sary therapy of non-existent disease which may be followed by superinfection.5 Obviously, the best treatment for colonization is to discontinue antimicrobials and permit the patient to reestablish his normal flora.. The distinction between coloni- zation and superinfection proposed by Tillotson and Finland is based upon recurrence of fever, after one or more afebrile days, associated with The Preventability increased lower respiratory tract signs and symp- toms and increased purulence of sputum. Sputum Of Birth Defects cultures from these patients often reveal many colonies of several resistant bacteria with different A TENET FUNDAMENTAL to all of medicine is that patterns of antibiotic sensitivity. Since the rela- prevention of a disease is generally to be preferred tive importance or even infralaryngeal presence over treatment, and birth defects are no exception. of these several types of bacteria may be unclear, As is well summarized in the comprehensive re- the patient often receives simultaneous treatment view by Bernfield elsewhere in this journal, much with more than one antimicrobial at least one of of the research in the area of birth defects is at which is potentially quite toxic. Additional studies present directed toward an elucidation of the are needed to establish more clearly the extent to mechanisms which produce these defects and of which in this particular situation tracheal aspira- their underlying causes. However, the overriding tion may improve upon early diagnosis by stained hope is that ways might ultimately be found to smear and be of assistance in resolving the often prevent their appearance, and it is therefore proper misleading and time-consuming results of culture. to ask whether birth defects are actually prevent- Hoeprich and his associates have generated some able. In this discussion, a birth defect will be of the best data available in this area, and a read- considered as "a structural or metabolic disorder ing of his article makes quite apparent some of present at birth, whether genetically defined or the shortcomings of the time-honored methods of as a result of environmental influence during em- bacteriological evaluation of lower respiratory bryonic or fetal life."* This definition is quite tract infection upon which we justify the wide- broad and, in addition to structural congenital mal- spread use of expensive and possibly dangerous formations and prenatally determined retardation, antimicrobial agents. It is difficult to escape the deafness and blindness, includes all genetically conviction that we are failing to employ better determined diseases. methods which are at hand, and reasonably simple The concept of preventability (not to be con- as well, and that our clinical judgment needs all the fused with treatability) is not an absolute one and sharpening it can get from the laboratory in man- must be qualified with regard to the point in time aging some of these difficult therapeutic problems. at which prevention is to take place and to the More information is still needed, however, to de- means of prevention that may be used. Preventing fine the place which these methods should be given conception of a child with a hereditary disease or in current laboratory practice. damage to a fetus by some exogenous agent is WILLIAM L. HEWITT, M.D. quite different from preventing birth of a child De,arttmmnt of Medicine Unwesersi of California, Los Angeles with a birth defect. Considering only the former, School of Meicine, Center for the Helth Sciences there are several groups of birth defects which Los Angeles are or will be preventable. These include many REFERENCES of the defects which result from maternal infection, to 1. Lapinski EM, Plaks ED, Taylor DC: An evaluation of some from exposure teratogenic agents, and from methods for culturing sputum from patients with bronchitis and em. causes such as physema. Amer Rev Res Dis 89:760-4, 1964 genetic chromosomal aberrations 2. Mulder J: Bacteriology of bronchitis. Proc Roy Soc Med 49: and abnormalities of specific genes. The possible 773-6, 1956 means of prevention varies with the etiologic 3. Austrian R: The bacterial flora of the respiratory tract. Some knowns and unknowns. Yale J Biol Med 40:400-13, 1968 factors. For birth defects resulting from maternal 4. Tillotson JR, Finland M: Bacterial colonization and clinical involves the identification of supra-infection of the res iratry tract complication andbiodc treat- infection, prevention ment of pneumonia. J In Dis 119:597-624, 1969 5. Weinstein L, Musher DM: Antibiotic induced supra-infection. Apgar V, Sticdle G: Birth defects-Their sigmicance as a public J Inf Dis 119:662-5, 1969 health problem. JAMA 204:371-374, 1968

62 FEBRUARY 1970 * 1 12 * 2 birth defect-producing infectious agents and the new mutations, and many sporadic defects for development of specific means to prevent fetal which no cause can be discovered may have the exposure. The same considerations apply to same etiologic base. To eliminate this group of teratogenic agents to which fetuses are exposed defects would require suppression of mutation, a during development. Many hereditary birth de- goal that may be neither achievable nor desirable fects can be prevented if parents known to be at in man. However, it is not suggested that agents risk of having defective children follow the rela- such as radiation and chemicals which increase tively simple although not necessarily pleasant the rate of mutation should not be avoided, since expedient of not having children. This approach there is little to be gained by deliberately creating is applicable to individuals who are known to be mutant genes. The preventability of chromosomal carriers of autosomal "dominant" or X-linked mu- abnormalities, both visible and, for the present at tant genes and to couples who have already had a least, invisible, is very much in the same situation child with an autosomal "recessive" birth defect. as the preventability of single gene mutations, and However, in the latter instance this method of the same considerations apply. birth defect prevention is somewhat after the fact One group of birth defects that has not yet been unless means were used, before child bearing, to considered is that composed of the abnormalities recognize those families in which both parents which occur with substantial frequencies and have were carrying the same deleterious gene or genes. ill-defined hereditary components. Included are While it is unlikely that all such genes could be many common congenital malformations such as screened, it is possible to visualize the development cleft lip and palate and congenitally dislocated of automated screening tests for several mutant hips. Recurrence risks in families of affected per- genes which have reasonably high frequencies in sons are relatively low, generally of the order of the population. 2 to 5 percent, but are definitely greater than in the Fortunately, many birth defects which could population at large. Many explanations have been result from chromosomal abnormalities are pre- advanced to explain these and other conditions vented by the spontaneous abortion of the affected with similar patterns of inheritance: the simul- embryos early in development. Of the chromo- taneous participation of mutant genes at several somal disorders compatible with viability, several separate genetic loci (polygenic inheritance); the show a pronounced maternal age effect-the older existence of many different forms of a gene at a the mother the greater the risk to the fetus. The single genetic locus; the interaction of genetic fac- prototype of this is trisomy 21 (mongolism) in tors, whether one or several, with internal and ex- which the overall incidence is approximately 1 in ternal environmental factors; or, despite the fa- 600 live births, ranging from 1 in 1,500 for moth- milial aggregation, the operation of environmental ers less than 30 years of age to 1 in 60 for mothers rather than hereditary factors. No matter which 45 or older. Regardless of how advancing ma- of these mechanisms is operative, it seems quite ternal age influences the occurrence of trisomy 21, unlikely that many defects of the types mentioned the incidence of the disease could be dramatically will be preventable at the time of their genesis. cut if women were to have their children during The recurrence risks are not so great nor the de- the third decade of life rather than spreading out fects so severe as to warrant restriction of family the child-bearing period over the third to the size. The genetic factors are likely to be many fifth decades. and relatively common in the population and Despite the conclusion that many of the birth therefore not readily controlled. And the environ- defects in the categories discussed will ultimately mental factors will to a large extent remain unde- be preventable, there are many which probably fined. will not. For both the infectious and teratogenic Without wishing to appear overly pessimistic, causes of defects, preventability requires recogni- it must be concluded that many birth defects are tion of the insulting agent, and this might not al- now and will remain unpreventable if prevention ways be possible. The agent might be so common is to occur at or before the time of causation. If or so occult as to defy identification, and, as prenatal intervention is considered an acceptable Bemfield points out, prospective studies designed mode of birth defect prevention, some but not to identify such agents have been unfruitful. Fur- all of these defects would become preventable. By thermore, hereditary birth defects often arise as testing all pregnancies, all chromosomal disorders

CALIFORNIA MEDICINE 63 The Western Journal of Medicine could be eliminated. With the development of to reduce the incidence of those serious birth de- suitable analytical methods, many hereditary dis- fects that are truly preventable. orders could also be prevented without the neces- CHARLES J. EPSTEIN, M.D. Unievrsily of California sity for the total avoidance of child bearing. It is San Pfracisco Medical Censer quite likely that both chromosomal and metabolic screening could be automated, and technical re- sources need not be a limiting factor. It is even possible to visualize the development of a fiber- optics amnioscope suitable for use in early preg- nancy so that external structural abnormalities not associated with chromosomal or metabolic disor- ders could be detected. I have deliberately omit- Important Advances ted "genetic engineering"-genetic intervention by molecular methods-since its hypothetical role in In Clinical Medicine birth defect prevention, as opposed to treatment, is still very much in question. THE ADVISORY PANELS to the Scientific Sections The more widely we speculate on what is the- which were established during the past year pro- vide a unique resource to the Scientific Board and oretically possible, the greater the attention that to the California Medical Association. Each ad- must be paid to questions of ends and means. visory panel is composed of the officers of the While no one seriously disputes the desirability section, a representative from the appropriate de- of eliminating birth defects, there are some who partment of each of California's eight medical cannot countenance prenatal diagnosis, with the schools and a representative from the pertinent possible consequence of interference with preg- professional societies in each specialty as they nancy, as a means of doing so. And many of those have been recognized by the Council. Thus each who do advocate its use would hesitate to apply it advisory panel reflects the knowledge and experi- to all pregnant women. Even at present, with ence to be found in academia and in practice- only a few indications for its use, they are con- and the base is quite broad. stantly faced by the dilemma of defining a cut-off Elsewhere in this journal (see pages 54 to 59) point, of deciding which conditions are serious we are beginning a new feature, "Important Ad- enough to merit prenatal intervention and which vances in Clinical Medicine," which is made pos- are not. How much greater will be the problem sible only because of the existence and cooperation when many more defects can be discovered early of these Advisory Panels to the Scientific Sections. in gestation. Each panel has been asked to identify those recent Leaving prenatal diagnosis aside, the same advances in its specialty which in the judgment of dilemma is inherent in all activities designed to the panelists are truly important in clinical medi- reduce the incidence of birth defects. In which cine, to epitomize them for the readers of this hereditary conditions should families be encour- journal, and in addition to provide references so the reader aged not to have children? When should time- may readily dig deeper into the specific subject or the general area if it is one with which consuming and expensive efforts be made to dis- he is not familiar. cover environmental factors which might in the It is hoped that these epitomized items of end turn out to be uncontrollable? What means medical progress, selected as they are by the of birth defect prevention are truly acceptable? judgment of very knowledgeable panels in each And, considering the likelihood that many birth field of interest, will be helpful to student, teacher defects are not preventable, for which defects and practitioner alike. They should make it easier should efforts at prevention be made at all? These for him to become aware of what it is he may not, questions are not easy to answer, and many an- yet probably should know, and to locate the infor- swers that could be given now might change as mation he will need to catch up with progress in more information is accumulated. Nevertheless, that particular subject. It should make possible answers must be found if the all too limited re- more precise use of the time a busy person can sources of society are to be most effectively utilized devote to "keeping up."

64 FEBRUARY 1970 * 112 * 2