centres and cause loss of the normal baseline variation of the heart rate and hypotonia.
- Phenytoin : is usually given to control epilepsy and it inhibits folio acid. Therefore, additional folic acid must be given when phenytoin is used during pregnancy.
Cardiovascular acting drugs
- Hexamethonium : may cause ileus in the new born.
- Reserpine : This drug will cause a transitory non-infective nasal discharge in the infant.
- Propanolol and Atenolol : These can cause fetal bradycardia and neonatal circulatory depression.
Injectible anticoagulants like heparin do not cross the placenta and therefore have not been shown to have any effect on the fetus. Oral anticoagulants like warfarin, however, cross the placenta and reach the fetus. It can cause bony or facial abnormalities if administered early in pregnancy. In late pregnancy, it can cause retroplacental haemorrhage or bleeding into the fetal tissues and intrauterine fetal death.
- Sulphonamides : They compete with bilirubin for binding sites on serum albumin and therefore can increase the possible risk of kernicterus after birth.
- Salicyclates : They produce similar effects like sulphonamides.
- Cotrimoxazole : is a folic acid antagonist and therefore a potential teratogen.
- Tetracyclines : The children of mothers taking tetracyclines during pregnancy may have greenish-yellow staining of their milk teeth and there may be interference with enamel growth leading to imperfect dentition.
- Streptomycin : Increase risk of damage to the 8th nerve of the fetus.
- Chloramphenicol : can cause postnatal collapse and hypothermia in the newborn.
- Androgens : Androgens like testosterone should not be given to pregnant women because they can cause virilization of the female fetus.
- Diethylstilboesterol : Should not be given in pregnancy because it can cause vaginal septal defect in female fetuses if administered early in pregnancy.
Radioactive isotopes of iodine, strontium and phosphorus cross the placenta and become localised in fetal tissues causing damages to those tissues.
Antithyroid drugs such as thiouracil or large doses of iodine may cause fetal goitre or hypothyroidism.
Cytotoxic and Alkylating drugs
Drugs including methotrexate, busulphan, cyclophosphamide, chlorambucil and many others used for cancer treatment can be very harmful to the fetus and should be avoided where possible.
It has been alleged that smoking is responsible for more neonatal pathology than any other known cause and it’s effects can continue to be manifested well into childhood. Smoking is harmful to the fetus and will cause reduction in birth weight and increase risk of perinatal mortality.
Raised maternal carbon monoxide levels from cigarette smoking produces an increase in carboxyhemoglobin which interferes with oxygen transport to the fetus. Nicotine causes vasoconstrictive effects on maternal blood vessels at the placenta which is aggravated if the mother is hypertensive already.
Children born to mothers drinking excessive alcohol will have low birth weight and an increased risk of neonatal and infant mortality. Some babies can have fetal alcohol syndrome which has a characteristic facial appearance of a broad nasal base, epicanthic folds, a long upper lip and a small lower jaw with mental retardation.
Geoffrey Chamberlain : “Harmful Drugs in Pregnancy” Obstetrics by Ten Teachers (16th edition).