Acta Obstet Gynecol Scand 58:3-7, 1979
ON IMPROVED OUTCOME OF TWIN PREGNANCIES Per-Hikan Persson, Lars Grennert, Gerhard Gennser and Stig Kullander From the Department of Obstetrics and Gynecology, University of Lund, Allmanna Sjukhuset, S-214 01 Malmo, Sweden
Abstract. During the past four years, an attempt has been made in Malmd t o reduce the frequency of preterm termination of twin pregnancies. For this purpose, the entire pregnant population of this medium-sized city was subjected to general ultrasonic screening in the second trimester. This detected 88 per cent of the twin pregnancies. The screening had a methodological error of 2 per cent. Eightysix of the women with twin pregnancy were subjected to bedrest in hospital for more than two weeks in the second half of gestation. The incidences of twins born with birth weight below 1 5 0 0 g and of twins light-for-gestational-age were reduced compared with those a decade earlier. Also the group of twins born before the 37th week decreased, and the perinatal mortality rate fell to the same level as in singleton pregnancies. Early detection of twin pregnancies followed by rest for the pregnant women seems t o contribute to an improved outcome of these gestations.
Neonatal mortality is affected by immaturity at birth (12, 37, 32). Measures to prevent preterm deliveries can be expected to reduce neonatal wastage. Multiple pregnancies involve a particular risk for premature termination of gestation (1, 20, 23, 28, 30, 34) and a high perinatal mortality (5, 15, 16, 23, 24, 28, 33, 36). Among twins, there is also a high percentage of infants with mental and neurological handicap inflicted at birth, reflecting the general finding that the incidence of these damages is increased in infants after preterm delivery (3, 4, 8). It has been repeatedly demonstrated that the impaired development of the central nervous system in twins is due to factors associated with low birth weight and preterm delivery (22, 25, 3 1 , 40, 41). An increase in the average gestational lenght of multiple pregnancies would therefore be expected to decrease the mortality of twin infants and reduce the chronic handicaps in the survivors. In the 1950’s, Bender (7) suggested that bedrest could prevent inadvertent preterm delivery of twins but only some later clinical studies have supported this hypothesis (6, 19, 25, 27). O n the other hand, an increased birth weight is reported to follow admission to hospital before term (2, 10, 21, 22). Preventive treatment of twin pregnancies with bedrest has been
widely attempted, but its intended effects have not been proved unanimously, for mainly two reasons: Multiple gestations - even if detected before delivery - have often been diagnosed too late for preventive measures to achieve their optimum results. Moreover, before the introduction of a general twin screening, the twins detected early in gestation and subjected to preventive treatment have presumably been the largest and most well-nourished fetuses. This has undoubtedly affected the interpretation of the results. An extensive and early diagnosis of gestational multiplicity is therefore of paramount importance for the evaluation of the effect of bedrest in reducing prematurity. This initiated the application of various methods for large-scale screening for multiple pregnancies, e.g., improved history taking, more alert physical examination (39), hormonal screening (17, 18, 29), and ultrasound (28, 35). Of these methods, large-scale ultrasonic examination has so far proved superior (1 8). The present paper summarizes a four-year experience of ultrasonic screening as a prerequisite for an extensive early hospitalization of women with twin pregnancies. It reports the outcome of these pregnancies concerning duration of gestation, birth weight, and perinatal mortality.
PATIENTS AND METHODS The study took place at the University Hospital of Malmo during 1.1.1973 - 30.4.1977, when 12 098 women were delivered. During this period, 110 pairs of twins were born: an apparent frequency of 1:110. The maternity hospital reported in the study is the only one serving a city of 250 OOO inhabitants and most of the population attend the antenatal clinics of the hospital. Private obstetricians working in close collaboration with the hospital staff saw 20 per cent of the pregnant women. Ninetyseven of the 110 twin pairs were detected early in gestation, and 86 women accepted the preventive programme. They comprise the study group (Group I). No conventional control group could be formed (see Discussion) but comparisons were made with the 24 women who were non-acceptors or whose twin pregnancy was not Acta Obsler Gynecol Scand 58 11979)
4
L . Grennert et al.
Table I. Birth weights. < I500 g
1500-2500 g > 2500 g
Total
Group
n
Vo
n
Vo
n
070
n
I I1 Ill
0 5 9
0 10 5
75 25 81
44 52 44
97 18 96
56 38 52
172 48 186
1/11 p
ance of a trained interviewer. In all women the gestational age was estimated from the last menstrual period by Naegele’s calculation and from the early clinical assessment of uterine size. The following statistical tests were used: Student’s t-test, Chi-square test with Yates’ correction and exact permutation test with each pregnancy (and not the individual twin) as the independent variable of comparison. All tests were one-sided.
< 0.01; I / I I I p < 0.05 RESULTS
detected before delivery (Group 11). Further comparisons were also made with the 93 twin pairs born at the same maternity hospital during 1963-1965, when both early diagnosis and prevention of prematurity were lacking (Group Ill). During this period, 11 733 deliveries occurred (apparent twin frequency 1:122). All the pregnant women were referred to ultrasonic screening at their first attendance at the antenatal clinic. The ultrasonic examinations were initially performed in the 28th week. During the course of the investigation, it was found desirable to perform the screening as early as practical. This reduced the average gestational age for the ultrasonic screening to 19 weeks. Two obstetricians and especially trained midwives at the Ultrasonic Laboratory performed the examinations, every operator doing, in turn, 25 screenings a day,. T o avoid monotony, the midwives did part-time ultrasonic screening alternating with duties at the delivery ward. This schedule avoided fatigue and diagnostic failures. Every examination was scheduled to take 15 min, and apart for the number of fetuses, the position of the fetus and the placenta, and the size of the fetal head were assessed. Most examinations were performed with a Kretz-Technik Combison 11. After the diagnosis of multiple pregnancies, the women were prescribed abscence from work and rest at home. They were seen at three-weekly intervals at the clinics until the beginning of the 29th week, when they were admitted into the maternity hospital. During the subsequent hospitalization, the prevention for preterm delivery consisted solely of rest, no drugs for uterine relaxation being used even when uterine contractions occurred. The mean duration of hospitalization was 5 5 days. The women were supervised for the appearance of pre-eclamptic signs, and their domestic and nursing problems were taken care of by social welfare officers. If no further complications occurred, the women were allowed home for weekends. After the end of the 36th week, they were discharged form the hospital provided that their pregnancy course had been completely normal. Otherwise, hospital care was extended until delivery. Few multiple pregnancies were allowed t o exceed the 38th week, at which time inductions were performed by amniotomy and i.v. oxytocin administration. In a few patients, preventive hospitalization commenced later than the 28th week and was terminated (mostly for social reasons) before the 36th week. No twin pregnancies lasting less than 28 gestational weeks are included in this report. Triplets are excluded. T o evaluate the benefit of improved history-taking for diagnosis, a detailed questionnaire regarding the familiar incidence of multiplicity was answered by 5 272 of the pregnant women before the ultrasonic examination under the guidAcra Obstet Gynecol Scand 58 (19791
During the study period, ultrasound was used to screen an increasing part of the pregnant population. When the programme was in full effect, more than 90 per cent of the women participated. Ninetyseven out of the 110 twin pregnancies were detected in the programme, i.e. a discrimination rate of 88 per cent. Two of the examined twin pregnancies (2 per cent) were mistakenly interpreted as singletons. No falsely positive diagnosis of twins was made. The net magnitude of methodological error (2 per cent) agrees well with our over-all twin detection results, as we have hitherto detected 145 out of 148 twin pairs by ultrasound. The average gestational age of twin pregnancies at the time of the detection was 35 weeks during 1963 1965. The mean gestational age for twin detection decreased from 30 weeks in 1973 to 20 weeks in 1977. The percentage of twin pregnancies discovered only after the birth of the first twin was 57 per cent in 1963 - 1965 and 2 per cent during 1973 - 1977. There was no increase in the average birth weight of the twins in the study group from 1973 - 1977 (Group I) compared with Groups I1 and 111. No consistent difference in birth weight between the first and second born twins was noted. Fortynine per cent of twins born in 1973 - 1977 had a birth weight below 2 500 g; the corresponding figure for 1963 - 1965 was 48 per cent. No twins with very low birth weight ( < 1 500 g) appeared in the group with bedrest (Group I), Table I. Also the percentage of twins that were light for gestational age (below the mean -2 SD of Swedish standard values for singletons [14]) was less in Group I (16 per cent) than in Groups I1 (27 per cent) and 111 (24 per cent). All twins born light for gestational age in Group I were born after the 35th week of gestation. The frequency of pre-term deliveries (before the 37th week) in Group I was 20 per cent and in Group I1 and 111 33 per cent. When only the twins born during the last 1% years were considered, during which period the programme was carried through most con-
On twin pregnancies Table 11. Mean gestational age of preterm delivered twins. Gestational age Group
Day
Week
n
1
240 233 235
34.6 33.5 33.8
17 8 31
11 111
5
Table 111. Perinatal mortality. Ante partum Post partum Total Group
n
Vo
n
Vo
n
Vo
I I1 I11
1
0.6 4.2 1.6
0
2 3
0 6.3 4.3
1 5 11
0.6 10.5 5.9
1/11 p
3 8
< 0.02; ”111 < 0.02
DISCUSSION sistently both concerning early detection of twins and the extent of hospitalization, a significant decrease in pre-term deliveries to 10 per cent was noted compared with the controls from 1963 - 1965 (p
ON IMPROVED OUTCOME OF TWIN PREGNANCIES Per-Hikan Persson, Lars Grennert, Gerhard Gennser and Stig Kullander From the Department of Obstetrics and Gynecology, University of Lund, Allmanna Sjukhuset, S-214 01 Malmo, Sweden
Abstract. During the past four years, an attempt has been made in Malmd t o reduce the frequency of preterm termination of twin pregnancies. For this purpose, the entire pregnant population of this medium-sized city was subjected to general ultrasonic screening in the second trimester. This detected 88 per cent of the twin pregnancies. The screening had a methodological error of 2 per cent. Eightysix of the women with twin pregnancy were subjected to bedrest in hospital for more than two weeks in the second half of gestation. The incidences of twins born with birth weight below 1 5 0 0 g and of twins light-for-gestational-age were reduced compared with those a decade earlier. Also the group of twins born before the 37th week decreased, and the perinatal mortality rate fell to the same level as in singleton pregnancies. Early detection of twin pregnancies followed by rest for the pregnant women seems t o contribute to an improved outcome of these gestations.
Neonatal mortality is affected by immaturity at birth (12, 37, 32). Measures to prevent preterm deliveries can be expected to reduce neonatal wastage. Multiple pregnancies involve a particular risk for premature termination of gestation (1, 20, 23, 28, 30, 34) and a high perinatal mortality (5, 15, 16, 23, 24, 28, 33, 36). Among twins, there is also a high percentage of infants with mental and neurological handicap inflicted at birth, reflecting the general finding that the incidence of these damages is increased in infants after preterm delivery (3, 4, 8). It has been repeatedly demonstrated that the impaired development of the central nervous system in twins is due to factors associated with low birth weight and preterm delivery (22, 25, 3 1 , 40, 41). An increase in the average gestational lenght of multiple pregnancies would therefore be expected to decrease the mortality of twin infants and reduce the chronic handicaps in the survivors. In the 1950’s, Bender (7) suggested that bedrest could prevent inadvertent preterm delivery of twins but only some later clinical studies have supported this hypothesis (6, 19, 25, 27). O n the other hand, an increased birth weight is reported to follow admission to hospital before term (2, 10, 21, 22). Preventive treatment of twin pregnancies with bedrest has been
widely attempted, but its intended effects have not been proved unanimously, for mainly two reasons: Multiple gestations - even if detected before delivery - have often been diagnosed too late for preventive measures to achieve their optimum results. Moreover, before the introduction of a general twin screening, the twins detected early in gestation and subjected to preventive treatment have presumably been the largest and most well-nourished fetuses. This has undoubtedly affected the interpretation of the results. An extensive and early diagnosis of gestational multiplicity is therefore of paramount importance for the evaluation of the effect of bedrest in reducing prematurity. This initiated the application of various methods for large-scale screening for multiple pregnancies, e.g., improved history taking, more alert physical examination (39), hormonal screening (17, 18, 29), and ultrasound (28, 35). Of these methods, large-scale ultrasonic examination has so far proved superior (1 8). The present paper summarizes a four-year experience of ultrasonic screening as a prerequisite for an extensive early hospitalization of women with twin pregnancies. It reports the outcome of these pregnancies concerning duration of gestation, birth weight, and perinatal mortality.
PATIENTS AND METHODS The study took place at the University Hospital of Malmo during 1.1.1973 - 30.4.1977, when 12 098 women were delivered. During this period, 110 pairs of twins were born: an apparent frequency of 1:110. The maternity hospital reported in the study is the only one serving a city of 250 OOO inhabitants and most of the population attend the antenatal clinics of the hospital. Private obstetricians working in close collaboration with the hospital staff saw 20 per cent of the pregnant women. Ninetyseven of the 110 twin pairs were detected early in gestation, and 86 women accepted the preventive programme. They comprise the study group (Group I). No conventional control group could be formed (see Discussion) but comparisons were made with the 24 women who were non-acceptors or whose twin pregnancy was not Acta Obsler Gynecol Scand 58 11979)
4
L . Grennert et al.
Table I. Birth weights. < I500 g
1500-2500 g > 2500 g
Total
Group
n
Vo
n
Vo
n
070
n
I I1 Ill
0 5 9
0 10 5
75 25 81
44 52 44
97 18 96
56 38 52
172 48 186
1/11 p
ance of a trained interviewer. In all women the gestational age was estimated from the last menstrual period by Naegele’s calculation and from the early clinical assessment of uterine size. The following statistical tests were used: Student’s t-test, Chi-square test with Yates’ correction and exact permutation test with each pregnancy (and not the individual twin) as the independent variable of comparison. All tests were one-sided.
< 0.01; I / I I I p < 0.05 RESULTS
detected before delivery (Group 11). Further comparisons were also made with the 93 twin pairs born at the same maternity hospital during 1963-1965, when both early diagnosis and prevention of prematurity were lacking (Group Ill). During this period, 11 733 deliveries occurred (apparent twin frequency 1:122). All the pregnant women were referred to ultrasonic screening at their first attendance at the antenatal clinic. The ultrasonic examinations were initially performed in the 28th week. During the course of the investigation, it was found desirable to perform the screening as early as practical. This reduced the average gestational age for the ultrasonic screening to 19 weeks. Two obstetricians and especially trained midwives at the Ultrasonic Laboratory performed the examinations, every operator doing, in turn, 25 screenings a day,. T o avoid monotony, the midwives did part-time ultrasonic screening alternating with duties at the delivery ward. This schedule avoided fatigue and diagnostic failures. Every examination was scheduled to take 15 min, and apart for the number of fetuses, the position of the fetus and the placenta, and the size of the fetal head were assessed. Most examinations were performed with a Kretz-Technik Combison 11. After the diagnosis of multiple pregnancies, the women were prescribed abscence from work and rest at home. They were seen at three-weekly intervals at the clinics until the beginning of the 29th week, when they were admitted into the maternity hospital. During the subsequent hospitalization, the prevention for preterm delivery consisted solely of rest, no drugs for uterine relaxation being used even when uterine contractions occurred. The mean duration of hospitalization was 5 5 days. The women were supervised for the appearance of pre-eclamptic signs, and their domestic and nursing problems were taken care of by social welfare officers. If no further complications occurred, the women were allowed home for weekends. After the end of the 36th week, they were discharged form the hospital provided that their pregnancy course had been completely normal. Otherwise, hospital care was extended until delivery. Few multiple pregnancies were allowed t o exceed the 38th week, at which time inductions were performed by amniotomy and i.v. oxytocin administration. In a few patients, preventive hospitalization commenced later than the 28th week and was terminated (mostly for social reasons) before the 36th week. No twin pregnancies lasting less than 28 gestational weeks are included in this report. Triplets are excluded. T o evaluate the benefit of improved history-taking for diagnosis, a detailed questionnaire regarding the familiar incidence of multiplicity was answered by 5 272 of the pregnant women before the ultrasonic examination under the guidAcra Obstet Gynecol Scand 58 (19791
During the study period, ultrasound was used to screen an increasing part of the pregnant population. When the programme was in full effect, more than 90 per cent of the women participated. Ninetyseven out of the 110 twin pregnancies were detected in the programme, i.e. a discrimination rate of 88 per cent. Two of the examined twin pregnancies (2 per cent) were mistakenly interpreted as singletons. No falsely positive diagnosis of twins was made. The net magnitude of methodological error (2 per cent) agrees well with our over-all twin detection results, as we have hitherto detected 145 out of 148 twin pairs by ultrasound. The average gestational age of twin pregnancies at the time of the detection was 35 weeks during 1963 1965. The mean gestational age for twin detection decreased from 30 weeks in 1973 to 20 weeks in 1977. The percentage of twin pregnancies discovered only after the birth of the first twin was 57 per cent in 1963 - 1965 and 2 per cent during 1973 - 1977. There was no increase in the average birth weight of the twins in the study group from 1973 - 1977 (Group I) compared with Groups I1 and 111. No consistent difference in birth weight between the first and second born twins was noted. Fortynine per cent of twins born in 1973 - 1977 had a birth weight below 2 500 g; the corresponding figure for 1963 - 1965 was 48 per cent. No twins with very low birth weight ( < 1 500 g) appeared in the group with bedrest (Group I), Table I. Also the percentage of twins that were light for gestational age (below the mean -2 SD of Swedish standard values for singletons [14]) was less in Group I (16 per cent) than in Groups I1 (27 per cent) and 111 (24 per cent). All twins born light for gestational age in Group I were born after the 35th week of gestation. The frequency of pre-term deliveries (before the 37th week) in Group I was 20 per cent and in Group I1 and 111 33 per cent. When only the twins born during the last 1% years were considered, during which period the programme was carried through most con-
On twin pregnancies Table 11. Mean gestational age of preterm delivered twins. Gestational age Group
Day
Week
n
1
240 233 235
34.6 33.5 33.8
17 8 31
11 111
5
Table 111. Perinatal mortality. Ante partum Post partum Total Group
n
Vo
n
Vo
n
Vo
I I1 I11
1
0.6 4.2 1.6
0
2 3
0 6.3 4.3
1 5 11
0.6 10.5 5.9
1/11 p
3 8
< 0.02; ”111 < 0.02
DISCUSSION sistently both concerning early detection of twins and the extent of hospitalization, a significant decrease in pre-term deliveries to 10 per cent was noted compared with the controls from 1963 - 1965 (p
