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Chorionic villus sampling and early amniocentesis for prenatal diagnosis
THE LANCET
pharmacists, especially in states with statutes on syringe prescription, cannot sell syringes over the counter, or may have to ask the customer intrusive questions and take his or her name and address. Consequently the large network of US pharmacies are not able effectively to take part in HIVprevention activities. Finally, IDUs themselves may be committing a criminal offence by complying with public-health advice to carry and use sterile syringes for each injection. Funding and expansion of needleexchange programmes, though important, are not sufficient HIVprevention strategies. A comprehensive, well-financed, strategy to prevent both drug use and HIV/AIDS among IDUs would: eliminate regulations that bar the availability and use of sterile druginjection equipment; expand access to high-quality treatment for drug and alcohol dependency; provide education and counselling on the harms of illicit drugs; adopt effective community strategies to discourage drug use and associated criminal activities; provide rehabilitation for offenders; and provide support for affected families and young people. Lawrence Gostin Georgetown University Law Centre, NW Washington, DC 20001, USA
1
2
3
4
Lurie P, Drucker E. An opportunity lost: HIV infections associated with lack of a national needle-exchange programme in the USA. Lancet 1997; 349: 604–08. Holmberg SD. The estimated prevalence and incidence of HIV in 96 large US metropolitan areas. Am J Pub Health 1996; 86: 642–54. Centers for Disease Control and Prevention. AIDS associated with injecting-drug use— United States, 1995. MMWR 1996; 45: 392–98. Gostin LO, Lazzarini Z, Jones TS, Flaherty K. Prevention of HIV/AIDS and other blood-borne diseases among injecting drug users: a national survey on the regulation of syringes and needles. JAMA 1997; 277: 53–62.
SIR—Lurie and Drucker (March 1, p 604)1 discuss the absence of a national needle exchange programme (NEP) in the USA, where most infections arise among injecting drug users (IDUs), their sexual partners, and children. Deregulation of the syringe prescription laws and drug paraphernalia laws is a more urgent necessity which will have a wider impact on HIV control, and costs nothing. Your editorial comment in the same issue2 that “political squeamishness over so-called moral concerns has hindered, diverted, or halted numerous sensible public health initiatives” aptly describes the USA situation. This squeamishness is expressed in the demand for definitive
Vol 349 • May 10, 1997
evidence of effectiveness before funding, although “logistical and ethical impediments to randomised trials [further] preclude such ‘definitive’ evidence”, according to Lurie and Drucker. The role of NEPs should be interpreted in the context of social and legal factors. Gostin and colleagues3 have said that “multiperson use of syringes is a complex behaviour initially reported as part of the subculture . . .; sharing was thought to be a sign of social bonding . . . . Increasingly, however, researchers have identified scarcity of syringes . . . as a leading factor in sharing behaviour”. In the USA, multiperson use is necessitated by syringe prescription laws in eight and drug paraphernalia laws in 47 states; IDUs pay a dollar or two or a share of drugs to use a syringe that costs about 25 US cents in an unrestricted market. Deregulation will abolish scarcity, increase availability, reduce cost, allow IDUs to carry their own without fear of arrest, undermine the need to share and have a general impact. Without deregulation, NEP effectiveness is severely limited. There seems to be a direct relation between syringe prescription laws in California, Delaware, Illinois, Massachusetts, New Hampshire, New Jersey, New York, and Rhode Island, and AIDS. IDU-associated AIDS accounts for greater than 50% of cases reported from Delaware (204 [65%] of 314 cases), Puerto Rico (1647 [63%] of 2604), Connecticut (1018 [61%] of 1676), Maryland (1382 [52%] of 2680), and Rhode Island (121 [52%] of 232), and for 49% from New York (6130 of 12 394) and New Jersey (2155 of 4364).4 Northeast accounts for 44% (11 284) of IDU associated AIDS cases.4 States with highest AIDS rates (New York [39·4 cases per 100 000 population], New Jersey [32·3], Connecticut [24·7], Massachusetts [12·5], Rhode Island [12·4], Delaware [27·8]), except Maryland (26·2), and Florida (19·3), also have syringe prescription laws. (There is a clear distinction between syringe prescription laws [a prescription is required to purchase a syringe] and drug paraphernalia laws [variably enforced according to the gravity of the local drug problem]. Strict enforcement is reported in Miami and Baltimore, among other cities. California and Illinois also have IDUrelated AIDS problems in large metropolitan areas.) Studies in Connecticut, which repealed syringe prescription laws in 1992, indicate that more IDUs obtain syringes from pharmacies than NEPs. Political resistance to paraphernalia deregulation, seen as a symbolic justification of drugs, is
understandable. Poverty and minority status of IDUs exacerbate this resistance.5 However, war on AIDS is a public heath emergency, not an appendage of the war on drugs. In the USA, which has the highest IDUrelated AIDS cases, bleach disinfection, with limited efficacy, is the general HIV-prevention strategy. Thus, deregulation, as a specific strategy of HIV control, is an urgent, critical need. In that liberalised context, NEPs could serve as points of access and a bridge to treatment. IDUs must be given an opportunity to avoid AIDS. Daniel Fernando 550 East 16th Street, Brooklyn, NY 11226, USA
1
2 3
4
5
Lurie P, Drucker E. An opportunity lost: HIV infections associated with lack of a national needle exchange programme in the USA. Lancet 1997; 349: 604–08. Editorial. The moral maze of public health. Lancet 1997; 349: 583. Gostin LO, Lazzarini Z, Jones S, et al. Prevention of HIV/AIDS and other bloodborne diseases among injecting drug users. JAMA 1997; 277: 53–62. AIDS associated with injection drug use— United States, 1995. MMWR 1996; 45: 392–98. Fernando D. AIDS and intravenous drug use: the influence of morality, politics, social science and race in the making of a tragedy. Connecticut: Praeger, 1993.
Chorionic villus sampling and early amniocentesis for prenatal diagnosis SIR—Stranc and colleagues (March 8, p 711)1 review the maternal risks associated with prenatal procedures for the diagnosis of genetic disorders and anomalies. But the impact of such procedures on the fetus and neonate must also be considered. Second trimester amniocentesis has been associated with an excess of lungfunction abnormalities, and chorionic villus sampling (CVS) up to 10 weeks of gestation with oromandibular limb hypogenesis syndrome and isolated fetal limb abnormalities. There is limited information on the effect of invasive procedures done at 10–14 weeks of gestation on infant morbidity. We, therefore, undertook a prospective study, funded by the Medical Research Council, in which we compared the outcome of infants whose mothers had undergone early amniocentesis (n=278), CVS (n=262), or no invasive antenatal procedures (controls; n=264). The groups were well matched apart from age: the control mothers were about 2 years younger than the others. Nevertheless, there was an excess of congenital anomalies in the early
1395
THE LANCET
amniocentesis (5%) and CVS (6%) groups compared with the control group (1·5%). Some of the anomalies affected only single infants, but there was a significant excess of talipes and congenital dislocated hip among infants in the early amniocentesis group: eight compared with two in the CVS group and none among controls (p<0·05, Fisher’s exact test). Minor digit anomalies occurred only in the CVS (six infants) and early amniocentesis (three infants) groups, but only among infants whose mothers were older than 35 years.2 A greater proportion of infants in the early amniocentesis (19) and CVS (eight) groups than in the control group (five) required admission to a neonatal intensive-care unit. Nine infants in the early aminocentesis group compared with only one in the CVS group were admitted because of respiratory problems.3 Perinatal studies of a subset showed that infants whose mothers had undergone early amniocentesis or CVS had worse lung function than controls: about 50% higher airways resistance and lower specific conductance.4 During the first year, early amniocentesis infants compared with CVS infants or controls were at least 1·5 times more likely to suffer respiratory symptoms, cough and wheeze, and require admission to hospital for chest-related disorders. Those findings were confirmed in a postal survey of outcome which involved more than 1200 infants. Infants in the early amniocentesis and CVS groups had significantly higher lung volumes than did the controls during the first 2 years. Hyperinflation was more common after early amniocentesis.5 Genetic testing during the first trimester is attractive because it allows early intervention should an abnormality be found. This reason is so important to many women that it has been shown to outweigh other factors such as related miscarriage rates, level of karyotypic error, or maternal morbidity. Our finding that amniocentesis or CVS at 10–14 weeks of gestation is associated with increased infant morbidity emphasises that the effect of such procedures on the infants should be considered when balancing relative risks and benefits.
3
4
5
Greenough A, Yuksel B, Naik S, Nicolaides KH. Invasive antenatal procedures and requirement for NICU admission. Eur J Pediatr (in press). Yüksel B, Greenough A, Naik S, Nicolaides KH. Perinatal lung function and invasive antenatal procedures. Thorax 1997; 52: 181–84. Greenough A, Yuksel B, Naik S, Nicolaides KH. Lung volume abnormalities in young children and invasive first trimester procedures. Eur Respir J 1996; 9: 466–67.
SIR—I was disappointed to read the seminar on chorionic villus sampling (CVS) and amniocentesis for prenatal diagnosis.1 This review of invasive techniques of prenatal diagnosis ignores much of the established published research, and gives misleading data for the risks of each procedure. I was particularly concerned by the comments on fetal blood sampling. To report a procedure-related loss rate of 6% is misleading. The few studies of the procedure-related losses after fetal blood sampling show that the loss rate relates to the indication for the procedure.2,3 In addition, a posterior placenta is certainly not a contraindication to fetal blood sampling, which can be performed from the umbilical cord at either placental origin or fetal origin, intrahepatic vein, or fetal heart. I also find it hard to understand the contraindications listed for midtrimester amniocentesis, CVS, and early amniocentesis. It should be emphasised that, particularly in the UK, amniocentesis is very rarely indicated in the diagnosis of neural-tube defects; diagnostic ultrasound has superseded invasive testing in most cases. Neither amniocentesis nor CVS can be used to diagnose structural defects. This diagnosis can only be confirmed on visualisation of the fetus by ultrasound. All those involved in prenatal diagnosis accept that invasive procedures carry a risk of pregnancy loss. The indications for each procedure take into careful consideration benefit-risk implications. Moreover, most units will carry out internal audits, which allows them to offer patients accurate information about their own loss rates for each procedure. Pam Johnson Institute of Obstetrics and Gynaecology, Queen Charlotte’s and Chelsea Hospital, London W6 0XG, UK
*Anne Greenough, Kypros H Nicolaides *Department of Child Health, King’s College Hospital, London SE5 9RS, UK; and Harris Birthright Research Centre for Fetal Medicine, King’s College School of Medicine and Dentistry, London
1
2
Stranc LC, Evans JA, Hameton JL. Chorionic villus sampling and amniocentesis for prenatal diagnosis. Lancet 1997; 349: 711–14. Greenough A. Congenital abnormalities and antenatal invasive procedures. Bio Neonate 1996; 70: 187–88.
1396
1
2
3
Stranc LC, Evans JA, Hamerton JL. Chorionic villus sampling and amniocentesis for prenatal diagnosis. Lancet 1997; 349: 711–14. Maxwell DJ, Johnson P, Hurley P, et al. Fetal blood sampling and pregnancy loss in relation to indication. Br J Obstet Gynaecol 1991; 98: 892–97. Bernaschek G, Yildiz A, Kolankaya A, et al. Complications of cordocentesis in high risk pregnancies: effects on fetal loss or preterm delivery. Prenat Diagn 1995; 15: 995–1000.
Authors’ reply S IR —Greenough and Nicolaides correctly state that fetal as well as maternal risks must be part of any discussion about whether or not to have prenatal diagnosis, and must be included in the assessment of different procedures when such a choice is available. As we stated in our seminar, the safety of early amniocentesis has not yet been determined. There has certainly been evidence to indicate that this procedure is not without risk to the fetus with increased rates of positional limb anomalies, respiratory difficulties, and preterm delivery having been reported. This increased risk has not been conclusively demonstrated, but several large trials are underway. We thank Greenough and Nicolaides for sharing the results of their work. Johnson comments that we ignore much of the published research on prenatal diagnosis. But we were specifically asked to compare midtrimester amniocentesis with chorionic villus sampling (CVS), and were constrained within space limits. Our discussion of other techniques for prenatal diagnosis was secondary. We are concerned by Johnson’s claim that we give misleading figures for the risks of each procedure. The figures for midtrimester amniocentesis and CVS were obtained from some of the largest and most rigorous studies of these techniques. With regards to the risk figures cited for cordocentesis: as Johnson notes, there is little available evidence of the risks to the fetus associated with this procedure. We attempted to put the figures into perspective by stating that these pregnancies were often at higher risk of complications. Regarding the procedural contraindications listed, these are not absolute. Although, it may be technically possible to perform these procedures when contraindicated, it may not be recommended. To the best of our knowledge, these are not out of line with current practice. We agree with Johnson that in some jurisdictions, and that includes our own province of Manitoba, amniocentesis is not used for severe, isolated neural-tube defects. However, in centres that do not routinely screen maternal serum for alpha-fetoprotein, or in cases in which it is difficult to visualise the fetus, amniocentesis is still appropriate to determine the fetal karyotype or measure amniotic-fluid protein concentrations. Also, if a neural-tube defect is suspected and other anomalies are seen on ultrasound, an amniocentesis may be carried out to determine the fetal karyotype and obtain further Vol 349 • May 10, 1997
pharmacists, especially in states with statutes on syringe prescription, cannot sell syringes over the counter, or may have to ask the customer intrusive questions and take his or her name and address. Consequently the large network of US pharmacies are not able effectively to take part in HIVprevention activities. Finally, IDUs themselves may be committing a criminal offence by complying with public-health advice to carry and use sterile syringes for each injection. Funding and expansion of needleexchange programmes, though important, are not sufficient HIVprevention strategies. A comprehensive, well-financed, strategy to prevent both drug use and HIV/AIDS among IDUs would: eliminate regulations that bar the availability and use of sterile druginjection equipment; expand access to high-quality treatment for drug and alcohol dependency; provide education and counselling on the harms of illicit drugs; adopt effective community strategies to discourage drug use and associated criminal activities; provide rehabilitation for offenders; and provide support for affected families and young people. Lawrence Gostin Georgetown University Law Centre, NW Washington, DC 20001, USA
1
2
3
4
Lurie P, Drucker E. An opportunity lost: HIV infections associated with lack of a national needle-exchange programme in the USA. Lancet 1997; 349: 604–08. Holmberg SD. The estimated prevalence and incidence of HIV in 96 large US metropolitan areas. Am J Pub Health 1996; 86: 642–54. Centers for Disease Control and Prevention. AIDS associated with injecting-drug use— United States, 1995. MMWR 1996; 45: 392–98. Gostin LO, Lazzarini Z, Jones TS, Flaherty K. Prevention of HIV/AIDS and other blood-borne diseases among injecting drug users: a national survey on the regulation of syringes and needles. JAMA 1997; 277: 53–62.
SIR—Lurie and Drucker (March 1, p 604)1 discuss the absence of a national needle exchange programme (NEP) in the USA, where most infections arise among injecting drug users (IDUs), their sexual partners, and children. Deregulation of the syringe prescription laws and drug paraphernalia laws is a more urgent necessity which will have a wider impact on HIV control, and costs nothing. Your editorial comment in the same issue2 that “political squeamishness over so-called moral concerns has hindered, diverted, or halted numerous sensible public health initiatives” aptly describes the USA situation. This squeamishness is expressed in the demand for definitive
Vol 349 • May 10, 1997
evidence of effectiveness before funding, although “logistical and ethical impediments to randomised trials [further] preclude such ‘definitive’ evidence”, according to Lurie and Drucker. The role of NEPs should be interpreted in the context of social and legal factors. Gostin and colleagues3 have said that “multiperson use of syringes is a complex behaviour initially reported as part of the subculture . . .; sharing was thought to be a sign of social bonding . . . . Increasingly, however, researchers have identified scarcity of syringes . . . as a leading factor in sharing behaviour”. In the USA, multiperson use is necessitated by syringe prescription laws in eight and drug paraphernalia laws in 47 states; IDUs pay a dollar or two or a share of drugs to use a syringe that costs about 25 US cents in an unrestricted market. Deregulation will abolish scarcity, increase availability, reduce cost, allow IDUs to carry their own without fear of arrest, undermine the need to share and have a general impact. Without deregulation, NEP effectiveness is severely limited. There seems to be a direct relation between syringe prescription laws in California, Delaware, Illinois, Massachusetts, New Hampshire, New Jersey, New York, and Rhode Island, and AIDS. IDU-associated AIDS accounts for greater than 50% of cases reported from Delaware (204 [65%] of 314 cases), Puerto Rico (1647 [63%] of 2604), Connecticut (1018 [61%] of 1676), Maryland (1382 [52%] of 2680), and Rhode Island (121 [52%] of 232), and for 49% from New York (6130 of 12 394) and New Jersey (2155 of 4364).4 Northeast accounts for 44% (11 284) of IDU associated AIDS cases.4 States with highest AIDS rates (New York [39·4 cases per 100 000 population], New Jersey [32·3], Connecticut [24·7], Massachusetts [12·5], Rhode Island [12·4], Delaware [27·8]), except Maryland (26·2), and Florida (19·3), also have syringe prescription laws. (There is a clear distinction between syringe prescription laws [a prescription is required to purchase a syringe] and drug paraphernalia laws [variably enforced according to the gravity of the local drug problem]. Strict enforcement is reported in Miami and Baltimore, among other cities. California and Illinois also have IDUrelated AIDS problems in large metropolitan areas.) Studies in Connecticut, which repealed syringe prescription laws in 1992, indicate that more IDUs obtain syringes from pharmacies than NEPs. Political resistance to paraphernalia deregulation, seen as a symbolic justification of drugs, is
understandable. Poverty and minority status of IDUs exacerbate this resistance.5 However, war on AIDS is a public heath emergency, not an appendage of the war on drugs. In the USA, which has the highest IDUrelated AIDS cases, bleach disinfection, with limited efficacy, is the general HIV-prevention strategy. Thus, deregulation, as a specific strategy of HIV control, is an urgent, critical need. In that liberalised context, NEPs could serve as points of access and a bridge to treatment. IDUs must be given an opportunity to avoid AIDS. Daniel Fernando 550 East 16th Street, Brooklyn, NY 11226, USA
1
2 3
4
5
Lurie P, Drucker E. An opportunity lost: HIV infections associated with lack of a national needle exchange programme in the USA. Lancet 1997; 349: 604–08. Editorial. The moral maze of public health. Lancet 1997; 349: 583. Gostin LO, Lazzarini Z, Jones S, et al. Prevention of HIV/AIDS and other bloodborne diseases among injecting drug users. JAMA 1997; 277: 53–62. AIDS associated with injection drug use— United States, 1995. MMWR 1996; 45: 392–98. Fernando D. AIDS and intravenous drug use: the influence of morality, politics, social science and race in the making of a tragedy. Connecticut: Praeger, 1993.
Chorionic villus sampling and early amniocentesis for prenatal diagnosis SIR—Stranc and colleagues (March 8, p 711)1 review the maternal risks associated with prenatal procedures for the diagnosis of genetic disorders and anomalies. But the impact of such procedures on the fetus and neonate must also be considered. Second trimester amniocentesis has been associated with an excess of lungfunction abnormalities, and chorionic villus sampling (CVS) up to 10 weeks of gestation with oromandibular limb hypogenesis syndrome and isolated fetal limb abnormalities. There is limited information on the effect of invasive procedures done at 10–14 weeks of gestation on infant morbidity. We, therefore, undertook a prospective study, funded by the Medical Research Council, in which we compared the outcome of infants whose mothers had undergone early amniocentesis (n=278), CVS (n=262), or no invasive antenatal procedures (controls; n=264). The groups were well matched apart from age: the control mothers were about 2 years younger than the others. Nevertheless, there was an excess of congenital anomalies in the early
1395
THE LANCET
amniocentesis (5%) and CVS (6%) groups compared with the control group (1·5%). Some of the anomalies affected only single infants, but there was a significant excess of talipes and congenital dislocated hip among infants in the early amniocentesis group: eight compared with two in the CVS group and none among controls (p<0·05, Fisher’s exact test). Minor digit anomalies occurred only in the CVS (six infants) and early amniocentesis (three infants) groups, but only among infants whose mothers were older than 35 years.2 A greater proportion of infants in the early amniocentesis (19) and CVS (eight) groups than in the control group (five) required admission to a neonatal intensive-care unit. Nine infants in the early aminocentesis group compared with only one in the CVS group were admitted because of respiratory problems.3 Perinatal studies of a subset showed that infants whose mothers had undergone early amniocentesis or CVS had worse lung function than controls: about 50% higher airways resistance and lower specific conductance.4 During the first year, early amniocentesis infants compared with CVS infants or controls were at least 1·5 times more likely to suffer respiratory symptoms, cough and wheeze, and require admission to hospital for chest-related disorders. Those findings were confirmed in a postal survey of outcome which involved more than 1200 infants. Infants in the early amniocentesis and CVS groups had significantly higher lung volumes than did the controls during the first 2 years. Hyperinflation was more common after early amniocentesis.5 Genetic testing during the first trimester is attractive because it allows early intervention should an abnormality be found. This reason is so important to many women that it has been shown to outweigh other factors such as related miscarriage rates, level of karyotypic error, or maternal morbidity. Our finding that amniocentesis or CVS at 10–14 weeks of gestation is associated with increased infant morbidity emphasises that the effect of such procedures on the infants should be considered when balancing relative risks and benefits.
3
4
5
Greenough A, Yuksel B, Naik S, Nicolaides KH. Invasive antenatal procedures and requirement for NICU admission. Eur J Pediatr (in press). Yüksel B, Greenough A, Naik S, Nicolaides KH. Perinatal lung function and invasive antenatal procedures. Thorax 1997; 52: 181–84. Greenough A, Yuksel B, Naik S, Nicolaides KH. Lung volume abnormalities in young children and invasive first trimester procedures. Eur Respir J 1996; 9: 466–67.
SIR—I was disappointed to read the seminar on chorionic villus sampling (CVS) and amniocentesis for prenatal diagnosis.1 This review of invasive techniques of prenatal diagnosis ignores much of the established published research, and gives misleading data for the risks of each procedure. I was particularly concerned by the comments on fetal blood sampling. To report a procedure-related loss rate of 6% is misleading. The few studies of the procedure-related losses after fetal blood sampling show that the loss rate relates to the indication for the procedure.2,3 In addition, a posterior placenta is certainly not a contraindication to fetal blood sampling, which can be performed from the umbilical cord at either placental origin or fetal origin, intrahepatic vein, or fetal heart. I also find it hard to understand the contraindications listed for midtrimester amniocentesis, CVS, and early amniocentesis. It should be emphasised that, particularly in the UK, amniocentesis is very rarely indicated in the diagnosis of neural-tube defects; diagnostic ultrasound has superseded invasive testing in most cases. Neither amniocentesis nor CVS can be used to diagnose structural defects. This diagnosis can only be confirmed on visualisation of the fetus by ultrasound. All those involved in prenatal diagnosis accept that invasive procedures carry a risk of pregnancy loss. The indications for each procedure take into careful consideration benefit-risk implications. Moreover, most units will carry out internal audits, which allows them to offer patients accurate information about their own loss rates for each procedure. Pam Johnson Institute of Obstetrics and Gynaecology, Queen Charlotte’s and Chelsea Hospital, London W6 0XG, UK
*Anne Greenough, Kypros H Nicolaides *Department of Child Health, King’s College Hospital, London SE5 9RS, UK; and Harris Birthright Research Centre for Fetal Medicine, King’s College School of Medicine and Dentistry, London
1
2
Stranc LC, Evans JA, Hameton JL. Chorionic villus sampling and amniocentesis for prenatal diagnosis. Lancet 1997; 349: 711–14. Greenough A. Congenital abnormalities and antenatal invasive procedures. Bio Neonate 1996; 70: 187–88.
1396
1
2
3
Stranc LC, Evans JA, Hamerton JL. Chorionic villus sampling and amniocentesis for prenatal diagnosis. Lancet 1997; 349: 711–14. Maxwell DJ, Johnson P, Hurley P, et al. Fetal blood sampling and pregnancy loss in relation to indication. Br J Obstet Gynaecol 1991; 98: 892–97. Bernaschek G, Yildiz A, Kolankaya A, et al. Complications of cordocentesis in high risk pregnancies: effects on fetal loss or preterm delivery. Prenat Diagn 1995; 15: 995–1000.
Authors’ reply S IR —Greenough and Nicolaides correctly state that fetal as well as maternal risks must be part of any discussion about whether or not to have prenatal diagnosis, and must be included in the assessment of different procedures when such a choice is available. As we stated in our seminar, the safety of early amniocentesis has not yet been determined. There has certainly been evidence to indicate that this procedure is not without risk to the fetus with increased rates of positional limb anomalies, respiratory difficulties, and preterm delivery having been reported. This increased risk has not been conclusively demonstrated, but several large trials are underway. We thank Greenough and Nicolaides for sharing the results of their work. Johnson comments that we ignore much of the published research on prenatal diagnosis. But we were specifically asked to compare midtrimester amniocentesis with chorionic villus sampling (CVS), and were constrained within space limits. Our discussion of other techniques for prenatal diagnosis was secondary. We are concerned by Johnson’s claim that we give misleading figures for the risks of each procedure. The figures for midtrimester amniocentesis and CVS were obtained from some of the largest and most rigorous studies of these techniques. With regards to the risk figures cited for cordocentesis: as Johnson notes, there is little available evidence of the risks to the fetus associated with this procedure. We attempted to put the figures into perspective by stating that these pregnancies were often at higher risk of complications. Regarding the procedural contraindications listed, these are not absolute. Although, it may be technically possible to perform these procedures when contraindicated, it may not be recommended. To the best of our knowledge, these are not out of line with current practice. We agree with Johnson that in some jurisdictions, and that includes our own province of Manitoba, amniocentesis is not used for severe, isolated neural-tube defects. However, in centres that do not routinely screen maternal serum for alpha-fetoprotein, or in cases in which it is difficult to visualise the fetus, amniocentesis is still appropriate to determine the fetal karyotype or measure amniotic-fluid protein concentrations. Also, if a neural-tube defect is suspected and other anomalies are seen on ultrasound, an amniocentesis may be carried out to determine the fetal karyotype and obtain further Vol 349 • May 10, 1997