By Prof. Rohan W Jayasekara

Published in ECHOMED Vol 1 No 1, October 1990.

It is usual to consider interferences with normal prenatal development from conception to birth as environmental, in contrast to a genetic intrusions which are predetermined by the time the zygote forms. In reality chromosomal and genetic anomalies are also attributable to environmental factors as for example the role of the maternal environment in the origin of cytogenetic changes and mitotic nondysjuncion after conception, which appears to be one of the first damages to the embryo caused by an adverse inner environment, which leads to chromosomal imbalances. In normal embryogenesis many genes act in an orderly sequence at certain phenocritical periods to bring about normal development. Should a specific gene fail to bring about an important and critical reaction, the whole process thereafter will be disorderly resulting in a congenital abnormality. Many environmental agents are know to produce congenital anomalies in man. These teratogens which are active during pregnancy include radiation, maternal disease, infections, drugs, harmful chemicals and alcohol.

X-irradiation can lead to congenital malformations in man like microcephaly, skull defects, spina bifida, microphthalmia, cleft palate, micromelia, clubfoot and a host of others as reported in the literature. Presently, not only medical technologies but other sources like industrial and laboratory procedures, nuclear tests and nuclear reactor accidents have to be considered. A great controversy yet unresolved concerns the emission of electromagnetic radiation of different frequencies from visual display units (VDU). The most dangerous of them is the high frequency x-rays or ionising radiation which has been associated with birth defects. Another type of radiation that is emitted from the side and back of VDUs is a non-ionising Extremely Low Frequency radiation (ELF) which will affect not only the operator but also those around the unit. ELF according to researchers, over long periods of time is absorbed by water in the body resulting in vibrations within the cells. This can bring about changes in the growth of cells that can cause chromosomal damage in the particularly vulnerable dividing foetal cells, by virtue of its electomagnetic radiation. This is presently a highly controversial topic which needs careful evaluation. However, present knowledge does not support the conclusion that women working on VDUs do have adverse pregnancy outcomes. This compels one to advise all pregnant females to avoid all forms of radiation. Those females working on VDUs should also be reminded of the need to keep away from such machines during pregnancy. All radiological examinations in a female should be carried out within seven days of the last regular menstrual period.

Among the common uncontrolled maternal disease which causes abnormalities at birth are diabetes mellitus which produces sacral agenesis in the newborn and phenylketonuria which by passive placental transfer of phenylalanine or its products produce irreversible neurochemical changes and mental retardation. Both these conditions are easily controlled and the resulting malformations avoided. Among the more rare maternal problems are accidental carbon monoxide poisoning, lead poisoning and a problem encountered in Japan, that of methyl mercury poisoning following the ingestion of fish from Minamata Bay. These three conditions produce neurological problems.

Among maternal infections, cytomegalovirus, rubella, toxoplasma and herpesvirus hominis are the more common ones. Like in others, in cytomegalovirus infection the clinical picture depends on the severity, time and duration of the infection, being especially vulnerable in the first trimester of pregnancy. Microcephaly and mental retardation are the commonest features with hepatospleenomegaly, jaundice, thrombocytopenic purpura, intrauterine growth retardation, anaemia, generalized oedema, intestitial pneumonia, gastrointestinal disturbances and ocular changes being the rare ones which complicate the picture. Vaccines are still in an experimental stage and hopefully would be available soon. The infection of pregnant females with the rubella virus in the first trimester can lead to the embryo being either aborted or deformed depending on the intensity of the infection. Congenital heart disease, deafness and cataract are some of the frequently seen abnormalities in this condition. Only 50 percent of Asian females have immunity to the virus and this highlights the need to immunize all female babies during infancy and if not have all school leaving you females screened for rubella. If they fail to show immunity they could be immunized even at this stage and thereby avoid complications. Prenatal infection with the protzoon Toxoplasma gondii can lead to destructive changes in the brain leading to microcephaly and hydrocephaly, in the eye causing choreoretinitis, resulting in a variety of functional disturbances in postnatal life. The free organisms are extremely sensitive to heat, cold, desiccation, gastric juice, medication and antibodies while the cysts are resistant to physical and chemical external influences. The parasites invade almost any tissue of mammals and birds and multiply in their living cells. The need for pregnant females to avoid contact with domestic pets like cats and birds or their faecal matter is therefore important in order to prevent an infection. Most infections are subclinical and overt cases are not always accompanied by specific clinical signs. Diagnosis is made using a Toxoplasma specific IgM test. In the case of herpes virus some reports have suggested that the genital herpes virus can produce congenital malformations similar to those produced by the cytomegalovirus. However, transplacental transmission of the virus to the foetus early in gestation can produce microcephaly, intracranial calcification, microphthalmia, cloudy lenses, retrolental masses and retinal dysplasia. For the purposes of screening and enzyme linked immunoadsorbent assay is available. No immunization is available as yet. The avoidance of extramarial sex whould also assist in preventing the transmission of this virus.

Of other infections like Poliomyelitis, Measles, Mumps. Coxsackie virus. ECHO virus, influenza and chicken pox, no clear causal relationship exists between them and birth defects. However, at least 21 cases of major birth defects following chicken pox infection during pregnancy have been reported. As a general rule it is advisable for a pregnant mother to avoid public swimming pools during polio epidemics, especially during her first trimester.

No pregnant woman needs to be reminded of the dangers inherent in taking drugs. The consequences may be quite serious but yet despite all that has been said and written on the subject, pregnant women still do take a remarkable amount of drugs. Of the many drugs considered harmful to the developing foetus, the commonly used ones which have proven teratogenic effects in humans are listed below with the malformations they produce.

Alcohol – Growth Retardation, Microcephaly, Mental Retardation
Anti-Thyroid – Hypothyroidism
Chloroquine – Deafness
Folic Acid Antagonists – CNS Malformations
Hormonal Pregnancy Tests – Various Malformations
Phenytoin – Cleft Lip and/or Palate
Progestins – Virilization
Smoking – Growth Retardation
Streptomycin – Deafness
Thalidomide – Phocomelia
Warfarin – Chondrodysplasia

Thalidomide and other drugs can produce congenital malformations under certain condition. This coupled with the evidence by experimental teratologists in producing congenital malformation in mammals by administration of drugs, has lead to demands to test drugs in pregnant animals before admitting them for use in humans. The extrapolation of these findings to humans should be done with great reservation. The fact that Thalidomide does not produce malformations in rats and mice while salicylates do, is a good illustration. The present of the use of subhuman primates in drug testing, although more expensive will be for more rewarding.

It must be remembered that certain indigenous medicinal preparations which do not indicate the compostition may very well contain certain drugs, which when taken by an unsuspecting pregnant female could result in malformations. What role organic and inorganic chemicals play in the causation of congenital anomalies is yet to be studied. The recent surge of agricultural research has lead to the use of a wide range of pesticide and other strong chemicals. This has lead to the exposure of pregnant research workers both in the laboratory and in the field, as well as those consuming the many varieties of food sprayed with these chemicals, to their undesirable and yet unknown teratogenic effects. The slow seepage of these hazardous chemical can further pollute sources of drinking water and even the fish life in them. Dyes, additives and preservative in various forms of food and drink consumed during pregnancy particularly in the first trimester should be viewed with greater caution although no direct evidence is available as to their role in teratogenesis.

The pain and suffering of a newborn with serious birth defects, the devastating effects on the family and its implications for society in general is an ample warning to us of the importance of stressing the need to educate the mother to be on the preventive aspect of birth defects. Usually, by the time a woman seeks the assistance of an obstetrician for her pregnancy she is well into her second trimester. By then her ignorance of the avoidable environmental insults have taken their heavy tool. When then should a female be instructed on these preventive aspects ? The ideal time would be at the time of leaving school. This could take the form of a compulsory visit to the nearest family health centre.