The human autonomous karyotype and the origins of prenatal testing: children, pregnant women and early Down's syndrome cytogenetics, Madrid 1962-1975.

Through their ability to reveal and record abnormal chromosomes, whether inherited or accidentally altered, chromosomal studies, known as karyotyping, became the basis upon which medical genetics was constructed. The techniques involved became the visual evidence that confirmed a medical examination and were configured as a material culture for redefining health and disease, or the normal and the abnormal, in cytological terms. I will show that the study of foetal cells obtained by amniocentesis led to the stabilisation of karyotyping in its own right, while also keeping pregnant women under the vigilant medical eye. In the absence of any other examination, prenatal diagnosis by foetal karyotyping became autonomous from the foetal body. Although medical cytogenetics was practiced on an individual basis, data collected about patients over time contributed to the construction of population figures regarding birth defects. I study this complex trajectory by focussing on a Unit for Cytogenetics created in 1962 at the Clínica de la Concepción in Madrid. I incorporate the work and training of the clinicians who created the unit, and worked there as well as at other units in the large new hospitals of the national health care system built in Madrid during the mid-1960s and early 1970s.

Prenatal diagnosis: the irresistible rise of the 'visible fetus'.

Prenatal diagnosis was developed in the 1970s, a result of a partly contingent coming together of three medical innovations-amniocentesis, the study of human chromosomes and obstetrical ultrasound-with a social innovation, the decriminalization of abortion. Initially this diagnostic approach was proposed only to women at high risk of fetal malformations. Later, however, the supervision of the fetus was extended to all pregnant women. The latter step was strongly favoured by professionals' aspiration to prevent the birth of children with Down syndrome, an inborn condition perceived as a source of suffering for families and a burden on public purse. Experts who promoted screening for 'Down risk' assumed that the majority of women who carry a Down fetus will decide to terminate the pregnancy, and will provide a private solution to a public health problem. The generalization of screening for Down risk increased in turn the frequency of diagnoses of other, confirmed or potential fetal pathologies, and of dilemmas linked with such diagnoses. Debates on such dilemmas are usually limited to professionals. The transformation of prenatal diagnosis into a routine medical technology was, to a great extent, an invisible revolution.

Noninvasive prenatal detection of aneuploidy.

Noninvasive prenatal testing (NIPT) uses cell-free fetal DNA from the plasma of pregnant women to provide valuable information about the potential risks for fetal aneuploidy. This article provides a historical overview of both invasive diagnostic testing and serum screening approaches, both biochemical and the newer molecular noninvasive prenatal testing assays, used to identify patients who would be best served by invasive testing.

Historical aspects of genetic counseling: why was maternal age 35 chosen as the cut-off for offering amniocentesis?

The justification for offering amniocentesis to women age 35 or older is that by age 35 the risk of having a child with chromosome problem is greater than the risk of amniocentesis. In fact, this seemingly objective statement is not supported by historical analysis. Maternal age 35 was chosen for the cutoff based mostly on economic cost-benefit analysis rather than objective medical assessment. The story of why 35 was chosen illustrates how collective memory can affect, and be influenced by, the guiding ethical principles of a medical profession.