second trimester chorionic villus (placental) biopsy

1
969 We believe that our improved success rate is directly attributable to the change in technique. The use of anaesthesia renders the child relaxed, still, and pain-free, thereby facilitating the procedure. In only 1 case in group 2 was hydrostatic reduction attempted without sedation and this was unsuccessful. We have no doubt that, provided there are no contraindications, attempted hydrostatic reduction is safe, effective, and the treatment of choice in acute intussusception in childhood. Leicester Royal Infirmary, Leicester LE1 5WW H. L. SMITH A. C. LAMONT P. G. F. SWIFT 1. Poston GJ, Singh MP Management of acute intussusception in childhood Lancet 1985; ii 1118. 2 Liu KW, MacCarthy J, Guiney EJ, Fitzgerald RJ. Intussusception. Current trends in management Arch Dis Child 1986, 61: 75-77. 3 Sterner GM. Essential paediatric radiology for radiologists and casualty officers Oxford: Blackwell, 1983. 4. Dennison WM, Shaker M. Intussusception in infancy and childhood Br J Surg 1970, 57: 679-84. SECOND TRIMESTER CHORIONIC VILLUS (PLACENTAL) BIOPSY SIR,-Mr Nicolaides and his colleagues (March 8, p 543) report six cases of successful prenatal diagnosis by placental biopsy in the second or third trimester (five cases of fetal karyotyping and one with a positive diagnosis of sickle-cell anaemia). We report a case of second-trimester exclusion of aI-antitrypsin (al AT) deficiency by DNA analysis of placental biopsy material. The woman had a daughter with al AT deficiency (PiZZ) in whom severe cirrhosis of the liver developed; at the age of 7 years an attempt at constructing a portacaval shunt was unsuccessful. In three subsequent pregnancies the woman underwent fetal blood sampling by fetoscopy in the 18th to 20th weeks of gestation (al AT phenotypes can be determined in fetal blood but not in cultured amniotic fluid cells’). Two of the fetuses were affected and these pregnancies terminated; in the other pregnancy the fetus was not affected but miscarriage occurred 3 days after fetal blood sampling. In the 15th week of her fifth pregnancy the woman sought fetal blood sampling again. She was informed of the possibility of prenatal diagnosis by placental biopsy (at that time we had successfully done such biopsies in six cases of elective pregnancy termination in the l6th to 21st week). She agreed to this procedure since it seemed that a diagnosis could be established before fetal movements were perceptible. In week 16, a placental biopsy specimen was obtained by transabdominal aspiration through a 19 gauge (1’ 0 mm) needle and sent by a courier to the laboratory of the Hospital for Sick Children, Toronto, Canada for analysis of al AT using genomic probes.2 The fetus was found to be non-affected. 2 weeks after sampling the pregnancy is continuing uneventfully. We find that aspiration biopsy from the large second-trimester placenta is easy and agree with Nicolaides et al that placental biopsy need not be restricted to the first trimester. We thank Dr Diane Wilson Cox for the DNA analysis. Department of Obstetrics and Gynaecology, University Hospital, S-221 85 Lund, Sweden BJORN GUSTAVII HELÉNE EDVALL ELISABETH SVALENIUS KERSTIN DAHLANDER CONNIE JORGENSEN 1 Jeppsson JO, Cordesius E, Gustavii B, et al. Prenatal diagnosis of alpha -antitrypsin deficiency by analysis of fetal blood obtained at fetoscopy. Pediatr Res 1981, 15: 254-56 2 Cox DW, Mansfield T Prenatal diagnosis for alpha1-antitrypsin deficiency. Lancet 1985, i: 230. SIR,-Mr Nicolaides and colleagues present data on the value of fetal karyotyping in apparently non-lethal malformations (Feb 8, p 283) and the use of placental biopsy to obtain a fetal karyotype rapidly during the second or third trimester (March 8, p 543). Our experience oftrisomy 18 indicates that the development of a safe and reliable technique for determining fetal karyotype during the third trimester would be of great value when planning the mode of delivery of babies with intrauterine growth retardation (IUGR). In the six years 1980-85 21 babies with trisomy 18 were born in Leicestershire. 11 were delivered by caesarean section, elective in 4 and emergency in 7. In 9 of these 11 cases IUGR and/or poor placental function were noted before labour or elective section. Our observation confirms earlier reports of a high incidence of delivery by caesarean section in trisomy 181,2 and illustrates the potential value of the techniques outlined by Nicolaides et al. It has been estimated that 3% of growth-retarded newborn babies have a chromosome abnormality,3 so IUGR is likely to be a better marker for cytogenetic abnormality than advanced maternal age or previous history of non-disjunction. Department of Child Health, Leicester Royal Infirmary, Leicester LEI 5WW J. P. COOK I. D. YOUNG 1. David TJ, Glew S. Morbidity of trisomy 18 includes delivery by caesarean section. Lancet 1980; ii: 1295 2. Schneider AS, Mennuti MT, Zackai EH. High cesarean section rate in trisomy 18 births a potential indication for late prenatal diagnosis Am J Obstet Gynecol 1981; 140: 367-70 3 Defawe G, Le Marec B, Grall JY, et al Retard de croissance intra-utérin et aberratons chromosomiques. J Gynécol Obstet Biol Repr 1979; 8: 731-34. SiR,-Like Mr Nicolaides and his colleagues we have found transabdominal chorionic villus sampling useful for confirming the fetal diagnosis ofhaemoglobinopathy at the time of second trimester termination of pregnancy. However, the same approach should be considered in all late therapeutic abortions where fetal diagnosis may in future be by DNA analysis. Placental material is often unsuitable for analysis after late terminations because of degradation of DNA. Villi from a homozygote fetus will allow a complete family study so that the at-risk couple can be counselled. This approach has encouraged couples to take advantage of first trimester diagnosis of the haemoglobinopathies in subsequent pregnancies, but it is equally true for other genetic conditions. Another indication is late intrauterine death where fetus and placenta are also usually unsuitable for satisfactory fetal karyotyping after death. Department of Obstetrics and Gynaecology, Faculty of Clinical Sciences, University College London, London WC1E 6HX D. MAXWELL B. MODELL M. PETROU R. H. T. WARD CHORION VILLUS SAMPLING AND RANDOMISATION SIR,-Recent correspondence has highlighted concern about the problems and desirability of doing a randomised trial to compare the risks of chorionic villus sampling (CVS) and amniocentesis. From January, 1985, women in Oxfordshire seeking prenatal diagnosis, possibly by CVS, were counselled about possible risks of CVS and amniocentesis and were then invited to enter our own trial and; since July, 1985, the Medical Research Council’s multicentre trial of CVS, which allotted them randomly to prenatal diagnosis by CVS or amniocentesis. Total freedom of choice was acknowledged, however, and of 65 women none volunteered to be randomised. They all asked for CVS or for amniocentesis: Requested Volunteered Requested ammo- to be IndIcatIOn for test CVS centesis randomised Advanced age 30 16 0 Previous affected pregnancy* 9 1 0 X-linked disorder 5 0 0 Parental translocation 3 0 0 Other 1 0 0 Total 48 17 0 *Termmanon or delivery of a pregnancy with aneuptoidy, usually tnsomy 2 1. Women with a high risk of a positive diagnosis and those with experience of an affected pregnancy almost invariably asked for CVS while those at lower risk requested CVS or amniocentesis in the ratio 2:1. CVS is an invasive procedure done at a stage of pregnancy after which much fetal and placental development occurs. The effects of

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Page 1: SECOND TRIMESTER CHORIONIC VILLUS (PLACENTAL) BIOPSY

969

We believe that our improved success rate is directly attributableto the change in technique. The use of anaesthesia renders the childrelaxed, still, and pain-free, thereby facilitating the procedure. Inonly 1 case in group 2 was hydrostatic reduction attempted withoutsedation and this was unsuccessful. We have no doubt that,provided there are no contraindications, attempted hydrostaticreduction is safe, effective, and the treatment of choice in acuteintussusception in childhood.

Leicester Royal Infirmary,Leicester LE1 5WW

H. L. SMITHA. C. LAMONTP. G. F. SWIFT

1. Poston GJ, Singh MP Management of acute intussusception in childhood Lancet

1985; ii 1118.2 Liu KW, MacCarthy J, Guiney EJ, Fitzgerald RJ. Intussusception. Current trends in

management Arch Dis Child 1986, 61: 75-77.3 Sterner GM. Essential paediatric radiology for radiologists and casualty officers

Oxford: Blackwell, 1983.4. Dennison WM, Shaker M. Intussusception in infancy and childhood Br J Surg 1970,

57: 679-84.

SECOND TRIMESTER CHORIONIC VILLUS

(PLACENTAL) BIOPSY

SIR,-Mr Nicolaides and his colleagues (March 8, p 543) reportsix cases of successful prenatal diagnosis by placental biopsy in thesecond or third trimester (five cases of fetal karyotyping and onewith a positive diagnosis of sickle-cell anaemia). We report a case ofsecond-trimester exclusion of aI-antitrypsin (al AT) deficiency byDNA analysis of placental biopsy material.The woman had a daughter with al AT deficiency (PiZZ) in whom

severe cirrhosis of the liver developed; at the age of 7 years anattempt at constructing a portacaval shunt was unsuccessful. Inthree subsequent pregnancies the woman underwent fetal bloodsampling by fetoscopy in the 18th to 20th weeks of gestation (al ATphenotypes can be determined in fetal blood but not in culturedamniotic fluid cells’). Two of the fetuses were affected and thesepregnancies terminated; in the other pregnancy the fetus was notaffected but miscarriage occurred 3 days after fetal blood sampling.In the 15th week of her fifth pregnancy the woman sought fetalblood sampling again. She was informed of the possibility ofprenatal diagnosis by placental biopsy (at that time we had

successfully done such biopsies in six cases of elective pregnancytermination in the l6th to 21st week). She agreed to this proceduresince it seemed that a diagnosis could be established before fetalmovements were perceptible. In week 16, a placental biopsyspecimen was obtained by transabdominal aspiration through a 19gauge (1’ 0 mm) needle and sent by a courier to the laboratory of theHospital for Sick Children, Toronto, Canada for analysis of al ATusing genomic probes.2 The fetus was found to be non-affected. 2weeks after sampling the pregnancy is continuing uneventfully.We find that aspiration biopsy from the large second-trimester

placenta is easy and agree with Nicolaides et al that placental biopsyneed not be restricted to the first trimester.

We thank Dr Diane Wilson Cox for the DNA analysis.

Department of Obstetrics and Gynaecology,University Hospital,S-221 85 Lund, Sweden

BJORN GUSTAVIIHELÉNE EDVALLELISABETH SVALENIUSKERSTIN DAHLANDERCONNIE JORGENSEN

1 Jeppsson JO, Cordesius E, Gustavii B, et al. Prenatal diagnosis of alpha -antitrypsindeficiency by analysis of fetal blood obtained at fetoscopy. Pediatr Res 1981, 15:254-56

2 Cox DW, Mansfield T Prenatal diagnosis for alpha1-antitrypsin deficiency. Lancet1985, i: 230.

SIR,-Mr Nicolaides and colleagues present data on the value offetal karyotyping in apparently non-lethal malformations (Feb 8, p283) and the use of placental biopsy to obtain a fetal karyotyperapidly during the second or third trimester (March 8, p 543). Ourexperience oftrisomy 18 indicates that the development of a safe andreliable technique for determining fetal karyotype during the thirdtrimester would be of great value when planning the mode of

delivery of babies with intrauterine growth retardation (IUGR). Inthe six years 1980-85 21 babies with trisomy 18 were born inLeicestershire. 11 were delivered by caesarean section, elective in 4and emergency in 7. In 9 of these 11 cases IUGR and/or poorplacental function were noted before labour or elective section. Ourobservation confirms earlier reports of a high incidence of deliveryby caesarean section in trisomy 181,2 and illustrates the potentialvalue of the techniques outlined by Nicolaides et al. It has beenestimated that 3% of growth-retarded newborn babies have a

chromosome abnormality,3 so IUGR is likely to be a better markerfor cytogenetic abnormality than advanced maternal age or previoushistory of non-disjunction.Department of Child Health,Leicester Royal Infirmary,Leicester LEI 5WW

J. P. COOKI. D. YOUNG

1. David TJ, Glew S. Morbidity of trisomy 18 includes delivery by caesarean section.Lancet 1980; ii: 1295

2. Schneider AS, Mennuti MT, Zackai EH. High cesarean section rate in trisomy 18births a potential indication for late prenatal diagnosis Am J Obstet Gynecol 1981;140: 367-70

3 Defawe G, Le Marec B, Grall JY, et al Retard de croissance intra-utérin et aberratonschromosomiques. J Gynécol Obstet Biol Repr 1979; 8: 731-34.

SiR,-Like Mr Nicolaides and his colleagues we have foundtransabdominal chorionic villus sampling useful for confirming thefetal diagnosis ofhaemoglobinopathy at the time of second trimestertermination of pregnancy. However, the same approach should beconsidered in all late therapeutic abortions where fetal diagnosismay in future be by DNA analysis. Placental material is oftenunsuitable for analysis after late terminations because of

degradation of DNA. Villi from a homozygote fetus will allow acomplete family study so that the at-risk couple can be counselled.This approach has encouraged couples to take advantage of firsttrimester diagnosis of the haemoglobinopathies in subsequentpregnancies, but it is equally true for other genetic conditions.Another indication is late intrauterine death where fetus and

placenta are also usually unsuitable for satisfactory fetal

karyotyping after death.

Department of Obstetricsand Gynaecology,

Faculty of Clinical Sciences,University College London,London WC1E 6HX

D. MAXWELLB. MODELLM. PETROUR. H. T. WARD

CHORION VILLUS SAMPLING AND RANDOMISATION

SIR,-Recent correspondence has highlighted concern about theproblems and desirability of doing a randomised trial to compare therisks of chorionic villus sampling (CVS) and amniocentesis. FromJanuary, 1985, women in Oxfordshire seeking prenatal diagnosis,possibly by CVS, were counselled about possible risks of CVS andamniocentesis and were then invited to enter our own trial and;since July, 1985, the Medical Research Council’s multicentre trialof CVS, which allotted them randomly to prenatal diagnosis by CVSor amniocentesis. Total freedom of choice was acknowledged,however, and of 65 women none volunteered to be randomised.They all asked for CVS or for amniocentesis:

Requested Volunteered

Requested ammo- to be

IndIcatIOn for test CVS centesis randomisedAdvanced age 30 16 0Previous affected

pregnancy* 9 1 0

X-linked disorder 5 0 0

Parental translocation 3 0 0

Other 1 0 0

Total ’

48 17 0

*Termmanon or delivery of a pregnancy with aneuptoidy, usually tnsomy 2 1.

Women with a high risk of a positive diagnosis and those withexperience of an affected pregnancy almost invariably asked forCVS while those at lower risk requested CVS or amniocentesis inthe ratio 2:1.CVS is an invasive procedure done at a stage of pregnancy after

which much fetal and placental development occurs. The effects of