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Maternal complications and multiple pregnancy
263
Current aspects of twin pregnancy C. Sureau, Clinique Universitaire Paris Cedex 14, France
Baudelocque,
123 Boulevard
de Port-Royal,
75674
When pregnancy is followed in a chronological sequence, the main points are epidemiological and biological. What are the frequencies of monozygotic and dizygotic twin pregnancy, and what are their evolutions with respect to geography, environmental influences, and medical treatment. Consideration is also given to the biological evolution of the twin ovum: eventual and certainly frequent resorption of one ovum, profile of twin growth in utero, ways of evaluating the fetal welfare in the case of twins, influences of various types of zygosity on the fetal state and the occurrence of vascular anastomosis, ways of determining zygocity in the case of dichorionic pregnancy, and influences of twin pregnancy on maternal situation. These biological events are of paramount importance for the clinical and therapeutic approach to twin pregnancy. Improvement of fetal survival is based on reinforcement of prenatal care, dietetic measures, prevention of prematurity which may or may not result from a more liberal usage of cerclage and/or medical treatment such as progesterone therapy or tocolysis, and the choice of the optimal time for delivery. With respect to labor and delivery, there has long been controversy about the indications and contra-indications for oxytocic agents and the definition of the optimal interval between the two deliveries. Furthermore, the recent increase in the rate of cesarean sections has raised the need for specific indications for this procedure in case of twin pregnancy. The neonatal period is also a fundamental concern. For example, a specific problem requiring further consideration is the risk of prenatal encephalomalacia in the child whose twin has died in utero near the end of pregnancy. Finally, since medicine is progressively becoming a field of economic concern, attention must be given to the economic aspects of the care of twins, particularly with respect to the rate of prematurity.
Maternal complications aud multiple pregnancy
I. MacGillivray, Department Foresterhill,
of Obstetrics Aberdeen AB9 220, U.K,
and Gynaecoioa,
University
of Aberdeen,
Zntroduction
It is generally believed that all of the complications of pregnancy occur more frequently in twin pregnancies than in singleton pregnancies. However, on closer examination it appears that it is only some of the complications which are more frequent. Furthermore, it is also possible that there is a difference in the incidence of complications according to the zygosity of the twin pregnancies. Most of the studies which have been carried out into complications of twin pregnancies have only considered all pregnancies together and have not divided the complications according to zygosity. Indeed, the only studies which have tried to
264
distinguish the incidence of complications by zygosity have determined the zygosity on the basis of like- and unlike-sexed twins. We have, therefore, carried out studies in Aberdeen of the complications according to accurately determined zygosity in a total population. Since 195 1, over 1200 pairs of twins have been delivered and the details of the classification have been recorded and the zygosity determined by the study of sex, placentation and various genetically determined markers in blood and placental tissue [ 11. It will only be possible to consider some of the main complications of pregnancy and those that have been chosen are pre-eclampsia, anaemia and pre-term labour. Pre-eclampsia This is one of the most important complications in obstetrics and it is unfortunate
that no universally accepted definition is available. The definition which is used in Aberdeen is that of Nelson [2] in which pre-eclampsia is defined as a condition in which a rise of diastolic blood pressure to 90 mm Hg or more occurring after the 26th wk of pregnancy on two or more occasions separated at least by a day, or in which the rise showed a progressive pattern if the patient was in labour. This was defined as mild pre-eclampsia or late pregnancy hypertension. If, in addition to the hypertension, there was definite proteinuria (more than 0.25 g/l) then the condition was considered to be severe. The value of these criteria for defining pre-eclampsia was confirmed by a large study of the Aberdeen population [3]. The incidence of pre-eclampsia has been previously reported in viable twin pregnancies to be three times that in all viable pregnancies [4,5]. However, they considered all parities together and did not differentiate by zygosity. In 1971, Stevenson and coworkers [6] reported that pre-eclampsia was more common in women having unlike-sex rather than like-sexed twins. In 1976 he and his coworkers [7] reported that pre-eclamptic toxaemias were commoner when the twins were dizygotic. No difference was found by McFarlane and Scott [S] in the incidence of pre-eclampsia between monozygotic and dizygotic twin pregnancies. As neither of these groups of workers determined the zygosity accurately, a study was carried out in Aberdeen in 343 twin pregnancies of known zygosity [9]. The incidence of proteinuric pre-eclampsia was 20.9% in monozygotic twin pregnancies compared with 36.2% in dizygotic but the difference was not statistically significant. This was considered to be of considerable interest in relation to the possible immunological effect of monozygotic compared to dizygotic twins and it was concluded [9] that as there was no difference between monozygotic and dizygotic twin pregnancies an immunological basis for the pre-eclampsia was unlikely. The results indicated' that there was a balance between the antigenic differences and circulating immunosuppressive substances. The differences, although not statistically significant in this small series, suggested that there might be a higher incidence in dizygotic than monozygotic pregnancies. Accordingly, a much larger series of 1206 twin pregnancies from 195 1 to 1980 has been studied (Table I). This confirmed that there is a high incidence of proteinuric pre-eclampsia and primigravidas are more susceptible than multigravidas (Table II). There is no difference in the incidence between monozygotic and dizygotic twin pregnancies.
265 TABLE
I
Incidence
of pre-eclampsia
in 1206 twin pregnancies
Proteinuric pre-eclampsia
Twin zygosity
Monozygotic (n = 342) Dizygotic (n = 864) Total ( n = 1206)
TABLE
by zygosity
in N.E. Scotland,
1951- 1980
Normotensive
Late pregnancy hypertension
%
n
%
n
10.82 11.11 11.03
(37) (96) (133)
18.13 19.10 18.82
(62) (165) (227)
%
n
71.05 69.79 70.15
(243) (603) (846)
II
Incidence Scotland,
of pre-eclampsia 195 I- 1980
by zygosity
in 355 primigravid
Proteinuric pre-eclampsia
% Primigravidas Monozygotic Dizygotic (n Multigravidas Monozygotic Dizygotic (n a Including
( n = I 19) = 236)
17.65 18.64
(n = 223) = 628)
7.18 8.28
and 851 multigravid
I
in N.E.
Normotensive
Late pregnancy hypertension n
twin pregnancies
%
n
n
(21)” (44) B
26.89 24.15
(32) (57)
55.46 57.21
(66) (135)
(16) (52)
13.45 17.20
(30) (108)
79.37 74.52
(177) (468)
3 eclamptics.
The very frequent occurrence of pre-eclampsia in twin pregnancies, increases the risks, of course particularly in first pregnancies. The perinatal mortality in twin pregnancies complicated by proteinuric pre-eclampsia is much higher than in those without pre-eclampsia. The treatment is based on that for singleton pregnancies but possibly requires even finer judgement in determining the optimum time for delivery than in singleton pregnancies. Anaemia
This is another common condition of pregnancy, although it is not so dangerous for the fetus as pre-eclampsia, and again it is generally considered to be more common in twin pregnancies than in singleton pregnancies. Again, definitions can cause problems because simply taking haemoglobin concentration can be misleading because of haemodilution in singleton pregnancies. It has been shown that there is a steady fall in haemoglobin concentration to about 30 wk gestation because of the increasing plasma volume. There is a further marked increase in plasma volume in twin pregnancies thus resulting in even lower levels of haemoglobin in perfectly normal pregnancies. However, it is still difficult to determine the level which can be accepted as normal. The haemoglobin and PCV are unreliable indicators and it is much more preferable in determining anaemia that other criteria such as MCHC, the
266
serum folate and, of course, blood films should be used. Some studies using some of these criteria have been carried out and, for example, Guttmacher [4] found that there was a much higher proportion of women with twin pregnancies who had a haemoglobin level below 70%. However, it is likely that the lower haemoglobin levels in twin pregnancies were caused by a greater haemodilution [lO,ll]. Nylander [ 121, in his study of anaemia in Ibadan, in which he considered that there was anaemia if the PCV was less than 27%, found that the incidence was 10.6% in singleton pregnancies compared with 10.4% in twin pregnancies. This is, of course, contrary to the popular belief that anaemia is more common in pregnancy. It must be remembered, however, that in Nigeria the anaemias which are common are folate deficiency and haemolytic anaemia. Hall [13], in a study of folic acid deficiency in Aberdeen, did not find any evidence of a greater incidence of folate deficiency in twin pregnancies compared with singletons which is in agreement with the findings in the Nigerian study. In a more recent study [ 141of 123 twin pregnancies in Aberdeen, the incidence in all the twin pregnancies of iron deficiency anaemia was 15% (18 cases). On the basis of hypochromia on a peripheral blood film an additional 7% (8 cases) had equivocal changes. In the 27 women who had intensive study of sternal marrow aspiration there were 11 (40%) who had absent or reduced iron storage. The percentage of twin pregnancies with macrocytosis and nuclear hypersegmentation in the peripheral blood film, was not greater than in the singleton pregnancies not treated by folic acid. Sternal marrow aspirations on the other hand showed megaloblastic haemopoiesis in 8 (29.6%) of 27 twin pregnancies in the intensive study which was higher than the 13% recorded in singleton pregnancies by Chanarin and coworkers [ 151. Although a low haemoglobin level was found in a greater proportion of twin than singleton pregnancies, this was likely to be due mainly to the greater plasma volume expansion in multiple pregnancy and this is considered of doubtful clinical significance. Only 15% showed presumptive evidence of iron deficiency on a peripheral blood film, but 40% showed deficient iron stores in the sternal marrow.- Macrocytosis in the peripheral blood film was found in only 2.4% of twin pregnancies, which is similar to untreated singleton pregnancies, but almost 30% showed megaloblastic haemopoiesis on marrow examination. These authors [ 141 recommended, in spite of the evidence of iron and/or folic acid deficiency in the sternal marrow of twin pregnancies at 32-34 wk gestation, that routine iron or folic acid prophylaxis should not be practised because the incidence of clinically significant anaemia was low. This low incidence could be explained by the transient and self-limiting nature of the deficiencies. They preferred to give specific treatment only if iron or folic deficiency was accompanied by significant anaemia and concluded that any adverse effect of folic acid deficiency on pregnancy complications other than anaemia, and any benefits of prophylaxis remain to be etablished because Hall [ 161 failed to show any relationship between folic acid deficiency and congenital malformation or [17] between folic acid deficiency and abruption of the placenta. Routine and careful full blood examinations must be carried out in twin preg* nancies at fairly frequent intervals and treatment with iron or folic acid therapy commenced if a definite anaemia can be demonstrated and reliance should not be placed on simply prescribing routine prophylactic dosage of either iron or folic acid.
26-l
Pre-term labour This is another common complication of twin pregnancies and is, of course, particularly hazardous for the babies. The incidence of preterm labour in 624 twin pregnancies in the Aberdeen area from 1960 to 1977 have been studied with reference to zygosity and placentation. Pre-term labour was defined as that occurring before 37 wk, that is, 21 days before term or 259 days after the first day of the last menstrual period. Little is known of the cause of the high incidence of pre-term labour in twin pregnancy compared to singleton pregnancy. It has not previously been determined whether pre-term labour is more likely to occur in monozygotic compared to dizygotic twins. In this study, in which pre-term deliveries amounted to 28.2% of all twin deliveries, the onset was divided into those with spontaneous occurrence of labour compared with those with spontaneous rupture of the membanes before labour, and those in which labour had been induced or caesarean section performed. As might be expected, the reason for termination of the twin pregnancy was most commonly found to be proteinuric pre-eclampsia. When zygosity was considered to see which type was more likely to end in pre-term labour initiated by spontaneous uterine contraction, or by spontaneous rupture of the membranes, it was found that monozygotic was more likely (P -c 0.05) to have pre-term labour than dizygotic in all pre-term deliveries. When the pre-term deliveries were divided by the different causes it was found that in those in which labour was induced or caesarean section performed, there was no difference between the monozygotic and dizygotic twin pregnancies. There was also no difference in the spontaneous onset of premature labours. However, there were twice as many (P -c 0.01) pre-term deliveries associated with spontaneous rupture of the membranes, in the monozygotic pregnancies compared with the dizygotic twin pregnancies. As Hall and Carr-Hill [ 181 have shown that labours occurs at an earlier gestation in singleton pregnancies when the babies are boys rather than girls, the sex of twins in relation to pre-term labour was considered. There was again a preponderance of boys over girls in the pre-term deliveries which is in accord with the findings of Hall and Carr-Hill [ 181 in singleton pregnancies. This applied to both the pre-term onset of labour and the spontaneous rupture of membranes. The boy/girl combination is the least likely to be associated with pre-term delivery except in the group with spontaneous onset of labour. The pregnancies were divided by sex of baby and zygosity to try to determine whether it was the zygosity or the baby sex combinations which were associated with premature onset of labour. There is a preponderance of boy/boy compared with girl/girl combinations, the monozygotic twins having pre-term deliveries both with spontaneous premature labour and spontaneous rupture of the membranes. There was, however, no preponderance in those where labour was induced or caesarean section performed. On the other hand in the dizygotic twins there was no preponderance of boys over girls in either those with pre-term labours or in all the twins. The explanations for these findings are not easy to decide but the more common onset of preterm labour in monozygotic twinning might be related to the occurrence of hydramnios. The more occurrence in the boy/boy combination is possibly
268
hormonal in origin but even so, it is strange that the boy/boy combination is not more commonly associated with pre-term labour than the girl/girl combination in dizygotic twinning. In our studies in Aberdeen we have not been able to shown any benefit from the effects of bedrest, beta-sympathomimetic agents, cervical cerclage on pre-term labour in twin pregnancies and it is obvious that more knowledge of the causes of the onset of pre-term labour in these cases is needed. These observations on the presence of zygosity may help in unravelling them. There seem to be definite differences in the incidence of certain complications of twin pregnancies depending on the zygosity, and the determination of zygosity by ultrasound examinations or other means could help in the management of twin pregnancy. References 1. Comey G, Robson EB. In: MacGillivray I, Nylander PPS, Comey G, eds. Human multiple reproduction. London: WB Saunders, 1975. 2. Nelson TR. A clinical study of pre-eclampsia. J Obstet Gynaecol Br Emp 1955; 62: 48-57. 3. MacGillivray I. Hypertension in pregnancy and its consequences. J Obstet Gynaecol Br Cwlth 1961; 68: 557-569. 4. Guttmacher AF. Clinical aspects of twin pregnancy. Med Clin N Am 1939; 23: 427-447. 5. Bender S. Twin pregnancy. A review of 472 cases. J Obstet Gynaecol Br Emp 1952; 59: 510-517. 6. Stevenson AC, Davison BC, Say B et al. Contribution of fetal/maternal incompatibility to aetiology of pre-eclamptic toxaemia. Lancet 1971; 2: 1286-1289. 7. Stevenson AC, Say B, Ustaoglu S, Durmus Z. Aspects of pre-eclamptic toxaemia of pregnancy, consanguinity and twinning in Ankara. J Med Genet 1976; 13: l-8. 8. MacFarlane A, Scott JS. Pre-eclampsia/eclampsia in twin pregnancies. J Med Genet 1976; 13: 208-211. 9. Campbell DM, MacGillivray I. Comparison of maternal response in first and second pregnancies in relation to baby weight. J Obstet Gynaecol Br Cwlth 1972; 79: 684-693. 10. Campbell DM, MacGillivray I, Thompson B. Twin zygosity and pre-eclampsia. Lancet 1977; 2: 97. 11. Rovinsky JJ, Jaffin H. Cardiovascular hemodynamics in pregnancy. I. Blood and plasma volumes in pultiple pregnancy. Am J Obstet Gynecol 1965; 93: l-15. 12. Nylander PPS. In: MacGillivray I, Nylander PPS, Comey G, eds. Human multiple reproduction. London: WB Saunders, 1975. 13. Hall M. M.D. Thesis, Aberdeen University, 1970. 14. Hall MH, Campbell DM, Davidson IUL. Anaemia in twin pregnancy. Acta Genet Med Gemellol 1979; 28: 279-282. 15. Chanarin I, Rothman D, Ward A, Perry J. Folate status and requirement in pregnancy. Br med J 1968; 2: 390-397. 16. Hall MH. Folic acid deficiency and congenital malformation. J Obstet Gynaecol Br Cwlth 1972; 79: 159-161. 17. Hall MH. Folic acid deficiency and abruptio placentae. J Obstet Gynaecol Br Cwlth 1972; 79: 222-225. 18. Hall MH, Carr-Hill R. Impact of sex ratio on onset and management of labour. Br Med J 1982; 2: 401-403.
Current aspects of twin pregnancy C. Sureau, Clinique Universitaire Paris Cedex 14, France
Baudelocque,
123 Boulevard
de Port-Royal,
75674
When pregnancy is followed in a chronological sequence, the main points are epidemiological and biological. What are the frequencies of monozygotic and dizygotic twin pregnancy, and what are their evolutions with respect to geography, environmental influences, and medical treatment. Consideration is also given to the biological evolution of the twin ovum: eventual and certainly frequent resorption of one ovum, profile of twin growth in utero, ways of evaluating the fetal welfare in the case of twins, influences of various types of zygosity on the fetal state and the occurrence of vascular anastomosis, ways of determining zygocity in the case of dichorionic pregnancy, and influences of twin pregnancy on maternal situation. These biological events are of paramount importance for the clinical and therapeutic approach to twin pregnancy. Improvement of fetal survival is based on reinforcement of prenatal care, dietetic measures, prevention of prematurity which may or may not result from a more liberal usage of cerclage and/or medical treatment such as progesterone therapy or tocolysis, and the choice of the optimal time for delivery. With respect to labor and delivery, there has long been controversy about the indications and contra-indications for oxytocic agents and the definition of the optimal interval between the two deliveries. Furthermore, the recent increase in the rate of cesarean sections has raised the need for specific indications for this procedure in case of twin pregnancy. The neonatal period is also a fundamental concern. For example, a specific problem requiring further consideration is the risk of prenatal encephalomalacia in the child whose twin has died in utero near the end of pregnancy. Finally, since medicine is progressively becoming a field of economic concern, attention must be given to the economic aspects of the care of twins, particularly with respect to the rate of prematurity.
Maternal complications aud multiple pregnancy
I. MacGillivray, Department Foresterhill,
of Obstetrics Aberdeen AB9 220, U.K,
and Gynaecoioa,
University
of Aberdeen,
Zntroduction
It is generally believed that all of the complications of pregnancy occur more frequently in twin pregnancies than in singleton pregnancies. However, on closer examination it appears that it is only some of the complications which are more frequent. Furthermore, it is also possible that there is a difference in the incidence of complications according to the zygosity of the twin pregnancies. Most of the studies which have been carried out into complications of twin pregnancies have only considered all pregnancies together and have not divided the complications according to zygosity. Indeed, the only studies which have tried to
264
distinguish the incidence of complications by zygosity have determined the zygosity on the basis of like- and unlike-sexed twins. We have, therefore, carried out studies in Aberdeen of the complications according to accurately determined zygosity in a total population. Since 195 1, over 1200 pairs of twins have been delivered and the details of the classification have been recorded and the zygosity determined by the study of sex, placentation and various genetically determined markers in blood and placental tissue [ 11. It will only be possible to consider some of the main complications of pregnancy and those that have been chosen are pre-eclampsia, anaemia and pre-term labour. Pre-eclampsia This is one of the most important complications in obstetrics and it is unfortunate
that no universally accepted definition is available. The definition which is used in Aberdeen is that of Nelson [2] in which pre-eclampsia is defined as a condition in which a rise of diastolic blood pressure to 90 mm Hg or more occurring after the 26th wk of pregnancy on two or more occasions separated at least by a day, or in which the rise showed a progressive pattern if the patient was in labour. This was defined as mild pre-eclampsia or late pregnancy hypertension. If, in addition to the hypertension, there was definite proteinuria (more than 0.25 g/l) then the condition was considered to be severe. The value of these criteria for defining pre-eclampsia was confirmed by a large study of the Aberdeen population [3]. The incidence of pre-eclampsia has been previously reported in viable twin pregnancies to be three times that in all viable pregnancies [4,5]. However, they considered all parities together and did not differentiate by zygosity. In 1971, Stevenson and coworkers [6] reported that pre-eclampsia was more common in women having unlike-sex rather than like-sexed twins. In 1976 he and his coworkers [7] reported that pre-eclamptic toxaemias were commoner when the twins were dizygotic. No difference was found by McFarlane and Scott [S] in the incidence of pre-eclampsia between monozygotic and dizygotic twin pregnancies. As neither of these groups of workers determined the zygosity accurately, a study was carried out in Aberdeen in 343 twin pregnancies of known zygosity [9]. The incidence of proteinuric pre-eclampsia was 20.9% in monozygotic twin pregnancies compared with 36.2% in dizygotic but the difference was not statistically significant. This was considered to be of considerable interest in relation to the possible immunological effect of monozygotic compared to dizygotic twins and it was concluded [9] that as there was no difference between monozygotic and dizygotic twin pregnancies an immunological basis for the pre-eclampsia was unlikely. The results indicated' that there was a balance between the antigenic differences and circulating immunosuppressive substances. The differences, although not statistically significant in this small series, suggested that there might be a higher incidence in dizygotic than monozygotic pregnancies. Accordingly, a much larger series of 1206 twin pregnancies from 195 1 to 1980 has been studied (Table I). This confirmed that there is a high incidence of proteinuric pre-eclampsia and primigravidas are more susceptible than multigravidas (Table II). There is no difference in the incidence between monozygotic and dizygotic twin pregnancies.
265 TABLE
I
Incidence
of pre-eclampsia
in 1206 twin pregnancies
Proteinuric pre-eclampsia
Twin zygosity
Monozygotic (n = 342) Dizygotic (n = 864) Total ( n = 1206)
TABLE
by zygosity
in N.E. Scotland,
1951- 1980
Normotensive
Late pregnancy hypertension
%
n
%
n
10.82 11.11 11.03
(37) (96) (133)
18.13 19.10 18.82
(62) (165) (227)
%
n
71.05 69.79 70.15
(243) (603) (846)
II
Incidence Scotland,
of pre-eclampsia 195 I- 1980
by zygosity
in 355 primigravid
Proteinuric pre-eclampsia
% Primigravidas Monozygotic Dizygotic (n Multigravidas Monozygotic Dizygotic (n a Including
( n = I 19) = 236)
17.65 18.64
(n = 223) = 628)
7.18 8.28
and 851 multigravid
I
in N.E.
Normotensive
Late pregnancy hypertension n
twin pregnancies
%
n
n
(21)” (44) B
26.89 24.15
(32) (57)
55.46 57.21
(66) (135)
(16) (52)
13.45 17.20
(30) (108)
79.37 74.52
(177) (468)
3 eclamptics.
The very frequent occurrence of pre-eclampsia in twin pregnancies, increases the risks, of course particularly in first pregnancies. The perinatal mortality in twin pregnancies complicated by proteinuric pre-eclampsia is much higher than in those without pre-eclampsia. The treatment is based on that for singleton pregnancies but possibly requires even finer judgement in determining the optimum time for delivery than in singleton pregnancies. Anaemia
This is another common condition of pregnancy, although it is not so dangerous for the fetus as pre-eclampsia, and again it is generally considered to be more common in twin pregnancies than in singleton pregnancies. Again, definitions can cause problems because simply taking haemoglobin concentration can be misleading because of haemodilution in singleton pregnancies. It has been shown that there is a steady fall in haemoglobin concentration to about 30 wk gestation because of the increasing plasma volume. There is a further marked increase in plasma volume in twin pregnancies thus resulting in even lower levels of haemoglobin in perfectly normal pregnancies. However, it is still difficult to determine the level which can be accepted as normal. The haemoglobin and PCV are unreliable indicators and it is much more preferable in determining anaemia that other criteria such as MCHC, the
266
serum folate and, of course, blood films should be used. Some studies using some of these criteria have been carried out and, for example, Guttmacher [4] found that there was a much higher proportion of women with twin pregnancies who had a haemoglobin level below 70%. However, it is likely that the lower haemoglobin levels in twin pregnancies were caused by a greater haemodilution [lO,ll]. Nylander [ 121, in his study of anaemia in Ibadan, in which he considered that there was anaemia if the PCV was less than 27%, found that the incidence was 10.6% in singleton pregnancies compared with 10.4% in twin pregnancies. This is, of course, contrary to the popular belief that anaemia is more common in pregnancy. It must be remembered, however, that in Nigeria the anaemias which are common are folate deficiency and haemolytic anaemia. Hall [13], in a study of folic acid deficiency in Aberdeen, did not find any evidence of a greater incidence of folate deficiency in twin pregnancies compared with singletons which is in agreement with the findings in the Nigerian study. In a more recent study [ 141of 123 twin pregnancies in Aberdeen, the incidence in all the twin pregnancies of iron deficiency anaemia was 15% (18 cases). On the basis of hypochromia on a peripheral blood film an additional 7% (8 cases) had equivocal changes. In the 27 women who had intensive study of sternal marrow aspiration there were 11 (40%) who had absent or reduced iron storage. The percentage of twin pregnancies with macrocytosis and nuclear hypersegmentation in the peripheral blood film, was not greater than in the singleton pregnancies not treated by folic acid. Sternal marrow aspirations on the other hand showed megaloblastic haemopoiesis in 8 (29.6%) of 27 twin pregnancies in the intensive study which was higher than the 13% recorded in singleton pregnancies by Chanarin and coworkers [ 151. Although a low haemoglobin level was found in a greater proportion of twin than singleton pregnancies, this was likely to be due mainly to the greater plasma volume expansion in multiple pregnancy and this is considered of doubtful clinical significance. Only 15% showed presumptive evidence of iron deficiency on a peripheral blood film, but 40% showed deficient iron stores in the sternal marrow.- Macrocytosis in the peripheral blood film was found in only 2.4% of twin pregnancies, which is similar to untreated singleton pregnancies, but almost 30% showed megaloblastic haemopoiesis on marrow examination. These authors [ 141 recommended, in spite of the evidence of iron and/or folic acid deficiency in the sternal marrow of twin pregnancies at 32-34 wk gestation, that routine iron or folic acid prophylaxis should not be practised because the incidence of clinically significant anaemia was low. This low incidence could be explained by the transient and self-limiting nature of the deficiencies. They preferred to give specific treatment only if iron or folic deficiency was accompanied by significant anaemia and concluded that any adverse effect of folic acid deficiency on pregnancy complications other than anaemia, and any benefits of prophylaxis remain to be etablished because Hall [ 161 failed to show any relationship between folic acid deficiency and congenital malformation or [17] between folic acid deficiency and abruption of the placenta. Routine and careful full blood examinations must be carried out in twin preg* nancies at fairly frequent intervals and treatment with iron or folic acid therapy commenced if a definite anaemia can be demonstrated and reliance should not be placed on simply prescribing routine prophylactic dosage of either iron or folic acid.
26-l
Pre-term labour This is another common complication of twin pregnancies and is, of course, particularly hazardous for the babies. The incidence of preterm labour in 624 twin pregnancies in the Aberdeen area from 1960 to 1977 have been studied with reference to zygosity and placentation. Pre-term labour was defined as that occurring before 37 wk, that is, 21 days before term or 259 days after the first day of the last menstrual period. Little is known of the cause of the high incidence of pre-term labour in twin pregnancy compared to singleton pregnancy. It has not previously been determined whether pre-term labour is more likely to occur in monozygotic compared to dizygotic twins. In this study, in which pre-term deliveries amounted to 28.2% of all twin deliveries, the onset was divided into those with spontaneous occurrence of labour compared with those with spontaneous rupture of the membanes before labour, and those in which labour had been induced or caesarean section performed. As might be expected, the reason for termination of the twin pregnancy was most commonly found to be proteinuric pre-eclampsia. When zygosity was considered to see which type was more likely to end in pre-term labour initiated by spontaneous uterine contraction, or by spontaneous rupture of the membranes, it was found that monozygotic was more likely (P -c 0.05) to have pre-term labour than dizygotic in all pre-term deliveries. When the pre-term deliveries were divided by the different causes it was found that in those in which labour was induced or caesarean section performed, there was no difference between the monozygotic and dizygotic twin pregnancies. There was also no difference in the spontaneous onset of premature labours. However, there were twice as many (P -c 0.01) pre-term deliveries associated with spontaneous rupture of the membranes, in the monozygotic pregnancies compared with the dizygotic twin pregnancies. As Hall and Carr-Hill [ 181 have shown that labours occurs at an earlier gestation in singleton pregnancies when the babies are boys rather than girls, the sex of twins in relation to pre-term labour was considered. There was again a preponderance of boys over girls in the pre-term deliveries which is in accord with the findings of Hall and Carr-Hill [ 181 in singleton pregnancies. This applied to both the pre-term onset of labour and the spontaneous rupture of membranes. The boy/girl combination is the least likely to be associated with pre-term delivery except in the group with spontaneous onset of labour. The pregnancies were divided by sex of baby and zygosity to try to determine whether it was the zygosity or the baby sex combinations which were associated with premature onset of labour. There is a preponderance of boy/boy compared with girl/girl combinations, the monozygotic twins having pre-term deliveries both with spontaneous premature labour and spontaneous rupture of the membranes. There was, however, no preponderance in those where labour was induced or caesarean section performed. On the other hand in the dizygotic twins there was no preponderance of boys over girls in either those with pre-term labours or in all the twins. The explanations for these findings are not easy to decide but the more common onset of preterm labour in monozygotic twinning might be related to the occurrence of hydramnios. The more occurrence in the boy/boy combination is possibly
268
hormonal in origin but even so, it is strange that the boy/boy combination is not more commonly associated with pre-term labour than the girl/girl combination in dizygotic twinning. In our studies in Aberdeen we have not been able to shown any benefit from the effects of bedrest, beta-sympathomimetic agents, cervical cerclage on pre-term labour in twin pregnancies and it is obvious that more knowledge of the causes of the onset of pre-term labour in these cases is needed. These observations on the presence of zygosity may help in unravelling them. There seem to be definite differences in the incidence of certain complications of twin pregnancies depending on the zygosity, and the determination of zygosity by ultrasound examinations or other means could help in the management of twin pregnancy. References 1. Comey G, Robson EB. In: MacGillivray I, Nylander PPS, Comey G, eds. Human multiple reproduction. London: WB Saunders, 1975. 2. Nelson TR. A clinical study of pre-eclampsia. J Obstet Gynaecol Br Emp 1955; 62: 48-57. 3. MacGillivray I. Hypertension in pregnancy and its consequences. J Obstet Gynaecol Br Cwlth 1961; 68: 557-569. 4. Guttmacher AF. Clinical aspects of twin pregnancy. Med Clin N Am 1939; 23: 427-447. 5. Bender S. Twin pregnancy. A review of 472 cases. J Obstet Gynaecol Br Emp 1952; 59: 510-517. 6. Stevenson AC, Davison BC, Say B et al. Contribution of fetal/maternal incompatibility to aetiology of pre-eclamptic toxaemia. Lancet 1971; 2: 1286-1289. 7. Stevenson AC, Say B, Ustaoglu S, Durmus Z. Aspects of pre-eclamptic toxaemia of pregnancy, consanguinity and twinning in Ankara. J Med Genet 1976; 13: l-8. 8. MacFarlane A, Scott JS. Pre-eclampsia/eclampsia in twin pregnancies. J Med Genet 1976; 13: 208-211. 9. Campbell DM, MacGillivray I. Comparison of maternal response in first and second pregnancies in relation to baby weight. J Obstet Gynaecol Br Cwlth 1972; 79: 684-693. 10. Campbell DM, MacGillivray I, Thompson B. Twin zygosity and pre-eclampsia. Lancet 1977; 2: 97. 11. Rovinsky JJ, Jaffin H. Cardiovascular hemodynamics in pregnancy. I. Blood and plasma volumes in pultiple pregnancy. Am J Obstet Gynecol 1965; 93: l-15. 12. Nylander PPS. In: MacGillivray I, Nylander PPS, Comey G, eds. Human multiple reproduction. London: WB Saunders, 1975. 13. Hall M. M.D. Thesis, Aberdeen University, 1970. 14. Hall MH, Campbell DM, Davidson IUL. Anaemia in twin pregnancy. Acta Genet Med Gemellol 1979; 28: 279-282. 15. Chanarin I, Rothman D, Ward A, Perry J. Folate status and requirement in pregnancy. Br med J 1968; 2: 390-397. 16. Hall MH. Folic acid deficiency and congenital malformation. J Obstet Gynaecol Br Cwlth 1972; 79: 159-161. 17. Hall MH. Folic acid deficiency and abruptio placentae. J Obstet Gynaecol Br Cwlth 1972; 79: 222-225. 18. Hall MH, Carr-Hill R. Impact of sex ratio on onset and management of labour. Br Med J 1982; 2: 401-403.