Connected twins are always identical twins
Perinatal problems in multiples
Background: The changed childbearing age and the successes of reproductive medicine have led to an increase in the multiple birth rate in the industrialized world.
Methods: selective literature research
Results: The risks of premature birth, intrauterine growth restriction and prenatal death increase in these pregnancies; maternal risks such as preeclampsia, gestational diabetes, and bleeding are more evident. Of the monitoring procedures during pregnancy, prenatal including genetic diagnostics are important, especially ultrasound diagnostics for the detection of the fetofetal transfusion syndrome and zygosis.
Conclusions: When looking after multiple pregnancies, the cooperation of prenatal doctors, obstetricians and neonatologists is required. Particular attention must be paid to the cooperation between outpatient and inpatient care.
The number of multiple pregnancies has increased steadily due to advances in reproductive medicine. As a result, obstetric care for multiple pregnancies and neonatal care for multiples are particularly intensive and demanding. Prenatal doctors, obstetricians and neonatologists are required both in the clinic and in the private practice.
For the competent cooperation at these interfaces, core statements are compiled on the basis of the scientific and clinical findings as well as a selective literature search taking into account older national (1) and international (2) guidelines.
The frequency of multiples varies widely around the world. The rule already established by Hellin in 1895 is still essentially valid today in order to be able to estimate the frequency of multiples: If the frequency of twins is 1:85, it is 1: 85 × 85 for triplets and 1: for quadruplets: 85 × 85 × 85. The number is much higher in early pregnancy. Boklage observed the course of 325 twin pregnancies, 19% of these pregnancies ended as twins, 39% as singles, 43% without a living child. He calculated the probable conception rate of twins to be 1: 8 (3).
In most European countries the twin rate fell from around 12 to around 9.5 per 1,000 pregnancies in the 1960s, only to rise again to around 12 in the early 1980s and to around 13-14 per around 1990 1,000 pregnancies. While the course in the 1960s and 1970s was mainly caused by the change in the age structure of pregnant women (first an increase in younger pregnant women, later an increase in pregnant women over 35), the increase from 1990 onwards is the result of reproductive medicine efforts seen (4). Ovulation induction and IVF (in vitro fertilization) are mainly addressed as the cause of this increase.
For the frequency of dizygotic twins, the occurrence of multiple births in the mother's family is much more important than that in the father's family. Women who were born as dizygotic twins themselves also gave birth to twins in around 2 percent of cases. In contrast, the incidence of twins in women whose husbands were dizygous twins was only about 1 percent (e1).
Duration of pregnancy
The average length of pregnancy is significantly shorter in the case of multiple pregnancies (tablegifppt) (e2). In 1987 the premature birth rate was among twins (< 37+0 ssw)="" in="" den="" usa="" bei="" 44,5 prozent="" gegenüber="" 9,4 prozent="" bei="" einlingen="" (5).="" als="" ursachen="" der="" verminderten="" schwangerschaftsdauer="" wurden="" die="" mechanische="" belastung="" der="" zervix,="" die="" relativ="" zum="" gewicht="" von="" fet="" und="" plazenta="" verminderte="" uterusdurchblutung="" und="" die="" relativ="" verminderte="" plazentafunktion="" gesehen.="" außerdem="" scheinen="" die="" ausreifung="" der="" „gap-junctions“="" aufgrund="" der="" hohen="" östrogenaktivität="" und="" prostaglandinsynthese="" sowie="" die="" relative="" abnahme="" der="" progesteronaktivität="" bei="" der="" mehrlingsschwangerschaft="" bedeutungsvoll="" für="" die="" verkürzte="" schwangerschaftsdauer="" zu=""> 37+0>
Perinatal mortality has fallen due to the increased detection rate of multiple births during pregnancy. The ultrasound examinations carried out on all pregnant women in accordance with the maternity guidelines have led to an almost complete prenatal diagnosis of multiples in the Federal Republic of Germany. The early diagnosis of pregnancy is important for the management of the pregnancy, for the monitoring of mother and children as well as the intrapartum procedure and the preparation of the parents.
The diagnosis of multiple pregnancy, the determination of the gestational age and the monitoring of fetal growth are possible according to the standard curves. It is important to note that the fetal growth curves of head diameter and femur length do not differ statistically in singles and twins (e3, e4). A differentiated malformation examination is indicated.
In addition, the determination of zygosis and placentation are important as multiple-specific examinations.
Basics of zygotia determination
Monozygous twins result from the division of an embryo. It is estimated that there are around four monozygous twins for every 1,000 births. Embryo-fetal mortality is higher in monozygous twins than in dizygous twins and singles. The rate of major malformations in monozygous twins is given as 2.3% compared to 1% in singles and that of smaller malformations as 4.1% compared to 2.5%. The statistically worse results are recorded by the monochorionic, monoamniotic twins, with the cases with two girls showing the less bad results (e5). If the embryo divides up to the fifth day after fertilization, dichorionic-diamniotic twins are formed (about 30%). In the event of division between the fifth and seventh day after fertilization, monochorionic-diamniotic twins are formed (about 70%). If they split after day 8, monochorionic-monoamniotic twins are formed (about 1%). Connected twins result from incomplete division on days 15 to 17 after fertilization. Their frequency is around 1 in 33,000 births in Europe (e6).
The fertilization of two different egg cells from two different follicles results in dizygous twins. The growth of the follicles is regulated by the gonadotropins. It has been suggested that higher levels of FSH would lead to higher numbers of dizygous twins. FSH production is influenced by light and dark periods. In Scandinavia, for example, there should be a larger number of dizygotic twin conceptions in July compared to a lower number in January. The likelihood of having dizygous twins increases with maternal age up to about 39 years, after which it decreases again. It also falls during periods of malnutrition (e7).
Higher grade multiples
Higher-grade multiples can result from the fertilization of one, two or more egg cells or from the division of one or more fertilized egg cells, so that a simultaneous di- and monozygous multiple pregnancy arises.
Knowledge of zygotia is an important prerequisite for correctly assessing risk factors in pregnancy. For example, there may be a difference in growth in the intrauterine deficiency development of a twin or in the feto-fetal transfusion syndrome; the latter, however, only occurs in monozygous twins.
Today, ultrasound diagnostics are indispensable for clearing up zygosis. At 10 to 15 weeks of pregnancy, dichorionic pregnancies show a lambda-shaped structuring of the membranes at the transition to the placenta (illustration 1gifppt). Separate placentas or a (fused) placenta and membrane thickness (monozygous twins have a thin, dizygous twins have a thick partition) are important findings.
The physiological disappearance of an embryo or early fetus from a multiple pregnancy ("vanishing twin") leads to resorption, an empty fruit sac or a fetus papyraceus. Clinically, this process is usually only noticeable through ex utero bleeding.
Prenatal Genetic Diagnostics
Genetic diagnostics have been offered to women since the 1970s, which of course also applies to multiples.
In principle, amniocentesis in the second trimester or chorionic villus sampling can be used. The complication rate of amniocentesis in multiple births is reported to be five times higher (about 5%) compared to that in single pregnancies (0.6 to 1%) (e8).
The most frequent and most important dangers for multiple pregnancies are the shortened gestation period and the increased dangers for the mother: in triplets: 20 percent preeclampsia, 30 percent anemia, 35 percent postpartum bleeding; in quadruplets: 32 percent preeclampsia, 25 percent anemia, 21 percent postpartum bleeding (6, e9, e10).
The selective reduction from higher-grade multiple pregnancies to twin pregnancies is carried out in order to reduce the risks presented to the life of the mother or the fetuses. Based on the experience with the indicated fetocide in malformations of multiple births (7), it is carried out with various methods such as hysterotomy, cardiac puncture, air injection or
Injection of cardiotoxic substances.
Working groups that are frequently confronted with the problem of selective fetocide consider transabdominal intrathoracic potassium chloride injection to be the most effective method when the embryo is eleven to twelve weeks old (8). In the opinion of many authors, the benefit for the surviving multiples justifies the procedure (9, e11). Before injecting monozygous twins, it must be taken into account that the injection into the twin concerned could cause the cardiotoxic substances to overflow onto the other twin and thus pose a significant risk. Complete loss of pregnancy after selective fetocide can be expected in 10 percent of pregnant women.
The selective fetocide is ethically extremely problematic and should be avoided through the use of suitable reproductive medicine measures.
Feto-fetal transfusion syndrome (TTTS)
Monozygous, monochorionic twin pregnancies have interfetal vascular connections at the placental level, both arterio-arterial and veno-venous anastomoses on the chorionic plate and arterio-venous shunts in the cotyledons (e12). They are the basis for blood redistribution, the cause of which is ultimately not clear. Possibly there is an increased vascular resistance in the placental circulation of the donor as a result of placental insufficiency, which causes the blood redistribution. A twin, who becomes larger (9, e13), polyglobular and / or hypervolemic (acceptor) and develops polyhydramnios, is favored by the growth of the donor, who becomes anemic and hypovolemic and develops oligohydramnios. The association of intrauterine weight differences (over 20%) and the ultrasonographically determined amniotic fluid volume difference (polyhydramnios in the recipient, oligohydramnios in the donor) is diagnostic. The volume of amniotic fluid can decrease in such a way that the donor is pressed against the egg membrane as a small twin (stuck twin) (Figure 2gifppt).
The overall mortality rates in the TTTS are very high (56 to 100%). In 3 to 5 percent of cases, fetal death occurs intrauterine (10). After the death of a twin, a so-called “twin embolization” syndrome develops in up to 14 percent of cases (e14). This leads to arterial hypotension and the inundation of thromboplastic material from the dead to the surviving fetus. The consequences are disseminated intravascular coagulation and / or infarcts with, among other things, severe neurological damage (11), so that intervention should be taken before the intrauterine death of a fetus.
Today, the following are used to treat TTTS:
- repeated amniocentesis and amniotic fluid discharge; the pathogenetic mechanism of this treatment is unclear, but repeated amniocentesis is often an effective method (e15, e16).
- Elective coagulation of the vascular connections is the most logical and consistent form of treatment (e15, 12, 13).
Antepartal death of one or more multiple pregnancies is common (around 1 to 5 percent of all multiple pregnancies) (e17). In addition to the emotional and psychological burden on the parents, special attention should be paid to the condition of the surviving multiple births (e18).
In monochorionic multiples with a dead multiple, a high rate of neurological damage is to be expected in surviving multiples. These are attributed to the embolization of thrombogenic material from the dead multiple into the living.
Reduction of the risk of premature birth
The fact that multiple births are more at risk in the perinatal period than children from singleton pregnancies can be explained by the high rate of premature births and the higher frequency of intrauterine underdeveloped children. The complication rate due to immaturity and deficiency in weight is around 40% in twins. The rate of premature births for twin pregnancies is given as 30% and is thus three to five times higher than comparable collectives of single pregnancies. In addition to the early diagnosis of multiple pregnancy, early declaration of incapacity for work (around 20 weeks gestation) and physical restraint are recognized as preventive measures (e19, e20); Inpatient treatment without additional risk, preventive cerclage (e21), and prophylactic tocolysis (e22) are no longer recommended.
Intrauterine deficiency development
Various factors contribute to the development of intrauterine deficiency in multiple pregnancies, the frequency of which is reported to be around 60% in multiple pregnancies (e23): the nutritional status of the mother, reduced uterine blood flow, abnormalities of the umbilical cord, transport capacity of the placenta, placental fit, unequal proportions of the total placental mass Multiples and the FFTS.
Termination of pregnancy
In order to avoid intrauterine fetal death close to an appointment, the recommendation to terminate pregnancy after 38 weeks of pregnancy is often given. If vaginal birth conduction is intended, prostaglandin maturation of the cervix is usually started. For the following indications, the primarily indicated caesarean section is usually performed at this gestational age:
- Triplets or higher-grade multiples
- previous multiple in pelvic end (BEL) or transverse position (QL)
- Ultrasound estimate of the second twin's weight more than 500 g above that of the first twin
- Twins with an estimated ultrasound weight less than 1,800 g
- monoamniotic twins (cesarean section at 34 + 0 weeks of pregnancy) (Figure 3jpgppt).
Neonatal mortality and morbidity
On the question of whether and to what extent a multiple pregnancy per se increases neonatal mortality and morbidity, there are partly contradicting data in the literature. This is due, among other things, to different study populations, different study designs (prospective or retrospective survey) and different periods of time (before or after the introduction of surfactant and intrauterine laser therapy). Although the number of children in a pregnancy increases the neonatal mortality and morbidity, the length of pregnancy also decreases, so that the problems associated with premature birth increasingly come into play. When comparing singles and multiples, gestational age, weight at birth, and gender must always be taken into account (14, e24).
In twins from around 32 weeks of pregnancy and in triplets from around 29 weeks of gestation, intrauterine growth is delayed compared to singles (15). In multiples with a birth weight below the 10th percentile, neonatal mortality is increased. However, if one adjusts for gestational age, the extent of growth retardation, and gender, the neonatal mortality rate in twins with fetal growth retardation is similar to that in singles (e25, 15, 16). In this context, a weight discordance between twins seems to play an important role: an increased neonatal mortality has been described with a weight discordance of more than 25%. The smaller twin is particularly affected, especially if they have a birth weight below the 10th percentile (17–19). If the weight discordance is large, the larger twin also appears to have an increased risk of mortality (e26, 20).
Increased neonatal mortality has been observed in monochorionic compared to dichorionic twins, especially if one twin died intrauterine (21, 22).
There are different data on the question of whether the order of birth has an influence on the prognosis: For example, in the case of very small twins (birth weight less than 1,500 g), an increased mortality risk for the second twin has been described, regardless of the mode of birth (e27). Other authors did not find such differences (15).
Respiratory distress syndrome
The incidence of respiratory distress syndrome (IBS) increases with the number of multiples (around 23% in triplets, 65% in quadruplets, 75% in quintuplets), but with a simultaneous decrease in gestational age (e27, e24). The risk of respiratory problems is higher in boys and the second twin (23, e28).A complete cycle of steroids given prenatally reduces the incidence of IBS even in multiple pregnancies (e27). However, a decreasing effect of prenatal lung maturity induction with increasing plurality has been described (24).
As with singles, the frequency of cerebral damage is also very much influenced by gestational age and birth weight in multiples. But chorionicity and intrauterine fetal death of a multiple also play a major role. In a meta-analysis of 28 studies, the risk of neurological disorders in the surviving twin was four times higher in monochorionic than dichorionic twins (22).
The risk of necrotizing enterocolitis (NEC) in monochorionic twins after adjustment for gestational age and birth weight was found to be 4 times higher (3.8% versus 0.9%) (21).
Long term results
Children after multiple pregnancies have an increased risk of neurological abnormalities. Parents should be informed about this risk and appropriate follow-up examinations organized (25).
Conflict of interest
The authors declare that there is no conflict of interest within the meaning of the guidelines of the International Committee of Medical Journal Editors.
Taken in: May 12, 2009, revised version accepted on October 29, 2009
Address for the authors
Prof. Dr. med. Joachim W. Dudenhausen
Weill Cornell Medical College
Dept. OB / GYN
525 E 68th Street M-701
New York NY 10065
Email: [email protected]
Perinatal Problems in Multiple Births
Background: Multiple pregnancies have become more common in the industrialized world because of rising maternal ages and advances in reproductive medicine.
Methods: Selective literature review.
Results: Multiple pregnancy carries a higher risk of prematurity, intrauterine growth restriction, and prenatal death, as well as elevated risks to the mother including preeclampsia, diabetes, and hemorrhage during delivery. Genetic tests and ultrasonography are the most important tests for monitoring during pregnancy. Ultrasound aids in the detection of the feto-fetal transfusion syndrome and in the determination of zygosity.
Conclusions: The care of women with multiple pregnancies requires the collaboration of specialists in prenatal medicine, obstetrics, and neonatology as well as a properly functioning integration of outpatient and inpatient care.
How to cite: Dtsch Arztebl Int 2010; 107 (38): 663-8
@Literature marked with "e":
The German version of this article is available online:
and growth on neonatal outcome compared with singleton infants. Am J Obstet Gynecol 2004; 191: 700-7. MEDLINE
viable twin pregnancies. Obstet Gynecol 1994; 84: 107-9. MEDLINE
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