ANTENATAL DIAGNOSIS Amniocentesis
NIH Consensus
Development Conferences tection of essentially all cytogenetic (chromosomal) abnormalities in the fetus, for the diagnosis or exclusion of approximately 75 serious inborn metabolic disorders, and for the identification of fetal neural tube defects (eg., anencephaly or spina bifida), about 80 per cent of which will be associated with increased alpha fetoprotein in the amniotic fluid. In addition, fetal sex is readily determined in pregnancies where there is increased risk for X-linked disease in male offspring. In experienced centers, the overall accuracy of amniocentesis and related procedures in the assessment of fetal chromosomal constitution and in establishing the presence or absence of a detectable inborn error of metabolism exceeds 99.4 per cent (Tables 1 and 2). Several multi-centered studies (in the U.S., Canada and United Kingdom) have been conducted to determine the safety of the procedure for the mother, fetus, neonate and resultant offspring. In the American and recent British studies, critical, control, data were obtained from matched pregnancies in which amniocentesis was not performed. In the 1’~~C~I~ sponsored U.S. study (1971- 1974), no statisti:/-caHy~mgni:n.c.a.nt.~ differences were found between the two groups studied. ~Fctal loss~ rate,. perinatal problems, birth weights,, neonatal
Clinical ~~c~i~v~~-ic.~ has been presenting the summary, conclusions and recommendations of the National Institute of Child Health and Human 3~~~e~~~~~~tt’~ Task Force report on Predictors of Hereditary Disease or Congenital Defects. We continue this month with the summary and recommendations for current usage of mid-trimester amniocentesis, and conclude with their recommendations for future research in all four of the technologies covered by the report- amniocentesis, ~’et~~cr~py, ultrasound and alpha fetoprotein assay.
~~~~~~~~t~~~~
Summary
Diagnostic transabdominal amniocentesis is usually performed around the 16tb week of pregnancy (as denned from the beginning of the last regular menstrual period). Since 1968, the use of this procedure has increased dramatically and approximately 40,000 proce~
performed in the U.S. to date in (about 15,000 1 978).. I n more than 9,9 per cent of cases, the analyses indicated that the fetus is unaffected with the condition for which the test was performed . The procedure is dure have been
..
..
regarded in most areas as an accepted medical practice, applicable to specific pregnancies at increased risk such as hereditary ~~~~~i~~~i~~~ ~~~ ~i~~~~ ~.~f~~~~g ~~~~ no more :,. ~ common in the amniocentesis than in diseases or congenital defects in the, fetus, ’/Chile aa ~~~~r of indications are presented the cont,~rols ’,in the mne’-ccateys’m~oived). for the consideration of possible antenatal ;.~~ Similarly, no significant differences could be apprectatcd-m growth, development, behavior B diagnostic studies, the procedures should be, / or intellectual function at one -year of age in utilized only in pregnancies in which families have been and fully- informed ~~‘ children from tested and control pregnancies. the nature of the test and its implications ~.’ Increased complications (amniotic, fluid leakand who choose to have the test performed. B~.;. age., blood, spotting) were associated with the .~:~ ~’: &dquo;&dquo;’ At this t~ ~,~ ~~~~c~t~~ ~.~~i~ ~~~’~r ~i~~t~r~~ ~’.’. use of large gauge needles or where multiple ~’ amniotic. fluid cells can be used for the deuterine insertions of the needle were required. &dquo;’’ now
.
.
,
&dquo;
.
~
.
..~.
:
454 Downloaded from cpj.sagepub.com at NORTH DAKOTA STATE UNIV LIB on June 20, 2015
TABLE 1. Cumulative
Experience in Several U.S.
t Indudes one
group. Neonatal respiratory difficulties, orthopedic postural deformities and perinatal death were all increased about I per cent in the amniocentesis group. Certain late pregnancy complications (abruptio placenta, premature rupture of the membranes, postpartum hemorrhage) also seemed more frequent in the tested pregnancies. However, important issues are identified in the design and make-up of the British study which may accountfor the apparent differences they observe. Differences in age-matching of control patients, the timing of selection of their controls, and the fact that 4’l per cent of the study group had amniocentesis because of risk for fetal neural tube defects (nearly 10% because of elevated maternal serum AFP on a screening tes~)&dquo;all sugtest
reasons.
study involved 1,223 amnioin (1,040 the American study) and compared complications and outcomes with background provincial statistics. The percentage of fetal losses ~3.~~’~~ and neonatal deaths (0.79lc) were comparable to the U.S. findings and were not significantly different from the provincial control data. Overall accuracy in both studies was 99.4’~~. The Canadian
centeses
The recent United Kingdom study (1973l976) of 2,428 pregnancies with amniocentenumber of controls, found a loss (2.6% versus 1.1%) of fetal higher in the procedure group. In addition, an increase of the same magnitude was found an
equal
rate
’
I
TABLE s. ~es~ul~
fetus.
with certain abnormalities in newborns in the
Cesarean section was more frequent in the the amniocentesis subjects, for unapparent
sis and
Diagnosis 4,enters*
1978, pp 330-337
* Golbus, M: Prenatal diagnosis of genetic defectswhere it is and where it is going, Birth Defects. Edited by ~~’~ Littlefield, and J De Grouchy. Excerpta ~~~dic~,
.
Prenatal
of Prenatal 11~~~ta~~~a~~‘‘ar G’~rc~mas~~a~ r~~rc~rr~’’
―
di- ;~ It t~~~~~ ir~ ~~~°t e~~‘ c~~ ~~.~~ ~rc~vic~~~t i~~ ~a~ ~~ct age ~ ~~~ja.a~~i* ~: ~:~r~~p~~r~ ~~~pe~ier~~~ ~vit~’ ~ret~~t~l disease:a survey of f 6121 cases. groups been specified. Cyto~eni~t Ctli Geiiet 16- 453, 1976 ::~’~ ~;~ ~:~ ~~ ~ ~ LL;’- ~ ~ ~ ~ :..
agnosis of coGgeniwl
455 Downloaded from cpj.sagepub.com at NORTH DAKOTA STATE UNIV LIB on June 20, 2015
TAHt.K ,‘3. F?i’.
NIH Consensus
Development Conferences tection of essentially all cytogenetic (chromosomal) abnormalities in the fetus, for the diagnosis or exclusion of approximately 75 serious inborn metabolic disorders, and for the identification of fetal neural tube defects (eg., anencephaly or spina bifida), about 80 per cent of which will be associated with increased alpha fetoprotein in the amniotic fluid. In addition, fetal sex is readily determined in pregnancies where there is increased risk for X-linked disease in male offspring. In experienced centers, the overall accuracy of amniocentesis and related procedures in the assessment of fetal chromosomal constitution and in establishing the presence or absence of a detectable inborn error of metabolism exceeds 99.4 per cent (Tables 1 and 2). Several multi-centered studies (in the U.S., Canada and United Kingdom) have been conducted to determine the safety of the procedure for the mother, fetus, neonate and resultant offspring. In the American and recent British studies, critical, control, data were obtained from matched pregnancies in which amniocentesis was not performed. In the 1’~~C~I~ sponsored U.S. study (1971- 1974), no statisti:/-caHy~mgni:n.c.a.nt.~ differences were found between the two groups studied. ~Fctal loss~ rate,. perinatal problems, birth weights,, neonatal
Clinical ~~c~i~v~~-ic.~ has been presenting the summary, conclusions and recommendations of the National Institute of Child Health and Human 3~~~e~~~~~~tt’~ Task Force report on Predictors of Hereditary Disease or Congenital Defects. We continue this month with the summary and recommendations for current usage of mid-trimester amniocentesis, and conclude with their recommendations for future research in all four of the technologies covered by the report- amniocentesis, ~’et~~cr~py, ultrasound and alpha fetoprotein assay.
~~~~~~~~t~~~~
Summary
Diagnostic transabdominal amniocentesis is usually performed around the 16tb week of pregnancy (as denned from the beginning of the last regular menstrual period). Since 1968, the use of this procedure has increased dramatically and approximately 40,000 proce~
performed in the U.S. to date in (about 15,000 1 978).. I n more than 9,9 per cent of cases, the analyses indicated that the fetus is unaffected with the condition for which the test was performed . The procedure is dure have been
..
..
regarded in most areas as an accepted medical practice, applicable to specific pregnancies at increased risk such as hereditary ~~~~~i~~~i~~~ ~~~ ~i~~~~ ~.~f~~~~g ~~~~ no more :,. ~ common in the amniocentesis than in diseases or congenital defects in the, fetus, ’/Chile aa ~~~~r of indications are presented the cont,~rols ’,in the mne’-ccateys’m~oived). for the consideration of possible antenatal ;.~~ Similarly, no significant differences could be apprectatcd-m growth, development, behavior B diagnostic studies, the procedures should be, / or intellectual function at one -year of age in utilized only in pregnancies in which families have been and fully- informed ~~‘ children from tested and control pregnancies. the nature of the test and its implications ~.’ Increased complications (amniotic, fluid leakand who choose to have the test performed. B~.;. age., blood, spotting) were associated with the .~:~ ~’: &dquo;&dquo;’ At this t~ ~,~ ~~~~c~t~~ ~.~~i~ ~~~’~r ~i~~t~r~~ ~’.’. use of large gauge needles or where multiple ~’ amniotic. fluid cells can be used for the deuterine insertions of the needle were required. &dquo;’’ now
.
.
,
&dquo;
.
~
.
..~.
:
454 Downloaded from cpj.sagepub.com at NORTH DAKOTA STATE UNIV LIB on June 20, 2015
TABLE 1. Cumulative
Experience in Several U.S.
t Indudes one
group. Neonatal respiratory difficulties, orthopedic postural deformities and perinatal death were all increased about I per cent in the amniocentesis group. Certain late pregnancy complications (abruptio placenta, premature rupture of the membranes, postpartum hemorrhage) also seemed more frequent in the tested pregnancies. However, important issues are identified in the design and make-up of the British study which may accountfor the apparent differences they observe. Differences in age-matching of control patients, the timing of selection of their controls, and the fact that 4’l per cent of the study group had amniocentesis because of risk for fetal neural tube defects (nearly 10% because of elevated maternal serum AFP on a screening tes~)&dquo;all sugtest
reasons.
study involved 1,223 amnioin (1,040 the American study) and compared complications and outcomes with background provincial statistics. The percentage of fetal losses ~3.~~’~~ and neonatal deaths (0.79lc) were comparable to the U.S. findings and were not significantly different from the provincial control data. Overall accuracy in both studies was 99.4’~~. The Canadian
centeses
The recent United Kingdom study (1973l976) of 2,428 pregnancies with amniocentenumber of controls, found a loss (2.6% versus 1.1%) of fetal higher in the procedure group. In addition, an increase of the same magnitude was found an
equal
rate
’
I
TABLE s. ~es~ul~
fetus.
with certain abnormalities in newborns in the
Cesarean section was more frequent in the the amniocentesis subjects, for unapparent
sis and
Diagnosis 4,enters*
1978, pp 330-337
* Golbus, M: Prenatal diagnosis of genetic defectswhere it is and where it is going, Birth Defects. Edited by ~~’~ Littlefield, and J De Grouchy. Excerpta ~~~dic~,
.
Prenatal
of Prenatal 11~~~ta~~~a~~‘‘ar G’~rc~mas~~a~ r~~rc~rr~’’
―
di- ;~ It t~~~~~ ir~ ~~~°t e~~‘ c~~ ~~.~~ ~rc~vic~~~t i~~ ~a~ ~~ct age ~ ~~~ja.a~~i* ~: ~:~r~~p~~r~ ~~~pe~ier~~~ ~vit~’ ~ret~~t~l disease:a survey of f 6121 cases. groups been specified. Cyto~eni~t Ctli Geiiet 16- 453, 1976 ::~’~ ~;~ ~:~ ~~ ~ ~ LL;’- ~ ~ ~ ~ :..
agnosis of coGgeniwl
455 Downloaded from cpj.sagepub.com at NORTH DAKOTA STATE UNIV LIB on June 20, 2015
TAHt.K ,‘3. F?i’.
