Fetal therapy: practical ethical considerations

Progress in prenatal diagnosis can lead to the diagnosis of severe fetal abnormalities for which natural history anticipates a fatal outcome or the development of severe disability despite optimal postnatal care. Intrauterine therapy can be offered in these selected cases. Prenatal diagnosis is the only field of medicine in which termination is an option in the management of severe diseases. Fetal therapy has therefore developed as an alternative to fatalist expectant prenatal management as well as to termination of pregnancy (TOP). There are few standards of fetal care that have gone beyond the stage of equipoise and even fewer have been established based on appropriate studies comparing pre- and postnatal care. Several ethical questions are being raised as fetal surgery develops, including basic Hippocratic principles of patients' autonomy and doctors' duty of competence moving the boundaries between experimental surgery, therapeutic innovation and standard care. In addition, the technical success of a fetal intervention can only rarely fully predict the postnatal outcome. Managing uncertainty regarding long-term morbidity and the possibility for fetal therapy to change the risk of perinatal death into that of severe handicap remains a critical factor affecting women's choice for TOP as an alternative to fetal therapy. Copyright © 2011 John Wiley & Sons, Ltd.     

Screening for fetal Down syndrome with maternal serum hCG and oestriol: A prospective study

We report the preliminary results of a prospective study aimed at evaluating the effectiveness of Down syndrome (DS) screening using second-trimester measurement of maternal serum human chorionic gonadotrophin (hCG) and unconjugated oestriol (uE3) together with maternal age. Reference values for hCG, uE3, and the hCG/uE3 ratio in normal pregnancies were established from more than 3000 normal gestations and found to follow a log-normal statistical distribution. Risk evaluation was made using reference values for affected pregnancies from retrospective studies. Screening of 10 000 women under 38 years resulted in 412 amniocenteses and the prenatal diagosis of six cases of DS, whereas four cases remained undetected until term. In a parallel study, diagnostic amniocentesis was performed in women over 38 years and in women with a previous affected child, and an evaluation of the risk of fetal DS based on serum hCG and uE3 levels was made in all cases. Fourteen cases of DS were detected. Median values for hCG and uE3 in the 24 affected pregnancies were close to the 90th and tenth centiles of the normal reference values, respectively, and thus are in good agreement with the values reported by others in retrospective studies.     

Prenatal diagnosis of syndromes associating albinism and immune deficiencies (Chediak-Higashi syndrome and variant)

We have successfully undertaken the prenatal diagnosis of two hereditary syndromes associating albinism and immune defects. Because the genes responsible for these diseases have not yet been mapped and the immune abnormalities are too subtle to be diagnosed in utero, the prenatal diagnosis was made using a morphological approach. In the case of Chediak-Higashi syndrome, it was based on light microscopic examination of the hair shaft and on light and electron microscopic study of polymorphonuclear cells. In the syndrome associating immune deficiency and partial albinism, the Griscelli syndrome, only examination of the hair was feasible. The diagnosis was negative in 12 fetuses at risk and positive in four.     

Insights into the pathophysiology of twin–twin transfusion syndrome

Twin–twin transfusion syndrome (TTTS) is attributed to trans-anastomotic transfusion between twins. Anastomoses are ubiquitous in monochorionic (MC) placentae, yet TTTS develops in only 15%. Although ex vivo and in vivo studies fail to identify a unique anastomotic signature, TTTS placentae are typically associated with an imbalance in unidirectional arteriovenous anastomoses with absent bidirectional anastomoses. Doppler detection of an artery-artery anastomosis reduces the chance of TTTS, whereas, in those that develop the disease, it improves stage-independent survival. Selective laser is often curative, but an increasingly recognized risk of persistent or reverse TTTS may be attributable to atypical arteriovenous anastomoses not identifiable from the chorionic plate. Simple dysvolaemia fails to explain several phenotypic features, including haematological concordancy, recipient hypertension, and reversibly absent end diastolic flow in the donor. The renin-angiotensin system is upregulated in the donor and downregulated in the recipient's kidneys, while paradoxically raised renin levels in the recipient may contribute to raised afterload along with endothelin. Although research is limited in humans by therapy and the lack of a suitable experimental model, further studies of placental and vascular pathophysiology may not only refine current treatment modalities but may also, in addition, suggest further avenues for downstream management such as genetic predisposition testing or pharmacological intervention. Copyright © 2005 John Wiley & Sons, Ltd.