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Factors affecting the success of mid-trimester amniocentesis
EUROP. J. OBSTET. GYNEC. REPROD. BIOL., 1979,9/4,231-236 0 Elsevier/North-Holland Biomedical Press
Factors affecting the success of mid-trimester amniocentesis S.L.B. Duncan and B. Ginz UniversityDepartment of Obstetricsand Gynaecology, Northern General Hospital, Sheffield S5 7AU, U.K. Accepted for publication 23 January 1979 DUNCAN, S.L.B. and GINZ, B. (1979): Factors affecting the success of mid-trimester amniocentesis. Europ. .J. Obstet. Gynec. reprod. Biol., 9/4,231-236. Of 298 women who had mid-trimester amniocentesis carried out in a single hospital unit in a 6-yr period, an increasing proportion were carried out for detection of neural tube defects. A clinical decision could be made following the first amniocentesis in 77% of cases. There were 16% where liquor was not obtained at the first attempt, and a further 7% where cell growth or biochemical testing was unsatisfactory. The outcome was influenced by the experience of the operator and timing of procedure. The success of the first procedure was 59% before 16 wk of gestation and 86% between 16 and 20 wk. The incidence of blood-staining of the liquor was higher with an anterior placenta (19%). Despite difficulties, the abortion rate (3.5%) does not appear to be higher than would be expected. prenatal diagnosis; role of ultrasound; complications of amniocentesis
procedure is carried out by experienced operators (Bartsh et al., 1974; Doran et al., 1974; Milunsky and Atkins, 1974). With an increasing demand for the procedure such standards may not be maintained. The results described here are those obtained with a number of operators of varying skills carrying out the procedure.
Introduction
Recent advances in cytogenetic and biochemical analysis have increased the use of mid-trimester amniocentesis. There is, nowadays, a real prospect of reducing the large contribution that congenital abnormalities make to perinatal mortality. The current development of screening maternal serum for raised levels of alpha-fetoprotein (AFP) (U.K. Collaborative Study, 1977) is likely to lead to a further increase in the number of mid-trimester amniocenteses. The major experience of diagnostic amniocentesis had been gained in the third trimester in relation to rhesus iso-immunization and, more recently, tests of skin or lung maturity. The problems and risks of early mid-trimester amniocentesis are not necessarily the same. Many of the reports of outcome of mid-trimester amniocentesis to date record the results when the
Method and technique
In the Obstetrics and Gynaecology Unit at the Northern General Hospital, 298 patients had a midtrimester amniocentesis between 1972 and 1977, inclusive. The majority of the patients were booked for delivery at the hospital but some were referred from outlying hospitals. At the time of the booking visit those patients with an indication for amniocen231
S.L.B. Duncan and B. Ginz: Mid-trimesteramniocentesis
232
tesis had the procedure explained to them and their blood group determined. The timing of the first amniocentesis was influenced by factors such as gestation at booking, clinic doctor and timing of referral from other centres. Prior to amniocentesis the placenta, was generally localized by ultrasound and the biparietal diameter measured. Blood was taken before and 30 min after the procedure for Kleihauer and more recently for serum alpha-fetoprotein (AFP) estimations. The amniocentesis was carried out with an l&gauge spinal needle after skin infiltration with local anesthetic and 15-20 ml of liquor aspirated. A drop was tested for protein and sugar to confirm that the sample was amniotic fluid (Duncan, 1975). All rhesus-negative patients without antibodies were given 50 pg of anti-D gammaglobulin. Patients normally went home an hour or so after the procedure. Cytogenetic examinations were carried out in the Department of Human Genetics and the alpha-fetoprotein estimations in the Department of Immunology, Hallamshire Hospital.
MlSCELLANEO”S
60
0
1972
1973
1974
1975
1976
19i
Year
Fig. 1. Shows increasing demand for procedure tions among women who delivered 1972-1977.
and indica-
Results The indications for amniocentesis (Table I) show that the majority were carried out because of an increased risk of chromosome abnormality or neural tube defect. The proportion for the latter indication has increased (Fig. 1). Analysis relates to 349 amniocenteses in 298 patients. The outcome has been analyzed according to the experience of the operator, subdivided into junior staff in training and specialist obstetricians.
junior staff to perform the procedure earlier (Fig. 2). There was greater failure in obtaining liquor before 16 wk gestation. Failure to obtain liquor was greater among junior staff (24%) as compared with senior
60
40
First amniocentesis Number
The timing of the first amniocentesis varied with the experience of the operator, with a tendency of
of
Amniocenteses 20
TABLE I
Indications for amniocentesis
Indication
No. of cases
Maternal age 35 yr and over Previous child with chromosome abnormality Previous child with a neural tube defect Miscellaneous
165 19 14 40
Total
298
01
J
!S 14
JS 15
JI 16
iI JS
17
JS
18
JS 19
Weeks
Fig. 2. Distribution of first amniocentesis by week of gestation according to whether procedure was carried out by junior staff (J) or specialist obstetrician (S).
233
S.L.B. Duncan and B. Ginz: Mid-trimester amniocentesis TABLE II
Percentage where liquor was not obtained
Gestation (wk)
Junior (%)
Senior (%)
14 15 16 17 18 19
30.0 31.5 11.8 33.0 9.0 22.0
21.0 23.0 15.0 8.0 5.0 7.0
staff (12%). This differential was present at each week of gestation (Table II). In 230 patients (77%) the object of the test was achieved in that a clinical decision could be based on the answer. In 47 (16%) no liquor was obtained, and in 21 (7%) cell culture was not satisfactory. Subsequent amniocentesis Of the 68 patients where the initial amniocentesis was unsuccessful because of the ‘dry tap’ or the cells failing to grow, 21 did not have any further procedure ; 43 had a second amniocentesis which was successful, and 4 required a third amniocentesis. Blood-stained liquor Liquors were considered to be contaminated with blood if they were macroscopically discolored, even if in the latter case there was a free flow of fluid. Among 31 patients whose initial amniocentesis yielded bloodstained liquor, there were 4 where cell culture failed and 7 had a significant feto-maternal hemorrhage. Feto-maternal hemorrhage Using the Kleihauer method a significant fetomaternal transfusion was said to have occurred if the amount of fetal blood was greater than 0.1 ml. Fifteen patients (5% of the 298) had a significant transplacental bleed. In 8 this was associated with technical difficulty at the time of amniocentesis: one instance of failure to obtain liquor and 7 of macroscopically blood-stained liquor. The postamniocentesis maternal serum alpha-fetoprotein, where measured in 9 of these 15 patients, showed a marked rise.
TABLE III
Outcome of amniocentesis in relation to placental site
Clear liquor Blood-stained No liquor
Anterior
Posterior
Not known
No.
%
No.
%
No.
%
69 20 18
64 19 17
112 I 13
85 5 10
49 4 6
83 7 10
Thus, in this small group, the results of Kleihauer and serum alpha-fetoprotein were in agreement. Placental site Initially, in this series the placental site was not always localized before the procedure. There is little difference in the outcome of amniocentesis when the placenta is posterior or the site not known (Table III). However, where the placenta was known to be anterior, the incidence of blood-stained liquor was greater. There was, however, little difference in the incidence of failure to obtain liquor. Of the 15 patients with a significant feto-maternal transfusion, the placenta was anterior in 9, posterior in 3 and not known in 3. Thus, a posterior placenta is more favorable, with a 2% frequency of feto-maternal hemorrhage compared with 8% when anterior (significant at 0.05 level: Chi-squared test). One patient developed weak rhesus antibodies (less than 1 IV) by delivery, despite the administration of a double dose of anti-D given because of a positive Kleihauer test. Abortion Following amniocentesis 10 patients aborted before 28 wk gestation (Table IV). Three had had a failed amniocentesis, 4 blood-stained liquor, and 3 a techically easy amniocentesis. In 6 patients the fetus was almost certainly alive 4 wk later, and the contribution of amniocentesis to fetal loss must remain doubtful. In 3 patients where abortionoccurred within 1 wk the role of amniocentesis may have been more direct. One of these had an abnormal karyotype in the fetal cells. In patient no. 5, the liquor fMings suggest that fetal death was imminent at the first amniocentesis.
S.L.B. Duncan and B. Ginz: Mid-trimesteramniocentesis
234 TABLE IV Patient
Details of patients who aborted spontaneously Age
Amniocentesis
Amniocentesis/ abortion interval
Other details
alive 3 wk later
Indication
Gestation
Outcome
35
age
18 15 14 15 17 17 15 17
no liquor clear no liquor clear blood-stained clear brown fluid dark brown fluid
8 wk 1 wk 4 wk
24
age age previous chromosome abnormality previous NTD
43 37 32
3 days 4 wk
6 7
35 37
age age
14 13
clear no liquor
4 wk 5 wk
8
38
18
clear
1 day
9
38
previous chromosome abnormality age
16
blood-stained
9 wk
10
32
raised serum AFP
18
clear
8 wk
TABLE V Patient
poorgrowing cells but result obtained. Liquor AFP raised. Level much higher at repeat procedure, suggesting poor outcome vaginal bleeding at 11 and 18 wk. Aborted 2 days after admission culture unbalanced translocation fetal heart present 6 wk after amniocentesis aborted with features of abruptio placentae fetus 850 g
Details of patients with an abnormal fetus Age
Indication for amniocentesis
Abnormality in current pregnancy
Outcome
1 2
28 26
previous NTD serum AFP raised
terminated terminated
3 4 5 6 7 8 9 10 11 12 13 14 15
15 32 43 38 34 38 23 25 31 29 22 35 20
scan for gestation previous mongol age previous unbalanced translocation family history of translocation
spina bifida and hydrocephalus monozygotic twins: 1 normal, 1 missed abortion anencephalic anencephalic trisomy E unbalanced translocation triplets: unbalanced translocation 46XxX anencephalic hydrocephalic anencephalic anencephalic anencephalic anencephalic exomphalos
age serum AFP raised previous anencephalic serum AFP raised previous NTD serum AFP raised serum AFP raised serum AFP raised
terminated terminated terminated aborted spontaneously terminated terminated terminated stillbirth near term terminated terminated terminated terminated terminated
S.L.B. Duncan and B. Ginz: Mid-trimesteramniocentesis TABLE VI
Outcome of
pregnancy
Normal infant Twin delivery Perinatal deaths Spontaneous abortions Termination of pregnancy
264 3 8 10 13
Abnormal liquor results
Of the 298 patients who had an amniocentesis, there were 15 fetal abnormalities (Table V). One patient who had had an anencephalic pregnancy previously had 2 amniocenteses for AFP. In the first sample the level was above the normal range but, on repeating the amniocentesis, it was within the normal range. This patient subsequently delivered a stillborn hydrocephalic infant with spina bifida. Thirteen of the 14 patients with a known fetal abnormality had a termination of pregnancy, and one aborted spontaneously. Outcome of pregnancy
The outcome of pregnancy is summarized in Table VI. Of the 8 deaths after 28 wk of pregnancy and within 1 wk of birth (a rate of 29 per 1000 total births), there was one stillbirth to a diabetic mother, 3 stillbirths after placental abruption, 2 neonatal deaths due to rhesus immunization and one due to a large diaphragmatic hernia. The eighth was the hydrocephalic infant not detected by amniocentesis. Thus, together with the spontaneous abortions and terminations, 10.4% of the total group of 298 patients had a ‘pregnancy loss’.
Discussion
This study identifies some of the factors which increase the success rate of this apparently simple procedure. Important problems were failure to obtain liquor and failure of the sample to yield a result. This latter problem is more likely to arise with cell culture than where a biochemical test is involved (e.g. for AFP), so the indication for the procedure will affect the success rate in terms of a result. Previous results
235
(Wahlstriim et al., 1974; Young et al., 1976), predominantly from genetic centres, have included a larger proportion carried out for karyotyping. It is likely that an increasing proportion in future years will be for AFP estimations as maternal serum screening becomes more generally used. The ‘success’ rate will therefore tend to increase, as a result will virtually always be obtained, provided liquor is obtained. However, as amniocentesis becomes more frequent the procedure may be increasingly left in the hands of less experienced operators. The present study shows that the less experienced operators had a greater incidence of difficulties and that the timing of the procedure affected the outcome. These factors contributed to our greater incidence of failure to get a diagnostic answer from the first attempt compared with other reports (Atkins et al., 1974; Milunsky et al, 1974). Failure to obtain liquor at attempted amniocentesis is more likely to cause trauma to the uterus, fetus or placenta. In this series 5% had a feto-maternal hemorrhage of more than 0.1 ml. Although the figures are small the incidence was 5.5% for junior staff and 3% for senior staff. Bartsh (et al., 1974) also suggests that there may be a relationship to the experience of the operator. The group of women having amniocentesis include an undue proportion who have lost a child previously (neural tube or chromosome abnormality) as well as a number of older women with some degree of infertility, obesity or fibroids. There is thus both an increased tendency to abortion as well as a greater fear of it. The overall abortion rate of 3.5% is comparable to other reports of 1.5-5% (Bartsh et al., 1974; Doran et al., 1974; Young et al., 1976). An important recent study (National Institute of Child Health and Human Development Study, 1976) reported an abortion rate after amniocentesis of 3.5%, compared to 3.2% in the control group without amniocentesis. It is thus not certain yet whether the risk of abortion is any higher after amniocentesis than would have occurred in this relatively high risk group. The overall pregnancy loss of over 10% emphasizes the highly selected nature of this group. We have made no attempt to assess the psychological effects on the patient, especially where no answer is obtained or where the procedure has to be repeated, or where the result is equivocal or unexpected. These factors may well affect attitudes to the procedure in a future pregnancy.
236
The timing of amniocentesis tends to be critically balanced between adequate gestation to minimize failure, and early enough to enable cell culture and evaluation of results. in time to enable termination where the diagnosis is adverse. We have shown that failure is more likely before 16 wk, and suggest that the procedure be deferred until then. Where the indication is for liquor AFP estimation, the analysis is much quicker and the time scale less critical. Indication for amniocentesis as a result of maternal serum screening will tend to arise at or just after 16 wk. Where the indication is obvious in pregnancy (e.g. age or previous history), the temptation to seek a result as early as possible should be resisted. Methods of accurate assessment of gestation as early as possible in pregnancy are clearly important. In order to maximize the success of mid-trimester amniocentesis attention to timing, localization of the placenta and experience of operator are important. Widening of indication and the apparent ease of the procedure should not be allowed to obscure the technical problems.
S.L.B. Duncan and B. Ginz: Mid-trimesteramniocentesis References Atkins, L., Milunsky, A. and Shahood, J.M. (1974): Prenatal diagnosis: detailed chromosomal analysis in 500 cases. Clin. Genet., 6, 317-322. Bartsh, F.K., Lundberg, J. and Wahlstrom, J. (1974): The ’ technique, results and risks of amniocentesis for genetic reasons. J. Obstet. Gynaec. Brit. Cwlth, 81, 991-994. Doran, T.A., Rudd, N.L., Gardner, H.A., Lowden, J.A., Benzie, R.J. and Liedgren, S.I. (1974): The antenatal diagnosis of genetic disease. Amer. J. Obstet. Gynec., 118, 314-321. Duncan, S.L.B. (1975): Antenatal misdiagnosis of neural tube defects. Lancer, ii, 709. Milunsky, A. and Atkins, L. (1974): Prenatal diagnosis of genetic disorders. J. Amer. med. Assoc., 230, 232-235. National Institute of Child Health and Human Development Study (1976): Mid-trimester amniocentesis for prenatal diagn0sis.J. Amer. med. Assoc., 236, 1471-1476. U.K. Collaborative Study on Alpha-fetoprotein in Relation to Neural Tube Defects (1977): Screening for neural tube defects. Lancer, i, 1323-1332. Wahlstrom, J., Bartsh, F.K. and Lundberg, J. (1974): Prenatal chromosome determination - A study of 219 cases. C7in. Genet., 6, 184-191. Young, P.E., Matson, M.R. and Jones, O.W. (1976): Amniocentesis for antenatal diagnosis. Review of problems and outcomes in a large series. Amer. J. Obstet. Gynec., 125, 495-501.
Factors affecting the success of mid-trimester amniocentesis S.L.B. Duncan and B. Ginz UniversityDepartment of Obstetricsand Gynaecology, Northern General Hospital, Sheffield S5 7AU, U.K. Accepted for publication 23 January 1979 DUNCAN, S.L.B. and GINZ, B. (1979): Factors affecting the success of mid-trimester amniocentesis. Europ. .J. Obstet. Gynec. reprod. Biol., 9/4,231-236. Of 298 women who had mid-trimester amniocentesis carried out in a single hospital unit in a 6-yr period, an increasing proportion were carried out for detection of neural tube defects. A clinical decision could be made following the first amniocentesis in 77% of cases. There were 16% where liquor was not obtained at the first attempt, and a further 7% where cell growth or biochemical testing was unsatisfactory. The outcome was influenced by the experience of the operator and timing of procedure. The success of the first procedure was 59% before 16 wk of gestation and 86% between 16 and 20 wk. The incidence of blood-staining of the liquor was higher with an anterior placenta (19%). Despite difficulties, the abortion rate (3.5%) does not appear to be higher than would be expected. prenatal diagnosis; role of ultrasound; complications of amniocentesis
procedure is carried out by experienced operators (Bartsh et al., 1974; Doran et al., 1974; Milunsky and Atkins, 1974). With an increasing demand for the procedure such standards may not be maintained. The results described here are those obtained with a number of operators of varying skills carrying out the procedure.
Introduction
Recent advances in cytogenetic and biochemical analysis have increased the use of mid-trimester amniocentesis. There is, nowadays, a real prospect of reducing the large contribution that congenital abnormalities make to perinatal mortality. The current development of screening maternal serum for raised levels of alpha-fetoprotein (AFP) (U.K. Collaborative Study, 1977) is likely to lead to a further increase in the number of mid-trimester amniocenteses. The major experience of diagnostic amniocentesis had been gained in the third trimester in relation to rhesus iso-immunization and, more recently, tests of skin or lung maturity. The problems and risks of early mid-trimester amniocentesis are not necessarily the same. Many of the reports of outcome of mid-trimester amniocentesis to date record the results when the
Method and technique
In the Obstetrics and Gynaecology Unit at the Northern General Hospital, 298 patients had a midtrimester amniocentesis between 1972 and 1977, inclusive. The majority of the patients were booked for delivery at the hospital but some were referred from outlying hospitals. At the time of the booking visit those patients with an indication for amniocen231
S.L.B. Duncan and B. Ginz: Mid-trimesteramniocentesis
232
tesis had the procedure explained to them and their blood group determined. The timing of the first amniocentesis was influenced by factors such as gestation at booking, clinic doctor and timing of referral from other centres. Prior to amniocentesis the placenta, was generally localized by ultrasound and the biparietal diameter measured. Blood was taken before and 30 min after the procedure for Kleihauer and more recently for serum alpha-fetoprotein (AFP) estimations. The amniocentesis was carried out with an l&gauge spinal needle after skin infiltration with local anesthetic and 15-20 ml of liquor aspirated. A drop was tested for protein and sugar to confirm that the sample was amniotic fluid (Duncan, 1975). All rhesus-negative patients without antibodies were given 50 pg of anti-D gammaglobulin. Patients normally went home an hour or so after the procedure. Cytogenetic examinations were carried out in the Department of Human Genetics and the alpha-fetoprotein estimations in the Department of Immunology, Hallamshire Hospital.
MlSCELLANEO”S
60
0
1972
1973
1974
1975
1976
19i
Year
Fig. 1. Shows increasing demand for procedure tions among women who delivered 1972-1977.
and indica-
Results The indications for amniocentesis (Table I) show that the majority were carried out because of an increased risk of chromosome abnormality or neural tube defect. The proportion for the latter indication has increased (Fig. 1). Analysis relates to 349 amniocenteses in 298 patients. The outcome has been analyzed according to the experience of the operator, subdivided into junior staff in training and specialist obstetricians.
junior staff to perform the procedure earlier (Fig. 2). There was greater failure in obtaining liquor before 16 wk gestation. Failure to obtain liquor was greater among junior staff (24%) as compared with senior
60
40
First amniocentesis Number
The timing of the first amniocentesis varied with the experience of the operator, with a tendency of
of
Amniocenteses 20
TABLE I
Indications for amniocentesis
Indication
No. of cases
Maternal age 35 yr and over Previous child with chromosome abnormality Previous child with a neural tube defect Miscellaneous
165 19 14 40
Total
298
01
J
!S 14
JS 15
JI 16
iI JS
17
JS
18
JS 19
Weeks
Fig. 2. Distribution of first amniocentesis by week of gestation according to whether procedure was carried out by junior staff (J) or specialist obstetrician (S).
233
S.L.B. Duncan and B. Ginz: Mid-trimester amniocentesis TABLE II
Percentage where liquor was not obtained
Gestation (wk)
Junior (%)
Senior (%)
14 15 16 17 18 19
30.0 31.5 11.8 33.0 9.0 22.0
21.0 23.0 15.0 8.0 5.0 7.0
staff (12%). This differential was present at each week of gestation (Table II). In 230 patients (77%) the object of the test was achieved in that a clinical decision could be based on the answer. In 47 (16%) no liquor was obtained, and in 21 (7%) cell culture was not satisfactory. Subsequent amniocentesis Of the 68 patients where the initial amniocentesis was unsuccessful because of the ‘dry tap’ or the cells failing to grow, 21 did not have any further procedure ; 43 had a second amniocentesis which was successful, and 4 required a third amniocentesis. Blood-stained liquor Liquors were considered to be contaminated with blood if they were macroscopically discolored, even if in the latter case there was a free flow of fluid. Among 31 patients whose initial amniocentesis yielded bloodstained liquor, there were 4 where cell culture failed and 7 had a significant feto-maternal hemorrhage. Feto-maternal hemorrhage Using the Kleihauer method a significant fetomaternal transfusion was said to have occurred if the amount of fetal blood was greater than 0.1 ml. Fifteen patients (5% of the 298) had a significant transplacental bleed. In 8 this was associated with technical difficulty at the time of amniocentesis: one instance of failure to obtain liquor and 7 of macroscopically blood-stained liquor. The postamniocentesis maternal serum alpha-fetoprotein, where measured in 9 of these 15 patients, showed a marked rise.
TABLE III
Outcome of amniocentesis in relation to placental site
Clear liquor Blood-stained No liquor
Anterior
Posterior
Not known
No.
%
No.
%
No.
%
69 20 18
64 19 17
112 I 13
85 5 10
49 4 6
83 7 10
Thus, in this small group, the results of Kleihauer and serum alpha-fetoprotein were in agreement. Placental site Initially, in this series the placental site was not always localized before the procedure. There is little difference in the outcome of amniocentesis when the placenta is posterior or the site not known (Table III). However, where the placenta was known to be anterior, the incidence of blood-stained liquor was greater. There was, however, little difference in the incidence of failure to obtain liquor. Of the 15 patients with a significant feto-maternal transfusion, the placenta was anterior in 9, posterior in 3 and not known in 3. Thus, a posterior placenta is more favorable, with a 2% frequency of feto-maternal hemorrhage compared with 8% when anterior (significant at 0.05 level: Chi-squared test). One patient developed weak rhesus antibodies (less than 1 IV) by delivery, despite the administration of a double dose of anti-D given because of a positive Kleihauer test. Abortion Following amniocentesis 10 patients aborted before 28 wk gestation (Table IV). Three had had a failed amniocentesis, 4 blood-stained liquor, and 3 a techically easy amniocentesis. In 6 patients the fetus was almost certainly alive 4 wk later, and the contribution of amniocentesis to fetal loss must remain doubtful. In 3 patients where abortionoccurred within 1 wk the role of amniocentesis may have been more direct. One of these had an abnormal karyotype in the fetal cells. In patient no. 5, the liquor fMings suggest that fetal death was imminent at the first amniocentesis.
S.L.B. Duncan and B. Ginz: Mid-trimesteramniocentesis
234 TABLE IV Patient
Details of patients who aborted spontaneously Age
Amniocentesis
Amniocentesis/ abortion interval
Other details
alive 3 wk later
Indication
Gestation
Outcome
35
age
18 15 14 15 17 17 15 17
no liquor clear no liquor clear blood-stained clear brown fluid dark brown fluid
8 wk 1 wk 4 wk
24
age age previous chromosome abnormality previous NTD
43 37 32
3 days 4 wk
6 7
35 37
age age
14 13
clear no liquor
4 wk 5 wk
8
38
18
clear
1 day
9
38
previous chromosome abnormality age
16
blood-stained
9 wk
10
32
raised serum AFP
18
clear
8 wk
TABLE V Patient
poorgrowing cells but result obtained. Liquor AFP raised. Level much higher at repeat procedure, suggesting poor outcome vaginal bleeding at 11 and 18 wk. Aborted 2 days after admission culture unbalanced translocation fetal heart present 6 wk after amniocentesis aborted with features of abruptio placentae fetus 850 g
Details of patients with an abnormal fetus Age
Indication for amniocentesis
Abnormality in current pregnancy
Outcome
1 2
28 26
previous NTD serum AFP raised
terminated terminated
3 4 5 6 7 8 9 10 11 12 13 14 15
15 32 43 38 34 38 23 25 31 29 22 35 20
scan for gestation previous mongol age previous unbalanced translocation family history of translocation
spina bifida and hydrocephalus monozygotic twins: 1 normal, 1 missed abortion anencephalic anencephalic trisomy E unbalanced translocation triplets: unbalanced translocation 46XxX anencephalic hydrocephalic anencephalic anencephalic anencephalic anencephalic exomphalos
age serum AFP raised previous anencephalic serum AFP raised previous NTD serum AFP raised serum AFP raised serum AFP raised
terminated terminated terminated aborted spontaneously terminated terminated terminated stillbirth near term terminated terminated terminated terminated terminated
S.L.B. Duncan and B. Ginz: Mid-trimesteramniocentesis TABLE VI
Outcome of
pregnancy
Normal infant Twin delivery Perinatal deaths Spontaneous abortions Termination of pregnancy
264 3 8 10 13
Abnormal liquor results
Of the 298 patients who had an amniocentesis, there were 15 fetal abnormalities (Table V). One patient who had had an anencephalic pregnancy previously had 2 amniocenteses for AFP. In the first sample the level was above the normal range but, on repeating the amniocentesis, it was within the normal range. This patient subsequently delivered a stillborn hydrocephalic infant with spina bifida. Thirteen of the 14 patients with a known fetal abnormality had a termination of pregnancy, and one aborted spontaneously. Outcome of pregnancy
The outcome of pregnancy is summarized in Table VI. Of the 8 deaths after 28 wk of pregnancy and within 1 wk of birth (a rate of 29 per 1000 total births), there was one stillbirth to a diabetic mother, 3 stillbirths after placental abruption, 2 neonatal deaths due to rhesus immunization and one due to a large diaphragmatic hernia. The eighth was the hydrocephalic infant not detected by amniocentesis. Thus, together with the spontaneous abortions and terminations, 10.4% of the total group of 298 patients had a ‘pregnancy loss’.
Discussion
This study identifies some of the factors which increase the success rate of this apparently simple procedure. Important problems were failure to obtain liquor and failure of the sample to yield a result. This latter problem is more likely to arise with cell culture than where a biochemical test is involved (e.g. for AFP), so the indication for the procedure will affect the success rate in terms of a result. Previous results
235
(Wahlstriim et al., 1974; Young et al., 1976), predominantly from genetic centres, have included a larger proportion carried out for karyotyping. It is likely that an increasing proportion in future years will be for AFP estimations as maternal serum screening becomes more generally used. The ‘success’ rate will therefore tend to increase, as a result will virtually always be obtained, provided liquor is obtained. However, as amniocentesis becomes more frequent the procedure may be increasingly left in the hands of less experienced operators. The present study shows that the less experienced operators had a greater incidence of difficulties and that the timing of the procedure affected the outcome. These factors contributed to our greater incidence of failure to get a diagnostic answer from the first attempt compared with other reports (Atkins et al., 1974; Milunsky et al, 1974). Failure to obtain liquor at attempted amniocentesis is more likely to cause trauma to the uterus, fetus or placenta. In this series 5% had a feto-maternal hemorrhage of more than 0.1 ml. Although the figures are small the incidence was 5.5% for junior staff and 3% for senior staff. Bartsh (et al., 1974) also suggests that there may be a relationship to the experience of the operator. The group of women having amniocentesis include an undue proportion who have lost a child previously (neural tube or chromosome abnormality) as well as a number of older women with some degree of infertility, obesity or fibroids. There is thus both an increased tendency to abortion as well as a greater fear of it. The overall abortion rate of 3.5% is comparable to other reports of 1.5-5% (Bartsh et al., 1974; Doran et al., 1974; Young et al., 1976). An important recent study (National Institute of Child Health and Human Development Study, 1976) reported an abortion rate after amniocentesis of 3.5%, compared to 3.2% in the control group without amniocentesis. It is thus not certain yet whether the risk of abortion is any higher after amniocentesis than would have occurred in this relatively high risk group. The overall pregnancy loss of over 10% emphasizes the highly selected nature of this group. We have made no attempt to assess the psychological effects on the patient, especially where no answer is obtained or where the procedure has to be repeated, or where the result is equivocal or unexpected. These factors may well affect attitudes to the procedure in a future pregnancy.
236
The timing of amniocentesis tends to be critically balanced between adequate gestation to minimize failure, and early enough to enable cell culture and evaluation of results. in time to enable termination where the diagnosis is adverse. We have shown that failure is more likely before 16 wk, and suggest that the procedure be deferred until then. Where the indication is for liquor AFP estimation, the analysis is much quicker and the time scale less critical. Indication for amniocentesis as a result of maternal serum screening will tend to arise at or just after 16 wk. Where the indication is obvious in pregnancy (e.g. age or previous history), the temptation to seek a result as early as possible should be resisted. Methods of accurate assessment of gestation as early as possible in pregnancy are clearly important. In order to maximize the success of mid-trimester amniocentesis attention to timing, localization of the placenta and experience of operator are important. Widening of indication and the apparent ease of the procedure should not be allowed to obscure the technical problems.
S.L.B. Duncan and B. Ginz: Mid-trimesteramniocentesis References Atkins, L., Milunsky, A. and Shahood, J.M. (1974): Prenatal diagnosis: detailed chromosomal analysis in 500 cases. Clin. Genet., 6, 317-322. Bartsh, F.K., Lundberg, J. and Wahlstrom, J. (1974): The ’ technique, results and risks of amniocentesis for genetic reasons. J. Obstet. Gynaec. Brit. Cwlth, 81, 991-994. Doran, T.A., Rudd, N.L., Gardner, H.A., Lowden, J.A., Benzie, R.J. and Liedgren, S.I. (1974): The antenatal diagnosis of genetic disease. Amer. J. Obstet. Gynec., 118, 314-321. Duncan, S.L.B. (1975): Antenatal misdiagnosis of neural tube defects. Lancer, ii, 709. Milunsky, A. and Atkins, L. (1974): Prenatal diagnosis of genetic disorders. J. Amer. med. Assoc., 230, 232-235. National Institute of Child Health and Human Development Study (1976): Mid-trimester amniocentesis for prenatal diagn0sis.J. Amer. med. Assoc., 236, 1471-1476. U.K. Collaborative Study on Alpha-fetoprotein in Relation to Neural Tube Defects (1977): Screening for neural tube defects. Lancer, i, 1323-1332. Wahlstrom, J., Bartsh, F.K. and Lundberg, J. (1974): Prenatal chromosome determination - A study of 219 cases. C7in. Genet., 6, 184-191. Young, P.E., Matson, M.R. and Jones, O.W. (1976): Amniocentesis for antenatal diagnosis. Review of problems and outcomes in a large series. Amer. J. Obstet. Gynec., 125, 495-501.