ENVIRONMENTAL FACTORS OF CONGENITAL MALFORMATIONS

Several environmental factors ranging from irradiation, drugs, infections as well as nutritional status of mother are known to influence the development of the embryo. Even as far back as 1949, Waston suggested that certain factors in the maternal environment may affect the developing embryo. This suggestion received further emphasis by the observations of Gregg from his association on the congenital cataract with congenital rubella (Gregg, 1941) and that of Peter and others, that fetal diseases contracted by transplantational route may be a cause of congenital anomalies. It is at present,
estimated that approximately 10% of all known human malformations are caused by environmental factors, another 10% by genetic and chromosomal factors while the remaining 80% are presumably caused by the intricate interplacing of several genetic and environmental factors (Sadler, 1990)with the environmental factors accounting for the genetic changes observed.
Drugs: The use of drugs and chemical agents indiscriminately especially during the first trimester have been implicated in one form of malformation or the other (Smith, 1987). The use of these drugs is incorrectly meant to ameliorate some of the discomforts that come with the onset of pregnancy while others may be routine drugs. Perhaps the most teratogenic drug known is Thalidomide, a sedative first marketed in 1957. An anticonvulsant and sleeping pill, Thalidomide was taken by women often before they knew they were pregnant causing over 5,000 babies to be born total or partial absence of the extremities as well as defects of the heart, ears and intestines (Saladin, 1996). Aminopteria is a folic acid antagonist and an ant metabolite used in high doses to induce therapeutic abortion. At lower doses, it is known to induce malformations similar to cause anencephaly, hydrocephalus, meningocoele, cleft lip and cleft palate; obviously owing to incomplete stoppage of metabolic processes.
        Increase in the incidence of cleft palate and lip has been observed in infants whose mothers were exposed to diazepam (Smith and Asch, 1987), even the acne medicine Acutane has caused severe birth defects (Saladin, 1996). There is also increasing evidence that aspirin, an analgesic is one of the most commonly used drugs by pregnant women, is potentially harmful to the fetus when used in large doses (Sullivan, 1975).
        The use of diphenylhydration, an anticonvulsant by epileptic women is known to produce a broad spectrum of abnormalities like nail and digital hypoplasia, craniofacial defects, abnormalities, all of which are given the designation – Fetal hydration syndrome (Sadller,1990). Trimethadine is also an anticonvulsant used in treatment of petitmal seizures; it leads to trimethadione syndrome characterized by defects such as malformed ears, cleft palate, cardiac defects, urogenital and skeletal abnormalities.
         Other drugs that induce and cause notable malformations in the embryo or fetus includes propylthiouracil and potassium iodides (goiter and mental retardation), Streptomycin (deafness), Sulfonamides (kernicterus), the anti depressant imipramine (limb deformity), Tetracyclines (bone and tooth anomalies), Amphytamines (oral cleft and cardiovascular abnormalities), the anti coagulant warafine (chondrodysplasia and microcephaly) and quinine (deafness) (Sadler, 1990).
Infections: Infections may cross through the placenta to the developing fetus and bringing about serious malformation. Most infections are transferred directly to the fetus and may manifest before or after birth. This alone accounts for over 8% of prenatal deaths in the United Kingdom (Chamberlain and Turnbull, 1993). The infant is frequently exposed to leads of micro-organisms which colonize or infect the female genital tract and since the fetus is still immunodeficient, it is susceptible to infections from the mother, the duo of Chamberlain and Turnbull further stress.
         Infection by Rubella had been noted to cause malformations like cataract and microphthalmus (Gregg, 1941). It may as well present with congenital deafness, persistence of duct’s ateriosus, arterial and ventricular septal defects and malformations of the enemal layer of the teeth (Rhodes, 1961, Tondary et al., 1952). It may also cause intrauterine growth retardation, myocardial damage and vascular abnormalities (Tondary et al., 1952). Rubella may be responsible for brain abnormalities and mental retardation and as a variation of the malformation, fetal death may occur depending on the time of infection (Sadler, 1990).
 Irradiation: Many malformations have been traced to the exposure of pregnant mothers to several types of radiation e.g. X-ray. It may also be the reason for still birth, mental and sub normality as well as malignant disease of childhood such as leukemia. It was reported that a dose as small as 50 radium can damage the fetus and the nature of malformation depends on the dose of radiation and the stage of development at which the radiation was given.
        Post-natally, the risk from irradiation excluding cardiac catheterization and computerized tomography indicates that one case of childhood cancer might be caused in the whole of the United Kingdom per year. This study also revealed the risk of not using radiography in intensive care of the newborn outweights the risk of either cancer or genetic (Chamberlain and Turnbull, 1993). There is how ever no evidence that ultrasound is harmful to the developing fetus but occupational irradiationhas been associated with chromosomal abnormalities (Bone and Bone, 1975)
         The observation of Kline and others (1975) in a study showed that there was no increased miscarriage rate at a drinking level of above 28.4cm of absolute alcohol twice a week. Fetal alcohol syndrome is a manifestation of excessive drinking and is characterized by neurologic, facial and other malformations as well as growth retardation. Growth retardation observed in the syndrome affects all parameters of growth namely length, weight and head circumference ratio and continues from the antenatal period into early life (Vonas and Smith, 1973). The opinion of Hadi, Hill and Castillo (1987) is that the reduced cell count observed in sufferers of fetal alcohol syndrome is responsible for the retarded growth.
       Hypoxia or height related incidence induce congenital malformations. This has been observed in experimental animals (Ingalls et al and Prindle, 1952). Humans born at high altitude are usually lighter in weight and smaller than those born near or at sea level. Also, women with cyanotic cardiovascular diseases often give birth to small infants but usually without gross but minor if not absent congenital malformations.
 Nutritional Status of Mothers: Nutrition in pregnant woman no doubt plays a significant role in congenital malformations. Nutrition in the developing fetus depends solely on food intake by the mother. Malformation is a common problem in the rural and poor urban areas and is responsible for some malformations (Ibrahim, 1985). Although low birth weight (LBW) is associated with under age mothers and repeated pregnancies, it is mainly a consequence of malnutrition in babies whose mother’s nutritional level was low. The average birth weight reflects the general nutritional status of pregnant woman and the community at large but however not all babies with birth weight below 2.5kg are at risk of a malformation because the average birth weight is not the same everywhere (Howie, 1986). Due to poor nutritional status of pregnant mothers in most developing countries, the growth of the fetus is at risk,hence the birth weight of over 20-40% of babies born in these countries fall within the low birth weight range compared with 6% or so in western Europe, as concluded by Howie. The large incidence of low birth weight in developing counties is a strong indication that the aetiology is different from those commonly described in the developed societies wiyh beeter nutrition although fetal malnutrition is an inevitable synergy (Ibrahim, 1981).
     It has however been shown by studies in Guatemala and India, that low birth weight is an important determinant of congenital malformation and that it extends throughout infancy. Out of 35,095 cases of infant deaths in the United States, 23% of them were found to be associated with low birth weight (Mckeown, 1976).
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