Genetic Disorders and the Fetus

43 36 Prenatal and Preimplantation Diagnosis: International Policy Perspectives Introduction Prenatal diagnosis Legal approaches Professional guidelines Preimplantation genetic diagnosis Sex selection in prenatal diagnosis and preimplantation genetic diagnosis Emerging technologies, new issues? References

44 37 Ethical Issues in the Diagnosis and Management of Genetic Disorders in the Fetus Professional ethics in obstetrics Clinical applications of professional ethics in obstetrics Ethical issues in clinical innovation and research Conclusion References

45 Index

46 End User License Agreement

1 Chapter 1 Table 1.1 The frequencies of genetic disorders in 1,169,873 births, 1952–1983 34 Table 1.2 Life expectancy with Down syndrome, between 1908–1981, to age 68 year... Table 1.3 Defects and complications associated with Down syndrome 132 – 165. Table 1.4 Single‐gene dominant disorders in offspring that are associated with ... Table 1.5 Genetic disorders in various ethnic groups. Table 1.6 Residual risk values for diseases in Ashkenazi Jewish populations. Table 1.7 Signs in females who are carriers of selected X‐linked recessive dise... Table 1.8 Selected examples of monogenic disorders with established somatic mos... Table 1.9 The frequency of emotions and somatic symptoms of 84 women and 68 men...

2 Chapter 2 Table 2.1 List of conditions for which preimplantation genetic testing (PGT) wa... Table 2.2 Clinical outcome of PGT‐M performed by polar body approach.

3 Chapter 3 Table 3.1 Amniotic fluid volume percentile values in relation to gestational ag... Table 3.2 Biochemical constituents and other characteristics of amniotic fluid ... Table 3.3 Trace elements in amniotic fluid (see also Table 3.5) Table 3.4 Hormones measured in amniotic fluid during the second or third trimes... Table 3.5 Examples of environmental drugs and chemicals in the fetal environmen... Table 3.6 Examples of toxicants reported in amniotic fluid Table 3.7 The classification of human second‐trimester amniotic fluid cells in ...

4 Chapter 4 Table 4.1 Genomic and chromosomal defects affecting placental function and feta...

5 Chapter 6Table 6.1 Mean level in Down syndrome for each widely used marker, according to...Table 6.2 Mean α‐fetoprotein level in neural tube defect, according to gestatio...Table 6.3 Standard deviations and correlation coefficients of log 10MoM values ...Table 6.4 Second‐trimester screening policies, according to hCG typeTable 6.5 First‐trimester screening using NT alone and combined with serum mark...Table 6.6 Sequential screening according to strategy, according to first‐trimes...Table 6.7 Model predicted AFP screening DR and FPR according to gestational age...Table 6.8 Addition of ultrasound nasal bone determination to first‐trimester po...Table 6.9 Addition of further serum markers to the Combined test, according to ...Table 6.10 Addition of ultrasound nuchal skin‐fold, nasal bone length, and pren...Table 6.11 Detection rate and false‐positive rate given final cut‐off risk afor...Table 6.12 Previous Down syndrome pregnancy: detection rate and false‐positive ...Table 6.13 Mean level in unaffected twins and the expected mean in Down syndrom...Table 6.14 Edwards syndrome detection rate using a Down syndrome risk cut‐off a...

6 Chapter 7Table 7.1 Performance of cell‐free DNA screening for common aneuploidy and sex ...Table 7.2 Cell‐free DNA and positive predictive value.Table 7.3 Comparison of prenatal screening options for fetal aneuploidy 41.Table 7.4 Cell‐free DNA screening for trisomy 21 in twin gestations.

7 Chapter 8Table 8.1 Selected studies reporting noninvasive prenatal diagnosis (NIPD) for ...

8 Chapter 9Table 9.1 Summary of collaborative amniocentesis studies.Table 9.2 Summary of selected studies on loss rate from chorionic villus sampli...Table 9.3 Fetal loss rates (<28 weeks) from trials comparing transabdominal ver...

9 Chapter 10Table 10.1 Pregnancy outcome in 100,000 consecutive cases after the detection o...Table 10.2 The efficiency of detection of neural tube defects using qualitative...Table 10.3 Practical false‐positive rates after amniotic fluid α‐fetoprotein as...Table 10.4 The odds of having a fetus with open spina bifida after positive α ...Table 10.5 The risks of neural tube defect (NTD) according to family history 105Table 10.6 Syndromes and other disorders in which neural tube defects (NTDs) ha...Table 10.7 Selected complications in two original cohorts of 117 and 118 patien...

10 Chapter 11Table 11.1 Chromosomal abnormalities in liveborn babies.Table 11.2 Maternal age‐specific rates for Down syndrome and all chromosomal ab...Table 11.3 Estimates of spontaneous fetal loss rates subsequent to chorionic vi...Table 11.4 Crude maternal age‐specific rates (%) for chromosome abnormalities a...Table 11.5 The incidence of de novo balanced structural rearrangements and super...Table 11.6 The frequency of chromosomal abnormalities in unselected spontaneous...Table 11.7 Autosomal trisomy in spontaneous abortions.Table 11.8 The frequency of chromosomal abnormalities in stillbirths and neonat...Table 11.9 Typical prenatal screening marker patterns for some specific chromos...Table 11.10 Frequency and types of chromosome abnormalities in fetuses with ult...Table 11.11 Ultrasound abnormalities and frequency of fetal aneuploidy.Table 11.12 Segregation products at the time of prenatal diagnosis when a paren...Table 11.13 Segregation in Robertsonian translocations a.Table 11.14 Prenatal results for Robertsonian translocation involving a chromos...Table 11.15 Prenatal results for pericentric inversions ( n = 173) a.Table 11.16 Excess rates of Down syndrome and other aneuploidy in women who had...Table 11.17 Estimated excess second‐trimester risk for women who had a previous...Table 11.18 Definition and relative frequencies of different types of mosaicism...Table 11.19 The percentage of mosaicism excluded with 90, 95, and 99 percent co...Table 11.20 The percentage of mosiacism that will be detected with 95% probabil...Table 11.21 The frequency of mosaicism and pseudomosaicism.Table 11.22 The frequency of multiple‐cell pseudomosaicism (MCPM).Table 11.23 The frequency of single‐cell pseudomosaicism (SCPM).Table 11.24 The frequency of trisomy chromosome in multiple‐cell pseudomosaicis...Table 11.25 The frequency of trisomy chromosome in single‐cell pseudomosaicism.Table 11.26 A summary of prenatally diagnosed cases with 46/47,+20.Table 11.27 Summary of prenatally diagnosed cases with 46/47,+20 cytogenetic co...Table 11.28 Summary of pregnancy outcomes and confirmation rate for trisomy mos...Table 11.29 Major sex chromosome mosaicism diagnosed in amniocytes.Table 11.30 45,X/46,XY mosaicism diagnosed in amniocytes.Table 11.31 Guidelines for the management of cases with suspected amniocyte mos...Table 11.32 Summary of chromosome mosaicism and the percentage of abnormal outc...Table 11.33 The frequency (%) of de novo rearrangements diagnosed in newborns an...Table 11.34 The phenotypic outcome of de novo balanced rearrangement diagnosed a...Table 11.35 The incidence of supernumerary marker chromosomes.Table 11.36 Risks for abnormality for a subgroup of de novo supernumerary marker...Table 11.37 Incidence of uniparental disomy in carriers of Robertsonian translo...Table 11.38 The frequency of maternal cell contamination (MCC) in amniocytes.

11 Chapter 12Table 12.1 The incidence of various karyotypes among females with Turner syndrom...

12 Chapter 13Table 13.1 Incidence and spectrum of chromosome abnormalities in prenatal diagn...Table 13.2 Select microdeletion/microduplication syndromes by frequency and ass...Table 13.3 Imprinted chromosomes associated with uniparental disomy syndromes.Table 13.4 Frequency of the most common microdeletion/microduplications observe...Table 13.5 Frequency of the most common microdeletions/microduplications observ...