The term congenital malformations is usually applied to important structural defects present at birth that are not caused by a birth injury. The relative importance of congenital malformation has increased as more effective control has been exercised over the environmental agents of disease. In 1900, in the United States, approximately 3.3 per cent of the total infant mortality could be ascribed to congenital malformations, whereas in 1964 congenital malformations accounted for 25 per cent of the total infant mortality. During the first 15 years of life congenital malformations are responsible for approximately 15 per cent of the annual death rate.
It has been estimated that 7 per cent of children by the age of one year have a congenital malformation of consequence, yet only 43 per cent of such malformations are detectable at birth. In most malformations no major etiological factor can be identified, and it must be presumed that their existence depends on complicated interactions of genetic and environmental influences or on particular genetic combinations.
The frequency of many congenital malformations is compatible with a polytonic model with a threshold beyond which there is a risk of malformation. Thus, the well-known observation that first-degree relatives of an individual with a congenital malformation are more at risk than the general population can be accounted for by the fact that they will have a curve of distribution approximately halfway between the general population and those affected. As an example, in cleft lip and cleft palate, as compared with the population at large, the first-degree relatives (sibs and children1 of an affected individual will be 40 times as likely to develop the malformation. The approximate frequency of the major malformations.
What Is Congenital Malformations, Facts You Must Know Being A Doctor
Environmental Factors.
Contrary to popular belief, there is little direct evidence that environmental factors such as virus diseases, maternal ingestion of drugs, or maternal irradiation make a significant contribution to the common malformations, although each of these factors materially increases the frequency of certain specific malformations. Recent evidence suggests that approximately 70 per cent of mothers exposed to rubella during the first trimester give birth to children with severe congenital defects such as cataracts, deafness, heart disease, and neonatal thrombocytopenic purpura.
Some evidence indicates that first-born children are more likely to have a congenital defect than later children. This is particularly true of anen -cephaly, congenital dislocation of the hip, talipes equinovarus, and pyloric stenosis. Striking regional differences in congenital defects have been recognized, and have been well documented for autocephaly and spina bifida. An increased frequency of congenital dislocation of the hips in Lapps and certain American Indians is well recognized. Marked seasonal variation in the incidence of certain malformations has also been reported. It has been estimated that nearly one-third of the pregnancies that are complicated by hydramnios result in congenital malformations.
The risk that a congenital malformation will recur with subsequent pregnancies depends on the specific abnormality and its etiology. For the three most common neurologic malformations, autocephaly, hydrocephalus, and spina bifida, the recurrence rate in subsequent children is approximately 4 per cent after the first malformation, but much higher after two malformations.
Drug-induced Embryopathy.
Fetal malformations can be regarded as the consequence of developmental unpunctuality, and are liable to follow environmental insults during the first three months of fetal life. There is growing evidence that errors in embryonic development are particularly likely to arise between the sixth and eighth weeks. It is, therefore, clearly prudent to minimize unnecessary medication during the first three months of pregnancy.
The importance of drugs as possible etiology agents in congenital malformations has been emphasized, and perhaps overemphasize, by the thalidomide tragedy. Indeed, it is virtually impossible to specify any drug that will not result in an increased frequency of congenital malformations when administered in a certain dose to a sufficiently large.panel of different laboratory animals.
To assume that a drug that causes a congenital.malformation in one species will necessarily cause one in man is as misguided as to assume that if a drug is harmless in animals, it will be harmless in man. Moreover, it is worth emphasizing that if thalidomide, instead of producing the striking malformation of phocomelia, or so-called “seal extremities” had increased the frequency of a common malformation such as cleft lip of cleft palate, recognition of the causal association might have been long-delayed.
During the two to three-year period during which thalidomide (alpha-phthalimido glu- Laramide) was freely available, approximately 7000 infants throughout the world were born with thalidomide-induced deformities. Only thalidomide and the antitumor drug Aminopterin (4- amino pteroyl glutamate) have been reported to be definitely teratogen in humans.
