Type 1 diabetes is a serious and common disease, afflicting one per 200 of the population worldwide. It is widely believed to cause harmful physical maldevelopment--congenital malformations--and other consequences in the unborn children of women with the disease. This book considers the history of the disease in pregnant women and this belief that it causes anomalies since the time of the discovery of insulin in 1921, and presents a profound and critical appraisal of the subject of its supposed prenatal harmfulness.

To aid in unraveling the complexities of the causation of congenital malformations, various influences on their frequency are considered in this book. And of course the known and possible environmental bases of their occurrence are fully described. An introductory record of the history of perinatal mortality in the last three centuries gives foundation for the discussion of death in contemporary decades.

Teratology is at once among the oldest and youngest of human preoccupations. Coincident with man's first observations of the stars were his recordings of human and animal deformities. But, such aberrancies must have occurred even earlier, for although it is one of those things-like evolution-that cannot be proven, it is nevertheless indisputable that dysmorphogenesis must have occurred from the time complex forms of life first arose on our planet; and that from the beginnings of human awareness our species was conscious of such happenings. From the earliest recordings of this fascination with the form and meaning of abnormality a tortuous but continuous line extends to modern struggles to understand and control these manifestations. And now, after long occupying an honorable but peripheral place in the halls of philosophical and scientific pursuits, teratology has quite suddenly come to take a prominent position at the hub of a complex crossroads of human concerns. This shift in its fortune has taken several forms. Fetal maldevelopment has become the concern of environmentalists, activists of various persuasions, indus trial organizations, government agencies, ethicists, parents-i. e., individuals and groups whose actions are impelled by apprehension. Such motives are of course not without basis; the trauma of thalidomide left a scar yet raw. For still others clinicians, academics, experimentalists-the upsurge in the interest in fetal mal development is at a different level, and their pursuits are broad, taking external agents as but one of the causes of defective development."

A growing sophistication of the American populace about the nature and realities of the impact of the environment on prenatal development was not much in evi dence in 1983. Continuing accusations against Agent Orange and Bendectin high light what must be a deep credulousness and need to blame others for one's bio logical misfortunes. We despair that ignorance and nonaccountability can be dissipated by objective means. But one can only learn and teach and hope. The need to know what causes congenital malformations becomes more imperative as they become the last major holdout, the most unyielding of all the reasons babies still die and are seriously ill. In the aggregate, congenital malfor mations are now the cause of about one-third of the deaths of infants less than one month old and one-fifth of the deaths of those under one year old, up 50% in the last two decades. In the instance of one suspected cause of congenital malformations, maternal insulin-dependent diabetes mellitus, while the perinatal mortality rate of children of such women has gone down greatly since World War II, the fraction of deaths due to congenital malformations has grown correspondingly and is now approach ing 50%. Present-day knowledge of the causes of congenital malformations is most imperfect. A recent authoritative review found that there is understanding to one extent or another of the causation of less than half of all congenital malformations."

There is still no clear understanding of what causes the great majority of human congenital malformations. And since in most sorts of human disease and pathology that yet prevail prevention usually awaits understanding of cause, it is generally thought that the same is true of developmental aberrations. But is this true? For the relatively few congenital malformations whose causes are primarily environmental, it is plain that their discovery has enabled prevention, but not nec essarily immediately. It took a generation from the time of the discovery that maternal rubella was teratogenic to learn how to immunize against it. Much debate occurred before it was appreciated that thalidomide was a teratogen, and only its removal from the pharmacist's shelf and the end of the epidemic of limb defects attributed to the drug overcame the last doubts. For other proven environmental teratogens doubts and difficulties still con tinue. The claimed prevalence of fetal genital distortions due to female sex hor mones may have been exaggerated. Some potentially teratogenic therapeutic drugs, like anticoagulants, anticonvulsants, and anticancer chemicals, are still pre scribed despite this danger because of their benefits to pregnant women. For those congenital malformations whose basis is predominantly genetic or chromosomal it is different, however. Prevention has not been achieved by the discovery of such causes, as dramatic and revolutionary as some of them have been, except in the questionable sense of interference with reproduction by genetic coun seling or prenatal elimination. But this has not inhibited the romanticists.

Congenital malformations are worldwide occurrences striking in every condition of society. These severe physical abnormalities which are present at birth and affecting every part of the body happen more often than usually realized, once in every 33 births. The most common, after heart defects, are those of the neural tube (the brain and spinal cord) which happen in as many as one in every 350 births. They have been noted as curiousities in man and beast throughout recorded history and received great attention in our time by various fields of study, for example, their faulty prenatal development by embryologists, familial patterns by geneticists, causation by environmentalists and variability by population scientists.

Attention turned much in recent years to the relation of these malformations to deficiency of a particular dietary ingredient, folic acid, a subject this book analyzes in depth. The greatest conundrum of all, which this latest matter like so much else hinges on, is the amazing fact of the tremendous, almost universal decrease in the frequency of these anomalies since early in the 20th century. The puzzle is 'What can this downward trend possibly mean?' and at bottom 'Whether it is part of a long-term cyclical pattern'. This fascinating biological phenomenon is explored in the book together with various other topics.

Serious congenital malformations are a major contributor to the infant death rate worldwide. Their nonhereditary causes are multiple and complex, and include infectious and metabolic dangers, disease medication, nutritional inadequacy, medicinal products, environmental agents and pollutants, among them. The cause of many however is still unknown. The wide range of these causes makes the defects of interest to those of a wide range of medical and investigatory backgrounds, especialy clinicians, fundamental scientists, and environmentalists.

Congenital malformations are worldwide occurrences striking in every condition of society. These severe physical abnormalities which are present at birth and affecting every part of the body happen more often than usually realized, once in every 33 births. The most common, after heart defects, are those of the neural tube (the brain and spinal cord) which happen in as many as one in every 350 births. They have been noted as curiousities in man and beast throughout recorded history and received great attention in our time by various fields of study, for example, their faulty prenatal development by embryologists, familial patterns by geneticists, causation by environmentalists and variability by population scientists.

Attention turned much in recent years to the relation of these malformations to deficiency of a particular dietary ingredient, folic acid, a subject this book analyzes in depth. The greatest conundrum of all, which this latest matter like so much else hinges on, is the amazing fact of the tremendous, almost universal decrease in the frequency of these anomalies since early in the 20th century. The puzzle is 'What can this downward trend possibly mean?' and at bottom 'Whether it is part of a long-term cyclical pattern'. This fascinating biological phenomenon is explored in the book together with various other topics.

Congenital malformations are worldwide occurrences, they know no national borders, do not distinguish between races, ethnicities, rich or poor. These severe physical abnormalities, present at birth, happen more often than is usually realized, once in every 33 births. They strike every part of the body, limbs, head, heart, and all others.

The most frequent of them all are the many types of malformations of the cardiovascular system, the heart and its blood vessels, which happen in about once in every 250 births. Study of these conditions during the twentieth century took many forms, revolving about examination and analysis of their causes, genetic, nongenetic, and complex. To aid in unraveling the complexities of this causation, various influences on their frequency are considered, among them social conditions, maternal health, birthweight, newborn maturity. And of course the known and possible environmental bases of their occurrence are fully described.
The relation of infant death to cardiovascular malformation is noted; and puzzlement that the level of such deaths had not kept pace with the reduction of infant death itself and of that associated with other kinds of malformations during this period.

An introductory record of the history of perinatal mortality in the last three centuries gives foundation for the discussion of death in contemporary decades.

Type 1 diabetes is a serious and common disease, afflicting one per 200 of the population worldwide. It is widely believed to cause harmful physical maldevelopment--congenital malformations--and other consequences in the unborn children of women with the disease. This book considers the history of the disease in pregnant women and this belief that it causes anomalies since the time of the discovery of insulin in 1921, and presents a profound and critical appraisal of the subject of its supposed prenatal harmfulness.

My HalfLife in Teratology-As it Relates to the Origins of Cancer (R.W. Miller). Intergenerational Factors in Pregnancy Outcomes (I. Emanuel). Epidemiological Studies of Congenital Abnormalities in Hungary (A. Czeizel). A Contemporary Overview of Behavioral Teratology (D.E. Hutchings). Do Thresholds Exist for Developmental Toxicants? (G.P. Daston). The History of His Life and Career (E. Wolff). Index.